@article {pmid41958339,
year = {2026},
author = {Sutanto, H and Savitri, M and Hendarsih, E and Ashariati, A},
title = {Early hematologic dynamics and their association with patient-reported symptom burden in breast cancer pharmacotherapy: a prospective cohort study.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/14796694.2026.2656388},
pmid = {41958339},
issn = {1744-8301},
abstract = {BACKGROUND: Systemic pharmacotherapy for breast cancer frequently induces hematologic toxicity and inflammatory changes that may affect symptom burden and treatment tolerance. This study evaluated baseline hematologic profiles, early treatment-related changes, and their association with patient-reported outcomes during the first cycle of therapy.<br><br>METHODS: In this prospective cohort study, 106 women receiving systemic pharmacotherapy at two secondary referral centers in Indonesia were enrolled. Hematologic parameters and inflammatory indices-including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV)-were measured. Patient-reported outcomes were assessed using the EORTC QLQ-C30.<br><br>RESULTS: The mean age was 51.9&#x2009;&#xb1;&#x2009;9.7&#x2009;years, with most patients presenting with locally advanced disease and invasive ductal carcinoma. Early pharmacotherapy caused marked hematologic suppression, with leukocyte and neutrophil nadirs at week 1 and partial recovery by week 3 (p&#x2009;<&#x2009;0.001). PLR, MLR, and PIV changed significantly over time (p&#x2009;<&#x2009;0.001). Anemia increased from 51.9% to 74.0%, while neutropenia rose to 41.7% at week 1 before declining to 1.1% by week 3. Selected hematologic biomarkers correlated with patient-reported symptom burden, and only baseline MLR differed between survival subgroups (p&#x2009;=&#x2009;0.043).<br><br>CONCLUSION: Early breast cancer pharmacotherapy induces dynamic hematologic and inflammatory changes associated with patient-reported symptoms, supporting integrated monitoring to improve toxicity management.},
}
@article {pmid41963621,
year = {2026},
author = {Leshem, Y and Golomb, I and Zubkov, A and Bar, Y and Strulov Shachar, S and Lerner, S and Keren-Khadmy, N and Sonnenblick, A},
title = {Neoadjuvant twelve weekly paclitaxel-carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer.},
journal = {Breast cancer research and treatment},
volume = {217},
number = {1},
pages = {},
pmid = {41963621},
issn = {1573-7217},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology/genetics/mortality/metabolism ; Middle Aged ; Paclitaxel/administration &amp; dosage/adverse effects ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration &amp; dosage ; Aged ; Neoadjuvant Therapy ; *Erb-b2 Receptor Tyrosine Kinases/metabolism/genetics ; Trastuzumab/administration &amp; dosage ; Carboplatin/administration &amp; dosage/adverse effects ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Retrospective Studies ; Adult ; Treatment Outcome ; Neoplasm Staging ; Aged, 80 and over ; },
abstract = {PURPOSE: Standard neoadjuvant therapy for early HER2-positive breast cancer consists of 18 weeks of carboplatin, docetaxel, trastuzumab, and pertuzumab. However, treatment intensity may limit feasibility in frail patients and exceed therapeutic needs in selected early-stage disease. We report here real-world clinical outcomes of patients receiving a shortened 12-week neoadjuvant regimen of weekly paclitaxel and carboplatin administered with trastuzumab and pertuzumab (12wTCHP).<br><br>METHODS: We conducted a retrospective analysis of patients with HER2-positive breast cancer treated with neoadjuvant 12wTCHP in a single tertiary medical center.<br><br>RESULTS: Of forty-four eligible patients receiving 12wTCHP, 41 had invasive ductal carcinoma (IDC, 93%), and 64% were ER-positive. The majority of the cohort had stage IIA (73%, median age 59&#xa0;years), while the remainder had stage IIB&#xa0;or&#xa0;stage&#xa0;III disease and were significantly older (median age 64 and 76&#xa0;years,&#xa0;respectively; p&#x2009;=&#x2009;0.007). Grade 3-4 neutropenia (20%) and diarrhea (19%) were the most frequent toxicities. No treatment-related deaths occurred. Pathological complete response (pCR) rate was 61%: 54% in ER-positive tumors and 75% in ER-negative tumors (p&#x2009;=&#x2009;0.208). After a median follow-up of 30 months, only two recurrences (5%) were observed. None of the 30 patients with stage IIA IDC had disease recurrence.<br><br>CONCLUSIONS: In this retrospective cohort study, neoadjuvant 12wTCHP was well tolerated and associated with high pCR and low early recurrence rates. These findings are hypothesis-generating and support further evaluation of de-escalated 12wTCHP regimen in selected patients.},
}
@article {pmid41776559,
year = {2026},
author = {Siddique, H and Khan, A and Salomon, I and Hashmi, AH},
title = {Unusual metastasis of breast cancer to the paranasal sinuses: a case report.},
journal = {Journal of medical case reports},
volume = {20},
number = {1},
pages = {},
pmid = {41776559},
issn = {1752-1947},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/therapy ; Aged ; *Paranasal Sinus Neoplasms/secondary/diagnostic imaging/therapy ; Fatal Outcome ; *Carcinoma, Ductal, Breast/secondary/pathology/therapy ; Palliative Care ; Tomography, X-Ray Computed ; Paranasal Sinuses/pathology ; },
abstract = {BACKGROUND: Breast cancer is the most common malignancy in women, with invasive ductal carcinoma being the predominant subtype. Although metastases commonly affect the bones, liver, lungs, and brain, involvement of the paranasal sinuses is exceedingly rare and poses significant diagnostic challenges.<br><br>CASE PRESENTATION: A 70-year-old postmenopausal woman from Pakistan with a history of left-sided mastectomy and chemotherapy for invasive ductal carcinoma presented with an altered sensorium, aphasia, and reduced oral intake. Imaging revealed an aggressive, destructive lesion in the left frontal sinus, ethmoid air cells, and posterior parietal bone. Biopsy confirmed metastasis from the primary breast carcinoma. The patient received palliative radiotherapy and supportive care owing to her preference to avoid invasive interventions. Despite management, her condition progressively deteriorated, and she succumbed 2 years later. Paranasal sinus metastases are uncommon and often mimic rhinosinusitis, leading to a delayed diagnosis. Breast cancer metastasis to this region underscores the unpredictability of metastatic spread even years after the initial diagnosis. Management focuses on symptom control because surgical intervention is typically limited by anatomical constraints and the patient's overall health.<br><br>CONCLUSION: This case highlights the importance of maintaining a high index of suspicion for atypical metastatic sites in survivors of breast cancer. Multidisciplinary approaches and patient-centered care are critical for optimizing quality of life in advanced disease stages.},
}
@article {pmid41944070,
year = {2026},
author = {Li, N and Taherdangkoo, K and Baatsch, IM and Guduru, T and Meng, Q and Li, S and Zhou, Y and Li, X and Zhu, M and Polczer, S and Geissler, C and Briem, E and Megens, RTA and Na, H and Kumbrink, J and Richter, D and Li, Y and Jethwa, C and Bartelt, A and Döring, Y and von Hundelshausen, P and Enard, W and Weber, C and Nazari-Jahantigh, M and Schober, A},
title = {Mir147 Limits the Contribution of Non-Foamy Macrophages to Atherosclerosis.},
journal = {Circulation},
volume = {},
number = {},
pages = {},
doi = {10.1161/CIRCULATIONAHA.125.077821},
pmid = {41944070},
issn = {1524-4539},
abstract = {BACKGROUND: Hypercholesterolemia and a high-fat diet promote 2 macrophage subtypes involved in atherosclerosis by inducing lipid droplet accumulation in foamy macrophages (FMs) and inflammatory activation in non-foamy macrophages (NFMs). MicroRNAs are key regulators of macrophage function; for instance, miR-10a-5p reduces atherosclerosis and improves mitochondrial health in FMs, whereas miR-155-5p accelerates atherosclerosis by impairing efferocytosis. miR-147-3p is upregulated by inflammatory stimuli in macrophages and in atherosclerotic lesions, suggesting a role in NFMs.<br><br>METHODS: The role of miR-147-3p in myeloid cells, with or without enhanced green fluorescent protein expression, on atherosclerosis was examined in Apoe[-/-]Mir147[flox/flox]LysMCre[+] mice. Using live-plaque 4D confocal imaging, we assessed lipid droplets, caspase-3 activation, apoptotic DNA, cholesterol crystal (CC) formation, and mitochondrial function. We also imaged macrophage migration, phagocytosis of apoptotic DNA, and the formation of tubular membrane extensions. We tested mitochondrial function in live-plaque tissue by Seahorse assay. GFP-tagged Argonaute 2 immunoprecipitation combined with prime RNA sequencing was performed using atherosclerotic aortas from Apoe[-/-]LSL-tAgo2/Mir147[flox/flox]LysMCre[+] and control mice. The effect of the galectin-3 inhibitor GB1107 was studied using 4D live-plaque imaging.<br><br>RESULTS: Unlike FMs, NFMs are primarily located in the plaque core and show higher miR-147-3p levels in both mouse and human atherosclerosis. Knocking out Mir147 in myeloid cells increases atherosclerosis, with enhanced CC formation and apoptotic DNA accumulation in necrotic cores. Removing Mir147 reduces mitochondrial activity and elevates caspase-3 activity in NFMs, but not in FMs, and lowers the spare respiratory capacity of plaque macrophages. Moreover, deleting Mir147 impairs NFM uptake of apoptotic DNA, increases extracellular apoptotic DNA, and promotes CC formation. Additionally, Mir147 deficiency in NFMs induces caspase-3 activation in endothelial cells, facilitating the transendothelial extension of FM projections. The Lgals3 transcript, encoding galectin-3, was reduced in the tagged Argonaute 2 immunoprecipitate after Mir147 knockout. A miR-147-3p binding site in the Lgals3 3'-UTR was functionally confirmed. GB1107 treatment reversed the Mir147 knockout effect in macrophages.<br><br>CONCLUSIONS: miR-147-3p reduces atherosclerosis by suppressing the harmful effects of NFMs on endothelial cells and by enhancing their clearance of apoptotic DNA through targeting galectin-3. Increasing miR-147-3p levels might thus slow the expansion of the necrotic core and reduce atherothrombosis caused by NFM-induced endothelial damage.},
}
@article {pmid41939568,
year = {2026},
author = {Sriram, A and Polhemus, L and Rodriguez, W and Singh, D and Kafaie, J},
title = {Opsoclonus-Myoclonus-Ataxia Syndrome Related to Pembrolizumab Treatment for Invasive Ductal Carcinoma: A Case Report.},
journal = {Cureus},
volume = {18},
number = {3},
pages = {e104726},
pmid = {41939568},
issn = {2168-8184},
abstract = {Immune checkpoint inhibitors (ICIs) such as pembrolizumab have become integral to the treatment of various metastatic malignancies. However, their use is associated with a growing spectrum of immune-related adverse events, including rare neurological complications. This report adds to the limited existing literature on ICI-associated opsoclonus-myoclonus-ataxia syndrome (OMAS) and highlights the importance of prompt recognition and multidisciplinary management of such cases. We present a case of a 67-year-old female who presented with rapid, chaotic eye movements, truncal ataxia, and full-body myoclonus two months after beginning a combined immunotherapy and chemotherapy regimen of paclitaxel, carboplatin, and pembrolizumab for triple-negative invasive ductal carcinoma. The case highlights pembrolizumab, an ICI targeting the programmed death-1 receptor, as a cause of adult-onset OMAS. In our discussion, we expand upon the mechanism of action of ICIs, notably the immune pathways underlying their use. We follow this with how this immunotherapy causes damage to peripheral tissues, focusing on the neurological side effects. We finish by discussing currently implemented treatment options for patients who experience these adverse events, and future directions in the field of autoimmune and paraneoplastic neurology. This case describes the onset of OMAS following pembrolizumab therapy in a patient with triple-negative breast cancer, a rare but clinically significant adverse event. As ICIs are increasingly used, clinicians must remain vigilant for uncommon neurological immune-related adverse events. Early recognition and immunosuppressive treatment can mitigate long-term sequelae. This case underscores the need for further research and interdisciplinary awareness in the evolving field of autoimmune and paraneoplastic neurology.},
}
@article {pmid41939661,
year = {2026},
author = {Abarca Ruiz, JW and Suárez Caicedo, MN and Redroban Tufino, EJ and Arteaga Morocho, EA and Corella Sanguil, PH},
title = {Acute Pancreatitis as the Initial Presentation of Metastatic Breast Cancer Due to Malignant Hypercalcemia: A Case Report.},
journal = {Cureus},
volume = {18},
number = {3},
pages = {e104627},
pmid = {41939661},
issn = {2168-8184},
abstract = {Hypercalcemia-induced acute pancreatitis is a rare condition, most commonly associated with primary hyperparathyroidism or advanced malignancies, and represents a metabolic emergency. We report the case of a 63-year-old woman who presented with severe epigastric abdominal pain, constipation, and episodes of disorientation. Laboratory tests revealed elevated pancreatic enzymes and severe hypercalcemia. Acute pancreatitis secondary to hypercalcemia was diagnosed, and normal parathyroid hormone (PTH) levels excluded primary hyperparathyroidism. The presence of anemia, thrombocytopenia, and multiple lytic bone lesions initially suggested multiple myeloma; however, this diagnosis was ruled out due to the absence of monoclonal gammopathy. Further imaging revealed an irregular right breast mass with axillary lymphadenopathy, classified as BI-RADS 5. Tumor markers were markedly elevated, and core needle biopsy confirmed human epidermal growth factor receptor 2 (HER2)-positive invasive ductal carcinoma with bone metastases. Despite intensive treatment with intravenous hydration and zoledronic acid, neurological deterioration occurred; hence, after 25 days of hospitalization, the patient was discharged for home-based palliative care at the family's request. This case highlights the importance of considering metastatic malignancies, particularly breast cancer, in patients with pancreatitis of unclear etiology and severe hypercalcemia.},
}
@article {pmid41926512,
year = {2026},
author = {Li, J and Li, S and Li, C and Chen, Z and Ding, Y},
title = {Prosthetic Loosening in a Total Hip Arthroplasty Patient After Breast Cancer Chemotherapy and Hormonal Therapy: A Case Report.},
journal = {Drug, healthcare and patient safety},
volume = {18},
number = {},
pages = {543323},
doi = {10.2147/DHPS.S543323},
pmid = {41926512},
issn = {1179-1365},
abstract = {BACKGROUND: Studies have shown that there are a lot of risk factors that could cause periprosthetic osteolysis and aseptic loosening, threatening the life-span of the hip prosthesis. Breast cancer is one of the most frequent malignancy in women. However, the use of breast cancer chemotherapy and hormonal therapy has been shown to significantly elevate the risk of osteoporosis. Chemotherapy can systematically suppress the anabolism of various organs, ultimately leading to bone metabolism dysfunction and osteolysis. Aromatase inhibitors (AI) function by inhibiting the conversion of androgens to estrogen, thereby reducing systemic estrogen levels, which is essential for maintaining bone mass; however, prolonged estrogen deprivation can lead to osteoporosis, which has been proven to pose a significant threat to the survival of hip implants.<br><br>CASE PRESENTATION: In this case, the patient suffered hip joint tuberculosis and took intertrochanteric osteotomy procedure at age 24. Seventeen years after, she took Total Hip Arthroplasty (THA). She then undertook chemotherapy and hormonal therapy for breast invasive ductal carcinoma (BI-RADS category III), 1 year after her primary THA. Three years later, she was diagnosed with aseptic loosening of her hip prosthesis. A summary and analysis of her treatment were conducted.<br><br>CONCLUSION: Breast cancer chemotherapy and hormonal therapy might be a threat to the stability of THA prosthesis. More attention should be paid when a Total Hip Arthroplasty patient received chemotherapy and hormonal therapy. Further research is needed to fully understand the impact of breast cancer treatments, as current therapies like hormonal therapy can increase the risk of osteoporosis and fractures.},
}
@article {pmid41899990,
year = {2026},
author = {Wen, W and Qin, J and Chang, Q},
title = {Semi-Supervised Graph Attention Network for Screw Pump Fault Diagnosis: Revealing the Dynamic Coupling of Multi-Source Information.},
journal = {Entropy (Basel, Switzerland)},
volume = {28},
number = {3},
pages = {},
doi = {10.3390/e28030338},
pmid = {41899990},
issn = {1099-4300},
abstract = {The screw pump is a critical device for elevating downhole petroleum to the surface, and screw pump failure can significantly disrupt the production of oil wells. Due to the complex structure of the screw pump, the same pump fault can cause different changes in the monitoring parameters, and different faults can also cause the same parameter change. In consequence of the complexity, it requires a large amount of labeled data for a diagnosis model to achieve fault diagnosis of a screw pump in practical application. Aiming for this kind of condition, we discovered the dynamic coupling effect between multi-source information through detailed research on the collected data of screw pumps. To fully leverage the information dynamic coupling (IDC) effect, a semi-supervised learning graph attention network (SSL-GAT) fault diagnosis method is proposed. This approach integrates the semi-supervised learning framework and graph attention neural network for the fault diagnosis of a screw pump. The experimental validation of the SSL-GAT method demonstrates its outstanding performance in screw pump fault diagnosis.},
}
@article {pmid41821026,
year = {2026},
author = {Möser, C and Prystupa, K and Schön, M and Yurchenko, I and Bódis, KB and Huttasch, M and Michelotti, F and Kupriyanova, Y and Schrauwen-Hinderling, V and Granata, C and Bönhof, GJ and Strom, A and Herder, C and Dörr, D and Trenkamp, S and Heilmann, G and Bobrov, P and Straßburger, K and Szendroedi, J and Cramer, M and Polzin, A and Jung, C and Kelm, M and Burkart, V and Wagner, R and Roden, M and Zaharia, OP},
title = {Cohort profile: The DIabetes and ST-segment Elevation Myocardial Infarction (DISTEMI) Study.},
journal = {Cardiovascular diabetology},
volume = {25},
number = {1},
pages = {},
pmid = {41821026},
issn = {1475-2840},
mesh = {Humans ; *ST Elevation Myocardial Infarction/epidemiology/diagnosis/physiopathology/blood/diagnostic imaging/therapy ; *Diabetes Mellitus, Type 2/diagnosis/blood/epidemiology/physiopathology ; Male ; Prospective Studies ; Middle Aged ; Female ; Biomarkers/blood ; Insulin Resistance ; Longitudinal Studies ; *Blood Glucose/metabolism ; Time Factors ; *Prediabetic State/diagnosis/blood/epidemiology/physiopathology ; Risk Assessment ; Aged ; Prognosis ; Glucose Tolerance Test ; Risk Factors ; Energy Metabolism ; *Non-alcoholic Fatty Liver Disease/epidemiology/diagnosis/blood/physiopathology ; },
abstract = {BACKGROUND: Humans with type 2 diabetes and/or metabolic dysfunction-associated steatotic liver disease (MASLD) are at higher risk of ST-segment elevation myocardial infarction (STEMI) and worse prognosis. However, mechanisms, prognostic factors and risk subtypes in humans with STEMI and (pre)diabetes with or without MASLD, are not fully understood.<br><br>METHODS: The DIabetes and ST-segment Elevation Myocardial Infarction (DISTEMI) study is a prospective longitudinal cohort study, recruiting humans with different degrees of glucose tolerance after recent STEMI. This cohort study has the primary objective to detect changes in glycemia and insulin sensitivity derived from the oral glucose tolerance test (OGTT) and their relationships to cardiac function. Secondary objectives address tissue-specific insulin sensitivity and organ function, focusing on adipose tissue, liver and heart. Exploratory objectives comprise multiomic analyses and measures of mitochondrial function and quality of life. At 2 and 12&#xa0;months after STEMI, participants undergo comprehensive cardiometabolic phenotyping (OGTT, modified Botnia clamp-test, magnetic resonance imaging/spectroscopy/elastography, high-resolution respirometry). Magnetic resonance-based techniques are employed to assess cardiovascular function and structure, adipose tissue distribution, skeletal muscle and hepatic lipid deposition and fibrosis, and hepatic energy metabolism. Exploratory analyses include multiomics of blood, urine, and stool samples. Multiomics analyses shall allow detecting biomarkers for stratification of cardiovascular disease risk. Currently, 100 participants have been included in DISTEMI, of whom 29% have type 2 diabetes.<br><br>CONCLUSION: The DISTEMI study integrates comprehensive cardiometabolic phenomic with multiomic profiling to identify cardiometabolic STEMI subtypes and predictors of outcomes, and to improve precision risk stratification and targeted prevention.<br><br>TRIAL REGISTRATION: NCT05046483.},
}
@article {pmid41890485,
year = {2026},
author = {Rajbongshi, H and Gogoi, M and Goswami, S and Duara, BK},
title = {Diagnostic Role of Shear Wave Elastography for Differentiating Benign and Malignant Breast Lesions With Histopathological Examination (HPE) Correlation.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e104103},
pmid = {41890485},
issn = {2168-8184},
abstract = {Breast cancer is a leading cause of mortality worldwide, with invasive ductal carcinoma being the most common malignant tumor. Ultrasonography (USG) is the initial imaging modality for breast lesions, but its low specificity often necessitates invasive histopathological examination (HPE). Shear wave elastography (SWE) is a novel technique that assesses tissue stiffness non-invasively, providing promising results in differentiating benign and malignant breast lesions. This study evaluates the diagnostic accuracy of SWE combined with B-mode USG in characterizing breast lesions and correlates findings with HPE results. A hospital-based prospective observational study was conducted on 50 female patients aged 18 years and above with breast lesions categorized as Breast Imaging-Reporting and Data System (BI-RADS) 3 or higher. SWE demonstrated a sensitivity of 72.72%, a specificity of 85.71%, and a diagnostic accuracy of 80%, highlighting its potential to reduce unnecessary biopsies. This study concludes that SWE is a valuable adjunct to conventional USG for breast lesion evaluation.},
}
@article {pmid41894312,
year = {2026},
author = {Mohamed, Z and Abdulkarim, A and Abdullah, AR and Al-Azab, M and Baklola, M},
title = {Molecular subtypes of breast cancer in Libyan women and their clinicopathological associations: A retrospective observational study from eastern Libya.},
journal = {Medicine},
volume = {105},
number = {13},
pages = {e48215},
doi = {10.1097/MD.0000000000048215},
pmid = {41894312},
issn = {1536-5964},
mesh = {Humans ; Female ; Libya/epidemiology ; Retrospective Studies ; *Breast Neoplasms/pathology/epidemiology/genetics/classification ; Middle Aged ; Adult ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; Aged ; Ki-67 Antigen/metabolism ; },
abstract = {Breast cancer (BC) is the most commonly diagnosed cancer among women globally, with significant regional variations in its molecular subtypes, clinical presentation, and management. Despite advancements in oncology, limited data exist on the molecular and clinical characteristics of BC in Libya. This study aims to analyze the prevalence of molecular subtypes, clinicopathological features, and treatment patterns among Libyan women with BC at Tobruk Medical Center. This retrospective observational study included BC patients diagnosed between January 2019 and December 2020 at Tobruk Medical Center. Demographic, clinical, pathological, and treatment-related data were extracted from medical records. Molecular subtyping was based on immunohistochemical assessment of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67. Statistical analyses were performed using SPSS version 28 (IBM Corp., Armonk). Among 115 patients analyzed, the median age at diagnosis was 46 years. Invasive ductal carcinoma accounted for 89.6% of cases, with grade II tumors being the most common (69.6%). Luminal B was the predominant molecular subtype (67.8%), followed by luminal A (14.8%), HER2-enriched (10.4%), and triple-negative BC (7.0%). Advanced-stage diagnoses (stage III and IV) were observed in 57.4% of cases. Hormone receptor positivity was detected in 82.6%, and HER2 positivity in 25.2% of cases. This study highlights the high prevalence of advanced-stage BC and the predominance of the aggressive luminal B subtype in Libya. Targeted early detection programs and improved treatment access are urgently needed to address these challenges.},
}
@article {pmid41703656,
year = {2026},
author = {Bekai, C and Stirling, M},
title = {Metastatic breast cancer presenting with dyspeptic symptoms: a case report.},
journal = {Journal of medical case reports},
volume = {20},
number = {1},
pages = {},
pmid = {41703656},
issn = {1752-1947},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Aged ; *Dyspepsia/etiology ; *Stomach Neoplasms/secondary/diagnostic imaging/complications/diagnosis ; *Carcinoma, Lobular/secondary/pathology/diagnostic imaging ; *Bone Neoplasms/secondary/diagnostic imaging ; Diagnosis, Differential ; Melena/etiology ; },
abstract = {BACKGROUND: Breast cancer is among the most commonly diagnosed malignancies worldwide. While distant metastases typically involve the bone, lung, liver, and brain, metastasis to the gastrointestinal tract is uncommon and occurs disproportionately in invasive lobular carcinoma (ILC). The clinical presentation is often nonspecific, which can delay diagnosis. This case presents the synchronous diagnosis of both primary breast cancer and gastric metastasis.<br><br>CASE PRESENTATION: A 78-year-old woman presented with chronic belching, dyspepsia, and intermittent melena. Initial treatment and improvement with proton pump inhibitor therapy, suggested a primary gastrointestinal disorder. However, gastric biopsy confirmed metastatic invasive lobular carcinoma, and subsequent imaging revealed diffuse bony metastases.<br><br>CONCLUSIONS: This case highlights the synchronous diagnosis of gastric metastases originating from invasive lobular carcinoma with its associated diagnostic complexities and the limitations&#xa0;of traditional imaging modalities in detecting such metastases. Early recognition and accurate diagnosis are crucial for guiding appropriate treatment and improving patient outcomes. Therefore, we present a case that suggests considering breast cancer metastasis in the differential diagnosis for patients presenting with nonspecific gastrointestinal symptoms, even in the absence of breast-related complaints, is a reasonable clinical approach.},
}
@article {pmid40875574,
year = {2026},
author = {Perez, A and Schaverien, MV and George-Palop, M and Chang, EI and Barcenas, CH and Viola, GM},
title = {The Impact of Vascularized Lymph Node Transfer in Reducing the Rate of Cellulitis in Breast Cancer-Related Lymphedema.},
journal = {Plastic and reconstructive surgery},
volume = {157},
number = {4},
pages = {463e-470e},
doi = {10.1097/PRS.0000000000012412},
pmid = {40875574},
issn = {1529-4242},
mesh = {Humans ; Female ; *Cellulitis/prevention &amp; control/etiology/epidemiology ; Middle Aged ; Aged ; *Breast Cancer Lymphedema/surgery/etiology/complications ; Mastectomy/adverse effects ; Adult ; *Lymph Nodes/transplantation/blood supply ; Retrospective Studies ; Lymph Node Excision/adverse effects ; *Breast Neoplasms/surgery/complications ; Young Adult ; Treatment Outcome ; Upper Extremity ; *Lymphedema/etiology/surgery ; Follow-Up Studies ; },
abstract = {BACKGROUND: Poorly managed breast cancer-related lymphedema may lead to recurrent cellulitis. Advances in the management of lymphedema have evolved beyond conservative decongestive therapy to include vascularized lymph node transfer (VLNT). In this article, the authors analyze the impact of VLNT in the reduction of upper extremity cellulitis in breast cancer survivors.<br><br>METHODS: The authors reviewed all patients at their institution who had breast cancer, underwent mastectomy, experienced upper extremity lymphedema, and proceeded with VLNT from 2017 to 2021. Patients were included if they had 1 or more episodes of cellulitis within the year before VLNT and were followed up for at least 12 months.<br><br>RESULTS: The authors included 66 patients who fulfilled their strict inclusion criteria, with a median age of 57 years (interquartile range, 23 to 76 years). All patients were female, and most were White (88%), with a mean &#xb1; SD body mass index of 29.4 &#xb1; 6.7 kg/m 2 . Many presented with invasive ductal carcinoma (82%), had axillary lymph node dissection (98%), and received chemotherapy (94%) and radiation therapy (86%). VLNT was performed at a median of 92 months after mastectomy (interquartile range, 32 to 156 months). Overall, 58 (88%) patients remained infection-free with an infection rate decrease from an average of 2.27 before the index VLNT to 0.17 (P < 0.0001) after VLNT.<br><br>CONCLUSIONS: VLNT is associated with significantly decreased cellulitis rates. It should be considered as part of the treatment for infectious diseases of recurrent upper extremity cellulitis caused by breast cancer-related lymphedema with no adequate clinical improvement from conservative management alone.},
}
@article {pmid41880302,
year = {2026},
author = {Nath, S and Illa, SK and Worku, D and Mukherjee, S and Mukherjee, A and Yata, VK},
title = {Composite selection signal analysis: Uncovering candidate genes and quantitative trait loci in Indian sheep breeds.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0344299},
doi = {10.1371/journal.pone.0344299},
pmid = {41880302},
issn = {1932-6203},
mesh = {Animals ; *Quantitative Trait Loci ; Polymorphism, Single Nucleotide ; India ; Breeding ; *Selection, Genetic ; Sheep/genetics ; },
abstract = {Selective pressures, both natural and artificial, have significantly influenced the genomic architecture of domesticated sheep. Understanding their underlying molecular mechanisms is critical for developing efficient breeding programs to conserve and improve economically important traits in native breeds. In this study, we analysed high-density 50K SNP data from three Indigenous sheep breeds: Chanthangi (CHA, n = 29), Garole (GAR, n = 24), and Deccani (IDC, n = 26), each native to diverse climatic regions of India. We implemented a novel SNP-based de-correlated composite of multiple signals (DCMS) statistic, which integrates p-values from five selection metrics viz., FST, H1, H12, Tajima's D, and nucleotide diversity (π) into a unified measure. The SNP-based DCMS approach offers finer resolution and complements window-based methods by enabling more precise localisation of selection signals and candidate genes. Multiple testing correction was applied at a False Discovery Rate (FDR) threshold of <5% to detect significant genomic regions. Comprehensive gene and quantitative trait loci (QTL) annotation and enrichment analysis of these regions were also performed for each breed. The DCMS analysis identified 21, 10, and 14 novel and breed-specific putative genes in the Chanthangi, Garole, and Deccani breeds, respectively, as well as 10, 28, and 13breed-specific QTL regions. The identified genes and QTLs are associated with diverse phenotypic traits, including growth and muscle development (CNTNAP5, DOCK3), reproduction (TCERG1L, BUB1, UNC5C, C2CD5, BBX), wool trait (TPPP3, P2RY6, FGF10, POU2F1, FAM168A), disease resistance (MTSS1, B4GALNT3), environment adaptation (TRMT12, MAPKAPK3), domestication (LRRC36). The QTLs identified are associated with body conformation (body measurements and bone area), production (milk fat yield), reproduction (total lambs born), disease resistance (hemonchus resistance, foot rot, and pneumonia susceptibility), and health (platelet count and entropion). Our SNP-based DCMS method enabled high-resolution detection of breed-specific selection signatures. It facilitated the discovery of both known and novel genomic regions, candidate genes, and QTLs unique to Indian sheep breeds. This comprehensive approach provides valuable insights into the molecular mechanisms underlying economically important traits and offers a robust foundation for targeted genetic improvement and conservation of indigenous sheep breeds.},
}
@article {pmid41605126,
year = {2026},
author = {Watanabe, R and Miura, N and Kikugawa, T and Saika, T and Haffner, MC and Nelson, PS},
title = {Molecular pathology of rare histologic variants and treatment-resistant lineages of prostate cancer.},
journal = {Urologic oncology},
volume = {44},
number = {4},
pages = {110987},
doi = {10.1016/j.urolonc.2025.110987},
pmid = {41605126},
issn = {1873-2496},
mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/genetics ; Pathology, Molecular/methods ; },
abstract = {Rare histological variants of prostate cancer-including ductal adenocarcinoma, intraductal carcinoma of the prostate (IDC-P), neuroendocrine carcinoma, basal cell/adenoid cystic carcinoma, squamous cell carcinoma, sarcomatoid carcinoma, and stromal tumors-exhibit highly diverse biological behaviors and distinct molecular features. Accurate pathological recognition is essential, as these entities frequently diverge from conventional acinar adenocarcinoma in morphology, genomic alterations, therapeutic responsiveness, and clinical outcomes. Intraductal carcinoma of the prostate (IDC-P) and ductal adenocarcinoma often display genomic instability and aggressive clinical behavior, including enrichment for homologous recombination repair (HRR) defects and hypoxia-related pathways. Neuroendocrine subtypes, including de novo and treatment-related NEPC as well as double-negative prostate cancer (DNPC), are characterized by androgen receptor (AR) independence, RB1/TP53 loss, low prostate-specific antigen (PSA) production, and poor prognosis, reflecting lineage plasticity under therapeutic pressure. Other rare tumors-such as basal cell carcinoma/adenoid cystic carcinoma, squamous cell carcinoma, and stromal tumors (STUMP and prostatic stromal sarcoma)-demonstrate unique pathological patterns and limited responsiveness to standard systemic therapies, underscoring the importance of tailored diagnostic and management strategies. This review integrates the histopathological, molecular, and emerging spatial transcriptomic insights across this spectrum of rare and treatment-resistant prostate cancer subtypes. By highlighting shared mechanisms such as genomic instability, androgen receptor (AR) pathway bypass, and microenvironmental remodeling, we outline key diagnostic considerations and evolving therapeutic implications relevant to precision oncology.},
}
@article {pmid41835638,
year = {2026},
author = {Mainer, S and Lachmayr, H and Lemon, B and Killorin, W},
title = {Breast Cancer Metastasis with a Ureteral Obstruction and Bladder Mass.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e103428},
pmid = {41835638},
issn = {2168-8184},
abstract = {Breast cancer is the most common cause of cancer mortality in females globally, and a significant proportion of patients develop metastatic disease. Common metastatic sites of breast cancer include bone, lung, liver, and brain. Secondary neoplasms (metastases from other primary sites) represent a minority of all malignant bladder tumors In this report, we describe a case of breast cancer metastasis with ureteral obstruction and bladder mass in a 60-year-old African-American female. For over a decade, this patient was asymptomatic and had been under surveillance following bilateral radical mastectomy for invasive ductal carcinoma (IDC) with adjuvant chemoradiotherapy. Unrelated imaging revealed an incidental finding of right hydronephrosis. Subsequent cystoscopy revealed a bladder mass obstructing the right ureteral orifice. Transurethral resection of a bladder tumor and ureteral stent placement were performed, and the pathology findings favored metastatic breast cancer. The details of the case are intended to help further knowledge of urinary bladder metastases. This case is unusual in that the patient was asymptomatic, her breast cancer type is associated with a lower incidence of bladder metastases, and the bladder was the solitary location of metastasis.},
}
@article {pmid41764344,
year = {2026},
author = {Williams, AE and Hoffmann, EJ and Inman, DR and Gari, MK and Zhou, C and Burkel, BM and Haidar, N and Pan, Y and Halambeck, M and Moore, BN and Wisinski, KB and McGregor, SM and Kerr, SC and Arendt, LM and Ponik, SM},
title = {Obesity and breast density enhance immune exclusion in the primary tumor microenvironment and promote breast cancer metastasis.},
journal = {Oncogene},
volume = {45},
number = {11},
pages = {1057-1064},
pmid = {41764344},
issn = {1476-5594},
support = {R01CA179556, R01CA206458, U54CA268069//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; R01CA179556, R01CA227542//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; P30CA014520//University of Wisconsin Carbone Cancer Center (UW Carbone Cancer Center)/ ; GT1453//Howard Hughes Medical Institute (HHMI)/ ; R25GM083252//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
mesh = {*Tumor Microenvironment/immunology ; Female ; Animals ; Humans ; *Breast Neoplasms/pathology/immunology ; Mice ; *Obesity/immunology/pathology/complications ; *Breast Density ; Risk Factors ; Neoplasm Metastasis ; Macrophages/immunology/pathology ; Disease Models, Animal ; Lung Neoplasms/secondary/immunology ; *Carcinoma, Ductal, Breast/pathology/immunology ; T-Lymphocytes/immunology ; },
abstract = {Recent epidemiological studies suggest that breast density and obesity together increase breast cancer risk. Although these risk factors have been explored individually, little is known about how they combine to alter the tumor immune microenvironment (TIME) and promote disease progression. To address this gap, we developed a murine model of both risk factors. Spatial analysis of the TIME revealed macrophages and T-cells predominantly localized in the stroma of both risk factor groups, indicating an immune exclusion phenotype. Mice with dual risk factors had significantly increased lung metastasis. To establish the human relevance of this model, we interrogated the TIME in biopsies from 158 patients with invasive ductal carcinoma and 10 years of follow-up data. We found that patients with both risk factors had the highest incidence of metastasis (45%). Furthermore, spatial immune profiling revealed exacerbated stromal localization of macrophages and T-cells in the dual risk factor group that progressed to metastasis. Overall, we uncovered an immune exclusion phenotype in metastatic breast cancer patients with obesity and breast density, and we present a relevant murine model that parallels human disease. The murine model will enable future investigation into therapies that intercept the mechanisms by which dual risk factors modulate the TIME.},
}
@article {pmid41822488,
year = {2026},
author = {Song, C and Quan, Y and Shan, Y and Chen, Y and Du, J and Li, K and Li, N},
title = {Prognostic significance and regulatory role of ACOT7 in the tumor immune microenvironment of breast invasive ductal carcinoma: a multi-omics analysis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1735908},
pmid = {41822488},
issn = {1664-3224},
mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; Female ; *Breast Neoplasms/immunology/genetics/mortality/pathology/metabolism ; Prognosis ; *Carcinoma, Ductal, Breast/immunology/genetics/mortality/pathology/metabolism ; Gene Expression Regulation, Neoplastic ; *Biomarkers, Tumor/genetics ; Protein Interaction Maps ; *Thiolester Hydrolases/genetics/metabolism ; Computational Biology/methods ; Gene Expression Profiling ; Kaplan-Meier Estimate ; Multiomics ; },
abstract = {BACKGROUND: Invasive Ductal Carcinoma (IDC), which is the most common histological subtype of breast cancer, is highly aggressive and progresses rapidly. Acyl-CoA thioesterase 7 (ACOT7) is a key regulator of cell survival, the cell cycle, and lipid and glucose metabolism. However, the mechanism of ACOT7 in IDC is still unclear. Our study aims to investigate the clinical significance of ACOT7 in IDC.<br><br>METHODS: A comparative analysis of ACOT7 expression in IDC and matched normal tissues was performed using the limma R package on datasets from GEO and TCGA. Prognostic evaluation was conducted using Kaplan-Meier survival curves from the Kaplan-Meier plotter. Furthermore, a protein-protein interaction (PPI) network of ACOT7 was constructed by GeneMANIA, and the correlation between ACOT7 expression and the level of tumor immune infiltration was explored via the TIMER database. In order to further analyze the biological functions of ACOT7, we performed Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Gene Set Enrichment Analysis (GSEA) using the clusterProfiler package. To validate this, we profiled ACOT7 mRNA expression across clinical samples (tumor and adjacent normal) and in vitro models (cell lines) via Real-Time quantitative Polymerase Chain Reaction (RT-qPCR).<br><br>RESULTS: Bioinformatic analysis of public databases revealed that ACOT7 mRNA expression was significantly upregulated in IDC patients compared to normal tissues. Elevated ACOT7 expression was associated with poorer overall survival, a finding further validated in cell lines and clinical tissue samples. Furthermore, ACOT7 transcriptional levels showed a significant correlation with the degree of tumor immune infiltration. Functional enrichment analysis indicated that ACOT7 is primarily involved in cancer-related regulation, autoimmune diseases, and multiple metabolic pathways.<br><br>CONCLUSION: Our study indicates that elevated ACOT7 expression is a significant marker of adverse clinical outcomes. This effect it likely mediated through the remodeling of the tumor immune microenvironment and the reprogramming of metabolic pathways, which collectively fuel the malignant procession of IDC. These results provide a solid theoretical foundation for targeting ACOT7 as both a prognostic biomarker and a potential therapeutic target in IDC.},
}
@article {pmid37671834,
year = {2023},
author = {Giroud, M and Kotschi, S and Kwon, Y and Le Thuc, O and Hoffmann, A and Gil-Lozano, M and Karbiener, M and Higareda-Almaraz, JC and Khani, S and Tews, D and Fischer-Posovszky, P and Sun, W and Dong, H and Ghosh, A and Wolfrum, C and Wabitsch, M and Virtanen, KA and Blüher, M and Nielsen, S and Zeigerer, A and García-Cáceres, C and Scheideler, M and Herzig, S and Bartelt, A},
title = {The obesity-linked human lncRNA AATBC stimulates mitochondrial function in adipocytes.},
journal = {EMBO reports},
volume = {24},
number = {10},
pages = {e57600},
pmid = {37671834},
issn = {1469-3178},
support = {//Helmholtz Zentrum M&#xfc;nchen (Helmholtz Centre Munich, German Research Center for Environmental Health)/ ; //Alexander von Humboldt-Stiftung (AvH)/ ; FI1700/7#x2010;1//Deutsche Forschungsgemeinschaft (DFG)/ ; TE912/2#x2010;2//Deutsche Forschungsgemeinschaft (DFG)/ ; TRR205//Deutsche Forschungsgemeinschaft (DFG)/ ; SFB1123//Deutsche Forschungsgemeinschaft (DFG)/ ; //Deutsches Zentrum f&#xfc;r Herz-Kreislaufforschung (DZHK)/ ; //EC | H2020 | PRIORITY 'Excellent science' | H2020 European Research Council (ERC)/ ; },
mesh = {Humans ; *Obesity/genetics/metabolism/pathology ; *Mitochondria/metabolism/genetics ; *RNA, Long Noncoding/genetics/metabolism ; Animals ; *Adipocytes/metabolism ; Mice ; Thermogenesis/genetics ; Leptin/blood ; Male ; Adipose Tissue/metabolism ; Female ; },
abstract = {Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, thermogenic adipocytes are linked to cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this plasticity could help improving metabolism. Here, we show that the lncRNA Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Comparing transcriptional profiles of human adipose tissues and cultured adipocytes we discovered that AATBC was enriched in thermogenic conditions. Using primary and immortalized human adipocytes we found that AATBC enhanced the thermogenic phenotype, which was linked to increased respiration and a more fragmented mitochondrial network. Expression of AATBC in adipose tissue of mice led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, BMI, and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.},
}
@article {pmid37592911,
year = {2023},
author = {Rosa, C and Singh, P and Chen, P and Sinha, A and Claës, A and Preiser, PR and Dedon, PC and Baumgarten, S and Scherf, A and Bryant, JM},
title = {Cohesin contributes to transcriptional repression of stage-specific genes in the human malaria parasite.},
journal = {EMBO reports},
volume = {24},
number = {10},
pages = {e57090},
pmid = {37592911},
issn = {1469-3178},
support = {MOE2018-T2-2-131//Academic Research Fund of the Ministry of Education, Singapore/ ; ANR-21-CE15-0010 PlasmoVarOrg//Agence Nationale de la Recherche (ANR)/ ; ANR-11-LABEX-0024-01 ParaFrap//Agence Nationale de la Recherche (ANR)/ ; //Alliance Fran&#xe7;aise contre les Maladies Parasitaires (ParaFrap)/ ; PlasmoSilencing 670301//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; PlasmoEpiRNA 947819//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; EMBO ALTF 1444-2016//European Molecular Biology Organization (EMBO)/ ; EMBO ALTF 632-2018//European Molecular Biology Organization (EMBO)/ ; EMBO ALTF 180-2015//European Molecular Biology Organization (EMBO)/ ; //Institut Pasteur/ ; 6.11.18//Merlion Project/ ; //Ministry of Education, Singapore/ ; //National Research Foundation Singapore (NRF)/ ; },
mesh = {*Plasmodium falciparum/genetics/growth &amp; development/metabolism ; *Chromosomal Proteins, Non-Histone/metabolism/genetics ; Cohesins ; *Cell Cycle Proteins/metabolism/genetics ; Humans ; *Protozoan Proteins/genetics/metabolism ; *Transcription, Genetic ; Promoter Regions, Genetic ; Erythrocytes/parasitology ; *Gene Expression Regulation ; Life Cycle Stages/genetics ; Malaria, Falciparum/parasitology ; Chromatin/metabolism ; Gene Expression Regulation, Developmental ; Protein Binding ; },
abstract = {The complex life cycle of the human malaria parasite, Plasmodium falciparum, is driven by specific transcriptional programs, but it is unclear how most genes are activated or silenced at specific times. There is an association between transcription and spatial organization; however, the molecular mechanisms behind genome organization are unclear. While P. falciparum lacks key genome-organizing proteins found in metazoans, it has all core components of the cohesin complex. To investigate the role of cohesin in P. falciparum, we functionally characterize the cohesin subunit Structural Maintenance of Chromosomes protein 3 (SMC3). SMC3 knockdown during early stages of the intraerythrocytic developmental cycle (IDC) upregulates a subset of genes involved in erythrocyte egress and invasion, which are normally expressed at later stages. ChIP-seq analyses reveal that during the IDC, SMC3 enrichment at the promoter regions of these genes inversely correlates with gene expression and chromatin accessibility. These data suggest that SMC3 binding contributes to the repression of specific genes until their appropriate time of expression, revealing a new mode of stage-specific gene repression in P. falciparum.},
}
@article {pmid37560809,
year = {2023},
author = {Alfaro, AJ and Dittner, C and Becker, J and Loft, A and Mhamane, A and Maida, A and Georgiadi, A and Tsokanos, FF and Klepac, K and Molocea, CE and El-Merahbi, R and Motzler, K and Geppert, J and Karikari, RA and Szendrödi, J and Feuchtinger, A and Hofmann, S and Karaca, S and Urlaub, H and Berriel Diaz, M and Melchior, F and Herzig, S},
title = {Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism.},
journal = {EMBO reports},
volume = {24},
number = {10},
pages = {e55981},
pmid = {37560809},
issn = {1469-3178},
support = {314061271//Deutsche Forschungsgemeinschaft (DFG)/ ; 329628492//Deutsche Forschungsgemeinschaft (DFG)/ ; A01//Deutsche Forschungsgemeinschaft (DFG)/ ; //Edith-Haberland-Wagner Stiftung/ ; 2020 EKSE.23//Else K&#xf6;ner-Fresenius-Stiftung (EKFS)/ ; ZT-0026//Helmholtz Gemeinschaft/ ; //DKFZ-ZMBH Alliance/ ; //Open Access funding enabled and organized by Projekt DEAL/ ; },
mesh = {Animals ; Prospero-Related Homeobox 1 Protein ; *Fasting/metabolism ; *Tumor Suppressor Proteins/metabolism/genetics ; *Liver/metabolism ; *Sumoylation ; Mice ; *Cholesterol/metabolism ; *Homeodomain Proteins/metabolism/genetics ; Hepatocytes/metabolism ; Obesity/metabolism ; Humans ; Male ; Mice, Inbred C57BL ; Diet, High-Fat ; },
abstract = {Accumulation of excess nutrients hampers proper liver function and is linked to nonalcoholic fatty liver disease (NAFLD) in obesity. However, the signals responsible for an impaired adaptation of hepatocytes to obesogenic dietary cues remain still largely unknown. Post-translational modification by the small ubiquitin-like modifier (SUMO) allows for a dynamic regulation of numerous processes including transcriptional reprogramming. We demonstrate that specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 is highly SUMOylated on lysine 556 in the liver of ad libitum and refed mice, while this modification is abolished upon fasting. In the context of diet-induced obesity, Prox1 SUMOylation becomes less sensitive to fasting cues. The hepatocyte-selective knock-in of a SUMOylation-deficient Prox1 mutant into mice fed a high-fat/high-fructose diet leads to a reduction of systemic cholesterol levels, associated with the induction of liver bile acid detoxifying pathways during fasting. The generation of tools to maintain the nutrient-sensitive SUMO-switch on Prox1 may thus contribute to the development of "fasting-based" approaches for the preservation of metabolic health.},
}
@article {pmid41804625,
year = {2025},
author = {Vasari, L and Špoljarić Carević, S and Tomić Babić, L and Bakula, M},
title = {A Rare Case of Paraneoplastic Raynaud's Phenomenon and Uveal Melanoma.},
journal = {Acta dermatovenerologica Croatica : ADC},
volume = {33},
number = {2},
pages = {89-91},
pmid = {41804625},
issn = {1847-6538},
mesh = {Humans ; *Melanoma/complications/diagnosis ; *Raynaud Disease/etiology/diagnosis ; Middle Aged ; Female ; Uveal Melanoma ; *Uveal Neoplasms/complications/diagnosis ; *Paraneoplastic Syndromes ; },
abstract = {Raynaud's phenomenon (RP) presents as acral skin pallor, cyanosis, and erythema, usually after cold exposure or emotional stress. Symptoms of RP affect 3-5% of the general population, with the incidence four times higher in women than in men. Paraneoplastic RP is extremely rare and is thought to involve plasma hyperviscosity and blood hypercoagulability, which are present in patients with malignant diseases. Paraneoplastic RP often presents abruptly and, besides changes in skin color, it includes erosions, ulcerations, and necrosis, resulting in severe pain. We present a case of a 62-year-old female patient who suddenly developed symptoms of RP, characterized by periodic skin pallor without erosions or associated pain in all fingers, lasting 10-15 minutes after cold exposure. She was diagnosed with uveal melanoma three months prior and was also in a 14-year remission from invasive ductal carcinoma. Investigations confirmed positive antinuclear antibodies (ANA) with PCNA (proliferating cell nuclear antigen) and myositis-specific antibodies including anti-Jo, anti-mitochondrial antibody (AMA-M2), and anti-benzylpenicilloyl antibody (BPO).},
}
@article {pmid41443500,
year = {2026},
author = {Sekiya, N and Okamoto, K and Fukushima, K and Hosoda, T and Takahashi, K and Gu, Y},
title = {Prognostic stratification in cancer candidemia under routine infectious disease consultation: Palliative Prognostic Index identifies patients with favorable short-term outcomes.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {164},
number = {},
pages = {108338},
doi = {10.1016/j.ijid.2025.108338},
pmid = {41443500},
issn = {1878-3511},
mesh = {Humans ; Male ; Female ; *Neoplasms/complications/mortality ; Retrospective Studies ; *Candidemia/mortality/diagnosis/drug therapy ; Aged ; Middle Aged ; Prognosis ; Referral and Consultation ; Aged, 80 and over ; Palliative Care ; Japan/epidemiology ; Candida/isolation &amp; purification/classification ; },
abstract = {OBJECTIVES: Although consultations with infectious disease physicians (IDC) improve adherence to guidelines and reduce mortality in candidemia, data on mortality risk during routine IDC are scarce, especially in cancer patients.<br><br>METHODS: This retrospective cohort study included cancer patients with candidemia between January 2013 and December 2023 at a Japanese cancer center and assessed the European Confederation of Medical Mycology Quality of Clinical Candidaemia Management (EQUAL) score and factors associated with 30-day mortality during routine IDC using Firth's penalized likelihood logistic regression.<br><br>RESULTS: Of 227 patients with candidemia, 197 were included in the final analysis. Most cases were hospital-acquired (91%), and the 30-day mortality was 28%. Solid tumors (78%) and central venous catheter placement (82%) were common. The most frequent species were Candida albicans (37%), C. parapsilosis (23%), and C. glabrata (20%). The median EQUAL score with and without CVC placement was 22 (interquartile range [IQR]: 20-22) and 19 (IQR: 17-19), respectively. Factors associated with 30-day mortality were the Palliative Prognostic Index (PPI) score (adjusted odds ratio [aOR]: 14.64; 95% confidence interval [CI]: 6.21-38.51; P < .001) and the EQUAL score (aOR: 0.019; 95%CI: 0.003-0.073; P < .001). These findings were consistent in patients with solid tumors. Patients with a low PPI score (< 4) had a 30-day mortality of 10.9%.<br><br>CONCLUSIONS: The PPI score before candidemia onset independently predicted mortality during routine IDC in cancer patients. These results highlight IDC mortality benefits stratified by PPI and may stimulate discussion about ID's role in end-of-life cancer care practice.},
}
@article {pmid41776715,
year = {2026},
author = {De Coster, I and Leroux-Roels, I and Withanage, K and Suykens, L and D'Onofrio, V and Leroux-Roels, G and van Damme, P and Ciarlet, M and Adams, EM and Rida, W and Wen, J and MacDonald, M and Price, J and Kanesa-Thasan, N},
title = {A first-in-human Phase 1/1b randomized trial evaluating the safety and immunogenicity of a respiratory syncytial virus (RSV) virus-like particle subunit vaccine (IVX-121) in healthy young and older adults.},
journal = {Human vaccines &amp; immunotherapeutics},
volume = {22},
number = {1},
pages = {2633021},
pmid = {41776715},
issn = {2164-554X},
mesh = {Humans ; Middle Aged ; Male ; Female ; Aged ; Adult ; *Respiratory Syncytial Virus Vaccines/immunology/adverse effects/administration &amp; dosage ; Antibodies, Viral/blood ; *Respiratory Syncytial Virus Infections/prevention &amp; control/immunology ; Adolescent ; Young Adult ; Vaccines, Subunit/immunology/administration &amp; dosage/adverse effects ; Adjuvants, Immunologic/administration &amp; dosage ; *Respiratory Syncytial Virus, Human/immunology ; *Immunogenicity, Vaccine ; *Vaccines, Virus-Like Particle/immunology/administration &amp; dosage/adverse effects ; Injections, Intramuscular ; Aluminum Hydroxide/administration &amp; dosage ; Antibodies, Neutralizing/blood ; Healthy Volunteers ; Double-Blind Method ; },
abstract = {Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease in all age groups, with substantial burden in older adults. Here, we report the safety and immunogenicity of IVX-121, an investigational virus-like particle vaccine against RSV. This Phase 1/1b trial (EudraCT number: 2020-003633-38) randomized 90 healthy young (18-45 y of age; Phase 1) and 130 older adults (60-75 y of age; Phase 1b) to receive a single intramuscular injection of IVX-121 at low (25 µg), medium (75 µg), or high (250 µg) dose, with/without the adjuvant aluminum hydroxide (Al[OH]3), or placebo. Outcomes were assessed through Day 180. Older adult participants who had received IVX-121 or placebo could continue into an extension study in which safety was assessed for an additional 6 months before receiving IVX-121 (75 µg, unadjuvanted, open-label) on Day 365; safety and immunogenicity were assessed up to Day 546. Adverse reactions were generally mild, and there were no vaccine-related serious adverse events. All IVX-121 dose levels and formulations boosted preexisting RSV neutralizing antibody (nAb) responses. Although not statistically powered to compare treatment groups, there was no clear dose response and the adjuvant Al(OH)3 did not appear to improve immunogenicity. For both age groups, IVX-121 induced nAbs against RSV A and B, which remained above baseline levels for at least 6 months. A second dose of IVX-121 in older adults elicited a modest increase in nAbs against RSV A but not RSV B. Overall, IVX-121 had a favorable safety profile and induced immune responses against RSV in young and older adults.},
}
@article {pmid41702510,
year = {2026},
author = {Vu, ATT and Shrestha, P and Le Thi, TH and Giri, A and Pham, KY and Nguyen, TTK and Cho, J and Kweon, S and Lee, NK and Hong, IS and Kwon, TK and Kang, JS and Jeong, JH and Yook, S},
title = {Protein corona-guided delivery of dextran-PLGA NPs for enhanced dendritic cell uptake, maturation and improved cancer immunotherapy.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {392},
number = {},
pages = {114733},
doi = {10.1016/j.jconrel.2026.114733},
pmid = {41702510},
issn = {1873-4995},
mesh = {Animals ; *Dendritic Cells/immunology/metabolism/drug effects ; *Dextrans/administration &amp; dosage/chemistry/pharmacokinetics ; *Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Immunotherapy/methods ; *Nanoparticles/administration &amp; dosage/chemistry ; Mice, Inbred C57BL ; *Protein Corona/metabolism ; Humans ; Mice ; Cell Line, Tumor ; Female ; Melanoma, Experimental/therapy/immunology ; Tissue Distribution ; },
abstract = {The formation of a protein corona (PC) significantly influences the behavior of nanoparticles (NPs) in biological fluids; however, its impact on immune modulation and therapeutic efficacy has not been completely understood. The dextran coating of NPs has demonstrated promising effects, including complement system activation and enhanced immune cell uptake. The stimulator of interferon genes (STING) pathway plays a vital role in coordinating innate and adaptive immunity, making STING agonists attractive candidates for cancer immunotherapy. In this study, we developed dextran-coated PLGA nanoparticles loaded with SR717 (Dex-PLGA@SR717 NPs) for enhanced uptake by immature dendritic cells (iDCs) and for promoting tumor-targeted immune activation. Following incubation with human serum (HS), Dex-PLGA NPs formed a PC enriched in the complement component C3, which resulted in superior cellular internalization compared with uncoated PLGA NPs. The significant role of Dex-PLGA@SR717 NPs in promoting iDC maturation and enhancing antigen presentation was confirmed through in vitro studies. This facilitated robust T cell activation and cytotoxicity against B16F10 melanoma cells. Biodistribution analysis revealed preferential accumulation of Dex-PLGA@SR717 NPs in immune-related organs, such as the spleen and lymph nodes, further supporting their immunostimulatory potential. In a murine tumor model, intravenous administration of Dex-PLGA@SR717 NPs (10 mg/kg SR717) was observed to effectively suppressed tumor growth by eliciting a potent antitumor immune response. These findings highlight the potential of Dex-PLGA@SR717 NPs as a promising immunotherapeutic nanoplatform for enhancing dendritic cell-mediated cancer treatment.},
}
@article {pmid41719937,
year = {2026},
author = {Westermann, S and Bennühr, BC and Fumo, AR and Rohm, M and Hiller, K},
title = {Muscle-immune metabolic crosstalk: shared pathways in cachexia and exercise.},
journal = {Current opinion in biotechnology},
volume = {98},
number = {},
pages = {103455},
doi = {10.1016/j.copbio.2026.103455},
pmid = {41719937},
issn = {1879-0429},
mesh = {*Cachexia/metabolism/immunology ; Humans ; *Exercise/physiology ; *Muscle, Skeletal/metabolism/immunology ; Animals ; Signal Transduction ; *Immune System/metabolism ; },
abstract = {Skeletal muscle and the immune system continuously exchange metabolites and signals that are essential for homeostasis. Disruption of this communication, such as during infection, inflammation, or cancer, triggers cachexia, a severe wasting syndrome characterized by altered amino acid flux, mitochondrial dysfunction, and systemic energy imbalance. By contrast, regular exercise activates overlapping pathways but directs them toward regeneration and hypertrophy, supported by controlled cytokine release and metabolite exchange. This review outlines the metabolic reprogramming that underlies muscle-immune crosstalk in cachexia and exercise, emphasizing how identical mediators, including interleukin-6, can promote either catabolism or adaptation depending on context. Understanding these shared yet divergent pathways opens avenues for therapeutic strategies that target metabolism and immune-metabolic communication.},
}
@article {pmid41760667,
year = {2026},
author = {Swellam, M and Ramadan, A and Sobeih, ME and Bakr, NM},
title = {Clinical impact of the methylation status of SMAD4 and AKR1B1 genes in a liquid biopsy sample as a prognostic marker for breast cancer.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {41760667},
issn = {2045-2322},
mesh = {Humans ; Female ; *DNA Methylation ; *Breast Neoplasms/genetics/pathology/mortality/diagnosis ; *Smad4 Protein/genetics ; *Biomarkers, Tumor/genetics ; Middle Aged ; Prognosis ; Adult ; Liquid Biopsy ; Aged ; ROC Curve ; Kaplan-Meier Estimate ; Gene Expression Regulation, Neoplastic ; Aldehyde Reductase ; },
abstract = {The role of DNA methylation in the prognosis of breast cancer, particularly concerning small mothers against decapentaplegic 4 (SMAD4) and aldo-keto reductase family 1 member B1 (AKR1B1), remains largely unexplored. This study aimed to investigate the clinical role of SMAD4 and AKR1B1 methylation as noninvasive prognostic biomarkers in breast cancer. The study included 140 individuals. The patients were stratified into two groups based on their diagnostic investigation: women diagnosed with cancer in breast (N = 80) and cases with benign lesions in breast (N = 30). Additionally, a group of subjects considered as healthy served as the control group (N = 30). Methylation levels of SMAD4 and AKR1B1 were quantified using the Methyl II quantitative PCR system. The methylation specificity and sensitivity were examined through performing a receiver operating characteristic (ROC) curve analysis. The association of the methylation of investigated patterns with breast cancer clinical features and response to treatment was also examined. Survival patterns were assesed using Kaplan-Meier analyses. The outcomes revealed that hypermethylation of SMAD4 and AKR1B1 was upregulated in cancerous patients relative to the benign group and healthy subjects. Based on the values of the area under the curve (AUC) (0.945 and 0.935, respectively) for SMAD4 and AKR1B1, both markers demonstrated superior diagnostic accuracy, surpassing conventional biomarkers for instance cancer antigen 15 - 3 (CA 15 - 3; AUC = 0.698) as well as carcinoembryonic antigen (CEA; AUC = 0.537). Remarkably, SMAD4 and AKR1B1 hypermethylation exhibited a significant association with invasive duct carcinoma (IDC), particularly in early stages, high grades, and cases with lymph node metastasis. A significant difference was observed in methylation status concerning both items and treatment response. Additionally, survival outcomes indicated that hypermethylation of SMAD4 and AKR1B1 was associated with worse DFS and OS. In conclusion, SMAD4 and AKR1B1 methylation may serve as significant epigenetic markers affecting breast cancer prognosis, potentially indicating more aggressive disease and poorer outcomes in these patients.},
}
@article {pmid41768803,
year = {2025},
author = {Roy, B and Rathore, R and Singhal, S and Halder, S and Singh, N},
title = {Vaginal Neoplasm in a Breast Cancer Survivor.},
journal = {JNMA; journal of the Nepal Medical Association},
volume = {63},
number = {286},
pages = {433-435},
pmid = {41768803},
issn = {1815-672X},
mesh = {Humans ; Female ; *Vaginal Neoplasms/secondary/drug therapy/diagnosis/pathology/diagnostic imaging ; Cancer Survivors ; Paclitaxel/therapeutic use ; Middle Aged ; *Triple Negative Breast Neoplasms/pathology/therapy ; Positron Emission Tomography Computed Tomography ; *Breast Neoplasms/pathology/therapy ; Mastectomy, Modified Radical ; Magnetic Resonance Imaging ; Antineoplastic Agents, Phytogenic/therapeutic use ; },
abstract = {According to GLOBOCAN 2022 data, Carcinoma breast is the second most common malignancy worldwide after lung and ranks 4[th] in mortality worldwide. Breast cancer can metastasize to various organs. The incidence of vaginal metastasis in carcinoma breast is 1-2%. Here we present a patient with post menopausal bleeding with vaginal mass. She had a history of Triple negative carcinoma left breast 3 years back, treated by Modified Radical Mastectomy followed by chemo radiotherapy. Vaginal biopsy was suggestive of a metastatic carcinoma breast. MRI and PET CT showed isolated vaginal growth. Due to poor performance status and multiple medical comorbidities, decision was taken to treat her with single agent Paclitaxel 3weekly until disease progression. This case report points out the necessity for thorough gynaecological examination in a cancer survivor, either via clinical examination, routine PAP smear or imaging.},
}
@article {pmid41760005,
year = {2026},
author = {Li, P and Wu, S and Ma, H and Ji, W and Wang, Y and Wang, L and Dai, Y},
title = {Occult metastasis of hormone receptor-positive breast cancer to the ovary: A case report and literature review.},
journal = {Medicine},
volume = {105},
number = {9},
pages = {e47830},
pmid = {41760005},
issn = {1536-5964},
support = {L2024-QCY-ZYYJJQ-270//Xianyang Municipal Science and Technology Bureau/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/therapy ; Adult ; *Ovarian Neoplasms/secondary/therapy/surgery ; *Carcinoma, Ductal, Breast/secondary/pathology/therapy ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {RATIONALE: Breast cancer is the most common malignancy among women worldwide. It typically metastasizes to the bone, lungs, and liver, while ovarian involvement is relatively uncommon. This report aims to illustrate the clinical features, diagnostic approach, and treatment strategies for this rare type of metastasis through a case study, thereby enhancing clinicians' awareness and management capabilities.<br><br>PATIENT CONCERNS: A 32-year-old premenopausal woman presented with a palpable nodule in the left breast. Comprehensive diagnostic evaluation, including mammography, ultrasonography, contrast-enhanced computed tomography, and core needle biopsy, confirmed invasive ductal carcinoma, classified as Luminal A subtype (estrogen receptor/progesterone receptor-positive, human epidermal growth factor receptor 2-negative).<br><br>DIAGNOSES: Invasive ductal carcinoma of the left breast (pT3N3M1, stage IV) with ovarian metastasis.<br><br>INTERVENTIONS: The patient received 6 cycles of docetaxel/doxorubicin/cyclophosphamide chemotherapy (docetaxel, doxorubicin, and cyclophosphamide), followed by left modified radical mastectomy with axillary lymph node dissection, achieving R0 resection. Laparoscopic bilateral adnexectomy was also performed for ovarian ablation. Final pathology confirmed metastatic breast carcinoma in the ovaries.<br><br>OUTCOMES: The patient successfully achieved surgical tumor reduction, recovered well postoperatively, and showed no clinical evidence of disease progression.<br><br>LESSONS: This case highlights the distinct characteristics of ovarian metastases in HR+/HER2- breast cancer and their critical importance in differential diagnosis, particularly in distinguishing them from primary gynecologic tumors. For patients with a history of breast cancer, the presence of pelvic lesions should prompt consideration of metastatic potential to guide appropriate comprehensive treatment.},
}
@article {pmid39840832,
year = {2025},
author = {Giuliano, AR and Palefsky, JM and Goldstone, SE and Bornstein, J and De Coster, I and Guevara, AM and Mogensen, O and Schilling, A and Van Damme, P and Vandermeulen, C and Ellison, MC and , and Kaplan, S and Lin, J and Bonawitz, R and Luxembourg, A},
title = {Immunogenicity of the 9-valent human papillomavirus vaccine: Post hoc analysis from five phase 3 studies.},
journal = {Human vaccines &amp; immunotherapeutics},
volume = {21},
number = {1},
pages = {2425146},
pmid = {39840832},
issn = {2164-554X},
mesh = {Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Young Adult ; *Antibodies, Viral/blood ; Clinical Trials, Phase III as Topic ; *Immunogenicity, Vaccine ; *Papillomavirus Infections/prevention &amp; control/immunology ; *Papillomavirus Vaccines/immunology/administration &amp; dosage ; },
abstract = {Post hoc analyses of 9-valent human papillomavirus (9vHPV) vaccine immunogenicity were conducted in five Phase 3 studies that enrolled males. Month 7 antibody geometric mean titers (GMTs) after three 9vHPV vaccine doses were analyzed in 10,024 males/females aged 16-26 years from studies 001 (NCT00543543), 002 (NCT00943722), 003 (NCT01651949), and 020 (NCT02114385). Covariates considered were age, gender, sexual orientation, region of residence, and race. GMTs among 2599 males/females aged 9-15 years (studies 002 and 010 [NCT01984697]) were assessed 6 months after one, two, and three 9vHPV vaccine doses. 9vHPV vaccine immunogenicity was robust across populations. Month 7 GMTs were generally higher in participants aged 16-21 versus 22-26 years. Region and race minimally impacted immunogenicity. Adjusted integrated analysis showed lower immunogenicity in men who have sex with men (MSM) versus heterosexual men (HM) for nine HPV types, and higher immunogenicity in HM versus females for seven HPV types. Among 9-15-year-olds, trends toward higher GMTs in males versus females post-Dose 3, similar GMTs post-Dose 2, and lower post-Dose 1 were observed. In conclusion, 9vHPV vaccine immunogenicity was robust in males aged 16-26 years across a range of baseline characteristics. GMT ratios for males versus females aged 9-15 years tended to increase with more doses.},
}
@article {pmid41735610,
year = {2026},
author = {Sadeghi, M and Ghaderi, A and Mousavi, P and Sabetian, S and Ramezani, A and Haghshenas, MR},
title = {FN1 as a key gene in modulating the integrin cell surface pathway in breast cancer.},
journal = {Medical oncology (Northwood, London, England)},
volume = {43},
number = {4},
pages = {},
pmid = {41735610},
issn = {1559-131X},
support = {4000409//deputy of Research in the Hormozgan University of Medical Sciences, Bandar Abbas, Iran./ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/metabolism/pathology ; *Fibronectins/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/genetics ; DNA Methylation ; *Integrins/metabolism/genetics ; Antigens, CD/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Promoter Regions, Genetic ; Middle Aged ; Cadherins ; },
abstract = {Breast carcinoma represents the most prevalent form of invasive neoplasia among the female population globally, and is distinguished by its molecular heterogeneity by significant genomic instability. The discipline of bioinformatics provides essential tools for the identification of novel biomarkers and enhances the prospects for subsequent experimental investigations. Differentially expressed messenger RNAs were assembled by employing datasets sourced from the Gene Expression Omnibus repository. Intersection of DEGs and proteins involving in the integrin cell surface interactions were done. Ce-RNA network were constructed and Functional analysis were done. Protein expression analysis, methylation and, Correlation analysis as well as drug sensitivity analysis for the hub genes were performed. The expression of FN1 were evaluated using Real-Time PCR for 45 invasive ductal carcinoma breast tissues and adjacent normal samples. We found FN1, CDH1, COMP, SPP1 and ITGA7 to act in integrin cell surface interactions. The Ce-RNA network consisted of 126 nodes and 192 edges which the network nodes were significantly enriched in known cancer pathways. Protein expressions of FN1, CDH1, COMP was upregulated while ITGA7 were downregulated. The methylation levels in ITGA7 and SPP1 promoter regions were significantly altered across all stages compared to normal. In contrast, FN1 and CDH1 promoter regions exhibited dysregulation only in stage 3 relative to normal. A correlation study identified five positive and three negative gene correlations. Altered expression of FN1, SPP1, CDH1, and ITGA7 in breast cancer enhanced cancer cell susceptibility to specific pharmacological molecules. FN1 expression was markedly higher in breast cancer tissues compared to non-cancerous tissues, showing a threefold increase (p < 0.0001). Both early-stage and advanced-stage cancers showed higher FN1 levels (p = 0.002, p = 0.01). Additionally, FN1 was higher in lower histological grade tissues (p = 0.0002). In ROC curve analysis with limited stage III samples, FN1 showed potential for diagnosing IDC, achieving an AUC of 0.82. We identified FN1 as a highly connected component of integrin cell-surface interactions in breast cancer and provide hypothesis-generating associations with drug sensitivity; these findings require further protein-level validation and functional testing before translational application.},
}
@article {pmid41727395,
year = {2026},
author = {Javed, A and Dreyer, J and Cassidy, D and Amin, S},
title = {Metastatic lobular breast cancer masquerading as achalasia.},
journal = {VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy},
volume = {11},
number = {2},
pages = {41-45},
pmid = {41727395},
issn = {2468-4481},
abstract = {BACKGROUND AND AIMS: A 64-year-old woman with stage IV breast cancer taking exemestane presented with weight loss of 10 to 15 pounds and dysphagia of 3 to 6 months in duration. Upper endoscopy and positron emission tomography/computed tomography did not reveal a pathologic diagnosis. Esophageal manometry was suggestive of achalasia. The patient was referred for an esophageal peroral endoscopic myotomy (E-POEM) procedure. We aim to describe a rare finding encountered during submucosal dissection in an E-POEM that may result in an incomplete, aborted, technically challenging, or ineffective procedure.<br><br>METHODS: An E-POEM using a posterior approach is our preferred method. E-POEM was planned in the standard fashion. A mucosotomy followed by submucosal injection and dissection was performed, with plan for an extended circular and full-thickness myotomy of the lower esophageal sphincter.<br><br>RESULTS: During submucosal dissection, atypical yellow-brown tissue was encountered within the submucosal tunnel. This was initially thought to be related to fibrosis from severe achalasia. In total, 3 tunnels were created with eventual abortion of the procedure because this abnormal tissue was found 3 to 4 cm proximal to the esophagogastric junction in each tunnel. This tissue was biopsied, and all tunnels were closed without any postprocedural adverse event. Pathology demonstrated metastatic lobular breast cancer.<br><br>CONCLUSIONS: Invasive lobular breast cancer has a propensity to spread to the GI tract as compared with other forms of cancer such as invasive ductal carcinoma. Endoscopists who perform E-POEM who encounter difficulty expanding the submucosal plane during E-POEM should keep malignancy and metastatic disease in mind as a rare cause of pseudoachalasia, even in the absence of nondiagnostic pre-peroral endoscopic myotomy evaluation.},
}
@article {pmid40824585,
year = {2026},
author = {Sakata, S and Hisa, T and Ito, Y and Nishiyama, S and Kudo, A and Yamada, T and Osera, S and Fukushima, H and Hamura, R and Shiozawa, S},
title = {Pancreatic ductal adenocarcinoma originating from focal pancreatic parenchymal atrophy demonstrated by transabdominal ultrasonography.},
journal = {Clinical journal of gastroenterology},
volume = {19},
number = {1},
pages = {8-15},
pmid = {40824585},
issn = {1865-7265},
mesh = {Humans ; Male ; Atrophy ; Aged, 80 and over ; *Pancreatic Neoplasms/diagnostic imaging/pathology/surgery ; *Carcinoma, Pancreatic Ductal/diagnostic imaging/pathology/surgery/etiology ; *Pancreas/pathology/diagnostic imaging ; Ultrasonography ; },
abstract = {In this report, we present an 80-year-old man referred for evaluation of a pancreatic mass detected by transabdominal ultrasonography during health screening. Additional examinations revealed severe, long-segment focal atrophy from the pancreatic head to the body, appearing as a cord-like hypoechoic lesion on transabdominal and endoscopic ultrasonography. Although cytological examination of pancreatic juice was recommended, the patient opted for a follow-up. Three years later, a hypoechoic mass with upstream main pancreatic duct dilatation developed in the atrophic region. Cytological examination of pancreatic juice revealed adenocarcinoma, and pancreaticoduodenectomy was performed. Histopathology revealed Stage IIB invasive ductal carcinoma and carcinoma in situ within the atrophic region. Retrospective review showed that focal atrophy was present on transabdominal ultrasonography 11 years before the invasive carcinoma mass appeared, progressing without main pancreatic duct dilatation until its development. During follow-up of focal atrophy, early diagnosis of carcinoma in situ or microinvasive carcinoma before main pancreatic duct dilatation is crucial. The present case suggests that severe, long-segment focal pancreatic parenchymal atrophy can be detected by transabdominal ultrasonography and that carcinoma in situ within the focal pancreatic parenchymal atrophy may progress to invasive carcinoma.},
}
@article {pmid41707646,
year = {2026},
author = {Cheng, Y and Wan, L and Huang, E and Zheng, B and Ding, X and Tan, S and Ma, G and Li, W and Chu, C and Wu, T and Chen, S and Zhuang, J and Na, R and Chen, Z and Teng, G and Zhang, D and Ju, S and Chen, M and Xu, B},
title = {A conserved eIF1A[+] luminal cell-centered hypoxic and "cold" tumor microenvironment promotes pan-subtype prostate cancer progression.},
journal = {Cell reports. Medicine},
volume = {7},
number = {2},
pages = {102619},
doi = {10.1016/j.xcrm.2026.102619},
pmid = {41707646},
issn = {2666-3791},
mesh = {Male ; Humans ; *Prostatic Neoplasms/pathology/metabolism/genetics ; *Tumor Microenvironment ; Disease Progression ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Animals ; Cell Line, Tumor ; Mice ; },
abstract = {Prostate cancer (PCa) is a malignancy with high heterogeneity arising from tumor microenvironment and histological subtypes. Identifying conserved progression drivers within such heterogeneity is essential for improving clinical outcomes. Using imaging mass cytometry, this study analyzes 38 proteins across paracancerous tissue and four histological subtypes: low-grade prostate acinar adenocarcinoma (LgPAC), high-grade PAC (HgPAC), intraductal carcinoma (IDC), and ductal adenocarcinoma (DAC). Results reveal that eIF1A is overexpressed in high-risk subtypes including HgPAC, IDC, and DAC and correlates with poor prognosis. In luminal cells, EIF1A knockdown and the translation inhibitor homoharringtonine (HHT) both suppress HIF-1α translation and tumor growth, while promoting infiltration of anticancer immune cells including PD-1[-] T cells and CD163[-] macrophages. Clinically, neoadjuvant HHT combined with androgen deprivation therapy reduces hypoxia and enhances immune cell infiltration, as shown by single-cell RNA sequencing. Collectively, this work defines conserved molecular features across PCa subtypes, providing promising insights for clinical management. This study was registered at Clinicaltrials.gov (NCT06834321).},
}
@article {pmid41151718,
year = {2026},
author = {Palatella, M and Kruse, F and Ji, H and Loriani Fard, AK and Becker, M and Daniel, C and Rohm, M and Huehn, J},
title = {Acsbg1 maintains intestinal immune homeostasis and controls inflammation by regulating ST2[+] Tregs.},
journal = {Mucosal immunology},
volume = {19},
number = {1},
pages = {1526-1537},
doi = {10.1016/j.mucimm.2025.10.009},
pmid = {41151718},
issn = {1935-3456},
mesh = {Animals ; *T-Lymphocytes, Regulatory/immunology/metabolism ; Mice ; Homeostasis ; Mice, Knockout ; *Citrobacter rodentium/immunology/physiology ; *Th17 Cells/immunology ; *Colitis/immunology ; *Inflammation/immunology ; *Intestinal Mucosa/immunology/metabolism ; *Enterobacteriaceae Infections/immunology ; Disease Models, Animal ; Mice, Inbred C57BL ; Immunity, Mucosal ; },
abstract = {The immune balance in mucosal tissues depends on a delicate interplay between inflammatory T helper 17 (Th17) cells and immunosuppressive regulatory T cells (Tregs). But what happens when this balance is disturbed? In this study, we uncovered a critical role for Acyl-CoA synthetase bubblegum family member 1 (Acsbg1) in shaping Th17 and Treg dynamics. Using Acsbg1-deficient mice, we show that while its absence does not disrupt homeostasis under steady-state conditions, it significantly alters Treg populations, particularly in gut-associated tissues. Under high-fat diet-induced metabolic stress, Acsbg1-deficient mice display mild metabolic changes but maintain systemic immune and metabolic function, indicating that Acsbg1 is dispensable for metabolic adaptation in vivo. However, upon infection with Citrobacter rodentium, these mice exhibit excessive Th1/Th17-driven inflammation and impaired resolution, accompanied by a strong reduction in IL-10-producing and ST2[+] Treg subsets. The impact is even more striking in an adoptive transfer colitis model, where Acsbg1-deficient Tregs fail to control inflammation, resulting in severe colitis and tissue damage. Our findings identify Acsbg1 as a key regulator of ST2[+] Treg function and a central player in mucosal immune homeostasis, highlighting its potential as a therapeutic target for inflammatory bowel disease and colorectal cancer.},
}
@article {pmid40035809,
year = {2026},
author = {Rammal, R and Seethala, RR and Bilofsky, EJ and Freeman, TJ and Lajara, S},
title = {Intraductal carcinoma of the parotid gland, mixed intercalated duct and oncocytic subtype with mucinous and serous acinar differentiation: cytologic and histologic features of a novel morphology.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {488},
number = {2},
pages = {429-434},
pmid = {40035809},
issn = {1432-2307},
mesh = {Humans ; Female ; Aged ; *Parotid Neoplasms/pathology/genetics ; Biomarkers, Tumor/analysis/genetics ; Cell Differentiation ; Oxyphil Cells/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/genetics ; *Carcinoma, Ductal/pathology/genetics ; *Acinar Cells/pathology/chemistry ; },
abstract = {Intraductal carcinoma (IDC) of the salivary gland is rare. Histologic subtypes include intercalated duct, oncocytic, apocrine, and hybrid/mixed. Molecular correlates have been described, with intercalated duct IDC typically harboring NCOA4::RET, while TRIM33::RET, or BRAF[V600E] pathogenic variants predominating in oncocytic IDC. We describe the case of a 77-year-old female with a parotid mass. Fine needle aspiration showed a population of low-grade epithelial cells with frequent cytoplasmic vacuolization, which were positive for S-100, SOX-10, and mammaglobin, and was interpreted as compatible with secretory carcinoma. A dual cell population was recognized on surgical resection, predominantly oncocytic, with at least one focus prototypical of intercalated IDC. Luminal secretions were positive for mucicarmine, while PAS after diastase highlighted the latter in addition to zymogen-like cytoplasmic granules. RNA sequencing detected a NCOA4::RET fusion. This is the first report of the cyto-histologic features of the mixed intercalated duct and oncocytic subtype IDC with mucous and serous acinar-like differentiation.},
}
@article {pmid39812957,
year = {2026},
author = {Wei, C and Li, H and Li, J and Liu, Y and Zeng, J and Tian, Q},
title = {Machine learning-based prognostic modeling and surgical value analysis of de novo metastatic invasive ductal carcinoma of the breast.},
journal = {Updates in surgery},
volume = {78},
number = {1},
pages = {415-428},
pmid = {39812957},
issn = {2038-3312},
support = {No.81960441//National Natural Science Foundation of China/ ; No.20232BAB206100//Jiangxi Provincial Natural Science Foundation of China/ ; },
mesh = {Humans ; *Breast Neoplasms/surgery/pathology/mortality ; Female ; *Machine Learning ; Prognosis ; Middle Aged ; *Carcinoma, Ductal, Breast/surgery/mortality/secondary/pathology/diagnosis ; SEER Program ; Aged ; Adult ; *Mastectomy ; },
abstract = {Whether primary lesion surgery improves survival in patients with de novo metastatic breast cancer (dnMBC) is inconclusive. We aimed to establish a prognostic prediction model for patients with de novo metastatic breast invasive ductal carcinoma (dnMBIDC) based on machine learning algorithms and to investigate the value of primary site surgery. The data used in our study were obtained from the Surveillance, Epidemiology, and End Results database (SEER, 2010-2021) and the First Affiliated Hospital of Nanchang University (1st-NCUH, June 2013-June 2023). We used COX regression analysis to identify prognostic factors. We divided patients into training and validation groups and constructed Extreme Gradient Boosting (XGBoost) prognostic prediction model. In addition, we used propensity score matching (PSM), K-M survival analysis, and COX regression analysis to explore the survival benefit of patients undergoing primary lesion surgery. A total of 13,383 patients were enrolled, with 13,326 from SEER and 57 from 1st-NCUH. The results showed that XGboost had good predictive ability (training set C-index = 0.726, 1 year AUC = 0.788, 3 year AUC = 0.774, 5 year AUC = 0.774; validation set C-index = 0.723, 1 year AUC = 0.785.1, 3 year AUC = 0.770, 5 year AUC = 0.764), which has better predictive power than the Coxph model. We used Shiny-Web to make our model easily available. Furthermore, we found that surgery was associated with a better prognosis in dnMBIDC patients. Based on the XGboost, we can accurately predict the survival of dnMBIDC patients, which can provide a reference for clinicians to treat patients. In addition, surgery may bring survival benefits to dnMBIDC patients.},
}
@article {pmid41685010,
year = {2026},
author = {Purohit, T and Sahu, S and Dandekar, M and Verma, D},
title = {Expression of PTEN and p53 and Their Clinicopathological Correlation in Breast Cancer.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e101323},
pmid = {41685010},
issn = {2168-8184},
abstract = {BACKGROUND: Breast cancer is one of the most common malignancies in women and is a major cause of cancer-related mortality. Alterations in the expression of tumor suppressor genes such as PTEN and p53 may influence tumor behavior and prognosis. This study aimed to evaluate the immunohistochemical expression of PTEN and p53 in breast carcinoma and analyze their association with clinicopathological parameters.<br><br>METHODS: A cross-sectional study was conducted on 50 histologically confirmed female breast carcinoma cases. Immunohistochemistry (IHC) for PTEN and p53 was performed using standard protocols. PTEN expression was assessed based on cytoplasmic and nuclear staining intensity and categorized as positive or negative. p53 expression was evaluated as nuclear positivity and categorized similarly. Statistical analysis was done using standard significance tests.<br><br>RESULTS: The mean patient age was 49.8 years. The most common histologic subtype was infiltrating ductal carcinoma (IDC). Loss of PTEN expression was found in most of the cases and was associated with higher tumor grade and lymph node metastasis. Most cases exhibited p53 overexpression, which showed trends toward an association with higher tumor grade, premenopausal status, and lymph node positivity. An inverse relationship was noted between PTEN loss and p53 positivity.<br><br>CONCLUSIONS: PTEN loss and p53 overexpression were frequent in breast carcinoma and correlated with aggressive tumor features. Combined assessment of these biomarkers may provide prognostic value and support therapeutic decision-making in breast cancer.},
}
@article {pmid41684983,
year = {2026},
author = {Sikandar, F and Zahid, S and Basit Ali, A and Younas, A and Mani Tripathi, K and Fatima, P and Fatima, F},
title = {Clinicopathological Characteristics and Postoperative Outcomes of Patients Undergoing Modified Radical Mastectomy: A Retrospective Study.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e101373},
pmid = {41684983},
issn = {2168-8184},
abstract = {Background Breast cancer remains the most common malignancy among women worldwide and a leading cause of cancer-related mortality, particularly in developing countries where delayed presentation and limited screening facilities persist. Objective The objective of this study is to evaluate the clinicopathological profile and short-term (30-day) postoperative outcomes of patients with breast cancer undergoing modified radical mastectomy (MRM) in a resource-limited tertiary care setting while exploring factors that may influence surgical complications. Methods This retrospective observational study included 210 female patients who underwent MRM between January 2022 and December 2024. Demographic, clinical, histopathological, perioperative, and 30-day postoperative outcome data were extracted from hospital records and analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY). Results The mean age was 51.4 ± 10.2 years, with 63.8% of patients being postmenopausal. Invasive ductal carcinoma was the predominant histological subtype (89.5%). Most patients presented with locally advanced disease (stage IIIC, 60%), and axillary lymph node involvement was observed in 65.7%. Estrogen receptor (ER) positivity was noted in 62.9%, progesterone receptor (PR) positivity in 57.1%, human epidermal growth factor receptor 2 (HER2/neu) overexpression in 25.7%, and triple-negative breast cancer in 17.1% of cases. The mean operative time was 115 ± 25 minutes, and the mean blood loss was 210 ± 60 mL. Postoperative complications occurred in 27.6% of patients, most commonly seroma formation (16.2%). No 30-day postoperative mortality was observed. Conclusion Modified radical mastectomy remains a safe and effective surgical option for breast cancer management in resource-limited settings, providing acceptable morbidity and reliable short-term outcomes, particularly among patients presenting with advanced disease.},
}
@article {pmid41673677,
year = {2026},
author = {Baena, JC and Cabrera-Salcedo, SC and Carrera Suárez, Y and Biancha-Vasco, JM and Rios-Serna, LJ and García-Mantilla, MD and Estrada-Schweineberg, M and Victoria Hincapie, JS and Toro-Pedroza, A and Garcia-Robledo, JE and Cañas, CA and Ortiz-Guzman, J and Loukanov, A},
title = {The avatar principle: exosomal dynamics guiding tumor adaptation and next-generation therapeutic strategies.},
journal = {Journal of nanobiotechnology},
volume = {24},
number = {1},
pages = {159},
pmid = {41673677},
issn = {1477-3155},
mesh = {*Exosomes/metabolism ; Humans ; *Neoplasms/therapy/immunology ; Tumor Microenvironment ; Immunotherapy/methods ; Animals ; Receptors, Chimeric Antigen ; Avatar ; },
abstract = {Exosomes are nanoscale extracellular vesicles that transfer proteins, nucleic acids, and lipids, reflecting the state of their parent cells. A persistent scientific challenge is that tumor-derived exosomes (TDEs) facilitate immune evasion, remodel the tumor microenvironment, and create premetastatic niches, intensifying tumor aggressiveness and undermining therapeutic efficacy, ultimately narrowing treatment options to palliative strategies in advanced settings. Yet their dual roles as suppressive agents and potential therapeutic tools remain poorly integrated within current cancer immunotherapy frameworks. This review examines the molecular mechanisms underlying TDE-mediated immune suppression and therapeutic resistance, while also highlighting engineering strategies to exploit or counteract exosome biology. Exosomes derived from chimeric antigen receptor (CAR) T cells preserve antigen specificity and cytotoxic components without the risks of uncontrolled proliferation or cytokine release, offering a safer class of cell free immunotherapies. Advances in genetic engineering, hybrid vesicle design, and nanotechnology have extended exosome applications to the delivery of CRISPR/Cas systems, chemotherapeutic agents, immunoregulatory RNAs, and vaccines, with liposome or nanoparticle integration enhancing targeting and efficacy. Remaining obstacles include the lack of standardized protocols, scalability issues in production, and unresolved regulatory frameworks. Drawing on The Art of War, exosomes can be envisioned as avatars of strategy, discreet messengers capable of undermining host defenses while simultaneously carrying the potential to redirect immunity against the tumor. By embodying both deception and counterattack, they illustrate the capacity to penetrate hidden barriers and redefine the therapeutic battlefield, opening new horizons for precision cancer immunotherapy.},
}
@article {pmid41660202,
year = {2026},
author = {López-Ponce-de-León, JD and Muñoz-Ordoñez, JA and Toro-Pedroza, A and Arango-Ibanez, JP and Azcarate-Rodriguez, V and Naranjo-Ramírez, MC and León-Giraldo, H and Largo, J and Carrillo-Gomez, D and Arteaga-Tobar, AA and Escalante-Forero, M and Olaya, P and Florez, N and Olaya, N and Rivera-Muñoz, EL and Barbosa-Rengifo, MM and Nativi-Nicolau, J and Gómez-Mesa, JE},
title = {Survival in Adult Patients Undergoing Heart Transplantation 1995-2024: A Report of the RETRAC Registry.},
journal = {Global heart},
volume = {21},
number = {1},
pages = {7},
pmid = {41660202},
issn = {2211-8179},
mesh = {Humans ; Male ; *Heart Transplantation/mortality ; Female ; Middle Aged ; *Registries ; Survival Rate/trends ; Adult ; *Heart Failure/surgery/mortality ; Colombia/epidemiology ; Retrospective Studies ; Aged ; Follow-Up Studies ; },
abstract = {BACKGROUND: Heart transplantation (HT) remains the definitive treatment for advanced heart failure that is refractory to both medical and invasive therapies. Although global registries offer extensive data on survival outcomes, there is a relative paucity of information regarding HT outcomes in Latin America (LATAM), particularly in Colombia.<br><br>METHODS: This study analyzed adult patients who underwent HT between 1995 and 2024, using data obtained from an institutional HT registry (RETRAC) in Cali, Colombia. Survival outcomes were evaluated using Kaplan-Meier curves and Cox proportional hazards models.<br><br>RESULTS: We included 260 patients who underwent HT in this 29-year cohort from a LATAM country. The median age at transplantation was 51 years, and 77.7% were male. The primary etiologies were idiopathic/dilated cardiomyopathy (IDC) (41.3%), ischemic cardiomyopathy (IC) (27.0%), and valvular heart disease (VHC) (9.7%). The most prevalent comorbidities were hypertension (HTN) (48.3%), diabetes mellitus (DM) (18.9%), and chronic kidney disease (CKD) (13.1%). The overall median survival following HT was 7.4 years. One-year survival was 74.6% (n = 194), five-year survival was 56.9% (n = 147), and ten-year survival was 46.9% (n = 122). Survival differed significantly by age and sex, with patients aged <40 years demonstrating the highest median survival (8.4 years) and those aged &#x2265;60 years the lowest (2.2 years) (p = 0.038). The 40- to 49-year age group exhibited the most pronounced reduction in survival; however, this effect was attenuated after adjustment. Among patients under 40 years, females had significantly higher mortality compared to males (p = 0.0078), with younger males exhibiting better survival. Additionally, patients transplanted between 2016 and 2020 had higher survival rates. CKD was identified as a significant independent risk factor for increased mortality (hazard ratio (HR) = 1.79; 95% CI: 1.15-2.79; p = 0.01).<br><br>CONCLUSIONS: HT patients in Colombia exhibit demographic and clinical profiles comparable to global cohorts; however, they demonstrate lower survival rates and poorer clinical outcomes compared to international registries, such as the International Society for Heart and Lung Transplantation registry. Nonetheless, clinical outcomes are more favorable than those reported in other studies from the LATAM region. CKD emerged as a significant independent predictor of mortality. These findings highlight the need for region-specific strategies aimed at improving HT outcomes in LATAM.},
}
@article {pmid41649045,
year = {2026},
author = {Nafissi, N and Mahadevan, A and Chiao, E and Rijal, N and Parajuli, R},
title = {Triple Negative Breast Cancer With Choroidal Metastasis Responsive to Sacituzumab Govitecan and Radiation Therapy.},
journal = {Cancer reports (Hoboken, N.J.)},
volume = {9},
number = {2},
pages = {e70462},
doi = {10.1002/cnr2.70462},
pmid = {41649045},
issn = {2573-8348},
mesh = {Humans ; Female ; *Triple Negative Breast Neoplasms/pathology/therapy ; Middle Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; *Immunoconjugates/therapeutic use ; *Choroid Neoplasms/secondary/therapy ; *Camptothecin/analogs &amp; derivatives/therapeutic use/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Carcinoma, Ductal, Breast/therapy/secondary ; Treatment Outcome ; },
abstract = {BACKGROUND: Orbital metastases are rare in patients with breast cancer. However, medical management of orbital metastases is limited by the inability of treatment options to penetrate the blood-brain barrier. In patients with triple negative breast cancer (TNBC), these treatment options are further limited. Sacituzumab govitecan, an antibody-drug conjugate, has emerged as a promising agent for metastatic TNBC. However, to date, patients with central nervous system (CNS) disease have been excluded from corresponding clinical trials, making the efficacy of sacituzumab govitecan in patients with orbital metastases unclear.<br><br>CASE: A 61-year-old female was initially diagnosed with a left breast hormone receptor positive invasive ductal carcinoma, receiving neoadjuvant chemotherapy with doxorubicin, cyclophosphamide, and docetaxel and a partial mastectomy. Several years later, the patient presented with a cough and was subsequently diagnosed with metastatic triple negative breast cancer with hepatic, osseous, and right supraclavicular and thoracic nodal metastases. Concurrently, the patient noted floaters in her vision, later found to be consistent with orbital metastases. The patient received radiation therapy to both eyes and was started on Sacituzumab govitecan. Following cycle 1, the ophthalmic exam showed a dramatic decrease in the size of choroidal metastases.<br><br>CONCLUSION: This case report documents the first case of orbital metastases successfully treated with radiation therapy and sacituzumab govitecan. As such, this case highlights the importance of sacituzumab govitecan as a potentially effective option for TNBC patients with CNS disease. Further studies and real-world data are needed to investigate the efficacy of combined radiotherapy and sacituzumab govitecan toward ocular metastases.},
}
@article {pmid41539423,
year = {2026},
author = {Cingir Koker, S and Mhamane, A and Geppert, J and Shakir, G and Guillamat-Prats, R and Chen, B and Katra, P and Geiger, M and Tsokanos, FF and Wolff, G and Szendrödi, J and Rohm, M and Daniel, C and Maegdefessel, L and Steffens, S and Herzig, S},
title = {Nuclear receptor co-factor TBL1X/TBL1XR1 T cell activity protects against atherosclerosis.},
journal = {Molecular metabolism},
volume = {104},
number = {},
pages = {102318},
pmid = {41539423},
issn = {2212-8778},
mesh = {Animals ; *Atherosclerosis/metabolism/immunology ; Humans ; Mice ; *Repressor Proteins/metabolism/genetics ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Mice, Knockout ; Male ; *CD4-Positive T-Lymphocytes/metabolism/immunology ; Mice, Inbred C57BL ; *Nuclear Proteins/metabolism/genetics ; Female ; Plaque, Atherosclerotic/metabolism ; },
abstract = {Atherosclerosis is a long-term complication of obesity and diabetes and as such a key driver of vascular dysfunction and eventually mortality in affected patients. Both aberrant lipid metabolism and inflammatory reactions promote atherosclerotic plaque development in the vessel wall by triggering a cascade of cellular events involving multiple cell types, including smooth muscle cells, monocytic macrophages, and lymphocytes. Despite its eminent impact on human health, molecular drivers of cellular dysfunction in atherosclerosis remain poorly defined and therapeutic options are scarce. Here we show by single-cell RNA sequencing that the expression of the nuclear receptor co-factors, TBL1X and TBL1XR1, was particularly prominent in the CD4[+] T cell population of human carotid artery plaques. Indeed, genetic double deletion of TBL1X/TBL1XR1 in CD4[+] T cells led to a substantial shift from naïve CD44[low]CD62L[hi] cells to CD44[hi]CD62L[low] effector and Foxp3[+] Tregs. CD4[+] TBL1X/TBL1XR1 KO cells exhibited enhanced cytokine production capacity upon ionomycin/PMA stimulation, correlating with the induction of pro-inflammatory and cytokine-producing transcriptional pathways in these cells. Consistently, transplantation of bone marrow from CD4[+]-specific TBL1X/TBL1XR1 knock out mice into LDLR KO recipients doubled the development of atherosclerotic plaques in the aortic arch compared with wild-type bone marrow transplanted littermates. As TBL1X/TBL1XR1 expression levels were diminished in carotid arteries from patients with advanced unstable plaques compared to stable plaques or healthy controls, these data suggest that aberrant inhibition of TBL1X/TBL1XR1 in CD4[+] T cells may contribute to the development of atherosclerosis in humans. Restoration of TBL1X/TBL1XR1 functionality may thus serve as a novel, druggable strategy for preventing or limiting atherosclerosis progression.},
}
@article {pmid41391258,
year = {2026},
author = {Li, Y and Leberzammer, J and Blanchet, X and Duan, R and Lacy, M and Triantafyllidou, V and Eckardt, V and Briem, E and Jung, AS and Su, R and Guerra, J and Jansen, Y and Hristov, M and Enard, W and Bernhagen, J and Weber, C and Atzler, D and Bartelt, A and Döring, Y and Santovito, D and Kaltner, H and Ludwig, AK and von Hundelshausen, P},
title = {Galectin-1 induces macrophage immunometabolic reprogramming, modulates T cell immunity and attenuates atherosclerotic plaque formation.},
journal = {Atherosclerosis},
volume = {413},
number = {},
pages = {120608},
doi = {10.1016/j.atherosclerosis.2025.120608},
pmid = {41391258},
issn = {1879-1484},
mesh = {*Galectin 1/pharmacology/metabolism ; *Plaque, Atherosclerotic ; Animals ; Humans ; *Atherosclerosis/immunology/metabolism/pathology/prevention &amp; control/genetics ; *T-Lymphocytes/immunology/metabolism/drug effects ; *Macrophages/metabolism/immunology/drug effects ; Disease Models, Animal ; Mice, Knockout, ApoE ; Mice, Inbred C57BL ; Mice ; Foam Cells/metabolism/immunology/drug effects ; Interleukin-10/metabolism ; Male ; Cells, Cultured ; Energy Metabolism/drug effects ; Cell Differentiation ; Phenotype ; },
abstract = {BACKGROUND AND AIMS: Atherosclerosis is a chronic immunometabolic disease driven by lipid accumulation and immune cell infiltration. Macrophages and T cells play key roles throughout plaque development. Galectin-1 (Gal-1), a glycan-binding protein, modulates immune functions in these cells and has been reported to attenuate atherosclerosis, though its mechanisms remain incompletely understood. Here, we investigated the effects of Gal-1 on macrophages and T cells during plaque formation.<br><br>METHODS: Effects of Gal-1 on atherosclerosis, macrophages and T cells during lesion formation were studied in Apoe[-/-] mice treated with recombinant Gal-1. Complementary mouse peritoneal foam cell and in vitro macrophage and T cell culture experiments were performed to study T cell differentiation, macrophage function, polarization and energy metabolism. The impact of Gal-1 on human macrophages was further evaluated in endarterectomy specimens.<br><br>RESULTS: Gal-1 treatment reduced lesion size and increased circulating IL-10 levels, inversely correlating with plaque burden. Unexpectedly, IL-10 neutralization also mitigated atherosclerosis, indicating that its action is at least partially IL-10-independent. In plaques, Gal-1 promoted anti-inflammatory macrophage phenotypes, mirrored by a quiescent metabolic and anti-inflammatory profile in foamy macrophages ex vivo. The use of the Gal-1[E71Q] variant revealed that these effects were only partly dependent on glycan binding. Beyond IL-10, Gal-1 reshaped cytokine profiles by increasing IL-17, IL-22, and IL-23, consistent with a macrophage-driven regulatory Th17 response, alongside higher frequencies of IL-10-producing and regulatory T cells.<br><br>CONCLUSION: Gal-1 protects against atherosclerosis associated with reprogramming macrophages and tuning T cell immunity through glycan-dependent and -independent pathways.},
}
@article {pmid41639449,
year = {2026},
author = {Li, X and Lebeaupin, C and Kadianaki, A and Druelle-Cedano, C and Vesper, N and Rennert, C and Huguet-Pradell, J and Gomez Ramos, B and Fan, C and Piecyk, RS and Zizmare, L and Ramadori, P and Li, L and Frick, L and Qiu, M and Zhang, C and Martins Nascentes Melo, L and Ranvir, VP and Shen, P and Hanselmann, J and Kosla, J and Fernández-Vaquero, M and Vucur, M and Baskaran, P and Bao, X and Coleman, OI and Tang, Y and Cetin, M and Chen, Z and Jang, I and Del Prete, S and Rahbari, M and Zhang, P and Pham, TV and Hou, Y and Sun, A and Gu, L and Kim, LC and Rothermel, U and Heide, D and Ali, A and Gallage, S and Talvard-Balland, N and Piqué-Gili, M and Gris-Oliver, A and Bevilacqua, A and Schlicker, L and Duffey, A and Unger, K and Szydlowska, M and Hetzer, J and Odom, DT and Machauer, T and Bucci, D and Sant, P and Lee, JH and Rösler, J and Meckelmann, SW and Schreck, J and Murray, S and Simon, MC and Nahnsen, S and Schulze, A and Ho, PC and Jugold, M and Breuhahn, K and Mallm, JP and Schirmacher, P and Roth, S and Rahbari, N and Tschaharganeh, DF and Roessler, S and Goeppert, B and Bengsch, B and Andrieux, G and Boerries, M and Malek, NP and Prinz, M and Weber, A and Zeiser, R and Tamayo, P and Bronsert, P and Kurowski, K and Thimme, R and Yuan, D and Carretero, R and Luedde, T and Pinyol, R and Hartmann, FJ and Karin, M and Tasdogan, A and Trautwein, C and Mall, M and Hofmann, M and Llovet, JM and Haller, D and Kaufman, RJ and Heikenwälder, M},
title = {Activated ATF6α is a hepatic tumour driver restricting immunosurveillance.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41639449},
issn = {1476-4687},
abstract = {Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related mortality and there are limited therapies[1]. Although endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are implicated in HCC, the involvement of the UPR transducer ATF6α remains unclear[2]. Here we demonstrate the function of ATF6α as an ER-stress-inducing tumour driver and metabolic master regulator restricting cancer immunosurveillance for HCC, in contrast to its well-characterized role as an adaptive response to ER stress[3]. ATF6α activation in human HCC is significantly correlated with an aggressive tumour phenotype, characterized by reduced patient survival, enhanced tumour progression and local immunosuppression. Hepatocyte-specific ATF6α activation in mice induced progressive hepatitis with ER stress, immunosuppression and hepatocyte proliferation. Concomitantly, activated ATF6α increased glycolysis and directly repressed the gluconeogenic enzyme FBP1 by binding to gene regulatory elements. Restoring FBP1 expression limited ATF6α-activation-related pathologies. Prolonged ATF6α activation in hepatocytes triggered hepatocarcinogenesis, intratumoural T cell infiltration and nutrient-deprived immune exhaustion. Immune checkpoint blockade (ICB)[4] restored immunosurveillance and reduced HCC. Consistently, patients with HCC who achieved a complete response to immunotherapy displayed significantly increased ATF6α activation compared with those with a weaker response. Targeting Atf6 through germline ablation, hepatocyte-specific ablation or therapeutic hepatocyte delivery of antisense oligonucleotides dampened HCC in preclinical liver cancer models. Thus, prolonged ATF6α activation drives ER stress, leading to glycolysis-dependent immunosuppression in liver cancer and sensitizing to ICB. Our findings suggest that persistently activated ATF6α is a tumour driver, a potential stratification marker for ICB response and a therapeutic target for HCC.},
}
@article {pmid41540462,
year = {2026},
author = {Thabet, DM and Abu Bakr, ASWK},
title = {Immunohistochemical expression of CANT1 and B3GNT3 in invasive ductal carcinoma of the breast: diagnostic and prognostic significance in lymph node metastasis.},
journal = {Diagnostic pathology},
volume = {21},
number = {1},
pages = {12},
pmid = {41540462},
issn = {1746-1596},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/mortality/diagnosis ; *Lymphatic Metastasis/pathology ; Middle Aged ; *Biomarkers, Tumor/analysis ; Adult ; *N-Acetylglucosaminyltransferases/analysis/metabolism ; Immunohistochemistry ; Aged ; *Carcinoma, Ductal, Breast/pathology/mortality/diagnosis/secondary ; Prognosis ; Kaplan-Meier Estimate ; Progression-Free Survival ; Lymph Nodes/pathology ; NM23 Nucleoside Diphosphate Kinases ; },
abstract = {BACKGROUND: Breast cancer is a leading global health concern, with lymph node metastasis (LNM) being a key prognostic factor affecting patient outcomes. Glycosylation-related enzymes such as calcium-activated nucleotidase 1 (CANT1) and Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) have been implicated in tumour progression, yet their roles in breast cancer, particularly invasive ductal carcinoma (IDC), are not well defined. This study investigates the immunohistochemical expression and correlation of CANT1 and B3GNT3 in IDC and their potential role in predicting LNM and clinical outcomes.<br><br>MATERIALS AND METHODS: Slides from paraffin blocks of 140 IDC cases and 108 corresponding metastatic axillary lymph nodes were stained with CANT1 and B3GNT3 antibodies. Associations between markers' immunoreactivity and clinicopathological variables were evaluated. Progression-free survival (PFS) was analysed using the Kaplan-Meier method. The prognostic significance of each variable was evaluated using both univariate and multivariate Cox proportional hazards regression analyses.<br><br>RESULTS: High CANT1 and B3GNT3 expression was observed in 47.1% and 45.7% of cases, respectively. Both markers were significantly associated with tumour grade, tumour stage, Nottingham prognostic index, lymph node status, lymph node ratio, Her2 status, Ki-67 proliferative index and distant metastasis. A significant positive correlation was found between CANT1 and B3GNT3 expression (p&#x2009;<&#x2009;0.001). Co-expression of both markers was strongly associated with LNM, along with a significant difference in the expression levels of each marker between primary tumours and corresponding LNM. Univariate analysis showed that tumour grade, stage, ER status and high B3GNT3 expression were all significantly associated with worse PFS. Multivariate Cox regression identified B3GNT3 expression, tumour grade and tumour stage as independent predictors of poor prognosis in IDC. High expression levels of CANT1 and B3GNT3 were associated with reduced PFS across all IDC cases (p&#x2009;=&#x2009;0.035 and p&#x2009;=&#x2009;0.001, respectively).<br><br>CONCLUSIONS: High CANT1 and B3GNT3 expressions are associated with aggressive clinicopathological features in IDC and predict unfavourable outcomes. These markers may serve as potential prognostic indicators and independent predictors of LNM in IDC patients.},
}
@article {pmid41618616,
year = {2026},
author = {Buñay, J and Record, M and de Medina, P and Ayadi, S and Pucheu, L and Colacios, C and Ségui, B and Höring, M and Liebisch, G and Martin, H and Poirot, M and Silvente-Poirot, S},
title = {The Phospholipid Bis(monoacylglycero)Phosphate Confers Antitumour Immunogenicity to Exosomes Secreted by Dendrogenin A, Which Activates Its Biosynthesis in Tumour Cells.},
journal = {Journal of extracellular vesicles},
volume = {15},
number = {2},
pages = {e70225},
doi = {10.1002/jev2.70225},
pmid = {41618616},
issn = {2001-3078},
support = {PLBio 20-160//Institut National Du Cancer/ ; //Equipe labellis&#xe9;e par la Ligue Nationale Contre le Cancer/ ; //Institut National de la Sant&#xe9; et de la Recherche M&#xe9;dicale/ ; //Centre National de la Recherche Scientifique/ ; //Universit&#xe9; de Toulouse/ ; },
mesh = {*Exosomes/metabolism/immunology ; Animals ; Mice ; *Monoglycerides/metabolism ; Humans ; *Lysophospholipids/metabolism ; Dendritic Cells/immunology/metabolism ; Cell Line, Tumor ; Mice, Inbred C57BL ; Female ; *Antineoplastic Agents/pharmacology ; },
abstract = {Dendrogenin A (DDA) is a cholesterol-derived antitumour metabolite that promotes the secretion of immunogenic antitumour exosomes (DDA-sEV) enriched in bis(monoacylglycero)phosphate (BMP). BMP is a phospholipid specific to late endosomes and lysosomes, where it plays a crucial role in lipid degradation, regulates the fate of endosomal cholesterol, and contributes to intraluminal vesicle formation. Dysregulation of BMP biosynthesis is associated with multiple diseases. Here, we show that the DDA/LXRβ complex activates the transcription and activity of phospholipase D (PLD) and CLN5, two enzymes involved in BMP biosynthesis. Inhibition of PLD in DDA-treated tumour cells reduces BMP levels in DDA-sEV, impairs their release, and their antitumour immune activity. Blocking BMP on DDA-sEV with a specific antibody abolishes their antitumour reponse, prevents the recruitment of activated dendritic cells (DC) and T cells into tumours, and decreases mouse survival. This blockade also impairs DDA-sEV uptake by immature DC (iDC) and hinders DC maturation and Th1 T cell activation. Notably, neutralising the BMP-presenting receptor on iDC inhibits DDA-sEV uptake and DC maturation. Treatment of iDC with free BMP induces their functional maturation, confirming BMP as a key immune activator. Furthermore, BMP-containing DDA-sEV enhance the efficacy of anti-PD-1 therapy in melanoma. Targeting LXRβ with DDA represents an innovative strategy to stimulate anticancer immunity by increasing BMP levels in tumours and sEV.},
}
@article {pmid41540255,
year = {2026},
author = {Morigny, P and Vondrackova, M and Ji, H and Brejchova, K and Krakovkova, M and Makris, K and Trubacova, R and Samanci, TF and Kaltenecker, D and Ng, SP and Karthikaisamy, V and Chrysostomou, SE and Bidovec, A and Ponce-de-Leon, M and Krauss, T and Seeliger, C and Prokopchuk, O and Martignoni, ME and Claussnitzer, M and Hauner, H and Schweiger, M and Bindels, LB and Berriel Diaz, M and Herzig, S and Lutter, D and Kuda, O and Rohm, M},
title = {Multi-omics profiling of cachexia-targeted tissues reveals a spatio-temporally coordinated response to cancer.},
journal = {Nature metabolism},
volume = {8},
number = {1},
pages = {237-259},
pmid = {41540255},
issn = {2522-5812},
support = {949017//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; },
mesh = {*Cachexia/metabolism/etiology/genetics ; Animals ; *Neoplasms/metabolism/complications ; Mice ; Humans ; Male ; *Metabolomics/methods ; Disease Models, Animal ; Glucose/metabolism ; Muscle, Skeletal/metabolism ; Multiomics ; },
abstract = {Cachexia is a wasting disorder associated with high morbidity and mortality in patients with cancer. Tumour-host interaction and maladaptive metabolic reprogramming are substantial, yet poorly understood, contributors to cachexia. Here we present a comprehensive overview of the spatio-temporal metabolic reprogramming during cachexia, using integrated metabolomics, RNA sequencing and [13]C-glucose tracing data from multiple tissues and tumours of C26 tumour-bearing male mice at different disease stages. We identified one-carbon metabolism as a tissue-overarching pathway characteristic for metabolic wasting in mice and patients and linked to inflammation, glucose hypermetabolism and atrophy in muscle. The same metabolic rewiring also occurred in five additional mouse models, namely Panc02, 8025, Apc[Min], LLC and KPP, and a humanised cachexia mouse model. Together, our study provides a molecular framework for understanding metabolic reprogramming and the multi-tissue metabolite-coordinated response during cancer cachexia progression, with one-carbon metabolism as a tissue-overarching mechanism linked to wasting.},
}
@article {pmid41529373,
year = {2026},
author = {Erkan, S and Ghadage, K and Meister, P},
title = {Chromosome organization by Structural Maintenance of Chromosomes complexes in C. elegans.},
journal = {Current opinion in genetics &amp; development},
volume = {96},
number = {},
pages = {102430},
doi = {10.1016/j.gde.2025.102430},
pmid = {41529373},
issn = {1879-0380},
mesh = {Animals ; *Caenorhabditis elegans/genetics ; Chromosomal Proteins, Non-Histone/genetics ; Chromatin/genetics ; *Multiprotein Complexes/genetics ; *Adenosine Triphosphatases/genetics ; *Chromosomes/genetics ; *DNA-Binding Proteins/genetics ; Cohesins ; Dosage Compensation, Genetic/genetics ; Cell Cycle Proteins/genetics ; Caenorhabditis elegans Proteins/genetics ; X Chromosome/genetics ; Chromosome Segregation/genetics ; },
abstract = {Genome folding is a key regulator of transcription, chromosome segregation, and genome stability. In Caenorhabditis elegans, chromatin folding strategies have diverged from those observed in mammals or flies, resulting in the absence of visible topologically associating domains (TADs) on autosomes. Here, condensin I, rather than cohesin, serves as the primary long-range loop extruder, while distinct cohesin isoforms specialize in mitotic cohesion and loop extrusion, forming enhancer-associated 'fountains' that modulate neuronal gene expression. On the X chromosome, dosage compensation depends on the dosage compensation complex, which incorporates a specialized condensin I[DC] to establish TADs, regulate chromatin states, and repress transcription. These multilayered mechanisms illustrate the evolutionary versatility of 3D genome organization and its intimate links to development, physiology, and lifespan, positioning C. elegans as a powerful model for dissecting structural maintenance of chromosomes-mediated genome regulation.},
}
@article {pmid41592189,
year = {2026},
author = {Baboli, KM and Salehiazar, S and Tran, T},
title = {Encapsulated Papillary Carcinoma of the Breast: Two Cases with Literature Review and Molecular Insights.},
journal = {Rhode Island medical journal (2013)},
volume = {109},
number = {2},
pages = {7-10},
pmid = {41592189},
issn = {2327-2228},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/genetics/diagnosis/therapy/surgery ; Middle Aged ; Adult ; *Carcinoma, Papillary/pathology/genetics/diagnosis/therapy/surgery ; Class I Phosphatidylinositol 3-Kinases/genetics ; Mastectomy, Segmental ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; },
abstract = {INTRODUCTION: Encapsulated papillary carcinoma (EPC) of the breast is a rare subtype of breast cancer, accounting for 0.5-2% of cases, and typically affects postmenopausal women. Characterized by well-circumscribed lesions lacking peripheral and central myoepithelial cells, EPC is associated with favorable prognosis due to its indolent behavior and high hormone receptor positivity. However, its potential association with ductal carcinoma in situ (DCIS) or invasive carcinoma necessitates thorough diagnostic evaluation.<br><br>CASE PRESENTATION: This study presents two cases of EPC-one in a 57-year-old and the other in a 39-year-old female-each with focal DCIS and strong estrogen and progesterone receptor expression. Both patients underwent breast-conserving surgery and were managed with hormone therapy.<br><br>CONCLUSION: Histopathological and immunohistochemical analyses confirmed the EPC diagnosis, and molecular insights revealed common mutations, particularly in the PIK3CA gene. This report underscores the importance of integrating clinical, histological, and molecular findings to guide diagnosis and management of EPC, which, despite its low invasive potential, shares genetic features with invasive ductal carcinoma.},
}
@article {pmid41587557,
year = {2026},
author = {De Coster, I and AbdelGhany, M and Sarakinou, E and Fineschi, C and Marchetti, E and La Gaetana, R and Nigro, S and Carducci, M and Massai, L and Conti, V and Rossi, O and Luna Cilio, G and Serry-Bangura, A and Tessitore, P and Van Damme, P and Withanage, K and Micoli, F and Berlanda Scorza, F and Rondini, S and Nakakana, UN and Kumar Arora, A},
title = {Safety and immunogenicity of a conjugate vaccine candidate against Salmonella enterica serovars Typhi and Paratyphi A in healthy adults in Europe: a phase 1 randomised controlled trial.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00730-3},
pmid = {41587557},
issn = {1474-4457},
abstract = {BACKGROUND: Enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi A remains a major concern. No vaccines are licensed against Salmonella Paratyphi A. We aimed to assess the safety and immunogenicity of an investigational conjugate vaccine against Salmonella Typhi and Paratyphi A (Vi-CRM197+O:2-CRM197).<br><br>METHODS: In this observer-masked, randomised, controlled, dose-escalation, single-centre, phase 1 trial done during Nov 28, 2022, to April 2, 2024, at the Centre for Evaluation of Vaccination in Belgium, healthy adults (aged 18-50 years) were randomly assigned (2:1 or 2:2:1 across different steps using sealed envelopes following a randomisation schedule generated by an independent statistician) to receive two intramuscular doses (on day 1 and day 169) of one of four Vi-CRM197+O:2-CRM197 formulations (low dose or full dose, with or without aluminium hydroxide) or a control vaccine (Vi capsular polysaccharide vaccine and diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine for first and second dose). The primary outcome was vaccine safety (solicited events during 7 days and unsolicited adverse events during 28 days after vaccination, serious adverse events [SAEs], and adverse events or SAEs leading to study withdrawal or withholding of further study intervention administration from day 1 to day 197, and deviations from normal or baseline laboratory test values 7 days after vaccination). Secondary outcomes included long-term vaccine safety (SAEs and adverse events or SAEs leading to study withdrawal from day 197 to day 337), and immunogenicity, including anti-Vi and anti-O:2 IgG antibody geometric mean concentrations and geometric mean ratios (GMRs) by ELISA, and seroresponses (percentages of participants with anti-Vi IgG concentrations &#x2265;4&#xb7;3 &#x3bc;g/mL and &#x2265;2&#xb7;0 &#x3bc;g/mL; &#x2265;4-fold anti-O:2 IgG concentration increase from baseline) at day 1 (as applicable), day 29, day 169, day 176, and day 197. Safety analyses were done on the solicited safety set, unsolicited safety set, and the exposed set. The primary immunogenicity analysis was done on the per-protocol set defined by timepoint. The trial is registered with ClinicalTrials.gov (NCT05613205) and gsk-studyregister.com (205480), and is completed.<br><br>FINDINGS: 96 participants were randomly assigned, 12 to each low-dose group, 24 to each full-dose group, and 24 to the control group. The incidence of solicited administration-site events (mostly pain) ranged from six (50% [95% CI 21&#xb7;1-78&#xb7;9]) of 12 participants in the low-dose without aluminium hydroxide group to 23 (96% [78&#xb7;9-99&#xb7;9]) of 24 in the full-dose with aluminium hydroxide group, versus 22 (92% [73&#xb7;0-99&#xb7;0]) of 24 in the control group. Solicited systemic events (mostly fatigue, headache, and myalgia) ranged from eight (67% [34&#xb7;9-90&#xb7;1]) of 12 in the low-dose groups to 20 (83% [62&#xb7;6-95&#xb7;3]) of 24 in the full-dose with aluminium hydroxide group, versus 21 (88% [67&#xb7;6-97&#xb7;3]) of 24 in the control group. The incidence of unsolicited adverse events (mostly nasopharyngitis) ranged from seven (58% [27&#xb7;7-84&#xb7;8]) of 12 in the low-dose without aluminium hydroxide group to ten (83% [51&#xb7;6-97&#xb7;9]) of 12 in the low-dose with aluminium hydroxide group, versus 14 (58% [36&#xb7;6-77&#xb7;9]) of 24 in the control group. Most safety laboratory results were within reference ranges. No SAEs occurred. After dose 1 (ie, at day 29), full-dose without aluminium hydroxide and full-dose with aluminium hydroxide induced the highest anti-Vi IgG responses (GMR 53&#xb7;01 [95% CI 31&#xb7;94-87&#xb7;99] and 31&#xb7;55 [18&#xb7;74-53&#xb7;11], respectively) versus control (4&#xb7;50 [2&#xb7;93-6&#xb7;90]). Full-dose without aluminium hydroxide and low-dose without aluminium hydroxide induced the highest anti-O:2 IgG responses after dose 1 (GMR 162&#xb7;61 [91&#xb7;17-290&#xb7;04] and 114&#xb7;19 [44&#xb7;83-290&#xb7;86], respectively), versus control (1&#xb7;27 [1&#xb7;02-1&#xb7;60]). 89-100% and 82-100% of participants (lowest percentages for low-dose with aluminium hydroxide) had anti-Vi IgG &#x2265;4&#xb7;3 &#x3bc;g/mL at day 29 (in initially seronegative participants) and &#x2265;4-fold anti-O:2 IgG increase from baseline, respectively, versus 13 (54% [95% CI 32&#xb7;8-74&#xb7;4]) and one (4% [0&#xb7;1-21&#xb7;1]) of 24 participants in the control group, respectively. The second dose did not boost the responses.<br><br>INTERPRETATION: Vi-CRM197+O:2-CRM197 formulations did not raise safety concerns and showed immunogenicity with a single dose, supporting further clinical assessment of the full-dose without aluminium hydroxide in target populations (infants and older age groups) in endemic regions.<br><br>FUNDING: Wellcome Trust.},
}
@article {pmid41105173,
year = {2026},
author = {Chang, RC and Ehyaee, V and Wattar, R and Braun, A and Gattuso, P and Ahmed, A},
title = {Evaluation of PRAME Expression in Cases of Breast Carcinoma Metastatic to Skin.},
journal = {The American Journal of dermatopathology},
volume = {48},
number = {2},
pages = {107-113},
doi = {10.1097/DAD.0000000000003159},
pmid = {41105173},
issn = {1533-0311},
mesh = {Humans ; Female ; *Skin Neoplasms/secondary/mortality ; Middle Aged ; *Antigens, Neoplasm/analysis ; Retrospective Studies ; Aged ; *Biomarkers, Tumor/analysis ; Male ; *Breast Neoplasms/pathology/mortality ; *Triple Negative Breast Neoplasms/pathology/mortality ; Adult ; Immunohistochemistry ; Aged, 80 and over ; Prognosis ; *Carcinoma, Ductal, Breast/mortality/secondary ; },
abstract = {Cutaneous metastases of breast neoplasms indicate advanced disease with poor prognosis. The role of Preferentially Expressed Antigen in Melanoma (PRAME) expression in breast cancer skin metastases remains poorly understood. In this study, we investigate PRAME expression in breast carcinoma metastatic to the skin, particularly triple-negative breast cancers (TNBC). A retrospective review of breast cancer cases with skin metastasis was conducted from January 2005 to March 2023. PRAME immunostaining was performed on skin metastatic lesions and corresponding primary tumors. A comparison group of noncutaneous metastases (n = 11) was included. Thirty patients with cutaneous metastasis were identified (29 women, 1 man; mean age 63 years). The most common site of skin metastasis was chest (25 cases, 83%). Histologically, 25 cases (83%) were invasive ductal carcinoma. Eleven cases (37%) were TNBC. PRAME positivity was observed in 10 skin metastases (33%) with 70% being triple negative. Among 20 available primary samples, only 3 were PRAME positive with corresponding positive metastases. Comparison group showed minimal PRAME expression. In total, 40% of patients died, with TNBC associated with higher mortality (P = 0.04). All PRAME-positive TNBC patients with follow-up were deceased. In conclusion, PRAME expression occurred in approximately one-third of breast cancer skin metastases, with predominance in triple-negative breast cancer. These findings warrant further investigation of PRAME's role in cutaneous metastasis and its diagnostic implications.},
}
@article {pmid41546339,
year = {2025},
author = {Nishimura, A and Yatsuyanagi, M},
title = {[pT1c Breast Cancer Presenting with Skin Rupture without Skin Invasion-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {52},
number = {13},
pages = {1332-1334},
pmid = {41546339},
issn = {0385-0684},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/therapy/complications ; Aged ; Neoplasm Invasiveness ; *Carcinoma, Ductal, Breast/complications/pathology/therapy ; *Skin/pathology ; Rupture, Spontaneous/etiology ; Neoplasm Staging ; Sentinel Lymph Node Biopsy ; Mastectomy, Segmental ; },
abstract = {We report a case of breast bleeding caused by breast cancer without skin invasion. A woman in her 70s was aware of a mass in her right breast but left it untreated. About 6 months after noticing the mass, she visited our hospital due to bleeding from the right breast. Although needle biopsy did not reveal a diagnosis of breast cancer, we diagnosed her as having breast cancer based on clinical findings and recommended her to have surgery. Her consent was not obtained. Approximately 1 year later, she experienced bleeding from her right breast and visited our hospital. A tumor was identified, a biopsy was performed, and a diagnosis of breast cancer was made. A right lumpectomy and sentinel lymph node biopsy was carried out. Pathological diagnosis was invasive ductal carcinoma. No skin invasion was observed. The final diagnosis was pT1c, pN0 (sn), M0, pStageⅠ. After surgery, the patient was treated with tamoxifen and radiation therapy, and is currently free of recurrence.},
}
@article {pmid41546327,
year = {2025},
author = {Yoshioka, S and Hashizume, S and Sakai, S and Sawamura, N and Yasumoto, T and Ueda, R and Hayashi, S and Hara, A and Taniguchi, Y and Takeyama, H and Tanaka, N and Urano, N and Nishikawa, K and Okamura, S and Yokouchi, H},
title = {[Experience of Performing Liver Biopsy in Combination with TAE for Recurrence of HR-Positive HER2-Negative Breast Cancer with Rapid Appearance of Organ Metastases].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {52},
number = {13},
pages = {1297-1299},
pmid = {41546327},
issn = {0385-0684},
mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/pathology/therapy/chemistry/drug therapy/surgery ; *Liver Neoplasms/secondary/therapy ; Erb-b2 Receptor Tyrosine Kinases/analysis ; Biopsy ; Recurrence ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Liver/pathology ; },
abstract = {The patient was a 54-year-old woman diagnosed with right breast cancer at the age of 49 with cT4bN1M0, cStage ⅢB, and underwent radical surgery after preoperative chemotherapy. The histopathologic diagnosis was invasive ductal carcinoma, histological treatment effect Grade 1a, HR positive HER2 negative, chest wall irradiation and hormone therapy as postoperative treatment. At 5 years after surgery, there were no signs of recurrence on the imaging, but at a routine checkup 4 months later, left back pain and hip joint pain were observed, and bone metastases were diagnosed by MRI. PET- CT revealed multiple liver, lung, bone and lymph node metastases, and the course of recurrence was rapid in a short period of time. To re-evaluate the subtype, a liver biopsy was performed in combination with TAE to prevent bleeding for liver tumors with abundant blood flow. As a result, PgR turned negative, but there was no change in subtype. After irradiation to the pain area, paclitaxel and bevacizumab therapy was administered, and a marked reduction of pulmonary and liver metastases, and the disappearance of pain were observed. Local hepatic therapy with TAE followed by chemotherapy was thought to have helped the patient overcome the rapid tumor growth.},
}
@article {pmid41546284,
year = {2025},
author = {Oshima, K and Hasegawa, M and Ogino, Y and Yamaura, M and Anno, K and Yanagisawa, K and Shinke, G and Katsuyama, S and Kinoshita, M and Hiraki, M and Iwagami, Y and Sugimura, K and Yasui, M and Takeda, Y and Murata, K},
title = {[A Case of Ipsilateral Breast Tumor Recurrence in Which a Sentinel Lymph Node Was Identified in the Contralateral Axilla].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {52},
number = {13},
pages = {1168-1170},
pmid = {41546284},
issn = {0385-0684},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery ; Axilla/pathology ; Lymphatic Metastasis ; *Sentinel Lymph Node/pathology/surgery ; Aged, 80 and over ; Recurrence ; Sentinel Lymph Node Biopsy ; },
abstract = {The patient was a female in her 80s. She had undergone Bp+SN for left breast cancer 18 years ago. This time, she was referred to our department because of suspicion of ipsilateral breast tumor recurrence. Breast ultrasound revealed a 15 mm mass in the CA area of left breast, and biopsy revealed IDC, ER+, PgR+, HER2-. The diagnosis was cT1cN0M0, Stage Ⅰ, and the treatment plan was Bt+SN. Preoperative lymphoscintigraphy revealed a single accumulation in the contralateral axillary lymph node. Surgery was performed using the dye method, and the ipsilateral axilla was searched, but no sentinel lymph node was found. However, 1 sentinel lymph node in the contralateral axilla that only had RI uptake was found. Rapid diagnosis was negative for metastasis, so axillary dissection was omitted. Contralateral axillary lymph node metastasis is classified as distant lymph node metastasis according to the breast cancer treatment guidelines. However, contralateral axillary lymph node metastasis observed at the same time as ipsilateral breast tumor recurrence may be treated as regional lymph node metastasis if it is considered to be the result of changes in lymphatic flow caused by the initial surgery.},
}
@article {pmid41546264,
year = {2025},
author = {Kasagawa, T and Fujimori, T and Ishii, N and Ozaki, D and Yonemori, Y and Yasuda, S},
title = {[Three Cases of Esophageal Metastasis from Breast Cancer with Different Clinical Courses Based on Treatment Strategies].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {52},
number = {13},
pages = {1110-1112},
pmid = {41546264},
issn = {0385-0684},
mesh = {Humans ; Female ; *Esophageal Neoplasms/secondary/therapy ; Aged, 80 and over ; *Breast Neoplasms/pathology/therapy ; Aged ; Middle Aged ; Fatal Outcome ; },
abstract = {Esophageal metastasis from breast cancer is rare and seldom diagnosed before death, with no established standard treatment. We report 3 cases managed at our institution. Case 1:A 78-year-old woman previously underwent surgery for invasive ductal carcinoma(ER+, PgR+, HER2-)at the age of 65. Eight years postoperatively, the first recurrence occurred, followed by progressive dysphagia 5 years later, leading to the diagnosis of esophageal metastasis. Case 2:A 63-year-old woman had surgery at age 48 for invasive ductal carcinoma(ER+, PgR+, HER2-). Fourteen years postoperatively, she experienced a recurrence, and 1 month later, rapidly progressive dysphagia developed, resulting in the diagnosis of esophageal metastasis. Case 3:An 81-year-old woman was diagnosed with stage Ⅳ(bone)invasive ductal carcinoma(ER+, PgR+, HER2-)at age 73. After 8 years of systemic treatment, esophageal metastasis was diagnosed. In Cases 1 and 3, radiation therapy was selected, leading to symptomatic improvement and maintenance of oral intake until death. In contrast, Case 2, complicated by interstitial pneumonia, was treated with chemotherapy, but symptoms did not improve, and the patient remained unable to take food orally until death.},
}
@article {pmid41546236,
year = {2025},
author = {Adachi, K and Nagae, J and Kubota, H and Suzuki, S and Hirano, T and Ishibashi, N and Sakurai, K},
title = {[Bone Only Metastasis Breast Cancer with Effective Disease Control by Primary Tumor Resection-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {52},
number = {13},
pages = {1029-1031},
pmid = {41546236},
issn = {0385-0684},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/drug therapy ; Middle Aged ; *Bone Neoplasms/secondary/surgery/drug therapy ; Mastectomy ; *Carcinoma, Ductal, Breast/surgery/drug therapy/secondary ; },
abstract = {We report a case of metastatic breast cancer in the bones effectively treated with locoregional surgery. The patient was a 52-year-old woman who presented with an increasing right breast lump. A mass accompanied by skin redness 5 cm in diameter was palpable in the AC area of the right breast. Ultrasonography revealed multiple other masses in the bilateral breasts that were suspected to be malignant. Core needle biopsy led to the diagnosis of invasive ductal carcinoma in both breasts. Tumor marker 1-CTP was elevated, and bone scintigraphy showed multiple abnormal accumulations in the thoracic and lumbar spine, indicating multiple bone metastases. Bilateral mastectomy was first performed for local control. Histopathological diagnosis was invasive ductal carcinoma(scirrhous type)in both breasts, with multiple lesions, hormone receptor positive, and HER2 negative. After surgery, chemotherapy followed by endocrine therapy was administered, and tumor markers decreased, and bone metastases remained stable disease(SD). Two years and 2 months after surgery, no local recurrence or appearance of new lesions have been observed.},
}
@article {pmid41546229,
year = {2025},
author = {Sugimoto, Y and Terada, I and Nakamura, S and Aoki, T and Okamoto, J and Yamazaki, H and Zaimoku, R and Tsukioka, Y},
title = {[A Case of Sarcoid-Like Reaction That Was Difficult to Distinguish from Breast Cancer Relapse].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {52},
number = {13},
pages = {1008-1010},
pmid = {41546229},
issn = {0385-0684},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy/diagnosis ; Recurrence ; Aged, 80 and over ; Diagnosis, Differential ; *Carcinoma, Ductal, Breast/drug therapy/secondary ; *Sarcoidosis/diagnosis ; Lymphatic Metastasis ; Positron Emission Tomography Computed Tomography ; },
abstract = {An elderly woman in her 80s with a medical history of rheumatoid arthritis and chronic hepatitis B was diagnosed with Stage Ⅳ, ER-negative, HER2-positive invasive ductal carcinoma of the left breast, with mediastinal lymph node metastases. She received chemotherapy combined with anti-HER2 therapy and achieved a complete remission after 12 months. Three years and 7 months later, FDG-PET/CT revealed enlargement of the left axillary lymph nodes, and they were suggested as recurrences. Radiotherapy was administered, resulting in temporary reduction in lymph node size. However, 10 months later, the lymph nodes re-enlarged and were subsequently surgically resected. Histopathological examination revealed that they were non-caseating granulomas without any evidence of malignancy, consistent with a diagnosis of sarcoid-like reaction. The patient has been followed up postoperatively without recurrence for 12 months.},
}
@article {pmid41531577,
year = {2025},
author = {Nishimura, H and Mine, Y and Takahashi, Y and Deshpande, GA and Watanabe, J and Kutomi, G and Naito, T},
title = {Estrogen Receptor-Low Breast Cancer With Sternal Metastasis Presenting as "Stiff Neck" in a Young Female.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e99072},
pmid = {41531577},
issn = {2168-8184},
abstract = {A previously healthy 20-year-old Japanese woman was referred to the outpatient clinic for evaluation of right neck stiffness, which had persisted for two months, along with weight loss, malaise, and elevated inflammatory markers. On physical examination, spontaneous pain was noted in the right upper trapezius, along with incident pain around both clavicles and shoulders. Swelling was found around the sternal manubrium, and two palpable masses were present in the right breast. A computed tomography scan of the thorax revealed a low-density, lobulated area in the right breast, a soft-tissue mass in the sternal manubrium, multiple lymphadenopathies, and small nodules in the lungs and liver. Core needle biopsy of the breast mass confirmed estrogen receptor (ER)-low invasive ductal carcinoma, and testing for breast cancer susceptibility gene mutations was negative. Systemic chemotherapy was initiated for the treatment of metastatic triple-negative breast cancer. Breast cancer causing neck or shoulder pain is rare. The right neck stiffness likely resulted from brachial plexus compression due to bulky right axillary lymphadenopathy, leading to thoracic outlet syndrome. Lung metastasis could also cause referred pain through the vagus nerve. This case presented an atypical manifestation of "stiff neck" associated with thoracic tumors. Notably, the patient initially hesitated to share key symptoms, which may have contributed to a delayed diagnosis. We believe that the rapid progression of her lesions may have heightened her anxiety, which in turn further impaired her communication with the medical staff.},
}
@article {pmid41526224,
year = {2026},
author = {Wu, ZS and Huang, SM and Huang, YH},
title = {Tramadol induced hypoxia signaling and paraptosis-like cell death in breast cancer cells via HIF-1α and ATF4 dependent pathways.},
journal = {Redox report : communications in free radical research},
volume = {31},
number = {1},
pages = {2588866},
pmid = {41526224},
issn = {1743-2928},
mesh = {Humans ; *Tramadol/pharmacology ; *Activating Transcription Factor 4/metabolism/genetics ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; *Breast Neoplasms/metabolism/drug therapy/pathology ; Female ; Signal Transduction/drug effects ; Endoplasmic Reticulum Stress/drug effects ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism ; Cell Death/drug effects ; MCF-7 Cells ; Cell Survival/drug effects ; Cell Hypoxia/drug effects ; Paraptosis ; },
abstract = {OBJECTIVES: Tramadol, a clinically approved analgesic widely used for managing postoperative pain, has recently been shown to possess anticancer properties in several tumor models, especially in breast cancer. In this study, we explored the intricate molecular mechanisms by which tramadol induces cytotoxicity in breast cancer cell lines.<br><br>METHODS: Two invasive ductal carcinoma lines MCF-7 and MDA-MB-231 were used to verify the molecular cytotoxicity of tramadol using cell viability analysis, flow cytometry analysis, real-time polymerase chain reaction, western blotting, Seahorse biogenetic, and transmission electron microscopy analyses.<br><br>RESULTS: Our findings demonstrate that tramadol induces the normoxic stabilization and nuclear translocation of hypoxia-inducible factor- 1 alpha (HIF-1&#x3b1;) to activate hypoxia responsive genes. Concurrently, tramadol triggers endoplasmic reticulum (ER) stress and activates the p-eIF2&#x3b1;/ATF4/CHOP signaling axis, leading to the generation of reactive oxygen species, impaired autophagy, mitochondrial dysfunction, including mitochondrial membrane depolarization and the decline of ATP production, cytoplasmic vacuolization, and lipid droplet accumulation which is characteristics of paraptosis-like cell death. Notably, the knockout of HIF-1&#x3b1; or ATF4 significantly reduced tramadol-induced cytotoxicity, highlighting their crucial roles in mediating these cellular responses.<br><br>CONCLUSION: Tramadol induced breast cancer cell death via paraptosis which highlights its therapeutic potential in targeting resistant cancer subtypes such as triple-negative breast cancer.},
}
@article {pmid41521709,
year = {2026},
author = {Bujassoum Al-Bader, S and Al-Mulla, H and Al-Habish, H and Kusasi, S and Abduo, N and Bakheet, N and Ghazouani, H and Sidenna, M and Abbaszadeh, F and Alsulaiman, R},
title = {Identifying a Recurrent BRCA1 Variant in the Qatari Population With Unique Genotype-Phenotype Correlations.},
journal = {Molecular genetics &amp; genomic medicine},
volume = {14},
number = {1},
pages = {e70144},
pmid = {41521709},
issn = {2324-9269},
support = {//Hamad Medical Corporation/ ; },
mesh = {Humans ; Female ; Qatar/epidemiology ; *BRCA1 Protein/genetics ; Adult ; Middle Aged ; *Hereditary Breast and Ovarian Cancer Syndrome/genetics/epidemiology/pathology ; Genetic Association Studies ; Male ; Aged ; Retrospective Studies ; Ovarian Neoplasms/genetics ; },
abstract = {BACKGROUND: Hereditary breast and ovarian cancer syndrome (HBOC) is the most common cause of hereditary breast and ovarian cancers in Qatar and worldwide, which is caused by pathogenic variants in the BRCA1 and BRCA2 genes. The aim of this retrospective study is to describe a common recurrent pathogenic variant in the BRCA1 gene that was observed in the native Qatari population with unique genotype-phenotype correlations.<br><br>METHODS: Medical records of Qatari patients (affected and unaffected) with personal and/or family history of breast and ovarian cancers who carry pathogenic/likely pathogenic variants in the BRCA1 gene were reviewed between 2013 and 2020. Epidemiological information and clinical data were reviewed, including age, gender, ethnic background, personal history of cancer, tumour characteristics, and family history. We used frequencies and proportions to describe the data and used Kaplan-Meier curves and log-rank analysis to compare survival rates. For the analysis, we used Stata Corp. 2015. Stata Statistical Software: Release 14, College Station, TX: Stata Corp. LP.<br><br>ETHICAL COMPLIANCE: Ethical committee approval was obtained from Hamad Medical Corporation IRB committee (MRC-01-20-1086).<br><br>RESULT: Sixty-three Qatari affected patients and unaffected individuals who carry the BRCA1 variant were included in the study. Our result confirms the presence of a common recurrent pathogenic variant c.4787C>A p.(Ser1596Ter) among Qatari patients who belong to 8 consanguineous large families, followed by c.4065_4068del p.Asn1355fs, both in BRCA1. The BRCA1 c.4787C>A variant is highly associated with early onset breast cancer, specifically invasive ductal carcinoma (IDC) triple negative breast cancer (stage I, grade III), rather than ovarian cancer. Additionally, the c.4787C>A variant was found to exhibit high penetrance in families with early-onset breast cancer.<br><br>CONCLUSION: We showed that BRCA1 c.4787C>A pathogenic variant is a highly recurrent variant among Qatari consanguineous families and contributes to the early onset breast cancer in Qatar. Early identification of this variant can aid in improving patients' survival and guide early personalized treatment and prevention.},
}
@article {pmid41516506,
year = {2025},
author = {Zeng, K and Yu, W and Qin, X and Long, S},
title = {Small-Target Detection Algorithm Based on Improved YOLOv11n.},
journal = {Sensors (Basel, Switzerland)},
volume = {26},
number = {1},
pages = {},
pmid = {41516506},
issn = {1424-8220},
support = {2025JC-YBMS-255//Research on Semantic Change Detection in PolSAR Images with Limited Samples by Knowledge Guidance and Data Drive/ ; },
abstract = {Target detection in UAV aerial photography scenarios faces challenges of small targets and complex backgrounds. Thus, we proposed an improved YOLOv11n small-target detection algorithm. First, a detection head is added to the 160 × 160 resolution feature layer, and non-adjacent layer feature is fused via Asymptotic Feature Pyramid Network (AFPN) to alleviate feature loss caused by downsampling and reduce cross-level feature conflicts. Second, the Spatial Channel Attention SPPF (SCASPPF) module replaces the original Spatial Pyramid Pooling-Fast (SPPF) module to highlight key features and suppress irrelevant ones. Moreover, the loss function is enhanced by fusing MPDIoU and InnerIoU to boost detection accuracy. Finally, Inception Deep Convolution (IDC) is adopted to improve the C3k2 module, expanding the model's receptive field and enhancing small-target detection performance. Experiments on the Visdrone2019 dataset show that the algorithm achieves 39.256% mAP@0.5, 6.689% higher than 32.567% mAP@0.5 of the benchmark model (YOLOv11n).},
}
@article {pmid41510820,
year = {2026},
author = {Yoon, EJ and Jeong, J and Choi, Y and Kim, DH and Kim, TM and Choi, EK and Kim, YB and Park, D},
title = {Therapeutic effect of amniotic membrane mesenchymal stem cell-derived exosome-rich conditioned medium in cerebral palsy model.},
journal = {Stem cells translational medicine},
volume = {15},
number = {1},
pages = {},
pmid = {41510820},
issn = {2157-6580},
support = {NRF-2022R1A2C1003624//Ministry of Education/ ; },
mesh = {*Exosomes/metabolism ; *Mesenchymal Stem Cells/metabolism/cytology ; Culture Media, Conditioned/pharmacology ; Animals ; *Cerebral Palsy/therapy/pathology ; Humans ; *Amnion/cytology ; Disease Models, Animal ; Rats ; Cell Differentiation/drug effects ; Female ; Apoptosis/drug effects ; Oligodendroglia/metabolism ; Male ; },
abstract = {BACKGROUND: Cerebral palsy (CP), primarily caused by perinatal cerebral hypoxia and ischemia, is a devastating neurological disease in children characterized by motor, behavioral, and cognitive disorders. This study aimed to evaluate the therapeutic effects of amniotic membrane mesenchymal stem cell-derived exosome-rich conditioned medium (ERCM) in a CP model.<br><br>METHODS: ERCM components were analyzed using enzyme-linked immunosorbent assay. Biodistribution was examined via fluorescence-labeled ERCM in both normal and CP induced animals. In vitro, the neuroprotective effects of ERCM against lipopolysaccharide and potassium cyanide-induced cytotoxicity were assessed in human neural stem cells and oligodendrocyte progenitor cells, focusing on apoptosis, inflammation, and oligodendrocyte differentiation. In vivo, ERCM was injected into CP-induced animals, followed by evaluation of antiapoptotic and anti-inflammatory signaling, motor and cognitive function, and white matter integrity.<br><br>RESULTS: ERCM contained a broad array of growth factors and demonstrated enhanced retention in CP-affected brain regions. In vitro, ERCM significantly reduced apoptos is and inflammation, and promoted oligodendrocyte maturation via upregulation of Nkx2.2, CN Pase, and MBP. In vivo, ERCM treatment improved motor and cognitive performance, in hibited cell death and inflammatory responses, and increased expression of oligodendrocyte markers, including Nkx2.2, Olig2, CNPase, and MBP via increasing growth factor expression. Furthermore, ERCM attenuated demyelination in the corpus callosum, a region particularly vulnerable in CP.<br><br>CONCLUSION: ERCM confers therapeutic benefits in CP by preserving neural stem and oligodendrocyte progenitor cells, modulating apoptosis and inflammation, and enhancing oligodendrocyte differentiation. Accordingly, ERCM may present a good candidate as a CP therapeutic agent.},
}
@article {pmid41494265,
year = {2026},
author = {Chen, Y and Wang, P and Zeng, J and Tan, M and Shan, K and Nie, L and Xue, Y and Wang, T},
title = {MGScreener: A multi-view mammography-based model optimized with active learning for breast cancer diagnosis.},
journal = {Talanta},
volume = {301},
number = {},
pages = {129345},
doi = {10.1016/j.talanta.2025.129345},
pmid = {41494265},
issn = {1873-3573},
mesh = {Humans ; *Breast Neoplasms/diagnostic imaging/diagnosis ; *Mammography/methods ; Female ; Middle Aged ; Machine Learning ; },
abstract = {Breast cancer remains the leading cause of cancer-related mortality among women worldwide. Early screening and accurate subtype classification are critical for guiding clinical decision-making. In this study, we present MGScreener, an interpretable multi-view framework that integrates dual-view mammography images, including cranial-caudal (CC) and mediolateral oblique (MLO) views, with patient-level clinical data. The model incorporates an active learning strategy to address two key classification tasks: distinguishing benign from malignant breast lesions and identifying invasive ductal carcinoma (IDC) among malignant subtypes. An entropy-based uncertainty sampling method is employed to select highly informative cases from 210 unlabeled samples for prioritized annotation, substantially reducing manual labeling costs. Across two independent test sets, MGScreener-1 achieved an accuracy of 89.7 % and an ROC-AUC of 0.941 for benign-versus-malignant classification (Task 1), while MGScreener-2 achieved an accuracy of 88.2 % and an ROC-AUC of 0.884 for IDC identification (Task 2). With MGScreener assistance, radiologists improved their diagnostic accuracy by more than 10 % compared with independent reading. Overall, MGScreener offers a scalable and effective solution for precise breast cancer screening and molecular subtype classification.},
}
@article {pmid41459855,
year = {2025},
author = {Cabıoğlu, N and Türkyılmaz, Z and Özkurt, E and İğci, A and Müslümanoğlu, M and Kapkaç, M and Yeniay, L and Taşdelen, &#x130; and Aksaz, E and Haydaroğlu, A and Alanyalı, S and Çelik, V and Gazioğlu, E and Gökgöz, &#x15e; and Şenol, K and Önal, B and Özbaş, S and Ok, E and Akcan, A and Canturk, NZ and Koçak, S and Güllüoğlu, B and Demirer, S and Koyuncu, A and Tükenmez, M and Girgin, S and Çolak, T and Velidedeoglu, M and Karadeniz, E and Akçay, MN and Oltulu, M and Kebudi, A and Emiroğlu, S and Uras, C and Özmen, V},
title = {Poor Prognostic Clinicopathological Features of Young Women with Breast Cancer in the MF18-04 Turkish National Breast Cancer Registry Study.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {26},
number = {12},
pages = {4407-4417},
doi = {10.31557/APJCP.2025.26.12.4407},
pmid = {41459855},
issn = {2476-762X},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/metabolism/epidemiology ; Adult ; Turkey/epidemiology ; Middle Aged ; Prognosis ; Young Adult ; Adolescent ; Registries ; Aged ; Aged, 80 and over ; Follow-Up Studies ; Age Factors ; *Carcinoma, Ductal, Breast/pathology/surgery/metabolism ; Mastectomy ; Receptors, Estrogen/metabolism ; Neoplasm Staging ; Lymphatic Metastasis ; *Carcinoma, Lobular/pathology/surgery/metabolism ; Receptors, Progesterone/metabolism ; Lymph Node Excision ; Receptor, ErbB-2/metabolism ; Survival Rate ; },
abstract = {OBJECTIVE: The role of younger age as a prognostic factor in breast cancer remains debated. Despite its association with an aggressive clinical course, there is insufficient research on its etiology. This study aimed to analyze age-related differences in breast cancer diagnosis among Turkish women.<br><br>MATERIALS AND METHODS: Data from 23,594 patients in the National Breast Cancer Database (NBCD) were analyzed. The demographic, clinical, and pathological characteristics of patients aged &#x2264;40 years were compared with those >40 years.<br><br>RESULTS: The median age was 50 years (range 18-97). Among them, 4,535 patients (19%) were 40 years old or younger, with 84% of this subgroup being over 30 years old. Conversely, 19,059 patients (81%) were older than 40. Patients in the younger age group were less likely to have pathologic T1 disease (41% vs. 47%), N0 disease (49% vs. 55%), and Stage I disease (25% vs. 31%) compared to those over 40 (p<0.001). The rates of mastectomy (41% vs. 39%; p = 0.024) and axillary dissection (71% vs. 65%; p = 0.001) were higher among patients diagnosed at 40 years of age or younger. Multivariate analysis identified significant associations in younger patients, including invasive ductal carcinoma (95% CI, 1.06-1.43), estrogen receptor (ER) negativity (95% CI, 1.26-1.87), PR negativity (95% CI, 1.21-1.75), high histologic grade (95% CI, 1.43-1.87), multifocality/multicentricity (95% CI, 1.26-1.72), T3-T4 tumors (95% CI, 1.06-1.66), and axillary positivity (95% CI, 1.025-1.321).<br><br>CONCLUSIONS: Breast cancer diagnosed at &#x2264;40 years is more likely to exhibit aggressive biology, multifocality, or multicentricity presentation, and present at advanced stages. Consequently, younger patients experience higher rates of mastectomy and axillary dissection. These findings suggest a poorer prognosis, highlighting the need for more intensive therapeutic strategies in this population.},
}
@article {pmid41457395,
year = {2026},
author = {Dudipala, H and Nazari, SS and Werneck da Cunha, I and Coligado, N and Baca, Y and Wei, S and Elliott, A and Smith, ND and Geynisman, DM and Brown, JT and Zarrabi, KK and Agarwal, N and Antonarakis, ES and Herchenhorn, D and McKay, RR},
title = {Molecular alteration profiles characterize intraductal carcinoma of the prostate.},
journal = {Cancer},
volume = {132},
number = {1},
pages = {e70238},
doi = {10.1002/cncr.70238},
pmid = {41457395},
issn = {1097-0142},
mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology/surgery ; Aged ; Middle Aged ; Prostatectomy ; Mutation ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery ; *Biomarkers, Tumor/genetics ; *Carcinoma, Ductal/genetics/pathology ; Tumor Microenvironment ; High-Throughput Nucleotide Sequencing ; },
abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is an intra-acinar and/or intraductal neoplastic epithelial proliferation that is a distinct histological entity according to the 2016 World Health Organization (WHO) classification system. Clinically, it is associated with higher grade tumors and a more aggressive disease course. However, the molecular underpinnings of IDC-P are not well elucidated.<br><br>METHODS: This study identified radical prostatectomy (RP) cases from the Caris Life Sciences database, classified as prostatic adenocarcinoma with grade group 4/5 or with the words "cribriform," "necrosis," or "intraductal" in the pathology report. Digitized hematoxylin-eosin slides underwent central pathology review by a board-certified genitourinary pathologist to identify the presence of IDC-P according to the 2022 WHO classification. IDC-P cases (n&#xa0;=&#xa0;175) were compared to non-IDC-P cases (n&#xa0;=&#xa0;5334). Prostatic tumor specimens were sequenced via next-generation DNA/RNA sequencing.<br><br>RESULTS: Compared to non-IDC-P cases, the IDC-P cohort had significantly more mutations in MUTYH (4.5% vs. 1.4%; p&#xa0;<&#xa0;.01), FANCA (2.7% vs. 0.5%; p&#xa0;<&#xa0;.01), NBN (2.5% vs. 0.6%; p&#xa0;<&#xa0;.05), and MTOR (0.6% vs. 0.1%; p&#xa0;<&#xa0;.05). IDC-P tumors were enriched for DLL3 and CEACAM5 expression, with lower expression of STEAP1, TROP2, ERBB2, PSCA, and B7-H3, compared to non-IDC-P tumors. IDC-P had significantly higher neuroendocrine prostate cancer signature scores and IFN-&#x3b3; signature scores, and similar androgen receptor signature scores, compared to non-IDC-P. The tumor microenvironment of IDC-P had significantly higher cell fractions of M2 macrophages and fewer dendritic cells.<br><br>CONCLUSIONS: IDC-P possesses a distinct molecular and immunological profile. Understanding these molecular underpinnings is crucial for the development of personalized treatment strategies for histologically distinct prostate cancer subsets.},
}
@article {pmid41455364,
year = {2026},
author = {Hao, S and Zhou, J and Siriwardena, T and Javor, S and Gan, B and He, R and Song, Y and Wang, Z and Xiao, W},
title = {A novel polypeptide molecule attenuates atopic dermatitis by targeting CCR8-CCL1 axis.},
journal = {International immunopharmacology},
volume = {170},
number = {},
pages = {116051},
doi = {10.1016/j.intimp.2025.116051},
pmid = {41455364},
issn = {1878-1705},
mesh = {*Dermatitis, Atopic/drug therapy/immunology ; Animals ; Humans ; *Receptors, CCR8/metabolism/antagonists &amp; inhibitors ; *Peptides/therapeutic use/pharmacology ; *Chemokine CCL1/metabolism ; Mice ; Skin/pathology/drug effects/immunology ; Disease Models, Animal ; Dendritic Cells/drug effects/immunology ; Cell Movement/drug effects ; Mice, Inbred BALB C ; Mast Cells/drug effects/immunology ; Cytokines/metabolism ; Female ; },
abstract = {Atopic dermatitis (AD) is a common chronic inflammatory skin disease with diverse clinical phenotypes. Although a variety of drugs are available, the current clinical treatment still cannot meet the needs of patients with AD. In this study, we designed a series of polypeptides through a new drug discovery technology combined with big data and artificial intelligence in our polypeptide library and successfully screened 2 candidates by in vitro and in vivo study. As results showed that the 2 candidates have a high affinity for human CC chemokine receptor 8 (CCR8) and significantly inhibited interstitial dendritic cell (iDC) migration induced by CC chemokine ligand 1 (CCL1) via interfering with the CCL1-CCR8 axis. The efficacy of CCR8 polypeptide candidates on AD were further evaluated in two dermatitis mouse models. We found that applying SP-TG02 to the skin ameliorated MC903 and OXA-induced skin AD-like symptoms and histological damage, reduced mast cell infiltration and down-regulated the expression of pro-inflammatory cytokines in skin tissue. Collectively, SP-TG02 may be a promising novel CCR8 polypeptide inhibitor for the treatment of atopic dermatitis.},
}
@article {pmid41437607,
year = {2025},
author = {Ishikawa, Y and Ando, J and Takemae, M and Toyota, T},
title = {[Safe Use of Anti-HER2 Antibodies to a Patient with HER2-Positive Breast Cancer and Markedly Reduced Cardiac Function-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {52},
number = {12},
pages = {889-892},
pmid = {41437607},
issn = {0385-0684},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/physiopathology/pathology/surgery ; Middle Aged ; *Receptor, ErbB-2/immunology/analysis ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Trastuzumab/administration &amp; dosage ; Neoadjuvant Therapy ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; },
abstract = {The patient was a 53-year-old female diagnosed with right breast cancer cT2N2bM0, cStage ⅢA, and the histopathological findings revelaed invasive ductal carcinoma, NG2, HG2, ER 90%, PgR 30%, HER2 3+, and Ki-67 50%. Cardiac function tests to assess suitability for neoadjuvant chemotherapy revealed a left ventricular ejection fraction of 39.7% and left ventricular hypokinesis. Trastuzumab was the preferred treatment for the breast cancer, and after consultation with the cardiologist, trastuzumab+pertuzumab+paclitaxel was initiated as neoadjuvant chemotherapy, in combination with an angiotensin Ⅱ receptor blocker and a beta-blocker. Post-surgery, histopathological examination revealed a non-pathological complete response, and treatment was continued with a T-DM1+aromatase inhibitor. The patient's cardiac function remained stable during anti-HER2 antibodies. We encountered a case in which anti-HER2 antibodies were administered to a patient with a HER2-positive breast cancer and markedly reduced cardiac function. With regular monitoring, appropriate cardiac care, and cardioprotective medications, anti-HER2 antibodies can be safely administered to patients with impaired cardiac function.},
}
@article {pmid41436217,
year = {2025},
author = {Khan, NU and Ali, SM and Pandit, DG and Chhetri, SK},
title = {Anti-AMPA receptor limbic encephalitis as the initial manifestation of metastatic breast cancer.},
journal = {BMJ case reports},
volume = {18},
number = {12},
pages = {},
doi = {10.1136/bcr-2025-268324},
pmid = {41436217},
issn = {1757-790X},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/complications ; *Limbic Encephalitis/immunology/diagnosis/etiology/therapy ; *Receptors, AMPA/immunology ; *Carcinoma, Ductal, Breast/secondary/complications ; *Autoantibodies/cerebrospinal fluid ; Magnetic Resonance Imaging ; Middle Aged ; Plasma Exchange ; Diagnosis, Differential ; },
abstract = {Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor limbic encephalitis is a rare neurological disorder often associated with malignancies. We present the case of a patient in her forties who initially presented with symptoms misattributed to migraine, later progressing to fever, confusion, declining consciousness and focal seizures. MRI findings were consistent with encephalitis, and cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis with negative infectious workup. Despite initial empiric treatment for infectious encephalitis, her condition deteriorated. CT of the chest, abdomen and pelvis showed suspicious nodules in the left breast; biopsy confirmed the presence of metastatic invasive ductal carcinoma. She made a marked improvement following plasma exchange. Subsequently, the CSF autoimmune encephalitis panel returned positive for AMPA receptor antibodies, confirming the diagnosis of paraneoplastic encephalitis. This case underscores the need for early consideration of autoimmune and paraneoplastic causes in atypical or refractory encephalitis presentations, even prior to the availability of confirmatory antibody testing.},
}
@article {pmid41433251,
year = {2025},
author = {Joshua, D and Rahimi, H and Seni, J and Ally, M and Omar, M and Joshi, J and Ali, F and Mohammed, S and Poulsen, A and Lund, S and , },
title = {Serial C-Reactive Protein Point-of-Care testing to optimize antibiotic treatment in hospitalized children with signs of infection in Zanzibar: A feasibility study.},
journal = {PLOS global public health},
volume = {5},
number = {12},
pages = {e0004777},
pmid = {41433251},
issn = {2767-3375},
abstract = {Bacterial infections are among the leading causes of morbidity and mortality in children, especially in low- and middle- income countries. As a result, antibiotics are frequently prescribed to children with signs of infection, even when cause may not be bacterial. This contributes to antimicrobial resistance (AMR), a global health concern. Integrating serial CRP point-of-care testing with culture and susceptibility testing may improve decision-making by facilitating earlier differentiation between bacterial and non-bacterial infections, promoting more appropriate antibiotic use.The study examined the feasibility of serial CRP POCT to guide discontinuation of antibiotic treatment in children in selected hospitals in Zanzibar, and to determine barriers to methods and procedures for the upcoming randomised controlled trial (RCT) (ISRCTN25937092).This prospective, individually randomized feasibility study was conducted between February 5 and March 3 2024 in two hospitals in Zanzibar. Research assistants and healthcare workers (HCWs) were trained on the use and interpretation of CRP POCT. Eligible neonates and children were randomized to CRP-guided or standard care antibiotic management. Feasibility was assessed using Bowen's framework; clinical outcomes were interpreted as exploratory.Eighty-two children participated, with a 96.0% follow-up rate. The CRP POCT intervention was rated "very important" by 89.7% of 58 HCWs. Adherence to CRP-based antibiotic guidance was high, though early discharges due to caregiver pressure were noted. The intervention integrated successfully into existing workflows and HCWs adapted the flowcharts in practice. Exploratory analysis showed CRP guidance reduced antibiotic treatment days in neonates with signs of infection (5.1 vs 6.6 days), and children aged 6 months to 12 years with febrile illness or diarrhoea (4.8 vs 6.7 days) compared to standard care, but the study was not powered for statistical inferences. This study suggests that the RCT of serial CRP POCT in guiding antibiotic treatment decision is feasible, and operationally implementable in this setting.},
}
@article {pmid41432120,
year = {2025},
author = {Xu, W and Fan, L},
title = {Antitumor Effects of Tumor-Derived Exosomes in Murine Hepatocellular Carcinoma Models.},
journal = {Iranian journal of immunology : IJI},
volume = {22},
number = {4},
pages = {310-321},
doi = {10.22034/iji.2025.106436.3025},
pmid = {41432120},
issn = {1735-367X},
mesh = {Animals ; *Exosomes/metabolism/immunology ; *Carcinoma, Hepatocellular/immunology/therapy/pathology ; *Dendritic Cells/immunology ; Mice ; *Liver Neoplasms/immunology/therapy/pathology ; Disease Models, Animal ; Cell Line, Tumor ; Humans ; Antigens, Neoplasm/immunology/metabolism ; Cytokines/metabolism ; },
abstract = {BACKGROUND: Exosomes (EXOs) are small vesicles derived from endosomes and secreted by most living cells including tumor cells. In recent years, these vesicles have been recognized as key mediators of intercellular communication, playing essential roles in the regulation and orchestration of diverse physiological and pathological processes within the organism.<br><br>OBJECTIVE: To further investigate hepatocellular carcinoma (HCC)-derived exosomes containing tumor-associated antigens and to evaluate their immunostimulatory capacity and antitumor effects using in vitro and in vivo approaches.<br><br>METHODS: Following isolation from tumor cells, exosomes were characterized and subsequently co-cultured with dendritic cells (DCs). The expression of surface molecules associated with DC maturation was then assessed using flow cytometry. A mouse liver cancer model was established and animals were randomly assigned to three groups: a negative control group (treated with PBS), an iDC group, and a DC-TEXs (tumor-derived exosomes) group. Tumor volume was monitored in all groups, with a focus on changes in immune cell populations and cytokine levels.<br><br>RESULTS: Our in vitro studies showed that Hepa1-6 cell-derived EXOs dose-dependently enhanced dendritic cell (DC) maturation, as evidenced by increased expression of surface MHC-II molecules, co-stimulatory markers (CD40, CD80, CD86), and the maturation marker CD83. In vivo studies using subcutaneous HCC mouse models demonstrated that TEX administration significantly alters the tumor immune microenvironment, mainly through increased T lymphocyte infiltration and proliferation.<br><br>CONCLUSION: Our results suggest that TEXs can serve as endogenous immunotherapeutic agents by eliciting tumor-specific T lymphocyte responses through DC activation cascades. These findings provide novel insights into the therapeutic exploitation of tumor-derived vesicles for the treatment of hepatocellular carcinoma.},
}
@article {pmid41429548,
year = {2025},
author = {Mao, J and Wang, JQ and He, H and Li, YH and Peng, JQ and Peng, HZ and Xu, YQ and Xie, XB},
title = {[Analyzing the impact of chemotherapy on cellular heterogeneity and identifying potential therapeutic targets in breast cancer patients via single-cell RNA sequencing].},
journal = {Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]},
volume = {59},
number = {12},
pages = {2147-2156},
doi = {10.3760/cma.j.cn112150-20250425-00356},
pmid = {41429548},
issn = {0253-9624},
support = {22JBZ037//Hunan University of Chinese Medicine "Unveiling and Commanding" Program for Discipline Development/ ; kq2502082//Changsha Municipal Natural Science Foundation/ ; 2024CX123//Graduate Innovation Research Project of Hunan University of Chinese Medicine/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Single-Cell Analysis ; *Sequence Analysis, RNA ; Tumor Microenvironment ; Case-Control Studies ; Transcriptome ; },
abstract = {Objective: Profiling tumor cell heterogeneity before and after chemotherapy in breast cancer patients to delineate the cellular evolutionary trajectory at single-cell resolution, thereby identifying potential targets for intervention. Methods: Using a case-control study design, a female patient with breast cancer admitted to the Department of Breast Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine in September 2020 was enrolled as the subject. Fresh tumor tissue samples, collected both before and after chemotherapy, were subjected to single-cell RNA sequencing to assess transcriptomic profiles and observe the impact of chemotherapy on the intratumoral microenvironment. Specifically, a pre-chemotherapy biopsy sample was obtained in June 2020, and a post-chemotherapy surgical resection sample was obtained in September 2020. Pathological diagnosis confirmed Grade Ⅲ invasive ductal carcinoma for both samples, with a molecular subtype of Luminal B. Results: A significance threshold of |log2FC|>2 and a P-value <0.05 were set to define statistically significant differences for subsequent bioinformatic analysis. Sequencing data revealed that a total of 8 599 cells were profiled in this study, with 4 180 (48.6%) and 4 419 (51.4%) cells derived from pre- and post-chemotherapy tumor tissues, respectively. It characterized the cellular composition of the tumor microenvironment and identified 13 distinct cell clusters. These included basal cells, pericytes, plasma cells, T cells, B cells, fibroblasts, endothelial cells, NK cells, mast cells, epithelial cells, macrophages, cycling cells, and plasmacytoid dendritic cells. Signaling pathways and transcription factors associated with these cell clusters were subsequently analyzed and subjected to enrichment analysis. Furthermore, this study delineated the precise cellular architecture and developmental trajectories of breast cancer before and after chemotherapy. It also predicted that the APOD, ELN, and F2R genes may play pivotal roles in disease progression. Conclusion: This study utilized single-cell RNA sequencing to analyze intra-tumoral cellular heterogeneity in a breast cancer patient before and after chemotherapy. The findings may provide a clinically informative direction for identifying novel potential therapeutic targets during chemotherapy, prior to primary tumor resection.},
}
@article {pmid41425867,
year = {2025},
author = {Kumari, B and Lahariya, R},
title = {Somatic mutation counts as a surrogate marker for tumor mutation burden to predict progesterone receptor-positive (PR+) status in PIK3CA-mutated breast cancer.},
journal = {German medical science : GMS e-journal},
volume = {23},
number = {},
pages = {Doc16},
pmid = {41425867},
issn = {1612-3174},
mesh = {Humans ; Female ; *Class I Phosphatidylinositol 3-Kinases/genetics ; *Breast Neoplasms/genetics/pathology ; *Receptors, Progesterone/metabolism/genetics ; Retrospective Studies ; Middle Aged ; *Biomarkers, Tumor/genetics ; Mutation ; Adult ; *Carcinoma, Ductal, Breast/genetics/pathology ; Aged ; },
abstract = {OBJECTIVES: Invasive ductal carcinoma (IDC), the most prevalent subtype of breast cancer, is characterized by significant genomic heterogeneity. Tumor mutation burden (TMB) has emerged as a predictive biomarker for immunotherapy response, yet its estimation via whole-exome sequencing remains complex and costly. This study aimed to evaluate whether total somatic mutation count can serve as a practical surrogate for TMB and assess its association with progesterone receptor (PR) status in PIK3CA-mutated IDC patients.<br><br>METHODS: This retrospective observational study utilized publicly available data from a previously published breast cancer sequencing study. A total of 164 female IDC patients with confirmed PIK3CA mutations and documented PR status were included. Relevant genomic and demographic parameters - TMB, mutation count, and age - were extracted and analyzed. Statistical analyses included correlation, intergroup comparisons by PR status, and binary logistic regression. Predictive performance was assessed using area under the receiver operating characteristic (AUROC) curves.<br><br>RESULTS: Patients with PR-negative status exhibited significantly higher TMB and mutation count than PR-positive patients (p-value<0.001 for both). TMB and mutation count were positively correlated (r=0.61, p-value<0.001), indicating overlapping representation of genomic instability. Logistic regression showed that mutation count was a significant predictor of PR status (p-value=0.01). Mutation count demonstrated a slightly superior predictive performance (AUROC=0.738) compared to TMB (AUROC=0.737).<br><br>CONCLUSION: Total mutation count shows strong potential as a surrogate biomarker for TMB and a predictive marker for PR status in PIK3CA-mutated IDC, offering a cost-effective genomic tool in personalized breast cancer stratification.},
}
@article {pmid41398591,
year = {2025},
author = {Roy, P and Aggarwal, Y and Kochar, SK and Kochar, DK and Das, A},
title = {Integrative transcriptomic and machine learning approaches to decipher mitochondrial gene regulation in severe Plasmodium vivax malaria.},
journal = {Malaria journal},
volume = {25},
number = {1},
pages = {47},
pmid = {41398591},
issn = {1475-2875},
support = {PID: 2019-1121//Indian Council of Medical Research (ICMR)/ ; },
mesh = {*Machine Learning ; *Plasmodium vivax/genetics ; *Malaria, Vivax/parasitology ; Humans ; *Transcriptome ; Gene Expression Profiling ; *Gene Expression Regulation ; *Mitochondria/genetics ; *Genes, Mitochondrial ; },
abstract = {Mitochondria in Plasmodium vivax are functionally vital despite possessing a highly reduced genome and differing substantially from the human organelle. Beyond their classical role in energy production, they dynamically coordinate processes like pyrimidine biosynthesis and heme metabolism, adapting their functions across the intra-erythrocytic development cycle (IDC). Their unique architecture and stage-specific roles enable the parasite to fine-tune mitochondrial gene expression, involving both protein-coding sense transcripts and long non-coding natural antisense transcripts (NATs). This study unveils an unprecedented regulatory complexity by integrating transcriptomic profiling with advanced machine learning to decode the role of mitochondrial sense and natural antisense transcripts (NATs) in severe P. vivax malaria. We reveal distinct, clinically relevant expression signatures, where NATs emerge not as transcriptional by-products but as potent regulators tightly linked to mitochondrial pathways and translational machinery. This dual-layered transcriptomic landscape reflects an intricate molecular strategy by which the parasite fine-tunes mitochondrial function to survive under severe disease conditions. Importantly, while these findings illuminate novel regulatory mechanisms and position mitochondrial NATs as promising targets for antimalarial drug development, they represent preliminary insights derived from a limited clinical cohort and should not be interpreted as definitive clinical indicators. Validation in larger and diverse patient populations is essential to confirm their broader biological and clinical relevance. However, these results serve as indicators for potential innovative therapeutic interventions aimed at disrupting parasite bioenergetics and regulatory networks.},
}
@article {pmid41381594,
year = {2025},
author = {Makris, K and Fonda, V and Ramadhani, FF and Fadel, L and Davezac, M and Payet, B and Deligiannis, IK and Zhang, L and Horn, T and Heimerl, L and Jouffe, C and Heddes, M and Martinez-Jimenez, CP and Quagliarini, F and Uhlenhaut, NH},
title = {Hepatic metabolic reprogramming in male mice during short-term caloric restriction involves enhanced glucocorticoid rhythms.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {11106},
pmid = {41381594},
issn = {2041-1723},
support = {490946138//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 314061271//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 213249687//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; ERCCoG GRACE 101086997//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; },
mesh = {Animals ; *Caloric Restriction ; Male ; Receptors, Glucocorticoid/metabolism/genetics ; *Liver/metabolism ; *Glucocorticoids/metabolism ; Mice ; *Circadian Rhythm/physiology ; Mice, Inbred C57BL ; Signal Transduction ; Hepatocytes/metabolism ; Forkhead Box Protein O1/metabolism ; Mice, Knockout ; Metabolic Reprogramming ; },
abstract = {Caloric restriction prolongs lifespan and preserves health across species, with feeding times synchronized to day-night cycles further maximizing benefits. However, the mechanisms linking diet, diurnal rhythms, and lifespan remain unclear. In mice, the time point most strongly tied to dietary effects on lifespan coincides with the peak of glucocorticoid secretion (ZT12, lights-off). Caloric restriction raises circulating glucocorticoid hormone levels, implicating these signals as candidate mediators for its benefits. Here we show that in the liver, the glucocorticoid receptor (GR) is required for the metabolic response to caloric restriction. Hepatocyte-specific GR mutant males fail to mount this response, indicating that increased glucocorticoid amplitude is necessary for the adaptation. Using multiomics, we find that nutrient deprivation elicits a nuclear switch from active STAT signaling to increased FOXO1 activity, enabling GR to activate diet-specific gene expression programs. Our results suggest that glucocorticoid rhythms are crucial for caloric restriction-induced metabolic reprogramming.},
}
@article {pmid41360305,
year = {2026},
author = {Torki, F and Bendena, WG and Chin-Sang, ID},
title = {IDENTIFICATION of NLP-5 and NLP-6 as potential ligands for the NPR-9 receptor in Caenorhabditis elegans.},
journal = {General and comparative endocrinology},
volume = {376},
number = {},
pages = {114869},
doi = {10.1016/j.ygcen.2025.114869},
pmid = {41360305},
issn = {1095-6840},
mesh = {Animals ; *Caenorhabditis elegans/metabolism/genetics ; *Caenorhabditis elegans Proteins/metabolism/genetics ; *Neuropeptides/metabolism/genetics ; Ligands ; *Receptors, Neuropeptide/metabolism/genetics ; },
abstract = {Neuropeptides in Caenorhabditis elegans regulate physiological and behavioural responses to environmental cues, influencing locomotion, feeding, and fat storage via interactions with G-protein coupled receptors (GPCRs). C. elegans expresses a diverse repertoire of neuropeptides, including FMRFamide-related peptides, neuropeptide-like peptides (NLPs), and insulin-like peptides (INSs). Among these, the galanin/allatostatin-like GPCR, NPR-9, localized in the AIB interneurons, regulates locomotory behaviours (roaming and dwelling) and fat accumulation by inhibiting AIB activity. Recent studies identified NLP-1 as a ligand for NPR-9, modulating behaviour through direct receptor interaction. However, our research explored whether other neuropeptides, specifically NLP-5 and NLP-6 (allatostatin A-type/galanin-like neuropeptides), could also function as NPR-9 ligands, despite evidence suggesting NLP-1 as the primary ligand. In this study, we characterized phenotypes associated with NPR-9 receptor function, including Omega turns, roaming, and fat accumulation. Loss-of-function mutations in nlp-5, nlp-6, and nlp-1 exhibited behavioural phenotypes similar to npr-9 mutants, suggesting that NLP-5 and NLP-6 may act as additional ligands for NPR-9 or affect NPR-9 signalling. Furthermore, double-mutant analyses with candidate ligand genes suppressed phenotypes associated with NPR-9 overexpression, reinforcing the hypothesis that these neuropeptides may regulate NPR-9-mediated signalling.},
}
@article {pmid41354159,
year = {2026},
author = {Wang, Y and Miyamoto, H},
title = {Quantitative assessment of cribriform intraductal carcinoma of the prostate is useful for risk stratification after radical prostatectomy.},
journal = {Human pathology},
volume = {167},
number = {},
pages = {106008},
doi = {10.1016/j.humpath.2025.106008},
pmid = {41354159},
issn = {1532-8392},
mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery/mortality ; *Prostatectomy ; Retrospective Studies ; Aged ; Middle Aged ; Risk Assessment ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Risk Factors ; *Carcinoma, Ductal/pathology/surgery ; Treatment Outcome ; Kaplan-Meier Estimate ; *Adenocarcinoma/pathology/surgery ; },
abstract = {It remains uncertain if the extent of intraductal carcinoma of the prostate (IDC) exhibiting cribriform (Crib) morphology impacts on patient outcomes. We retrospectively analyzed long-term oncologic outcomes in 182 consecutive radical prostatectomy patients exhibiting Grade Group 2-4 conventional/acinar prostatic adenocarcinoma, along with Crib-IDC but no Gleason grade 5 patterns. A single Crib-IDC focus in the entire prostatectomy specimen was identified in 46 (25.3 %) cases, while others showed 2 (n = 36; 19.8 %), 3 (n = 27; 14.8 %), 4 (n = 11; 6.0 %), or ≥5 (n = 62; 34.1 %) Crib-IDC foci. The maximum Crib-IDC diameter in each case was ≤1-mm (n = 66; 36.3 %), >1/≤2-mm (n = 90; 49.5 %), >2/≤3-mm (n = 21; 11.5 %), or >3-mm (n = 5; 2.7 %). The summed maximum Crib-IDC diameters were ≤1-mm (n = 38; 20.9 %), >1/≤2-mm (n = 39; 21.4 %), >2/≤3-mm (n = 30; 16.5 %), >3/≤4-mm (n = 17; 9.3 %), >4/≤5-mm (n = 9; 4.9 %), or >5-mm (n = 49; 26.9 %). On univariate analyses, the risks of postoperative biochemical recurrence were significantly higher in cases with 3 (P = 0.022) or ≥3 (P < 0.001) Crib-IDCs (vs. 1-2) or ≥4 Crib-IDCs [P < 0.001 (vs. 1-3); P = 0.032 (vs. 3)]. Similarly, the recurrence risk was significantly higher in Crib-IDC cases with the maximum diameter of >1-mm (vs. ≤1-mm; P = 0.002) or the summed diameter of >3-mm (vs. ≤3-mm; P < 0.001). On multivariable Cox regression analyses, 3 [hazard ratio (HR) 2.742, P = 0.016], ≥3 (HR 3.969, P < 0.001), or ≥4 (HR 4.520, P < 0.001) Crib-IDCs (vs. 1-2) and the summed diameter of >3-mm (HR 3.074, P < 0.001) remained significantly predictive of recurrence. Quantitative assessment of Crib-IDC, particularly its number and cumulative diameter on prostatectomy, may thus enhance the postoperative risk stratification of Grade Group 2-4 prostate cancer.},
}
@article {pmid41327199,
year = {2025},
author = {Annamalai, K and Dilliker, S and Buchholz, E and Castro-Hernández, R and Panyam, N and Pommeranz, A and Wiederhake, P and Wery von Limont, N and Hempel, N and Ebner, V and Swarnkar, S and Mohamed, BA and Streckfuss-Bömeke, K and Steffens, S and Herzig, S and Ebert, A and Fischer, A and Toischer, K},
title = {Deregulation of m6A-RNA methylation impairs adaptive hypertrophic response and drives maladaptation via mTORC1-S6K1-hyperactivation and autophagy impairment.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {522},
pmid = {41327199},
issn = {1478-811X},
abstract = {BACKGROUND: Pressure overload first leads to compensated hypertrophy and secondary to heart failure. m6A-RNA methylation is a fast process for the adaptation of cell composition. m6A-RNA-methylation is regulated by the demethylase, fat mass and obesity-associated protein (FTO), and FTO protein levels are diminished in heart failure. Cardiomyocyte-specific FTO-transgenic/knockout-mice have shown the relevance of FTO in pressure overload remodeling. However, its functional downstream regulatory mechanisms are still unclear. In this study, we discover the harmful signaling pathways that are triggered by m6A imbalance and FTO loss, which eventually lead to adverse cardiac remodeling and heart failure.<br><br>METHODS: FTOcKO animals were generated by crossing FTO[fl/fl] mice with [Formula: see text]-MHC Cre mice using Cre-lox system. Control and the FTOcKO animals groups were subjected to TAC (transverse aortic constriction) surgery. Echocardiography was performed 1-week post-TAC surgery. MeRIP (m6A RNA immunoprecipitation) sequencing was performed from the heart tissues of mice after one week TAC surgery. Additionally, the mechanistical interrelation between the signaling pathways during FTO loss and adverse cardiac remodeling were investigated in human iPS-CMs (hiPS-CMs).<br><br>RESULTS: One week post-TAC surgery, FTOcKO mice showed impaired cardiac function (EF: CreC TAC (45%) vs. FTOcKO TAC (25%), p&#x2009;<&#x2009;0.0001) and increased LVID (CreC TAC(3.9&#xa0;mm) vs. FTOcKO TAC (4.8&#xa0;mm), p&#x2009;<&#x2009;0.0001), indicating a lack of adaption to pressure overload. Knockdown of FTO in hiPS-cardiomyocytes also reduced endothelin-induced hypertrophic response. MeRIP-seq data of FTOcKO mice showed that the differentially hypermethylated transcripts were associated with cardiac apoptosis inhibition (CDK1, CFLAR), mTORC1 signaling pathway (AKT1S1) and autophagy regulation (TFEB). mTORC1 was identified as a central player of dysregulation with hyperactivation of its canonical substrates phospho-S6K1 (Thr 389) and phospho-S6 (ser235/236) ex-vivo (FTOcKO) and in-vitro (FTO-KD-hiPS-CMs). Moreover, FTO-deficient cardiomyocytes cause autophagic flux impairment and defective autophagy. The effect of atrophy and induced apoptosis upon FTO-m6A imbalance could be rescued by pharmacological inhibiton of the mTORC1-S6K1 pathway.<br><br>CONCLUSIONS: Downregulation of FTO leads to mTORC1-S6K1 hyperactivation that shift the compensative hypertrophic response to atrophy and apoptosis leading to progressive heart failure. These findings might pave the way for the development of novel therapeutic targets for the early phases of heart failure treatments.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-025-02509-0.},
}
@article {pmid41318755,
year = {2025},
author = {Effiong, ME and Chinedu, SN and Afolabi, IS and Ezike, KN and Oguntebi, EE and Abdul, OA and Achusi, IB and Benye, TA and Bella-Omunagbe, M and Ogbodo, PN},
title = {Age-specific patterns of breast cancer in Nigerian women unraveled through histological analysis.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {128},
pmid = {41318755},
issn = {2045-2322},
support = {For Women in Science, Sub-Saharan Africa (2024)//United Nations Educational, Scientific and Cultural Organization/ ; },
mesh = {Humans ; Female ; Nigeria/epidemiology ; Middle Aged ; Adult ; *Breast Neoplasms/epidemiology/pathology ; Young Adult ; Adolescent ; Aged ; Child ; Age Factors ; Retrospective Studies ; Child, Preschool ; Aged, 80 and over ; Infant ; Risk Factors ; Infant, Newborn ; Prevalence ; },
abstract = {Sub-Saharan African women face a high burden of breast cancer, influenced by genetic and lifestyle factors. However, the lack of comprehensive, age-stratified data hinders the identification of risk factors and the development of effective, population-specific interventions. This study aimed to assess age-related variations in breast cancer prevalence among Nigerian women, providing insight into associated risk factors and disease trends. A retrospective review of 3,263 breast histopathology records (9.46% of total from 2015 to 2023) was conducted. Lesions-benign and malignant-were analyzed across five age groups: children and adolescents (0-19), young adults (20-39), middle-aged (40-59), higher-aged (60-79), and elderly (≥ 80), using MS Excel and GraphPad Prism 8.0. Statistical comparisons were performed by age and lesion type. Most cases were in young adults (45.97%) and middle-aged women (33.83%). The left breast was more commonly affected (46.86%) and had higher malignancy rates than the right (44.41%) or bilateral lesions (7.20%). Benign lesions were predominant (56.76%), especially among young adults (57.34%). Malignancy incidence increased with age, peaking in middle-aged women (53.30%). Fibroadenoma was the most frequent benign lesion in children and adolescents and young adults, while fibrosis predominated in middle age. Invasive ductal carcinoma (IDC) was the leading malignant subtype, with a sharp rise by 2023-particularly among middle-aged (172 cases) and young adult women (71 cases). Among 339 immunohistochemically profiled cases, triple-negative breast cancer (TNBC; 42.77%) and ER+/PR+ tumors (36.87%) were most common. TNBC was the only subtype detected in children and adolescents. Middle-aged women bore the highest burden of all subtypes, with a marked increase in TNBC and ER+/PR+ cases in 2023. The rising incidence of aggressive subtypes, particularly TNBC, highlights the need for enhanced molecular diagnostics and personalized therapies. Age-specific trends reinforce the urgency for targeted screening, especially for young and middle-aged Nigerian women.},
}
@article {pmid41315737,
year = {2025},
author = {Pazicky, S and Tjia, S and Farias, GB and Piwon, N and Philip, N and Sobota, RM and Waters, AP and Gilberger, TW and Bozdech, Z},
title = {MAP-X reveals distinct protein complex dynamics across Plasmodium falciparum blood stages.},
journal = {Nature microbiology},
volume = {10},
number = {12},
pages = {3229-3244},
pmid = {41315737},
issn = {2058-5276},
support = {MOE2019-T3-1-007//Ministry of Education - Singapore (MOE)/ ; NRF-CRP24-2020-0005//National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)/ ; MOH-001107//Ministry of Health -Singapore (MOH)/ ; GRK2771-No 453548970//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; ALTF 1115-2009//European Molecular Biology Organization (EMBO)/ ; 083811/Z/07/Z//Wellcome Trust (Wellcome)/ ; },
mesh = {*Plasmodium falciparum/growth &amp; development/metabolism/genetics ; *Protozoan Proteins/metabolism/genetics ; *Erythrocytes/parasitology ; Proteome ; Humans ; Malaria, Falciparum/parasitology ; Protein Interaction Maps ; *Protein Interaction Mapping/methods ; Proteomics/methods ; Life Cycle Stages ; },
abstract = {The malaria parasite Plasmodium falciparum undergoes a complex intraerythrocytic developmental cycle (IDC) that relies on a dynamic network of protein-protein interactions. These are usually mapped ex vivo, limiting our understanding of their dynamics and composition in natural environments. Here we introduce the meltome-assisted profiling of protein complexes (MAP-X) that maps the complexome through thermal proteome profiling in intact cells. We applied MAP-X across seven timepoints in the P. falciparum IDC. MAP-X predicted more than 20,000 interactions, resolving conserved protein complexes, reproducing previously identified interactions and finding previously unreported associations. We found that malaria protein complexes undergo distinct dynamic alterations, and we predicted their moonlighting subunits that dissociate from their native complex to assume different biological functions. Altogether, our findings provide a resource for uncovering Plasmodium biology and show that MAP-X can characterize protein complexes in intact cells to reveal cellular physiology at a proteome-wide level.},
}
@article {pmid41314093,
year = {2026},
author = {Addie, M and Miron, AD and Iny, E and Wong, SM and Ross, VMS and Prakash, I and Meterissian, S},
title = {Patients with positive axillary nodes undergoing upfront surgery: Can axillary dissection be safely omitted?.},
journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology},
volume = {52},
number = {1},
pages = {111304},
doi = {10.1016/j.ejso.2025.111304},
pmid = {41314093},
issn = {1532-2157},
mesh = {Humans ; Female ; Middle Aged ; *Lymph Node Excision/methods ; *Breast Neoplasms/pathology/surgery ; Axilla ; Retrospective Studies ; Aged ; Lymphatic Metastasis ; *Lymph Nodes/pathology/surgery/diagnostic imaging ; *Carcinoma, Ductal, Breast/surgery/pathology/secondary ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Staging ; },
abstract = {PURPOSE: To determine the extent of axillary disease in patients with non-palpable but preoperatively biopsy-proven positive nodes, and to identify predictors of extensive lymph node (LN) involvement, defined as ≥3 positive LNs (LN+).<br><br>METHODS: A retrospective cohort study of cT1-3 breast cancer patients diagnosed between 2005 and 2022. All patients had nonpalpable biopsy-proven axillary disease and underwent upfront axillary lymph node dissection (ALND). Patients were divided into two groups: 1-2 LN&#xa0;+&#xa0;on ALND versus &#x2265;3 LN+. Clinicopathologic factors were compared between groups. Multivariate regression was used to identify preoperative predictors of extensive (&#x2265;3) LN involvement.<br><br>RESULTS: Our cohort included 111 patients, with a median age of 63 years (IQR: 52-73 years) and tumour size of 20&#xa0;mm (IQR: 13-29&#xa0;mm). Most patients had invasive ductal carcinoma (90&#xa0;%, n&#xa0;=&#xa0;100). Most patients were HR+/HER2-disease (86&#xa0;%, n&#xa0;=&#xa0;96). Of the entire cohort, 46&#xa0;% (n&#xa0;=&#xa0;51) underwent breast-conserving surgery, and 54&#xa0;%(n&#xa0;=&#xa0;60) underwent mastectomy. On final pathology, 34&#xa0;%(n&#xa0;=&#xa0;38) of patients had 1-2 LN+, and 66&#xa0;%(n&#xa0;=&#xa0;73) had &#x2265;3 LN+. Multivariate analysis preoperative predictors of &#x2265;3 LN+: grade 3 disease (OR&#xa0;=&#xa0;5.43, 95&#xa0;% CI: 1.19-39.8, p&#xa0;=&#xa0;0.049), two abnormal lymph nodes on US (OR&#xa0;=&#xa0;9.11,95&#xa0;% CI: 2.66-42.7, p&#xa0;=&#xa0;0.001) and &#x2265;3 abnormal nodes on ultrasound (OR 30.0, 95&#xa0;% CI: 5.54-561, p&#xa0;=&#xa0;0.001).<br><br>CONCLUSION: Most women with preoperatively nonpalpable, biopsy-proven axillary metastases had extensive nodal disease, but those with limited nodal positivity on ultrasound could be suitable for a more targeted axillary approach to avoid ALND.},
}
@article {pmid41312922,
year = {2025},
author = {Baloch, AH and Shuja, J and Bangulzai, N and Jan, M and Sattar, A and Brohi, SA and Habibullah, H and Baloch, DM and Ahmad, J},
title = {Predisposition of an Intronic Duplication in CHEK2 Gene in the Cases of Breast Cancer from Balochistan.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {26},
number = {11},
pages = {3975-3979},
doi = {10.31557/APJCP.2025.26.11.3975},
pmid = {41312922},
issn = {2476-762X},
mesh = {Humans ; *Checkpoint Kinase 2/genetics ; Female ; *Breast Neoplasms/genetics/pathology/epidemiology ; *Genetic Predisposition to Disease ; *Introns/genetics ; Case-Control Studies ; Middle Aged ; Adult ; Prognosis ; Germ-Line Mutation ; *Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology/epidemiology ; Follow-Up Studies ; *Gene Duplication ; },
abstract = {OBJECTIVE: After BRCA 1&amp;2, CHEK2 is the most frequently predisposing altered gene causing breast cancer in female. The prime objective of the current study was to analyze germline CHEK2 variants and their association with breast cancer in Balochistani population.<br><br>METHODS: Breast cancer is among the most prevalent cancers worldwide and most common diagnosed cancer in women. Mutations in many proto-oncogenes and tumor suppressor genes lead to the development of cancer. Along with the highly penetrance genes BRCA1 and BRCA2 increase the risk of breast cancer, mutations in other genes including CHEK2, a tumor suppressor gene have also been reported to be associated with breast cancer. In current study CHEK2 gene was analyzed for variation in breast cancer patients and controls of Balochistani population. Sequencing results of the DNA samples of the registered cases of breast cancer in CENAR were analyzed using Chromas software and bioinformatics tools including BLAT and &#xa0;RNAfold web server.<br><br>RESULTS: An intronic variant c.319+38-43dupA falling 38 nucleotide away at splice donor site of the CHEK2 gene exon 2, &#xa0;in 9% &#xa0;breast cancer cases, was identified which has also been previously reported in non-Hodgkin Lymphoma cases. All the cases with identified variant, were affected with invasive ductal carcinoma. Higher tumor grade (III) was reported in >50% of the patients and > 70% of patients diagnosed with advanced stage of cancer. The RNA prediction results revealed the variant falling in the intronic region may code for miRNA that could play an important role in cancer progression.<br><br>CONCLUSION: Our results suggest that the intronic variant identified in breast cancer cases as well as reported previously may act as a cancer marker and causing a splice site disruption or altering the posttranscriptional modification of mRNA encoded by CHEK2 gene.},
}
@article {pmid41306262,
year = {2025},
author = {Gbadamosi, H and Nsaful, J and Mensah, YB and Dedey, F and Mensah, S and Essah, D and Clegg-Lamptey, JN},
title = {The Utilization of Wire-Guided Localization in the Management of Nonpalpable Breast Lumps at a Teaching Hospital in Ghana.},
journal = {Breast cancer : basic and clinical research},
volume = {19},
number = {},
pages = {11782234251392708},
pmid = {41306262},
issn = {1178-2234},
abstract = {INTRODUCTION: Breast cancer is the highest cause of female cancer deaths worldwide. Africa bears the brunt of this devastating disease mainly due to a lack of awareness and late presentation. Recently, a new cohort of patients in some jurisdictions in Africa have presented with small nonpalpable breast tumors due to early detection or following neoadjuvant chemotherapy.<br><br>AIM: This study documented the initial experience of wire-guided localization of nonpalpable breast tumors in a Ghanaian tertiary hospital, used to facilitate the achievement of negative surgical margins.<br><br>METHODS: This was a retrospective evaluation and analysis of clinical, radiological, and histopathological data of 45 patients who had image-guided wire localization of nonpalpable lumps immediately prior to surgical excision at the Korle Bu Teaching Hospital over more than a 4-year period. The study evaluated the preprocedural radiological diagnosis, tumor size, histology, and completeness of resection.<br><br>RESULTS: Median age at presentation was 50&#x2009;years. Clinical indications of these nonpalpable lesions included 13.3% post neoadjuvant chemotherapy and 40.0% of chemotherapy naive histologically diagnosed breast cancers. The median size of the excised lesions was 13&#x2009;mm. Excision was associated with clear margins in most cases. Up to 53.3% of the lesions were malignant, out of which invasive ductal carcinoma NST was the commonest histology.<br><br>CONCLUSION: Ultrasound-guided wire localization has proven to be a beneficial tool in breast-conserving surgery in an LMIC environment. More than half the pathologies localized were malignant, with 96% showing clear margins.},
}
@article {pmid41293157,
year = {2025},
author = {Han, H and Semenov, M and Li, C and Zhang, Y and Lin, T and Zheng, P and Cai, J},
title = {Case Report: Possible association between dermatomyositis and Trastuzumab Deruxtecan therapy of triple-negative breast cancer patient.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1636581},
pmid = {41293157},
issn = {1664-3224},
mesh = {Humans ; Female ; *Dermatomyositis/chemically induced/diagnosis/drug therapy ; *Trastuzumab/adverse effects/therapeutic use ; Adult ; *Triple Negative Breast Neoplasms/drug therapy ; *Lung Diseases, Interstitial/chemically induced/diagnosis ; *Antineoplastic Agents, Immunological/adverse effects ; Camptothecin/analogs &amp; derivatives ; Immunoconjugates ; },
abstract = {INTRODUCTION: we present the case of the first documented occurrence of concurrent dermatomyositis and interstitial pneumonia associated with Trastuzumab Deruxtecan (T-DXd) therapy. We hypothesize that T-DXd likely induced an autoimmune response through tumor antigen release, resulting in multi-system involvement of skin, muscle, and pulmonary tissues. The shared pathogenesis of dermatomyositis and interstitial pneumonia involves aberrant activation of the type I interferon pathway, NF-κB signaling, and TGF-β cascade, collectively driving inflammatory and fibrotic processes. Notably, progression of breast cancer temporally coincided with the onset of dermatomyositis. Although anti-TIF1-γ antibodies were not detected, the possibility of paraneoplastic dermatomyositis cannot be definitively excluded.<br><br>a 43-year-old woman initially diagnosed with Luminal B-type invasive ductal carcinoma of the left breast and experienced tumor recurrence after modified radical mastectomy. Lymph node biopsy confirmed triple-negative breast cancer (cT2N3cM0, stage IIIC) with HER2 ultra-low expression (1+). During palliative second-line treatment with Trastuzumab Deruxtecan, patient developed typical dermatomyositis symptoms and proximal muscle weakness 7 days after the first cycle of administration. Following glucocorticoid treatment, dermatomyositis symptoms showed partial relief. However, with continued administration of T-DXd in compliance with original protocol (cycles 2-6), the manifestation of dermatomyositis significantly worsened. The condition remained poorly controlled despite administration of Prednisone combined with Hydroxychloroquine, and showed no significant improvement after adding methotrexate. Concurrent tumor evaluation revealed disease progression, too. Following the third treatment cycle, chest CT revealed interstitial pneumonia.<br><br>CONCLUSION: reported here findings suggest that T-DXd may trigger multi-system involvement through immune-mediated mechanisms, resulting in drug-induced dermatomyositis and interstitial pneumonia. Our findings highlight the need for heightened vigilance regarding such immune-related adverse events during T-DXd therapy, where early recognition and intervention are critically important to avoid irreversible and possibly fatal complications.},
}
@article {pmid41287212,
year = {2026},
author = {Davies, I and Turland, A and Tran, HD and Wong, C and Cahn, O and Dunsterville, C and Sun, Y and Xiao, Y and Murphy, KG and Bloom, SR and Jones, B and Tan, TMM},
title = {A metabolic comparison of GIPR agonism versus GIPR antagonism in male mice.},
journal = {Diabetes, obesity &amp; metabolism},
volume = {28},
number = {2},
pages = {1160-1167},
pmid = {41287212},
issn = {1463-1326},
support = {BB/W001497/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/X017273/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; //Eli Lilly LRAP programme/ ; MR/N014103/1//MRC Doctoral Training Partnership/ ; /WT_/Wellcome Trust/United Kingdom ; MR/X021467/1/MRC_/Medical Research Council/United Kingdom ; 20/0006295/DUK_/Diabetes UK/United Kingdom ; MR/Y013980/1/MRC_/Medical Research Council/United Kingdom ; 310835/Z/24/Z/WT_/Wellcome Trust/United Kingdom ; //NIHR BRC/ ; MR/Y00132X/1/MRC_/Medical Research Council/United Kingdom ; 18/0005886/DUK_/Diabetes UK/United Kingdom ; //Metsera Inc/ ; 301619/Z/23/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Animals ; *Receptors, Gastrointestinal Hormone/agonists/antagonists &amp; inhibitors ; Male ; Mice ; *Obesity/metabolism/drug therapy/etiology ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Gastric Inhibitory Polypeptide/pharmacology ; Insulin Resistance ; Liver/metabolism/drug effects ; Energy Metabolism/drug effects ; Triglycerides/metabolism ; Adipose Tissue/metabolism/drug effects ; Eating/drug effects ; Blood Glucose/metabolism ; Body Weight/drug effects ; Weight Loss/drug effects ; },
abstract = {AIMS: Targeting the glucose dependent insulinotropic polypeptide receptor (GIPR) is of growing interest for treating type 2 diabetes and obesity, though the optimal approach remains unclear. Both GIPR agonism and antagonism, respectively, incorporated into drugs like tirzepatide and maridebart cafraglutide, have paradoxically both shown significant weight loss effects in humans.<br><br>MATERIALS AND METHODS: In this study, the metabolic impacts of a GIPR agonist (GIP108) and antagonist (NN-GIPR-Ant) were evaluated in lean and high-fat diet (HFD)-induced obese male mice. We assessed the impacts on food intake, body weight, glucose and insulin tolerance, liver triglyceride levels, bone markers and adipose tissue lipolytic gene expression.<br><br>RESULTS: In lean mice, neither peptide affected food intake or body weight, but GIP108 improved glucose tolerance. In obese mice, both agents reduced food intake and body weight, with NN-GIPR-Ant producing more sustained appetite suppression. Energy expenditure remained unchanged, as weight loss matched that of pair-fed controls. GIP108 improved glucose tolerance independently of weight loss, whereas NN-GIPR-Ant reduced insulin sensitivity compared to pair-fed controls. Both treatments slightly increased liver triglyceride content compared to their pair-fed controls, and no treatment significantly affected plasma bone marker levels. Finally, NN-GIPR-Ant reduced the expression of adipose tissue lipolytic genes.<br><br>CONCLUSIONS: Our data highlights the distinct metabolic effects of GIPR agonism and antagonism, offering insights for their future application in personalised metabolic disease treatments. Further human studies are needed to understand the long-term metabolic impacts of these therapies.},
}
@article {pmid41283126,
year = {2025},
author = {Ahuja, S and Singh, N and Yadav, AK and Ranga, S and Chintamani, C},
title = {Mathematical Pathological Approach as a Novel Tool for Prognosis in Breast Cancer.},
journal = {Indian journal of surgical oncology},
volume = {16},
number = {5},
pages = {1018-1025},
pmid = {41283126},
issn = {0975-7651},
abstract = {Breast cancer is the leading cause of cancer in women worldwide. The novel mathematical pathology approach was founded to identify important patient-specific predictors of tumor growth to improve the accuracy of intervention and prognosis. Diffusion penetration length, a model-derived mathematical function, measures how far chemotherapeutic agents diffuse through the tumor tissue. The present study evaluated the diffusion penetration length in patients of invasive ductal carcinoma and its correlation with histopathological type, grade, stage, and surrogate molecular classification. Routine histopathological processing followed by hematoxylin and eosin staining and immunohistochemistry for ER, PR, Her2neu, Ki67, and cleaved caspase-3. Each case was evaluated for histological type, grade, stage, and surrogate molecular classification. The proliferative and apoptotic index were calculated manually by hotspot counting. Mammographic measurements of tumor dimensions were performed by reviewing the images and the geometric mean was calculated. The above values were used to calculate diffusion penetration length in the mathematical working model. The diffusion penetration length was higher in Grade III than in Grade II. However, it was not statistically significant. The correlation of diffusion penetration length with pathological tumor size, nodal involvement, and the stage was found to be statistically insignificant. However, a significant correlation could be established between diffusion penetration length and surrogate molecular classification. Although diffusion penetration length could not be established as an independent prognostic parameter, its evaluation in infiltrating ductal carcinoma of breast may be of great utility.},
}
@article {pmid41278106,
year = {2025},
author = {Trabulsi, N and Alkhateeb, NA and Attiah, FO and Altaifi, R and Fakeeh, B and Shabkah, A and Farsi, A and Bawazeer, SS and Sait, S and Al-Hajeili, M},
title = {Short-term outcomes and mortality in older patients with breast cancer at a single tertiary center.},
journal = {Surgery in practice and science},
volume = {23},
number = {},
pages = {100313},
pmid = {41278106},
issn = {2666-2620},
abstract = {BACKGROUND: Breast cancer (BC) affect women worldwide, and with a rising global incidence, it represents a burden on health systems. In Saudi Arabia, the number of cases of BC and its age distribution have notably increased. Despite this increase, data on BC characteristics, management, and outcomes in this demographic are limited.<br><br>METHODS: We performed this retrospective descriptive study at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, spanning 2008 to 2020. It included older women (60 years or older) diagnosed with primary BC. Data from hospital records included patient demographics, comorbidities, treatments, and short-term outcomes within 30 days of treatment. We aimed to determine the significant associations of patient, disease and treatment factors with length of stay, short-term outcomes, and mortality.<br><br>RESULTS: The study included 115 older female patients with BC, with a mean age of 67 years. Comorbidities such as diabetes (39.1 %) and hypertension (40.9 %) were prevalent. Most patients were diagnosed with stage T2 (49 %) and N1 (42 %) nonmetastatic invasive ductal carcinoma (88.7 %). The recurrence rate was 21 %, while the crude all-cause mortality rate was 20 %. Short-term outcomes showed a 4.35 % readmission rate and a 2.6 % reoperation rate, with an average hospital stay of 3.61 days. Positive surgical margins, type of surgery, and the presence of metastasis significantly predicted extended hospital stays. Smoking was significantly linked to overall morbidities within 30 days.<br><br>CONCLUSION: This study highlights the unique characteristics and treatment outcomes of older women with BC. Comorbidities, tumor stage, and receptor status are crucial for its management and outcomes. The findings emphasize the need for tailored treatment strategies, in consideration of older patients' distinct profiles. Future research should include comparative analyses with younger cohorts to establish age-specific recommendations and optimize treatment approaches for older women.},
}
@article {pmid41275856,
year = {2025},
author = {Ghiarone, T and Hansen, E and Holaska, JM},
title = {Emerin expression stratification across breast cancer subtypes.},
journal = {Cancer treatment and research communications},
volume = {45},
number = {},
pages = {101037},
doi = {10.1016/j.ctarc.2025.101037},
pmid = {41275856},
issn = {2468-2942},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/metabolism/genetics/classification ; *Membrane Proteins/metabolism/genetics ; *Nuclear Proteins/metabolism/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Ductal, Breast/pathology/metabolism/genetics ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Middle Aged ; },
abstract = {Nuclear dysmorphism is a critical indicator of tumor aggressiveness, influencing cancer cell invasion and metastasis. Emerin, an integral nuclear envelope protein involved in nuclear architecture, is important for maintaining nuclear integrity. Our previous work demonstrated an inverse correlation between nuclear envelope-localized emerin expression and breast cancer aggressiveness. However, it failed to have the power to assess whether emerin loss correlates with cancer stage, grade, proliferation, or molecular phenotype. Here we analyzed emerin expression at the nuclear envelope across 243 breast cancer patient samples encompassing various tumor grades, stages, and molecular phenotypes. We found significantly reduced emerin expression in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS), compared to normal breast tissue. Notably, emerin loss correlated with advanced tumor stage, higher Ki-67 proliferation rates, elevated human epidermal growth factor receptor 2 (HER2) levels, and decreased estrogen receptor (ER) and progesterone receptor (PR) expression-markers associated with more aggressive breast cancers. Emerin expression was consistently reduced in triple-negative breast cancer (TNBC) and other receptor-negative subtypes, underscoring its potential role in tumor dedifferentiation and progression.},
}
@article {pmid41274530,
year = {2026},
author = {Toro-Pedroza, A and Victoria, JS and Cardona-Sepúlveda, M and García-Robledo, JE and Rios-Serna, LJ and Loukanov, A and Ortiz-Guzman, J and Hoyos, V and Mainguez-Rodriguez, JE and Cañas, CA and Jaramillo, FJ and Franco, W and Wills, B and Restrepo, JG and Baena, JC},
title = {Advancing CAR-T cell manufacturing in Latin America: Current landscape, future directions, and challenges.},
journal = {Critical reviews in oncology/hematology},
volume = {217},
number = {},
pages = {105041},
doi = {10.1016/j.critrevonc.2025.105041},
pmid = {41274530},
issn = {1879-0461},
mesh = {Humans ; Latin America ; *Immunotherapy, Adoptive/methods/trends ; *Receptors, Chimeric Antigen/immunology/therapeutic use ; },
abstract = {Chimeric antigen receptor T cell therapy has transformed outcomes in hematologic malignancies, yet access in Latin America remains limited by high costs, fragmented regulation, constrained manufacturing capacity, and uneven clinical readiness. This review synthesizes the regional landscape and distills practical strategies to advance sustainable manufacturing and delivery. We map the full value chain from discovery to routine care, highlighting instructive examples. India's talicabtagene autoleucel program built domestic vector and cell production to lower cost and shorten timelines, Brazil coupled a mature regulatory pathway with accredited centers and an emerging national platform for vectors and plasmids, Mexico demonstrated feasibility of hospital based closed system production under national oversight; Colombia and Chile are developing academic pipelines and locally relevant targets. From these experiences we propose a staged roadmap for Latin America that prioritizes domestic capability in vectors and cell processing, regulatory alignment to trusted standards, and workforce development anchored in manufacturing standards and consensus. Network models that combine reference centers with point of care manufacture can reduce logistics burden. Enabling systems are essential, reliable cold chain, precleared customs lanes for critical inputs, pharmacovigilance, and shared minimum datasets for outcomes and safety. Emerging technologies, including non viral nanoparticle transfection and artificial intelligence for construct selection and process control, can reduce costs and improve consistency if advanced through careful, stepwise evaluation. Finally, coordinated alliances among hospitals, professional societies, patient groups, academia, and industry are needed to secure policy support and public investment. Together, these measures provide with a realistic path to safe, equitable, and affordable access to CAR T therapy in Latin America.},
}
@article {pmid41271917,
year = {2025},
author = {Guo, Y and Zhou, X and Xu, H and Wang, G},
title = {SEPT9 methylation as a diagnostic and predictive biomarker in the progression of ductal carcinoma in situ to invasive breast cancer.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {41321},
pmid = {41271917},
issn = {2045-2322},
mesh = {Humans ; Female ; *Septins/genetics/metabolism ; *Breast Neoplasms/genetics/pathology/diagnosis/metabolism ; *DNA Methylation ; *Biomarkers, Tumor/genetics/metabolism ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/diagnosis/metabolism ; *Carcinoma, Ductal, Breast/genetics/pathology/diagnosis/metabolism ; Disease Progression ; Middle Aged ; Cell Line, Tumor ; Adult ; Aged ; MCF-7 Cells ; Decitabine/pharmacology ; Neoplasm Invasiveness ; },
abstract = {SEPT9 methylation has been closely linked to breast cancer, yet its role in differentiating disease stages remains unclear. In particular, Few studies previously have examined differences in SEPT9 methylation between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), or among DCIS lesions of varying nuclear grades. This study investigated SEPT9 methylation across 105 breast cancer cases, classified into pure DCIS, DCIS with invasive components (DCIS-INV), IDC alone, and metastatic breast cancer (MBC). Methylation levels were measured using real-time PCR, and in vitro experiments were conducted using MCF-7 and T47D cell lines treated with decitabine to explore the relationship between methylation and microtubule stability. SEPT9 methylation was significantly elevated in cancer cells compared to normal breast epithelium, with positivity rates of 90.6% in DCIS-INV, 77.8% in IDC, and 79.2% in MBC, versus only 18.2% in pure DCIS. SEPT9 methylation was negtive in low-grade DCIS and positive in 28.6% of intermediate- to high-grade cases. Positive methylation was significantly associated with high Ki-67 expression and lymph node metastasis (P < 0.05), but showed no correlation with age, menopausal status, tumor size, or hormone receptor status. Additionally, decitabine treatment induced a reduction in SEPT9 methylation levels, which affects microtubule stability, suggesting a potential mechanistic link to tumor invasion. These findings indicate that SEPT9 methylation is a promising biomarker for distinguishing invasive breast cancer from DCIS and for identifying high-risk DCIS lesions with greater potential for progression.},
}
@article {pmid41261306,
year = {2025},
author = {Bhavnagari, HM and Raval, AP and Tarapara, BV and Joshi, JS and Shah, FD},
title = {Translating genomic insights into therapy: an NGS-based mutation profiling study in breast cancer.},
journal = {Medical oncology (Northwood, London, England)},
volume = {43},
number = {1},
pages = {9},
pmid = {41261306},
issn = {1559-131X},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; *High-Throughput Nucleotide Sequencing/methods ; *Mutation ; Middle Aged ; Class I Phosphatidylinositol 3-Kinases/genetics ; Adult ; Aged ; DNA Copy Number Variations ; *Carcinoma, Ductal, Breast/genetics/pathology ; Genomics/methods ; DNA Mutational Analysis/methods ; Biomarkers, Tumor/genetics ; },
abstract = {The high prevalence of breast cancer is fairly frequent among women worldwide. In the current era of personalized medicine, understanding the molecular etiology of Breast Cancer is essential for better treatment options. Our investigation of the molecular alterations in tumors using next-generation sequencing targeted panels, specifically the Oncomine Precision Assay, has revealed clinically substantial somatic mutations. A total of 32 pretherapeutic invasive ductal carcinoma patients were enrolled in this study. The DNA extraction and quantification were carried out from tumor tissues and proceeded for the run and analyzed with genexus software. The analysis revealed a highly prevalent PIK3CA mutation which plays a significant role in tumorigenesis. PIK3CA mutation incorporated different single nucleotide variations including H1047R (COSMIC ID -775), E545K (COSMIC ID-763), E542K (COSMIC ID-760), H1047L (COSMIC ID-776) and N345K (COSMIC ID-754). While the most frequent copy number variations (CNV) were found for the ERBB2 gene. Apart from these frequent mutations, TP53 SNVs, FGFR, EGFR, CDKN2A, CD274, and PTEN Copy Number Variations were also present in the study cohort. The noteworthy observation is out of 7 Triple Negative Breast Cancer patients three patients were negative for any mutation. Hence, the association of genetic variation with clinicopathological parameters will be helpful in the selection of targeted treatment.},
}
@article {pmid41241870,
year = {2026},
author = {Hickey, A and De la Cruz Ku, G and King, C and Franco, C and Namazian, S and Roberts, S and Torres, KA and Persing, S and Nardello, S and Chatterjee, A},
title = {Do Racial and Income Disparities Exist in the Application of 21-Gene Recurrence Score?.},
journal = {Journal of surgical oncology},
volume = {133},
number = {1},
pages = {16-30},
doi = {10.1002/jso.70128},
pmid = {41241870},
issn = {1096-9098},
support = {//The study is self-funded./ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/ethnology ; *Neoplasm Recurrence, Local/genetics/pathology/ethnology/epidemiology ; Aged ; Middle Aged ; Adult ; Aged, 80 and over ; *Income/statistics &amp; numerical data ; United States/epidemiology ; *Biomarkers, Tumor/genetics ; SEER Program ; },
abstract = {BACKGROUND: The 21-gene recurrence score is a useful tool to predict the recurrence risk in patients with early hormone receptor positive (HR +) and human epidermal receptor-2 negative (HER2-) breast cancer, which helps to determine those patients who may benefit from chemotherapy. Our goal was to assess whether there was a disparity in the use of the 21-gene recurrence score, especially between races and income levels.<br><br>METHODS: Using the SEER Medicare database, we analyzed breast cancer patients diagnosed from 2012 to 2017. Inclusion criteria were HR&#x2009;+&#x2009;/HER2- phenotype, clinical stages I and II in post-menopausal women, and Stage 1 cancers in premenopausal women. Differences in the application of the 21-gene recurrence score with regard to race and income level were studied using chi-square analysis.<br><br>RESULTS: Overall, 124&#x2009;761 patients were included. Of these, 99.1% were females, and 32.9% had 21-gene recurrence score testing. The median age was 70 years (range 27-100). Most patients had invasive ductal carcinoma (86.6%) followed by invasive lobular carcinoma (13.4%), of which 66.0% were stage I and 34.0% as stage II. When comparing subgroups based on testing, White race had a lower application rate (83.8% vs. 84.3%, p&#x2009;=&#x2009;0.031), compared to African-Americans (8.7% vs. 8.3%, p&#x2009;=&#x2009;0.031). Similarly, patients with &#x2265;&#x2009;10% poverty index showed a lower frequency of testing (46.0% vs. 47.3%, p&#x2009;<&#x2009;0.001). However, clinically meaningful disparities by race or income were not observed. Underuse of 21-gene recurrence score was more evident among older patients (&#x2009;&#x2265;&#x2009;65, 76.9% vs. 61%, p&#x2009;<&#x2009;0.001), separated/divorced/widowed individuals (38.7% vs. 28.4%, p&#x2009;<&#x2009;0.001), and those undergoing mastectomy (39% vs. 29.5%, p&#x2009;<&#x2009;0.001) compared to breast-conserving surgery.<br><br>CONCLUSIONS: No clinically significant disparities were observed in race or income level in the application of the 21-gene recurrence score, which is reassuring, particularly as chemotherapy treatment regimens continue to trend appropriately trend toward de-escalation. However, underuse was more evident among older patients, separated/divorced/widowed individuals, and those undergoing mastectomy, highlighting opportunities to improve equity and adherence to guideline-based testing.},
}
@article {pmid41202469,
year = {2025},
author = {Esposito, A and Corsaro, L and Delle Cave, I and Nicolella, V and Palladino, R and Affinito, G and Selvaggi, F and Petracca, M and Carotenuto, A and Lanzillo, R and Portella, G and Castaldo, G and Brescia Morra, V and Moccia, M},
title = {Anti-EBV antibody reduction during ocrelizumab treatment is not associated with multiple sclerosis outcomes.},
journal = {Multiple sclerosis and related disorders},
volume = {104},
number = {},
pages = {106830},
doi = {10.1016/j.msard.2025.106830},
pmid = {41202469},
issn = {2211-0356},
mesh = {Humans ; Female ; Male ; Adult ; *Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology ; *Multiple Sclerosis/drug therapy/blood/immunology/virology/diagnostic imaging ; *Immunoglobulin G/blood ; Middle Aged ; *Immunologic Factors/therapeutic use/pharmacology ; *Herpesvirus 4, Human/immunology ; *Antibodies, Viral/blood ; *Epstein-Barr Virus Infections/immunology/drug therapy/complications ; Disease Progression ; Follow-Up Studies ; },
abstract = {BACKGROUND: The pathogenesis of multiple sclerosis (MS) involves genetic, environmental and immunological aspects. Epstein-Barr virus (EBV) infection is recognized as a major risk factor for MS, potentially contributing through infection and transformation of CD20 B cells. Monoclonal antibodies targeting CD20, such as ocrelizumab, may exert therapeutic effects by depleting memory B cells harbouring latent EBV.<br><br>OBJECTIVE: We aim to evaluate changes in serum anti-EBV immunoglobulin G (IgG) titres and clinical correlates during ocrelizumab treatment.<br><br>METHODS: We analysed serum samples from 58 patients treated with ocrelizumab, with levels of total IgG, anti-CMV IgG, and anti-EBV IgG before treatment initiation and after mean follow-up of 4.8 &#xb1; 1.5 years. Statistical analyses included paired t-tests to evaluate longitudinal changes in antibody levels, and linear regression models to investigate associations between IgG changes and relapse occurrence, MRI activity, EDSS progression and their combination.<br><br>RESULTS: Over 4.8 &#xb1; 1.5 years, we observed significant reductions in anti-EBV IgG (percentage mean change -8.2%, p = 0.03), comparable to the decline in total IgG (-8.8%, p < 0.01) and anti-CMV IgG (-7.8%, p < 0.01). No significant associations were identified between changes in anti-EBV IgG and different outcomes.<br><br>CONCLUSIONS: Ocrelizumab treatment was associated with reductions in total, anti-EBV and anti-CMV IgGs. Antibody-mediated response to EBV was not associated with disease worsening.},
}
@article {pmid41199300,
year = {2025},
author = {Mustafa, A and Armaghan, M and Shabbir, M and Badshah, Y and Khan, K and Meraj, L and Trembley, JH and Afsar, T and Almajwal, A and Razak, S},
title = {Role of PRKCZ non-synonymous genetic variants in breast cancer development.},
journal = {Cancer cell international},
volume = {25},
number = {1},
pages = {390},
pmid = {41199300},
issn = {1475-2867},
abstract = {BACKGROUND: Non- synonymous single nucleotide polymorphisms (nsSNPs) impact disease onset and progression. Protein kinase C zeta (PRKCZ) is involved in oncological, neurological, and diabetes pathogenesis. The goal of the research presented here was to investigate the role of nsSNPs in PRKCZ in breast cancer (BC) pathogenesis.<br><br>METHODS: Genotyping analysis was performed to determine the association of PRKCZ genetic variants rs1236161858 (G/T), rs367917640 (G/A/C), rs202071893(A/G), and rs757469768(G/A) with BC risk and clinicopathological variables through Tetra-ARMS PCR.<br><br>RESULTS: rs1236161858(G/T) was linked to higher BC risk in codominant (OR&#x2009;=&#x2009;5.227, RR&#x2009;=&#x2009;2.225), allele model, (OR&#x2009;=&#x2009;4.701, and RR&#x2009;=&#x2009;2.186) and log additive (OR&#x2009;=&#x2009;2.564). rs367917640 (G/A) was associated with increased BC risk in codominant model (OR&#x2009;=&#x2009;6.419, RR&#x2009;=&#x2009;2.350), recessive model (OR&#x2009;=&#x2009;12.09 and, RR&#x2009;=&#x2009;4.772) and log additive (OR&#x2009;=&#x2009;3.340). rs367917640(G/C) was linked to higher BC risk in dominant (OR&#x2009;=&#x2009;4.892, RR&#x2009;=&#x2009;2.208), recessive (OR&#x2009;=&#x2009;1.859, RR&#x2009;=&#x2009;1.34), over dominant (OR&#x2009;=&#x2009;3.675, RR&#x2009;=&#x2009;2.028) and log additive (1.579) models respectively. For rs202071893(A/G) codominant model (OR&#x2009;=&#x2009;2.295 RR&#x2009;=&#x2009;1.547), dominant model (OR&#x2009;=&#x2009;5.943, and RR&#x2009;=&#x2009;1.781) and over dominant model (OR&#x2009;=&#x2009;3.433, and RR&#x2009;=&#x2009;1.974) showed significantly higher BC association. rs757469768(G/A) was linked to higher BC risk in both dominant (OR&#x2009;=&#x2009;0.1479, and RR&#x2009;=&#x2009;0.4688) and over dominant (OR&#x2009;=&#x2009;2.005, and RR&#x2009;=&#x2009;1.455) models. However, rs757469768(G/A) was associated with reduced BC risk in log additive model (OR&#x2009;=&#x2009;0.4956).rs1236161858 correlated with DCIS and IDC. rs367917640(G/A/C) correlated with early cancer stage, LCIS, DCIS, IDC, luminal A and post-menopause. rs202071893 was associated with HER2[+]and IDC. rs757469768 was not associated with clinicopathological features and risk factors.<br><br>CONCLUSION: All five nsSNPs exhibited potential as predictive and prognostic biomarkers for BC. However, the current study findings should be validated by conducting research on large cohorts with representation from diverse population. Furthermore, biological mechanism by which these nsSNPs cause BC pathogenesis could be explored in future studies.},
}
@article {pmid41190515,
year = {2026},
author = {Dupuis, R and Fort, N and Mousset, C and Bruyère, F and Fromont, G},
title = {Spatial Characteristics of Intraductal Carcinoma of the Prostate.},
journal = {The Prostate},
volume = {86},
number = {3},
pages = {349-356},
doi = {10.1002/pros.70091},
pmid = {41190515},
issn = {1097-0045},
mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/metabolism/surgery/genetics ; Aged ; Biomarkers, Tumor/metabolism ; Middle Aged ; *Carcinoma, Ductal/pathology/metabolism ; Receptors, Androgen/metabolism ; Tumor Suppressor Protein p53 ; *Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/metabolism ; Ki-67 Antigen/metabolism ; Prostatectomy ; B7-H1 Antigen ; Glucose Transporter Type 1 ; PTEN Phosphohydrolase ; },
abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is most often considered a retrograde spread of invasive prostate cancer (PCa) into prostatic ducts, and its presence is associated with a poor prognosis. The aim of our study was to evaluate the differential expression between IDC-P and the associated invasive component and the heterogeneity of expression within IDC-P foci.<br><br>METHODS: We studied 79 cases of PCa with an intraductal component treated by prostatectomy. TMA blocks were constructed with the intraductal and invasive components and used for immunohistochemical analysis of markers involved in the cell cycle, androgen signaling, hypoxia, DNA repair, and immune checkpoints.<br><br>RESULTS: We found a good concordance of expression between both components for ERG, PTEN, p53, and MMR genes, which nevertheless show in some cases a loss restricted to the intraductal component. The expression of Ki67, PD-L1, and GLUT1 was increased in IDP-C compared to the invasive component. Furthermore, spatial heterogeneity was observed in the intraductal component: Ki67, ERG, androgen receptor and p53 were more expressed in the periphery of the lesion, while the expression of PD-L1 and GLUT1 was restricted to the center.<br><br>CONCLUSIONS: Our results support a relatedness between invasive PCa and IDC-P, and show increased expression of markers related to PCa aggressiveness in the intraductal component. The spatial heterogeneity within IDC-P suggests a higher degree of hypoxia in the center of the lesion. Increased PD-L1 expression and loss of expression of some MMR genes in IDC-P could lead to increased sensitivity to immunomodulatory treatments.},
}
@article {pmid41188210,
year = {2026},
author = {Shi, H and Wang, Y and Miyamoto, H},
title = {Intraductal Carcinoma of the Prostate With a Solid Nest Pattern May Be More Aggressive Than Gleason Grade 5 Conventional Prostatic Adenocarcinoma.},
journal = {The American journal of surgical pathology},
volume = {50},
number = {2},
pages = {156-162},
doi = {10.1097/PAS.0000000000002480},
pmid = {41188210},
issn = {1532-0979},
mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/mortality/surgery ; Neoplasm Grading ; Retrospective Studies ; Aged ; Middle Aged ; Prostatectomy ; *Adenocarcinoma/mortality/pathology/surgery ; Disease-Free Survival ; Kaplan-Meier Estimate ; Treatment Outcome ; Proportional Hazards Models ; Risk Factors ; },
abstract = {The grading of intraductal carcinoma of the prostate (IDC-P) associated with conventional prostatic adenocarcinoma (CPA) remains controversial, particularly regarding whether IDC-P exhibiting a solid nest pattern is prognostically equivalent to Gleason grade 5 CPA. We retrospectively analyzed consecutive radical prostatectomy patients with grade 5 CPA as a primary, secondary, or tertiary pattern, as well as cribriform IDC-P, while excluding cases exhibiting comedonecrosis within IDC-P. We then compared clinicopathologic features and long-term oncologic outcomes between those with (n=28 [24.3%]) and without (n=87 [75.7%]) solid-pattern IDC-P. Solid IDC-P cases were significantly associated with a higher incidence of lymph node metastasis, larger estimated tumor volume, and more frequent administration of adjuvant therapy immediately after prostatectomy. No significant differences were observed in preoperative prostate-specific antigen, Grade Group, pT stage, or surgical margin status between the 2 groups. Univariate analysis revealed significantly worse biochemical recurrence-free survival (P =0.010) and cancer-specific survival (P =0.003) in patients with solid IDC-P. In multivariable Cox regression analyses, solid IDC-P remained significantly predictive of postoperative recurrence when adjusting for prognostic factors, including Grade Group (hazard ratio 1.902, P =0.039) or the percentage of pattern 5 (hazard ratio 1.986, P =0.028). Solid-pattern IDC-P was thus found to represent an independent adverse prognostic indicator in men undergoing radical prostatectomy, further suggesting that the clinical impact of solid IDC-P versus Gleason grade 5 CPA (or cribriform IDC-P) was not comparable. It might therefore be inadequate to simply translate solid IDC-P as a grade 5 pattern.},
}
@article {pmid41179678,
year = {2025},
author = {Baracioli, LS and Rezende, CP and Dos Santos E Silva, L and Alves, DL and da Nóbrega, DF and Chuffa, LGA and Zuccari, DAPC},
title = {Immunohistochemical analysis of Enolase-1 sublocalization in benign and malignant breast tumors: potential implications for tumor progression and prognosis.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1636394},
pmid = {41179678},
issn = {2234-943X},
abstract = {Breast cancer is the second most common neoplasm in women and one of the main causes of premature mortality, with a high incidence before the age of seventy. Among its histological subtypes, invasive ductal carcinoma accounts for approximately 65% to 70% of cases and is characterized by significant molecular and prognostic heterogeneity. Although some molecular subtypes benefit from targeted therapies, triple-negative carcinomas remain a considerable clinical challenge, predominantly affecting young women who often subjected to highly aggressive and not always effective conventional treatments. The identification of prognostic and predictive biomarkers is essential to optimize therapeutic choices and anticipate potential resistance mechanisms. Enolase-1 (ENO1), a glycolytic enzyme involved in cellular energy homeostasis, has been widely associated with tumor progression and metabolic adaptation in malignant neoplasms. In this study, we investigated ENO1 expression in benign and malignant breast tumors using immunohistochemistry, analyzing both the tissue distribution pattern and staining intensity. Our results suggest that ENO1 may play a predictive diagnostic role, aiding in more individualized therapeutic strategies and contributing to the advancement of precision medicine in breast cancer.},
}
@article {pmid41176719,
year = {2025},
author = {Katai, Y and Kamitori, T and Saida, S and Uchihara, Y and Akazawa, R and Isobe, K and Mikami, T and Kubota, H and Kato, I and Umeda, K and Ueno, H and Takita, J},
title = {Clinical Impact of Immunoglobulin Heavy Chain Clonality in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.},
journal = {Cancer medicine},
volume = {14},
number = {21},
pages = {e71336},
pmid = {41176719},
issn = {2045-7634},
support = {JP19ck0106468//Japan Agency for Medical Research and Development/ ; 23ama221505//Foundation for Promotion of Cancer Research/ ; JP24ama221236//Foundation for Promotion of Cancer Research/ ; //Takeda Science Foundation/ ; //Princess Takamatsu Cancer Research Fund/ ; JP17H04224//Japan Society for the Promotion of Science/ ; JP18K19467//Japan Society for the Promotion of Science/ ; JP20H00528//Japan Society for the Promotion of Science/ ; JP21K19405//Japan Society for the Promotion of Science/ ; JP23K18264//Japan Society for the Promotion of Science/ ; JP24H00628//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; *Immunoglobulin Heavy Chains/genetics ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics/mortality/immunology/pathology ; Child ; Male ; Female ; Child, Preschool ; Neoplasm, Residual/genetics ; Prognosis ; Adolescent ; Infant ; },
abstract = {INTRODUCTION: Recent advancements in risk stratification have greatly improved outcomes in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite favorable prognostic indicators, including the absence of cytogenetic abnormalities and minimal residual disease (MRD) negativity, relapse remains a major clinical concern.<br><br>METHODS AND RESULTS: We investigated the clinical significance of immunoglobulin heavy chain (IGH) clonality using RNA sequencing data in BCP-ALL. We analyzed IGH clonality from 136 patients. IGH abundance followed a power law distribution, which enabled us to identify disease clones as outliers based on read count. In total, 330 disease clones were detected, and patients were categorized into three clonotype groups: undetectable disease clone (UDC), incomplete disease clone (IDC), and complete disease clone (CDC). Clinical outcomes were compared across clonotypes, including in subgroups with high hyperdiploidy (HHD) and MRD negativity. Among patients with HHD, significant prognostic differences were observed across clonotypes (event-free survival [EFS], p&#x2009;=&#x2009;0.01; overall survival [OS], p&#x2009;=&#x2009;0.08), even among those who were MRD-negative (EFS, p&#x2009;=&#x2009;0.01; OS, p&#x2009;=&#x2009;0.03). Furthermore, comparisons of IGH sequences between diagnosis and relapse indicated that while initial disease clones often contributed to relapse, newly expanded clones frequently emerged, particularly in patients with HHD.<br><br>CONCLUSIONS: These findings highlight the importance of analyzing the IGH repertoire in refining risk stratification and underscore the need for advanced sequencing-based MRD monitoring.},
}
@article {pmid41162834,
year = {2025},
author = {Abdullah, HM and Boi-Dsane, NAA and Wepeba, G and Dakurah, T},
title = {Intradural Extramedullary Spinal Cord Metastasis of Breast Cancer in a Male: A Case Report.},
journal = {Cancer reports (Hoboken, N.J.)},
volume = {8},
number = {11},
pages = {e70382},
pmid = {41162834},
issn = {2573-8348},
mesh = {Humans ; Male ; *Breast Neoplasms, Male/pathology/surgery ; Aged ; *Spinal Cord Neoplasms/secondary/diagnosis ; *Carcinoma, Ductal, Breast/secondary/pathology/surgery ; Magnetic Resonance Imaging ; Fatal Outcome ; Mastectomy ; },
abstract = {INTRODUCTION: Breast cancer in males is rare, accounting for just 0.5% to 1% according to World Health Organization data. This is the first reported case of IESCM from breast cancer in an African male, which makes it noteworthy. Furthermore, unlike previously reported cases in females, this case involved L1-L2 metastasis with sphincter dysfunction and a subsequent relapse leading to mortality, thereby expanding the documented spectrum of IESCM presentations and outcomes.<br><br>CASE PRESENTATION: This is a case of a 77-year-old male with invasive ductal carcinoma of the left breast and intradural extramedullary spinal cord metastasis diagnosed via Magnetic Resonance Imaging after presenting with neurological symptoms 4&#x2009;years post-mastectomy. He eventually passed away following a right Deep Venous Thrombosis, which led to bilateral pulmonary embolism after his second relapse.<br><br>CONCLUSION: Late presentation most likely contributed to the worsening of symptoms and poor prognosis. This report overstates the importance of prompt access to healthcare and the essence of thorough investigations, especially in breast cancer, where neurological symptoms may point to a metastatic diagnosis.},
}
@article {pmid41125144,
year = {2026},
author = {Hinrichs, A and Pafili, K and Sancar, G and Laane, L and Zettler, S and Torgeman, M and Kessler, B and Nono, JL and Kunz, S and Rathkolb, B and Barosa, C and Prehn, C and Cecil, A and Renner, S and Kemter, E and Kahl, S and Szendroedi, J and Bidlingmaier, M and Jones, JG and Hrabĕ de Angelis, M and Roden, M and Wolf, E},
title = {Transient juvenile hypoglycemia in GH insensitive Laron syndrome pigs is associated with insulin hypersensitivity.},
journal = {Molecular metabolism},
volume = {103},
number = {},
pages = {102273},
pmid = {41125144},
issn = {2212-8778},
mesh = {Animals ; *Insulin Resistance/physiology ; *Hypoglycemia/metabolism ; Swine ; *Insulin/metabolism ; *Laron Syndrome/metabolism ; Male ; Female ; Liver/metabolism ; Glucose Clamp Technique ; Receptors, Somatotropin/metabolism/genetics/deficiency ; Adipose Tissue/metabolism ; Lipolysis ; Glucose/metabolism ; Disease Models, Animal ; Growth Hormone/metabolism ; Blood Glucose/metabolism ; },
abstract = {BACKGROUND AND AIMS: Fasting hypoglycemia has clinical implications for children with growth hormone (GH)-insensitivity syndrome. This study investigates the pathophysiology of juvenile hypoglycemia in a large animal model for GH receptor (GHR) deficiency (the GHR-KO pig) and elucidates mechanisms underlying the transition to normoglycemia in adulthood.<br><br>METHODS: Insulin sensitivity was assessed in juvenile and adult GHR-KO pigs and wild-type (WT) controls via hyperinsulinemic-euglycemic clamp (HEC) tests. Glucose turnover was measured using D-[6,6-[2]H2] glucose and [2]H2O. Clinical chemical and targeted metabolomics parameters in blood serum were correlated with qPCR and western blot analyses of liver and adipose tissue.<br><br>RESULTS: GHR-KO pigs showed increased insulin sensitivity (p = 0.0019), especially at young age (M-value +34% vs. WT), insignificantly reduced insulin levels, and reduced endogenous glucose production (p = 0.0007), leading to fasting hypoglycemia with depleted liver glycogen, elevated &#x3b2;-hydroxybutyrate, but no increase in NEFA levels. Low hormone-sensitive lipase phosphorylation in adipose tissue suggested impaired lipolysis in young GHR-KO pigs. Metabolomics indicated enhanced fatty acid beta-oxidation and use of glucogenic amino acids, likely serving as compensatory pathways to maintain energy homeostasis. In adulthood, insulin sensitivity remained elevated but less pronounced (M-value +20%), while insulin levels were significantly reduced, enabling normoglycemia and improved NEFA availability. Increased fat mass, but not sex hormones, appeared key to this metabolic transition, as early castration had no effect.<br><br>CONCLUSIONS: Juvenile hypoglycemia in GH insensitivity results from excessive insulin sensitivity, reduced glucose production, and impaired lipolysis. Normoglycemia in adulthood emerges through increased adiposity and moderated insulin sensitivity, independently of sex hormones. These findings elucidate the age-dependent metabolic adaptations in GH insensitivity.},
}
@article {pmid41089131,
year = {2025},
author = {Kannappalli, K and Raju, K and Kamisetty, KP},
title = {Immunohistochemical Expression of Laminin 332 in Triple-Negative Breast Carcinoma: A Cross-Sectional Study.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e92206},
pmid = {41089131},
issn = {2168-8184},
abstract = {BACKGROUND: Breast carcinoma (BC) is the most common malignancy among women and is the leading cause of mortality among females. Triple-negative breast carcinoma (TNBC) is a diverse disease based on immunohistochemistry (IHC) and is estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor (HER2) negative. TNBC has a distinct molecular profile, is more aggressive, lacks targeted therapies, and has a worse prognosis than other types of breast cancer. Laminin is a glycoprotein that plays several roles in cancer progression, including cell proliferation, invasion, metastasis, and epithelial-mesenchymal transition.<br><br>AIM AND OBJECTIVES: This study aimed to evaluate the immunohistochemical expression of laminin 332 in TNBCs and&#xa0;to study the association of laminin 332 expression with clinicopathological parameters of TNBCs.<br><br>MATERIALS AND METHODS: All the cases of TNBC received from the Department of Surgery at RL Jalappa Hospital and Research Institute to the Department of Pathology attached to Sri Devaraj Urs Medical College, Tamaka, Karnataka, from January 2019 to September 2024 were considered for the study. Both prospective and retrospective cases were considered. The data and paraffin blocks were retrieved from the archives of the Department of Pathology. Histopathological parameters of TNBC cases were studied, and laminin 332 IHC was performed. The association of IHC expression of laminin 332 and histopathological parameters was evaluated.<br><br>RESULTS: Among 50 TNBC cases, 26 (56%) were elderly patients above 50 years of age. A higher proportion of cases, i.e., 23 (46%), were grade 3 tumors; 46 (92%) cases had infiltrating ductal carcinomas (IDC); 39 (78%) had lymphovascular invasion (LVI); 46 (92%) were without perineural invasion (PNI); and 22 (44%) had high-grade tumor-infiltrating lymphocytes (TILS). All the TNBC cases exhibited positivity for either a laminin 332 IHC score of 5 (64%) or a laminin 332 IHC score of 6 (36%). Laminin 332 IHC score of 5 (71.8%) was associated with the presence of LVI, and laminin IHC scores of 6 (p-value 0.041) and 7 (63.6%) were associated with the absence of LVI, which has a statistically significant association with p-value 0.041.<br><br>CONCLUSIONS: All the TNBC patients were positive for laminin 322, but there was a statistically significant association only with lymphovascular invasion. TNBC, hence, exhibits aggressive behavior and is associated with unfavorable clinicopathological outcomes.},
}
@article {pmid41088701,
year = {2025},
author = {Wang, Y and Li, Q and Sun, D and Yang, N and Kong, Y and Shen, Y and Zhang, F},
title = {m6A RNA methylation regulator heterogeneous nuclear ribonucleoprotein C: A prognostic biomarker for invasive ductal carcinoma validated through Mendelian randomization and transcriptome analyses.},
journal = {Medicine},
volume = {104},
number = {41},
pages = {e44733},
pmid = {41088701},
issn = {1536-5964},
support = {2021A1515010040//Natural Science Foundation of Guangdong Province, China/ ; 2023A1515010829//Natural Science Foundation of Guangdong Province, China/ ; 20242BAB25448//Jiangxi Province natural science Foundation project/ ; },
mesh = {Humans ; Female ; *Heterogeneous-Nuclear Ribonucleoprotein Group C/genetics/metabolism ; *Breast Neoplasms/genetics/pathology/mortality/metabolism ; Prognosis ; Biomarkers, Tumor/genetics/metabolism ; *Adenosine/analogs &amp; derivatives/metabolism ; *Carcinoma, Ductal, Breast/genetics/mortality/pathology/metabolism ; Gene Expression Profiling ; Methylation ; RNA-Binding Proteins/genetics/metabolism ; Middle Aged ; Gene Expression Regulation, Neoplastic ; RNA Splicing Factors/genetics ; RNA Methylation ; },
abstract = {Although aberrant N6-methyladenosine (m6A) RNA methylation has been linked to oncogenesis and tumor progression, the association between the deregulation of m6A regulators and invasive ductal carcinoma (IDC), the predominant subtype of breast cancer, remains unclear. In this study, we sought to determine the function of m6A RNA methylation regulators in IDC, with a particular focus on assessing their potential as prognostic biomarkers. To identify dysregulated m6A RNA methylation regulators, we systematically analyzed 656 samples from patients with IDC and 81 normal samples from The Cancer Genome Atlas (TCGA) database, and Cox univariate, LASSO-Cox regression, and stepwise regression analyses were conducted to construct a risk-prediction model for determining patient prognosis. Subsequently, we evaluated the prognostic value of the risk signature in IDC and assessed potential biological associations based on clinical survival analyses, examination of publicly available immunohistochemical staining data from the Human Protein Atlas, and two-sample Mendelian randomization. Among the IDC samples, we identified 12 m6A RNA methylation regulators characterized by significant dysregulation. Subsequently, a 4-gene signature comprising heterogeneous nuclear ribonucleoprotein C (HNRNPC), YTH domain-containing family proteins 2 and 3 (YTHDF2/3), and RNA-binding motif protein 15B (RBM15B) was constructed using machine learning algorithms. This signature was established to be an independent prognostic factor, particularly in patients with early stage IDC, and within the signature, HNRNPC was identified as a pivotal gene, the expression levels of which were demonstrated to be causally associated with the risk of IDC. On the basis of our findings in this study, we established a prognostic signature for IDC and identified a causal association between the expression of the signature gene HNRNPC and IDC risk. These findings indicate that m6A RNA methylation regulators could serve as molecular biomarkers for IDC and contribute to guiding therapeutic strategies.},
}
@article {pmid41084011,
year = {2025},
author = {Vignaroli, K and Perez, K and Lee, M and Raju, S and Nguyen, A and Malkoc, A and Martinetto, E and Burbank, R and Ibrahim, A and Ko, E and Ramiscal, JAB},
title = {Invasive ductal carcinoma of the breast with gallbladder metastasis: a rare case report.},
journal = {World journal of surgical oncology},
volume = {23},
number = {1},
pages = {367},
pmid = {41084011},
issn = {1477-7819},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/therapy/surgery ; *Carcinoma, Ductal, Breast/secondary/therapy/pathology ; Adult ; *Gallbladder Neoplasms/secondary/therapy ; Prognosis ; Fatal Outcome ; Mastectomy, Segmental ; },
abstract = {BACKGROUND: Invasive ductal carcinoma of the breast most commonly metastasizes to bone, lung, liver, and central nervous system. Breast cancer metastasis to the gallbladder is exceptionally rare, especially when it is secondary to breast cancer of ductal origin.<br><br>CASE PRESENTATION: We present the case of a pre-menopausal 43-year-old female with a history of major depressive disorder and no prior mammograms who was diagnosed with ER+/PR+/HER2+ invasive ductal carcinoma of the right breast. She developed late metastasis to the gallbladder, liver, lung and bone detected four years after breast conserving surgery with delayed neoadjuvant chemotherapy, adjuvant radiation, incomplete adjuvant biologic and hormone therapy, and lack of surveillance. The patient died three years and ten months after her lumpectomy.<br><br>CONCLUSIONS: Though rare, adequate suspicion should be maintained when evaluating patients with a history of breast cancer who present with symptoms of cholecystitis or biliary colic in order to promptly identify breast cancer metastasis to the gallbladder, as well as to more common metastatic sites.},
}
@article {pmid41072531,
year = {2025},
author = {Hassan, M and Al-Askeri, M and Jawad, N},
title = {PROGNOSTIC IMPACT OF EGFR2 AND KI-67 OVEREXPRESSION WITH DOWNREGULATION OF MIR-17 AND MIR-1307 IN FEMALE BREAST CANCER PATIENTS.},
journal = {Georgian medical news},
volume = {},
number = {364-365},
pages = {303-313},
pmid = {41072531},
issn = {1512-0112},
mesh = {Humans ; Female ; *MicroRNAs/genetics/metabolism ; *Breast Neoplasms/genetics/pathology/diagnosis/metabolism ; *Ki-67 Antigen/genetics/metabolism ; Middle Aged ; Prognosis ; *Biomarkers, Tumor/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Down-Regulation ; *Receptor, ErbB-2/genetics/metabolism ; Adult ; *Carcinoma, Ductal, Breast/genetics/pathology/diagnosis ; *Carcinoma, Lobular/genetics/pathology/diagnosis ; Aged ; Case-Control Studies ; },
abstract = {BACKGROUND: Breast cancer has distinct epidemiological patterns and heterogeneity. EGFR2 and Ki-67 are significant in determining the progression and therapeutic response in breast cancer. Additionally, miR-17 and miR-1307 are critical regulators of tumorigenesis. Our research investigates the function of these biomarkers across breast cancer progression, diagnostic and treatment response.<br><br>METHODS: Fifty-Three women with breast cancer and 25 healthy women were analyzed. ELISA was used to evaluate the concentrations of EGFR2 and Ki-67. For gene expression, qPCR was used to analyze the gene expression of miR-17 and miR-1307. The diagnostic value of the proteins and miRNAs, with significance set at a p-value <0.001 for all tests.<br><br>RESULTS: The study found a significant increase in EGFR2 and Ki-67 proteins in patients compared to controls. The concentration of EGFR2 in lobular carcinoma showed a significantly higher concentration compared to Invasive Ductal Carcinoma (IDC) and Mixed carcinoma, with a p-value of 0.001. Regarding Ki-67, Lobular carcinoma had significantly higher levels compared to IDC, with a p-value of 0.03. ROC curve analysis revealed excellent diagnostic accuracy for EGFR2 and Ki-67. Positive correlation was shown between EGFR2 and Ki-67 with each other, also miR-17 and miR-1307 showed a positive correlation with other. On the other hand, a negative correlation was seen between the protein level and gene expression.<br><br>CONCLUSION: This study found elevated EGFR2 and Ki-67 levels in breast cancer patients, indicating tumor aggressiveness, while the downregulation of miR-17 and miR-1307 suggests reduced tumor-suppressive activity. Their inverse correlation supports their use in diagnostic and treatment monitoring.},
}
@article {pmid41072030,
year = {2025},
author = {Vignaroli, KA and Malkoc, A and Perez, K and Daoud, A and Mamoun, L and Kim, SU and Guan, A and Ramiscal, JAB},
title = {Factors Associated with Positive Margin Requiring Re-Excision after Oncoplastic Breast-Conserving Surgery.},
journal = {Southern medical journal},
volume = {118},
number = {10},
pages = {663-666},
doi = {10.14423/SMJ.0000000000001887},
pmid = {41072030},
issn = {1541-8243},
mesh = {Humans ; Female ; Retrospective Studies ; *Mastectomy, Segmental/methods/statistics &amp; numerical data ; Middle Aged ; *Margins of Excision ; *Breast Neoplasms/surgery/pathology ; *Reoperation/statistics &amp; numerical data ; Aged ; Adult ; Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; Carcinoma, Ductal, Breast/surgery/pathology ; Risk Factors ; Carcinoma, Lobular/surgery/pathology ; },
abstract = {OBJECTIVE: Multiple factors are associated with re-excision after breast-conserving surgery (BCS), however there is minimal literature discussing factors associated with re-excision after oncoplastic BCS (OBCS). This retrospective study aimed to identify factors associated with positive margins requiring re-excision after OBCS.<br><br>METHODS: A retrospective review was performed on patients who underwent OBCS between October 2021 and May 2024. Subjects were divided into those who required re-excision and those who did not. Factors were evaluated including patient age, body mass index, smoking status, presence of hypertension and diabetes mellitus, tumor multifocality, microcalcifications, tumor size, human epidermal growth factor receptor 2[+] (HER2[+]) status, triple negative (estrogen receptor[-]/progesterone receptor[-]/HER2[-]) status, and tumor pathologies including ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and invasive lobular carcinoma.<br><br>RESULTS: The need for re-excision was significantly associated with a DCIS pathology (50% of patients, P = 0.021), and the lack of need for re-excision was associated with an IDC pathology (12.5% of patients, P = 0.005). There was no significant correlation in the need for margin re-excision based on age, body mass index, smoking status, the presence of hypertension or diabetes mellitus, tumor size, the presence of invasive lobular carcinoma, triple negative status, presence of HER2 or triple negative status, microcalcifications, or tumor multifocality.<br><br>CONCLUSIONS: Most factors associated with re-excision after BCS were not associated with re-excision after OBCS in our study. Similar to data published for BCS, however, our results show that DCIS pathology was significantly associated with re-excision in patients who undergo OBCS. In addition, the presence of IDC seemed to be negatively associated with re-excision after OBCS.},
}
@article {pmid41069925,
year = {2025},
author = {Sajid, J and Qureshi, R and Ahmad, H and Qureshi, AUR and Shafiq, A},
title = {Multi-modal Malignancies in Cowden Syndrome: Diagnostic Challenges in a Suspected Case From a Low-Resource Setting.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91827},
pmid = {41069925},
issn = {2168-8184},
abstract = {Cowden syndrome (CS), a rare autosomal dominant disorder caused by mutations in the PTEN tumor suppressor gene, predisposes individuals to a wide range of malignancies, including breast, thyroid, endometrial, and renal cancers. This report presents a case of a 69-year-old woman with a history of papillary thyroid carcinoma, recently diagnosed invasive ductal carcinoma of the breast, and incidental clear cell renal cell carcinoma (RCC) - clinically pointing toward the diagnosis of CS. Genetic testing and endoscopic evaluations were not possible, as the case occurred in the setting of a developing country, with limited resources and financial constraints. This case underscores the importance of early recognition of hereditary cancer syndromes in patients with multiple malignancies, as well as the need for comprehensive genetic counseling, surveillance, and tailored treatment strategies. A multidisciplinary approach involving oncology, surgery, radiology, and genetics is crucial in managing the complex clinical presentation of patients with CS. The case also highlights the challenges faced when establishing a formal diagnosis in resource-constrained settings. These challenges are related not only to limited resources, but also to patient compliance, health literacy, and access to healthcare services.},
}
@article {pmid41068218,
year = {2025},
author = {Giorello, MB and Borzone, FR and Padin, MDR and Mora, MF and Wernicke, A and Labovsky, V and Chasseing, NA},
title = {Breast microcalcifications as indicators of bone metastasis risk in early-stage breast cancer.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {35311},
pmid = {41068218},
issn = {2045-2322},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/mortality ; *Calcinosis/pathology/diagnostic imaging ; Middle Aged ; *Bone Neoplasms/secondary ; Prognosis ; Adult ; Aged ; Neoplasm Staging ; Risk Factors ; },
abstract = {Bone metastasis is a leading cause of reduced survival in patients with advanced breast cancer. Therefore, identifying prognostic markers for bone metastasis at early disease stages is crucial. Microcalcifications are common findings in mammographic imaging and often serve as early diagnostic indicators. Certain types of microcalcifications have been linked to unfavorable genetic and molecular tumor profiles and are associated with poor prognosis. In particular, calcifications located within large ducts-such as casting-type, duct-centric patterns-have been described as independent markers of adverse outcome when compared to tumors with other calcification types or without calcifications. This study evaluated the prognostic significance of anarchic microcalcifications, defined as calcifications with irregular borders and/or disorganized patterns, in patients with early-stage breast cancer. Hematoxylin and eosin staining was used to assess the presence of these microcalcifications in invasive ductal carcinoma samples (n = 350). Their association with clinical and pathological characteristics was analyzed, including local relapse and bone metastasis occurrence. The presence of tumor microcalcifications was significantly associated with an increased risk of local relapse (p = 0.0360) and bone metastasis (p = 0.0020). Moreover, patients with microcalcifications exhibited shorter local relapse-free survival and bone metastasis-free survival (p = 0.0080 and p = 0.0020, respectively). Importantly, multivariate analysis confirmed that microcalcifications were an independent prognostic factor for both outcomes (p = 0.0150 and p = 0.0020, respectively). These findings suggest that the presence of tumor microcalcifications may serve as an independent prognostic marker for bone metastasis in early-stage breast cancer. Incorporating the evaluation of microcalcifications into routine pathological assessments could improve prognostic precision and support personalized treatment strategies. Further research is needed to elucidate the molecular mechanisms underlying the association between tumor microcalcifications and breast cancer progression.},
}
@article {pmid41063232,
year = {2025},
author = {Teng, L and Du, J and Dong, Y and Li, K and Tao, W},
title = {Survival analysis of metachronous bilateral ectopic breast cancer utilizing the SEER database and the pioneering construction of a nomogram model.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {934},
pmid = {41063232},
issn = {2047-783X},
support = {2021J17//First&#xa0;Affiliated&#xa0;Hospital&#xa0;of&#xa0;Harbin&#xa0;Medical&#xa0;University&#xa0;Fund&#xa0;for&#xa0;Distinguished&#xa0;Young Medical&#xa0;Scholars/ ; YXJL-2021-0302-0287//BEIJING MEDICAL AWARD FOUNDATION/ ; },
mesh = {Humans ; *Nomograms ; Female ; SEER Program ; *Breast Neoplasms/mortality/pathology/epidemiology ; Middle Aged ; *Neoplasms, Second Primary/mortality/pathology/epidemiology ; Prognosis ; Aged ; Adult ; Survival Analysis ; Risk Factors ; },
abstract = {INTRODUCTION: Metachronous bilateral ectopic breast cancer (MBEBC) is clinically rare, but the incidence has been increasing in recent years and no clear therapeutic guidance or prognostic assessment is available.<br><br>METHODS: Data on MBEBC patients from the Surveillance, Epidemiology, and End Results (SEER) database were gathered and randomly split into a training set and a validation set at a 7:3 ratio. Independent prognostic risk factors were identified through both univariate and multivariate analyses, and a nomogram was constructed based on these factors to predict survival outcomes.<br><br>RESULTS: From the SEER database, we collected data on a total of 8240 patients spanning the years 2005-2015. These patients were then randomly divided into a training set (5768) and a validation set (2472) for analysis. The clinicopathological features indicated that Grade 2 tumors were the most prevalent, with invasive ductal carcinoma comprising 71.2% of the cases. Additionally, the majority of MBEBC patients were classified as N0, and only a small fraction (4.2%) exhibited distant metastases. A multivariate COX regression model was developed to identify independent prognostic risk factors for patients whose first and second tumors were both invasive ductal carcinomas, as well as those with more extensive pathological types. Nomograms were also constructed for survival prediction of overall survival (OS) and breast cancer-special survival (BCSS) at 3, 5, and 10&#xa0;years. Receiver operating characteristic (ROC) curves were plotted and area under the curve (AUC) values were calculated. The AUC was greater than 0.7 in all models, with a 10-year OS of 78.0 (76.0-80.0) and a BCSS of 77.6 (76.0-79.3) in all patients. The calibration curves and decision curve analysis (DCA) demonstrate that the nomogram possesses strong clinical predictive capability and high predictive accuracy.<br><br>CONCLUSION: This study detailed the clinicopathological characteristics of patients with the clinically rare MBEBC and identified independent prognostic risk factors across various pathology types. Additionally, a nomogram was developed for individualized prediction of patients' BCSS and OS, offering a new adjunctive tool for the clinical management of MBEBC patients.},
}
@article {pmid41054366,
year = {2025},
author = {Mohammed Mahmoud, M and Abdulla Kamil Abdulla, and Dler Omar Mohammed, },
title = {Molecular detection of Epstein-Barr virus in invasive ductal carcinoma of the breast: a case-control study.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
volume = {71},
number = {9},
pages = {105-110},
doi = {10.14715/cmb/2025.71.9.13},
pmid = {41054366},
issn = {1165-158X},
mesh = {Humans ; Female ; Case-Control Studies ; *Breast Neoplasms/virology/pathology ; *Herpesvirus 4, Human/genetics/isolation &amp; purification ; *Carcinoma, Ductal, Breast/virology/pathology ; Middle Aged ; Adult ; *Epstein-Barr Virus Infections/virology/complications ; Aged ; Viral Matrix Proteins/metabolism/genetics ; Receptor, ErbB-2/metabolism ; },
abstract = {The uncertain contribution of Epstein-Barr virus (EBV) to the etiological processes underlying invasive ductal carcinoma (IDC) of the mammary gland, especially in relation to its molecular interactions within inflamed histological contexts, remains to be elucidated. This case-control research assessed the link between EBV infection and mammary IDC in a population of Iraqi females from Kirkuk. A total of 300 breast tissue specimens preserved in paraffin blocks were evaluated, including 150 samples diagnosed with IDC and 150 samples classified as fibroadenoma serving as controls. EBV latent membrane protein-1 expression was identified through the application of immunohistochemical staining and polymerase chain reaction methodologies. EBV positivity, defined as detection by both IHC and PCR, was observed in 7.3% of IDC cases and 4% of controls, with no statistically significant difference between groups (P=0.996). No significant association was found between EBV presence and estrogen or progesterone receptor status, while Her-2 expression differed significantly between EBV-positive and EBV-negative patients (P<0.001). EBV was more frequently detected in grade I tumors and stage II breast cancers, and older patients showed a higher prevalence of EBV infection. The results indicate that although Epstein-Barr virus (EBV) is identifiable in a fraction of invasive ductal carcinoma (IDC) breast specimens, a definitive causative relationship between EBV presence and IDC occurrence within this demographic is not established. Nonetheless, EBV detection appears to exhibit higher frequency in specific histopathological grades, clinical stages, and patient age categories.},
}
@article {pmid41046212,
year = {2025},
author = {Zhou, Z and Sun, Z and Zhao, F and Jin, Y and Chen, Y and Zhu, L and Guo, Y and Wang, W},
title = {Predictive Value of Nomogram-Based Clinicopathological Biomarkers Combined with Multiparametric MRI for Tumour-Infiltrating Lymphocyte Expression in Breast Cancer.},
journal = {Academic radiology},
volume = {32},
number = {12},
pages = {7134-7145},
doi = {10.1016/j.acra.2025.09.017},
pmid = {41046212},
issn = {1878-4046},
mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/immunology ; *Lymphocytes, Tumor-Infiltrating/pathology ; *Nomograms ; Middle Aged ; *Multiparametric Magnetic Resonance Imaging/methods ; Adult ; Predictive Value of Tests ; Aged ; Sensitivity and Specificity ; Retrospective Studies ; Biomarkers, Tumor ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/immunology ; *Magnetic Resonance Imaging/methods ; },
abstract = {RATIONALE AND OBJECTIVES: To investigate the value of clinicopathological features and multiparametric magnetic resonance imaging (MRI) in predicting tumour-infiltrating lymphocyte (TIL) levels in breast cancer.<br><br>MATERIALS AND METHODS: A total of 171 patients diagnosed with invasive ductal carcinoma who underwent preoperative MRI (2023-2025) were included. The analysis focused on the clinicopathological characteristics alongside conventional MRI features and a range of quantitative parameters. Multiple logistic regression analysis identified independent predictors of high and low TIL levels. A nomogram was constructed based on the multivariable logistic regression model results.<br><br>RESULTS: Logistic regression analysis identified histological grade, D, D*, Ktrans, and Kep as independent factors in the training cohort. The nomogram's C-index was 0.944 in the training cohort and 0.964 in the validation cohort. The area under the curve (AUC) of the nomogram model was 0.954 (85.1% sensitivity, 91.1% specificity, and 87.4% accuracy) in the training cohort and 0.974 (96.7% sensitivity, 92.1% specificity, and 92.6% accuracy) in the validation cohort, both significantly higher than those of the individual models in the corresponding cohorts (Z=3.018-6.653, all P<0.05 and Z=2.546-5.668, all P<0.05).<br><br>CONCLUSION: Combining clinicopathological characteristics with multiparametric MRI parameters significantly improves prediction accuracy for TIL levels in breast cancer. This integrated model holds considerable clinical potential, providing robust support for personalised treatment strategies.},
}
@article {pmid41035082,
year = {2025},
author = {Sarmadi, A and Javanmard, SH and Zeinalian, M and Hosseinzadeh, M and Tabatabaiefar, MA},
title = {Mono-allelic MUTYH mutation as the likely inherited etiology of hereditary breast cancer in a patient from a multi-cancer family- report of a family and literature review.},
journal = {BMC medical genomics},
volume = {18},
number = {1},
pages = {146},
pmid = {41035082},
issn = {1755-8794},
mesh = {Humans ; *DNA Glycosylases/genetics ; Female ; *Breast Neoplasms/genetics/pathology ; Pedigree ; *Alleles ; *Mutation ; Middle Aged ; *Genetic Predisposition to Disease ; Adult ; Exome Sequencing ; },
abstract = {BACKGROUND: Breast cancer (BC) is the most prevalent cancer globally. Carriers of pathogenic variants in high- or moderate-penetrance genes, have an increased risk of developing hereditary BC (HBC). While, MUTYH is known to be associated with hereditary colonic polyposis and colorectal carcinoma, its role in BC is controversial. This study investigated the genetic cause of HBC in an Iranian family with a history of multiple cancer cases.<br><br>METHODS: Clinical examination and exome sequencing (ES) was performed in a patient suffering from invasive ductal carcinoma from a family with several cases of different types of cancer. The pathogenicity of detected variants was done based on American Collage of Medical Genetics (ACMG) and Sanger sequencing was carried out for its validation. Furthermore, we performed a comprehensive review of the literature.<br><br>RESULTS: Here, a pathogenic variant (p. A287Pfs*32) was identified in the MUTYH gene in mono-allelic status in four BC patients. However, this variant was previously reported as the cause of MutYH-associated polyposis (MAP) in homozygous status. The review of literature showed that the frequency of MUTYH mutation in BC patients population is in a range of 0.3-5.6%.<br><br>CONCLUSION: In this study, a heterozygous pathogenic variant in the MUTYH gene was identified as the possible cause of BC in a multi-cancer family using ES. While the potential association between mono-allelic MUTYH mutations and an elevated risk of BC remains controversial, these findings highlight the necessity for a careful interpretation when assessing the role of MUTYH mutations in BC risk.},
}
@article {pmid41026283,
year = {2025},
author = {Hawkins, KN and Dillard, J and Ye, Y and Wang, J and Hoffman, RM and Mcphail, K and Barsky, SH},
title = {Natural and induced epithelial-mesenchymal transition results in epigenetic silencing of HER2 overexpression.},
journal = {Journal of mammary gland biology and neoplasia},
volume = {30},
number = {1},
pages = {15},
pmid = {41026283},
issn = {1573-7039},
support = {U54 CA163069/CA/NCI NIH HHS/United States ; U54CA163069//Pathology Shared Resource Core, supported by NIH/ ; BC990959, BC024258, BC053405//Department of Defense Breast Cancer Research Program Grants/ ; },
mesh = {*Epithelial-Mesenchymal Transition/genetics ; Humans ; *Receptor, ErbB-2/genetics/metabolism ; Female ; *Epigenesis, Genetic ; *Gene Silencing ; Gene Expression Regulation, Neoplastic ; *Breast Neoplasms/genetics/pathology/metabolism ; Cell Line, Tumor ; Animals ; Transforming Growth Factor beta1 ; },
abstract = {Epithelial-mesenchymal transition (EMT) is a well-known phenomenon that has been implicated in diverse biological processes ranging from embryonal development to cancer invasion and metastasis. In epithelial-derived cancers which both invade and metastasize as epithelial clumps or clusters, EMT would have to be followed by MET (mesenchymal-epithelial transition) since both the initial cancer and the metastasis appear epithelial in nature. There is a rare subset of breast carcinomas, however, that exhibit biphasic epithelial and mesenchymal differentiation, so-called metaplastic carcinomas. Our initial studies were designed to examine whether EMT was indeed occurring in this unique subset of metaplastic breast carcinomas. Based on both RT-PCR and immunocytochemical studies, EMT was naturally occurring. Once this was confirmed, we wanted to investigate the effects of EMT beyond the immediate gene expression pattern that traditionally defined it. Although approximately 90% of metaplastic breast carcinomas are triple negative, 5-10% amplify and overexpress HER2. We then conducted both observational studies in these biphasic HER2 overexpressing metaplastic breast carcinomas and experimental studies with a HER2 overexpressing cell line, the HTB20, where TGFβ1 induced EMT. In the observational studies, HER2 gene amplification was equally present in both the epithelial and mesenchymal phases but both HER2 mRNA and protein levels were essentially silenced in the areas having undergone EMT. Similarly in the experimental studies where TGFβ1 induced EMT, HER2 gene amplification persisted but HER2 mRNA and protein levels were similarly silenced. These studies provide direct evidence that both naturally occurring and induced EMT results in epigenetically silencing of HER2 overexpression.},
}
@article {pmid41024216,
year = {2025},
author = {Kitagawa, Y and Nassiri, M and Mesa, H and Prakash, J and Popnikolov, N},
title = {Possible role of anastrozole-induced hormonal alterations in pathogenesis of mammary apocrine carcinoma and follicular lymphoma: a case report and review of the literature.},
journal = {Journal of medical case reports},
volume = {19},
number = {1},
pages = {465},
pmid = {41024216},
issn = {1752-1947},
mesh = {Aged, 80 and over ; Female ; Humans ; *Anastrozole/adverse effects ; Antineoplastic Agents, Hormonal/adverse effects ; *Aromatase Inhibitors/adverse effects ; *Breast Neoplasms/chemically induced/pathology/surgery ; *Carcinoma, Ductal, Breast/pathology/chemically induced/surgery ; *Lymphoma, Follicular/chemically induced/pathology ; Mammography ; Paget's Disease, Mammary/diagnosis/drug therapy ; },
abstract = {BACKGROUND: In postmenopausal women, aromatase inhibitors decrease estrogen levels and increase local dihydrotestosterone concentrations. In this case report, we describe interesting associations between aromatase-inhibitor-induced hormonal changes and the development of apocrine mammary carcinoma and follicular lymphoma.<br><br>CASE PRESENTATION: Here we report an 83-year-old Caucasian female patient who initially presented with Paget's disease of the right nipple and associated small focus of invasive ductal carcinoma (ER&#x3b1;&#x2009;+&#x2009;PR&#x2009;+&#x2009;HER2-). The patient did not pursue surgical resection and was treated only with anastrozole, and 5 years later, she was diagnosed with a 1.1&#xa0;cm ipsilateral periareolar apocrine mammary carcinoma (ER&#x3b1;-ER&#x3b2;&#x2009;+&#x2009;PR&#x2009;-&#x2009;AR&#x2009;+&#x2009;HER2-) that was detected during surveillance mammography. In addition to this tumor, the subsequent mastectomy specimen revealed an adjacent residual focus of the original invasive ductal carcinoma (ER&#x3b1;&#x2009;+&#x2009;ER&#x3b2;&#x2009;+&#x2009;PR&#x2009;+&#x2009;AR&#x2009;+&#x2009;HER2-) within the nipple and a focus of follicular lymphoma (ER&#x3b1;-ER&#x3b2;&#x2009;+&#x2009;AR[low]) in the retroareolar area. Sentinel lymph nodes and imaging studies were negative for malignancy. The patient was continued on observation. Anastrozole was stopped after 10&#xa0;months, and 2 months later, during a routine screening, a 1.8&#xa0;cm invasive apocrine carcinoma (ER&#x3b1;-ER&#x3b2;&#x2009;+&#x2009;PR-AR&#x2009;+&#x2009;HER2-) was detected in the patient's contralateral breast and she underwent simple mastectomy with sentinel lymph node biopsy. The sentinel lymph node was negative. No chemotherapy or radiation therapy was recommended. All carcinomas exposed to anastrozole expressed androgen-responsive molecules (GCDFP-15, NKX3.1). Germline genetic testing for 19 genes associated with hereditary breast cancer syndromes was negative, and 3 years later, the patient is still alive with no recurrences.<br><br>CONCLUSION: Our case suggests that unopposed local androgen exposure and loss of ER&#x3b2;-mediated suppressive effect of estrogens may be involved in development of apocrine mammary tumors and lymphomas, respectively. However, further studies are necessary to clarify the roles of steroid hormones in pathogenesis of apocrine carcinoma and follicular lymphoma. This case also illustrates the importance of patient follow-up during and after aromatase inhibitor therapy. Appropriate surveillance for lymphoma may also be considered for those patients. Finally, when lymphoid aggregates are encountered in specimens from patients with breast cancer, a clinical history of hormonal therapy should alert the pathologist for a possibility of lymphoma.},
}
@article {pmid41023513,
year = {2025},
author = {Aponte-Rueda, ME and Gómez-González, FM and Merck, B},
title = {Breast Cancer Heterogeneity in Latin America: A Scoping Review of Clinical-Pathological Characteristics, Molecular Subtypes, and Survival.},
journal = {World journal of surgery},
volume = {49},
number = {11},
pages = {3001-3025},
pmid = {41023513},
issn = {1432-2323},
mesh = {Humans ; Female ; Latin America/epidemiology ; *Breast Neoplasms/pathology/mortality/genetics/epidemiology ; Neoplasm Staging ; Middle Aged ; Neoplasm Grading ; },
abstract = {BACKGROUND: Breast cancer in Latin America (LATAM) exhibits distinct clinical-pathological and molecular features, shaped by genetic diversity and healthcare disparities. This scoping review evaluates these characteristics, focusing on histopathological, molecular subtype, and survival patterns and their implications for future research and public health initiatives.<br><br>METHODS: A systematic search across MEDLINE (via PubMed), LILACS (Latin American and Caribbean Health Sciences Literature), SciELO (Scientific Electronic Library Online), and Web of Science identified 54 studies across 19 Latin American countries. Data were extracted on histological grading, molecular subtypes, staging, and survival outcomes. Findings were analyzed in the context of regional and global trends.<br><br>RESULTS: Fifty-four studies involving 49,223 women from 19 countries were analyzed. The mean age at diagnosis was 54.3&#xa0;years. Invasive ductal carcinoma was the most common (79.2%). Advanced-stage disease (Stages III/IV) was identified in 36.1% of cases. Luminal subtypes were most prevalent (Luminal A: 36.95% and Luminal B: 28.72%), whereas triple-negative (TNBC) and HER2-enriched subtypes accounted for 17.45% and 12.69%, respectively. Subtype prevalence varied by country, age, and tumor grade. Five-year survival rates ranged from 50.5% to 92.5%, with worse outcomes linked to advanced stage, high grade, and TNBC or HER2-enriched tumors.<br><br>CONCLUSION: Breast cancer in LATAM is characterized by significant heterogeneity in biological subtypes and clinical presentation, often diagnosed at advanced stages, with limited capacity for molecular testing. These findings highlight the urgent need for standardized diagnostic protocols, equitable access to treatment, and region-specific cancer control strategies to improve outcomes for Latin American women.},
}
@article {pmid41018463,
year = {2025},
author = {Douligeris, CC and Boptsi, E and Theocharopoulos, C and Foteinou, D and Batis, A and Lampropoulos, P and Manolakos, O},
title = {A Rare Cause of Intestinal Obstruction: Invasive Lobular Breast Carcinoma Metastasizing to the Ileocecal Valve.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e90985},
pmid = {41018463},
issn = {2168-8184},
abstract = {Invasive lobular carcinoma (ILC) has a higher propensity for gastrointestinal metastases compared to invasive ductal carcinoma (IDC). We present the case of a 65-year-old woman with metastatic ILC who developed intestinal obstruction due to ileocecal metastases 30 months after undergoing total mastectomy and adjuvant therapy for left-sided breast cancer (BC). Abdominal computed tomography (CT) demonstrated a transition point at the ileocecal valve. Surgical resection was performed to relieve the small bowel obstruction, and histopathology confirmed metastatic ILC with receptor discordance compared to the primary tumor. This case highlights the diagnostic and therapeutic challenges of intestinal metastases from BC, including receptor conversion and resistance to therapy. Molecular profiling and tailored treatment are crucial for optimal management of complex metastatic disease.},
}
@article {pmid41005725,
year = {2025},
author = {Sulaj, A and Nguyen, PBH and Poschet, G and Kliemank, E and Fleming, T and Henke, L and Neibig, W and Kopf, S and Hell, R and Longo, VD and Herzig, S and Nawroth, PP and Menden, MP and Szendroedi, J},
title = {Periodic fasting induced reconstitution of metabolic flexibility improves albuminuria in patients with type 2 diabetes.},
journal = {Molecular metabolism},
volume = {102},
number = {},
pages = {102257},
pmid = {41005725},
issn = {2212-8778},
mesh = {Humans ; *Diabetes Mellitus, Type 2/metabolism/diet therapy/complications ; *Albuminuria/metabolism/diet therapy ; *Fasting/metabolism ; Male ; Female ; Middle Aged ; Diabetic Nephropathies/metabolism/diet therapy ; Aged ; Lipid Metabolism ; Metabolomics/methods ; Diet, Mediterranean ; Metabolome ; },
abstract = {OBJECTIVE: Metabolic inflexibility has been shown to be associated with type 2 diabetes (T2D) and diabetic nephropathy (DN). However, data are lacking, proving that reconstitution of metabolic flexibility by using a 6-month periodic fasting (PF) regimen may improve albuminuria.<br><br>METHODS: In this post hoc analysis of a randomized-controlled trial, we investigated whether the PF regimen enhanced metabolic flexibility in individuals with T2D and DN showing improvement of albuminuria (responders) compared to non-responders. Participants followed every month either a 5-day fasting-mimicking diet or a Mediterranean diet for 6 months. LC-MS/MS-based comprehensive metabolic profiling was performed in plasma samples before, during, and after the intervention. Changes in metabolomic patterns and enriched signalling pathways were analysed between study groups.<br><br>RESULTS: PF induced a sustained shift toward enhanced fatty acid oxidation, lipid utilization, and amino acids turnover, particularly in responders. Responders exhibited persistent elevations in short-chain acylcarnitines and cholesteryl esters, indicating more efficient lipid oxidation and tighter integration of lipid metabolism with the tricarboxylic acid cycle. Increased glycine and serine levels suggested enhanced cellular maintenance, a protein-sparing effect, and a metabolic shift favouring lipid over carbohydrate. In contrast, non-responders demonstrated only transient and limited metabolic shifts. Unsupervised clustering identified distinct metabolic response patterns, reinforcing the potential of personalized dietary interventions.<br><br>CONCLUSIONS: These findings demonstrate that diet-induced restoration of metabolic flexibility is associated with improved albuminuria in T2D, suggesting broader implications for precise nutritional strategies in diabetes management.},
}
@article {pmid40999310,
year = {2025},
author = {Fedko, VA and Artamonova, EV and Stroganova, AM and Mileyko, VA and Lisitsa, TS and Novikov, AK and Kovalenko, EI},
title = {Clinical and Morphological Features of gPALB2-Associated Breast Cancer in the Russian Population.},
journal = {Bulletin of experimental biology and medicine},
volume = {179},
number = {3},
pages = {355-358},
pmid = {40999310},
issn = {1573-8221},
mesh = {Humans ; Female ; Middle Aged ; Russia/epidemiology ; *Breast Neoplasms/genetics/pathology/drug therapy/epidemiology ; Adult ; Receptor, ErbB-2/genetics/metabolism ; Aged ; Mutation ; Receptors, Estrogen/metabolism/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology/drug therapy ; High-Throughput Nucleotide Sequencing ; Neoadjuvant Therapy ; },
abstract = {The analysis included 3,800 cases of breast cancer. Next-generation sequencing (NGS) of DNA extracted from peripheral blood leukocytes revealed mutations in the gPALB2 gene in 39 (1.03%) patients. The most frequent mutations were c.509_510del (25.64%), c.1592del (20.51%), and c.172_175del (10.26%). The predominant histological variant was invasive ductal carcinoma (84.62%) with moderate differentiation (G2) (48.72%). In most cases, luminal HER2[-] subtype (69.23%) was revealed, HER2[+] and triple-negative were less frequent (12.82 and 17.95%, respectively). Neoadjuvant chemotherapy was administered to 9 patients; a clinical response observed in 100% of cases. RCB-0 (pCR) was noted in 33.3%; RCB-I in 11.1%, RCB-II in 44.4%, and RCB-III in 11.1% of observations. All recorded cases of contralateral breast cancer (10.26%) were metachronous and presented as estrogen receptor-positive HER2[-] tumors.},
}
@article {pmid40993701,
year = {2025},
author = {Cheng, X and Zeng, W and Yin, B and Gui, J and Zhang, H and Lv, Z and Zhang, S and Zhou, Y},
title = {Spatiotemporal microenvironment landscape and malignant epithelial pattern transition in breast ductal carcinoma progression.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {996},
pmid = {40993701},
issn = {1479-5876},
support = {Grant nos. 2020-133-11, 2020-133-16//Science and Technology Bureau of Nanchang Municipality/ ; },
mesh = {Humans ; *Tumor Microenvironment/genetics ; *Disease Progression ; Female ; *Breast Neoplasms/pathology/genetics ; *Carcinoma, Ductal, Breast/pathology/genetics ; Cell Movement ; Gene Expression Regulation, Neoplastic ; Neoplasm Invasiveness ; Lymphatic Metastasis ; Cell Line, Tumor ; Cell Proliferation ; *Spatio-Temporal Analysis ; Prognosis ; },
abstract = {BACKGROUND: Owing to the complexity of TME components and the heterogeneity of cancer cells, the relationship between the niches of TME and prognosis in breast ductal carcinoma remains unknown. The staged characteristics of corresponding cancer cell behaviors are unclear. Our study aims to reveal spatial structures and specific cellular information of TME and cancer cells subgroups during the progression from DCIS to IDC and lymph node metastasis.<br><br>METHODS: Single-cell sequencing, spatial transcriptomics, bulk RNA sequencing datasets were used to explore the changes in microenvironmental components and transcriptional programs of tumor cells during the progression of breast ductal carcinoma. Immunohistochemistry, multiplex immunofluorescence, flow cytometry cell cycle detection, invasion migration experiments, and WB imprinting were employed for validation.<br><br>RESULTS: Analysis of TME cell type subsets revealed the accumulation of TEX, iTreg, and stress-phenotype TAM in the mammary gland in situ during the invasion process. Lymphatic metastases exhibited enrichment of nTregs and a more na&#xef;ve-like CD8 T cell population. Spatial analysis and survival analysis showed that the spatial niches of CD4 TN and phagocytic-phenotype macrophages were associated with a favorable prognosis, and these niches were lost during disease progression. The proliferative subpopulation of breast ductal carcinoma was enriched in lymphatic metastatic tissues, expressing high levels of FAM111B and exhibiting intense TCA and oxidative phosphorylation metabolism. Silencing FAM111B led to cell cycle arrest, decreased invasion and migration abilities, and downregulation of core mediator genes for cuproptosis and disulfidptosis.<br><br>CONCLUSIONS: The stage-specific microenvironmental characteristics of breast ductal carcinoma correspond to some extent to the behavior of tumor cells. During the progression of ductal carcinoma in breast tissue, the establishment of an immunosuppressive microenvironment occurs. The microenvironmental spectrum at lymph node metastases differs somewhat, corresponding to a more enriched turnover of cancer cell proliferation and death. Inhibitors of FAM111B and inducers of cuproptosis and disulfidptosis may serve as potential therapeutic targets for proliferative subgroups.},
}
@article {pmid40990786,
year = {2025},
author = {Tabassum, S and Saeed, U and Tahir, R and Khalid, Z and Piracha, ZZ and Uppal, R and Khan, AA and Ozsahin, DU and Waheed, Y and Ngozi, AJI and Ashraf, M},
title = {Estimating high mobility group box protein 1 (HMGB1) single nucleotide polymorphisms among hepatitis B virus infected patients of Pakistan origin.},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {85},
number = {},
pages = {e284560},
doi = {10.1590/1519-6984.284560},
pmid = {40990786},
issn = {1678-4375},
mesh = {Humans ; Pakistan ; *Polymorphism, Single Nucleotide/genetics ; *HMGB1 Protein/genetics ; Male ; Female ; Genotype ; Adult ; Middle Aged ; Genetic Predisposition to Disease ; *Hepatitis B/genetics ; Young Adult ; Gene Frequency ; *Hepatitis B, Chronic/genetics ; },
abstract = {HMGB1 is nuclear non-histone protein and unique member of cytokines. In viral hepatitis infection HMGB1 serum level increases and translocates towards cytoplasm and extracellular spaces where it activates single stimulating hepatic stellate cell proliferation which induces fibrogenic protein expression and causes hepatocellular carcinoma. In this study, total 150 subjects were recruited to assess the association between HMGB1 SNPs and HBV. Three types of genotypes were found visible in rs3742305 of HMGB1; wild type homozygous GG with 65%, homozygous minor type CC with 6% and heterozygous minor type GC with 26% frequency distribution. High prevalence of GG genotype in the selected population presenting that GG genotype may have higher risk for susceptibility to HBV infection. Our results showed significant correlation of HMGB1 polymorphism with HBV infection in the selected Pakistani population.},
}
@article {pmid40990784,
year = {2025},
author = {Uppal, R and Saeed, U and Tahir, R and Uppal, MR and Khan, AA and Rahman, C and Uppal, MS and Ozsahin, DU and Gilani, SS and Waheed, Y and Piracha, ZZ},
title = {Lymphopenia as a diagnostic biomarker in clinical COVID-19: insights from a comprehensive study on SARS-CoV-2 variants.},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {85},
number = {},
pages = {e284362},
doi = {10.1590/1519-6984.284362},
pmid = {40990784},
issn = {1678-4375},
mesh = {Humans ; *COVID-19/diagnosis/blood/complications ; *Lymphopenia/virology/blood/diagnosis ; *SARS-CoV-2/genetics ; Male ; Female ; Biomarkers/blood ; Adult ; Middle Aged ; Pakistan/epidemiology ; Young Adult ; Aged ; Adolescent ; Lymphocyte Count ; },
abstract = {The enduring SARS-CoV-2 pandemic necessitates robust tools for severity assessment. This study, conducted at Islamabad Diagnostic Center across Pakistan from January 2021 to August 2022, aimed to investigate hematological abnormalities among suspected SARS-CoV-2 subjects. Initial enrollment included 130,347 cases, with 53,078 confirmed positive and 77,269 negative. An additional 11,786 samples expanded the dataset to 142,133. The Omicron and Centaurus variants, in confirmed positive patients, exhibited a slightly higher frequency of hematological abnormalities (30.42%) than negative participants (27.01%). Notably, lymphocyte count reduction (40.95%) suggested its potential as an alternative diagnostic parameter for clinical COVID-19. Decreased levels of NA (37.99%), HGB (26.17%), MCV (20.60%), PLT (6.15%), and ALB (2.28%) were observed. Abnormally elevated NEU, CR, MONO, RBCs, WBC, and EOS levels affected 26.00%, 24.28%, 30.79%, 22.02%, 6.28%, and 5.53% of subjects, respectively. Comparatively, positive patients exhibited higher abnormal blood parameters-LYMP count (57.40%), NEU count (46.08%), EOS count (62.48%), MONO count (31.61%), RBC count (30.32%), ALC count (43.60%), CR count (30.91%), NA count (40.53%), CRP count (68.46%), and DD (63.08%) than negative counterparts. The study underscores lymphocytopenia's potential as a cost-effective, early diagnostic biomarker for clinical COVID-19, preceding real-time PCR diagnosis. This supports its consideration in resource-limited settings for strategic screening and policy-making in the ongoing SARS-CoV-2 battle.},
}
@article {pmid40990674,
year = {2025},
author = {Vera-Tizatl, CE and Vera-Hernández, A and Leija-Salas, L and Vega-López, MA and Ramírez-Estudillo, MDC and Fariña, GIG and Vera-Tizatl, AL},
title = {The Vietnamese swine as a translational model of invasive ductal carcinoma of the breast.},
journal = {Animal models and experimental medicine},
volume = {8},
number = {11},
pages = {1997-2007},
pmid = {40990674},
issn = {2576-2095},
mesh = {Animals ; Female ; *Breast Neoplasms/pathology/chemically induced ; *Carcinoma, Ductal, Breast/pathology/chemically induced ; *Disease Models, Animal ; *Mammary Neoplasms, Experimental/pathology/chemically induced ; Swine ; Tumor Microenvironment ; Vietnam ; },
abstract = {BACKGROUND: The Vietnamese swine represents a promising animal model due to its anatomical, physiological, and pathophysiological similarities to humans. Notably, the arrangement of lobes and ducts in the mammary glands is highly comparable to that of humans and is histologically indistinguishable. Leveraging these advantages through the chemical induction of carcinogenesis in this model offers a robust approach to mimic human exposure to carcinogenic compounds.<br><br>METHODS: This study elaborates on a protocol for developing a representative model of MNU-induced invasive breast carcinoma in three Vietnamese swine, validated histologically and immunologically. It evaluates not only the tissue similarity with humans, but also the development of chemically induced mammary tumors in an immunologically competent animal. Moreover, this study addresses the existing gap in histological knowledge regarding mammary tissue in the porcine model.<br><br>RESULTS: Our findings suggest that this model encompasses the full spectrum of cancer. It incorporates the key elements of a tumor microenvironment that enable tumor growth and propagation, such as immune cells, blood vessels, fibroblasts, extracellular matrix, fatty acids, and signaling molecules.<br><br>CONCLUSIONS: This model offers significant potential to advance the understanding of cancer pathogenesis and facilitate the development of innovative therapeutic strategies by closely replicating human tumor biology.},
}
@article {pmid40982417,
year = {2025},
author = {Adenwalla, SF and Worboys, HM and Lawday, D and Gray, LJ and Hull, KL and Churchward, DR and Highton, PJ and Young, HML and Graham-Brown, MPM and Burton, JO and March, DS},
title = {The effect of a six-month programme of intradialytic cycling on survival and hospitalisations in people requiring haemodialysis: 5-year follow-up of the CYCLE-HD randomised controlled trial.},
journal = {PloS one},
volume = {20},
number = {9},
pages = {e0332389},
pmid = {40982417},
issn = {1932-6203},
mesh = {Humans ; *Renal Dialysis/methods/mortality ; Male ; *Hospitalization/statistics &amp; numerical data ; Female ; Middle Aged ; Follow-Up Studies ; Aged ; *Kidney Failure, Chronic/therapy/mortality ; Cardiovascular Diseases/mortality ; Proportional Hazards Models ; Adult ; },
abstract = {We have previously shown that a six-month programme of intradialytic cycling (IDC) improved cardiovascular structure and function, it is unclear whether these changes are associated with long-term benefits. The aim of this post-trial analysis was to evaluate a programme of IDC on all-cause mortality, hospitalisations and cardiovascular events at five-years. Mortality and hospitalisation data were collected from Hospital Episode Statistics and death certificates. Models were fitted unadjusted and adjusted for age, sex, diabetes, duration of dialysis, and receiving a kidney transplant. Cox proportional hazard models were used for time-to-event analysis to evaluate all-cause mortality. Hospitalisations were analysed using a negative binomial regression model, and length of stay using a generalised linear model. A composite outcome of time to first cardiovascular event, combining cardiovascular mortality and hospitalisations, was evaluated using a Cox model. There was no evidence of a statistically significant effect of treatment allocation on survival (hazard ratio (HR) 1.09, 95% confidence interval (CI): 0.68-1.76, p = 0.71). After adjustment, results remained non-significant (HR 1.22, 95% CI: 0.74-2.01, p = 0.43). There was no evidence of a significant effect on all-cause hospitalisations for unadjusted (p = 0.20) or adjusted (p = 0.25) models. Similar results are reported for cardiovascular hospitalisations (p = 0.30 and p = 0.17). For time to first cardiovascular event there was no evidence of a statistically significant effect (HR 1.39, 95% CI: 0.79-2.72, p = 0.26). The main findings show no evidence that a six-month programme of IDC affected all-cause mortality, hospitalisations, cardiovascular events, or length of stay in hospital at five-years.},
}
@article {pmid40979608,
year = {2025},
author = {Shaikh, K and Arif, A and Mooghal, M and Vohra, L},
title = {Unveiling the Clinicopathological Outcomes of Breast Cancer in Young Women: A perspective from resource-limited settings.},
journal = {Sultan Qaboos University medical journal},
volume = {25},
number = {1},
pages = {658-665},
pmid = {40979608},
issn = {2075-0528},
mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/therapy/diagnosis ; Adult ; Retrospective Studies ; Adolescent ; Incidence ; Young Adult ; Risk Factors ; Registries/statistics &amp; numerical data ; Resource-Limited Settings ; },
abstract = {OBJECTIVES: This study aimed to assess the incidence of breast cancer in young women over a ten-year period and examine its association with clinical characteristics, risk factors, treatment modalities, and survival outcomes.<br><br>METHODS: A retrospective analysis of the Breast Cancer Registry at our institution was conducted. Of the 2,238 women diagnosed with breast cancer between 2012 and 2021, 535 (23.9%) were aged 40 years or younger at the time of diagnosis. Cases with missing data for independent variables were excluded from the respective analyses.<br><br>RESULTS: The mean age at diagnosis was 34.5 years (range: 15-40). The most common clinical stage at presentation was IIB (25.2%), followed by IIA (24.4%), while 7.6% of patients presented with metastatic disease. Invasive ductal carcinoma was the predominant histological type (88.8%), and 57.4% of tumours were high grade. Triple-negative breast cancer accounted for 27.0% of cases, and 18.4% were ERBB2-enriched. Bilateral disease was observed in 2.5% of cases, and 7.5% were diagnosed during pregnancy. A family history of breast cancer was reported in 23.6%. Genetic testing was performed in 10.9% of patients, with BRCA1 mutations being the most frequently identified (12.1%). Modified radical mastectomy was performed in 38.2% of patients, and 8.2% underwent reconstructive surgery. Neoadjuvant chemotherapy was administered in 49.9% of cases, and 68.2% received adjuvant radiotherapy. The five-year overall survival rate was 93.9%, with 12 patients (2.4%) experiencing distant and one (0.2%) experiencing local recurrence within five years.<br><br>CONCLUSION: Young women with breast cancer in resource-limited settings demonstrate distinct sociodemographic and clinicopathological characteristics, underscoring the importance of early detection strategies and personalised treatment approaches.},
}
@article {pmid40964799,
year = {2025},
author = {Takahara, T and Taniguchi, N and Sassa, N and Tsuzuki, T},
title = {Spatial transcriptomics of intraductal carcinoma of the prostate.},
journal = {Histopathology},
volume = {87},
number = {5},
pages = {745-756},
doi = {10.1111/his.15551},
pmid = {40964799},
issn = {1365-2559},
support = {//21K06933/ ; //24K10131/ ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology ; *Transcriptome ; Gene Expression Profiling ; DNA Copy Number Variations ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Biomarkers, Tumor/genetics ; Aged ; Middle Aged ; },
abstract = {AIMS: Intraductal carcinoma of the prostate (IDC-P) is a strong indicator of poor prognosis in prostate cancer (PCa). We utilized the Visium Spatial Gene Expression platform to characterize the gene expression profiles and copy number variations (CNVs) of IDC-P.<br><br>METHODS AND RESULTS: Manually annotated IDC-P components were relatively enriched in a single transcriptomic cluster identified by principal component analysis, which exhibited elevated expression of FOLH1 (PSMA), PSCA and PLA2G2A. Differential gene expression analysis between IDC-P and non-IDC-P cancer tissues revealed up-regulation of pathways related to chemotaxis and leukocyte migration, as well as gene sets associated with small cell lung carcinoma, suggesting a potential link to treatment-related neuroendocrine prostate carcinoma. In contrast, non-IDC-P components showed increased expression of genes associated with extracellular matrix organization. InferCNV analysis identified distinct CNV patterns differentiating IDC-P from non-IDC-P cancer components in four out of six cases. However, no common CNV alterations were shared across these cases, indicating molecular diversity among IDC-P lesions. In the remaining cases, IDC-P clustered with Gleason pattern 5 carcinoma, and no CNV alterations distinguishing IDC-P from adjacent non-IDC-P components were identified.<br><br>CONCLUSIONS: These findings suggest that IDC-P represents a biologically distinct component from conventional acinar adenocarcinoma and may reflect spatial tumour progression through pre-existing ductal structures. Our study also suggests that the molecular mechanisms underlying IDC-P progression may differ between patients, while the limited sample size (n&#x2009;=&#x2009;6) warrants cautious interpretation and further validation in larger cohorts.},
}
@article {pmid40957887,
year = {2025},
author = {Kadri, S and Fischer, A and Mück-Häusl, M and Han, W and Kadri, A and Lin, Y and Yang, L and Hu, S and Ye, H and Ramesh, P and Ansari, M and Schiller, HB and Machens, HG and Rinkevich, Y},
title = {A mesothelial differentiation gateway drives fibrosis.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8295},
pmid = {40957887},
issn = {2041-1723},
mesh = {Mice, Inbred C57BL ; Animals ; Mice ; Fibrosis ; *Epithelium/embryology/metabolism ; *Cell Differentiation ; Single-Cell Gene Expression Analysis ; Humans ; *Pulmonary Fibrosis/etiology ; Metabolic Reprogramming ; },
abstract = {Internal organs are encased by a supportive epithelial monolayer of mesodermal origin, termed mesothelium. The nature, evolution and function of mesothelial cells, and their genetic regulation impacting disease development are insufficiently understood. Here, we generate a comprehensive organ-wide single-cell transcriptomic compendium of mesothelium across healthy and diseased mouse and human organs, delineating the evolution of conserved activated states of mesothelial cells in response to disease. We uncover genetic drives behind each cell state and reveal a conserved metabolic gate into multipotent proteolytic, inflammatory and fibrotic cell differentiation, in mouse and human. Using lung injury models in mice, in combination with mesothelial cell-specific viral approaches, we show that direct metabolic reprogramming using Ifi27l2a and Crip1 on organ surfaces, blocks multipotent differentiation and protects mouse lungs from fibrotic disease. These findings place mesothelial cells as cellular exemplars and gateway to fibrotic disease, opening translational approaches to subvert fibrosis across a range of clinical indications.},
}
@article {pmid40950543,
year = {2025},
author = {Abon, JCR and Valparaiso, AP and Yuga, ACQ},
title = {Necrotizing Fasciitis of Bilateral Breasts following Unilateral Modified Radical Mastectomy for Invasive Ductal Carcinoma: A Case Report and Review of Literature.},
journal = {Acta medica Philippina},
volume = {59},
number = {11},
pages = {98-104},
pmid = {40950543},
issn = {2094-9278},
abstract = {Necrotizing fasciitis of the breast is a rare but potentially fatal soft tissue infection. It may occur primarily in patients without any direct cause, and less commonly after undergoing elective surgical procedures such as cosmetic mammoplasties and oncologic resections. This is a case of a 46-year-old female with stage IIIA invasive ductal carcinoma of the left breast treated with modified radical mastectomy presenting with a necrotizing infection involving the bilateral breast regions and left lateral abdomen six days after operation. She was managed with broad-spectrum antibiotics and radical debridement with right mastectomy, followed by wound coverage with split-thickness skin grafting. This is the eight case of breast necrotizing fasciitis occurring after mastectomy for breast cancer reported in the literature.},
}
@article {pmid40944124,
year = {2025},
author = {Mrosewski, I and Fleming, T and Schulze-Tanzil, G and Werner, C and Gögele, C and Mantel, V and Kokozidou, M and Bertsch, T},
title = {Menaquinone-7 Supplementation Increases Multiple Advanced Glycation End-Products and Oxidation Markers in Zucker Diabetic Fatty Rats.},
journal = {Nutrients},
volume = {17},
number = {17},
pages = {},
pmid = {40944124},
issn = {2072-6643},
support = {SZ_FP_008.18//Kerscher&#xb4;sche Stiftung/ ; SZ_FP_164.20//Kerscher&#xb4;sche Stiftung/ ; },
mesh = {Animals ; *Glycation End Products, Advanced/blood/metabolism ; Rats, Zucker ; Male ; *Vitamin K 2/analogs &amp; derivatives/pharmacology/administration &amp; dosage ; Biomarkers/blood/urine ; *Oxidative Stress/drug effects ; *Diabetes Mellitus, Type 2/blood/metabolism/drug therapy ; *Dietary Supplements ; Oxidation-Reduction ; Rats ; Blood Glucose/metabolism ; *Diabetes Mellitus, Experimental/blood ; },
abstract = {Background: Dicarbonyls and advanced glycation end-products (AGEs) contribute to oxidative stress, inflammation, and complications in type 2 diabetes mellitus (T2DM). Menaquinone-7 (MK-7), a vitamin K2 subtype, has shown benefits for glucose tolerance and vascular health in some studies. We evaluated the impact of MK-7 on dicarbonyls, free AGEs, and protein nitration/oxidation adducts in a rat model of T2DM. Methods: Male heterozygous (fa/+, control) and homozygous (fa/fa, diabetic) Zucker Diabetic Fatty rats were fed a diabetogenic diet without or with MK-7 for 12 weeks. After sacrifice, plasma dicarbonyls as well as plasma and urinary levels of free AGEs and protein nitration/oxidation adducts were quantified by isotope dilution tandem mass spectrometry. Results: Diabetic rats showed significantly increased plasma glyoxal, 3-deoxyglucosone, and fructosyl-lysine with non-significant trends toward increased methylglyoxal-derived hydroimidazolone and methionine sulfoxide, as well as reductions in methylglyoxal and dityrosine. Urinary carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine (all significant), and dityrosine (non-significant) were elevated in diabetic rats; glucosepane (non-significant) was reduced. MK-7 supplementation reduced no measured parameter but was associated with non-significant further increases in plasma glyoxal-derived hydroimidazolone, carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine, 3-nitrotyrosine, and methionine sulfoxide, as well as in urinary glyoxal-derived hydroimidazolone, carboxyethyl-lysine, fructosyl-lysine, and 3-nitrotyrosine, in diabetic rats. Correlation analysis revealed significant associations between glucose, dicarbonyls, AGEs, and oxidative markers. Conclusions: High-dose MK-7 supplementation did not improve dicarbonyl stress, AGE burden, or protein nitration/oxidation. With respect to available scientific evidence and our observations, the combination of glycemia-driven amplification of glycation and oxidative stress, as well as MK-7-induced glutathione depletion, were likely causative.},
}
@article {pmid40929383,
year = {2025},
author = {Uppal, R and Rehan Uppal, M and Tahir, R and Saeed, U and Khan, AA and Uppal, MS and Ali, Z and Ozsahin, DU and Tariq, MN and Waheed, Y and Piracha, ZZ},
title = {Bacterial infections and antimicrobial resistance patterns: a comprehensive analysis of health dynamics across regions in Pakistan (2013-2023).},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {85},
number = {},
pages = {e285605},
doi = {10.1590/1519-6984.285605},
pmid = {40929383},
issn = {1678-4375},
mesh = {Pakistan/epidemiology ; Humans ; Female ; Male ; Adult ; Infant ; Middle Aged ; Adolescent ; *Bacterial Infections/epidemiology/microbiology/drug therapy ; Prevalence ; *Drug Resistance, Bacterial ; Young Adult ; Child, Preschool ; *Anti-Bacterial Agents/pharmacology ; Child ; Aged ; Infant, Newborn ; Escherichia coli/drug effects/isolation &amp; purification ; Urinary Tract Infections/microbiology/epidemiology ; Salmonella/drug effects/isolation &amp; purification ; },
abstract = {Antimicrobial resistance (AMR) is a significant public health concern globally, and Pakistan is no exception. The misuse and overuse of antibiotics, inadequate regulation of their sale, and a lack of awareness contribute to the rising levels of AMR in the country. study presents a detailed analysis of blood and urine samples collected in Pakistan over various periods, focusing on pathogen prevalence, gender distribution, and age-wise patterns. From January 2013 to 2017, the North region exclusively contributed to the blood sample dataset, with Salmonella emerging as the primary pathogen, particularly affecting infants and neonates. Subsequently, from January 2017 to December 2020, a significant dataset emerged from the North and Punjab regions, with Salmonella and E.coli prevalent across all age groups, notably impacting adults and infants. In the period from January 2021 to the present, blood samples predominantly originated from the North and Punjab regions, with Salmonella and E.coli remaining significant pathogens, affecting adults and the elderly. Regarding urine samples, from January 2013 to December 2017, E.coli was the dominant pathogen, with females showing a higher susceptibility to urinary tract infections (UTIs), particularly among the elderly. Similarly, from January 2017 to December 2020, E.coli remained predominant, with UTIs more prevalent in females and the elderly. In the most recent period, the North region significantly contributed to UTI cases, with E.coli remaining predominant and females exhibiting a higher susceptibility, especially among the elderly. This comprehensive analysis provides crucial insights into the epidemiology of blood and urinary tract infections in Pakistan, informing public health strategies and interventions aimed at addressing these health challenges.},
}
@article {pmid40921139,
year = {2025},
author = {Xiao, Y and Song, L and Xie, WJ and Chen, RW and Lin, ZJ and Lin, XY and Liu, Y and Jiang, Y and Xu, S and Xu, JP},
title = {Histone Methyltransferase EHMT2 Promotes the Progression of Breast Ductal Carcinoma by Regulating the Hippo Pathway.},
journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer},
volume = {44},
number = {3},
pages = {63-74},
doi = {10.1615/JEnvironPatholToxicolOncol.2025056721},
pmid = {40921139},
issn = {2162-6537},
mesh = {Humans ; *Histone-Lysine N-Methyltransferase/metabolism/genetics/antagonists &amp; inhibitors ; Female ; Hippo Signaling Pathway ; *Breast Neoplasms/pathology/metabolism/genetics ; Animals ; Cell Line, Tumor ; *Protein Serine-Threonine Kinases/metabolism/genetics ; Mice ; *Carcinoma, Ductal, Breast/pathology/metabolism/genetics ; Signal Transduction ; Disease Progression ; Reactive Oxygen Species/metabolism ; Apoptosis ; Mice, Nude ; Cell Proliferation ; *Histocompatibility Antigens/metabolism/genetics ; },
abstract = {Invasive ductal carcinoma (IDC) is a major type of breast cancer. The utilization of inhibitors targeting histone methyltransferases introduces novel therapeutic avenues for the treatment of cancer. Immunohistochemistry, Western blot, and reverse transcription quantitative polymerase chain reaction experiments were applied to assess the levels of EHMT2 in IDC and adjacent tissues. HCC70 cells were treated with EHMT2 inhibitors (UNC0646 and BIX-01294), and assessed using Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and transwell assays to evaluate cell viability, apoptosis, and migratory capacity, respectively. The reactive oxygen species (ROS) levels were assessed using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. The expressions of Hippo pathway were analyzed via Western blot assay. Immunofluorescence staining was employed to detect the subcellular localization changes in YAP expression. A xenograft tumor model of HCC70 cells was applied to validate the tumor-suppressive influences of EHMT2 inhibitors in vivo. We observed significant upregulation of EHMT2 in both IDC clinical samples and IDC cell lines, with high EHMT2 expression correlating with poor prognosis. After treatment with EHMT2 inhibitors UNC0646 or BIX-01294, HCC70 cells exhibited inhibition of proliferation and migratory capacity, alongside an increase in apoptosis rate and ROS production levels. UNC064 or BIX-01294 promoted the phosphorylation levels of MST1, LATS1, MOB1A, and YAP, indicating the activation of the Hippo pathway by EHMT2 inhibitors. Moreover, UNC0646 and BIX-01294 enhanced the cytoplasmic expression of YAP while inhibiting its nuclear localization, preventing its nuclear activation. EHMT2 was upregulated in IDC, and EHMT2 inhibitors suppressed IDC progression by modulating the Hippo signaling pathway.},
}
@article {pmid40918116,
year = {2025},
author = {Li, H and Zhang, H and Dai, R and Zheng, D and Zhao, J and Jing, H and Ma, X and Zhang, L and Sun, W and Suo, Z},
title = {CD68 as a multi-omic prognostic biomarker in digestive system cancers: correlations with tumor-infiltrating immune cells and immune checkpoints.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1599677},
pmid = {40918116},
issn = {1664-3224},
mesh = {Humans ; *Biomarkers, Tumor/genetics/metabolism ; *Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; Prognosis ; *Antigens, CD/genetics/metabolism/immunology ; *Antigens, Differentiation, Myelomonocytic/genetics/metabolism/immunology ; Female ; Male ; *Digestive System Neoplasms/immunology/mortality/metabolism/pathology/genetics ; *Immune Checkpoint Proteins/metabolism ; Middle Aged ; Tumor Microenvironment/immunology ; Multiomics ; CD68 Molecule ; },
abstract = {BACKGROUND AND OBJECTIVE: CD68 plays a crucial role in promoting phagocytosis. However, its expression level, prognostic value and the correlations with tumor-infiltrating immune cells (TIICs) or common tumor immune checkpoints (TICs) in human digestive system cancers (DSC) remain poorly understood. This study aims to investigate the expression levels, prognostic significance, and clinical implications of CD68, as well as its correlations with six TIICs and four common TICs in DSC.<br><br>MATERIALS AND METHODS: We analyzed CD68 mRNA and protein expression using online databases and immunohistochemistry (IHC) on tissue microarray (TMA) sections, comparing DSC tumor tissues with adjacent normal tissues. Overall survival (OS) was calculated to evaluate the prognostic value of CD68 in DSC. Additionally, correlations between CD68 expression and six TIICs (B cells, CD4+ T cells, CD8+ T cells, macrophages, NK cells, and cancer-associated fibroblasts) or four common TICs (PDCD1, CTLA4, IDO1, and CD40) were assessed using the Tumor Immune Estimation Resource (TIMER).<br><br>RESULTS: CD68 mRNA expression was significantly higher in esophageal carcinoma (ESCA) and stomach adenocarcinoma (STAD) tissues compared to adjacent normal tissues, but lower in colon adenocarcinoma (COAD), liver hepatocellular carcinoma (LIHC), and pancreas invasive ductal carcinoma (PAAD). Protein expression of CD68 was significantly higher in COAD than in adjacent normal tissues, but lower in ESCA, LIHC, PAAD, and STAD. CD68 protein expression served as a prognostic marker in COAD and STAD. Furthermore, CD68 expression showed strong positive correlations with the six TIICs and significant positive correlations with the four TICs in DSC.<br><br>CONCLUSION: CD68 may serve as an essential prognostic biomarker in COAD and STAD and could be a promising candidate for diagnostic, prognostic, and therapeutic targeting in human DSC.},
}
@article {pmid40914542,
year = {2025},
author = {Wang, Q and Huang, J and Wu, S and Wang, J and Yu, T and Wei, W and Yang, T and Wu, X and Zhai, J and Zhang, X},
title = {Neuro-immuno-stromal context in colorectal cancer: An enteric glial cell-driven prognostic model via machine learning predicts survival, recurrence, and therapy response.},
journal = {Experimental cell research},
volume = {452},
number = {1},
pages = {114733},
doi = {10.1016/j.yexcr.2025.114733},
pmid = {40914542},
issn = {1090-2422},
mesh = {Humans ; *Colorectal Neoplasms/pathology/genetics/immunology/mortality/therapy ; *Machine Learning ; Prognosis ; *Neoplasm Recurrence, Local/pathology/genetics ; *Neuroglia/pathology/metabolism/immunology ; Tumor Microenvironment/immunology ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Biomarkers, Tumor/genetics ; },
abstract = {BACKGROUND: Enteric glial cells (EGCs) have been implicated in colorectal cancer (CRC) progression. This study aimed to develop and validate a prognostic model integrating EGC- and CRC-associated gene expression to predict patient survival, recurrence, metastasis, and therapy response.<br><br>METHODS: Bulk and single-cell RNA sequencing data were analyzed, and a machine learning-based model was constructed using the RSF random forest algorithm. The model's prognostic value was evaluated through survival analysis, pathway enrichment, immune profiling, and therapy response predictions.<br><br>RESULTS: The model effectively stratified patients into high- and low-risk groups, with high-risk patients exhibiting significantly worse overall survival (OS) and an increased likelihood of recurrence and metastasis. Gene Set Enrichment Analysis (GSEA) identified key pathways associated with tumor progression, immune regulation, and microenvironmental interactions. The model was significantly correlated with immune cell infiltration and chemokine signaling. High-risk patients exhibited reduced immune therapy efficacy and distinct drug sensitivity profiles, suggesting its potential to guide personalized treatment strategies.<br><br>CONCLUSION: This model serves as a valuable tool for CRC prognosis and treatment stratification, with potential clinical applications pending further validation.},
}
@article {pmid40873579,
year = {2025},
author = {Baena, JC and Victoria, JS and Toro-Pedroza, A and Aragón, CC and Ortiz-Guzman, J and Garcia-Robledo, JE and Torres, D and Rios-Serna, LJ and Albornoz, L and Rosales, JD and Cañas, CA and Adolfo Cruz-Suarez, G and Osorio, FO and Fleitas, T and Laponogov, I and Loukanov, A and Veselkov, K},
title = {Smart CAR-T Nanosymbionts: archetypes and proto-models.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1635159},
pmid = {40873579},
issn = {1664-3224},
mesh = {Humans ; *Immunotherapy, Adoptive/methods ; *Receptors, Chimeric Antigen/immunology/genetics ; Animals ; *Nanoparticles ; Artificial Intelligence ; Precision Medicine/methods ; *Neoplasms/therapy/immunology ; Nanotechnology/methods ; },
abstract = {Personalized medicine has redefined cancer treatment by aligning therapies with each patient's unique biological profile. A key example is chimeric antigen receptor T-cell (CAR-T) therapy, in which a patient's own T cells are genetically modified to recognize and destroy cancer cells. This approach has delivered remarkable results in hematologic malignancies and is beginning to show promise in solid tumors and autoimmune diseases. However, its broader adoption is limited by major challenges, including complex manufacturing, high costs, limited efficacy in solid tumors, and potentially severe toxicities. Nanotechnology offers exciting possibilities to overcome many of these barriers. Engineered nanoparticles can improve gene delivery, target tumors more precisely, enhance immune cell function, and enable in vivo CAR-T production, reducing the need for labor-intensive ex vivo processes. However, despite this promise, translation into clinical settings remains difficult due to regulatory hurdles, scalability issues, and inconsistent reproducibility in human models. At the same time, artificial intelligence (AI), with its powerful algorithms for data analysis and predictive modeling, is transforming how we design, evaluate, and monitor advanced therapies, including the optimization of manufacturing processes. In the context of CAR-T, AI holds strong potential for better patient stratification, improved prediction of treatment response and toxicity, and faster, more precise design of CAR constructs and delivery systems. Leveraging these three technological pillars, this review introduces the concept of Smart CART Nanosymbionts, an integrated framework in which AI guides the design and deployment of nanotechnology-enhanced CAR-T therapies. We explore how this convergence enables optimization of lipid nanoparticle formulations for mRNA transfection, specific targeting and modification of the tumor microenvironment, real-time monitoring of CAR-T cell behavior and toxicity, and improved in vivo CAR-T generation and overcoming barriers in solid tumors. Finally, it's important we also address the ethical and regulatory considerations surrounding this emerging interface of living therapies and computational driven systems. The Smart CART Nanosymbionts framework (Figure 1:) represents a transformative step forward, promising to advance personalized cancer treatment toward greater precision, accessibility, and overall effectiveness.},
}
@article {pmid40863096,
year = {2025},
author = {Cioroianu, RA and Schenker, M and Rădulescu, VM and Berisha, TC and Cioroianu, GO and Popescu, M and Ciofiac, CM and Petrescu, AM and Mogoantă, S&#x218;},
title = {Therapeutic Patterns and Surgical Decision-Making in Breast Cancer: A Retrospective Regional Cohort Study in Romania.},
journal = {Clinics and practice},
volume = {15},
number = {8},
pages = {},
pmid = {40863096},
issn = {2039-7275},
abstract = {Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ[2] = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania's shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program.},
}
@article {pmid40849879,
year = {2025},
author = {Oolbekkink, S and Wolthaus, JWH and van Asselen, B and Stijnman, PRS and Raaymakers, BW},
title = {Development and demonstration of end-to-end testing for intra-fraction motion-managed workflows.},
journal = {Medical physics},
volume = {52},
number = {9},
pages = {e18042},
pmid = {40849879},
issn = {2473-4209},
support = {18495//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; },
mesh = {*Workflow ; Movement ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Dosage ; Humans ; Radiometry ; },
abstract = {BACKGROUND: Intra-fraction motion management techniques, including beam gating and intra-fraction drift correction (IDC), have recently been introduced on the Unity MR-linac (Elekta AB, Stockholm, Sweden) to mitigate the dosimetric impact of motion during treatment. However, residual motion (e.g., within the gating window) still affects the delivered dose, causing deviations from the statically planned dose. Conventional end-to-end (E2E) testing does not incorporate such (known) motion, hampering evaluation of motion managed workflows.<br><br>PURPOSE: This study develops and demonstrates novel methods that incorporate known motion before treatment delivery. Using such a reference dose distribution allows for E2E testing of intra-fraction motion-managed&#xa0;workflows.<br><br>METHODS: A novel approach was developed to assess the E2E accuracy for motion-managed delivery techniques by comparing the measured dose distribution to a reference dose distribution that incorporates the applied motion during the delivery. Two motion-included reference dose distributions were generated and evaluated: (1) A Priori Motion-Included (APriMI) dose distribution which uses the known (periodic) motion to estimate the influence of anatomical motion on the dose distribution, and incorporates this into a new dose distribution; and (2) the Posteriori Motion-Included (PostMI) dose distribution, which adds an external trigger to relate the beam-on/off time to the motion of the setup. This allows for evaluation of non-periodic motion, or a drift motion during IDC workflows. In addition to these, the conventionally used static treatment planning system (TPS) dose distribution was used as a reference dose&#xa0;distribution. Several scenarios were evaluated: static (no phantom motion), two unmanaged, and two motion-managed scenarios using the Comprehensive Motion Management (CMM) software (Elekta AB, Stockholm, Sweden) for gated and IDC workflows, with cos 4 $\mathrm{cos^4}
$ and linear drift motion patterns. All measurements were performed on a clinical Unity MR-linac equipped with CMM software, using film dosimeters for high spatial resolution dose distribution assessment. The geometric and dosimetric E2E accuracy of the workflow were evaluated for all&#xa0;scenarios.<br><br>RESULTS: First, the static benchmark scenario was evaluated and showed high agreement between the measured dose distribution and all reference dose distributions (i.e., static, APriMI, and PostMI). For the motion-included scenarios, excellent agreement was observed between the measured and calculated dose distributions in both unmanaged and managed cases when using either APriMI or PostMI. The largest geometric shift in the motion included scenarios was 0.3&#xa0;mm, comparable to the static scenario. Dosimetric accuracy, evaluated using a global gamma index (2%/2&#xa0;mm), exceeded 95.5%. As expected, larger deviations occurred when the static dose distribution was used as a reference, with geometric shifts up to 9.0&#xa0;mm and gamma pass rates as low as 17.8%.<br><br>CONCLUSIONS: E2E testing of intra-fraction motion-managed workflows is possible using APriMI and PostMI dose distributions. Strong agreement was observed with these motion-included distributions, while larger deviations were seen with the static dose distribution. These findings highlight the need for reference dose files that account for actual motion in the measurement setup to assess E2E accuracy of motion-included&#xa0;workflows.},
}
@article {pmid40841699,
year = {2025},
author = {SeyedForootan, F and Mahdavi, N and Koopaie, M},
title = {Mandibular metastasis of invasive ductal carcinoma of the breast: a case report.},
journal = {Journal of medical case reports},
volume = {19},
number = {1},
pages = {423},
pmid = {40841699},
issn = {1752-1947},
mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology ; *Mandibular Neoplasms/secondary/diagnostic imaging ; *Carcinoma, Ductal, Breast/secondary/pathology ; *Mandibular Fractures/etiology/diagnostic imaging ; Lung Neoplasms/secondary ; Liver Neoplasms/secondary ; Fatal Outcome ; *Fractures, Spontaneous/etiology ; },
abstract = {BACKGROUND: Metastasis of breast carcinoma to the oral cavity is an uncommon event, and mandibular involvement is even rarer. This case is notable owing to the delayed occurrence of mandibular metastasis 6 years after the primary diagnosis, highlighting its aggressive behavior, which resulted in a pathological mandibular fracture. Reporting such rare presentations can aid clinicians in identifying atypical metastatic patterns in breast cancer survivors.<br><br>CASE PRESENTATION: A 45&#xa0;year-old Persian female with a history of invasive ductal breast carcinoma, diagnosed initially and treated 6 years earlier, presented with facial swelling and pain in the left lower jaw. She had been receiving bisphosphonate therapy for bone metastases. Clinical and radiographic evaluations revealed a radiolucent mandibular lesion with cortical bone perforation. Histopathological and immunohistochemical analyses confirmed metastasis from the primary breast cancer. Despite subsequent radiotherapy and chemotherapy, the lesion progressed, resulting in a pathological mandibular fracture and further metastases to the lungs and liver.<br><br>CONCLUSION: This case underscores the importance of considering metastatic disease in diagnosing oral lesions in patients with a history of malignancy. Early recognition of atypical presentations such as mandibular metastasis may facilitate timely intervention, although prognosis remains poor in such advanced stages.},
}
@article {pmid40829155,
year = {2026},
author = {Wang, H and Huang, R and Huang, J and Feng, L and Zhang, W},
title = {Mandibular Osteosarcoma Mimicking Bisphosphonate-associated Osteonecrosis on 99m Tc-MDP Bone Scan in a Patient With Breast Cancer.},
journal = {Clinical nuclear medicine},
volume = {51},
number = {1},
pages = {68-69},
doi = {10.1097/RLU.0000000000006105},
pmid = {40829155},
issn = {1536-0229},
mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/complications ; Adult ; Diagnosis, Differential ; *Technetium Tc 99m Medronate ; *Osteosarcoma/diagnostic imaging/complications ; *Diphosphonates/adverse effects ; Radionuclide Imaging ; *Mandibular Neoplasms/diagnostic imaging ; *Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnostic imaging ; },
abstract = {We present the case of a 27-year-old woman with a history of left breast invasive ductal carcinoma who developed mandibular osteosarcoma, as documented by 2 MDP bone scans. She had undergone a radical mastectomy, chemotherapy, radiotherapy, and intravenous zoledronic acid therapy. An initial bone scan 1 year later showed increased MDP uptake in the right mandible, suggesting drug-related osteonecrosis, but concurrent CT scans were normal. A follow-up bone scan performed 16 months later demonstrated increased MDP uptake in both mandibles. Subsequent partial mandibulectomy confirmed conventional osteosarcoma.},
}
@article {pmid40810087,
year = {2025},
author = {Suzuki, D and Oshi, M and Nishikawa, A and Kawashima, K and Sasamoto, M and Shibata, Y and Adachi, S and Narui, K and Takase, H and Yamada, A and Fujii, S and Endo, I},
title = {Breast Cancer With Airway Edema Caused by Metastatic Fracture of the Cervical Vertebra.},
journal = {World journal of oncology},
volume = {16},
number = {4},
pages = {422-425},
pmid = {40810087},
issn = {1920-454X},
abstract = {Bone is a common site of breast cancer metastasis, with the spine showing a particularly high affinity. An 83-year-old Japanese woman with Alzheimer's disease presented with a palpable mass in her left breast. A needle biopsy revealed invasive ductal carcinoma of the breast, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, with lymph node metastasis. Chest dynamic computed tomography showed no distant metastases. She was diagnosed with luminal-type, stage IIB (T2N1M0) breast cancer and underwent surgery. During induction of general anesthesia, intubation was difficult due to airway edema, necessitating bronchoscopy. The day after surgery, she reported neck pain, and radiography revealed a compression fracture of the third cervical vertebra. Magnetic resonance imaging confirmed a metastatic lesion in the third cervical vertebra. Postoperatively, she received endocrine therapy with letrozole, radiation therapy with zoledronic acid, and a cervical collar for cervical metastases. Seven months later, the osteolytic lesion calcified, and her pain improved. This case is unique because solitary cervical vertebral metastases from breast cancer, leading to compression fractures and airway edema, are rare. The case highlights the importance of considering cervical metastases in patients with breast cancer who develop airway difficulties or unexplained neck pain, particularly in the perioperative setting. Early recognition and intervention are crucial for preventing complications and optimizing patient outcomes.},
}
@article {pmid40809963,
year = {2025},
author = {Bellesini, JA and Foo, KY and Li, J and Sanderson, RW and Zilkens, R and Gale, L and Hardie, M and Hamza, S and Rijhumal, A and Saunders, CM and Kennedy, BF},
title = {Three-dimensional dynamic optical coherence tomography for breast tumor margin assessment.},
journal = {Biomedical optics express},
volume = {16},
number = {8},
pages = {3061-3074},
pmid = {40809963},
issn = {2156-7085},
abstract = {Intraoperative margin assessment techniques are needed to reduce the re-excision rate in breast-conserving surgery. Optical coherence tomography (OCT) is a non-invasive imaging technique capable of rapid three-dimensional (3-D) imaging of the internal microstructure of tissues. However, there is often low contrast between morphological features in breast tissue. Dynamic OCT (d-OCT), which provides additional contrast derived from the temporal variance of the OCT signal caused by intrinsic motion within the tissue, may provide a solution. However, few studies have applied it to breast tumor margin assessment. In this study, we acquired 3-D d-OCT images of ten human mastectomy specimens and three wide local excisions from breast-conserving surgery (BCS) procedures and, in each case, performed co-registered histology for validation. To optimize the trade-off between spatial resolution, temporal resolution, and acquisition time, we considered a range of acquisition settings. Several methods for visualizing d-OCT images were investigated, including Fourier weighted mean frequency, Fourier power spectral analysis, using red-green-blue (RGB) and hue-saturation-value (HSV) color spaces, and phase variance. We present d-OCT images of invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), invasive lobular carcinoma (ILC), and lobular carcinoma in situ (LCIS), and show that the contrast between malignant and benign regions is consistently higher with d-OCT than using OCT intensity alone. The improved contrast may derive from increased proliferation rates and collagen deposition in cancerous tissue compared to benign tissue. We believe that our results demonstrate that d-OCT has the potential to improve intraoperative tumor margin assessment during breast-conserving surgery.},
}
@article {pmid40809661,
year = {2025},
author = {Vulasala, SR and Louviere, CD and Navarro, F and Adler, GA and Gopireddy, DR and Hatch, P and Abu Hana, R},
title = {Systemic Sarcoidosis Mimicking Metastatic Invasive Ductal Carcinoma of the Breast.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e87860},
pmid = {40809661},
issn = {2168-8184},
abstract = {Sarcoidosis is a granulomatous inflammatory disorder of uncertain etiology that can closely mimic metastatic malignancies, particularly when it presents with multi-organ involvement. In patients with a confirmed diagnosis of cancer, to avoid misdiagnosis and subsequent inappropriate treatment, distinguishing between sarcoidosis and metastatic disease is essential. Histologic confirmation through tissue sampling and correlation with tumor markers are critical tools in this process. We report a case of a 36-year-old female with invasive ductal carcinoma of the breast who presented with suspicious findings that indicated metastatic disease involving her lungs, liver, and bones. However, tumor marker levels and histopathology revealed systemic sarcoidosis, not metastatic spread.},
}
@article {pmid40789889,
year = {2025},
author = {Pintican, R and Duma, MM and Spada, AM and Szep, M and Eniu, D and Chiorean, A},
title = {COVID-19 pandemic resulted in more metastatic breast cancer cases at diagnosis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {29296},
pmid = {40789889},
issn = {2045-2322},
mesh = {Humans ; *COVID-19/epidemiology/virology ; Female ; *Breast Neoplasms/diagnosis/pathology/epidemiology ; Middle Aged ; Retrospective Studies ; Aged ; Adult ; SARS-CoV-2 ; Neoplasm Staging ; Pandemics ; Neoplasm Metastasis ; },
abstract = {The study aimed to assess the impact of the COVID-19 pandemic on breast cancer diagnosis, tumor characteristics, and staging in an Eastern-European country. This retrospective study included 11,635 breast cancer patients and clients presenting between March 2019 and March 2022. Patients were categorized into pre-pandemic, pandemic, and post-pandemic groups. Data included age, sex, pathology, tumor characteristics (histologic type, grade, ER/PR/HER2 status), and TNM staging. Statistical analysis compared these parameters across the three-time intervals.During the pandemic, breast cancer diagnosis decreased significantly compared to the pre-pandemic period (9.1% vs. 13.17%, p < 0.001) but increased post-pandemic (11%, p = 0.013). Invasive ductal carcinoma of non-special type (IDC-NST) was predominant in all three-time periods. Aggressive tumors (Nottingham grade 3, ER negative) increased during the pandemic and post-pandemic times. Molecular subtypes showed variations across time intervals, with triple-negative tumors rising significantly. Larger tumors, increased lymph node involvement (9-19%), and distant metastasis characterized the pandemic and post-pandemic periods. Compared to pre-pandemic patients, post-pandemic ones were 7 times more likely to be metastatic at diagnosis (p < 0.05). The COVID-19 pandemic led to a significant decrease in breast cancer diagnosis, particularly during the pandemic period. Tumors appeared more aggressive, with higher lymph node and distant metastatic involvement. The long-term prognosis and healthcare cost implications remain uncertain. These findings emphasize the need for adapted cancer screening programs and healthcare system readiness during pandemics.COVID-19 pandemic has resulted in a lower detection rate among patients diagnosed with breast cancer and increased TNM stage.},
}
@article {pmid40787784,
year = {2025},
author = {Köker, SC and Tsokanos, FF and El-Merahbi, R and Jha, AK and Cicatelli, K and Weber, P and Mhamane, A and Kaltenecker, D and Morigny, P and Loft, A and Klepac, K and Maida, A and Molocea, CE and Hass, D and Vogl, ES and Alfaro, AJ and Sun, W and Zitzelsberger, H and Unger, K and Szendrödi, J and Li, Y and Diaz, MB and Wolfrum, C and Bartelt, A and Herzig, S and Georgiadi, A},
title = {The TBLR1/TBL1 Co-Factor Complex Acts as a Transcriptional Checkpoint in the Brown Adipose Tissue Response to Prolonged Cold Exposure.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {15},
pages = {e70886},
pmid = {40787784},
issn = {1530-6860},
support = {450149205-TRR333/1//Deutsche Forschungsgemeinschaft (DFG)/ ; //Deutsches Zentrum f&#xfc;r Herz-Kreislaufforschung (DZHK)/ ; J4224-B34//Austrian Science Fund (FWF)/ ; },
mesh = {Animals ; *Adipose Tissue, Brown/metabolism ; Mice ; *Cold Temperature ; Thermogenesis/physiology ; *Transducin/metabolism/genetics ; Histone Deacetylases/metabolism/genetics ; Energy Metabolism ; Male ; *Nuclear Proteins/metabolism/genetics ; Mice, Transgenic ; Mice, Inbred C57BL ; Lipolysis ; Adipocytes, Brown/metabolism ; Mice, Knockout ; *Transcription, Genetic ; },
abstract = {Brown adipose tissue (BAT) is a key thermogenic organ, whose activation in response to cold environmental temperatures and β-adrenergic stimulation requires the proper function of the NCOR/HDAC3 corepressor complex in brown adipocytes. The NCOR/HDAC3 complex is large and multi-component, including the transducin beta-like 1 (TBL1) and TBL1-related 1 (TBLR1) proteins. Loss of TBL1 in the hepatocytes and TBLR1 in the white adipocytes has been shown to impair fasting- and β-adrenergic-induced lipolysis. However, their roles in BAT thermogenesis remain unknown. Here, we report that deletion of TBLR1 alone in brown adipocytes does not impair the adaptive thermogenic response to prolonged cold exposure. In contrast, simultaneous deletion of TBL1 and TBLR1 dampens β-adrenergic-induced lipolysis and mitochondrial respiration in cultured mouse brown adipocytes. Transgenic mice with UCP1-Cre mediated double deletion of TBLR1 and TBL1 exhibit reduced whole-body energy expenditure during prolonged cold exposure, lower core body temperature, increased appearance of unilocular adipocytes in BAT, and suppressed expression of metabolic and myogenic PRDM16 target genes. Also, we present some evidence that TBLR1 and TBL1 interact with HDAC3 and PRDM16 in brown adipocytes, potentially suggesting a direct involvement in the PRDM16-controlled transcriptional program. These findings identify the TBLR1/TBL1 complex as a critical regulator of BAT adaptation to prolonged cold and systemic energy homeostasis, shedding light on the context-dependent functions of corepressor complexes.},
}
@article {pmid40761960,
year = {2025},
author = {Rios Herrera, O and De La Torre, M and Melnikau, S and Bogati, N and Debebe, K and Melhem, A and Johnson, RW and Pagé, J and Zamaro, A and Raeburn, T},
title = {Necrotizing Soft Tissue Infection of the Breast: A Unique Presentation of Underlying Invasive Breast Cancer.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e87310},
pmid = {40761960},
issn = {2168-8184},
abstract = {Necrotizing soft tissue infections (NSTIs) are life-threatening infections that most commonly affect the extremities, perineum, and abdominal wall. These infections begin with the presence of toxin-producing bacteria that invade through a defect in the skin barrier, such as a wound, laceration, trauma, or recent surgical incision. These bacteria cause subsequent tissue destruction and necrosis that can involve the superficial skin, subcutaneous tissue, fascia, and/or muscle. NSTIs can progress quickly, leading to severe sepsis, shock, and even death. NSTIs associated with the breast are an exceedingly rare occurrence, requiring early diagnosis and prompt surgical intervention. In this article, we report the case of a 46-year-old woman with an NSTI of the left breast, which required serial debridement initially, and subsequently a modified radical mastectomy given a pathological diagnosis of invasive ductal carcinoma.},
}
@article {pmid40761476,
year = {2025},
author = {Takahashi, A and Fujiwara, S and Takahashi, Y and Isoda, M and Yasukawa, M and Goda, K and Yamanaka, T and Yamashita, T and Yuguchi, S},
title = {A Case of Drug-Induced Pancytopenia due to Tamoxifen.},
journal = {Surgical case reports},
volume = {11},
number = {1},
pages = {},
pmid = {40761476},
issn = {2198-7793},
abstract = {INTRODUCTION: Tamoxifen (TAM) is a well-established treatment for hormone receptor-positive breast cancer with a known side-effect profile that includes hot flashes, genital bleeding, and diarrhea (0.1%-5%). Other notable side effects include liver damage, abnormal vaginal discharge, depression, dizziness, and headaches of unknown frequency. However, blood cell count reduction has not yet been reported as a side effect in Japan.<br><br>CASE PRESENTATION: A 46-year-old female patient was diagnosed with right breast cancer (cT1N0M0). The patient underwent partial right breast resection and sentinel lymph node biopsy. Owing to the positive surgical resection margin, a mastectomy was performed. Pathological analysis of the surgical specimen confirmed invasive ductal carcinoma (estrogen receptor [ER]: 95%, progesterone receptor [PgR]: 85%, HER2: 2+ [fluorescence in situ hybridization, FISH negative]), with macrometastasis in one sentinel lymph node. Postoperative treatment included chemotherapy (dose-dense adriamycin and cyclophosphamide [AC] to dose-dense paclitaxel [PTX]), irradiation, and TAM. While initial blood test results before starting TAM showed mild anemia (Hb: 8.9 g/dL Grade 2), a follow-up blood test 5 months after initiating TAM revealed a significant decrease in blood cell counts (white blood cell [WBC]: 2600/&#x3bc;L Grade 2, neutrophil [neu]: 0.55 &#xd7; 10&#xb3;/&#x3bc;L Grade 3, Hb: 7.7 g/dL Grade 2, platelet [PLT]: 13.3 &#xd7; 10&#x2074;/&#x3bc;L). Considering the onset of symptoms following TAM administration, drug-induced pancytopenia was suspected. TAM and its concomitant medication pregabalin were discontinued. However, the blood cell counts continued to decline, necessitating further investigation. Myelodysplastic syndrome (MDS) was suspected, leading to multiple bone marrow biopsies. However, no definitive hematological disorder was diagnosed. The patient received transfusions and granulocyte colony-stimulating factor (G-CSF) injections based on the blood cell count. Approximately 4 months after the onset of neutropenia, gradual recovery was observed and spontaneous remission occurred. Given the rarity of spontaneous recovery from MDS, TAM is considered a potential causative agent of the observed decline in blood cell counts.<br><br>CONCLUSIONS: We report a case of suspected drug-induced cytopenia associated with tamoxifen administration.},
}
@article {pmid40754350,
year = {2025},
author = {Represa, M and Lima, O and Ávila, M and Rubiñán, P and Torres, C and Sansón-León, S and Lugo, J and Álvarez-Fernández, M and Rubianes, M and Legarra, JJ and Pérez-Rodríguez, MT},
title = {Impact of infectious diseases consultation and oral sequential therapy in the management of post-surgical mediastinitis.},
journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)},
volume = {43},
number = {7},
pages = {383-388},
doi = {10.1016/j.eimce.2025.06.005},
pmid = {40754350},
issn = {2529-993X},
mesh = {Humans ; *Mediastinitis/drug therapy/microbiology/etiology ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; *Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; *Referral and Consultation ; *Postoperative Complications/drug therapy/microbiology ; Administration, Oral ; *Cardiac Surgical Procedures/adverse effects ; Length of Stay/statistics &amp; numerical data ; Treatment Outcome ; },
abstract = {INTRODUCTION: Post-cardiac surgery mediastinitis (PSM) is a serious, complex, and multifactorial complication of surgical procedures. Infectious diseases consultation (IDC) has demonstrated improvement in other complex infectious diseases. The objective of the study was to evaluate the impact of IDC in the management and outcome of patients with PSM.<br><br>METHODS: Observational retrospective study, of adult patients with PSM between January 2010 and June 2021. After January 2016, IDC was performed in all the patients with PSM. The primary endpoint was clinical success, a composite variable of clinical cure, and absence of adverse events, or recurrence. Also, in-hospital stay, and clinical cure was evaluated in patients that received oral sequential therapy (OST).<br><br>RESULTS: A total of 84 patients with PSM were included, 48 pre-IDC and 36 in IDC period. No differences in clinical success were observed between the two periods (pre-IDC 60% vs, IDC 77%, p=0.104). During the IDC period the rate of adequate targeted antibiotic treatment was higher (pre-IDC 71% vs. IDC 94%, p=0.016). Gram-negative bacilli infections (pre-IDC 42% vs. IDC 78%, p=0.002) and polymicrobial infections (pre-IDC 37% vs. IDC 63%, p=0.004) increased in the IDC period. Multivariate analysis did not show any variable associated with clinical success. OST was similar in both periods, and a shorter in-hospital stay was observed in the patients who underwent OST (no-OST, 70 days vs. OST, 44 days, p=0.003).<br><br>CONCLUSIONS: IDC was related with a higher adequate targeted antimicrobial therapy. We observed that OST offers a promising strategy in the management of this infection.},
}
@article {pmid40736024,
year = {2025},
author = {Fang, W and Kozai, Y and Acevedo, DS and Brodine, R and Gorrepati, HS and Arviso, N and Cote, P and Thompson, A and Gerdes, Z and Espinoza, A and Bergeron, N and Brownfield, A and Cheng, N},
title = {Cooperative CCL2/CCR2 and HGF/MET signaling enhances breast cancer growth and invasion associated with metabolic reprogramming.},
journal = {Cancer biology &amp; therapy},
volume = {26},
number = {1},
pages = {2535824},
pmid = {40736024},
issn = {1555-8576},
support = {P30 CA168524/CA/NCI NIH HHS/United States ; R01 CA172764/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/metabolism/genetics ; *Chemokine CCL2/metabolism/genetics ; Animals ; *Proto-Oncogene Proteins c-met/metabolism/genetics ; Signal Transduction ; *Receptors, CCR2/metabolism/genetics ; Mice ; *Hepatocyte Growth Factor/metabolism/genetics ; Cell Proliferation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Xenograft Model Antitumor Assays ; Metabolic Reprogramming ; },
abstract = {With over 60,000 cases diagnosed in women annually, ductal carcinoma in situ (DCIS) is the most common form of pre-invasive breast cancer in the US. Despite standardized therapy, under-treatment and over-treatment are prevailing concerns. By understanding the mechanisms regulating DCIS progression, we may develop tailored strategies to improve treatment. CCL2/CCR2 and HGF/MET signaling pathways are upregulated in breast cancers. Our studies indicate that these pathways cooperate to promote DCIS progression and metabolism. DCIS and IDC tissues were immunostained for CCL2 and HGF expression. DCIS.com and HCC1937 cells were analyzed for cell proliferation through PCNA immunostaining, apoptosis through cleaved caspase-3 immunostaining, and invasion through Matrigel transwell assays. AKT, AMPK, p42/44MAPK and PKC activities were analyzed in vitro through immunoblot and pharmacologic inhibition. CCL2 and HGF-mediated metabolism were analyzed by LC-MS. Glucose uptake and lactate production were measured biochemically. CCR2 and MET were targeted in breast xenografts through CCR2 knockout and treatment with Merestinib. Significant associations between CCL2 and HGF were detected in DCIS and IDC tissues. CCL2 and HGF co-treatment enhanced breast cancer cell growth, survival, and invasiveness over individual CCL2 or HGF treatment. These CCL2/HGF-mediated phenotypes were associated with metabolic changes including glycolysis and increased AKT, AMPK, p42/44MAPK and PKC signaling. CCL2/HGF-mediated glycolysis was reduced with AKT, AMPK and p42/44MAPK inhibition. CCR2 knockout combined with Merestinib treatment inhibited growth, survival, and stromal reactivity of breast xenografts more than CCR2 or MET targeting alone. CCL2/CCR2 and HGF/MET cooperate to enhance breast cancer progression and metabolic reprogramming.},
}
@article {pmid40734184,
year = {2025},
author = {Bai, Y and Guo, X and Liu, K and Zheng, B and Wei, Y and Wang, Y and Zhang, W and Luo, Q and Yin, J and Wu, L and Li, Y and Zhang, Y and Chen, A and Wang, X and Xu, X and Liu, C and Jin, X},
title = {SpaSEG: unsupervised deep learning for multi-task analysis of spatially resolved transcriptomics.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {230},
pmid = {40734184},
issn = {1474-760X},
support = {2022YFC3400400//National Key Research and Development Program of China/ ; },
mesh = {Humans ; *Deep Learning ; *Gene Expression Profiling/methods ; *Transcriptome ; Breast Neoplasms/genetics ; *Unsupervised Machine Learning ; Female ; Carcinoma, Ductal, Breast/genetics ; },
abstract = {Spatially resolved transcriptomics (SRT) for characterizing spatial cellular heterogeneities in tissue environments requires systematic analytical approaches to elucidate gene expression variations within their physiological context. Here, we introduce SpaSEG, an unsupervised deep learning model utilizing convolutional neural networks for multiple SRT analysis tasks. Extensive evaluations across diverse SRT datasets generated by various platforms demonstrate SpaSEG's superior robustness and efficiency compared to existing methods. In the application analysis of invasive ductal carcinoma, SpaSEG successfully unravels intratumoral heterogeneity and delivers insights into immunoregulatory mechanisms. These results highlight SpaSEG's substantial potential for exploring tissue architectures and pathological biology.},
}
@article {pmid40727474,
year = {2025},
author = {Gu, W and Yuan, J and Dong, M and Sheng, J and Jiang, K},
title = {Case Report: Advanced breast invasive ductal carcinoma with erysipeloid cutaneous metastasis misdiagnosed as erysipelas.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1535421},
pmid = {40727474},
issn = {2234-943X},
abstract = {BACKGROUND: Breast cancer has become the second most common cancer after lung cancer. Patients may present with skin manifestations at the time of initial diagnosis, while erysipel-like carcinoma typically appears later, following initial treatment. This delay increases the risk of misdiagnosis.<br><br>CASE PRESENTATION: The patient was a 51-year-old female. A modified radical mastectomy for left breast carcinoma (pT2N3M0, stage IIIC; tumor size 4.6 cm &#xd7; 4.5 cm &#xd7; 1.6 cm, 14/21 axillary lymph nodes involved), HER2-positive type, was performed on April 21, 2021. In April 2024 (three years post-surgery), the patient developed unexplained redness and swelling in the skin of the left upper limb, accompanied by increased skin temperature. This was misdiagnosed as erysipelas of the upper limb. After one week of antibiotic treatment, the redness and swelling slightly subsided. In May 2024, the patient experienced dizziness and headaches without any obvious cause. Enhanced cranial MRI revealed multiple brain metastases, with possible lymph node metastasis in the left cervical region. The patient underwent whole-brain radiotherapy. During radiotherapy, erysipelas-like rashes developed on the left chest wall, upper limb, and right breast skin. In June 2024, a skin biopsy of the chest wall confirmed cutaneous metastasis. Following systemic anti-tumor treatment, both the skin and brain metastasis improved.<br><br>CONCLUSION: Pathological biopsy should be emphasized when breast cancer patients develop localized rashes. Understanding the unique inflammatory manifestations of cutaneous metastasis is crucial for breast oncologists to enable early diagnosis, timely treatment, and improved overall survival.},
}
@article {pmid40705266,
year = {2025},
author = {Mukhtar, RA and Dimitroff, K and Yau, C and Chien, AJ and Connolly, EP and Howard-McNatt, M and Rao, R and Ladores, V and Golshan, M and Sauder, CA and Ahmed, K and Lancaster, R and Fox, J and Gutnik, L and Lee, MC and Tchou, J and Prionas, N and Arciero, CA and Reyna, C and Kuerer, H and Switalla, K and Taunk, N and Tuttle, TM and Moran, MS and Postlewait, LM and Perlmutter, J and DeMichele, A and Yee, D and Hylton, N and Symmans, WF and Rugo, HS and Shatsky, R and Isaacs, C and Esserman, LJ and Van't Veer, L and Boughey, JC},
title = {Impact of Neoadjuvant Chemotherapy on Surgical Outcomes and Conversion to Node-Negativity in Invasive Lobular Breast Cancer: Analysis of Molecularly High-Risk Tumors by Histologic Subtype on the I-SPY2 Clinical Trial.},
journal = {Annals of surgical oncology},
volume = {32},
number = {11},
pages = {8243-8253},
pmid = {40705266},
issn = {1534-4681},
support = {K08 CA256047/CA/NCI NIH HHS/United States ; P01 CA210961/CA/NCI NIH HHS/United States ; K08CA256047/CA/NCI NIH HHS/United States ; P01CA210961/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis/genetics/metabolism ; *Breast Neoplasms/drug therapy/genetics/pathology/surgery ; *Carcinoma, Ductal, Breast/drug therapy/genetics/pathology/surgery ; *Carcinoma, Lobular/drug therapy/genetics/pathology/surgery ; Chemotherapy, Adjuvant ; Follow-Up Studies ; Lymph Node Excision ; *Lymph Nodes/pathology ; Lymphatic Metastasis ; *Mastectomy ; *Neoadjuvant Therapy ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) has lower response rates to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma. While ILC often has low-risk biology, there is a high-risk subset within this heterogeneous tumor type. We compared surgical treatment and response rates by histology in I-SPY2, a multicenter NAC trial.<br><br>METHODS: We evaluated 1329 patients with stage II-III breast cancer and high-risk 70-gene assay. Patients with classic, pleomorphic, or mixed lobular/ductal histology were included in the lobular cohort. We evaluated rates of mastectomy, positive margins, axillary dissection, and conversion from clinical node-positive (cN+) to pathologic node-negative (ypN-) status after NAC.<br><br>RESULTS: Overall, 124 patients (9.3%) had lobular histology, with 69% being hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-). There was no difference in mastectomy rate (57.2% for lobular vs. 55.8% for non-lobular). The ILC cohort had more positive margins after lumpectomy than the non-ILC cohort (21.2% vs. 7.9%; p&#xa0;=&#xa0;0.023). Within cN0 cases, axillary dissection was significantly more common among the lobular cases (24.1% vs. 14.0%; p&#xa0;=&#xa0;0.039). Conversion from cN+ to ypN0 did not differ statistically between lobular and non-lobular cases (40.9% vs. 51.2%; p&#xa0;=&#xa0;0.11). The nodal conversion rate among cN+lobular tumors was 30.6% in HR+/HER2-, 72.7% in HER2+, and 66.7% in triple-negative cases.<br><br>CONCLUSIONS: These data demonstrate the challenges of surgical management for ILC but hold promise that molecular classification can improve treatment selection. While high genomic risk is generally less common among ILC, our findings suggest that gene expression assays in cN+ILC patients can identify a subset who may benefit from NAC.},
}
@article {pmid40695279,
year = {2025},
author = {Kaltenecker, D and Fisker Schmidt, S and Weber, P and Loft, A and Morigny, P and Machado, J and Geppert, J and Saul, KB and Benedikt, P and Molocea, CE and Scott, R and Haase, K and Martignoni, ME and Alfaro, AJ and Chow, KK and Simoes, E and Pinhata Otoch, J and Lima, JDCC and Swanton, C and Spielmann, N and Hrabé de Angelis, M and Elsner, M and Ertürk, A and Dyar, KA and Rohm, M and Prokopchuk, O and Jamal-Hanjani, M and Seelaender, M and Backs, J and Herzig, S and Berriel Diaz, M},
title = {Functional liver genomics identifies hepatokines promoting wasting in cancer cachexia.},
journal = {Cell},
volume = {188},
number = {17},
pages = {4549-4566.e22},
doi = {10.1016/j.cell.2025.06.039},
pmid = {40695279},
issn = {1097-4172},
mesh = {*Cachexia/metabolism/genetics/pathology ; Humans ; Animals ; *Liver/metabolism ; *Neoplasms/complications/metabolism/genetics ; Mice ; Hepatocytes/metabolism ; Male ; Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism/genetics ; Genomics ; Female ; Transcriptome ; Mice, Inbred C57BL ; },
abstract = {In cancer cachexia, the presence of a tumor triggers systemic metabolic disruption that leads to involuntary body weight loss and accelerated mortality in affected patients. Here, we conducted transcriptomic and epigenomic profiling of the liver in various weight-stable cancer and cancer cachexia models. An integrative multilevel analysis approach identified a distinct gene expression signature that included hepatocyte-secreted factors and the circadian clock component REV-ERBα as key modulator of hepatic transcriptional reprogramming in cancer cachexia. Notably, hepatocyte-specific genetic reconstitution of REV-ERBα in cachexia ameliorated peripheral tissue wasting. This improvement was associated with decreased levels of specific cachexia-controlled hepatocyte-secreted factors. These hepatokines promoted catabolism in multiple cell types and were elevated in cachectic cancer patients. Our findings reveal a mechanism by which the liver contributes to peripheral tissue wasting in cancer cachexia, offering perspectives for future therapeutic interventions.},
}
@article {pmid40693684,
year = {2025},
author = {Liu, Y and Liu, J},
title = {Male Breast Cancer Complicated With Leukocytosis Resembling Leukemia Reaction After Chemotherapy: A Case Report.},
journal = {Cancer reports (Hoboken, N.J.)},
volume = {8},
number = {7},
pages = {e70280},
pmid = {40693684},
issn = {2573-8348},
mesh = {Humans ; Male ; Middle Aged ; *Breast Neoplasms, Male/drug therapy/pathology/complications ; *Leukocytosis/chemically induced/diagnosis/drug therapy ; *Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Diagnosis, Differential ; *Carcinoma, Ductal, Breast/drug therapy/pathology/surgery ; *Filgrastim/adverse effects/administration &amp; dosage ; Polyethylene Glycols/adverse effects/administration &amp; dosage ; Mastectomy, Modified Radical ; *Leukemia/diagnosis/chemically induced ; Granulocyte Colony-Stimulating Factor/adverse effects ; },
abstract = {INTRODUCTION: Male breast cancer (MBC) accounts for less than 1% of all cancers in men, with invasive ductal carcinoma being the most common type. The chemotherapy regimens used for MBC are similar to those for female breast cancer. However, the incidence of chemotherapy-induced complications such as leukocytosis resembling leukemia reaction is not well documented in MBC. This case highlights a rare complication in an MBC patient, induced by prophylactic PEG-rhG-CSF following chemotherapy.<br><br>CASE PRESENTATION: A 51-year-old male with left breast invasive ductal carcinoma underwent modified radical mastectomy. Postoperative pathology revealed high-risk features, and the patient received 8&#x2009;cycles of chemotherapy with the ddAC-T regimen, followed by PEG-rhG-CSF for febrile neutropenia prevention. After the fifth chemotherapy cycle, the patient developed leukocytosis resembling leukemia reaction, characterized by a white blood cell count exceeding 50&#x2009;&#xd7;&#x2009;10[9]/L, along with intermittent fever up to 42.5&#xb0;C. The condition was attributed to the PEG-rhG-CSF administration, and the patient was treated with NSAIDs and dexamethasone. Leukocytosis resolved after adjusting the PEG-rhG-CSF dose.<br><br>CONCLUSION: Leukocytosis resembling leukemia reaction induced by PEG-rhG-CSF post-chemotherapy is a rare complication, particularly in MBC patients. This case underscores the importance of careful monitoring and differential diagnosis to avoid misdiagnosis and unnecessary interventions. Personalized treatment strategies and dose adjustments for PEG-rhG-CSF are crucial in managing this rare reaction, emphasizing the need for awareness and individualized care in MBC patients undergoing chemotherapy.},
}
@article {pmid40690467,
year = {2025},
author = {Kretzmann, HG and Adeniyi, OV},
title = {Clinicopathological and molecular subtypes of breast cancer in the Eastern Cape, South Africa: A two-year retrospective study.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0325387},
pmid = {40690467},
issn = {1932-6203},
mesh = {Humans ; Female ; South Africa/epidemiology ; Middle Aged ; Retrospective Studies ; *Breast Neoplasms/pathology/epidemiology/classification/metabolism/genetics ; Adult ; Aged ; Cross-Sectional Studies ; Triple Negative Breast Neoplasms/pathology/epidemiology ; },
abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer in women worldwide and the most frequent cause of cancer death in women in low- and middle-income countries (LMIC). The incidence of BC in Africa is on the rise, expected to double by 2050, primarily owing to late presentation and weak health infrastructure in sub-Saharan Africa (SSA). This study addresses the lack of recent data on BC cases in the Eastern Cape Province of South Africa.<br><br>OBJECTIVE: The objectives of this study were to describe the clinicopathological characteristics and molecular subtypes of BC and, in addition, to examine the association between the clinicopathological characteristics and the molecular subtypes of BC in a single tertiary hospital in the Eastern Cape Province of South Africa.<br><br>METHODS: A two-year (2022-2023) retrospective cross-sectional clinical record review study was conducted on patients treated for invasive BC at a tertiary hospital in the Eastern Cape Province, South Africa. The demographic, clinical and pathological characteristics and molecular subtypes were reported. Associations were investigated between the BC molecular subtypes identified and the clinicopathological characteristics of the patients.<br><br>RESULTS: A total of 282 patients met the study's inclusion criteria. Most patients were female (98.6%) and African (88.1%). The mean age of the patients was 58.7 years, with BC most prevalent in the age group >70 (25.2%) and postmenopausal (77.4%). Breast lump was the most common presenting complaint (98.6%), with 61% of patients presenting three months after noticing the anomaly. The most common tumour size (59.4%) was&#x2009;>&#x2009;5&#x2009;cm (mean&#x2009;=&#x2009;6.37&#x2009;&#xb1;&#x2009;3.6), with the most common clinical T stage being T4 (50.4%). Lymph node involvement was seen in 50.4% of cases. Patients mostly presented in Stages III and IV of the disease (60.1%). Invasive ductal carcinoma not otherwise specified (NOS) was the most common histopathological subtype (86.2%). Grade 2 (56.2%) and Grade 3 (29.5%) BC accounted for the majority of cases. Luminal B was found in 47.4% of cases, Luminal A in 28.5%, triple negative breast cancer (TNBC) in 18.6% and human epidermal growth factor receptor 2 (HER2) enriched in 5.5% of cases, respectively.<br><br>CONCLUSION: In our setting, most patients consulted at a late stage of the disease with a large tumour size, positive lymph node status and a high histological grade. Luminal B tumours are the most common molecular subtype. These results indicate the need for more intensive breast cancer awareness campaigns, early detection, and timely referral and treatment.},
}
@article {pmid40679946,
year = {2025},
author = {Yıldırım, S and Mhamane, A and Lösch, S and Wieder, A and Ermis, E and König, AC and Yilmaz, S and Hauck, SM and Kocabas, F and Szendroedi, J and Herzig, S and Ekim, B},
title = {TSC22D1 is a newly identified inhibitor of insulin secretion in pancreatic beta cells.},
journal = {The FEBS journal},
volume = {292},
number = {23},
pages = {6307-6329},
pmid = {40679946},
issn = {1742-4658},
support = {EK108-1/1//Deutsche Forschungsgemeinschaft/ ; //Scientific and Technological Research Council of Turkey (TUBITAK)/ ; },
mesh = {*Insulin-Secreting Cells/metabolism ; *Insulin Secretion/genetics ; Animals ; Glucose/metabolism/pharmacology ; *Insulin/metabolism/genetics ; Humans ; Rats ; Mice ; Gene Expression Regulation ; Cell Line ; },
abstract = {The loss of pancreatic beta cell function leads to chronically high blood glucose levels, contributing to diabetes mellitus, one of the leading causes of morbidity and mortality worldwide. Understanding the molecular mechanisms that regulate beta cell function could pave the way for the development of more effective antidiabetic treatments. In this study, we identify the evolutionarily conserved transforming growth factor β-1 stimulated clone D1 (TSC22D1) protein as a previously unknown regulator of beta cell function. TSC22D1 depletion in INS-1E cells enhances the expression of key beta cell identity genes, including Ins1, Ins2, Pdx1, Slc2a2, and Nkx6.1, and promotes glucose-stimulated insulin secretion without altering intracellular insulin content. Mechanistically, TSC22D1 and Forkhead box protein O1 (FoxO1) interact and regulate each other in a reciprocal manner to control beta cell function. Our follow-up interactome and RNA-Seq analyses reveal that TSC22D1 is crucial for glucose-responsive cellular processes in beta cells, including mRNA processing, ribonucleoprotein complex biogenesis, and Golgi vesicle transport. Overall, our findings indicate that TSC22D1 plays a significant role in regulating beta cell function at multiple levels, with potential implications for metabolic diseases, such as diabetes.},
}
@article {pmid40679713,
year = {2025},
author = {Bae, SY and Kim, CW and Chin, J and Lee, JA and Kim, D and Lee, YJ and Yoon, CI and Park, WC},
title = {Clinical subtypes and prognosis of invasive breast cancer with Paget's disease: a SEER study.},
journal = {Breast cancer research and treatment},
volume = {213},
number = {2},
pages = {281-289},
pmid = {40679713},
issn = {1573-7217},
mesh = {Humans ; Female ; *Paget's Disease, Mammary/pathology/mortality/epidemiology/metabolism/genetics ; SEER Program ; *Breast Neoplasms/pathology/mortality/metabolism/epidemiology ; Prognosis ; Receptor, ErbB-2/metabolism/genetics ; Aged ; Middle Aged ; Receptors, Estrogen/metabolism/genetics ; *Carcinoma, Ductal, Breast/pathology/mortality/metabolism ; Aged, 80 and over ; Adult ; Receptors, Progesterone/metabolism ; Biomarkers, Tumor ; Neoplasm Staging ; },
abstract = {PURPOSE: Paget's disease of the breast is rare but commonly associated with underlying carcinoma. Despite frequent HER2 overexpression, its clinical relevance in Paget's disease remains unclear. We evaluated the prognostic impact of ER and HER2 expression in invasive ductal carcinoma (IDC) with Paget's disease and assessed whether clinical subtypes affect survival outcomes.<br><br>METHODS: Using SEER 17 data, we identified patients with IDC and HER2 status available, diagnosed from 2010 onward. Two groups were analyzed: IDC with Paget's disease (ICD-O-3 code 8541/3, n&#x2009;=&#x2009;1,000) and IDC alone (ICD-O-3 code 8500/3, n&#x2009;=&#x2009;487,162).<br><br>RESULTS: Compared to IDC alone, patients with Paget's disease had lower ER (60.5% vs. 82.0%) and PR (45.5% vs. 71.7%) expression, and higher HER2 overexpression (52.5% vs. 15.4%) (all P&#x2009;<&#x2009;0.001). The ER&#x2009;+&#x2009;HER2&#x2009;-&#x2009;subtype was less common in the Paget's group (34.9% vs. 71.6%), while ER&#x2009;-&#x2009;HER2&#x2009;+&#x2009;was more frequent (29.2% vs. 4.8%) (P&#x2009;<&#x2009;0.001). Among ER&#x2009;+&#x2009;HER2&#x2009;-&#x2009;and ER&#x2009;+&#x2009;HER2&#x2009;+&#x2009;subtypes, those with Paget's disease had worse breast cancer-specific survival (BCSS) than those with IDC alone (HR 1.519, 95% CI 1.074-2.149; HR 1.030, 95% CI 1.027-1.033, respectively). No BCSS differences were observed in ER&#x2009;-&#x2009;HER2&#x2009;-&#x2009;and ER&#x2009;-&#x2009;HER2&#x2009;+&#x2009;subtypes.<br><br>CONCLUSION: ER&#x2009;+&#x2009;HER2&#x2009;-&#x2009;subtype in IDC with Paget's disease is linked to worse BCSS, differing from IDC alone. These findings suggest distinct tumor biology in IDC with Paget's disease, highlighting the need for subtype-specific management strategies.},
}
@article {pmid40679712,
year = {2025},
author = {Zhan, H and Chan, NNN and Khaimova, R and Aung, TN and Gaule, P and Robbins, CJ and Rimm, DL},
title = {Quantitative assessment of HER2 expression in invasive ductal carcinoma and co-existing DCIS.},
journal = {Breast cancer research and treatment},
volume = {213},
number = {2},
pages = {273-279},
pmid = {40679712},
issn = {1573-7217},
support = {BCRF 23-138//Breast Cancer Research Foundation/ ; },
mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology/metabolism/genetics ; *Receptor, ErbB-2/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism/genetics ; Middle Aged ; *Carcinoma, Ductal, Breast/pathology/metabolism/genetics ; *Biomarkers, Tumor/metabolism ; Aged ; Neoplasm Grading ; Adult ; Immunohistochemistry ; },
abstract = {PURPOSE: Previous studies have demonstrated that ductal carcinoma in situ (DCIS) component often exhibits higher HER2 expression than the invasive component when assessed by immunohistochemistry, while some other studies showed concordant HER2 expression between these two components. In this study, we used our high-sensitivity HER2 (HS-HER2) quantitative immunofluorescence assay to compare HER2 expression in IDC and co-existing DCIS and correlate with clinicopathologic characteristics.<br><br>METHODS: We included 36 IDC&#x2009;+&#x2009;DCIS cases from the Yale Pathology department. DCIS was classified according to the three-tier nuclear grading system: low (grade 1), intermediate (grade 2), and high (grade 3) nuclear grade. Invasive carcinoma was graded according to the modified Bloom-Richardson histologic grading system. Cases were divided into two groups: low to intermediate-grade DCIS (G1-2) with co-existing invasive carcinoma (n&#x2009;=&#x2009;26) and high-grade DCIS (G3) with co-existing invasive carcinoma (n&#x2009;=&#x2009;10). Separate regions of interest for IDC and DCIS were annotated by two board-certified pathologists. Serial sections of FFPE tumor specimens were used to accurately measure the HER2 protein expression by the HS-HER2 assay in attomole/mm[2] unit and the acquisition by QuPath v.04 with the Qymia extension.<br><br>RESULTS: Low to intermediate-grade DCIS expressed higher HER2 levels (4295&#x2009;&#xb1;&#x2009;449 amol/mm[2]) than co-existing invasive carcinoma (2880&#x2009;&#xb1;&#x2009;413 amol/mm[2]). Similarly, high-grade DCIS expressed higher HER2 levels (4953&#x2009;&#xb1;&#x2009;700 amol/mm[2]) than co-existing invasive carcinoma (3560&#x2009;&#xb1;&#x2009;688 amol/mm[2]). Neither of these trends toward lower expression levels in the IDC were statistically significant. Additionally, no significant statistic difference was noted between low to intermediate-grade DCIS versus high-grade DCIS or between their corresponding co-existing invasive carcinomas in this cohort.<br><br>CONCLUSION: Using the HS-HER2 assay, our results demonstrated comparable HER2 expression levels in DCIS and paired invasive carcinoma regardless of histopathological grade or HER2 immunohistochemical score. These findings contributed to a more nuanced understanding of HER2 biology in early breast carcinogenesis and may inform future biomarker-driven therapeutic strategies.},
}
@article {pmid40667287,
year = {2025},
author = {Wang, R and Fridman, G},
title = {Ionic Direct Current Enables Millimeter- and Millisecond-Scale Cortical Gain Control in vivo.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40667287},
issn = {2692-8205},
support = {R01 NS110893/NS/NINDS NIH HHS/United States ; },
abstract = {Precise, reversible modulation of cortical gain at mesoscale resolution remains a major challenge for neuroscience. Here, we introduce ionic direct current (iDC) delivered through non-penetrating electrolyte-filled microcatheters on the cortical surface as a method for targeted neuromodulation at millimeter spatial scales and millisecond onset/offset. In rat primary somatosensory cortex (S1HL), laminar recordings under urethane revealed that cathodic iDC attenuated and anodic iDC amplified both spontaneous delta oscillations and sensory-evoked responses, without causing time-locked spiking or state disruption. Computational modeling reproduced these effects and implicated dendritic summation at the axon initial segment as the mechanism for bidirectional gain control. In awake animals, iDC modulation of S1HL altered tactile sensitivity to Von Frey stimulation, demonstrating behavioral relevance. Together, these results establish iDC as a versatile platform for precise, rapidly reversible, and non-disruptive manipulation of cortical gain in vivo, enabling new approaches for dissecting mesoscale circuit interactions and linking column-scale physiology to behavior.},
}
@article {pmid40644582,
year = {2025},
author = {Wang, G and Liu, X and Si, Z and Wang, Z and Wang, X},
title = {A Scallop-shaped Photopenic Region in the Urinary Bladder Area on Tc-99m MDP Bone Scan Caused by a Uterine Cervical Leiomyoma.},
journal = {Clinical nuclear medicine},
volume = {50},
number = {12},
pages = {1243-1244},
doi = {10.1097/RLU.0000000000006049},
pmid = {40644582},
issn = {1536-0229},
mesh = {Humans ; Female ; Middle Aged ; *Technetium Tc 99m Medronate ; *Leiomyoma/diagnostic imaging ; *Urinary Bladder/diagnostic imaging ; *Uterine Cervical Neoplasms/diagnostic imaging ; Radionuclide Imaging ; *Bone and Bones/diagnostic imaging ; },
abstract = {A 46-year-old woman with right breast invasive ductal carcinoma and sternalgia underwent Tc-99m methylene diphosphonate (MDP) whole-body bone scintigraphy, on which a scallop-shaped photopenic region in the urinary bladder area was found, besides increased radioactivity in the sternum region and both breasts. By reviewing a previous CT scan, a pelvic mass oppressing the right wall of the urinary bladder was noted, which was confirmed to be a rare uterine cervical leiomyoma by biopsy.},
}
@article {pmid40639624,
year = {2025},
author = {Borella, F and Gallio, N and Giurdanella, M and Capella, G and Cassoni, P and Castellano, I},
title = {Triple-negative lobular breast cancer: focus on pathology and clinical challenges.},
journal = {Human pathology},
volume = {162},
number = {},
pages = {105871},
doi = {10.1016/j.humpath.2025.105871},
pmid = {40639624},
issn = {1532-8392},
mesh = {Humans ; *Triple Negative Breast Neoplasms/pathology/genetics/therapy ; Female ; *Carcinoma, Lobular/pathology/genetics/therapy ; *Biomarkers, Tumor/genetics ; Prognosis ; },
abstract = {Triple-negative invasive lobular carcinoma is a rare and under-characterized subtype of breast cancer, distinct from the more common triple-negative invasive ductal carcinoma. While triple-negative invasive ductal carcinoma is generally recognized for its aggressive clinical behavior and lack of targeted treatment options, triple-negative invasive lobular carcinoma presents unique histopathological and molecular features that may influence its prognosis and therapeutic responsiveness. Despite these differences, triple-negative invasive lobular carcinoma remains poorly studied, leading to a reliance on treatment strategies adapted from ductal histotype, which may not fully address its biological complexities. This review aims to provide a comprehensive overview of triple-negative invasive lobular carcinoma by analyzing its clinicopathological characteristics, prognostic factors, and emerging therapeutic approaches. We explore the genetic alterations commonly observed in triple-negative invasive lobular carcinoma, their potential implications for treatment selection, and the challenges in current management strategies. Furthermore, we discuss the need for specialized research efforts and clinical trials to define treatment paradigms better. As precision oncology continues to evolve, understanding the biological distinctions of triple-negative invasive lobular carcinoma will be essential for optimizing patient outcomes and developing more effective treatment strategies.},
}
@article {pmid40629116,
year = {2025},
author = {Wang, R and Zhao, F and Yan, T and Li, Y and Cheng, D and Wang, W and Tian, C and Yu, H},
title = {Gallbladder metastasis in invasive ductal breast cancer with concurrent gallstones and gallbladder carcinoma.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {1287},
pmid = {40629116},
issn = {2730-6011},
support = {AHWJ2023A10015//2023 Health research project of Anhui Health Commission/ ; YZ2023H2A006//Anhui University of Science and Technology 2023 medical special cultivation project/ ; NO. 2023AH040405//Scientific research project (Natural science) of Anhui University/ ; NO.2023szsfkc069//2023 Provincial new era education quality engineering (graduate education) project/ ; },
abstract = {The gallbladder is an uncommon location for tumor metastases. Breast cancer seldom spreads to the gallbladder, although melanoma and renal cell tumors typically do. We report a case of a 58-year-old woman with chronic cholecystitis caused by gallstones. Following a laparoscopic cholecystectomy, a nodule was discovered on the gallbladder wall. Based on her medical history and pathological tissue molecular typing, the diagnosis was determined to be gallbladder metastasis of invasive breast ductal carcinoma, with a negative hormone receptor. Two years prior, the patient had undergone a modified radical mastectomy for left breast cancer. The postoperative pathology revealed grade III invasive ductal carcinoma, pT2N1M0, and a negative hormone receptor. This case report highlights the rare occurrence of invasive breast ductal carcinoma metastasizing to the gallbladder.},
}
@article {pmid40604374,
year = {2025},
author = {Pardo, J and Capdevila-Lacasa, C and Segura, B and Pané, A and Moreno, PJ and Garrabou, G and Grau-Junyent, JM and Junqué, C and , },
title = {Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria.},
journal = {Journal of neurodevelopmental disorders},
volume = {17},
number = {1},
pages = {37},
pmid = {40604374},
issn = {1866-1955},
mesh = {Humans ; *Phenylketonurias/blood/diagnostic imaging/psychology/diet therapy/pathology/complications ; *Phenylalanine/blood ; Adult ; Male ; Female ; Diffusion Tensor Imaging ; *White Matter/diagnostic imaging/pathology ; *Cognition/physiology ; Young Adult ; *Brain/diagnostic imaging ; Neuropsychological Tests ; },
abstract = {BACKGROUND: Altered white matter (WM) is consistently reported in patients with phenylketonuria (PKU). However, the knowledge about WM microstructural integrity in early-treated adults with classical PKU and its relationship with cognition and metabolic parameters is inconclusive. This study aims to explore the cerebral WM microstructural alterations in adult patients with early-treated classical PKU and their association with blood phenylalanine (Phe) levels and neuropsychological performance using whole-brain diffusion tensor imaging (DTI).<br><br>METHODS: Twenty-nine patients with early-treated classical PKU (mean age = 30.86, SD = 7.74) and 31 healthy controls (mean age = 32.45, SD = 9.40) underwent neuropsychological assessment and MRI. Phe dry blood spot (DBS-Phe) samples, along with venous Phe levels, were collected from the PKU sample to calculate the index of dietary control (IDC). Tract-based spatial statistics (TBSS) of the mean diffusivity (MD), and fractional anisotropy (FA), were carried out with FSL v6.0.4 to assess between-group differences and to explore associations with both cognitive and clinical data.<br><br>RESULTS: Patients exhibited a widespread white matter tract involvement, with lower MD and higher FA values compared to controls. The most affected tracts were the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus for MD, and the anterior corona radiata, uncinate fasciculus and forceps minor for FA. MD negatively correlated with IDC and venous Phe levels, whereas FA negatively correlated with full-scale intelligence quotient (FSIQ) (p-value &#x2264;0.05 FWE-corrected).<br><br>CONCLUSIONS: Microstructural WM alterations were present in adults with early-treated classical PKU, and these abnormalities were related to global intelligence and metabolic control markers. Although our results suggest the importance of proper disease management, further studies are needed to determine its long-term relevance.},
}
@article {pmid40597443,
year = {2025},
author = {Bullock, E and Rozyczko, A and Shabbir, S and Tsoupi, I and Young, AIJ and Travnickova, J and Gómez-Cuadrado, L and Mabruk, Z and Carrasco, G and Morrow, E and Pennel, K and Kloosterman, P and Houthuijzen, JM and Jonkers, J and Avalle, L and Poli, V and Iggo, R and Xiao, X and Guo, J and Zhu, X and Mallon, E and Edwards, J and Patton, EE and Brunton, VG},
title = {Cancer-associated fibroblast driven paracrine IL-6/STAT3 signaling promotes migration and dissemination in invasive lobular carcinoma.},
journal = {Breast cancer research : BCR},
volume = {27},
number = {1},
pages = {121},
pmid = {40597443},
issn = {1465-542X},
support = {Pakistan-Programme 2020-2024//Punjab Educational Endowment Funds/ ; MC_UU_00035/13/MRC_/Medical Research Council/United Kingdom ; C157/A24837/CRUK_/Cancer Research UK/United Kingdom ; NO. 2022YFS0601//Sichuan Provincial Science and Technology Support Program/ ; 68730/MRA/Melanoma Research Alliance/United States ; S3181//NHS Lothian Charity/ ; /WT_/Wellcome Trust/United Kingdom ; },
mesh = {*STAT3 Transcription Factor/metabolism/genetics ; *Interleukin-6/metabolism/genetics ; Humans ; Animals ; Female ; Mice ; Cell Movement ; *Breast Neoplasms/pathology/metabolism/genetics ; *Carcinoma, Lobular/pathology/metabolism/genetics ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Zebrafish ; Signal Transduction ; Paracrine Communication ; Cell Line, Tumor ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal carcinoma of no special type (NST), accounting for 10-15% of diagnoses. Despite the myriad molecular, histological and clinical differences between ILC and NST tumors, patients are treated in the same way, and although prognosis initially is good, ILC patients have poorer long-term outcomes. Understanding the differences between these two subtypes and identifying ILC-enriched therapeutic targets is necessary to improve patient care.<br><br>METHODS: Human and mouse cancer-associated fibroblasts (CAFs), ILC cell lines and patient-derived organoids were used for in vitro and in vivo studies, including western blotting, migration, organotypic invasion assays and dissemination in zebrafish embryos. RNASeq was used to identify CAF and interleukin-6 (IL-6)-derived gene signatures. Bioinformatic analysis of public databases and immunohistochemical of human tumor microarrays was carried out.<br><br>RESULTS: We identified IL-6 as a paracrine CAF-derived factor that activates Signal-Transducer-and-Activator-of-Transcription-3 (STAT3) in human and mouse ILC models. Analysis of human breast tumors showed that the IL-6/JAK/STAT3 pathway is enriched in ER&#x2009;+&#x2009;ILC compared to ER&#x2009;+&#x2009;NST. A 42-gene CAF dependent IL-6 gene signature and 64-gene consensus IL-6 gene signature were generated and were significantly enriched in ER&#x2009;+&#x2009;ILC, with many of the genes overexpressed in ILC tumors. IL-6 treatment suppressed downstream estrogen signaling and also led to the acquisition of a more mesenchymal-like phenotype associated with increased migration and invasion. Finally, IL-6 treatment significantly increased ILC cell dissemination following injection into zebrafish embryos.<br><br>CONCLUSIONS: CAF-derived IL-6 drives paracrine activation of the IL6/JAK/STAT3 signaling pathway which is enriched in ILC. This leads to the acquisition of pro-tumorigenic phenotypes, highlighting the pathway as a potential therapeutic target in ILC.},
}
@article {pmid40595592,
year = {2025},
author = {Mello, RM and Gomez Ceballos, D and Sandate, CR and Wang, S and Jouffe, C and Agudelo, D and Uhlenhaut, NH and Thomä, NH and Simon, MC and Lamia, KA},
title = {BMAL1 and ARNT enable circadian HIF2α responses in clear cell renal cell carcinoma.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {5834},
pmid = {40595592},
issn = {2041-1723},
support = {UL1TR002550//U.S. Department of Health &amp; Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; CA271500//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; R01 CA211187/CA/NCI NIH HHS/United States ; R01 CA271500/CA/NCI NIH HHS/United States ; 450149205//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; UL1 TR002550/TR/NCATS NIH HHS/United States ; DK136780//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; CA211187//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; },
mesh = {*ARNTL Transcription Factors/metabolism/genetics ; *Basic Helix-Loop-Helix Transcription Factors/metabolism/genetics/antagonists &amp; inhibitors ; *Carcinoma, Renal Cell/genetics/metabolism/pathology/drug therapy ; Humans ; *Kidney Neoplasms/genetics/metabolism/pathology/drug therapy ; *Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism/genetics ; Animals ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; *Circadian Rhythm/genetics ; Mice ; Xenograft Model Antitumor Assays ; Cell Proliferation/drug effects ; Female ; },
abstract = {Circadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). The core circadian transcription factor BMAL1 is closely related to ARNT, and we show that BMAL1-HIF2α regulates a subset of HIF2α target genes in ccRCC cells. Depletion of BMAL1 selectively reduces HIF2α chromatin association and target gene expression and reduces ccRCC growth in culture and in xenografts. Analysis of pre-existing data reveals higher BMAL1 in patient-derived xenografts that are sensitive to growth suppression by a HIF2α antagonist (PT2399). BMAL1-HIF2α is more sensitive than ARNT-HIF2α is to suppression by PT2399, and the effectiveness of PT2399 for suppressing xenograft tumor growth in vivo depends on the time of day at which it is delivered. Together, these findings indicate that an alternate HIF2α heterodimer containing the circadian partner BMAL1 influences HIF2α activity, growth, and sensitivity to HIF2α antagonist drugs in ccRCC cells.},
}
@article {pmid40589310,
year = {2025},
author = {Shan, M and Chen, L and Wang, J and Wen, L},
title = {Dual-Channel Off-Axis Ion Funnel With a Deflection Electrode.},
journal = {Rapid communications in mass spectrometry : RCM},
volume = {39},
number = {20},
pages = {e10103},
doi = {10.1002/rcm.10103},
pmid = {40589310},
issn = {1097-0231},
support = {2023ZY01073//Ministry of Industry and Information Technology/ ; 2022S012//Public welfare project in Ningbo/ ; 2024S002//Public welfare project in Ningbo/ ; 2021Z055//Major projects in Ningbo/ ; //K.C. Wong Magna Fund in Ningbo University/ ; },
abstract = {RATIONALE: In electrospray ionization mass spectrometry (ESI-MS) systems, two critical challenges persist: (1) under-expanded supersonic jets at the atmospheric pressure interface (API) cause ion losses and reduced transmission efficiency; (2) residual solvents and charged droplets entering vacuum stages lead to contamination and elevated chemical noise, degrading analysis accuracy.<br><br>METHODS: A dual-channel off-axis ion funnel with a deflection electrode (DC-OFIDE) was developed to address these challenges. This device integrates three core components: an ion drift channel (IDC), an ion funnel channel (IFC), and a deflection electrode. The IDC and IFC are separated by conjoined gaps. Ions within the gas stream emanating from the API are extracted from the IDC via a deflection field, while a retarding axial field prolongs ions' residence time, ensuring efficient transfer to the IFC. This DC-OFIDE features an enlarged entrance aperture (&#x3a6;18&#x2009;mm) to accommodate a multi-capillary interface, enhancing compatibility with high-conductance sample introduction systems.<br><br>RESULTS: Compared with the original conventional ion funnel (CIF), the DC-OFIDE achieved a threefold enhancement in caffeine ion intensity and a broader m/z transmission window. It demonstrated robust neutral and droplet suppression, maintaining 80% ion intensity even under tripled serum volume infused. In drug screening of hair samples, baseline noises in drug ion peaks were reduced by 36%-82%, with a quadrupled signal-to-noise ratio improvement observed for 6-monoacetylmorphine.<br><br>CONCLUSIONS: This DC-OFIDE significantly enhances ion transmission efficiency and chemical noise suppression in ESI-MS, establishing its potential for high-fidelity analysis of complex samples.},
}
@article {pmid40585989,
year = {2025},
author = {Song, W and Wang, J and Gong, S and Wang, X and Xu, J and Wu, R and Jiang, Z and Zhang, H and Wu, L and Wang, Y and Su, Y and Wang, H and Gu, Y},
title = {FAK signaling suppression by OCT4-ITGA6 mediates the effectively removal of residual pluripotent stem cells and enhances application safety.},
journal = {Theranostics},
volume = {15},
number = {14},
pages = {7127-7153},
pmid = {40585989},
issn = {1838-7640},
mesh = {Animals ; *Octamer Transcription Factor-3/metabolism/genetics ; Mice ; *Pluripotent Stem Cells/metabolism/cytology ; Signal Transduction ; Humans ; Cell Differentiation ; Coculture Techniques ; Teratoma/pathology ; *Focal Adhesion Kinase 1/metabolism ; },
abstract = {Rationale: Pluripotent stem cells (PSCs) serve as a critical source of seed cells for regenerative therapies due to their unlimited proliferative capacity and ability to differentiate into all three germ layers. Despite their potential, the risk of teratoma formation caused by residual PSCs within differentiated cell populations poses a significant barrier to clinical applications. This study aims to develop a novel strategy to selectively remove residual PSCs while preserving the safety and functionality of PSC-derived differentiated cells (iDCs). Methods: The calcium- and magnesium-free balanced salt solution (BSS(Ca-Mg-)) was employed to selectively target PSCs in a co-culture system comprising PSCs and four types of iDCs. The effect of BSS(Ca-Mg-) treatment on teratoma formation was evaluated in immunodeficient mice following cell transplantation. Comparative analysis and gene knockdown experiments were conducted to explore the molecular mechanisms underlying the differential response of PSCs and iDCs to BSS(Ca-Mg-), focusing on FAK signaling and its interaction with OCT4 and ITGA6. Results: The BSS(Ca-Mg-) treatment effectively induced the detachment of PSCs in the co-culture system without disrupting iDC adhesion. In vivo experiments confirmed that cells treated with BSS(Ca-Mg-) did not form teratomas upon implantation into immunodeficient mice. Mechanistic studies revealed that PSCs exhibit lower activation of FAK signaling compared to iDCs, contributing to their selective detachment. Additionally, OCT4 and ITGA6 were found to maintain each other's protein expression, forming a feedback loop that suppressed FAK signaling, while FAK suppression further enhanced OCT4 expression. Conclusions: The study presents a safe, effective, and cost-efficient method for the selective removal of residual PSCs. This approach enhances existing safety measures for iDC applications, improving the clinical feasibility of iDC-based cell therapies.},
}
@article {pmid40578985,
year = {2025},
author = {Woo, HY and Jung, YY and Kim, HS},
title = {Metastatic Invasive Lobular Breast Carcinoma Involving Tamoxifen-related Endometrial Polyp in a Patient With Metachronous Bilateral Breast Carcinomas: A Case Report.},
journal = {In vivo (Athens, Greece)},
volume = {39},
number = {4},
pages = {2456-2463},
pmid = {40578985},
issn = {1791-7549},
mesh = {Humans ; Female ; *Tamoxifen/adverse effects/therapeutic use ; *Breast Neoplasms/pathology/drug therapy/diagnosis ; Adult ; *Polyps/pathology/diagnosis/chemically induced ; *Carcinoma, Lobular/pathology/drug therapy/diagnosis ; *Endometrial Neoplasms/secondary/diagnosis/pathology ; Antineoplastic Agents, Hormonal/adverse effects ; *Neoplasms, Second Primary/pathology ; },
abstract = {BACKGROUND/AIM: Metastasis of extragenital malignancies to the female genital tract, particularly the uterus, is exceedingly rare. Invasive lobular carcinoma (ILC) is the most common histological type of breast carcinoma that metastasizes to gynecologic organs.<br><br>CASE REPORT: A 42-year-old woman receiving tamoxifen presented with an irregularly thickened endometrium on transvaginal ultrasonography. She had previously undergone bilateral partial mastectomies - eight years prior for right-sided invasive ductal carcinoma, and three years prior for left-sided ILC. Hysteroscopic evaluation revealed an endometrial polyp. Microscopic examination of the polypectomy specimen showed variably sized, irregularly shaped branching glands embedded in densely fibrotic stroma. Within the stroma, monomorphic tumor cells with hyperchromatic, eccentrically located nuclei were arranged in single files, thin cords, or nests. Immunostaining revealed that the tumor cells were positive for GATA-binding protein 3 and negative for paired box 8, supporting a diagnosis of metastatic carcinoma from the breast. The final pathological diagnosis was metastatic ILC involving a tamoxifen-associated endometrial polyp.<br><br>CONCLUSION: Although rare, breast carcinoma may metastasize to endometrial polyps. Clinicians and pathologists should consider this possibility when evaluating abnormal ultrasonographic findings in the female genital tract, particularly in patients with a history of breast carcinoma receiving tamoxifen therapy. Abnormal ultrasonographic findings in the uterus of such patients warrant a comprehensive diagnostic workup to exclude metastatic disease.},
}
@article {pmid40574925,
year = {2025},
author = {Lin, YT and Hong, ZJ and Liao, GS and Dai, MS and Chao, TK and Tsai, WC and Sung, YK and Chiu, CH and Chang, CK and Yu, JC},
title = {Unexpected contralateral axillary lymph node metastasis without ipsilateral involvement in triple-negative breast cancer: A case report and review of literature.},
journal = {World journal of clinical cases},
volume = {13},
number = {18},
pages = {103571},
pmid = {40574925},
issn = {2307-8960},
abstract = {BACKGROUND: Breast cancer is a leading cause of cancer-related mortality among women worldwide, with invasive ductal carcinoma (IDC) being the most prevalent subtype. Lymph node metastasis is the primary prognostic indicator, typically evaluated via biopsy of the ipsilateral sentinel or axillary lymph nodes. Contralateral axillary metastasis (CAM) without ipsilateral involvement is exceedingly rare, particularly in early-stage breast cancer. This report presents a case of CAM in a patient with triple-negative breast cancer (TNBC), underscoring diagnostic and therapeutic complexities.<br><br>CASE SUMMARY: A 73-year-old female presented with left-sided early-stage IDC in February 2023. Despite a modified radical mastectomy and pathologically negative ipsilateral lymph nodes, a postoperative positron emission tomography (PET) scan detected fluorodeoxyglucose-avid nodes in the contralateral axilla. Biopsy confirmed metastatic ductal carcinoma with triple-negative status, resulting in an upstaged diagnosis of metastatic breast cancer, stage IV, M1. The patient underwent six cycles of adjuvant chemotherapy, with follow-up PET imaging showing regression of the contralateral lesion. This case highlights the importance of advanced imaging in TNBC for precise staging and treatment optimization.<br><br>CONCLUSION: This case highlights the aggressive nature of TNBC and the need for advanced imaging to ensure accurate staging and effective management.},
}
@article {pmid40561128,
year = {2025},
author = {Deng, M and March, DS and Churchwood, DR and Young, HML and Highton, PJ and Denniff, MJ and Graham-Brown, MPM and Burton, JO and Baker, LA},
title = {Exploring a role for Chemerin in the cardiovascular and musculoskeletal benefits of intradialytic exercise in the hemodialysis population.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0321497},
pmid = {40561128},
issn = {1932-6203},
mesh = {Humans ; *Chemokines/blood ; *Renal Dialysis ; Male ; Female ; Middle Aged ; *Intercellular Signaling Peptides and Proteins/blood ; *Cardiovascular Diseases/blood/prevention &amp; control ; Aged ; *Exercise/physiology ; Adult ; *Exercise Therapy/methods ; Retrospective Studies ; },
abstract = {BACKGROUND: Cardiovascular disease is the leading cause of death for people receiving hemodialysis. Intradialytic cycling (IDC) has been shown to improve cardiovascular health in the hemodialysis population, but specific mechanisms require elucidation. Chemerin is an adipokine which contributes to the inflammatory process and may be associated with the cardiovascular benefits of IDC and physical function in hemodialysis population.<br><br>METHODS: Adults undertaking &#x2265;3 months hemodialysis were randomized to either IDC (30&#x2009;min each time, moderate intensity, thrice weekly) and usual care; or usual care only (control group). 88 blood samples were retrospectively analyzed for chemerin concentrations using ELISA. Unadjusted and adjusted linear regression was used to understand how changes in chemerin are associated with changes in cardiovascular and musculoskeletal health in response to IDC.<br><br>RESULTS: There was a significant increase of plasma chemerin concentration after 6 months in both groups. A positive association was detected between chemerin and short physical performance battery at baseline (&#x3b2;&#x2009;=&#x2009;0.264, p&#x2009;=&#x2009;0.017). There was no correlation of chemerin with cardiovascular, body composition, and other physical function markers.<br><br>CONCLUSIONS: This study is the first to show plasma level of chemerin increases with time on hemodialysis. No evidence was found to support a role for chemerin in modifying cardiac structure and function in people undertaking IDC. Further studies should investigate the associations between chemerin and physical performance.},
}
@article {pmid40544078,
year = {2025},
author = {Ao, Y and Li, X and Mu, L and Zhao, J and Chen, H and Wang, Y and Zhang, S and Yang, S and Zhang, N and Qiu, L},
title = {Time-Dependent Apparent Diffusion Coefficient Changes in Breast MR Images With Contrast for Tumor Characterization.},
journal = {Clinical breast cancer},
volume = {25},
number = {8},
pages = {817-825},
doi = {10.1016/j.clbc.2025.05.019},
pmid = {40544078},
issn = {1938-0666},
mesh = {Humans ; Female ; *Contrast Media/administration &amp; dosage ; *Breast Neoplasms/pathology/diagnostic imaging/diagnosis ; *Diffusion Magnetic Resonance Imaging/methods ; Middle Aged ; Adult ; Aged ; Breast/diagnostic imaging/pathology ; Time Factors ; Diagnosis, Differential ; ROC Curve ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology/diagnostic imaging ; Aged, 80 and over ; },
abstract = {BACKGROUND: To assess the effect of scan time after contrast injection on breast MRI DWI sequence ADC values and its role in lesion differentiation.<br><br>PATIENTS AND METHODS: Between 2022 and 2023, two hundred and fifty-one breast magnetic resonance (MR) images were collected from 251 patients, who had a total of 258 lesions. Pathology results obtained within 1 month of the MR imaging were utilized. Apparent diffusion coefficient (ADC) values were measured at 3 time-points: precontrast, 3 minutes postcontrast, and 6 minutes postcontrast. For the analysis, statistical methods including the Friedman test, linear mixed models, Bonferroni correction, receiver operating characteristic (ROC) curve analysis, and DeLong test were applied.<br><br>RESULTS: Contrast agents cause ADC values to decrease within 3 minutes after injection and recover within 6 minutes (e.g., invasive ductal carcinoma). ADC can distinguish between benign tumors and cancers but not between carcinoma in situ and invasive carcinoma. Time-dependent changes do not affect the differentiation of benign from malignant lesions.<br><br>CONCLUSION: Contrast injection time has little effect on the effectiveness of ADC in differentiating benign from malignant lesions on DWI sequences. The findings support the feasibility of postcontrast DWI without compromising diagnostic accuracy.},
}
@article {pmid40539820,
year = {2025},
author = {Zhang, X and Yin, Y and Ye, Z and Zhang, X and Wei, W and Hao, Y and Zeng, L and Yang, T and Li, D and Wang, J and Zhao, D and Chen, Y and Lei, S and Jiang, Y and Zhang, Y and Xu, S and Nanding, A and Gong, Y and Li, S and Yu, Y and Zhao, S and Liu, S and Zhao, Y and Chen, Z and Yu, S and Fan, JB and Pang, D},
title = {An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing.},
journal = {Cancer medicine},
volume = {14},
number = {12},
pages = {e71004},
pmid = {40539820},
issn = {2045-7634},
support = {2019B121205010//Science and Technology Program of Guangdong Province/ ; GA20C016//Heilongjiang Province Applied Technology Research and Development/ ; 201909010010//Scheme of Guangzhou for Leading Team in Innovation/ ; 82073410//China National Science Foundation/ ; 82272623//China National Science Foundation/ ; 82173235//China National Science Foundation/ ; 202201010943//Guangzhou Basic and Applied Basic Research Project/ ; 2016007//Scheme of Guangzhou for Leading Talents in Innovation and Entrepreneurship/ ; 2023ZX06C10//Key Special Projects of Heilongjiang Province Key Research and Development Program/ ; Nn10//Nn10 Program of Harbin Medical University Cancer Hospital/ ; JJZD2020-08//Haiyan Foundation of Harbin Medical University Cancer Hospital/ ; 2020GH15//2020 Guangzhou Development Zone International Science and Technology Cooperation Project/ ; 2017-L152//Scheme of Guangzhou Economic and Technological Development District for Leading Talents in Innovation and Entrepreneurship/ ; JD22C004//Key R&amp;D Plan Projects of Heilongjiang Province, Da Pang/ ; },
mesh = {Humans ; *Breast Neoplasms/genetics/diagnosis/blood ; Female ; *DNA Methylation ; Diagnosis, Differential ; *Biomarkers, Tumor/genetics/blood ; *Circulating Tumor DNA/genetics/blood ; Middle Aged ; Mammography ; Aged ; Adult ; },
abstract = {BACKGROUND: Breast ultrasonography and mammography remain predominant in breast tumor evaluations, yet they often result in false positives, particularly for tumors classified as BI-RADS 4a or those no more than 10 mm, which are not ideal for core needle biopsy (CNB). Early-stage breast cancer detection via circulating tumor DNA (ctDNA) methylation holds potential to bridge these diagnostic gaps.<br><br>METHODS: We curated a breast cancer-specific panel by harnessing methylation profiles from in-house and public databases. Leveraging breast tissue-plasma-leukocyte samples, we identified breast cancer-specific markers, culminating in a 103-marker methylation model which underwent rigorous validation in two independent cohorts. To assess its performance, we compared it against the accuracy of ultrasonography, mammography, and CNB.<br><br>RESULTS: The 103-marker model exhibited remarkable proficiency in discerning benign from malignant breast tumors in plasma, with AUCs of 0.838, 0.838 and 0.823 in the validation set and two independent test sets, respectively. In BI-RADS 4a breast cancer, when compared to ultrasonography or mammography, the model augmented breast cancer diagnostic accuracy by 40.58% and 25.49%, separately. Retrospective analyses suggested that our model achieved a sensitivity of 66.67% (4/6) and a specificity of 80.36% (45/56) for surgical patients in the BI-RADS 4a category with tumors &#x2264;&#x2009;10&#x2009;mm, who did not undergo CNB, potentially sparing 45 benign patients from overtreatment. Notably, significant differences emerged in cancer scores between DCIS and invasive ductal carcinoma (p&#x2009;<&#x2009;0.05). Higher cancer scores correlated with a more unfavorable prognosis (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: The 103-marker methylation model demonstrates impressive performance in distinguishing between malignant and benign tumors, facilitating precise early diagnosis of BC, and holds promise as a prognostic tool.},
}
@article {pmid40516663,
year = {2025},
author = {Göransson, S and Olofsson, H and Johansson, HJ and Yan, F and Vogiatzakis, C and Liang, S and Bellato, HM and Masvidal, L and Aksoylu, I and Hartman, J and Hajj, GN and Larsson, O and Lehtiö, J and Strömblad, S},
title = {Mechanical control of breast cancer malignancy by promotion of mevalonate pathway enzyme synthesis.},
journal = {Matrix biology : journal of the International Society for Matrix Biology},
volume = {140},
number = {},
pages = {1-15},
doi = {10.1016/j.matbio.2025.05.005},
pmid = {40516663},
issn = {1569-1802},
mesh = {Humans ; *Mevalonic Acid/metabolism ; *Breast Neoplasms/pathology/metabolism/genetics ; Female ; *Mechanotransduction, Cellular ; Extracellular Matrix/metabolism/pathology ; *Hydroxymethylglutaryl-CoA Synthase/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; rac1 GTP-Binding Protein/metabolism/genetics ; Cell Line, Tumor ; Cell Proliferation ; },
abstract = {In breast cancer, mechanotransduction from stiffened extracellular matrix (ECM) drives proliferation and invasion. Here, we use a model of matrix stiffening mimicking progression of breast ductal carcinoma in situ to invasive ductal carcinoma. Quantitative mass spectrometry identified enrichment of ECM-stiffness upregulated mevalonate pathway enzymes, indicating sterol/isoprenoid metabolism reprogramming. Consistently, the first committed mevalonate pathway enzyme, Hydroxymethylglutaryl-CoA Synthase (HMGCS1), was upregulated in human breast cancer specimens and spatially correlated with cross-linked ECM. ECM-stiffness promoted HMGCS1 protein synthesis without corresponding mRNA level alterations, indicating post-transcriptional regulation of mevalonate biosynthesis via microenvironmental mechanical cues to impose rapid metabolic alterations. Moreover, HMGCS1-RNAi blocked the stiffness-driven breast cancer proliferative and invasive phenotype. Mechanistically, mechanotransduction signaling, through integrin and Rac1 to promote HMGCS1 protein expression, drives the breast cancer malignant phenotype. Intriguingly, the Rac1-P29S cancer mutant promoted a malignant phenotype without stiff ECM in a mevalonate-dependent manner. In summary, we define a mechano-responsive pathway controlling mevalonate pathway enzyme synthesis that drives breast cancer malignant behaviors.},
}
@article {pmid40513789,
year = {2025},
author = {Kavazis, C and Ekmektzoglou, A and Kokolakis, A and Liappis, T and Douganiotis, G and Natsiopoulos, I},
title = {The role of PIK3CA mutation in lobular breast cancer in the era of precision oncology - A systematic review.},
journal = {Critical reviews in oncology/hematology},
volume = {214},
number = {},
pages = {104805},
doi = {10.1016/j.critrevonc.2025.104805},
pmid = {40513789},
issn = {1879-0461},
mesh = {Humans ; *Class I Phosphatidylinositol 3-Kinases/genetics ; *Breast Neoplasms/genetics/diagnosis ; *Mutation ; Female ; *Carcinoma, Lobular/genetics/diagnosis ; Prognosis ; Precision Medicine/methods ; },
abstract = {BACKGROUND: Ιnvasive lobular carcinoma (ILC) is a distinct subtype of breast cancer with unique clinical and molecular features. Although ILC generally responds to endocrine therapy, it tends to exhibit lower chemotherapy sensitivity, underscoring the need for tailored therapeutic approaches. PIK3CA mutations are frequently observed in ILC. This systematic review evaluates the prevalence of PIK3CA mutations in ILC and examines their prognostic and predictive significance.<br><br>METHODS: We searched PubMed and Scopus for studies reporting PIK3CA mutations in lobular breast cancer. Inclusion criteria encompassed studies on stage I-III ILC examining mutation frequency, prognosis, or predictive value. Data on mutation prevalence in ILC (and comparisons to invasive ductal carcinoma, IDC) and associated outcomes were extracted. Meta-analyses were performed with assessment of heterogeneity and publication bias.<br><br>RESULTS: Ten relevant studies (nine cohorts) were included. The prevalence of PIK3CA mutations in ILC ranged from &#x223c;30&#x202f;% to &#x223c;50&#x202f;%. Statistic analysis showed that nearly half of ILCs harbor PIK3CA mutations. Mutation rates in ILC were generally higher than in IDC. No significant association between PIK3CA mutation status and patient prognosis was observed in the available studies. There were limited data ontreatment response.<br><br>CONCLUSIONS: PIK3CA is a commonly mutated gene in ILC, but current evidence does not demonstrate a clear impact on prognosis or definite predictive value for therapy response in this subtype. Nonetheless, the high mutation frequency provides a rationale for targeted therapeutic approaches. PIK3CA testing may be considered in advanced ILC to identify candidates for PI3K inhibitor therapy, although further research is needed.},
}
@article {pmid40507963,
year = {2025},
author = {Zeiringer, S and Derler, M and Mussbacher, M and Kolesnik, T and Fröhlich, E and Leitinger, G and Kolb, D and Tutz, S and Vargas, C and Keller, S and Roblegg, E},
title = {Immune Modulation with Nanodiscs: Surface Charge Dictates Cellular Interactions and Activation of Macrophages and Dendritic-like Cells.},
journal = {International journal of molecular sciences},
volume = {26},
number = {11},
pages = {},
pmid = {40507963},
issn = {1422-0067},
mesh = {Humans ; *Dendritic Cells/immunology/drug effects/metabolism/cytology ; *Macrophages/immunology/drug effects/metabolism/cytology ; *Cell Communication/drug effects/immunology ; *Nanostructures/chemistry ; Cytokines/metabolism ; Lipid Bilayers/chemistry ; Reactive Oxygen Species/metabolism ; Cell Survival/drug effects ; },
abstract = {The immunological barrier is among the most significant barriers in vivo. Macrophages and dendritic cells play a crucial role in immune responses, involving phagocytosis, antigen presentation, and triggering adaptive responses. Nanoscale drug-delivery vehicles, such as polymer-encapsulated lipid-bilayer nanodiscs, are of particular interest in the development of new therapeutic approaches, but require well-characterized human in vitro cell models. To this end, the present study differentiated human monocytes into two distinct states, resting macrophages and immature dendritic-like cells (iDCs). These cells served as model systems to assess the efficacy of lipid-bilayer nanodiscs encapsulated by anionic glyco-DIBMA (diisobutylene-maleic acid) or electroneutral sulfo-DIBMA polymers. Nanodisc-cell interaction studies-including cell viability, reactive oxygen species production, cytokine release, particle uptake, and activation marker expression-demonstrated that immune responses depend sensitively on the cell type and polymer and thus on the surface charge of the nanodiscs. Sulfo-DIBMA nanodiscs induced minimal immune cell activation, accompanied by cytokine release and reduced uptake of the nanodiscs by immune cells. In contrast, glyco-DIBMA nanodiscs exhibited increased interactions with cells, elicited pro-inflammatory immune responses, and promoted iDC maturation. This involved co-stimulatory and antigen-presenting molecules, potentially leading to T-cell activation. These findings underscore the potential of glyco-DIBMA nanodiscs to modulate immune responses through receptor-specific interactions, paving the way for immunotherapeutic strategies.},
}
@article {pmid40484435,
year = {2025},
author = {Iurillo, AM and Abraham, O and McQuillan, J and Newton, E},
title = {Treatment of breast cancer in a patient with sickle cell disease.},
journal = {BMJ case reports},
volume = {18},
number = {6},
pages = {},
doi = {10.1136/bcr-2024-263661},
pmid = {40484435},
issn = {1757-790X},
mesh = {Humans ; Female ; *Breast Neoplasms/therapy/complications/pathology ; *Anemia, Sickle Cell/complications/therapy ; *Carcinoma, Ductal, Breast/therapy/complications/pathology ; Adult ; Trastuzumab/therapeutic use ; Neoadjuvant Therapy/methods ; Chemotherapy, Adjuvant ; Mastectomy, Modified Radical ; Aromatase Inhibitors/therapeutic use ; },
abstract = {We present a woman in her 30s with sickle cell disease (SCD) treated with monthly exchange transfusions who had suffered cerebrovascular complications, presented with a 4-cm left breast mass and was ultimately diagnosed with Estrogen receptor-positive, human epidermal growth factor receptor 2 positive (ER+HER2/Neu+) invasive ductal carcinoma with axillary metastasis. She was treated with neoadjuvant trastuzumab-based chemotherapy, followed by a left-modified radical mastectomy and had residual invasive disease. She received postmastectomy radiation followed by adjuvant trastuzumab emtansine. Given the ER positivity, she also began adjuvant ovarian suppression (OS) and an aromatase inhibitor (AI). Throughout treatment, her SCD remained well-controlled, highlighting the potential for effective and tolerable cancer therapy in patients with SCD and the importance of interdisciplinary collaboration. This case underscores the importance of tailored oncological management and the need for further research on chemotherapy safety in this population.},
}
@article {pmid40478792,
year = {2025},
author = {Li, H and Luo, M and Luo, W and Li, H and Cong, S},
title = {Integrated decision-control for social robot autonomous navigation considering nonlinear dynamics model.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0324341},
pmid = {40478792},
issn = {1932-6203},
mesh = {*Robotics/methods ; *Nonlinear Dynamics ; Humans ; Algorithms ; Reward ; Decision Making ; Reinforcement, Psychology ; Walking ; },
abstract = {Reinforcement learning (RL) has demonstrated significant potential in social robot autonomous navigation, yet existing research lacks in-depth discussion on the feasibility of navigation strategies. Therefore, this paper proposes an Integrated Decision-Control Framework for Social Robot Autonomous Navigation (IDC-SRAN), which accounts for the nonlinearity of social robot model and ensures the feasibility of decision-control strategy. Initially, inverse reinforcement learning (IRL) is employed to tackle the challenge of designing pedestrian walking reward. Subsequently, the Four-Mecanum-Wheel Robot dynamic model is constructed to develop IDC-SRAN, resolving the issue of dynamics mismatch of RL system. The actions of IDC-SRAN are defined as additional torque, with actual torque and lateral/longitudinal velocities integrated into the state space. The feasibility of the decision-control strategy is ensured by constraining the range of actions. Furthermore, a critical challenge arises from the state delay caused by model transient characteristics, which complicates the articulation of nonlinear relationships between states and actions through IRL-based rewards. To mitigate this, a driving-force-guided reward is proposed. This reward guides the robot to explore more appropriate decision-control strategies by expected direction of driving force, thereby reducing non-optimal behaviors during transient phases. Experimental results demonstrate that IDC-SRAN achieves peak accelerations approximately 8.3% of baseline methods, significantly enhancing the feasibility of decision-control strategies. Simultaneously, the framework enables goal-oriented autonomous navigation through active torque modulation, attaining a task completion rate exceeding 90%. These outcomes further validate the intelligence and robustness of the proposed IDC-SRAN.},
}
@article {pmid40470417,
year = {2025},
author = {Matsuo, T and Tanaka, T and Shien, T and Muraoka, A and Doihara, H},
title = {Detailed Ophthalmic and Pathological Features of Choroidal Metastasis From Breast Cancer: A Case Series of Five Patients.},
journal = {Cureus},
volume = {17},
number = {5},
pages = {e83484},
pmid = {40470417},
issn = {2168-8184},
abstract = {Breast cancer causes choroidal metastases on rare occasions. This study presented the eye manifestations of choroidal metastases from breast cancer and their response to treatments in detail as well as their pathological correlation in five patients. The patients' age at the diagnosis of breast cancer ranged from 24 to 69 years (median: 37 years). The time from the diagnosis of breast cancer to the detection of metastases was concurrent in one patient, two years later in three patients, and six years later in the other patient. The time from the detection of systemic metastases to the detection of choroidal metastases was the same in one patient, while it ranged from one to seven years later in four patients. Choroidal metastases were in the unilateral eye of four patients, whereas they were in both eyes of one patient. Choroidal metastases manifested as one or a few nodular or flat choroidal lesions with serous retinal detachment. As for the treatment of choroidal metastases, enucleation of the right eye was chosen based on the patient's wish as well as the family's wish in the earliest patient when cancer notification was not the norm in Japan. In the other four patients, whole-eye radiation was performed to reduce the choroidal metastatic lesions. As regards the prognosis, which was available in four patients, three patients died within one year from the diagnosis of choroidal metastases, while one patient died one year and eight months later. Regarding the pathology of breast cancer, which was available in four patients, immunostaining of the preserved enucleated eye in the earliest patient revealed that breast cancer cells in the choroidal metastatic lesion were positive for estrogen receptor and negative for progesterone receptor and human epidermal growth factor receptor 2 (HER2). Invasive ductal carcinoma in two patients was positive for estrogen receptor and negative for HER2, while invasive ductal carcinoma in the other patient was triple-negative for estrogen receptor, progesterone receptor, and HER2 with a high Ki-67 index. In conclusion, the prognosis for life was poor in patients with breast cancer who developed choroidal metastases. Choroidal metastatic lesions showed a response to whole-eye radiation to improve the quality of vision at the end of life. Vision-related symptoms should be monitored in the course of chemotherapy for systemic metastases.},
}
@article {pmid40469556,
year = {2025},
author = {Suzuki, A and Komiya, T and Fujita, H and Shimada, K and Nonaka, M and Hanano, M and Takeishi, M and Ishikawa, T and Matsumura, H},
title = {Surgical Site Infection Owing to Mycobacterium mageritense After Immediate Breast Reconstruction Using a Deep Inferior Epigastric Perforator Flap.},
journal = {Plastic and reconstructive surgery. Global open},
volume = {13},
number = {6},
pages = {e6823},
pmid = {40469556},
issn = {2169-7574},
abstract = {Mycobacterium mageritense is a rare, rapidly growing, nontuberculosis mycobacterium that belongs to type IV of the rapidly growing mycobacteria. These bacteria are found in soil and water, and cause localized skin and soft tissue infections; however, they are challenging to culture, leading to diagnostic delays. To our knowledge, there have been 12 reported cases of surgical site infections (SSIs) caused by M. mageritense, with only 2 cases following breast reconstruction. A 51-year-old woman underwent nipple-sparing mastectomy and immediate breast reconstruction using a deep inferior epigastric perforator flap for invasive ductal carcinoma of the left breast. One month after surgery, she developed an SSI caused by M. mageritense. Despite initial outpatient treatment, the infection persisted, requiring multiple hospitalizations, administration of intravenous antibiotics, and several debridements under general anesthesia. Negative pressure wound therapy and a coordinated approach among various medical specialties are essential for managing infections. The patient experienced side effects from prolonged antibiotic use but eventually exhibited no signs of infection recurrence. This case highlights the challenges in diagnosing and treating M. mageritense SSIs, emphasizing the need for comprehensive surgical and medical management, together with patient-centered care, to effectively manage long-term treatment.},
}
@article {pmid40455366,
year = {2025},
author = {Qiu, X and Tian, B and Gu, Y and Yin, K and Zhao, J and Wang, J},
title = {Novel nomograms for predicting overall survival and cancer-specific survival in invasive lobular carcinoma of the breast.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {984},
pmid = {40455366},
issn = {2730-6011},
support = {TRYJ2021JC18//Screening and preliminary functional analysis of specific metabolites of breast malignant tumors/ ; },
abstract = {PURPOSE: Currently, the clinical diagnosis and treatment for invasive lobular carcinoma of the breast (ILC) often draw on the treatment approaches used for invasive ductal carcinoma (IDC), despite significant differences between the two. Studies evaluating the risk and prognosis of ILC are limited; thus, our goal was to construct a predictive model for the prognosis of ILC.<br><br>METHODS: Clinical data of patients diagnosed with unilateral primary ILC from 2010 to 2015 were acquired from the SEER database. Independent prognostic factors affecting patients' overall survival (OS) and cancer-specific survival (CSS) were determined through univariate and multivariate analyses based on COX proportional hazards model and Fine-Gray competing risks model. Nomograms were constructed to forecast the 1-year, 3-year, and 5-year OS and CSS of the patients.<br><br>RESULTS: A total of 6,616 patients with ILC were included, with 1,083 deaths, of which 541 were attributed to ILC, and 542 to other causes. The univariate and multivariate analyses indicated that age, N stage, stage, surgery, PR status, radiotherapy, and brain metastasis are independent risk factors for OS of ILC patients, while age, N stage, stage, surgery, PR status, and brain metastasis are independent risk factors for CSS of ILC patients. The C-index, area under the ROC curve, and calibration curve of the 1-, 3-, and 5-year OS and CSS prediction models confirmed that it had good predictive capability.<br><br>CONCLUSIONS: This study has developed subtype-specific predictive models for OS and CSS of patients with ILC, offering clinicians a regimen. Reference for assessing patient prognosis and formulating individualized treatment.},
}
@article {pmid40449850,
year = {2025},
author = {Dubois, C and Chesnel, C and Teng, M and Vivier, M and Noël, C and Amarenco, G and Hentzen, C},
title = {Effect on sensory and motor parameters of a first intradetrusor botulinum neurotoxin A injection in patients with neurogenic bladder: A retrospective study.},
journal = {The French journal of urology},
volume = {35},
number = {8},
pages = {102914},
doi = {10.1016/j.fjurol.2025.102914},
pmid = {40449850},
issn = {2950-3930},
mesh = {Humans ; Retrospective Studies ; *Botulinum Toxins, Type A/administration &amp; dosage/therapeutic use ; Female ; Male ; Middle Aged ; *Urinary Bladder, Neurogenic/drug therapy/physiopathology/etiology ; Adult ; *Neuromuscular Agents/administration &amp; dosage ; *Urinary Bladder, Overactive/drug therapy/etiology/physiopathology ; Urodynamics/drug effects ; Aged ; Urinary Bladder/drug effects/innervation/physiopathology ; Injections, Intramuscular ; Administration, Intravesical ; Treatment Outcome ; },
abstract = {BACKGROUND: Overactive bladder (OAB) is common in suprasacral neurological disorders and often associated with detrusor overactivity (DO). Botulinum neurotoxin A (BoNT-A) is a second-line treatment inducing reversible chemical denervation. While its motor effects are well documented, its impact on sensory parameters in neurogenic bladder dysfunction remains poorly understood.<br><br>AIM: To evaluate sensory and motor bladder changes following BoNT-A injection in neurogenic DO (NDO).<br><br>METHOD: This retrospective single-center study included patients with NDO who received a first BoNT-A injection (from 2015 to 2024). Urodynamic assessments were performed pre- and 2-6months post-injection. Changes in OAB symptoms and urodynamic parameters were analyzed, including sensory (first desire to void [FDV], strong desire to void [SDV]), and motor parameters (DO occurrence, volume at first involuntary detrusor contraction (IDC)).<br><br>RESULTS: Among 90 patients (mean age 50.4&#xb1;15.6years, 61% female, 53 with multiple sclerosis, 35 with spinal cord injury), urgency and urgency urinary incontinence significantly decreased (from 84% to 52% and from 80% to 42%, respectively; P<0.001). DO occurrence declined from 97% to 42% (P<0.001). Bladder sensations (FDV and SDV) persisted in 84% of patients but were significantly delayed.<br><br>CONCLUSION: BoNT-A is an effective treatment for neurogenic overactive bladder in multiple sclerosis and spinal cord injury, improving both urgency and urinary incontinence. Its clinical efficacy is associated with resolution of detrusor overactivity, alongside with sensory changes. Preserved but delayed filling sensations after treatment suggests that BoNT-A may modulate afferent signaling. However, whether its clinical benefits are primarily driven by sensory modulation or motor inhibition remains uncertain.},
}
@article {pmid40439394,
year = {2025},
author = {Khan, L and Khan, M and Shakeel, F and Ali, T and Hina, M and Arif, A and Rahim Sarfaraz, F and Tariq, M and Hafiz, A and Qureshi, BM and Abbasi, AN and Ali, N},
title = {Effect of DIBH Coaching on Dosimetric Parameters of Heart and Lung Doses in Patients Undergoing Adjuvant Breast Radiotherapy.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {26},
number = {5},
pages = {1809-1813},
pmid = {40439394},
issn = {2476-762X},
mesh = {Humans ; Female ; Middle Aged ; *Heart/radiation effects ; Radiotherapy, Adjuvant/adverse effects/methods ; *Lung/radiation effects ; *Unilateral Breast Neoplasms/radiotherapy ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Dosage ; *Organs at Risk/radiation effects ; *Breath Holding ; Follow-Up Studies ; *Mentoring/methods ; Adult ; *Breast Neoplasms/radiotherapy ; *Radiation Injuries/prevention &amp; control/etiology ; Prognosis ; },
abstract = {INTRODUCTION: Radiation exposure to the heart in women with left-sided breast cancer can lead to cardiac disease and increased mortality. Several techniques, including deep inspiration breath hold (DIBH), have been used to reduce cardiac exposure during radiotherapy. DIBH coaching prior to radiation planning can further reduce cardiac doses. This study aims to compare heart and lung dosimetric parameters between coached and non-coached patients using the DIBH technique for left-sided breast cancer treatment.<br><br>METHODS: All patients with left-sided breast cancer who received adjuvant radiotherapy (RT) using the DIBH were included. The first cohort, designated as the non-coached group, received verbal guidance on the breath hold technique but did not undergo formal coaching. The second cohort involved a comprehensive coaching protocol, which began in January 2022. This protocol, led by a physician, included demonstrations and instructions for performing the DIBH technique in the clinic and encouraged patients to practice at home before and during RT to optimize cardiac protection.<br><br>RESULTS: A total of 40 patients met the inclusion criteria for the study, with a mean age of 45.7 &#xb1; 8.38 years. Most patients had IDC and Stage II disease, and radiation was primarily delivered using 3DCRT with 4256 cGy in 16 fractions regimes. In terms of cardiac dose exposure, coached patients had slightly lower mean and maximum point cardiac doses, but these differences were not statistically significant. Coached patients also had a significantly lower mean V17 for left lung volume exposure compared to non-coached patients (18.3 vs. 21.6, p < 0.05).<br><br>CONCLUSION: DIBH coaching and home practice prior to RT planning can further reduce cardiac and lung doses, offering a cost-effective intervention, particularly in resource-limited settings, though further controlled studies with larger sample sizes and longer follow-up are needed to assess its clinical impact.},
}
@article {pmid40437613,
year = {2025},
author = {Zheng, Y and Tang, H and Liu, Q and Zhang, Y and Zhao, P and Zhang, S and Wang, C},
title = {Mutational analysis and protein expression of PI3K/AKT pathway in four mucinous cystadenocarcinoma of the breast.},
journal = {Diagnostic pathology},
volume = {20},
number = {1},
pages = {68},
pmid = {40437613},
issn = {1746-1596},
support = {81672606//National Natural Science Foundation of China/ ; ZR2022MH206//Natural Science Foundation of Shandong Province/ ; },
mesh = {Humans ; Female ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Middle Aged ; *Cystadenocarcinoma, Mucinous/genetics/pathology ; *Breast Neoplasms/genetics/pathology ; DNA Mutational Analysis ; Mutation ; *Biomarkers, Tumor/genetics/analysis ; Aged ; Adult ; *Phosphatidylinositol 3-Kinases/metabolism/genetics ; Signal Transduction ; Immunohistochemistry ; High-Throughput Nucleotide Sequencing ; },
abstract = {INTRODUCTION: Primary mucinous cystadenocarcinoma of the breast (BMCA) is a rare neoplasm with few reports in the literature. Its molecular characteristics, prognosis, and treatment protocols are not well understood, and there is a lack of consensus concerning the optimal management of this condition.<br><br>METHODS: Four cases of clinical and pathological data were collected from 2018 to 2024. Next generation sequencing with a 654 cancer-associated gene panel was utilized to detect gene mutations. Immunohistochemistry was carried out to evaluate protein expression levels.<br><br>RESULTS: Firstly, we combined clinical imaging examinations and IHC to exclude the possibility of metastasis from ovarian or pancreatic origins. BMCA was composed of cystically dilated ducts lined by tall columnar mucin-containing epithelium. The morphological spectrum of MCA varied from MCA alone to MCA combined with carcinoma in situ (CIS) to MCA associated with invasive ductal carcinoma (IDC). ER/PR/HER2 and CK20 were all negative, while CK7 and GATA3 were positive by IHC in four cases. Although the prognosis of the other three patients was favorable during the follow-up periods of 13, 10, and 3 months, respectively, case 2# experienced a recurrence of the primary focus after 42 months. No lymphatic metastasis was identified in cases 1-4#. In addition, next-generation sequencing (NGS) identified 17 mutated genes and 25 mutation sites in four cases. TP53, PIK3CA, AKT, PTEN, and RB1 were the highest frequency mutated genes. Given that AKT mutations typically refer to AKT1(E17K) rather than AKT2 or AKT3, AKT protein expression was detected only in Case 2# (AKT1, E17K). PTEN protein was expressed in case 4# (corresponded to missense mutation), loss of PTEN expression were corresponding with splicing mutation in case1#. In brief, AKT and PTEN protein expression could be corresponded to gene mutation in a certain extent. However, PIK3CA protein expression was positive in Case 2# but negative in Case 1#, which did not fully accordance with the NGS-detected missense mutations. No associated germline variations were detected. Additionally, neither PDL-1 expression nor microsatellite instability-high (MSI-H) status was identified.<br><br>CONCLUSION: The tumorigenesis and development of BMCA may be regulated to the PI3K/AKT pathway. Consequently, a comprehensive genetic analysis of more cases could elucidate the molecular mechanisms underlying this rare tumor.},
}
@article {pmid40433185,
year = {2025},
author = {Rezaianzadeh, A and Hosseini-Bensenjan, M and Sephidbakht, S and Haghpanah, S and Khosravizadegan, Z and Asmarian, N and Ramzi, M},
title = {Bayesian Spatial Analysis of the Incidence Rate of Patients with Breast Cancer in Southern Iran.},
journal = {Iranian journal of medical sciences},
volume = {50},
number = {5},
pages = {316-323},
pmid = {40433185},
issn = {1735-3688},
mesh = {Humans ; *Breast Neoplasms/epidemiology ; Female ; Iran/epidemiology ; Incidence ; Bayes Theorem ; Adult ; Spatial Analysis ; Middle Aged ; Registries/statistics &amp; numerical data ; Cohort Studies ; Risk Factors ; Aged ; },
abstract = {BACKGROUND: In the female population, breast cancer is the most common cancer and a leading cause of cancer death. This study was designed to investigate the geographical pattern of breast cancer risk in different counties of Fars province in the south of Iran from 2001 to 2018.<br><br>METHODS: In this historical cohort study, data of Shiraz Population-Based Cancer Registry between 2001 and 2018 was used. The geographical variations of breast cancer incidence rate in 36 counties of Fars province were analyzed using the Bayesian spatiotemporal model.<br><br>RESULTS: Overall, the averages of relative risk (RR), temporal trend (TT), and &#x3b4;i for breast cancer were 1.59, 1.025, and 0.00 in the total female population; 1.21, 1.002, and 0.00 in the young female population (under 40 years of age); and 1.54, 1.02, and 0.00 in the female population with invasive ductal carcinoma (IDC), respectively. The steady increase in RR of breast cancer and IDC during 2001-2018 was observed in most counties located in the non-central part of the Fars geographic map. Moreover, a steady increase of young breast cancer RR was observed mainly in southern regions and some northern cities of Fars province.<br><br>CONCLUSION: Between 2001 and 2018 in Fars province, a steady annual increase of approximately 2% was observed in the total female population for all types of breast cancer, including IDC. High-risk areas, TTs, and changing patterns of breast cancer incidence were determined in this region. Furthermore, areas with a high risk of young breast cancer were identified, which requires special attention.},
}
@article {pmid40418704,
year = {2025},
author = {Hassan, F and Zhang, H and Idiaquez, DW and Pakasticali, N and Hyjek, E and Hussaini, M},
title = {KRAS may facilitate transformation of chronic lymphocytic leukemia to histiocytic sarcoma with indeterminate dendritic cell features.},
journal = {American journal of clinical pathology},
volume = {164},
number = {2},
pages = {157-162},
doi = {10.1093/ajcp/aqaf041},
pmid = {40418704},
issn = {1943-7722},
mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/pathology/genetics ; *Histiocytic Sarcoma/pathology/genetics ; Male ; Aged ; *Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; *Dendritic Cells/pathology ; *Cell Transformation, Neoplastic/pathology/genetics ; Mutation ; Biomarkers, Tumor/genetics ; },
abstract = {OBJECTIVE: We sought to investigate the molecular mechanism underlying transformation of chronic lymphocytic leukemia (CLL) to histiocytic sarcoma (HS) with indeterminate dendritic cell (IDC) features.<br><br>METHODS: Extensive NGS-based genomic profiling was performed on samples of a patient who had CLL, secondary HS with IDC features, and CMML. Clonotypic evaluation of VDJ rearrangement status was performed to confirm clonal relatedness.<br><br>RESULTS: HS is a rare proliferation of malignant tissue histiocytes that is usually primary, although secondary HS exists and often demonstrates mutations in the Ras/Raf/MAPK or PI3K/AKT/mTOR pathways, but HS with indeterminate dendritic cell (IDC) features has not been previously reported. A 77-year-old man with chronic lymphocytic leukemia (CLL) presented with an oropharyngeal mass. Biopsy specimen showed large atypical histiocytic cells with oval-to-irregular indented nuclei. They were positive for CD33, CD4, CD68 (subset, weak), CD163 (subset, weak), BCL6, S100 (subset), CD1a, cyclin D1 (subset), and lysozyme (weak) but negative for Langerin, BRAF V600E, CD21, CD23, CD35, CD123, TCF4, TCL1, MPO, CD20, CD79a, CD10, MUM1, and BCL2. The patient was diagnosed with secondary HS with IDC features as well as chronic myelomonocytic leukemia (CMML) in the bone marrow. Careful genomic dissection of all 3 types of malignant cells showed that SF3B1 p.E622D was present in both CLL and HS but not CMML. In addition, the HS acquired KRAS p.G13D, which we hypothesize drove the transdifferentiation of CLL to HS. Moreover, next-generation sequencing (NGS) clonotypic evaluation of variable-diversity-joining (VDJ) rearrangements in both the HS and CLL established relatedness but not the CMML.Conclusion: This is the first report of secondary HS with IDC features arising from CLL. We establish by both IGH NGS analysis and mutational profiling that the CLL and HS are clonally-related and posit that acquisition of KRAS p.G13D drove transdifferentiation. This has therapeutic implications for targeting the RAS-BRAF-MAPK-ERK pathway.},
}
@article {pmid40407816,
year = {2025},
author = {Lu, D and Han, Y and Xu, R and Wang, C and Qin, M and Shi, J and Ye, F and Zhang, J and Luo, Z and Wang, Y and Lin, H and Jia, P and Zhu, J and Wang, C},
title = {Respiratory transmission potential of severe fever with thrombocytopenia syndrome bunyavirus: evidence from intranasal exposure in a humanized mouse model.},
journal = {Emerging microbes &amp; infections},
volume = {14},
number = {1},
pages = {2511134},
pmid = {40407816},
issn = {2222-1751},
mesh = {Animals ; Mice ; *Severe Fever with Thrombocytopenia Syndrome/transmission/virology/pathology/immunology ; Disease Models, Animal ; Humans ; *Phlebovirus/physiology/pathogenicity ; Lung/pathology/virology ; Administration, Intranasal ; Female ; },
abstract = {Severe Fever with Thrombocytopenia Syndrome Bunyavirus (SFTSV) is a highly lethal pathogen with expanding endemic regions in Asia. While primarily transmitted by ticks, recent evidence suggests potential airborne transmission, raising significant public health concerns. This study investigates the potential for respiratory transmission and pathogenesis using humanized NCG mice inoculated with SFTSV via subcutaneous injection challenge (SIC) or intranasal drop challenge (IDC). Both groups demonstrated rapid systemic dissemination, marked by viremia, weight loss, and multi-organ injury, with hemorrhagic manifestations observed in high-dose infection groups. Histopathological evaluations revealed lung pathology in the intranasal drop challenge mice, including extensive alveolar disruption and inflammatory cell infiltration. Transcriptomic analyses further confirmed that respiratory route inoculation resulted in heightened expression of inflammatory signalling pathways such as IL-17 and NF-κB, potentially contributing to severe local immunopathology. Subcutaneous infection provoked an earlier systemic immune response, with significant upregulation of antigen-processing genes in peripheral blood mononuclear cells. Nevertheless, both routes ultimately culminated in widespread injury to the liver, spleen, kidney, highlighting the systemic nature of SFTSV pathogenesis. These findings underscore the need for preventive strategies addressing respiratory spread.},
}
@article {pmid40406802,
year = {2025},
author = {Kumar, SV and Kishore Singh, B and Gopal Madakshira, M and Kumar, V and Kumar Mishra, S and Sati, A and V Kumar, N},
title = {Fluorodeoxyglucose positron emission tomography - computed tomography (FDG PET-CT) negative orbital metastasis secondary to breast carcinoma: a diagnostic pitfall.},
journal = {Orbit (Amsterdam, Netherlands)},
volume = {44},
number = {6},
pages = {815-820},
doi = {10.1080/01676830.2025.2507374},
pmid = {40406802},
issn = {1744-5108},
mesh = {Humans ; Female ; *Fluorodeoxyglucose F18 ; *Breast Neoplasms/pathology/diagnostic imaging ; *Orbital Neoplasms/secondary/diagnostic imaging/radiotherapy ; *Positron Emission Tomography Computed Tomography ; *Radiopharmaceuticals ; Magnetic Resonance Imaging ; Adult ; *Carcinoma, Lobular/diagnostic imaging/secondary/radiotherapy ; *Carcinoma, Ductal, Breast/diagnostic imaging/secondary ; Biopsy ; },
abstract = {Orbital metastases from breast carcinoma are uncommon and often present diagnostic challenges. Fluorodeoxyglucose positron emission tomography - computed tomography (FDG PET-CT) is widely used in oncologic imaging, but may fail to detect small or metabolically inactive orbital lesions. We report a 41 -year-old female with a history of hormone receptor-positive invasive lobular breast carcinoma who presented with a painless progressive swelling of the lower eyelid and proptosis over 3 months. Magnetic resonance imaging (MRI) orbit revealed a lesion in the inferolateral aspect of the left lower eyelid and extraconal compartment of the left orbit. FDG PET-CT did not demonstrate any metabolic activity in the orbit. A biopsy was performed, confirming metastatic breast carcinoma. The patient underwent external beam radiotherapy directed at the eyelid and orbital region, resulting in a favorable clinical response. This case illustrates the limitations of FDG PET-CT in detecting orbital metastasis from breast carcinoma, particularly in lobular subtypes ,and emphasizes the importance of correlating imaging with clinical suspicion and biopsy in such clinical scenarios.Abbreviations: FDG PET-CT= Fluorodeoxyglucose positron emission tomography - computed tomography, MRI= Magnetic resonance imaging,ILC= Invasive lobular carcinoma, IDC= Invasive ductal carcinoma.},
}
@article {pmid40394843,
year = {2025},
author = {Raeisi, N and Saber Tanha, A and Jafari Zarrin Ghabaei, F and Barashki, S and Aryana, K},
title = {Favorable Palliative Effect of 177 Lu-FAPI-2286 in Two Breast Cancer Patients With Refractory Bone Pains.},
journal = {Clinical nuclear medicine},
volume = {50},
number = {9},
pages = {e564-e567},
doi = {10.1097/RLU.0000000000005753},
pmid = {40394843},
issn = {1536-0229},
mesh = {Female ; Humans ; *Bone Neoplasms/secondary/complications/radiotherapy ; *Breast Neoplasms/pathology/complications ; *Lutetium/therapeutic use ; *Pain/complications ; *Palliative Care ; Radioisotopes/therapeutic use ; },
abstract = {We present 2 women with advanced invasive ductal carcinoma who developed skeletal metastases despite extensive treatment, including surgery, chemotherapy, and hormonal therapy. Both patients experienced debilitating pain and were evaluated for bone palliation therapy using 177 Lu-FAPI-2286, after 99m Tc-FAPI-46 scintigraphy showed suitable uptake. Remarkably, both patients reported significant pain relief shortly after treatment. The only adverse effect noted was grade III thrombocytopenia in 1 patient. These cases highlight the potential of 177 Lu-FAPI-2286 in providing rapid and effective palliation for breast cancer patients suffering from refractory pain, suggesting further investigation into its role in theranostics and palliative care. In this report, we also conducted a comprehensive literature review on radio-ligand therapy with 177 Lu-FAPI in breast cancer.},
}
@article {pmid40389885,
year = {2025},
author = {Ndlovu, AK and Kasvosve, I and Rantshabeng, PS and Sharma, K and Govender, D and Naidoo, R},
title = {Female breast cancer classification using immunohistochemistry biomarkers staining in Botswana.},
journal = {BMC cancer},
volume = {25},
number = {1},
pages = {893},
pmid = {40389885},
issn = {1471-2407},
support = {PhD Scholarship//University of Botswana, Human resources/ ; },
mesh = {Humans ; Female ; Botswana/epidemiology ; *Breast Neoplasms/classification/pathology/metabolism ; *Biomarkers, Tumor/metabolism ; Immunohistochemistry/methods ; Middle Aged ; Retrospective Studies ; Adult ; Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {Breast cancer remains the most diagnosed cancer among women world-wide and a leading cause of cancer-related deaths accounting for 15% of deaths in 2018. Worldwide, the incidence increased from 1.4 million in 2011 to over 2 million in 2018 with a concomitant increase in mortality from 458,400 to 626,679 in the same period. Low- and middle-income countries, such as Botswana, have a disproportionate burden of breast cancer incidence and mortality and there is an urgent need to characterise the unique tumour molecular profiles that may be influencing mortality in these populations. Methods A retrospective study of 125 archived mastectomy specimens (from 2006 to 2009) from women with breast cancer in Botswana was conducted. We determined molecular characteristics of breast cancers by carrying out four immunohistochemistry (IHC)classification (PR, ER, HER2 receptors and Ki 67), cytokeratin 5/6 and EGFR1.Statistical software STATA and SPSS were used to determine the relationship between histology, IHC of biomarkers of interest. Results Out of 125 breast cancer tissues, the distribution of molecular subtypes were as follows: Luminal A (44/125; 35.2%), Luminal B (and TNBC (23/125; 18,4%), HER2 Enriched (17/125; 13.6%), and Luminal B HER2 Enriched (9/125; 7.2%), Basal (9/125; 7.2%), and CK5/6 was expressed by 12.8% (16/125) of tumours. Furthermore 6% of the tumours were basal positive luminal tumours. Morphological 76% of tumours were IDC-NOS and 24% were special type, majority were grade 2 (40%) followed by grade 1(30.4%), grade 3 (23.2%) was and mucinous types were 6.4%. Clinical staging and tumour involvement data were incomplete. Conclusion The discovery of basal positive luminal breast tumours in women from Botswana original not accounted for in the four distinct molecular subtype calls for an expanded antibody panel 6-IHC panel) in order to stratify women of African descent patients into good/poor prognostic groups. Characterising tumour subtypes will better inform optimal therapeutic regimens for women with breast cancer in Botswana.},
}
@article {pmid40386043,
year = {2025},
author = {Han, Y and Hu, X and Xiong, H and Zeng, L and Peng, Y and Su, T},
title = {CEP55 as a prognostic indicator and a predictive marker in oral squamous cell carcinoma.},
journal = {International journal of medical sciences},
volume = {22},
number = {10},
pages = {2446-2459},
pmid = {40386043},
issn = {1449-1907},
mesh = {Humans ; *Mouth Neoplasms/pathology/immunology/mortality/genetics/diagnosis ; *Biomarkers, Tumor/metabolism/genetics ; *Cell Cycle Proteins/metabolism/genetics ; Prognosis ; Female ; Male ; Middle Aged ; *Carcinoma, Squamous Cell/pathology/immunology/mortality/genetics ; Gene Expression Regulation, Neoplastic ; Aged ; *Squamous Cell Carcinoma of Head and Neck/pathology/immunology/mortality/genetics ; Lymphocytes, Tumor-Infiltrating/immunology ; Immunohistochemistry ; *Nuclear Proteins/metabolism ; },
abstract = {Objective: To investigate the role of CEP55 in the occurrence and development of oral squamous cell carcinoma (OSCC). Materials and Methods: Through the utilization of the online OSCC database and bioinformatic analysis, we examine CEP55 expression and its correlation with prognosis, pathways, and immune infiltration. CEP55 and other biomarkers were stained using immunohistochemical methods in 57 cases of OSCC and 44 cases of adjacent paired tissues, demonstrating the clear involvement of CEP55. Results: The expression levels of CEP55 were significantly higher in OSCC tissues compared to normal tissues. Additionally, higher levels of CEP55 were associated with a worse prognosis. CEP55 expression levels were significantly higher in OSCC tissues compared to normal tissues. Additionally, higher levels of CEP55 were associated with a worse prognosis. GSEA results indicated a correlation between CEP55 and the cell cycle. Immunohistochemical staining revealed a significant positive correlation between CEP55 and cell cycle-related protein markers (PCNA, P16, P21, and P53). Furthermore, CEP55 was found to significantly inhibit tumor immune infiltration. As a result, CEP55 expression decreased infiltration of 9 types of immune cells (iDC, mast cells, pDC, DC, Th17 cells, TFH, Treg, T cells, and neutrophils), while increasing infiltration of only 3 types of immune cells (Tcm, T Helper cells, and Th2 cells). Conclusion: The results suggest that CEP55 plays a crucial role in the progression of OSCC promoting cell cycle progression and suppressing immune infiltration.},
}
@article {pmid40376199,
year = {2025},
author = {Bian, Y and Song, C and Nie, Y and Shen, X and Hui, F and Yu, G},
title = {Breast cancer metastasis to the nasopharynx: A case report.},
journal = {Oncology letters},
volume = {30},
number = {1},
pages = {331},
pmid = {40376199},
issn = {1792-1082},
abstract = {Breast cancer is a leading cause of cancer-related mortality in women, with metastasis posing a significant clinical challenge. However, spread to the nasopharynx and nasal cavity is exceptionally rare. The current study presents the case of a 53-year-old woman diagnosed with invasive ductal carcinoma of the right breast, which later metastasized to the nasopharynx. Despite undergoing modified radical mastectomy, chemotherapy and endocrine therapy, the patient developed symptoms indicative of distant metastasis. The present study reviews the diagnostic and therapeutic approaches for such rare occurrences, offering insights into effective management. The study analyzes this case alongside previously reported instances with the aim of enhancing awareness and facilitating early detection and intervention.},
}
@article {pmid40350661,
year = {2025},
author = {Farzan, JJ and Guart, JA and Kulkarni, N and Roberts, S and De la Cruz-Ku, G and Czerniach, DR and Dinh, KH},
title = {Managing Necrotizing Soft-Tissue Infection in Breast Cancer: A Case of Emergency Toilet Mastectomy.},
journal = {The American journal of case reports},
volume = {26},
number = {},
pages = {e946669},
pmid = {40350661},
issn = {1941-5923},
mesh = {Humans ; Female ; *Breast Neoplasms/surgery/complications/pathology ; Aged ; *Mastectomy/methods ; *Carcinoma, Ductal, Breast/surgery/complications ; *Soft Tissue Infections/surgery/etiology ; Debridement ; Necrosis ; },
abstract = {BACKGROUND This case report presents a rare instance of advanced breast cancer presenting with superimposed necrotizing soft-tissue infection (NSTI) and sepsis, uniquely managed with an emergency toilet mastectomy. Toilet mastectomies have become increasingly rare and controversial in modern surgical oncology and are generally limited to palliative indications. This report contributes to the limited literature on NSTI of the breast in the setting of malignancy and highlights the potential utility of toilet mastectomy as a palliative option for carefully selected patients with advanced breast cancer complicated by infection. CASE REPORT A 71-year-old woman presented with a large fungating right breast mass after 50 years of receiving no health care. She was septic, with clinical signs of NSTI. Emergency surgical intervention involved a toilet mastectomy with extensive debridement. Histopathological analysis confirmed high-grade invasive ductal carcinoma of the breast with skin involvement, ER/PR-positive, HER2-negative, pT4bN0Mx. Cultures were consistent with type 1 NSTI. The postoperative course was complicated, requiring prolonged ICU care, multiple debridements, and advanced wound management. Significant complications included septic shock, acute kidney injury, and wound dehiscence. CONCLUSIONS This case is notable for 3 key aspects: (1) NSTI and sepsis are rare but serious complications of advanced breast cancer, underscoring the need for clinicians to maintain a high index of suspicion for this condition; (2) timely and aggressive management of NSTI, regardless of its association with underlying malignancy, is critical for reducing morbidity and mortality; and (3) toilet mastectomy, although less commonly performed today, remains an appropriate palliative intervention in select cases.},
}
@article {pmid40340873,
year = {2025},
author = {Gao, Y and Ali, H and Hu, Z and Sun, H},
title = {Sarcoid-like Reaction in Breast Cancer Tumor Bed and Axillary Lymph Nodes Following Neoadjuvant Chemotherapy: A Case Report.},
journal = {Annals of clinical and laboratory science},
volume = {55},
number = {2},
pages = {281-285},
pmid = {40340873},
issn = {1550-8080},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy/surgery ; *Neoadjuvant Therapy/adverse effects ; *Lymph Nodes/pathology ; Axilla/pathology ; Middle Aged ; Lymphatic Metastasis ; *Sarcoidosis/pathology ; *Carcinoma, Ductal, Breast/drug therapy/pathology ; },
abstract = {Although granulomatous change is not commonly seen in breast cancer tumor bed and/or lymph node after neoadjuvant chemotherapy (NCT), they may mimic lymph node metastasis or tumor progression or recurrence. We present a case of diffuse sarcoid-like reaction (SLR) developed in both the breast tumor bed and axillary lymph nodes after NCT. A postmenopausal Hispanic woman presented with a 11.4 cm left breast mass with swollen lymph nodes in her left axilla. A core biopsy of the breast mass was performed, leading to the diagnosis of grade 3 invasive ductal carcinoma. The tumor is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receoptor-2 overexpression. The patient received NCT with three cycles of doxorubicin and cyclophosphamide, followed by weekly paclitaxel for 12 weeks. After NCT, the tumor in her left breast significantly reduced in size, but the lymph nodes remained swollen. She subsequently underwent left modified radical mastectomy. Histological examination of the treated tumor bed revealed residual invasive tumor with frequent non-caseating granulomatous change. The granulomatous reaction was also seen in several axillary lymph nodes, of which only one had residual metastatic tumor cells. Idiopathic granulomatous mastitis, sarcoidosis, and infective etiologies were excluded based on the patient's medical history, imaging, and histological findings. We report a case of localized SLR in response to NCT in breast cancer tumor bed and axillary lymph nodes. Recognizing this feature is important to avoid misdiagnosis and overtreatment of SLR as residual cancer.},
}
@article {pmid40314919,
year = {2025},
author = {Takano, Y and Mizuno, K and Iwase, M and Morita, S and Torii, N and Kikumori, T and Ando, Y},
title = {Tumor mutational burden status and clinical characteristics of invasive lobular carcinoma of the breast.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {32},
number = {4},
pages = {816-825},
pmid = {40314919},
issn = {1880-4233},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality ; Middle Aged ; *Carcinoma, Lobular/genetics/pathology ; *Biomarkers, Tumor/genetics ; Mutation ; *Carcinoma, Ductal, Breast/genetics/pathology ; Aged ; Adult ; Tumor Burden/genetics ; Prognosis ; Retrospective Studies ; },
abstract = {BACKGROUND: High tumor mutational burden (TMB-H) is an established biomarker for a favorable response to immune checkpoint inhibitors. However, tumor mutational burden (TMB) in invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) has not been sufficiently investigated.<br><br>METHODS: We collected data of patients with ILC or IDC from the Center for Cancer Genomics and Advanced Therapeutics database between June 2019 and August 2023. Furthermore, we examined the clinicopathological factors and TMB status.<br><br>RESULTS: Patients with ILC (n&#x2009;=&#x2009;170) had a median TMB score of 4.00 mut/Mb (interquartile range, 2.00-7.14 mut/Mb), whereas those with IDC (n&#x2009;=&#x2009;2598) had a score of 3.90 mut/Mb (2.00-6.00 mut/Mb). TMB-H was more common in patients with ILC than in those with IDC (18.2% vs. 10.1%, P&#x2009;<&#x2009;0.001), particularly in the ER+&#x2009;/HER2-&#x2009;subtype. Multivariate analysis revealed that the pathological diagnosis of ILC (P&#x2009;=&#x2009;0.006), tissue samples collected from metastatic sites (P&#x2009;<&#x2009;0.001), and older age (50&#xa0;years, P&#x2009;<&#x2009;0.001) were independent factors for TMB-H.<br><br>CONCLUSIONS: Patients with ILC were more likely to have TMB-H than those with IDC. The findings of this study would be invaluable in selecting treatment strategies for patients with ILC.},
}
@article {pmid40269494,
year = {2025},
author = {Nakamura, S and Fujii, K and Sakai, M and Sakai, K and Hanazawa, H and Nishimura, K and Notohara, K and Yamaguchi, K and Itasaka, S},
title = {Arm-Behind-the-Back Position for Breast Cancer Radiotherapy in Patients with Lupus Erythematosus and Shoulder Arthropathy: A Case Report.},
journal = {The American journal of case reports},
volume = {26},
number = {},
pages = {e946674},
pmid = {40269494},
issn = {1941-5923},
mesh = {Humans ; Female ; *Breast Neoplasms/radiotherapy/complications/surgery ; Adult ; *Lupus Erythematosus, Systemic/complications ; *Carcinoma, Ductal, Breast/radiotherapy/complications/surgery ; *Shoulder Joint ; *Patient Positioning/methods ; *Radiotherapy, Conformal/methods ; },
abstract = {BACKGROUND When 3-dimensional conformal radiation therapy (3DCRT) for postoperative breast cancer is performed in the supine position, patients are required to raise their arms to spare the arms from the irradiation field. However, patients with collagen vascular disease can experience severe joint symptoms. CASE REPORT A 43-year-old woman with a history of systemic lupus erythematosus (SLE) 10 years ago received a diagnosis of invasive ductal carcinoma of the left breast. Breast-conserving surgery and sentinel lymph node biopsy were performed. The pathological stage was IA. Physical and immunological examinations indicated that SLE disease activity was stable preoperatively and postoperatively. She had difficulty holding her left arm in a raised position because of arthritis related to SLE and steroid therapy. For postoperative radiation therapy, we developed an arm-behind-the-back position, in which a platform was placed between the patient's body and couch. In this position, the patient's arm was lowered behind the back, such that the arm did not interfere with the irradiation field of 3DCRT. The treatment plan achieved an acceptable homogeneity index, low dose to the lungs and heart, and no problematic hotspots. Although the time required for position matching and irradiation tended to be longer than that in the regular supine position, scheduled irradiation was safely completed. Grade 2 radiation dermatitis was observed. The patient showed no signs of local recurrence or distant metastases after 15 months. No radiation pneumonitis was observed. CONCLUSIONS The ingenuity of positioning can achieve radiotherapy in patients with collagen vascular disease and shoulder joint symptoms.},
}
@article {pmid40262013,
year = {2025},
author = {Young, R and Zaworski, E and Hart, M and Grewe, B and Liang, E and Pierpont, Y},
title = {Sarcoidosis Masquerading as Breast Implant- Associated Anaplastic Large Cell Lymphoma - The Importance of Definitive Pathology to Guide Therapy.},
journal = {WMJ : official publication of the State Medical Society of Wisconsin},
volume = {124},
number = {1},
pages = {71-73},
pmid = {40262013},
issn = {2379-3961},
mesh = {Humans ; Female ; Middle Aged ; Carcinoma, Ductal, Breast/surgery ; Breast Neoplasms/surgery ; *Breast Implants/adverse effects ; Mammaplasty/adverse effects/instrumentation ; *Postoperative Complications/diagnosis/etiology/pathology ; *Lymphoma, Large-Cell, Anaplastic/diagnosis ; *Sarcoidosis/diagnosis/etiology/pathology ; Diagnosis, Differential ; *Seroma/diagnosis/etiology/pathology ; },
abstract = {INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare critical outcome of breast implantation that typically presents 8 to 10 years after textured-implant placement with periprosthetic seroma. Treatment consists of implant removal and capsulectomy, which is typically curative. But in rare case, malignant infiltration through the capsule results in disseminated disease, necessitating aggressive treatment with systemic chemotherapy. Sarcoidosis, a chronic systemic granulomatous disease characterized by noncaseating granulomas, is another rare cause of periprosthetic seroma.<br><br>CASE PRESENTATION: A 61-year-old female with a history of invasive ductal carcinoma of the breast status post textured implant-based reconstruction presented with late periprosthetic seroma and overlying rash. Cytology of seroma aspirate was suggestive of BIA-ALCL, and positron emission tomography-computed tomography was concerning for invasive disease. Surgical specimen pathology of the implant-capsule complex and skin punch biopsy of the overlying rash revealed only granulomatous inflammation. The patient was diagnosed with sarcoidosis and spared systemic chemotherapy treatment for disseminated BIA-ALCL.<br><br>CONCLUSIONS: BIA-ALCL should be ruled out in all cases of late periprosthetic seroma. Definitive surgical pathology is necessary to prevent misdiagnosis and inappropriate treatment of masquerading entities, such as sarcoidosis.},
}
@article {pmid40237521,
year = {2025},
author = {Irazoki, A and Frank, E and Pham, TCP and Braun, JL and Ehrlich, AM and Haid, M and Riols, F and Hansen, CHF and Jørgensen, AR and Andersen, NR and Hidalgo-Corbacho, L and Meneses-Valdes, R and Ali, MS and Raun, SH and Modvig, JL and Gallero, S and Larsen, S and Gerhart-Hines, Z and Jensen, TE and Rohm, M and Treebak, JT and Fajardo, VA and Sylow, L},
title = {Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses to Cancer in Mice.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {16},
number = {2},
pages = {e13781},
pmid = {40237521},
issn = {2190-6009},
support = {0169-00013B//Independent Research Fund Denmark/ ; 101108282//European Union's Horizon program, Marie Sk&#x142;odowska-Curie Actions/ ; R449-2023-1468//Lundbeck Foundation/ ; NNF23SA0084103//Novo Nordisk Foundation/ ; /ERC_/European Research Council/International ; 949017//European Union's Horizon 2020 research and innovation program/ ; },
mesh = {Animals ; Mice ; *Cachexia/etiology/metabolism ; *Temperature ; *Housing, Animal ; *Neoplasms/complications/metabolism ; Disease Models, Animal ; Male ; Thermogenesis ; Female ; },
abstract = {BACKGROUND: Cancer cachexia, affecting up to 80% of patients with cancer, is characterized by muscle and fat loss with functional decline. Preclinical research seeks to uncover the molecular mechanisms underlying cachexia to identify potential targets. Housing laboratory mice at ambient temperature induces cold stress, triggering thermogenic activity and metabolic adaptations. Yet, the impact of housing temperature on preclinical cachexia remains unknown.<br><br>METHODS: Colon 26 carcinoma (C26)-bearing and PBS-inoculated (Ctrl) mice were housed at standard (ST; 20&#xb0;C-22&#xb0;C) or thermoneutral temperature (TN; 28&#xb0;C-32&#xb0;C). They were monitored for body weight, composition, food intake and systemic factors. Upon necropsy, tissues were weighed and used for evaluation of ex&#xa0;vivo force and respiration, or snap frozen for biochemical assays.<br><br>RESULTS: C26 mice lost 7.5% body weight (p&#x2009;=&#x2009;0.0001 vs. Ctrls), accounted by decreased fat mass (-35%, p&#x2009;<&#x2009;0.0001 vs. Ctrls), showing mild cachexia irrespective of housing temperature. All C26 mice exhibited reduced force (-40%, p&#x2009;<&#x2009;0.0001 vs. Ctrls) and increased atrogene expression (3-fold, p&#x2009;<&#x2009;0.003 vs. Ctrls). Cancer altered white adipose tissue (WAT)'s functional gene signature (49%, p&#x2009;<&#x2009;0.05 vs. Ctrls), whereas housing temperature reduced brown adipose tissue (BAT)'s (-78%, p&#x2009;<&#x2009;0.05 vs. ST Ctrl). Thermogenic capacity measured by Ucp1 expression decreased upon cancer in both WAT and BAT (-93% and -63%, p&#x2009;<&#x2009;0.0044 vs. Ctrls). Cancer-driven glucose intolerance was noted at ST (26%, p&#x2009;=&#x2009;0.0192 vs. ST Ctrl), but restored at TN (-23%, p&#x2009;=&#x2009;0.005 vs. ST C26). Circulating FGF21, GDF-15 and IL-6 increased in all C26 mice (4-fold, p&#x2009;<&#x2009;0.009 vs. Ctrls), with a greater effect on IL-6 at TN (76%, p&#x2009;=&#x2009;0.0018 vs. ST C26). Tumour and WAT Il6 mRNA levels remained unchanged, while cancer induced skeletal muscle (SkM) Il6 (2-fold, p&#x2009;=&#x2009;0.0016 vs. Ctrls) at both temperatures. BAT Il6 was only induced in C26 mice at TN (116%, p&#x2009;=&#x2009;0.0087 vs. ST C26). At the bioenergetics level, cancer increased SkM SERCA ATPase activity at ST (4-fold, p&#x2009;=&#x2009;0.0108 vs. ST Ctrl) but not at TN. In BAT, O2 consumption enhanced in C26 mice at ST (119%, p&#x2009;<&#x2009;0.03 vs. ST Ctrl) but was blunted at TN (-44%, p&#x2009;<&#x2009;0.0001 vs. ST C26). Cancer increased BAT ATP levels regardless of temperature (2-fold, p&#x2009;=&#x2009;0.0046 vs. Ctrls), while SERCA ATPase activity remained unchanged at ST and decreased at TN (-59%, p&#x2009;=&#x2009;0.0213 vs. TN Ctrl).<br><br>CONCLUSIONS: In mild cachexia, BAT and SkM bioenergetics are susceptible to different housing temperatures, which influences cancer-induced alterations in glucose metabolism and systemic responses.},
}
@article {pmid40234077,
year = {2025},
author = {Ajmani, A and Witheiler, DW and Kivelevitch, D},
title = {Carcinoma erysipeloides secondary to male breast cancer in a patient with BRCA1 and BRCA2 mutations: a clinical presentation and management.},
journal = {BMJ case reports},
volume = {18},
number = {4},
pages = {},
doi = {10.1136/bcr-2024-264429},
pmid = {40234077},
issn = {1757-790X},
mesh = {Humans ; Male ; *Breast Neoplasms, Male/genetics/pathology/drug therapy/complications ; *Carcinoma, Ductal, Breast/genetics/drug therapy/pathology ; Aged, 80 and over ; BRCA1 Protein/genetics ; Germ-Line Mutation ; BRCA2 Protein/genetics ; *Skin Neoplasms/secondary/genetics/drug therapy/pathology ; },
abstract = {We report a rare case of carcinoma erysipeloides (CE) in a man in his 80s. The patient exhibited a 15 year history of progressive nodularity over the right areola, accompanied by violaceous erythema extending from the right chest to both the right and left abdomen. The diagnostic workup confirmed invasive ductal carcinoma beneath the areola, intralymphatic carcinoma consistent with CE involving the regional skin and metastatic involvement of a single lymph node. The tumour tested positive for oestrogen and progesterone receptors but negative for HER2; genetic testing revealed the patient harboured germline mutations for BRCA1 and BRCA2. Oncology initiated anastrozole and palbociclib treatment, resulting in objective improvement in his breast cancer and his CE. This case highlights a unique presentation of male breast cancer with CE in the context of BRCA mutations and underscores the importance of genetic evaluation and tailored treatment in men with familial breast cancer syndromes.},
}
@article {pmid40214389,
year = {2025},
author = {Kumar, W and Lohia, S and Agrawal, A and Yadav, V},
title = {A rare case of synchronous cervical squamous cell carcinoma and invasive ductal carcinoma of breast.},
journal = {Journal of cancer research and therapeutics},
volume = {21},
number = {1},
pages = {281-283},
doi = {10.4103/jcrt.jcrt_2653_23},
pmid = {40214389},
issn = {1998-4138},
mesh = {Humans ; Female ; *Uterine Cervical Neoplasms/pathology/diagnosis/therapy ; Middle Aged ; *Neoplasms, Multiple Primary/pathology/diagnosis ; *Carcinoma, Squamous Cell/pathology/diagnosis/therapy ; *Breast Neoplasms/pathology/diagnosis ; *Carcinoma, Ductal, Breast/pathology/diagnosis/therapy ; },
abstract = {Multiple primary neoplasms in the same patient can be of synchronous and metachronous types and are related to common etiologies and common genetic factors. We present a case report of 56-year-old female with the synchronous primary of breast and cervix and the unique challenges we faced in the management. Breast and cervical malignancies have contrasting risk factors and hence lies the significance of this synchronous presentation. The only identifiable commonality lies in the STK gene. We also present a review of the literature regarding similar presentations and a discussion on the possible source of origin of such a unique scenario.},
}
@article {pmid40213483,
year = {2024},
author = {Garcia-Peiro, JI and Guerrero-López, P and Hornos, F and Hueso, JL and Garcia-Aznar, JM and Santamaria, J},
title = {The Pattern of Copper Release in Copper-Based Nanoparticles Regulates Tumor Proliferation and Invasiveness in 3D Culture Models.},
journal = {Small science},
volume = {4},
number = {12},
pages = {2400206},
pmid = {40213483},
issn = {2688-4046},
abstract = {Cancer is a leading cause of death worldwide. Glioblastoma (GBM) is a major challenge in oncology due to its highly invasive nature and limited treatment options. GBM's aggressive migration beyond tumor margins and rapid tumor growth hinders success in patient treatment. Localized therapeutic delivery, such as the use of transition metals like copper, is highlighted as a novel therapeutic agent for many potential biomedical applications. Herein, it is aimed to study the effects of Cu release on the proliferation and invasiveness of cancer cells. To this end, novel copper-based nanostructures with different release patterns are designed. Using a complex 3D cell culture model to mimic the tumor microenvironment, it is shown that different patterns of copper ion release have a strong impact on GBM progression and invasiveness. The findings highlight the importance of optimizing localized copper release patterns to tailor different tumor treatment strategies. They also show the potential and suitability of 3D microchips as instruments to study the behavior of tumor spheroids. In spite of their limitations, these 3D microdevices enable a controlled and close monitoring of the influence of environmental factors (such as the presence of Cu ions) on the proliferation and invasiveness of the cells, with a better approach to reality compared to 2D models and with a more controlled environment, compared to an in vivo model.},
}
@article {pmid40203054,
year = {2025},
author = {Trombley, J and Rakozy, AI and McClear, CA and Jash, E and Csankovszki, G},
title = {Condensin IDC, DPY-21, and CEC-4 maintain X chromosome repression in C. elegans.},
journal = {PLoS genetics},
volume = {21},
number = {4},
pages = {e1011247},
pmid = {40203054},
issn = {1553-7404},
support = {P40 OD010440/OD/NIH HHS/United States ; R35 GM149543/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; *Caenorhabditis elegans/genetics ; *X Chromosome/genetics ; *Caenorhabditis elegans Proteins/genetics/metabolism ; Dosage Compensation, Genetic/genetics ; *Adenosine Triphosphatases/genetics/metabolism ; *Multiprotein Complexes/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Male ; Histones/metabolism/genetics ; Genes, X-Linked ; Gene Expression Regulation, Developmental ; Female ; },
abstract = {Dosage compensation in Caenorhabditis elegans equalizes X-linked gene expression between XX hermaphrodites and XO males. The process depends on a condensin-containing dosage compensation complex (DCC), which binds the X chromosomes in hermaphrodites to repress gene expression by a factor of 2. Condensin IDC and an additional five DCC components must be present on the X during early embryogenesis in hermaphrodites to establish dosage compensation. However, whether the DCC's continued presence is required to maintain the repressed state once established is unknown. Beyond the role of condensin IDC in X chromosome compaction, additional mechanisms contribute to X-linked gene repression. DPY-21, a non-condensin IDC DCC component, is an H4K20me2/3 demethylase whose activity enriches the repressive histone mark, H4 lysine 20 monomethylation, on the X chromosomes. In addition, CEC-4, a protein that tethers H3K9me3-rich chromosomal regions to the nuclear lamina, also contributes to X-linked gene repression. To investigate the necessity of condensin IDC during the larval and adult stages of hermaphrodites, we used the auxin-inducible degradation system to deplete the condensin IDC subunit DPY-27. While DPY-27 depletion in the embryonic stages resulted in lethality, DPY-27 depleted larvae and adults survive. In these DPY-27 depleted strains, condensin IDC was no longer associated with the X chromosome, the X became decondensed, and the H4K20me1 mark was gradually lost, leading to X-linked gene derepression (about 1.4-fold). These results suggest that the stable maintenance of dosage compensation requires the continued presence of condensin IDC. A loss-of-function mutation in cec-4, in addition to the depletion of DPY-27 or the genetic mutation of dpy-21, led to even more significant increases in X-linked gene expression (about 1.7-fold), suggesting that CEC-4 helps stabilize repression mediated by condensin IDC and H4K20me1.},
}
@article {pmid40189767,
year = {2025},
author = {Kawata, C and Terakawa, H and Kurokawa, Y and Ohe, Y and Mohri, R and Hirata, M and Kitahara, T and Moriyama, H and Kinoshita, J and Kawashima, H and Inaki, N},
title = {[A Case of Advanced Breast Cancer with Axillary Lymph Node Metastasis Complicated by Neurofibromatosis Type 1].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {52},
number = {3},
pages = {255-257},
pmid = {40189767},
issn = {0385-0684},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/complications/drug therapy ; Middle Aged ; *Neurofibromatosis 1/complications ; Axilla ; Lymphatic Metastasis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Lymph Node Excision ; },
abstract = {The patient was a 55-year-old woman who had been diagnosed with neurofibromatosis type 1(NF1)since she was young. A 50 mm mass with skin changes was palpated on the outside of the left breast. As a result of a detailed examination of the whole body, invasive ductal carcinoma of Luminal B like was observed, and cT4N1M0, Stage ⅢB left breast cancer was diagnosed. After preoperative chemotherapy, total left mastectomy and axillary lymph node dissection were performed. NF1 is an autosomal overt inherited disease characterized by multiple neurofibromas and pigment spots. It is called von Recklinghausen disease, and it is said that there are many complications of malignant tumors such as breast cancer, mainly nervous system tumors. In breast cancer complicated by NF1, there is a high rate of diagnosis as advanced cancer due to delayed awareness of breast masses due to unique skin lesions and a tendency to refrain from visiting medical institutions or medical examinations due to latent shame about appearance. In this study, we report 1 case of advanced breast cancer complicated by NF1.},
}
@article {pmid40189766,
year = {2025},
author = {Mizuyama, Y and Takashima, T},
title = {[A Case of Pulmonary Tuberculosis Developed During Neoadjuvant Chemotherapy for HER2-Enriched Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {52},
number = {3},
pages = {252-254},
pmid = {40189766},
issn = {0385-0684},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/surgery/chemistry ; *Neoadjuvant Therapy/adverse effects ; Aged ; *Tuberculosis, Pulmonary/drug therapy/etiology ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; *Receptor, ErbB-2/analysis ; *Carcinoma, Ductal, Breast/drug therapy/surgery ; Antitubercular Agents/therapeutic use ; },
abstract = {In the 1990s, the number of newly registered tuberculosis patients in Japan was about 40,000 per year. It has been gradually decreasing and the number of new patients became 10,235 in 2022 with the incidence rate of 8.2 per 100,000 population. However it is still occasionally encountered even in recent years. Herein, we report a case of human epidermal growth factor receptor 2(HER2)-enriched breast cancer patient developed pulmonary tuberculosis just after finishing neoadjuvant chemotherapy and was successfully treated for both disease simultaneously. A 68 years old woman presented due to right breast mass was diagnosed with hormonal receptor-negative, HER2-positive invasive ductal carcinoma. Neoadjuvant chemotherapy with paclitaxel, trastuzumab and pertuzumab was started. After 12 courses of chemotherapy, CT scan revealed disappearance of the right breast tumor and infiltrating shadow in the left lower lung field. Sputum polymerase chain reaction test for tuberculosis was positive. Anti-tuberculosis chemotherapy was started. Four days after starting isoniazid, partial mastectomy was performed under local anesthesia and radiation therapy for the breast was omitted. There are no signs of recurrence of breast cancer and pulmonary tuberculosis for 5 years. Chemotherapy for breast cancer and premedication with corticosteroid may have inhibited cellular immunity, causing endogenous relapse of tuberculosis.},
}
@article {pmid40186732,
year = {2025},
author = {Stamey, T and Armel, K and Ju, AW and Chen, S and Navaid, M and Bhatt, A and Larkins, MC},
title = {Treatment outcomes and comparative survival analysis of intraductal carcinoma of the prostate.},
journal = {International urology and nephrology},
volume = {57},
number = {10},
pages = {3143-3149},
pmid = {40186732},
issn = {1573-2584},
mesh = {Humans ; Male ; *Prostatic Neoplasms/mortality/therapy ; Aged ; Treatment Outcome ; Middle Aged ; Survival Rate ; Survival Analysis ; *Carcinoma, Intraductal, Noninfiltrating/mortality/therapy ; SEER Program ; Retrospective Studies ; Prostatectomy ; },
abstract = {PURPOSE: Intraductal carcinoma of the prostate is a rare subset of prostate cancer, for which no consensus treatment guidelines exist. We seek to investigate treatment and survival outcomes for IDC-P in the context of current NCCN guidelines.<br><br>METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with intraductal carcinoma of the prostate diagnosed between 2000 and 2020. Cox regression analysis and log-rank comparisons of both overall and cause-specific survival over 5- and 10-year timeframes were conducted.<br><br>RESULTS: 945 patients were identified. Cox regression analysis demonstrated treatment with unimodal surgery (hazard ratio (HR)&#x2009;=&#x2009;3.70, p&#x2009;=&#x2009;0.005) was associated with decreased 10-year cause-specific survival, while unimodal treatment with radiotherapy was associated with decreased 5- and 10-year overall survival (HR&#x2009;=&#x2009;2.14, p&#x2009;=&#x2009;0.025; HR&#x2009;=&#x2009;2.16, p&#x2009;=&#x2009;0.005, respectively). Univariate survival subanalysis of treatment regimens demonstrated decreased 5-year cause-specific (p&#x2009;=&#x2009;0.004) and overall (p&#x2009;=&#x2009;0.019) survival among patients that received only radiotherapy as treatment. Radical prostatectomy alone was non-inferior to radical prostatectomy with adjuvant radiotherapy in the context of 10-year overall survival (90% vs 80%; p&#x2009;=&#x2009;0.58).<br><br>CONCLUSION: Differences in both 5- and 10-year overall survival and cause-specific survival were present among patients diagnosed with IDC-P. Treatment with unimodal radiotherapy among patients with IDC-P was associated with decreased survival compared to treatment with radical prostatectomy&#x2009;&#xb1;&#x2009;adjuvant radiotherapy, while radical prostatectomy alone was non-inferior to radical prostatectomy with adjuvant radiotherapy. Further research into the risk stratification and optimal treatment of these patients is warranted.},
}
@article {pmid40156779,
year = {2024},
author = {Arinola, G and Onifade, AA and Adigun, K and Oshingbesan, MB},
title = {Review of immune-metabolic studies and re-purposed treatments of Nigerian COVID-19 patients: A pointer to mild, gender- and age-based status of admitted patients.},
journal = {Nigerian journal of physiological sciences : official publication of the Physiological Society of Nigeria},
volume = {39},
number = {2},
pages = {177-183},
doi = {10.54548/njps.v39i2.2},
pmid = {40156779},
issn = {0794-859X},
mesh = {Humans ; *COVID-19/immunology/metabolism/therapy/epidemiology ; Nigeria/epidemiology ; *COVID-19 Drug Treatment ; SARS-CoV-2 ; Age Factors ; Antiviral Agents/therapeutic use ; Sex Factors ; Female ; Male ; },
abstract = {When Severe Acute Respiratory human Coronavirus 2 (SARS-hCOV 2) infection began in December 2019, detailed knowledge about the virus was lacking. This included non-availability of anti-viral treatment or vaccine, no knowledge of virus-human interaction, and lack of prognostic factors for stages of illness among others. A publication in Nigerian Journal of Physiological Sciences (2020). 35: 20-25 titled "Immune Responses During Human Coronavirus Infection: Suggestions For Future Studies" adduced investigations into immune parameters of COVID-19 patients so as to throw more light on the immunopathogenesis of SAR-CoV-2 infection, in order to create avenue for the development of vaccines or herd immunity. This present publication is a review of studies carried out on COVID-19 patients in one Infectious Diseases Center (I.D.C), Ibadan, Nigeria as a response to the gaps in knowledge raised in above mentioned publication. Cummulatively, immune-metabolic studies from this IDC revealed mild, age- and sex-dependent status of COVID-19 in patients admitted into this center. Thus, explaining the basis for the effectiveness of adopted re-purposed drugs (chloroquine or hydroxychloroquine, zinc, vitamins C and D and or antibiotics), physiotherapy and nutritional support used for the management of admitted COVID-19 patients. Also, this paper vindicated that inflammation was heightened during SARS-CoV 2 infection; therefore therapeutic interventions to control the inflammatory processes, oxidative stress, antibodies against structural and non-structural proteins or blocks receptor sites were proposed. In addition, development of herd immunity and efficacy of COVID-19 vaccines (Astrazeneca and Moderna) were elucidated in general population. However, study to determine host genetic factors in hCoV infection was lacking. This review concluded that interdisciplinary collaborative approach will be useful in the management of future emerging or re-emerging infection.},
}
@article {pmid40144454,
year = {2025},
author = {Arcanjo, AM and de Souza, AF and de Souza Quedas, EP and de Menezes Correia-Deur, JE and Ferreira, DL and de Almeida Toledo, SP and Lourenço, DM},
title = {Primary hypertrophic osteoarthropathy: phenotypic variability and penetrance rate in heterozygotes for SLCO2A1 variants.},
journal = {JBMR plus},
volume = {9},
number = {4},
pages = {ziaf026},
pmid = {40144454},
issn = {2473-4039},
abstract = {Primary hypertrophic osteoarthropathy (PHO) is a rare autosomal recessive disease caused by pathogenic variants (PVs) in HPGD and SLCO2A1 genes whose phenotypes are, respectively, designated as PHOAR1 and PHOAR2. Recently, a dominant inherited form (PHOAD) was identified in SLCO2A1 heterozygotes whose PHO penetrance is widely unknown, and data on phenotype are markedly limited. Our aim was to reveal the penetrance and extend/refine data on phenotype of SLCO2A1 heterozygotes. Both genes were sequenced using Sanger sequencing. The 4 probands had a typical complete form (CF) of PHO. Mean ages at symptom onset and clinical diagnosis were, respectively, 18.5 ± 2.7 (16-22) years and 22 ± 3.4 (18-26) years. They were homozygotes for SLCO2A1 (p.Q188R, p.C420F, p.A176T; p.G104[*]) PVs; 2 were novel variants. We focused on 14 SLCO2A1 heterozygous screened relatives from 3 families: 5 elderly individuals (mean age: 78 ± 6.7 [72-86] years) of the parental generation were affected, 2 by incomplete form (IF) and 3 with isolated digital clubbing (IDC). Combining our 14 carriers and 33 reported so far, the estimated overall PHO penetrance was 70%, being significantly higher in men (83% vs 50%; p = .024) and individuals carrying truncated SLCO2A1 PVs (88% vs 53%; p = .053). In turn, the periostosis penetrance rate in women was 28% (5/18), including our oldest patient (86 years). In the probands, the predominant phenotypes were CF (64%) and IF (36%). Among screened carriers, phenotypes were IDC (41%) followed by IF and fruste form (FF) (28%, each), whereas IDC and FF were the predominant phenotypes in screened men and women, respectively. As a novelty, we uncovered an incomplete penetrance of PHO in SLCO2A1 heterozygotes, with higher rates in elderly individuals, males, and those with truncated PVs. Regarding phenotype, PHO is more pronounced in males, periostosis is likely more frequent in females than previously documented in PHOAR2, and IDC may represent a distinct clinical feature in SLCO2A1 heterozygotes.},
}
@article {pmid40124702,
year = {2025},
author = {Sahoo, AS and Salman, M and Singh, B and Weston-Petrides, G and Ragad, L and Elayyan, R},
title = {Scout In, Scout out: Savi scout reflector traversing a dilated duct to the nipple in breast cancer localisation-a case report.},
journal = {Oxford medical case reports},
volume = {2025},
number = {3},
pages = {omae196},
pmid = {40124702},
issn = {2053-8855},
abstract = {INTRODUCTION: Savi scout system is being widely used for localising and excising breast tumours. While the migration of scout reflectors has been documented, this is the first case of a Savi Scout reflector migrating through a dilated duct near the lesion and coming out of the nipple.<br><br>CASE PRESENTATION: A 56-year-old postmenopausal woman with a history of right breast intraductal papilloma which transformed to Grade II Invasive Ductal Carcinoma (IDC) has a Savi Scout reflector placed in the tumour. However, it migrated through a dilated duct and emerged at the nipple, causing severe pain. The reflector was then surgically removed, and the patient subsequently underwent wide local excision with skin marker localisation.<br><br>CONCLUSION: Anatomical variations such as presence of dilated ducts need to be considered before placing scout reflectors. Appropriate positioning would prevent them from migrating through such ducts avoiding patient discomfort and further procedures for localisation.},
}
@article {pmid40119428,
year = {2025},
author = {Fortunato, A and Mallo, D and Cisneros, L and King, LM and Khan, A and Curtis, C and Ryser, MD and Lo, JY and Hall, A and Marks, JR and Hwang, ES and Maley, CC},
title = {Evolutionary measures show that recurrence of DCIS is distinct from progression to breast cancer.},
journal = {Breast cancer research : BCR},
volume = {27},
number = {1},
pages = {43},
pmid = {40119428},
issn = {1465-542X},
support = {U2C CA233254/CA/NCI NIH HHS/United States ; U54 CA217376/NH/NIH HHS/United States ; U2C CA233254/NH/NIH HHS/United States ; ADHS18-198847//Arizona Biomedical Research Commission/ ; U54 CA217376/CA/NCI NIH HHS/United States ; BC132057//Congressionally Directed Medical Research Programs/ ; R01 CA140657/CA/NCI NIH HHS/United States ; R21 CA257980/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/genetics/therapy ; *Carcinoma, Intraductal, Noninfiltrating/pathology/genetics/therapy ; Disease Progression ; *Neoplasm Recurrence, Local/pathology/genetics ; Middle Aged ; Exome Sequencing ; Biomarkers, Tumor/genetics ; Aged ; Adult ; Cross-Sectional Studies ; Longitudinal Studies ; Prognosis ; },
abstract = {BACKGROUND: Progression from pre-cancers like ductal carcinoma in situ (DCIS) to invasive disease (cancer) is driven by somatic evolution and is altered by clinical interventions. We hypothesized that genetic and/or phenotypic intra-tumor heterogeneity would predict clinical outcomes for DCIS since it serves as the substrate for natural selection among cells.<br><br>METHODS: We profiled two samples from two geographically distinct foci from each DCIS in both cross-sectional (n&#x2009;=&#x2009;119) and longitudinal cohorts (n&#x2009;=&#x2009;224), with whole exome sequencing, low-pass whole genome sequencing, and a panel of immunohistochemical markers.<br><br>RESULTS: In the longitudinal cohorts, the only statistically significant associations with time to non-invasive DCIS recurrence were the combination of treatment (lumpectomy only vs mastectomy or lumpectomy with radiation, HR 12.13, p&#x2009;=&#x2009;0.003, Wald test with FDR correction), ER status (HR 0.16 for ER+&#x2009;compared to ER-, p&#x2009;=&#x2009;0.0045), and divergence in SNVs between the two samples (HR 1.33 per 10% divergence, p&#x2009;=&#x2009;0.018). SNV divergence also distinguished between pure DCIS and DCIS synchronous with invasive disease in the cross-sectional cohort. In contrast, the only statistically significant associations with time to progression to invasive disease were the combination of the width of the surgical margin (HR&#x2009;0.67 per mm, p&#x2009;=&#x2009;0.043) and the number of mutations that were detectable at high allele frequencies (HR&#x2009;1.30 per 10 SNVs, p&#x2009;=&#x2009;0.02). No predictors were significantly associated with both DCIS recurrence and progression to invasive disease, suggesting that the evolutionary scenarios that lead to these clinical outcomes are markedly different.<br><br>CONCLUSIONS: These results imply that recurrence with DCIS is a clinical and biological process different from invasive progression.},
}
@article {pmid40068648,
year = {2025},
author = {D'Iorio, A and Aiello, EN and Vitale, C and Amboni, M and Verde, F and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B and Santangelo, G},
title = {Diagnostics and Ecological Validity of the Italian Version of the Parkinson's Disease Cognitive Rating Scale.},
journal = {Dementia and geriatric cognitive disorders},
volume = {54},
number = {5},
pages = {347-351},
doi = {10.1159/000545090},
pmid = {40068648},
issn = {1421-9824},
mesh = {Humans ; *Parkinson Disease/psychology/diagnosis/complications ; Male ; Female ; Aged ; Italy ; Middle Aged ; Reproducibility of Results ; *Neuropsychological Tests ; Mental Status and Dementia Tests ; ROC Curve ; *Cognitive Dysfunction/diagnosis ; Sensitivity and Specificity ; Cognition ; },
abstract = {INTRODUCTION: This study aimed to assess the diagnostics and ecological validity of the Parkinson's Disease Cognitive Rating Scale (PD-CRS) within an Italian cohort of non-demented Parkinson's disease (PD) patients.<br><br>METHODS: N = 128 non-demented PD patients were administered the PD-CRS, Montreal Cognitive Assessment (MoCA), and Parkinson's Disease Cognitive Functioning Rating Scale (PD-CFRS). Receiver-operating characteristic analyses were performed to explore the diagnostics of both raw and adjusted PD-CRS scores, by operationalizing the positive state as a below-cut-off MoCA score. Correlational analyses were run to test the ecological validity of the PD-CRS against the PD-CFRS.<br><br>RESULTS: Both raw and adjusted PD-CRS scores accurately identified patients with a defective MoCA scores (AUC = 0.84-0.85), yielding optimal diagnostics. A cut-off of <73.93, as identified on demographically adjusted PD-CRS scores, yielded the best diagnostics (sensitivity = 0.70; specificity = 0.89; positive and negative predictive values = 0.83 and 0.79; positive and negative likelihood ratios: 6.23 and 0.37: number needed for screening utility: 0.78). The PD-CRS was related to the PD-CFRS (rs = -0.24; p = 0.018).<br><br>CONCLUSIONS: The Italian PD-CRS is a diagnostically sound and ecologically valid screener for cognitive impairment in non-demented PD patients.},
}
@article {pmid40055309,
year = {2025},
author = {El Bounkari, O and Zan, C and Yang, B and Ebert, S and Wagner, J and Bugar, E and Kramer, N and Bourilhon, P and Kontos, C and Zarwel, M and Sinitski, D and Milic, J and Jansen, Y and Kempf, WE and Sachs, N and Maegdefessel, L and Ji, H and Gokce, O and Riols, F and Haid, M and Gerra, S and Hoffmann, A and Brandhofer, M and Avdic, M and Bucala, R and Megens, RTA and Willemsen, N and Messerer, D and Schulz, C and Bartelt, A and Harm, T and Rath, D and Döring, Y and Gawaz, M and Weber, C and Kapurniotu, A and Bernhagen, J},
title = {An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {2297},
pmid = {40055309},
issn = {2041-1723},
mesh = {Animals ; *Lipogenesis/genetics ; *Atherosclerosis/metabolism/pathology/genetics ; Mice ; *Liver/metabolism/pathology ; Receptors, CXCR4/metabolism ; Humans ; *Macrophage Migration-Inhibitory Factors/metabolism/genetics ; Male ; *Intramolecular Oxidoreductases/metabolism/genetics ; *Chemokines/metabolism/genetics ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; Antigens, Differentiation, B-Lymphocyte/metabolism ; Signal Transduction ; Hepatocytes/metabolism ; Mice, Knockout ; Apolipoproteins E/genetics ; Histocompatibility Antigens Class II ; },
abstract = {Atherosclerosis is the underlying cause of myocardial infarction and ischemic stroke. It is a lipid-triggered and cytokine/chemokine-driven arterial inflammatory condition. We identify D-dopachrome tautomerase/macrophage migration-inhibitory factor-2 (MIF-2), a paralog of the cytokine MIF, as an atypical chemokine promoting both atherosclerosis and hepatic lipid accumulation. In hyperlipidemic Apoe[-/-] mice, Mif-2-deficiency and pharmacological MIF-2-blockade protect against lesion formation and vascular inflammation in early and advanced atherogenesis. MIF-2 promotes leukocyte migration, endothelial arrest, and foam-cell formation, and we identify CXCR4 as a receptor for MIF-2. Mif-2-deficiency in Apoe[-/-] mice leads to decreased plasma lipid levels and suppressed hepatic lipid accumulation, characterized by reductions in lipogenesis-related pathways, tri-/diacylglycerides, and cholesterol-esters, as revealed by hepatic transcriptomics/lipidomics. Hepatocyte cultures and FLIM-FRET-microscopy suggest that MIF-2 activates SREBP-driven lipogenic genes, mechanistically involving MIF-2-inducible CD74/CXCR4 complexes and PI3K/AKT but not AMPK signaling. MIF-2 is upregulated in unstable carotid plaques from atherosclerotic patients and its plasma concentration correlates with disease severity in patients with coronary artery disease. These findings establish MIF-2 as an atypical chemokine linking vascular inflammation to metabolic dysfunction in atherosclerosis.},
}
@article {pmid40053423,
year = {2025},
author = {Pecora, V and Samynathan, A and Rosenfeld, A and Tariq, Z and Saardi, K},
title = {Cutaneous metastases mimicking hidradenitis suppurativa: a diagnostic challenge.},
journal = {Wounds : a compendium of clinical research and practice},
volume = {37},
number = {2},
pages = {63-67},
doi = {10.25270/wnds/24155},
pmid = {40053423},
issn = {1943-2704},
mesh = {Humans ; *Breast Neoplasms/pathology ; Diagnosis, Differential ; *Hidradenitis Suppurativa/diagnosis/pathology ; *Skin Neoplasms/secondary/diagnosis/pathology ; },
abstract = {BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, and debilitating inflammatory condition characterized by abscesses, comedones, and nodules. The heterogeneous presentation of HS often leads to diagnostic challenges, with clinical mimics such as cutaneous metastases (CMs) being of particular importance. CMs can present as initial manifestations of metastatic disease, necessitating accurate identification to guide potentially lifesaving treatment. However, the diagnostic and therapeutic approaches for HS and CMs differ significantly, underscoring the need for prompt and accurate differentiation.<br><br>CASE REPORT: This report presents 3 cases of primary malignancies in which CMs mimicked HS. Case 1 had diffuse large B-cell lymphoma; case 2 had a history of right breast atypical ductal hyperplasia and borderline low-grade ductal carcinoma in situ, along with triple-negative invasive ductal carcinoma of the left breast with extensive metastasis to the iliac bone and lung; and case 3 had invasive mammary carcinoma of the right breast with axillary lymph node involvement. All 3 patients presented with nodular lesions resembling HS, but further investigation, including molecular testing, confirmed the diagnosis of CMs.<br><br>CONCLUSION: The clinical overlap between HS and CMs, which can present with similar features such as nodules, abscesses, and draining lesions, underscores the critical importance of distinguishing these entities. Despite their similar clinical appearance, HS and CMs have vastly different management protocols. Accurate diagnosis of CMs enables timely and appropriate intervention, which in turn aids in optimizing clinical outcomes and ensuring the use of effective treatment strategies for affected patients.},
}
@article {pmid40042344,
year = {2025},
author = {Raeisi, N and Saber Tanha, A and Aryana, K and Akbari Oryani, M and Barashki, S},
title = {99m Tc-FAPI-46 Uptake in Simultaneous Occurrence of Benign Thyroid Nodule and Mixed-Mucinous-Invasive Ductal Breast Carcinoma.},
journal = {Clinical nuclear medicine},
volume = {50},
number = {5},
pages = {e297-e299},
doi = {10.1097/RLU.0000000000005729},
pmid = {40042344},
issn = {1536-0229},
mesh = {Humans ; Female ; Aged ; *Breast Neoplasms/diagnostic imaging/complications/pathology/metabolism ; *Thyroid Nodule/diagnostic imaging/complications/metabolism ; *Carcinoma, Ductal, Breast/diagnostic imaging/complications ; *Organotechnetium Compounds/metabolism ; Biological Transport ; Positron Emission Tomography Computed Tomography ; Neoplasm Invasiveness ; Radionuclide Imaging ; },
abstract = {We present a case of a 65-year-old woman diagnosed with mixed mucinous-invasive ductal carcinoma, a rare subtype of breast cancer. Utilizing 99m Tc-FAPI-46 scintigraphy, we observed a high target-to-background ratio in the breast mass and metastatic axillary lymph nodes. Notably, a benign follicular nodule was also detected in the thyroid which showed absent 99m Tc-FAPI uptake. Our findings suggest that 99m Tc-FAPI-46 shares similar characteristics with 68 Ga-FAPI and may outperform 18 F-FDG PET/CT in mucinous breast cancer. This case highlights the potential of FAPI as a predictive biomarker for malignancy and its role in benign findings.},
}
@article {pmid40039929,
year = {2024},
author = {Rukhsana, and Khan, WA and Conway, M and Lee, YJ and Khattak, AM},
title = {BCAT2 Expression in IDC Breast Cancer subtypes: A Weighted Feature-Based Approach to Identify and Rank Associated Genes Across Public Datasets.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2024},
number = {},
pages = {1-4},
doi = {10.1109/EMBC53108.2024.10782766},
pmid = {40039929},
issn = {2694-0604},
mesh = {Humans ; *Breast Neoplasms/genetics/classification ; Female ; *Transaminases/genetics/metabolism ; *Gene Expression Regulation, Neoplastic ; *Carcinoma, Ductal, Breast/genetics ; Gene Expression Profiling/methods ; Databases, Genetic ; },
abstract = {It has been observed that breast cancer is associated with dysregulation of several metabolic pathways that produce metabolite addiction, such as the dependence on glutamine for tumor development. These discoveries might be applied to personalized treatment of this heterogeneous illness by employing specific gene expression or metabolites in cancer therapy. BCAT1 and BCAT2 encode the human branched-chain aminotransferase proteins (hBCAT) involved in cellular metabolism process. Here BCAT2 is exploited through weighted feature-based approach to identify and rank associated genes across public datasets of breast cancer invasive ductal carcinoma patients. BCAT2 lower expression was observed to have the worst prognosis, and BCAT2 gene expression which might be associated with triggering the risk, are ranked, and visualized in different subtypes of breast cancer. These findings give a strong clue to further investigate through experimental approach.},
}
@article {pmid40038709,
year = {2025},
author = {Reunanen, VLJ and Jokinen, TS and Lilja-Maula, L and Hytönen, MK and Lappalainen, AK},
title = {Allelic frequency of 12-FGF4RG and the association between the genotype with number of calcified intervertebral discs visible on radiographs in Coton de Tuléar and French Bulldog breeds.},
journal = {BMC veterinary research},
volume = {21},
number = {1},
pages = {140},
pmid = {40038709},
issn = {1746-6148},
mesh = {Animals ; Dogs ; *Dog Diseases/genetics/diagnostic imaging ; *Intervertebral Disc Degeneration/genetics/diagnostic imaging/veterinary ; Genotype ; Male ; Female ; *Gene Frequency ; Retrospective Studies ; Radiography/veterinary ; Intervertebral Disc/diagnostic imaging/pathology ; *Calcinosis/diagnostic imaging/genetics/veterinary ; Breeding ; Prospective Studies ; *Fibroblast Growth Factor 4/genetics ; Intervertebral Disc Displacement ; },
abstract = {BACKGROUND: Intervertebral disc disease (IVDD) is a major welfare issue in chondrodystrophic dogs. It is a consequence of chondroid metaplasia of the nucleus pulposus, leading to premature degeneration and calcification of the intervertebral discs (IVDs). Radiographic grading based on the number of calcified discs visible on radiograph (CDVR) between the ages of 24-48 months is an established method for selective breeding against IVDD in dogs. Premature IVD degeneration has a genetic background, and a FGF4 retrogene insertion on chromosome 12 (12-FGF4RG) has been shown to be involved. The aim of this study was to determine the 12-FGF4RG allele frequency and genotype proportions, and the influence of the 12-FGF4RG genotype on number of CDVR in a study population of young adult Coton de Tuléars and French Bulldogs. In this combined prospective and retrospective analytical study, we investigated dogs radiographically screened at 24-48 months of age. The first dataset consisted of 12-FGF4RG genotyping results of 465 Coton de Tuléars and intervertebral disc calcification (IDC) grading results (no, mild, moderate, or severe) for 222 of them. The second dataset included 12-FGF4RG genotypes and IDC grading results (no or severe) of 81 French Bulldogs.<br><br>RESULTS: We observed 12-FGF4RG homozygous, heterozygous and wildtype individuals in both studied breeds. The 12-FGF4RG allele frequencies were also lower than previously reported in the studied breeds and Coton de Tul&#xe9;ars had lower allele frequency (0.35) than French Bulldogs (0.85). The distribution of IDC grading results were 59% no, 16% mild, 9% moderate and 16% severe in Coton de Tul&#xe9;ars and 59% no and 41% severe in French Bulldogs. In both breeds, every copy of the 12-FGF4RG allele significantly increased the risk for a higher number of CDVR, indicating incomplete dominance.<br><br>CONCLUSIONS: Our results confirm the significant association between the 12-FGF4RG allele and the number of CDVR and IDC grade in two different chondrodystrophic breeds in age-controlled cohorts of young adult dogs. Our results also suggest that radiographic screening of CDVR and genetic testing of 12-FGF4RG could be used to breed against IVD degeneration predisposing to IVDD.},
}
@article {pmid40016543,
year = {2025},
author = {Botty van den Bruele, A and Ren, Y and Thomas, SM and Ntowe, KW and Rosenberger, LH and Menendez, C and Grimm, LJ and Chiba, A and Plichta, JK},
title = {High risk surveillance MRI may not be necessary in BRCA1/2 mutation carriers over 70 years old.},
journal = {Breast cancer research and treatment},
volume = {211},
number = {2},
pages = {421-429},
pmid = {40016543},
issn = {1573-7217},
support = {K12 AR084231/AR/NIAMS NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; P30CA014236/NH/NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/diagnostic imaging/epidemiology/diagnosis/pathology ; Middle Aged ; Aged ; Adult ; *Magnetic Resonance Imaging/methods ; *Mutation ; *BRCA2 Protein/genetics ; *BRCA1 Protein/genetics ; Heterozygote ; Genetic Predisposition to Disease ; Retrospective Studies ; Mammography ; Genetic Testing ; Early Detection of Cancer ; Age Factors ; Genes, BRCA1 ; Genes, BRCA2 ; },
abstract = {BACKGROUND: The risk of developing breast cancer up to age 80 for women with BRCA1/2 mutations is approximately 69-72%. The risk estimates, however, become labile in the later years of life. Many older BRCA1/2 mutation carriers who have not developed breast cancer continue to undergo high-risk surveillance. We evaluated breast cancers in women age ≥ 70 and identified which modality diagnosed the malignancy.<br><br>METHODS: Females with BRCA1/2 mutations identified between 1996 and 2022 were included in this single institution retrospective review. The cohort was divided by age at BRCA1/2 diagnosis (30-59, 60-69 &amp;&#x2009;&#x2265;&#x2009;70). The number of malignancies and imaging modality which led to the diagnosis were recorded.<br><br>RESULTS: There were 316 patients with BRCA1/2 mutations: 266/316 (84.2%) were 30-59&#xa0;years old at the time of genetic testing, 35/316 (11.1%) were 60-69, and 15/316 (4.7%) were&#x2009;&#x2265;&#x2009;70. Median follow-up was 57&#xa0;months (IQR 21.6-114.6). There were 178 (56.3%) breast malignancies diagnosed; 161/266 (60.5%) age 30-59, 11/35 (31.4%) ages 60-69, and 6/15 (40%) age&#x2009;&#x2265;&#x2009;70 (p&#x2009;=&#x2009;0.002). Of patients with a malignant diagnosis (n&#x2009;=&#x2009;178), 140/178 (78.7%) had their cancers discovered on either screening or diagnostic mammogram, 30/178 (16.9%) by MRI, 1 /178 (0.6%) on ultrasound, and 1/178 (0.6%) was discovered on surgical pathology. Of the breast cancers diagnosed in patients age&#x2009;&#x2265;&#x2009;70, 66.7% (4/6) were found on mammogram.<br><br>CONCLUSIONS: In women&#x2009;&#x2265;&#x2009;70 with BRCA1/2 mutations, mammograms may be sufficient surveillance. Given that a number of older BRCA1/2 carriers may never develop breast cancer, our data supports individualized care and consideration for de-escalated surveillance in those&#x2009;&#x2265;&#x2009;70.},
}
@article {pmid40013144,
year = {2025},
author = {Li, X and Wu, N and Wang, C and Pei, B and Ma, X and Xie, J and Yang, W},
title = {NALCN expression is down-regulated and associated with immune infiltration in gastric cancer.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1512107},
pmid = {40013144},
issn = {1664-3224},
mesh = {Humans ; *Stomach Neoplasms/immunology/genetics/pathology/metabolism ; Cell Line, Tumor ; *Gene Expression Regulation, Neoplastic ; *Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; Down-Regulation ; Tumor Microenvironment/immunology ; Female ; Cell Proliferation ; Male ; },
abstract = {BACKGROUND: NALCN has been identified as a tumor suppressor gene, and its role in human cancer progression has garnered significant attention. However, there is a paucity of experimental studies specifically addressing the relationship between NALCN and immune cell infiltration in gastric cancer (GC).<br><br>METHODS: The expression levels of NALCN in tumor tissues, peripheral blood and gastric cancer cells lines from patients with GC were assessed using RNA sequencing, immunohistochemistry (IHC) staining and RT-qPCR. Data obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were utilized to investigate the correlation between NALCN expression and immune cell infiltration in GC. Subsequently, the relationship between NALCN expression and infiltrating immune cells in GC tissues was examined through immunofluorescence method. Additionally, in vitro experiments were conducted to evaluate the impact of NALCN knockdown on T cells function in GC cell lines.<br><br>RESULTS: RNA sequencing analysis revealed that NALCN expression was significantly downregulated in GC tissues. Specifically, NALCN levels were lower in GC tumor tissues and plasma compared to adjacent non-tumor tissues and healthy controls. Consistent with these findings, the expression trend of NALCN mRNA in the GEO database mirrored the experimental results. Mechanistically, NALCN knockdown markedly enhanced cell proliferation, colony formation and migration while reducing apoptosis rates in AGS and GES-1 cells. Analysis of the TCGA database indicated a positive correlation between NALCN expression and the infiltration of B cells, cytotoxic cells, immature dendritic cells (iDC) cells, CD8[+] T cells, and others in GC tissue. Conversely, Th17 and Th2 cells infiltration exhibited a negative correlation with NALCN expression. Immunofluorescence staining confirmed that B cells and CD8 T cells were more abundant in GC tumor tissues with high NALCN expression, whereas Th17 and Th2 cells were less prevalent. Subsequently, we co-cultured GC cells transfected with NALCN knockdown or control vectors along with their supernatants with T cells. The results demonstrated that NALCN knockdown in GC cells or their supernatants inhibited T cell proliferation compared to control conditions. Moreover, NALCN may play a role in glucose and glutamine uptake.<br><br>CONCLUSIONS: NALCN facilitates immune cell aggregation in GC and has potential as a biomarker for immune infiltration.},
}
@article {pmid40011966,
year = {2025},
author = {Pirooznia, P and Meighani, EM and Ghaffari, F},
title = {Exploring new frontiers in oncofertility preservation: a case of ovarian stimulation during pregnancy.},
journal = {Journal of ovarian research},
volume = {18},
number = {1},
pages = {39},
pmid = {40011966},
issn = {1757-2215},
mesh = {Humans ; Female ; *Ovulation Induction/methods ; Pregnancy ; *Fertility Preservation/methods ; Adult ; *Breast Neoplasms/therapy/complications/drug therapy ; Letrozole ; *Pregnancy Complications, Neoplastic ; },
abstract = {BACKGROUND: The standard treatment for Pregnancy-Associated Breast Cancer (PABC) includes surgery and neoadjuvant chemotherapy, which can impair fertility, emphasizing the critical need for fertility preservation in these patients. This case report discusses a breast cancer patient who was found to be pregnant shortly after starting treatment. Despite the pregnancy and increased levels of βHCG and progesterone, the ovarian stimulation cycle yielded a satisfactory number of mature oocytes and high-quality embryos.<br><br>CASE PRESENTATION: A 40-year-old woman, G1Ab1 (Gravida1Abortion1), who was diagnosed with Invasive Ductal Carcinoma with negative receptors (Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2) was referred to the oncofertility unit of the Royan Infertility Center for fertility preservation prior to the commencement of chemotherapy. Following necessary consultations and procedures, and confirming a negative pregnancy test, a random start letrozole-based protocol was initiated for ovarian stimulation. During the cycle, a positive pregnancy test was encountered. Despite the positive test, the cycle continued, and on day 13 of the cycle, triggering was performed with a GnRH agonist. A puncture was performed 36&#xa0;h later, yielding 12 oocytes and 8 embryos.<br><br>CONCLUSION: This case highlights the feasibility of adapting random-start ovarian stimulation protocols during pregnancy, warranting further investigation in similar clinical scenarios.},
}
@article {pmid39985623,
year = {2025},
author = {Randall Armel, S and Malcolmson, J and Volenik, A and Maganti, M and Watkins, N and Charames, GS and McCuaig, J},
title = {Genetic counseling referral rates and genetic testing outcomes in women with young breast cancer: a 20-year Canadian review.},
journal = {Breast cancer research and treatment},
volume = {211},
number = {2},
pages = {321-330},
pmid = {39985623},
issn = {1573-7217},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/epidemiology/diagnosis/pathology ; *Referral and Consultation/statistics &amp; numerical data ; *Genetic Counseling/statistics &amp; numerical data ; *Genetic Testing/statistics &amp; numerical data ; Adult ; Canada/epidemiology ; Retrospective Studies ; Young Adult ; Genetic Predisposition to Disease ; },
abstract = {PURPOSE: Despite guidelines recommending genetic testing for all cases of very young breast cancer (VYBC), poor uptake has been reported. This study aimed to examine genetic testing referral rates and outcomes over a 20-year period within the Canadian context.<br><br>METHODS: A retrospective chart review of all incident VYBC cases (at or below 35 years of age) between January 1, 2000 and December 31, 2019 was conducted. Descriptive statistics were used to summarize demographic factors and logistic regression analyses were performed to identify the predictors associated with referral for genetic counseling and positive genetic test results.<br><br>RESULTS: 628 women were identified with VYBC. Most women presented with stage 2 (42%), hormone receptor-positive (HR&#x2009;+) and HER2-negative (54%) invasive ductal carcinoma (94%). Over the study period, referral rates increased from 44 to 84%. Of women initially tested for BRCA1/BRCA2, only 21% were referred for updated panel testing. Among those tested, 19% had a pathogenic variant, 21% of whom reported no family history of cancer. Predictors of referral included stage 0-2 disease while predictors of positive test results included a second breast cancer diagnosis and positive family history.<br><br>CONCLUSION: Despite guidelines based on age alone, barriers to referral persist. Results of this study suggest the need for new models of care that ensure equitable access to genetic testing for all women diagnosed with VYBC regardless of family history, ethnicity, or disease stage. As genetic testing criteria evolve, protocols must address these barriers to prevent missed opportunities for testing.},
}
@article {pmid39974553,
year = {2025},
author = {Maeda, Y and Ikeda, T and Sato, A and Matsumoto, A and Jinno, H},
title = {Breast Cancer with a Newly Diagnosed Variant in the PTEN Gene: A Case Report.},
journal = {Surgical case reports},
volume = {11},
number = {1},
pages = {},
pmid = {39974553},
issn = {2198-7793},
abstract = {INTRODUCTION: The phosphatase and tensin homolog hamartoma tumor syndrome (PHTS) refers to a spectrum of disorders caused by variants of the phosphatase and tensin homolog (PTEN) gene, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, adult Lhermitte-Duclos disease, and autism spectrum disorders associated with macrocephaly. PHTS is characterized by hamartomas in multiple organs and is associated with an increased risk of developing malignant tumors including, breast, thyroid, endometrial, colorectal, and kidney tumors. Breast cancer is the most common malignancy associated with PHTS.<br><br>CASE PRESENTATION: We describe the case of a 44-year-old female patient with invasive ductal carcinoma of the right breast. Cobblestone papillomatosis was present in the gingiva. She had a medical history of bilateral adenomatous goiters for 10 years. Her mother had been diagnosed with breast cancer, thyroid and tongue tumors, gastric polyps, hepatic hemangioma, and collagen disease. Additionally, the patient's maternal grandmother had a history of colon cancer. Based on the patient's family history and physical findings, CS was suspected, and direct DNA sequencing analysis revealed a haplotype c.634del mutation in exon 7 of the PTEN gene. Although there is no clear evidence supporting risk-reducing surgery for PHTS, a right nipple-sparing mastectomy, sentinel lymph node biopsy, and tissue expander reconstruction were performed.<br><br>CONCLUSIONS: We report a case of breast cancer with a newly diagnosed c.634del mutation in the PTEN gene. We also reviewed the current literature on PTEN genetic variants and breast cancer subtypes.},
}
@article {pmid39962573,
year = {2025},
author = {Deng, J and Wei, L and Chen, Y and Li, X and Zhang, H and Wei, X and Feng, X and Qiu, X and Liang, B and Zhang, J},
title = {Identification of benzo(a)pyrene-related toxicological targets and their role in chronic obstructive pulmonary disease pathogenesis: a comprehensive bioinformatics and machine learning approach.},
journal = {BMC pharmacology &amp; toxicology},
volume = {26},
number = {1},
pages = {33},
pmid = {39962573},
issn = {2050-6511},
mesh = {*Pulmonary Disease, Chronic Obstructive/genetics/chemically induced ; Humans ; *Benzo(a)pyrene/toxicity ; *Machine Learning ; Computational Biology ; Molecular Docking Simulation ; Protein Interaction Maps ; Nomograms ; Oxidative Stress/drug effects ; },
abstract = {BACKGROUND: Chronic obstructive pulmonary disease (COPD) pathogenesis is influenced by environmental factors, including Benzo(a)pyrene (BaP) exposure. This study aims to identify BaP-related toxicological targets and elucidate their roles in COPD development.<br><br>METHODS: A comprehensive bioinformatics approach was employed, including the retrieval of BaP-related targets from the Comparative Toxicogenomics Database (CTD) and Super-PRED database, identification of differentially expressed genes (DEGs) from the GSE76925 dataset, and protein-protein interaction (PPI) network analysis. Functional enrichment and immune infiltration analyses were conducted using GO, KEGG, and ssGSEA algorithms. Feature genes related to BaP exposure were identified using SVM-RFE, Lasso, and RF machine learning methods. A nomogram was constructed and validated for COPD risk prediction. Molecular docking was performed to evaluate the binding affinity of BaP with proteins encoded by the feature genes.<br><br>RESULTS: We identified 72 differentially expressed BaP-related toxicological targets in COPD. Functional enrichment analysis highlighted pathways related to oxidative stress and inflammation. Immune infiltration analysis revealed significant increases in B cells, DC, iDC, macrophages, T cells, T helper cells, Tcm, and TFH in COPD patients compared to controls. Correlation analysis showed strong links between oxidative stress, inflammation pathway scores, and the infiltration of immune cells, including aDC, macrophages, T cells, Th1 cells, and Th2 cells. Seven feature genes (ACE, APOE, CDK1, CTNNB1, GATA6, IRF1, SLC1A3) were identified across machine learning methods. A nomogram based on these genes showed high diagnostic accuracy and clinical utility. Molecular docking revealed the highest binding affinity of BaP with CDK1, suggestive of its pivotal role in BaP-induced COPD pathogenesis.<br><br>CONCLUSIONS: The study elucidates the molecular mechanisms of BaP-induced COPD, specifically highlighting the role of oxidative stress and inflammation pathways in promoting immune cell infiltration. The identified feature genes may serve as potential biomarkers and therapeutic targets. Additionally, the constructed nomogram demonstrates high accuracy in predicting COPD risk, providing a valuable tool for clinical application in BaP-exposed individuals.},
}
@article {pmid39962362,
year = {2025},
author = {Simoes, E and Uchida, R and Nucci, MP and Duran, FLS and Lima, JDCC and Gama, LR and Costa, NA and Otaduy, MCG and Bin, FC and Otoch, JP and Alcantara, P and Ramos, A and Laviano, A and Diaz, MB and Esiri, MM and DeLuca, GC and Herzig, S and Filho, GB and Seelaender, M},
title = {Cachexia Alters Central Nervous System Morphology and Functionality in Cancer Patients.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {16},
number = {1},
pages = {e13742},
pmid = {39962362},
issn = {2190-6009},
mesh = {Humans ; *Cachexia/etiology/pathology/physiopathology ; Male ; Female ; Middle Aged ; *Neoplasms/complications/pathology/physiopathology ; Aged ; Magnetic Resonance Imaging ; *Central Nervous System/pathology/physiopathology ; Aged, 80 and over ; },
abstract = {BACKGROUND: Cachexia is a clinically challenging multifactorial and multi-organ syndrome, associated with poor outcome in cancer patients, and characterised by inflammation, wasting and loss of appetite. The syndrome leads to central nervous system (CNS) function dysregulation and to neuroinflammation; nevertheless, the mechanisms involved in human cachexia remain unclear.<br><br>METHODS: We used in&#xa0;vivo structural and functional magnetic resonance imaging (Cohort 1), as well as postmortem neuropathological analyses (Cohort 2) in cachectic cancer (CC) patients compared to weight stable cancer (WSC) patients. Cohort 1 included treatment-na&#xef;ve adults diagnosed with colorectal cancer, further divided into WSC (n&#x2009;=&#x2009;12; 6/6 [male/female], 61.3&#x2009;&#xb1;&#x2009;3.89&#x2009;years) and CC (n&#x2009;=&#x2009;10; 6/4, 63.0&#x2009;&#xb1;&#x2009;2.74&#x2009;years). Cohort 2 was composed by human postmortem cases where gastrointestinal carcinoma was the underlying cause of death (WSC n&#x2009;=&#x2009;6; 3/3, 82.7&#x2009;&#xb1;&#x2009;3.33&#x2009;years and CC n&#x2009;=&#x2009;10; 5/5, 84.2&#x2009;&#xb1;&#x2009;2.28&#x2009;years).<br><br>RESULTS: Here we demonstrate that the CNS of CC patients presents regional structural differences within the grey matter (GM). Cachectic patients presented an augmented area within the region of the orbitofrontal cortex, olfactory tract and the gyrus rectus (coordinates X, Y, Z&#x2009;=&#x2009;6, 20,-24; 311 voxels; pFWE&#x2009;=&#x2009;0.023); increased caudate and putamen volume (-10, 20, -8; 110 voxel; pFWE&#x2009;=&#x2009;0.005); and reduced GM in superior temporal gyrus and rolandic operculum (56,0,2; 156 voxels; pFWE&#x2009;=&#x2009;0.010). Disrupted functional connectivity was found in several regions such as the salience network, subcortical and temporal cortical areas of cachectic patients (20 decreased and 5 increased regions connectivity pattern, pFDR < 0.05). Postmortem neuropathological analyses identified abnormal neuronal morphology and density, increased microglia/macrophage burden, astrocyte profile disruption and mTOR pathway related neuroinflammation (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: Our results indicate that cachexia compromises CNS morphology mostly causing changes in the GM of cachectic patients, leading to alterations in regional volume patterns, functional connectivity, neuronal morphology, neuroglia profile and inducing neuroinflammation, all of which may contribute to the loss of homeostasis control and to deficient information processing, as well as to the metabolic and behavioural derangements commonly observed in human cachexia. This first human mapping of CNS cachexia responses will now pave the way to mechanistically interrogate these pathways in terms of their therapeutic potential.},
}
@article {pmid39948972,
year = {2024},
author = {Takeda, S and Terakawa, H and Kawata, C and Kurokawa, Y and Machi, R and Tanaka, H and Nishimura, Y and Mohri, R and Hirata, M and Kitahara, T and Moriyama, H and Kinoshita, J and Kawashima, H and Inaki, N},
title = {[A Case in Which Multiple Biopsies from Breast Cancer Skin Metastases Were Performed and Trastuzumab Deruxtecan Was Used after Low HER2 Expression Was Confirmed].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {51},
number = {13},
pages = {1702-1703},
pmid = {39948972},
issn = {0385-0684},
mesh = {Humans ; Middle Aged ; Female ; *Receptor, ErbB-2/analysis/metabolism ; *Trastuzumab/therapeutic use ; *Skin Neoplasms/secondary/drug therapy ; *Breast Neoplasms/pathology/drug therapy ; Biopsy ; *Camptothecin/analogs &amp; derivatives/therapeutic use ; *Immunoconjugates/therapeutic use ; },
abstract = {In March 2023, Trastuzumab deruxtecan(T-DXd)was added for the treatment of inoperable or recurrent breast cancer with low HER2 expression who has a history of chemotherapy. The patient was a 61-year-old woman who had undergone surgery for bilateral breast cancer, and was diagnosed with Stage ⅡA triple negative(HER2-IHC score 0)on the right and non-invasive ductal carcinoma of the breast on the left. Biopsy from metastases was triple-negative(HER2-IHC score 0, PD-L1 negative). Exacerbation of skin metastases was observed despite repeated regimen changes 3rd skin biopsy was diagnosed with low expression of HER2 for the first time, and T-DXd was started. The therapeutic effect of T-DXd was temporarily observed, such as a decrease in tumor markers. It is useful to repeatedly collect tissues from primary and metastatic lesions and re-evaluate biomarkers in order to develop an appropriate treatment plan.},
}
@article {pmid39948901,
year = {2024},
author = {Nakakuma, T and Yamasaki, K and Ueno, S and Tabei, T},
title = {[A Case of Resection for a Late-Stage Solitary Hepatic Metastasis from Very Early Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {51},
number = {13},
pages = {1492-1494},
pmid = {39948901},
issn = {0385-0684},
mesh = {Humans ; Female ; Middle Aged ; *Liver Neoplasms/secondary/surgery/drug therapy ; *Breast Neoplasms/pathology/surgery ; Hepatectomy ; Neoplasm Staging ; *Carcinoma, Ductal, Breast/surgery/secondary ; },
abstract = {A 57-year-old woman underwent left breast conserving surgery(Bp+Ax)for breast cancer at 46 years of age. Histopathological findings were invasive ductal carcinoma(tubule forming type), pN0(0/17), Ly0, V0, NG1, HG1, pT1aN0M0, Stage Ⅰ, ER 100%, HER2 score 0. Postoperatively, only radiotherapy to the preserved breast was performed and no adjuvant drug therapy was administered. This time, a 45 mm liver tumor in segment 4/3 was found by abdominal ultrasound for health checkup. Enhanced ultrasonography showed poor contrast, CT showed a low density tumor with calcification, MRI showed no diffusion reduction, and PET showed no FDG uptake. Although the findings were not typical for suspecting malignancy, but cholangiocellular carcinoma or metastatic liver cancer could not be ruled out. Laparoscopic liver resection was performed. Histopathological findings revealed liver metastasis of breast cancer. We report a rare case, a late-stage solitary hepatic metastasis from very early breast cancer. Although the concept of breast cancer as a systemic disease is well-established, in this case there is a possibility that recurrence would not have occurred if postoperative adjuvant drug therapy had been performed. The importance of postoperative adjuvant drug therapy for breast cancer was suggested. At present, she remains disease-free after hepatectomy.},
}
@article {pmid39948851,
year = {2024},
author = {Fujimori, T and Kasagawa, T and Ishii, N and Kusashio, K and Yonemori, Y and Ozaki, D},
title = {[A Case of Bladder Metastasis from Invasive Ductal Carcinoma of the Breast-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {51},
number = {13},
pages = {1345-1347},
pmid = {39948851},
issn = {0385-0684},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery/therapy/drug therapy ; Aged ; *Urinary Bladder Neoplasms/secondary/drug therapy ; *Carcinoma, Ductal, Breast/secondary/therapy/surgery/drug therapy/pathology ; Neoplasm Invasiveness ; },
abstract = {We report a patient with left breast cancer who underwent total mastectomy and axillary dissection as primary surgery. The patient, a 78-year-old woman, noticed a tumor about 4 cm in the left breast. She was diagnosed with left breast cancer (cT2N2M0, cStage ⅢA). The pathology revealed invasive lobular carcinoma, 46×31 mm, ly(+), v(0), histological grade: 2, n2, hormone receptor positive, HER2 negative, and pStage ⅢA. We recommended adjuvant chemotherapy, but she did not desire. She started oral administration of an aromatase inhibitor and radiation therapy. When DFI was 3 years, an examination was carried out because the increase in CEA value, CT scan revealed a mass extending from the bladder. We suspected bladder cancer. She underwent a bladder biopsy. The result was bladder metastasis of breast cancer. Later, we introduced chemotherapy. Routine screening of the lower urinary tract is not necessary for all patients, but women with a history of breast cancer presenting with urinary symptoms should undergo a thorough examination of the urinary tract.},
}
@article {pmid39945142,
year = {2025},
author = {Cremer, A and Rosewick, N and Kelsey, M and Trépo, E and Libert, F and De Vos, M and Baert, F and Moreels, T and Louis, E and Rahier, JF and Demetter, P and Sedivy, JM and Vermeire, S and Franchimont, D},
title = {A transcriptomic score to classify the inflammation-dysplasia-cancer sequence lesions in inflammatory bowel disease.},
journal = {Journal of Crohn's &amp; colitis},
volume = {19},
number = {3},
pages = {},
pmid = {39945142},
issn = {1876-4479},
support = {//Research Foundation against Cancer-Belgium/ ; //Erasme Foundation/ ; R01 AG016694/AG/NIA NIH HHS/United States ; //Televie/ ; P01 AG051449/NH/NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; *Inflammatory Bowel Diseases/genetics/pathology/complications ; *Transcriptome ; Middle Aged ; Adult ; *Colorectal Neoplasms/genetics/pathology/etiology ; Gene Expression Profiling ; Inflammation/genetics/pathology ; *Colitis-Associated Neoplasms/genetics/pathology ; Intestinal Mucosa/pathology ; RNA, Long Noncoding/genetics ; },
abstract = {BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is associated with a higher risk of developing colorectal cancer, according to the inflammation-dysplasia-cancer (IDC) sequence from inflammation to colitis-associated colorectal cancer (CAC). The objective of this study was to identify and generate a transcriptomic signature and score, related to the IDC sequence, that could ultimately classify dysplasia and cancer in IBD.<br><br>METHODS: Demographics, clinical parameters, histological characteristics, and RNA-sequencing data were evaluated on 134 formalin-fixed paraffin-embedded lesions from 2 independent cohorts of IBD patients with low- or high-grade dysplasia (LGD, HGD) and/or CAC. An ordinal logistic regression screened for significant IDC sequence-associated genes that were computed in a transcriptomic signature score.<br><br>RESULTS: Principal component analysis and unsupervised clustering on 1% of the most variable genes showed a good clustering between the 4 lesion groups (Normal Mucosa, Inflamed Mucosa, LGD/HGD, and CAC). A gene signature was identified on 27 genes that correlated with the lesion groups in the exploratory cohort. The most weighted gene in this transcriptomic signature was the long non-coding regulatory RNA KCNQ1OT1, a gatekeeper against genomic instability and transposon activation. Based on the expression of these 27 genes, we built and validated a transcriptomic signature score to classify dysplasia and CAC. The overall accuracy of the transcriptomic signature score was 85.71% in the exploratory cohort and 90.91% in the validation cohort.<br><br>CONCLUSION: We identified a tissue-based transcriptomic score to classify IDC lesions in IBD patients and uncovered some of the pivotal genes in carcinogenesis related to inflammation in IBD.},
}
@article {pmid39937427,
year = {2025},
author = {Kato, M and Sato, H and Naito, Y and Yamamoto, A and Kawanishi, H and Nakano, Y and Nishikimi, T and Kobayashi, M and Kondo, A and Hirabayashi, H and Katsuno, S and Sakamoto, F and Kimura, T and Yamamoto, S and Araki, H and Tochigi, K and Ito, F and Hatsuse, H and Sassa, N and Hirakawa, A and Akamatsu, S and Tsuzuki, T},
title = {Prospective observational study on the relationships between genetic alterations and survival in Japanese patients with metastatic castration-sensitive prostate cancer: the impact of IDC-P.},
journal = {International journal of clinical oncology},
volume = {30},
number = {4},
pages = {789-796},
pmid = {39937427},
issn = {1437-7772},
mesh = {Humans ; Male ; Aged ; Prospective Studies ; Japan/epidemiology ; Middle Aged ; Mutation ; Aged, 80 and over ; *Prostatic Neoplasms, Castration-Resistant/genetics/pathology/mortality ; Prognosis ; *Prostatic Neoplasms/genetics/mortality/pathology ; Tumor Suppressor Protein p53/genetics ; East Asian People ; BRCA2 Protein ; Hepatocyte Nuclear Factor 3-alpha ; },
abstract = {BACKGROUND: Intraductal Carcinoma of the Prostate (IDC-P) is a significant prognostic indicator for prostate cancer, which demonstrates significant associations with homologous recombination repair gene mutations (HRRm) and alterations in tumor suppressor genes. However, no study in Japan has investigated the association between IDC-P and genetic mutations in men with metastatic castration-sensitive prostate cancer (mCSPC).<br><br>METHODS: This prospective observational study enrolled 102 de novo mCSPC (LATITUDE high-risk) patients diagnosed between 2018 and 2021, with subsequent monitoring of survival outcomes. A single genitourinary pathologist evaluated all needle biopsy slides. Genetic analyses were performed using the Myriad myChoice HRD plus&#x2122;. These genetic analyses covered 108 genetic loci, including 15 HRRm genes, with a success rate of 91%.<br><br>RESULTS: Genetic alterations were observed in 79 patients (77.5%), with 20 exhibiting HRRm (19.6%). Common genetic alterations included FOXA1 (29.4%) and TP53 (17.6%) mutations; BRCA (9.8%) mutations were the most frequent HRRm (BRCA1:2 cases, BRCA2:8 cases, including 6 biallelic). IDC-P-positive patients demonstrated a significantly higher frequency of genetic aberrations (82.6% vs. 50%, p&#x2009;=&#x2009;0.0082). Patients with biallelic BRCA2, TP53, and PTEN mutations exhibited significantly poorer cancer-specific survival. Multivariate analysis identified lactate dehydrogenase (LDH) (HR 1.005, p&#x2009;=&#x2009;0.035), TP53 mutations (HR 5.196, p&#x2009;<&#x2009;0.001), biallelic BRCA2 mutations (HR 10.686, p&#x2009;=&#x2009;0.005), and IDC-P as independent predictors of poor cancer-specific survival. No cancer-related deaths occurred in IDC-P-negative cases.<br><br>CONCLUSION: Our study emphasizes the significant association between IDC-P and an elevated incidence of genetic alterations in Japanese mCSPC patients, emphasizing the need for early genetic testing to guide therapeutic decision-making.},
}
@article {pmid39936988,
year = {2025},
author = {González-Martínez, S and Palacios, J and Carretero-Barrio, I and Lanza, VF and García-Cosío Piqueras, M and Caniego-Casas, T and Hardisson, D and Esteban-Rodríguez, I and Cortés, J and Pérez-Mies, B},
title = {Single-Cell RNA Sequencing on Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue Identified Multi-Ciliary Cells in Breast Cancer.},
journal = {Cells},
volume = {14},
number = {3},
pages = {},
pmid = {39936988},
issn = {2073-4409},
support = {PI22/01892, PMP22/00054, PMP21/00107//Instituto de Salud Carlos III/ ; },
mesh = {Humans ; *Breast Neoplasms/genetics/pathology ; *Paraffin Embedding/methods ; Female ; *Single-Cell Analysis/methods ; *Formaldehyde/chemistry ; *Tissue Fixation/methods ; *Sequence Analysis, RNA/methods ; Immunohistochemistry ; },
abstract = {The purpose of this study was to evaluate the suitability of formalin-fixed and paraffin-embedded (FFPE) samples and fixed fresh (FF) samples for single-cell RNA sequencing (scRNAseq). To this end, we compared single-cell profiles from FFPE and matched FF tissue samples of one invasive carcinoma of no special type carcinoma (invasive ductal carcinoma-IDC) and one invasive lobular carcinoma (ILC) to assess consistency in cell type distribution and molecular profiles. The results were validated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and electron microscopy. Additionally, immune cell proportions identified by IHC were quantified using QuPath and compared to the scRNAseq results. FFPE- and FF-derived libraries demonstrated high-quality sequencing metrics, and cellular heterogeneity was similar. No exclusive cell populations were identified by either approach. The four samples analysis identified six types of epithelial cells, as well as tumoral microenvironment populations. The scRNAseq results from epithelial neoplastic cells were concordant with common IHC markers. The proportion of immune cells identified by IHC in FFPE sections were similar to those obtained by scRNAseq. We identified and validated a previously poorly recognized subpopulation of neoplastic multi-ciliated cells (MCCs) (FOXJ1, ROPN1L). Analysis of FOXJ1 in 214 ER-positive invasive carcinomas demonstrated protein expression in one third of tumors, suggesting frequent focal MCC differentiation. Our results support the suitability of scRNAseq analysis using FFPE tissue, and identified a subpopulation of neoplastic MCC in breast cancer.},
}
@article {pmid39925473,
year = {2025},
author = {Maxey, J and Harvey, D},
title = {Neisseria weaveri: Atypical Infection in Breast Implant-Based Reconstruction.},
journal = {Plastic and reconstructive surgery. Global open},
volume = {13},
number = {2},
pages = {e6505},
pmid = {39925473},
issn = {2169-7574},
abstract = {Surgical site infection (SSI) following breast implant surgery can have devastating complications. Infection is most commonly from coagulase-negative Staphylococcus bacteria. Neisseria weaveri is a gram-negative bacterium that is associated with animal bites. We present the first known case of N. weaveri causing SSI following breast implant reconstruction. We report the case of a 61-year-old woman with invasive ductal carcinoma who underwent bilateral skin-sparing mastectomy with immediate implant-based reconstruction. She presented on postoperative day 24 with malodorous drainage from her Jackson-Pratt drain. The patient explained that she has a shih tzu at home that frequently licked her. Cultures from the drain grew N. weaveri. The patient's antibiotic regimen was transitioned, and she completed her course without complications. Practitioners should counsel their patients on adequate postsurgery hygiene and take into consideration rare causes of SSI and how this may affect patient care.},
}
@article {pmid39912231,
year = {2025},
author = {Palanjian, R and Welk, B and Myers, JB and Lenherr, SM and Elliott, SP and O'Dell, D and Stoffel, JT},
title = {Impact of Bladder Management Strategies on Autonomic Dysreflexia Severity in People With Spinal Cord Injuries.},
journal = {Neurourology and urodynamics},
volume = {44},
number = {4},
pages = {754-759},
pmid = {39912231},
issn = {1520-6777},
support = {//Patient Centered Outcomes Research Institute Award-CER14092138./ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Autonomic Dysreflexia/etiology/physiopathology/diagnosis/therapy ; Intermittent Urethral Catheterization ; Neurogenic Bowel/etiology/physiopathology ; Prospective Studies ; Quality of Life ; Registries ; Severity of Illness Index ; *Spinal Cord Injuries/complications/physiopathology ; *Urinary Bladder/physiopathology/innervation ; *Urinary Bladder, Neurogenic/etiology/therapy/physiopathology/diagnosis ; Urinary Catheterization ; },
abstract = {PURPOSE: We investigated whether severity of autonomic dysreflexia (AD) was associated with more patient-reported bladder and bowel symptoms and compared AD severity by bladder management strategy in people with spinal cord injury (SCI).<br><br>METHODS: The Neurogenic Bladder Research Group SCI Registry is a prospective study which evaluated quality of life after SCI. Bladder and bowel symptoms were assessed through Neurogenic Bladder Symptom Score and Neurogenic Bowel Dysfunction score, respectively. AD severity was assessed with the Autonomic Dysreflexia Following Spinal Cord Injury (ADFSCI) instrument. Bladder management was classified as volitional voiding, clean intermittent catheterization (CIC), indwelling catheter (IDC), and surgery (augmentation and diversion).<br><br>RESULTS: AD scores were identified for 1473 people. The mean age was 45. Bladder management was CIC in 754 (51%), IDC in 271 (18%), surgery in 195 (13%) and voiding in 259 (18%). On univariate analysis, higher ADFSCI scores occurred with complete injuries (3.1 vs 3.4, p&#x2009;=&#x2009;0.03), cervical/thoracic injuries (3.8 vs 1.5, p&#x2009;<&#x2009;0.0001), and chronic pain (3.9 vs 2.9, p&#x2009;=&#x2009;0.0004). IDC (5.2) and surgery (4.5) had higher ADFSCI scores than CIC (3.0) and volitional voiding (2.8) (p&#x2009;<&#x2009;0.0001). Sub-analysis showed bladder augmentation had significantly higher ADSCI scores than diversion (4.7 vs 3.7, p&#x2009;=&#x2009;0.03). On multivariate analysis, level of injury, bladder management, and bowel and bladder symptoms remained associated with worse AD.<br><br>CONCLUSION: Level of injury, age, worse bowel and bladder symptoms and bladder management type were associated with higher AD scores. Bladder management with surgery, particularly bladder augment, and IDC had associated greater AD symptoms compared to CIC or voiding.<br><br>TRIAL REGISTRATION: clinicaltrials.gov NTC06216081 and HSRP20153564, U.S. National Library of Medicine, wwwcf.nlm.nih.gov.},
}
@article {pmid39909175,
year = {2025},
author = {Jean, J and Jochelson, MS and Moo, TA and Solomon, SB and Bryce, Y},
title = {Breast Cancer Recurrence after Cryoablation in Patients Who Are Poor Surgical Candidates or Who Refuse Surgery.},
journal = {Journal of vascular and interventional radiology : JVIR},
volume = {36},
number = {6},
pages = {971-978},
doi = {10.1016/j.jvir.2025.01.048},
pmid = {39909175},
issn = {1535-7732},
support = {P30 CA 008748/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Cryosurgery/adverse effects ; Female ; *Breast Neoplasms/surgery/pathology/diagnostic imaging ; Retrospective Studies ; *Neoplasm Recurrence, Local ; Middle Aged ; Aged ; Treatment Outcome ; Time Factors ; Risk Factors ; *Treatment Refusal ; Adult ; Risk Assessment ; *Carcinoma, Ductal, Breast/surgery/pathology ; Aged, 80 and over ; *Carcinoma, Lobular/surgery/pathology ; Patient Selection ; Tumor Burden ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; },
abstract = {PURPOSE: To evaluate in-breast recurrence rates after cryoablation in patients with primary breast cancer who were poor surgical candidates or refused surgery.<br><br>MATERIALS AND METHODS: Patients with primary breast cancer who were poor surgical candidates or who refused surgery and were treated with cryoablation at a single academic cancer center between October 2018 and June 2023 were retrospectively reviewed. Of the 60 treated patients, 45 had invasive ductal carcinoma, 6 had invasive lobular carcinoma, 2 had multicentric ductal carcinoma in situ, and 7 had other histology. Tumor size ranged from 0.3 to 9 cm, with a mean of 2.7 cm. Recurrence was defined as new tumor or regrowth of residual tumor in the ipsilateral breast.<br><br>RESULTS: With a mean follow-up of 21 months and median follow-up of 9.8 months, there was a recurrence rate of 10% (6 of 60 patients). Patients in the recurrence group had more poorly differentiated disease than those in the nonrecurrence group (66.7% vs 22.2%; P = .038). Tumor size did not differ between nonrecurrence and recurrence groups (nonrecurrence group mean, 2.7 cm [SD &#xb1; 2.6]; recurrence group mean, 2.5 cm [SD &#xb1; 1.0]; P = .506). Patients who were treated with palliative intent rather than curative intent were significantly older (79.7 years [SD &#xb1; 12.2] vs 72.5 years [SD &#xb1; 11.3]; P = .032).<br><br>CONCLUSIONS: Cryoablation can be considered a treatment option in patients who are poor surgical candidates or who refuse surgery, with a 10% recurrence rate at a mean follow-up of 21 months in this retrospective review that included patients with tumors up to 9 cm, unfavorable pathology, and multicentric disease.},
}
@article {pmid39906646,
year = {2025},
author = {Shi, J and Qi, X and Ran, Y and Zhou, Q and Ding, Y and Li, L and Zeng, Y and Qiu, D and Cai, Z and Cai, X and Pan, Y},
title = {Saliva-acquired pellicle inspired multifunctional gargle with wet adhesion, photodynamic antimicrobial, and In situ remineralization properties for dental caries prevention.},
journal = {Bioactive materials},
volume = {47},
number = {},
pages = {212-228},
pmid = {39906646},
issn = {2452-199X},
abstract = {Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues. Traditional remineralization treatments often have limited efficacy due to their lack of antibacterial activity. According to the Interrupting Dental Caries (IDC) theory, ideal caries-preventive materials should possess both antibacterial and remineralizing properties. Furthermore, effective adhesion to dental surfaces is crucial. Inspired by the wet adhesion properties of the salivary acquired pellicle, we developed a multifunctional gargle named Ce6@PDN-SAP (CP-SAP). This formulation employed peptide dendrimer nanogels (PDN) as a carrier for the photosensitizer Ce6, further functionalized with saliva-acquired peptide (SAP) to confer wet adhesion properties. CP-SAP rapidly adhered to the dental surface and remained effective for extended periods. Upon laser irradiation, Ce6 generated reactive oxygen species (ROS), disrupting bacterial outer membrane integrity, causing protein leakage, and reducing ATP levels, thereby achieving potent antibacterial effects. Following this, PDN and SAP acted as nucleation templates to promote in situ remineralization of demineralized dental hard tissues. In vivo studies using rat models demonstrated that CP-SAP provided significantly superior caries-preventive effects compared to chlorhexidine gargle. In conclusion, CP-SAP, as an innovative approach grounded in the IDC theory, holds great promise for the prevention and treatment of dental caries.},
}
@article {pmid39880998,
year = {2025},
author = {Mooshage, CM and Tsilingiris, D and Schimpfle, L and Fleming, T and Herzig, S and Szendroedi, J and Heiland, S and Bendszus, M and Kopf, S and Kurz, F and Jende, J and Kender, Z},
title = {Intradermal Advanced Glycation End-products Relate to Reduced Sciatic Nerve Structural Integrity in Type 2 Diabetes.},
journal = {Clinical neuroradiology},
volume = {35},
number = {2},
pages = {385-394},
pmid = {39880998},
issn = {1869-1447},
mesh = {Humans ; Female ; Male ; *Diabetes Mellitus, Type 2/complications/metabolism ; *Glycation End Products, Advanced/metabolism ; Middle Aged ; *Sciatic Nerve/diagnostic imaging/pathology/metabolism ; Diffusion Tensor Imaging ; *Diabetic Neuropathies/diagnostic imaging/metabolism/pathology ; Skin/metabolism ; Aged ; Anisotropy ; Adult ; Pulse Wave Analysis ; Vascular Stiffness ; Case-Control Studies ; },
abstract = {BACKGROUND: Cardiovascular risk management is beneficial, but stringent glycemic control does not prevent the progression of distal sensorimotor polyneuropathy (DSPN). Persistent hyperglycemia-induced alterations and cardiovascular factors may contribute to diabetes-associated nerve damage. This study aimed to evaluate the correlation between skin auto-fluorescence (sAF), an indicator of dermal advanced glycation end-product (AGE) accumulations, cardiovascular risk, and changes in peripheral nerve integrity.<br><br>METHODS: Sixty-two individuals with type&#xa0;2 diabetes (T2D) (20&#xa0;women and 42&#xa0;men), including 29 diagnosed with DSPN (7&#xa0;women and 22&#xa0;men), and 10&#xa0;healthy controls (HC) underwent diffusion tensor MR imaging of the sciatic nerve to assess fractional anisotropy (FA), an indicator of nerve structural integrity. sAF measurements were combined with clinical, serological, and electrophysiological evaluations. Arterial stiffness was assessed via pulse wave velocity (PWV).<br><br>RESULTS: sAF (HC 2.1&#x202f;&#xb1;&#x2009;0.25 AU, nDSPN 2.3&#x202f;&#xb1;&#x2009;0.47, DSPN 2.6&#x202f;&#xb1;&#x2009;0.43; p&#x202f;=&#x2009;0.005) was higher in individuals with DSPN compared to HC (p&#x202f;=&#x2009;0.010) and individuals without DSPN (p&#x202f;=&#x2009;0.035). Within the group of T2D FA correlated negatively with sAF (r&#x202f;=&#x2009;-0.49, p&#x202f;<&#x2009;0.001), PWV (r&#x202f;=&#x2009;-0.40, p&#x202f;=&#x2009;0.009) and high-sensitivity troponin&#xa0;T (hsTNT), a&#xa0;marker of microvascular damage (r&#x202f;=&#x2009;-0.39, p&#x202f;<&#x2009;0.001). In DSPN, sAF correlated positively with hsTNT (r&#x202f;=&#x2009;0.58, p&#x202f;=&#x2009;0.005) and with PWV (r&#x202f;=&#x2009;0.52, p&#x202f;=&#x2009;0.007), the sciatic nerve's FA correlated negatively with PWV (r&#x202f;=&#x2009;-0.47, p&#x202f;=&#x2009;0.010).<br><br>CONCLUSIONS: This study is the first to show close correlations between reduced peripheral nerve integrity and both intradermal AGE deposition and arterial stiffness in individuals with T2D. These findings highlight a&#xa0;mechanistic link between glycation-related vascular injury and neuronal damage emphasizing the importance of cardiovascular risk management in preventing DSPN.},
}
@article {pmid39879501,
year = {2025},
author = {Uppal, R and Saeed, U and Khattak, ME and Khan, AA and Uppal, MR and Piracha, ZZ and Khan, MN and Shaikh, D and Tariq, U and Mahmood, AR and Ali, SS and Muhammad, B and Tariq, MN and Gilani, SS and Ozsahin, DU and Uzun, B and Ozsahin, I},
title = {Epidemiological analysis of Leishmaniasis prevalence in Pakistan during 2016-2023.},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {84},
number = {},
pages = {e284742},
doi = {10.1590/1519-6984.284742},
pmid = {39879501},
issn = {1678-4375},
mesh = {Pakistan/epidemiology ; Humans ; Prevalence ; Male ; Child ; Female ; Adult ; Retrospective Studies ; Adolescent ; Child, Preschool ; Young Adult ; Middle Aged ; *Leishmaniasis/epidemiology/transmission ; Infant ; Aged ; },
abstract = {Leishmaniasis, caused by the Leishmania parasite, remains a persistent public health challenge in Pakistan. Despite control efforts, the disease prevalence continues to rise, particularly among pediatric populations. Understanding prevalence patterns and transmission dynamics is critical for effective control strategies. This study aims to analyze leishmaniasis prevalence data from January 2016 to July 2023 in Pakistan. Specific objectives include assessing temporal trends, demographic patterns, and geographical hotspots of transmission, while emphasizing the need for enhanced surveillance and research for targeted interventions. Retrospective analysis was conducted on leishmaniasis prevalence data collected from multiple healthcare facilities across Pakistan. Data included results from diagnostic tests on suspected cases, encompassing both pediatric and adult patients. Descriptive statistical analysis was employed to evaluate prevalence rates, demographic characteristics, and geographical distribution of positive cases. Analysis revealed an increasing trend in leishmaniasis prevalence over the study period. Initially, from 2016 to 2020, a positivity rate of 27% was observed exclusively among pediatric patients in Islamabad, with no adult cases. Subsequently, from 2017 to 2022, the positivity rate increased to 42%, affecting both pediatric and adult populations in Islamabad, Rawalpindi, and Swat. Notably, between July 2022 and July 2023, the positivity rate surged to 56%, primarily impacting adult males in the identified hotspots. The study provides evidence of rising leishmaniasis prevalence in Pakistan, particularly among pediatric patients. Identified hotspots suggest localized transmission, warranting targeted interventions. Enhanced surveillance and research efforts are crucial for understanding disease dynamics and implementing effective control measures. Priority should be given to vulnerable populations and high-burden regions to mitigate leishmaniasis impact in Pakistan.},
}
@article {pmid39879500,
year = {2025},
author = {Piracha, ZZ and Saeed, U and Uppal, R and Uppal, MR and Khan, AA and Abdullah, M and Mari, K and Basra, A and Gilani, SS and Tariq, MN and Ozsahin, DU and Uzun, B and Ozsahin, I},
title = {Prevalence and clinical profile of hepatitis C virus infections in multitransfused thalassemic patients in the capital twin cities of Pakistan.},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {84},
number = {},
pages = {e284453},
doi = {10.1590/1519-6984.284453},
pmid = {39879500},
issn = {1678-4375},
mesh = {Humans ; Pakistan/epidemiology ; Male ; Female ; Prevalence ; Adult ; *Hepatitis C/epidemiology ; Young Adult ; Adolescent ; *beta-Thalassemia/therapy/complications/epidemiology ; Middle Aged ; Child ; Alanine Transaminase/blood ; Transfusion Reaction ; },
abstract = {Hepatitis C virus (HCV) presents a significant global health concern, affecting 3.3% of the world's population. The primary mode of HCV transmission is through blood and blood products. Patients with beta thalassemia, who rely on lifelong blood transfusions, are particularly vulnerable to HCV infections. This study aimed to assess the prevalence of hepatitis C virus infections among multitransfused thalassemic patients in the twin cities of Pakistan's capital. The clinical research, involving the enrollment of 262 multitransfused beta thalassemic patients residing in the capital twin cities of Pakistan. The investigation encompassed the evaluation of hepatitis C virus presence, alanine aminotransferase (ALT) levels, serum creatinine, hepatomegaly, splenomegaly, and the occurrence of splenectomy. The overall prevalence of Hepatitis C virus infections was notably high at 55.73%. This was particularly pronounced among patients aged 20 years and older, with a 100% infection rate. In HCV-positive thalassemic patients, the average ALT level was observed to be 98 U/L, while average creatinine values stood at 0.39 mg/dL. Additionally, hepatomegaly was prevalent in 82.20% of HCV-positive thalassemic patients, featuring an average liver size increase of 4.33 cm. Splenomegaly was evident in 67.12% of HCV-positive thalassemic patients, with an average spleen size augmentation of 4.46 cm. Splenectomy was identified in 15.75% of cases. The incidence of HCV infections in the thalassemic population of Pakistan is alarmingly high. Furthermore, the risk of contracting HCV infections escalates with the advancing age of thalassemic patients. Elevated ALT levels and hepatomegaly were pervasive among the majority of HCV-positive thalassemic patients. Consequently, there is a compelling need for rigorous screening of blood products prior to transfusion to mitigate the future burden of HCV in Pakistan.},
}
@article {pmid39864363,
year = {2025},
author = {Metzger Filho, O and Cardoso, F and Poncet, C and Desmedt, C and Linn, S and Wesseling, J and Hilbers, F and Delaloge, S and Pierga, JY and Brain, E and Vrijaldenhoven, S and Neijenhuis, PA and Rutgers, EJT and Piccart, M and van 't Veer, LJ and Viale, G},
title = {Survival outcomes for patients with invasive lobular cancer by MammaPrint: Results from the MINDACT phase III trial.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {217},
number = {},
pages = {115222},
doi = {10.1016/j.ejca.2025.115222},
pmid = {39864363},
issn = {1879-0852},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/mortality/pathology/therapy ; *Carcinoma, Lobular/genetics/mortality/pathology/therapy ; Middle Aged ; Disease-Free Survival ; Aged ; Adult ; Gene Expression Profiling/methods ; Prognosis ; *Biomarkers, Tumor/genetics ; Neoplasm Invasiveness ; Transcriptome ; },
abstract = {BACKGROUND: Evaluation of the prognostic performance and clinical utility of the MammaPrint 70-gene signature in early-stage invasive lobular carcinoma (ILC) for whom such analyses in a randomized trial is awaited.<br><br>PATIENTS AND METHODS: Exploratory subgroup analysis of MINDACT trial patients with centrally assessed histology (n&#x202f;=&#x202f;5929) with invasive breast cancer of no-special-type (NST), or pure ILC. In the trial patients were categorized based on the 70-gene signature for genomic risk and modified Adjuvant!Online for clinical risk. Survival outcomes at 8.7 years median follow-up by 70-gene signature were compared between NST and ILC for Distant Metastasis-Free Survival (DMFS), Disease-Free Survival (DFS) and Overall Survival (OS).<br><br>RESULTS: 5313 patients were ILC (n&#x202f;=&#x202f;487) or NST (n&#x202f;=&#x202f;4826). ILC was further classified into classic ILC (n&#x202f;=&#x202f;255) or ILC variants (n&#x202f;=&#x202f;232). The 70-gene signature classified 16.2&#x202f;% of ILC and 39.1&#x202f;% of NST as genomic high-risk (gH). Survival outcomes for ILC vs. NST revealed similar estimates according to genomic risk overall and across subsets. The 70-gene signature classified 10.2&#x202f;% of classic ILC and 22.8&#x202f;% of ILC variants as gH. 5-yr DFS estimates for ILC variants 88.4&#x202f;% (95&#x202f;%CI: 83.1-92.1) was inferior to classic ILC 93.0&#x202f;% (95&#x202f;%CI: 88.7-95.7).<br><br>CONCLUSIONS: Sixteen percent of ILC were classified high genomic risk by the 70-gene signature, with unfavorable survival outcomes. Survival estimates were similar for patients with ILC and NST classified as either low- or high-genomic risk, suggesting that the 70-gene signature also has prognostic value in ILC and may be a clinically useful tool for adjuvant treatment decision-making in ILC.},
}
@article {pmid39863086,
year = {2025},
author = {Taylor, H and Spruill, L and Jensen-Smith, H and Rujchanarong, D and Hulahan, T and Ivey, A and Siougiannis, A and Bethard, JR and Ball, LE and Sandusky, GE and Hollingsworth, MA and Barth, JL and Mehta, AS and Drake, RR and Marks, JR and Nakshatri, H and Ford, M and Angel, PM},
title = {Spatial localization of collagen hydroxylated proline site variation as an ancestral trait in the breast cancer microenvironment.},
journal = {Matrix biology : journal of the International Society for Matrix Biology},
volume = {136},
number = {},
pages = {71-86},
doi = {10.1016/j.matbio.2025.01.006},
pmid = {39863086},
issn = {1569-1802},
support = {P30 CA036727/CA/NCI NIH HHS/United States ; P20 GM130447/GM/NIGMS NIH HHS/United States ; S10 OD030212/OD/NIH HHS/United States ; R21 CA286287/CA/NCI NIH HHS/United States ; R01 CA253460/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Tumor Microenvironment ; Female ; Hydroxylation ; *Breast Neoplasms/metabolism/pathology/genetics ; *Proline/metabolism ; *Collagen/metabolism/genetics/chemistry ; Proteomics/methods ; Protein Processing, Post-Translational ; Extracellular Matrix/metabolism ; },
abstract = {Collagen stroma interactions within the extracellular microenvironment of breast tissue play a significant role in breast cancer, including risk, progression, and outcomes. Hydroxylation of proline (HYP) is a common post-translational modification directly linked to breast cancer survival and progression. Changes in HYP status lead to alterations in epithelial cell signaling, extracellular matrix remodeling, and immune cell recruitment. In the present study, we test the hypothesis that the breast cancer microenvironment presents unique PTMs of collagen, which form bioactive domains at these sites that are associated with spatial histopathological characteristics and influence breast epithelial cell signaling. Mass spectrometry imaging proteomics targeting collagens were paired with comprehensive proteomic methods to identify novel breast cancer-related collagen domains based on spatial localization and regulation in 260 breast tissue samples. As ancestry plays a significant role in breast cancer outcomes, these methods were performed on ancestry diverse breast cancer tissues. Lumpectomies from the Cancer Genome Atlas (TCGA; n=10) reported increased levels of prolyl 4-hydroxylase subunit alpha-3 (P4HA3) accompanied by spatial regulation of fibrillar collagen protein sequences. A concise set of triple negative breast cancer lumpectomies (n=10) showed spatial regulation of specific domain sites from collagen alpha-1(I) chain. Tissue microarrays identified proteomic alterations around post-translationally modified collagen sites in healthy breast (n=81) and patient matched normal adjacent (NAT; n=76) and invasive ductal carcinoma (n=83). A collagen alpha-1(I) chain domain encompassing amino acids 506-514 with site-specific proline hydroxylation reported significant alteration between patient matched normal adjacent tissue and invasive breast cancer. Functional testing of domain 506-514 on breast cancer epithelial cells showed proliferation, chemotaxis and cell signaling response dependent on site localization of proline hydroxylation within domain 506-514 variants. These findings support site localized collagen HYP forms novel bioactive domains that are spatially distributed within the breast cancer microenvironment and may play a role in ancestral traits of breast cancer.},
}
@article {pmid39843553,
year = {2025},
author = {Nishida, H and Kato, A and Kaimori, R and Kawamura, K and Daa, T},
title = {Relationship between androgen receptor and androgen receptor-related protein expression in breast cancers focusing on morphologically identified carcinoma with apocrine differentiation.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {2892},
pmid = {39843553},
issn = {2045-2322},
mesh = {Humans ; *Receptors, Androgen/metabolism/genetics ; Female ; *Breast Neoplasms/pathology/metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Adult ; Aged ; Biomarkers, Tumor/metabolism ; Receptors, Estrogen/metabolism ; Cell Differentiation ; Receptors, Progesterone/metabolism ; *Apocrine Glands/pathology/metabolism ; *Carcinoma, Ductal, Breast/pathology/metabolism ; Immunohistochemistry ; Hepatocyte Nuclear Factor 3-alpha/metabolism ; },
abstract = {Breast cancer (BC) is classified based on the expression of histopathological markers, namely, estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). Carcinomas with apocrine differentiation (CAD) are classified based on morphology. Androgen receptor (AR) is highly expressed in CAD; however, no study has comprehensively examined AR-related proteins in CAD. Therefore, we examined the expression of AR-related proteins and AR, compared protein expression patterns between morphologically identified CAD and other BC subtypes, and investigated CAD characteristics. We performed immunohistochemistry for AR and various AR-related proteins in 66 invasive ductal carcinoma (32 ER+/PgR+/HER2-, 8 ER+/PgR+/HER2+, 12 ER-/PgR-/HER2+, and 14 ER-/PgR-/HER2- [triple-negative breast cancer)), 21 invasive lobular carcinoma, and 27 CAD cases. In the CAD group, all cases were AR-positive; some AR-related proteins were highly expressed. Nuclear phosphorylated-mammalian target of rapamycin was highly expressed in CAD cases compared with that in other BC groups, with a 33.3% sensitivity and 97.7% specificity. AR-expressing CAD cases exhibited high expression of other AR-related proteins. Specifically, the combination of AR+, GCDFP15+, and ER - or AR+, FOXA1+, and ER - may be useful for the diagnosis and treatment of AR-positive BC and CAD. These results may assist in androgen-related molecular targeted therapy research.},
}
@article {pmid39829405,
year = {2025},
author = {Mansour, A and Ben-David, BM and Sasson, A and Farraj, J and Mansour, A and Roth, Y and Icht, M},
title = {Association between oral feeding versus enteral feeding and cerumen impaction in older hospitalized adults: A retrospective cohort study.},
journal = {JPEN. Journal of parenteral and enteral nutrition},
volume = {49},
number = {3},
pages = {341-348},
doi = {10.1002/jpen.2724},
pmid = {39829405},
issn = {1941-2444},
mesh = {Humans ; Retrospective Studies ; Aged ; Male ; Female ; *Enteral Nutrition/adverse effects ; *Hospitalization ; Aged, 80 and over ; *Cerumen ; Length of Stay ; Deglutition Disorders ; Risk Factors ; *Diet ; },
abstract = {BACKGROUND: Chewing involves jaw movements that propel cerumen along the ear canal. This mechanism may be reduced in dysphagia, especially for older individuals who are enterally fed. Those patients may be at a higher risk for cerumen impaction and may require longer hospital stays. Examining the relationship between diet type, cerumen impaction, and hospital stay duration was the focus of the present study.<br><br>METHODS: We performed a retrospective cohort study (not registered) among 114 hospitalized older adults. Data were collected on diet type: (1) oral feeding (individuals fed a solid diet or a pureed diet) or (2) enteral feeding (individuals fed via a feeding tube). The results of an otoscopy that quantified cerumen were recorded, as well as hospital stay duration.<br><br>RESULTS: In a mediation analysis, a hospital stay of >1 month was associated with an increased risk of enteral feeding, which in turn, increased the risk of cerumen impaction. Analysis indicated that the link between longer hospitalization and a more severe level of cerumen impaction was fully mediated by diet type (enteral feeding).<br><br>CONCLUSIONS: Enteral feeding seems to be a risk factor for cerumen impaction, rather than merely hospitalization length, in our sample of geriatric patients. These results highlight the importance of continuous monitoring by ear, nose, and throat specialists, as well as regular auditory assessments for patients who are enterally fed for early detection and treatment of cerumen impaction. Particular attention should be paid to cases of prolonged hospitalization, which is associated with the severity of dysphagia.},
}
@article {pmid39822422,
year = {2024},
author = {Aleksiev, T and Popov, V and Dobrev, H},
title = {Radiation-Associated Herpes Zoster: A Clinical Case.},
journal = {Cureus},
volume = {16},
number = {12},
pages = {e75857},
pmid = {39822422},
issn = {2168-8184},
abstract = {Herpes zoster (HZ) is a viral infection caused by the reactivation of endogenous and latent varicella-zoster virus that remains dormant in the cranial nerve or dorsal root ganglia. HZ occurs in a portion of the general population, with a higher incidence observed in high-risk individuals. Patients with impaired immunity, including human immunodeficiency virus infection, organ transplantation, old age, and cancer-related treatments such as chemotherapy (CT) and radiotherapy (RT) were found more prone to HZ infection. We present a case of a 50-year-old patient who underwent a surgical excision of an invasive ductal carcinoma of the right breast. Following 15 fractions of RT, the patient presented with HZ appearing in the radiation field. The patient was treated successfully with Acyclovir, and RT was continued while on maintenance therapy with antiviral drugs. This case presents the importance of early diagnosis and the right choice of treatment in cancer patients and HZ due to the higher risk of complications and further development of the primary condition.},
}
@article {pmid39821030,
year = {2025},
author = {Bullock, E and Brunton, VG},
title = {E-Cadherin-Mediated Cell-Cell Adhesion and Invasive Lobular Breast Cancer.},
journal = {Advances in experimental medicine and biology},
volume = {1464},
number = {},
pages = {259-275},
pmid = {39821030},
issn = {0065-2598},
mesh = {Humans ; *Cadherins/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism/genetics ; Female ; *Carcinoma, Lobular/pathology/metabolism/genetics ; *Cell Adhesion ; Epithelial-Mesenchymal Transition ; Neoplasm Invasiveness ; Adherens Junctions/metabolism/pathology ; Animals ; },
abstract = {E-cadherin is a transmembrane protein and central component of adherens junctions (AJs). The extracellular domain of E-cadherin forms homotypic interactions with E-cadherin on adjacent cells, facilitating the formation of cell-cell adhesions, known as AJs, between neighbouring cells. The intracellular domain of E-cadherin interacts with α-, β- and p120-catenins, linking the AJs to the actin cytoskeleton. Functional AJs maintain epithelial tissue identity and integrity. Transcriptional downregulation of E-cadherin is the first step in epithelial-to-mesenchymal transition (EMT), a process essential in development and tissue repair, which, in breast cancer, can contribute to tumour progression and metastasis. In addition, loss-of-function mutations in E-cadherin are a defining feature of invasive lobular breast cancer (also known as invasive lobular carcinoma (ILC)), the second most common histological subtype of breast cancer. ILC displays a discohesive, single-file invasive growth pattern due to the loss of functional AJs. Despite being so prevalent, until recently there has been limited ILC-focused research and historically ILC patients have often been excluded from clinical trials. Despite displaying a number of good prognostic indicators, such as low grade and high rates of estrogen receptor positivity, ILC patients tend to have similar or poorer outcomes relative to the most common subtype of breast cancer, invasive ductal carcinoma (IDC). In ILC, E-cadherin loss promotes hyperactivation of growth factor receptors, in particular insulin-like growth factor 1 receptor, anoikis resistance and synthetic lethality with ROS1 inhibition. These features introduce clinical vulnerabilities that could potentially be exploited to improve outcomes for ILC patients, for whom there are currently limited tailored treatments available.},
}
@article {pmid39821022,
year = {2025},
author = {Nair, I and Behbod, F},
title = {Models for Studying Ductal Carcinoma In Situ Progression.},
journal = {Advances in experimental medicine and biology},
volume = {1464},
number = {},
pages = {95-108},
pmid = {39821022},
issn = {0065-2598},
mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology/genetics/metabolism ; Disease Progression ; Female ; *Breast Neoplasms/pathology/genetics/metabolism ; Tumor Microenvironment ; *Models, Biological ; *Carcinoma, Ductal, Breast/pathology ; },
abstract = {An estimated 55,720 new cases of ductal carcinoma in situ (DCIS) will be diagnosed in 2023 in the USA alone because of the increased use of screening mammography. The treatment goal in DCIS is early detection and treatment with the hope of preventing progression into invasive disease. Previous studies show progression into invasive cancer as well as reduction in mortality from treatment is not as high as previously thought. So, are we overdiagnosing and over-treating DCIS? An understanding of the natural progression of DCIS is paramount to address this. The purpose of this chapter is to describe various models that have been developed to simulate the processes involved in DCIS to invasive ductal carcinoma (IDC) transition. While each model possesses a unique set of strengths and weaknesses, they have collectively contributed to the current understanding of the molecular and cellular mechanisms underlying this transition. Even though much has been learned, continued advancement of the current models to best match the composition of DCIS epithelial and stromal microenvironment including the extracellular matrix (ECM), stromal cell types, and immune microenvironment will be essential. These advances will undoubtedly pave the way toward a full understanding of mechanisms associated with progression and in predicting when a DCIS lesion remains indolent and when triggers tip in the balance toward progression to malignancy.},
}
@article {pmid39815122,
year = {2025},
author = {Sossa-Melo, C and Abello-Polo, V and Salazar, LA and Peña, AM and Luna-González, M and Cuervo-Lozada, D and Quintero-Vega, GE and Daza, J and Omaña-Orduz, OP and Mantilla, W and Perdomo, I and Galvez, K and Díaz-Correa, LM and Guerrero-Burbano, PA and Herrera, JM and Idrobo, H and Gaviria, LM and Correa-Correa, ME and Lobatón, J and Bermúdez, CD and Pedraza-Morales, JE and Serrano-Casas, JC and Jaramillo, F and Gómez, R and Rosales, C and Solano, MH and Varón, C and Rodríguez-Veiga, R and Martínez-Cuadrón, D and Montesinos, P},
title = {Characteristics, outcomes and treatment patterns in acute myeloid leukemia patients 60 years or older in Colombia: a RENEHOC-PETHEMA study.},
journal = {Annals of hematology},
volume = {104},
number = {1},
pages = {369-381},
pmid = {39815122},
issn = {1432-0584},
mesh = {Humans ; Male ; *Leukemia, Myeloid, Acute/genetics/therapy/mortality/epidemiology/drug therapy/diagnosis ; Female ; Colombia/epidemiology ; Aged ; Middle Aged ; Retrospective Studies ; Aged, 80 and over ; Nucleophosmin ; Treatment Outcome ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Registries ; Survival Rate ; Cytarabine/administration &amp; dosage ; Mutation ; },
abstract = {There is a limited information available on the clinical characteristics, treatment patterns and outcomes on older patients diagnosed with Acute Myeloid Leukemia (AML) in Latin-America. This multicenter retrospective study analyzed 269 patients over 60 years of age diagnosed with AML in Colombia, using data from RENEHOC-PETHEMA registry, from 2009 to 2023. The median age at diagnosis was 70 years (Range:60-98), 55% were men, 61% had an ECOG < 2, and 75.5% had de novo AML. FLT3-ITD or NPM1 mutations were performed in 23.4% and 15.6% patients, and detected in 14.3% and 16.7% of cases, respectively. Treatment included intensive chemotherapy (IC) (36.8%), Low-Intensity Regimen Based on Low-Dose Cytarabine (LDAC-based) (12.6%), hypomethylating agents (HMAs, with/without venetoclax) (35.3%), and supportive care (15.2%). The overall survival (OS) rate was 35.2% at 1 year and 5.6% at 5 years (13.7% for IC, 9.4% for LDAC-based, and 0% for other treatments); with median OS of 8.2 months (10.6 months after IC, 8.8 months after non-IC, 8.9 months after azacitidine/decitabine, 8.2 months after azacitidine-venetoclax, and 1.9 months with supportive care). Only 1.5% of patients underwent a transplant in the first line. The Leukemia-free survival (LFS) rate was 45.8% at 1-year and 13.7% at 5-years (22.4% for IC, 9.4% and 0% for other treatments); with median LFS of 9.5 months (17.3 months after IC, 7.4 months after LDAC-based, and 10.8 months after HMA). This study provides new insights into the management of patients in Colombia, highlighting the need for a highly individualized approach in treating AML in elderly patients.},
}
@article {pmid39806949,
year = {2025},
author = {Gallas, AE and Morenikeji, GO and King, RE and Adegbaju, MS and Ayoola, A and Taiwo, G and Morenikeji, OB},
title = {An Overview of Invasive Ductal Carcinoma (IDC) in Women's Breast Cancer.},
journal = {Current molecular medicine},
volume = {25},
number = {4},
pages = {361-371},
pmid = {39806949},
issn = {1875-5666},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/genetics/therapy/diagnosis/etiology/metabolism ; *Carcinoma, Ductal, Breast/genetics/pathology/therapy/diagnosis/etiology/metabolism ; Biomarkers, Tumor/genetics ; DNA Methylation ; Prognosis ; Mutation ; Gene Expression Regulation, Neoplastic ; },
abstract = {Invasive ductal carcinoma (IDC) is the most common type of breast cancer, primarily affecting women in the United States and across the world. This review summarizes key concepts related to IDC causes, treatment approaches, and the identification of biological markers for specific prognoses. Furthermore, we reviewed many studies, including those involving patients with IDC and ductal carcinoma in situ (DCIS) that progressed to IDC. We reported various studies on the causes of IDC, including mutations on BRCA1 and BRCA2, different levels of expression of specific genes in signaling pathways, menopause status, alcohol consumption, aging, and hormone imbalances that cause IDC while p-SMAD4 expressions, DNA methylation, regulations of hub genes, and underestimation of IDC affecting prognoses. Prompt IDC diagnosis and early intervention have been reported to demonstrate a greater probability of eradicating IDC and preventing further recurrence in the future. It is crucial for physicians and researchers to equip patients with the best information possible to proactively manage their health, whether it be for IDC prevention or treatment. Overall, our review provided a comprehensive understanding of IDC that enables patients to grasp the nature of the disease with the hope of mitigating IDC risk, decrease the anxiety of a cancer diagnosis, and encourage patients to become more involved in making informed decisions for their healthcare.},
}
@article {pmid39805165,
year = {2025},
author = {Michelon, I and Castro, CER and Madeira, T and Dacoregio, MI and Stecca, C and Soares, LR and Saeed, A and Vilbert, M and Cavalcante, L},
title = {Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: A systematic review and updated meta-analysis.},
journal = {Cancer treatment reviews},
volume = {133},
number = {},
pages = {102882},
doi = {10.1016/j.ctrv.2025.102882},
pmid = {39805165},
issn = {1532-1967},
mesh = {Humans ; *Breast Neoplasms/drug therapy/pathology/metabolism ; *Trastuzumab/therapeutic use/pharmacology ; Receptor, ErbB-2/metabolism ; *Brain Neoplasms/secondary/drug therapy/metabolism ; Female ; *Immunoconjugates/therapeutic use ; *Antineoplastic Agents, Immunological/therapeutic use ; Camptothecin/analogs &amp; derivatives ; },
abstract = {BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease.<br><br>METHODS: A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses.<br><br>RESULTS: We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4&#xa0;%; disease control rate [DCR], 94.4&#xa0;%; and clinical benefit rate [CBR], 79.3&#xa0;%) and a 12-month PFS of 64.7&#xa0;% and OS of 82.7&#xa0;%. Intracranial ORR, DCR, and CBR were seen in 62.2&#xa0;%, 88.6&#xa0;%, and 68.6&#xa0;% of patients, respectively, and 67.4&#xa0;% achieved intracranial PFS at 12&#xa0;months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95&#xa0;% confidence interval 1.3-10.8, p&#xa0;=&#xa0;0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4&#xa0;% and 94.1&#xa0;% of patients, respectively.<br><br>CONCLUSIONS: This updated meta-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.},
}
@article {pmid39804847,
year = {2025},
author = {Wang, K and Fischer, A and Maccio, U and Zitzmann, K and Robledo, M and Lauseker, M and Bauer, J and Bechmann, N and Gahr, S and Maurer, J and Peischer, L and Reul, A and Nieß, H and Zimmermann, P and Ilmer, M and Schilbach, K and Knösel, T and Kroiss, M and Fassnacht, M and Müller, SA and Morand, GB and Huber, A and Vetter, D and Lehmann, K and Kulcsar, Z and Mohr, H and Pellegata, NS and Hantel, C and Reincke, M and Beuschlein, F and Pacak, K and Grossman, AB and Auernhammer, CJ and Nölting, S},
title = {Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.},
journal = {European journal of endocrinology},
volume = {192},
number = {1},
pages = {46-60},
doi = {10.1093/ejendo/lvae163},
pmid = {39804847},
issn = {1479-683X},
support = {314061271 - TRR 205//German Research Foundation/ ; },
mesh = {Humans ; *Neuroendocrine Tumors/pathology/drug therapy/metabolism/genetics ; *Pheochromocytoma/pathology/drug therapy/metabolism/genetics ; *Paraganglioma/pathology/drug therapy/metabolism/genetics ; *Pancreatic Neoplasms/pathology/drug therapy/metabolism/genetics ; Female ; *Intestinal Neoplasms/pathology/drug therapy/metabolism/genetics ; Male ; *Adrenal Gland Neoplasms/pathology/drug therapy/metabolism/genetics ; *Stomach Neoplasms/drug therapy/pathology/metabolism/genetics ; *Gonadal Steroid Hormones/pharmacology ; Middle Aged ; Adult ; Estradiol/pharmacology ; Testosterone/pharmacology ; Estrogen Receptor alpha/metabolism ; Progesterone/pharmacology ; Dehydroepiandrosterone Sulfate/pharmacology ; Aged ; *Gastrointestinal Neoplasms/drug therapy/pathology/metabolism ; Cell Survival/drug effects ; },
abstract = {OBJECTIVE: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).<br><br>METHODS: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).<br><br>RESULTS: In PPGLs, estradiol and progesterone (1&#x2005;&#xb5;m) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants. Estrogen receptor alpha (ER&#x3b1;) positivity was detected in 11/36 PPGLs, including 4/4 head-and-neck paragangliomas (HNPGLs). ER&#x3b1;-positive tumors responded with a significant cell viability decrease to estradiol. DHEAS and testosterone (1&#x2005;&#xb5;m) displayed no effects, but higher doses of testosterone (10&#x2005;&#xb5;m) demonstrated significant antitumor effects, including a pheochromocytoma lung metastasis with strong androgen receptor positivity (30%). Driven by the antitumor effects of estrogen, we evaluated G-protein-coupled estrogen receptor (GPER) agonist G-1 as a potential therapeutic option for PPGLs and found strong significant antitumor potential, with the strongest efficacy in tumors with NF1 pathogenic variants. Moreover, we detected sex-related differences-tumors from male patients showed significantly stronger responsivity to G-1 compared with tumors from female patients. In GEP-NETs, sex hormones showed overall no effects, especially no tumor growth-promoting effects.<br><br>CONCLUSION: We provide novel data on the effects of elevated sex hormone levels, potentially seen during pregnancy or hormone replacement therapy, on PPGL/GEP-NET tumor growth. G-1 might offer a novel therapeutic approach for some PPGLs depending on patient's sex and the individual tumor's genetic/molecular background. All HNPGLs showed ER&#x3b1; positivity.},
}
@article {pmid39799921,
year = {2025},
author = {Fu, J and Wang, J and Ma, Z and Yuan, D and Zhang, Y and Wang, L and Luo, Y},
title = {CaCO3-coated indoxacarb deep eutectic solvent complexed with diatomaceous earth improves insecticidal activity against the red imported fire ants.},
journal = {Ecotoxicology and environmental safety},
volume = {289},
number = {},
pages = {117709},
doi = {10.1016/j.ecoenv.2025.117709},
pmid = {39799921},
issn = {1090-2414},
mesh = {Animals ; *Ants/drug effects ; *Insecticides/chemistry/toxicity ; *Oxazines/chemistry/toxicity ; *Diatomaceous Earth/chemistry ; *Calcium Carbonate/chemistry ; *Deep Eutectic Solvents/chemistry ; Nanoparticles/chemistry ; Fire Ants ; },
abstract = {The red imported fire ants (RIFAs) are a globally important invasive pest that severely affects the ecosystem and human health, and its current control is primarily through chemical pesticides. However, the extensive use of chemical pesticides causes environmental problems, and alternative strategies for controlling this pest are being explored. In our study, we aimed to design a deep eutectic solvent (DES)-CaCO3 system in which RIFAs were used as target insects to increase the lethal activity and behavioural regulation effects on RIFAs via contact and feeding. Indoxacarb (IDC) was made into DESs with three fatty acids, oleic acid (OA), linoleic acid (LA), and linolenic acid (LNA), which showed a significant increase in lethal activity against worker ants compared with IDC. OA@IDC@CaCO3, LA@IDC@CaCO3, and LNA@IDC@CaCO3 nanoparticles were prepared via interfacial precipitation. Characterization of the structures of the three pesticide-carrying nanoparticles revealed that all three fatty acid eutectic solvents formed spherical CaCO3 nanoparticles, with average particle sizes between 0.59 and 0.90 μm, which increased with increasing degree of fatty acid unsaturation. The pesticide loading ranged from 2.13 %⁓3.43 %, and the surfaces were all positively charged and well dispersed. OA@IDC@CaCO3 was relatively more effective and was able to dramatically inhibit the abandonment and foraging behaviours of RIFAs, prolong the time required for these behaviours, and decrease the number of feeding worker ants and the amount of food consumed. OA@IDC@CaCO3 was subsequently compounded with diatomaceous earth (DA), and spiked into baits, which significantly increased the contact and feeding activity of worker ants, inhibited the feeding, digging, and corpse-discarding behaviours of RIFAs. In the field trial, the combined control effect of the DA + OA@IDC@CaCO3 group was 83.38 %, which was greater than the 69.65 % of the commercial agent control group. In this study, IDC bait was co-prepared by using acid as a comelting solvent, CaCO3 as a coating, and DA as a pesticide adjuvant, which improved the activity against RIFAs, prolonged the holding period of IDC, and improved the prevention and control of RIFAs. Therefore, our research provides a simple and feasible approach for designing and constructing novel nanopesticides for RIFAs control.},
}
@article {pmid39795975,
year = {2024},
author = {Caca, J and Bartelt, A and Egea, V},
title = {Hypoxia Regulates Brown Adipocyte Differentiation and Stimulates miR-210 by HIF-1α.},
journal = {International journal of molecular sciences},
volume = {26},
number = {1},
pages = {},
pmid = {39795975},
issn = {1422-0067},
mesh = {*MicroRNAs/genetics/metabolism ; Animals ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; *Adipocytes, Brown/metabolism/cytology ; *Cell Differentiation/genetics ; Mice ; Thermogenesis/genetics ; Cell Hypoxia ; },
abstract = {MicroRNAs (miRNAs) are short sequences of single-stranded non-coding RNAs that target messenger RNAs, leading to their repression or decay. Interestingly, miRNAs play a role in the cellular response to low oxygen levels, known as hypoxia, which is associated with reactive oxygen species and oxidative stress. However, the physiological implications of hypoxia-induced miRNAs ("hypoxamiRs") remain largely unclear. Here, we investigate the role of miR-210 in brown adipocyte differentiation and thermogenesis. We treated the cells under sympathetic stimulation with hypoxia, CoCl2, or IOX2. To manipulate miR-210, we performed reverse transfection with antagomiRs. Adipocyte markers expression, lipid accumulation, lipolysis, and oxygen consumption were measured. Hypoxia hindered BAT differentiation and suppressed sympathetic stimulation. Hypoxia-induced HIF-1α stabilization increased miR-210 in brown adipocytes. Interestingly, miR-210-5p enhanced differentiation under normoxic conditions but was insufficient to rescue the inhibition of brown adipocyte differentiation under hypoxic conditions. Although adrenergic stimulation activated HIF-1α signaling and upregulated miR-210 expression, inhibition of miR-210-5p did not significantly influence UCP1 expression or oxygen consumption. In summary, hypoxia and adrenergic stimulation upregulated miR-210, which impacted brown adipocyte differentiation and thermogenesis. These findings offer new insights for the physiological role of hypoxamiRs in brown adipose tissue, which could aid in understanding oxidative stress and treatment of metabolic disorders.},
}
@article {pmid39788307,
year = {2025},
author = {Doan, VTH and Imai, T and Kawazoe, N and Chen, G and Yoshitomi, T},
title = {Regulation of antigen presentation and interleukin 10 production in murine dendritic cells via the oxidative stimulation of cell membrane using a polycation-porphyrin-conjugate-immobilized cell culture dish.},
journal = {Acta biomaterialia},
volume = {193},
number = {},
pages = {231-241},
doi = {10.1016/j.actbio.2025.01.004},
pmid = {39788307},
issn = {1878-7568},
mesh = {Animals ; *Dendritic Cells/cytology/metabolism/immunology/drug effects ; *Porphyrins/chemistry/pharmacology ; *Cell Membrane/metabolism/drug effects ; *Interleukin-10/biosynthesis ; Mice ; *Antigen Presentation/drug effects ; Polyelectrolytes ; Oxidation-Reduction ; *Cells, Immobilized/metabolism/cytology ; *Polyamines/chemistry/pharmacology ; },
abstract = {Tolerogenic dendritic cells with professional antigen presentation via major histocompatibility complex molecules, co-stimulatory molecules (CD80/86), and interleukin 10 production have attracted significant attention as cellular therapies for autoimmune, allergic, and graft-versus-host diseases. In this study, we developed a cell culture dish equipped with polycation-porphyrin-conjugate-immobilized glass (PA-HP-G) to stimulate immature murine dendritic cell (iDCs). Upon irradiation with a red light at 635 nm toward the PA-HP-G surface, singlet oxygen was generated by the immobilized porphyrins on the PA-HP-G surface. When iDCs were cultured on the PA-HP-G surface, moderate light irradiation generated lipid radicals without excessive generation of reactive oxygen species in the cytoplasm and nucleus, which led to the oxidative stimulation of the iDC cell membrane without cell death. Light irradiation changed the morphology of dendritic cells on the PA-HP-G surface to a tree-like structure with dendrites, accelerated their maturation, and enhanced the antigen-presenting ability for the ovalbumin peptide via major histocompatibility complex class I molecules. Additionally, the antigen-presenting dendritic cells on the PA-HP-G surface produced the anti-inflammatory cytokine interleukin 10 upon light irradiation. These results indicated that upon moderate light irradiation, the PA-HP-G surface regulated the maturation of iDCs into tolerogenic dendritic cells. STATEMENT OF SIGNIFICANCE: • Cell culture dish is developed for selective oxidative stimulus of cell membrane. • [1]O2 is generated from polycation/porphyrin-immobilized glass by light irradiation. • Lipid radicals are generated without generation of ROS in cytoplasm and nuclei. • Immature dendritic cells are maturated by oxidative stimulation of cell membrane. • Oxidative membrane stimulus enhances antigen-presentation and IL-10 secretion.},
}
@article {pmid39734136,
year = {2025},
author = {Huws, AM and Davies, GR and Lewis, PD and Morgan, C},
title = {Comparison of Systemic Inflammatory Indices With the Oncotype DX Recurrence Score and the Nottingam Prognostic Index in Early Hormone Receptor Positive Ductal Breast Cancer.},
journal = {Clinical breast cancer},
volume = {25},
number = {4},
pages = {358-367},
doi = {10.1016/j.clbc.2024.11.022},
pmid = {39734136},
issn = {1938-0666},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/genetics/immunology/blood ; Middle Aged ; *Neoplasm Recurrence, Local/pathology/epidemiology/immunology/genetics ; Prognosis ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology/genetics/immunology ; Aged ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Biomarkers, Tumor ; *Inflammation/blood ; Receptor, ErbB-2/metabolism ; },
abstract = {BACKGROUND: Adjuvant therapy decisions in hormone receptor positive, HER2 negative breast cancer are evolving. Gene panel testing has reduced the number of patients recommended for chemotherapy by up to two thirds. Identifying low risk genomic cases before testing could represent a significant economic impact. Systemic inflammatory indices have shown promise as prognostic markers in early breast cancer. We investigated the utility of four systemic inflammatory indices with the Nottingham Prognostic Index to predict the Oncotype DX® recurrence scores threshold level (low or high score), in women aged 50 and over with node negative invasive ductal carcinoma of the breast.<br><br>METHODS: A retrospective review of 245 patients with Oncotype DX&#xae; Recurrence Score testing from 2007 to 2021 were identified. The Nottingham Prognostic Index and systemic inflammatory indices ratios were estimated from histology results and preoperative peripheral blood samples respectively.<br><br>RESULTS: 22.4% of the cohort had a Recurrence Score in the higher risk group. This group had a greater percentage of grade 3 tumours, progesterone receptor negativity, higher Nottingham Prognostic Scores, and inflammatory indices ratios than the lower risk group. A decision tree incorporating the Neutrophil Lymphocyte Ratio with clinicopathological features showed potential as an indicator of a high Oncotype DX&#xae; RS score, such that further investigation is warranted to assess whether Recurrence Score testing could be triaged in certain cohorts of patients. In this study, 38% of patients might be able to avoid genomic testing based on the decision tree analysis.<br><br>CONCLUSION: Utility of inflammatory indices with clinicopathological features may help triage gene panel testing.},
}
@article {pmid39724992,
year = {2025},
author = {Wang, Y and Zhang, J and Wang, Y and Liu, Y and Shi, B and Li, X and He, J and Zhang, H},
title = {Lower expression of MMP2, FLNA, and CFL1 is correlated with favorable prognosis in invasive micropapillary breast cancer.},
journal = {Gene},
volume = {940},
number = {},
pages = {149192},
doi = {10.1016/j.gene.2024.149192},
pmid = {39724992},
issn = {1879-0038},
mesh = {Humans ; *Breast Neoplasms/genetics/pathology/metabolism/mortality ; Female ; Prognosis ; *Matrix Metalloproteinase 2/genetics/metabolism ; *Filamins/genetics/metabolism ; Middle Aged ; Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; Retrospective Studies ; *Carcinoma, Papillary/genetics/pathology/metabolism/mortality ; *Carcinoma, Ductal, Breast/genetics/pathology ; Nomograms ; Aged ; },
abstract = {PURPOSE: Despite its recognized aggressive clinical manifestations, invasive micropapillary carcinoma has a controversial prognosis in comparison to invasive ductal carcinoma of the breast. This retrospective study aimed to explore the prognosis and underlying molecular mechanisms of invasive micropapillary carcinoma.<br><br>METHODS: Through the SEER database, we compared patients survival outcomes with invasive micropapillary carcinoma versus invasive ductal carcinoma, and developed a nomogram to predict the overall survival of the former group. We explored gene profiles of invasive micropapillary carcinoma in the GEO database. Hub genes were identified as the top ten genes in the PPI network with the highest degrees of connectivity, and three of them were selected for validation by immunohistochemistry.<br><br>RESULTS: Invasive micropapillary carcinoma patients had better overall survival and breast cancer-specific survival than invasive ductal carcinoma patients did. Multivariate analysis revealed age, marital status, TN stage, ER status, and chemotherapy as independent prognostic factors for invasive micropapillary carcinoma patients, which were used to construct a nomogram with good performance. A total of 294 DEGs were identified, with ten hub genes, including MMP2, FLNA and CFL1, which were expressed at lower levels in invasive micropapillary carcinoma patients than in invasive ductal carcinoma patients, indicating favorable outcomes.<br><br>CONCLUSIONS: Patients with invasive micropapillary carcinoma generally have a better prognosis than those with invasive ductal carcinoma does, which could be attributed to the lower expression of pro-oncogenic genes in the former group; however, the underlying mechanism needs further investigation.},
}
@article {pmid39724567,
year = {2025},
author = {Yang, M and Wang, C and Ouyang, L and Zhang, H and Lin, J},
title = {Establishment of prognostic model for invasive ductal carcinoma with distant metastasis within the triple-negative breast cancer: a SEER population-based study.},
journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)},
volume = {34},
number = {5},
pages = {392-404},
doi = {10.1097/CEJ.0000000000000925},
pmid = {39724567},
issn = {1473-5709},
mesh = {Humans ; *Triple Negative Breast Neoplasms/pathology/mortality/therapy ; Female ; SEER Program/statistics &amp; numerical data ; *Nomograms ; Retrospective Studies ; Prognosis ; Middle Aged ; *Carcinoma, Ductal, Breast/mortality/secondary/therapy/pathology ; Aged ; Adult ; Risk Factors ; Follow-Up Studies ; *Bone Neoplasms/secondary ; *Liver Neoplasms/secondary ; Survival Rate ; },
abstract = {Triple-negative breast cancer (TNBC) is a complex and diverse group of malignancies. Invasive ductal carcinoma (IDC) is the predominant pathological subtype and is closely linked to the ominous potential for distant metastasis, a pivotal factor that significantly influences patient outcomes. In light of these considerations, the present study was conceived with the objective of developing a nomogram model. This model was designed to predict the prognosis observed in IDC with distant metastasis in TNBC. This was a retrospective study based on the SEER database. Data of 9739 IDC-TNBC patients diagnosed from 2010 to 2020 were included in our study. Independent risk factors were screened by univariate and multivariate Cox regression analyses successively, which were used to develop a nomogram model predicting for prognosis. Cox multivariable analysis showed statistical significance in bone metastasis, liver metastasis, surgery, and chemotherapy. Incorporating statistically significant variables, as well as clinically significant age, lung metastasis, and brain metastasis into the construction of the prediction model, the C-indexes of the training group and validation group were 0.702 (0.663-0.741) and 0.667 (0.600-0.734), respectively, while the calibration curves were all close to the eideal 45° reference line, and decision curve analysis curves show excellent net benefit in the predictive model. The prognostic prediction model developed in this study demonstrated enhanced predictive accuracy, enabling a more precise evaluation of mortality risks associated with IDC with distant metastasis in TNBC.},
}
@article {pmid39723668,
year = {2025},
author = {Mitsa, G and Florianova, L and Lafleur, J and Aguilar-Mahecha, A and Zahedi, RP and Del Rincon, SV and Basik, M and Borchers, CH and Batist, G},
title = {Clinical Proteomics Reveals Vulnerabilities in Noninvasive Breast Ductal Carcinoma and Drives Personalized Treatment Strategies.},
journal = {Cancer research communications},
volume = {5},
number = {1},
pages = {138-149},
pmid = {39723668},
issn = {2767-9764},
mesh = {Humans ; Female ; *Proteomics/methods ; *Breast Neoplasms/metabolism/pathology/therapy/genetics ; *Precision Medicine/methods ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology/therapy/genetics ; *Biomarkers, Tumor/metabolism ; *Proteome ; },
abstract = {ABSTRACT: Ductal carcinoma in situ (DCIS) is the most common type (80%) of noninvasive breast lesions in women. The lack of validated prognostic markers, limited patient numbers, and variable tissue quality have a significant impact on the diagnosis, risk stratification, patient enrollment, and results of clinical studies. In this study, we performed label-free quantitative proteomics on 50 clinical formalin-fixed, paraffin-embedded biopsies, validating 22 putative biomarkers from independent genetic studies. Our comprehensive proteomic phenotyping reveals more than 380 differentially expressed proteins and metabolic vulnerabilities, which can inform new therapeutic strategies for DCIS and invasive ductal carcinoma. Due to the readily druggable nature of proteins and metabolic enzymes or metabolism inhibitors, this study is of high interest for clinical research and the pharmaceutical industry. To further evaluate our findings, and to promote the clinical translation of our study, we developed a highly multiplexed targeted proteomics assay for 90 proteins associated with cancer metabolism, RNA regulation, and signature cancer pathways, such as PI3K/AKT/mTOR and EGFR/RAS/RAF.<br><br>SIGNIFICANCE: This study provides real-world evidence for DCIS, a disease for which currently no molecular tools or biomarkers exist, and gives an unbiased, comprehensive, and deep proteomic profile, identifying >380 actionable targets.},
}
@article {pmid39721789,
year = {2024},
author = {Nagahara, M and Tezuka, K},
title = {[Invasive Ductal Carcinoma with Total Infarction and Necrosis-Case Report and Literature Review].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {51},
number = {12},
pages = {1255-1258},
pmid = {39721789},
issn = {0385-0684},
mesh = {Humans ; Female ; Aged ; *Necrosis ; *Breast Neoplasms/pathology/complications/surgery ; *Infarction/etiology/pathology ; *Carcinoma, Ductal, Breast/complications/pathology/surgery ; Mastectomy ; },
abstract = {A 71-year-old woman visited our hospital with pain and itching in her left breast which had commenced the day before admission. On palpation, we detected a 2.0 cm nodule, indicative of an elastic and hard tumor located centrally in the left breast. Mammography revealed an oval, microlobulated mass in the central quadrant of the left breast. Ultrasonography indicated a 1.5×1.3 cm hypoechoic lesion at the 12 o'clock position near the left nipple. Core needle biopsy revealed an invasive ductal carcinoma. Therefore, we mastectomized the left breast. Histologically, the tumor mass exhibited total necrosis, with viable carcinoma cells detected in a paramammary lymph node at the resected breast edge. Consequently, the tumor was diagnosed as a solid tubular carcinoma with total infarction and necrosis. Here, we present a rare case of breast cancer associated with infarction and necrosis.},
}
@article {pmid39710328,
year = {2025},
author = {Denimal, L and Klein, C and Capon, G and Alezra, E and Bernhard, JC and Estrade, V and Blanc, P and Bladou, F and Robert, G},
title = {Impact of clean intermittent self-catheterization and indwelling catheterization on perioperative outcomes in patients with urinary retention undergoing BPH surgery: A comparative monocentric retrospective study.},
journal = {The French journal of urology},
volume = {35},
number = {1},
pages = {102851},
doi = {10.1016/j.fjurol.2024.102851},
pmid = {39710328},
issn = {2950-3930},
mesh = {Humans ; Male ; *Urinary Retention/etiology/therapy ; *Prostatic Hyperplasia/surgery/complications ; Retrospective Studies ; Aged ; *Catheters, Indwelling/adverse effects ; Treatment Outcome ; Postoperative Complications/epidemiology/etiology ; Middle Aged ; *Intermittent Urethral Catheterization/methods ; Aged, 80 and over ; *Prostatectomy ; Urinary Catheterization ; Self Care ; },
abstract = {INTRODUCTION AND OBJECTIVES: In case of acute urinary retention (AUR) due to benign prostatic hyperplasia (BPH) first trial without catheter (TWOC) may fail in about 30% of cases. In this situation most of patients have to keep an indwelling catheter (IDC) or to perform clean intermittent self-catheterization (CISC) until surgery. Although CISC has shown several advantages over IDC in neurologic patients, it is barely proposed in case of acute or chronic urinary retention due to BPH and comparative data on the outcomes of BPH surgery are very sparse. The aim of this study was to evaluate peri-operative outcomes of BPH surgery depending on the type of urinary drainage (IDC or CISC) in a population of patients with acute or chronic urinary retention and TWOC failure.<br><br>PATIENTS AND METHOD: We retrospectively analyzed a prospectively maintained database on BPH surgery to retrieve the records of all men admitted for surgical treatment of BPH following acute or chronic urinary retention with TWOC failure over a one-year period of time (January to December 2022). Two groups were constituted depending on the type of urinary drainage at the time of surgery (IDC or CISC). Peri-operative outcomes were compared between groups regarding pre-operative urine culture, antibiotic consumption, post-operative complications, length of hospital stay, and spontaneous voiding after catheter removal.<br><br>RESULTS: Between January and December 2022, 59 patients underwent BPH surgery after urinary retention and TWOC failure. At the time of surgery, 28 patients were on IDC (47%) and 31 patients were on CISC (53%). Despite a shorter delay between AUR and surgery in the IDC group (42days vs. 80days, P<0.01), patients had a significantly higher rate of pre-operative positive urine culture (100% vs. 51.6%, P<0.01), received antibiotics more frequently (93% vs. 42%, P<0.01), had a higher rate of post-operative complications (50% vs. 13%, P<0.01), stayed longer in the hospital (3days vs. 2days, P=0.02), and had a higher rate of post-operative retention (36% vs. 6.5%, P<0.01).<br><br>CONCLUSION: In our experience, the use of CISC before BPH surgery improved peri-operative outcomes as compared to IDC. CISC reduced antibiotic consumption, post-operative complications, length of hospital stay, and improved micturition recovery after catheter removal.},
}
@article {pmid39708123,
year = {2024},
author = {Xie, T and Fan, G and Tang, L and Xing, P and Shi, Y},
title = {Artificial neural network systems to predict the response to sintilimab in squamous-cell non-small-cell lung cancer based on data of ORIENT-3 study.},
journal = {Cancer immunology, immunotherapy : CII},
volume = {74},
number = {1},
pages = {29},
pmid = {39708123},
issn = {1432-0851},
mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/drug therapy/immunology ; *Neural Networks, Computer ; *Lung Neoplasms/drug therapy/immunology ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Male ; Female ; Biomarkers, Tumor ; Prognosis ; Middle Aged ; Carcinoma, Squamous Cell/drug therapy/immunology ; Aged ; },
abstract = {BACKGROUND: Existing biomarkers and models for predicting response to programmed cell death protein 1 monoclonal antibody in advanced squamous-cell non-small cell lung cancer (sqNSCLC) did not have enough accuracy. We used data from the ORIENT-3 study to construct artificial neural network (ANN) systems to predict the response to sintilimab for sqNSCLC.<br><br>METHODS: Four ANN systems based on bulk RNA data to predict disease control (DC), immune DC (iDC), objective response (OR) and immune OR (iOR) were constructed and tested for patients with sqNSCLC treated with sintilimab. The mechanism exploration on the bulk and the spatial level were performed in patients from the ORIENT-3 study and the real world, respectively.<br><br>FINDINGS: sqNSCLC&#xa0;patients with different responses to sintilimab&#xa0;showed each unique transcriptomic spectrum. Four ANN&#xa0;systems showed high accuracy in the test cohort (AUC of DC, iDC, OR and iOR were 0.83, 0.89, 0.93 and 0.94, respectively). The performance of ANN systems was better than that of linear model systems and showed high stability. The mechanism exploration on the bulk level suggested that patients with lower ANN system scores (worse response) had a higher ratio of immune-related pathways enrichment. The mechanism exploration on the spatial level indicated that patients with better response to immunotherapy had fewer clusters of both tumor and cytotoxicity T cell spots.<br><br>INTERPRETATION: The four ANN systems showed high accuracy, robustness and stability in predicting the response to sintilimab for patients with sqNSCLC.},
}
@article {pmid39684874,
year = {2024},
author = {Galappaththi, SPL and Smith, KR and Alsatari, ES and Hunter, R and Dyess, DL and Turbat-Herrera, EA and Dasgupta, S},
title = {The Genomic and Biologic Landscapes of Breast Cancer and Racial Differences.},
journal = {International journal of molecular sciences},
volume = {25},
number = {23},
pages = {},
pmid = {39684874},
issn = {1422-0067},
support = {1R21MD019400-01/MD/NIMHD NIH HHS/United States ; },
mesh = {Humans ; *Breast Neoplasms/genetics/pathology/epidemiology ; Female ; *Genomics/methods ; Dysbiosis ; Racial Groups/genetics ; },
abstract = {Breast cancer is a significant health challenge worldwide and is the most frequently diagnosed cancer among women globally. This review provides a comprehensive overview of breast cancer biology, genomics, and microbial dysbiosis, focusing on its various subtypes and racial differences. Breast cancer is primarily classified into carcinomas and sarcomas, with carcinomas constituting most cases. Epidemiology and breast cancer risk factors are important for public health intervention. Staging and grading, based on the TNM and Nottingham grading systems, respectively, are crucial to determining the clinical outcome and treatment decisions. Histopathological subtypes include in situ and invasive carcinomas, such as invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). The review explores molecular subtypes, including Luminal A, Luminal B, Basal-like (Triple Negative), and HER2-enriched, and delves into breast cancer's histological and molecular progression patterns. Recent research findings related to nuclear and mitochondrial genetic alterations, epigenetic reprogramming, and the role of microbiome dysbiosis in breast cancer and racial differences are also reported. The review also provides an update on breast cancer's current diagnostics and treatment modalities.},
}
@article {pmid39684409,
year = {2024},
author = {Feng, M and Cui, H and Li, S and Li, L and Zhou, C and Chen, L and Cao, Y and Gao, Y and Li, D},
title = {Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications.},
journal = {International journal of molecular sciences},
volume = {25},
number = {23},
pages = {},
pmid = {39684409},
issn = {1422-0067},
support = {22YF1407800//Shanghai Municipal Commission of Science and Technology/ ; No.82103429//National Natural Science Foundation of China/ ; No.82303311//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Breast Neoplasms/genetics/immunology/pathology/metabolism ; Female ; *Ubiquitin-Activating Enzymes/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; Prognosis ; *Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; },
abstract = {Ubiquitin-Activating Enzyme E1 (UBA1), an E1 enzyme involved in the activation of ubiquitin enzymes, has been involved in the onset and progression of different cancers in humans. Nevertheless, the precise contribution of UBA1 in breast cancer (BC) is still poorly characterized. In this study, a thorough investigation was carried out to elucidate the significance of UBA1 and validate its functionality in BC. Through the analysis of mRNA sequencing data of BC patients, the mRNA expression of UBA1 was observed to be notably enhanced in cancer tissues relative to controls, and high UBA1 expression was linked to worse overall survival (OS), disease-specific survival (DSS), and progress-free survival (PFS). Moreover, UBA1 exhibited potential as an independent prognostic and diagnostic biomarker for individuals with BC. Additionally, functional enrichment analysis revealed the involvement of UBA1 in inflammation-linked pathways, like the TNF-α signaling pathway, the IL-6 signaling pathway, and various immune-related biological processes. Notably, single-sample gene set enrichment analysis (ssGSEA) aided in the identification of a negative link between UBA1 expression and the levels of infiltrating mast cells, Th1 cells, iDC cells, B cells, DC cells, Tem cells, Cytotoxic cells, T cells, CD8T cells, and pDC cells. Finally, this study demonstrated that silencing UBA1 significantly impeded the growth and development of BC cell lines. These findings highlight UBA1 as a potential prognostic biomarker linked to immune infiltration in BC, thereby depicting its potential as a new therapeutic target for individuals with BC.},
}
@article {pmid39658630,
year = {2025},
author = {Papargyriou, A and Najajreh, M and Cook, DP and Maurer, CH and Bärthel, S and Messal, HA and Ravichandran, SK and Richter, T and Knolle, M and Metzler, T and Shastri, AR and Öllinger, R and Jasper, J and Schmidleitner, L and Wang, S and Schneeweis, C and Ishikawa-Ankerhold, H and Engleitner, T and Mataite, L and Semina, M and Trabulssi, H and Lange, S and Ravichandra, A and Schuster, M and Mueller, S and Peschke, K and Schäfer, A and Dobiasch, S and Combs, SE and Schmid, RM and Bausch, AR and Braren, R and Heid, I and Scheel, CH and Schneider, G and Zeigerer, A and Luecken, MD and Steiger, K and Kaissis, G and van Rheenen, J and Theis, FJ and Saur, D and Rad, R and Reichert, M},
title = {Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.},
journal = {Nature biomedical engineering},
volume = {9},
number = {6},
pages = {836-864},
pmid = {39658630},
issn = {2157-846X},
mesh = {*Carcinoma, Pancreatic Ductal/pathology/genetics/drug therapy/metabolism ; Animals ; Humans ; *Pancreatic Neoplasms/pathology/genetics/drug therapy/metabolism ; Mice ; *Organoids/pathology/drug effects/metabolism ; Phenotype ; Epithelial-Mesenchymal Transition ; Cell Line, Tumor ; },
abstract = {In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo. We also show that phenotype-specific therapeutic vulnerabilities and modes of treatment-induced phenotype reprogramming can be captured in phenotypic heterogeneity maps. Our methodology and analyses of tumour-cell heterogeneity in PDAC may guide the development of phenotype-targeted treatment strategies.},
}
@article {pmid39654368,
year = {2025},
author = {Krings, G and Shamir, ER and Laé, M and Bean, GR and Post, MD and Schnitt, SJ and Chen, YY},
title = {Serous-like breast carcinomas: immunophenotypic, genetic, and clinicopathologic characterization of a morphologically distinct group of tumours.},
journal = {Histopathology},
volume = {86},
number = {5},
pages = {779-792},
doi = {10.1111/his.15385},
pmid = {39654368},
issn = {1365-2559},
mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology/genetics ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Immunophenotyping ; *Cystadenocarcinoma, Serous/pathology/genetics/diagnosis ; Diagnosis, Differential ; Aged, 80 and over ; },
abstract = {AIMS: Unusual morphologic patterns of breast carcinomas can raise diagnostic consideration for metastasis or special breast cancer subtypes with management implications. We describe rare invasive breast cancers that mimic serous carcinoma of the gynaecologic tract (serous-like breast carcinomas, SLBC) and characterize their clinicopathologic, immunophenotypic, and genetic features.<br><br>METHODS AND RESULTS: All patients were female (n&#x2009;=&#x2009;15, median age 49&#x2009;years) without a history of gynaecologic malignancy. SLBC were characterized histologically by angulated, branched, sometimes anastomosing glands with micropapillary and/or pseudopapillary luminal projections in desmoplastic stroma. Most SLBC were triple-negative (TN, n&#x2009;=&#x2009;10) or HER2-positive (n&#x2009;=&#x2009;2) and grade 2 or 3, while some were oestrogen receptor (ER) low-positive/HER2-negative and low-grade (n&#x2009;=&#x2009;3). CK5/6 was positive irrespective of grade or receptor status (10/10). All SLBC expressed GATA3 (14/15), TRPS1 (7/7), and/or mammaglobin (4/13). SOX10 was positive in most TN (9/10) and all ER low-positive (3/3) cases, but negative in HER2-positive tumours. WT1 was universally negative, and PAX8 was focal in one mammaglobin-positive tumour. All ER-negative SLBC were p53-aberrant and 9/11 were p16-aberrant, whereas ER-positive tumours were wildtype for both markers (3/3). TP53 was the only frequently mutated gene, altered in all ER-negative (10/10) but no ER-positive (0/4) tumours. Clinical behaviour was variable. Only 1/6 patients achieved pathologic complete response to neoadjuvant chemotherapy.<br><br>CONCLUSION: SLBC is a rare morphologic pattern of invasive breast carcinoma that mimics metastatic serous gynaecologic carcinoma, a potential diagnostic pitfall. SLBC are heterogeneous with respect to grade, receptor profile, and oncogenic driver alterations, without specific genetic underpinnings identified. Additional studies are warranted to further evaluate the clinical behaviour of these tumours.},
}
@article {pmid39654135,
year = {2024},
author = {Rasheed, U and Khalid, M and Noor, A and Saeed, U and Uppal, R and Zafar, S},
title = {Genetic assessment of apolipoprotein E polymorphism and PRNP genotypes in rapidly progressive dementias in Pakistan.},
journal = {Prion},
volume = {18},
number = {1},
pages = {1-7},
pmid = {39654135},
issn = {1933-690X},
mesh = {Humans ; Pakistan ; *Prion Proteins/genetics ; *Genotype ; *Apolipoproteins E/genetics ; Female ; Male ; Polymorphism, Genetic/genetics ; Creutzfeldt-Jakob Syndrome/genetics ; Dementia/genetics ; Mutation/genetics ; Alleles ; Gene Frequency/genetics ; Middle Aged ; Alzheimer Disease/genetics ; Aged ; },
abstract = {Rapidly progressive dementias (RPDs) are a type of fatal dementias that cause rapid progression of neuronal dysfunction. This study aimed to assess the prevalence of APOE genotypes (ε2, ε3, ε4) and PRNP mutations (E200K, M129V) in the general population of Pakistan because of their association with RPDs, including Rapidly Progressive Alzheimer's Disease (rpAD) and Creutzfeldt-Jakob Disease (CJD). Blood samples (n = 100) were collected from healthy Pakistani population and the stated mutations were assessed using polymerase chain reaction. In the analysis of the APOE genotype, ε3/ε3 genotype was the most common (95%), followed by ε3/ε4 (5%) and ε2 allele was completely absent. A low frequency of ε4 allele and the absence of a protective ε2 allele is associated with an increased risk of rpAD. In the case of PRNP mutations, the most common genotype was M129-Ε200 (71%) and V129-Ε200 (29%). E200K mutation was completely absent from the given population. It is noteworthy that the MM homozygous genotype was present in 71 samples, VV genotype was present in 29. Homozygosity on codon 129, as observed in most of our samples, has been associated with more efficient production of PrP[Sc] and disease pathology. This study provides preliminary data indicating that rpAD and CJD pose a significant threat to the Pakistani population.},
}
@article {pmid39645755,
year = {2024},
author = {Parmar, DS and Thakur, MN and Agarwal, I and Ganesh, SR and Vogel, G},
title = {Report of stray sightings of Dendrelaphis proarchos (Wall, 1909) (Serpentes: Colubridae) in Surat, Gujarat, western India.},
journal = {Zootaxa},
volume = {5433},
number = {2},
pages = {231-248},
doi = {10.11646/zootaxa.5433.2.4},
pmid = {39645755},
issn = {1175-5334},
mesh = {Animals ; India ; Male ; *Animal Distribution ; Female ; *Colubridae/anatomy &amp; histology/classification/growth &amp; development ; Animal Structures/anatomy &amp; histology/growth &amp; development ; Body Size ; Ecosystem ; Organ Size ; Humans ; },
abstract = {We here report on likely human-mediated, stray sightings of Dendrelaphis proarchos (Wall, 1909) in an unnatural range-Surat, Gujarat in western India. This population shows the following characters: (1) vertebral scales distinctly enlarged, larger than the dorsals of the first row; (2) 185-194 ventrals; (3) 139-142 divided subcaudals in complete tails; (4) 15 dorsal scale rows at midbody; (5) cloacal shield undivided; (6) one loreal scale; (7) three supralabials touching the eye; (8) a moderate first sublabial that touches two infralabials; (9) 11-12 temporal scales; (10) preoculars 1 or 2; (11) two or three postoculars; (12) maximum total length 1150 mm; (13) interparietal spot absent; (14) a black temporal stripe that does not starts on the postnasal or loreal but starts on the center of the eye follows postoculars (middle or second postocular) covers the majority of the temporal region and extends onto the neck; (15) a distinct, bright ventrolateral stripe bordered by one black line at the bottom; (16) dorsal interstitial color blue and (17) tongue color red with black tip. Data from a partial fragment of the mitochondrial 16S gene also reveal genetic congruence with published sequences from Sagaing and Ayeyarwady in Myanmar and Mizoram, India, further attesting the morphological conclusions. Absence of any sighting of this form in the wild despite long-term (> 15 years) studies in south Gujarat by us, the lack of previous reports of this population especially in natural habitats in Gujarat by colleagues, and reports of many such stray populations of non-native herpetofauna in the coastal port city of Surat together, indicate an unnatural, probably human-mediated, transportation of D. proarchos to Surat. Such likely human-mediated introductions of species outside their native range are a cause for concern and require awareness campaigns among snake rescuers not to 'release' such snakes in the Gujarat forests, but to keep them in zoos or return to the actual point of wild origin, if known or feasible.},
}
@article {pmid39639228,
year = {2024},
author = {Hu, J and Ke, J and Xu, S and Pei, L and Cao, L and Zhou, H and Zhu, X},
title = {The combination of focal breast edema and adjacent vessel sign to assess the behavior of mass-type invasive ductal carcinoma.},
journal = {BMC medical imaging},
volume = {24},
number = {1},
pages = {332},
pmid = {39639228},
issn = {1471-2342},
mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/complications ; Middle Aged ; Retrospective Studies ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/complications ; *Magnetic Resonance Imaging/methods ; *Edema/diagnostic imaging/pathology ; Adult ; Aged ; Breast/diagnostic imaging/pathology/blood supply ; Lymphatic Metastasis/diagnostic imaging ; Neoplasm Invasiveness ; Neoplasm Grading ; },
abstract = {BACKGROUND: The objective of this study was to investigate the association between focal breast edema (FBE) and adjacent vessel sign (AVS) with tumor size, histologic grade, lymphovascular invasion, axillary lymph node status, Ki-67 index, and molecular subtype in breast cancer. These findings have provided valuable insights into the biological characteristics and prognosis of mass-type invasive ductal carcinoma (M-IDC).<br><br>METHODS: We retrospectively included patients with M-IDC between January 2016 and December 2021. FBE was evaluated using T2-weighted sequence. AVS was assessed using maximum-intensity projection images obtained using early dynamic contrast-enhanced magnetic resonance imaging. The breast peritumor score (BPS) was defined as follows: BPS 1, absence of both edema and AVS; BPS 2, AVS without edema; BPS 3, AVS with peritumoral edema; BPS 4, AVS with prepectoral edema; and BPS 5, AVS with subcutaneous edema. The correlation between different BPS scores and clinicopathological variables was examined using Kendall's tau-b correlation coefficient. The DeLong test was used to compare the performances of three clinicopathological models combined with peritumoral features (FBE, AVS, and BPS) in predicting luminal A-like M-IDC.<br><br>RESULTS: In 228 patients with M-IDC, BPS was positively correlated with tumor size, histologic grade, lymphovascular invasion, axillary lymph node status, Ki-67 index, and negatively correlated with estrogen receptor expression (all P&#x2009;<&#x2009;0.05). Furthermore, BPS 1 was more likely to be present in patients with luminal A-like breast cancer (P&#x2009;<&#x2009;0.001). Among the three prediction models, the clinicopathological model combined with the BPS model demonstrated superior diagnostic performance for luminal A-like breast cancer.<br><br>CONCLUSIONS: The BPS is a valuable, non-invasive biomarker for assessing the aggressiveness of M-IDC and can facilitate treatment planning.},
}
@article {pmid39639029,
year = {2024},
author = {Nayak, S and Peto, TJ and Kucharski, M and Tripura, R and Callery, JJ and Quang Huy, DT and Gendrot, M and Lek, D and Nghia, HDT and van der Pluijm, RW and Dong, N and Long, LT and Vongpromek, R and Rekol, H and Hoang Chau, N and Miotto, O and Mukaka, M and Dhorda, M and von Seidlein, L and Imwong, M and Roca, X and Day, NPJ and White, NJ and Dondorp, AM and Bozdech, Z},
title = {Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {10625},
pmid = {39639029},
issn = {2041-1723},
mesh = {*Artemisinins/pharmacology/therapeutic use ; *Plasmodium falciparum/genetics/drug effects ; Cambodia ; *Drug Resistance/genetics ; Humans ; *Malaria, Falciparum/parasitology/drug therapy ; *Antimalarials/pharmacology/therapeutic use ; *Polymorphism, Single Nucleotide ; Vietnam ; Protozoan Proteins/genetics/metabolism ; Transcriptome ; Genomics ; Gene Expression Profiling ; },
abstract = {The emergence of Plasmodium falciparum parasites resistant to artemisinins compromises the efficacy of Artemisinin Combination Therapies (ACTs), the global first-line malaria treatment. Artemisinin resistance is a complex genetic trait in which nonsynonymous SNPs in PfK13 cooperate with other genetic variations. Here, we present population genomic/transcriptomic analyses of P. falciparum collected from patients with uncomplicated malaria in Cambodia and Vietnam between 2018 and 2020. Besides the PfK13 SNPs, several polymorphisms, including nonsynonymous SNPs (N1131I and N821K) in PfRad5 and an intronic SNP in PfWD11 (WD40 repeat-containing protein on chromosome 11), appear to be associated with artemisinin resistance, possibly as new markers. There is also a defined set of genes whose steady-state levels of mRNA and/or splice variants or antisense transcripts correlate with artemisinin resistance at the base level. In vivo transcriptional responses to artemisinins indicate the resistant parasite's capacity to decelerate its intraerythrocytic developmental cycle (IDC), which can contribute to the resistant phenotype. During this response, PfRAD5 and PfWD11 upregulate their respective alternatively/aberrantly spliced isoforms, suggesting their contribution to the protective response to artemisinins. PfRAD5 and PfWD11 appear under selective pressure in the Greater Mekong Sub-region over the last decade, suggesting their role in the genetic background of the artemisinin resistance.},
}
@article {pmid39637037,
year = {2024},
author = {Jha, A and Chaudhary, RK and Shrivastav, S and Khanal, U},
title = {Ultrasonographic and pathological correlation of asymmetric retroareolar density on mammogram.},
journal = {PloS one},
volume = {19},
number = {12},
pages = {e0301180},
pmid = {39637037},
issn = {1932-6203},
mesh = {Humans ; Female ; Middle Aged ; *Mammography/methods ; Adult ; *Breast Neoplasms/diagnostic imaging/pathology ; Aged ; Nipples/diagnostic imaging/pathology ; Mastitis/diagnostic imaging/pathology ; Ultrasonography/methods ; Breast Density ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Ultrasonography, Mammary/methods ; },
abstract = {BACKGROUND: Retroareolar region refers to the region within two centimeters from the nipple and/or involves the nipple-areolar complex on mammogram. In this study, we graded asymmetric retroareolar density on mammography and determined the underlying cause.<br><br>OBJECTIVES: To identify and grade retroareolar densities and evaluate characteristics of lesion using ultrasonography and histopathology.<br><br>METHODS: Mammograms with asymmetric retroareolar density done in our tertiary care hospital were included. Retroareolar density was categorized into three grades based on morphological appearance in mammography. Sonography was performed in all patients and tissue diagnosis was obtained for suspicious lesions.<br><br>RESULTS: Of the 100 patients included in the study, most of the patients with mammographic grade 1, grade 2 and 3 retroareolar asymmetry had normal sonography, pathologically proven mastitis and invasive ductal carcinoma, respectively. Presenting indication usually was diagnostic (n = 87), lump being most common. Benign (58%) diagnosis was more often present, with equal number of normal studies and malignancies (21%). Frequently pathologically proven malignant lesions (n = 17) had grade 3 asymmetry and none were grade 1. Invasive ductal carcinoma was the most common malignancy while mastitis the most common benign disease.<br><br>CONCLUSIONS: Grade I retroareolar asymmetric density on mammography was normal or had a benign etiology while grade 2 or 3 asymmetric density had underlying pathology, often malignancy.<br><br>CONTRIBUTION: Grading retroareolar density in mammogram may improve the evaluation of retroareolar region and increase emphasis on higher grades.},
}
@article {pmid39621168,
year = {2024},
author = {Im, YJ and Yoon, YC and Sung, DH},
title = {Brachial plexopathy due to perineural tumor spread: a retrospective single-center experience of clinical manifestations, diagnosis, treatments, and outcomes.},
journal = {Acta neurochirurgica},
volume = {166},
number = {1},
pages = {490},
pmid = {39621168},
issn = {0942-0940},
mesh = {Humans ; Middle Aged ; Female ; Retrospective Studies ; *Brachial Plexus Neuropathies/diagnosis/etiology ; Male ; Adult ; *Positron Emission Tomography Computed Tomography/methods ; Aged ; *Breast Neoplasms/pathology/diagnostic imaging ; *Peripheral Nervous System Neoplasms/diagnostic imaging/pathology/diagnosis ; Lung Neoplasms/pathology/diagnostic imaging/diagnosis ; Treatment Outcome ; Magnetic Resonance Imaging ; Carcinoma, Ductal, Breast/pathology/diagnostic imaging/diagnosis ; Thyroid Cancer, Papillary/pathology/diagnostic imaging/diagnosis/surgery/therapy ; Fluorodeoxyglucose F18 ; Brachial Plexus/pathology/diagnostic imaging ; Adenocarcinoma of Lung/pathology/diagnostic imaging/diagnosis ; },
abstract = {BACKGROUND: Perineural tumor spread (PNTS) to the brachial plexus (BP) is a rare and challenging condition. This study aimed to elucidate the clinical presentations, diagnostic challenges, and outcomes of patients with PNTS to the BP.<br><br>METHODS: We retrospectively reviewed patients diagnosed with PNTS to the BP at our institution between January 2009 and June 2024. Clinical characteristics, magnetic resonance imaging (MRI), [18]F-fluorodeoxyglucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) findings, and treatment outcomes were analyzed.<br><br>RESULTS: Seven patients (mean age, 50.3 years) were identified. The primary cancer diagnoses included invasive ductal carcinoma of the breast (n&#x2009;=&#x2009;3), metaplastic carcinoma of the breast (n&#x2009;=&#x2009;1), lung adenocarcinoma (n&#x2009;=&#x2009;2), and papillary thyroid carcinoma (n&#x2009;=&#x2009;1). The median time from the initial cancer diagnosis to PNTS symptom onset was 71.0 months. All patients initially presented with progressive unilateral pain or paresthesia, followed by motor weakness. Lower trunk plexopathy was the most common electrodiagnostic finding (n&#x2009;=&#x2009;5). In most patients, BP MRI showed diffuse tubular enlargement and T2 hyperintensity throughout the BP (n&#x2009;=&#x2009;6), with gadolinium enhancement primarily in the proximal regions (n&#x2009;=&#x2009;7). [18]F-FDG PET/CT demonstrated increased uptake in the BP, most prominently at the cervical spinal root or trunk levels (n&#x2009;=&#x2009;6). Despite treatment, neurological outcomes were generally poor. Six of the seven patients died after a median follow-up of 19 months post-PNTS diagnosis.<br><br>CONCLUSIONS: PNTS to the BP can occur years after initial cancer diagnosis and may signify cancer progression. A high index of suspicion is crucial for timely diagnosis, particularly in patients with cancer and progressive upper extremity symptoms. Comprehensive imaging, including BP MRI and PET/CT, is essential for diagnosis. Despite treatment, prognosis remains poor, highlighting the need for improved diagnostic and therapeutic strategies.},
}
@article {pmid39616738,
year = {2025},
author = {Rivera, A and Plumber, N and Louis, M and Grabill, N and Strom, P},
title = {Surgical stress as a potential trigger for spontaneous coronary artery dissection: A case report.},
journal = {International journal of surgery case reports},
volume = {126},
number = {},
pages = {110644},
pmid = {39616738},
issn = {2210-2612},
abstract = {INTRODUCTION AND IMPORTANCE: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome, predominantly affecting women without traditional cardiovascular risk factors. It is often underdiagnosed, especially in postoperative patients, due to its atypical presentation and the challenges in distinguishing it from other causes of chest pain.<br><br>CASE PRESENTATION: We report the case of a 62-year-old woman with type 2 diabetes mellitus, hypertension, hyperlipidemia, and recent bilateral mastectomy for invasive ductal carcinoma, who presented three days post-surgery with sudden onset of chest pain radiating to her left arm. Electrocardiography revealed ST-segment depression suggestive of anterior ischemia, and cardiac biomarkers were significantly elevated. Imaging studies were limited due to recent surgery, but urgent coronary angiography identified spontaneous coronary artery dissections.<br><br>CLINICAL DISCUSSION: This case highlights the potential role of surgical stress as a precipitating factor for SCAD in patients without traditional cardiovascular risk factors. The physiological stress of major surgery may contribute to arterial wall vulnerability and dissection. Diagnostic challenges in the postoperative setting necessitate a high index of suspicion for timely identification. Conservative management was pursued, aligning with current guidelines that favor non-invasive treatment in stable SCAD cases to prevent further dissection or complications.<br><br>CONCLUSION: SCAD should be considered in the differential diagnosis of acute coronary syndrome in postoperative patients presenting with chest pain, even in the absence of significant cardiovascular risk factors. Early recognition and appropriate management are crucial for improving patient outcomes.},
}
@article {pmid39612651,
year = {2024},
author = {Shrestha, LB and Tungatt, K and Aggarwal, A and Stubis, A and Fewings, NL and Fichter, C and Akerman, A and Rodrigo, C and Tedla, N and Lee, S and Lloyd, AR and Brilot, F and Britton, WJ and Kelleher, A and Caterson, ID and Douglas, MW and Rockett, R and Tangye, SG and Triccas, JA and Turville, SG and Sandgren, KJ and Bull, RA and Cunningham, AL and , },
title = {Bivalent Omicron BA.1 vaccine booster increases memory B cell breadth and neutralising antibodies against emerging SARS-CoV-2 variants.},
journal = {EBioMedicine},
volume = {110},
number = {},
pages = {105461},
pmid = {39612651},
issn = {2352-3964},
mesh = {Humans ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; *SARS-CoV-2/immunology ; *Memory B Cells/immunology ; *COVID-19/immunology/prevention &amp; control ; *Antibodies, Viral/immunology ; *Antibodies, Neutralizing/immunology ; *Immunization, Secondary ; *Spike Glycoprotein, Coronavirus/immunology ; Adult ; Female ; Male ; Middle Aged ; Immunologic Memory ; B-Lymphocytes/immunology ; },
abstract = {BACKGROUND: Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to monovalent or a bivalent ancestral/Omicron BA.1 COVID-19 booster vaccine.<br><br>METHODS: At baseline and 1-month post-booster, neutralisation activity and frequencies of receptor binding domain (RBD)-specific MBCs and Spike-specific memory T cells were measured against a panel of variants.<br><br>FINDINGS: Both vaccines boosted neutralising antibodies to 5 variants - Wuhan-Hu-1, Delta, BA.1, BA.5 and JN.1, the&#xa0;latter of which had not yet emerged at the time of sample collection. The bivalent vaccine induced a significantly larger increase in nAb against BA.1 and JN.1. Both vaccines boosted RBD-specific MBC responses to Wuhan-Hu-1, Delta, BA.1 and BA.5 variants with a significantly greater increase for BA.1 in the bivalent group. The breadth of MBCs was significantly higher in those who received the bivalent boost and correlated with nAb breadth. Both vaccines significantly boosted Spike-specific T cell responses to the Wuhan-Hu-1 and BA.5 variants, but only the bivalent vaccine boosted BA.1 responses.<br><br>INTERPRETATION: These results suggest that the bivalent vaccine confers an advantage against future novel variants due to increased frequency of broadly reactive RBD-specific B cells.<br><br>FUNDING: Work supported by NSW Health for the NSW Vaccine, Infection and Immunology Collaborative (VIIM).},
}
@article {pmid39610583,
year = {2024},
author = {Yasin, R and Zafar, G and Rooman Ali Syed, F and Afzal, S and Fatima, M and Rathore, Z and Chughtai, A and Chughtai, A},
title = {CK5/6 Expression in Molecular Subtypes of Invasive Ductal Carcinoma.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e72608},
pmid = {39610583},
issn = {2168-8184},
abstract = {Background Breast cancer (BC) is the leading cause of cancer-related deaths in women worldwide. There has been a significant increase in the incidence of BC in Pakistan. Family history, older age, obesity, tobacco use, oral contraceptive use, early menarche, and hormonal replacement therapy are among the major risk factors. The most common histological subtype of BC is invasive ductal carcinoma (IDC). Molecular subtypes of BC include mainly Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER-2) enriched, and triple-negative BC subtypes, with the triple-negative subtype having the worst prognosis. CK5/6 serves as a basal keratin biomarker. This aimed to assess the expression of CK5/6 in IDC of the breast belonging to different molecular classes and to compare its expression with traditionally defined prognostic factors for different molecular subtypes. Methodology A cross-sectional, observational study was conducted at the Chughtai Institute of Pathology after approval from the Institutional Review Board (approval number: 1198/IRB/CIP). All cases during a period of six months (April 2023 to September 2023) were sampled using non-probability convenient sampling. All mastectomy samples diagnosed as IDC were included in the study. After standard tissue processing, paraffin tissue blocks and slides were prepared followed by hematoxylin &amp; eosin staining. Hormonal receptors (estrogen receptor, progesterone receptor, HER-2) were assessed for cases to segregate them into molecular subtypes. CK5/6 antibody was then applied and the data were collected on a pre-designed proforma. SPSS version 25.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Results Of a total of 85 cases, 19 (22.3%) were positive for CK5/6. Of these 19 cases, the majority (68%, p = 0.001) belonged to the triple-negative class of tumors, comprising 13 cases. No case from the Luminal A class showed expression for CK5/6 stain (p = 0.028). Overall, four cases of the Luminal B subtype showed CK5/6 positivity (10.8%, p = 0.022) while two cases of the HER-2-enriched subtype were positive for the stain (33.3%, p > 0.05). These results were analyzed in relation to different prognostic factors. The majority of CK5/6-positive cases showed lymphovascular invasion (42%) and belonged to grade 3 tumors (57.8%). Conclusions The expression of CK5/6 in IDC of the breast is associated with poor prognostic factors such as triple-negative molecular subtypes, high histological grade, lymphovascular invasion, positive nodal status, and high pathological stage.},
}
@article {pmid39605123,
year = {2024},
author = {Noroozpoor, M and Mozdarani, H and Rahbar Parvaneh, R and Lashkari, M},
title = {Evaluation of TP53TG1 and PANDA lncRNAs expression in association with adjuvant chemotherapy response in the peripheral blood of invasive ductal carcinoma patients.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
volume = {70},
number = {10},
pages = {58-63},
doi = {10.14715/cmb/2024.70.10.9},
pmid = {39605123},
issn = {1165-158X},
mesh = {Humans ; Female ; Chemotherapy, Adjuvant ; *RNA, Long Noncoding/genetics/blood ; *Breast Neoplasms/drug therapy/genetics/blood ; Middle Aged ; *Gene Expression Regulation, Neoplastic/drug effects ; Carcinoma, Ductal, Breast/drug therapy/genetics/blood ; Adult ; Biomarkers, Tumor/genetics/blood ; },
abstract = {Breast cancer is the most common malignancy in women. Breast cancer, the second leading cause of cancer deaths, affects 2.1 million women each year and is estimated to have killed 627,000 women worldwide in 2018. Unfortunately, the age of onset of this cancer in our country IRAN is about 10 years lower than the global average and is close to 45 years. Chemotherapy is one of the basic treatments for cancer. Predicting the benefits of chemotherapy is challenging. Studies are now underway to use gene expression tests to pinpoint patients who are most likely to benefit from adjuvant chemotherapy. In the present study, the expression of two long non-coding RNAs TP53TG1 and PANDA in the blood of breast cancer patients before and after receiving chemotherapy compared with this amount in the blood of normal people using Real-Time RT PCR technique to find a meaningful relationship ¬ Compared statistically. Compared to normal samples, the expression level of TP53TG1 in the blood of patients was reduced. Although it was not statistically significant. Its expression also increased after receiving chemotherapy. Compared to normal samples, the expression of PANDA in the blood of patients was increased, which was statistically significant. Also, its expression decreased after receiving chemotherapy. These findings suggest that PANDA and TP53TG1 expression levels may be possible markers associated with tumorigenesis and may also be considered as possible indicators of response to chemotherapy.},
}
@article {pmid39593081,
year = {2024},
author = {Trippler, L and Ali, SM and Masoud, MO and Mohammed, ZH and Amour, AK and Suleiman, KR and Ame, SM and Kabole, F and Hattendorf, J and Knopp, S},
title = {Impact of chemical snail control on intermediate host snail populations for urogenital schistosomiasis elimination in Pemba, Tanzania: findings of a 3-year intervention study.},
journal = {Parasites &amp; vectors},
volume = {17},
number = {1},
pages = {489},
pmid = {39593081},
issn = {1756-3305},
support = {PR00P3_179753 / 1//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; },
mesh = {Animals ; Tanzania/epidemiology ; *Schistosomiasis haematobia/prevention &amp; control/epidemiology/drug therapy/transmission ; *Schistosoma haematobium/drug effects/physiology ; *Bulinus/parasitology ; Humans ; *Niclosamide/pharmacology ; Snails/parasitology ; Disease Eradication ; Fresh Water/parasitology ; },
abstract = {BACKGROUND: The World Health Organization (WHO) has set the goal of eliminating schistosomiasis as a public health problem globally by 2030 and to interrupt transmission in selected areas. Chemical snail control is one important measure to reduce transmission and achieve local elimination. We aimed to assess the impact of several rounds of chemical snail control on the presence and number of the Schistosoma haematobium intermediate snail host (Bulinus spp.) in water bodies (WBs) on Pemba Island, Tanzania, a setting targeted for elimination of urogenital schistosomiasis.<br><br>METHODS: During the three annual intervention periods of the SchistoBreak study implemented in the north of Pemba from 2020 to 2024, malacological surveys were conducted up to four times per period in WBs of hotspot implementation units (IUs). Present freshwater snail species, vegetation, and WB characteristics were recorded. If Bulinus were found, the snails were inspected for Schistosoma infection and snail control with niclosamide was conducted.<br><br>RESULTS: Across the three intervention periods, a total of 112 WBs were identified in 8 hotspots IUs. The spatial distribution of WBs with Bulinus per IU was heterogeneous, ranging from 0.0% (0/15) of WBs infested in one IU in 2022 to 80.0% (8/10) of WBs infested in one IU in 2021. Bulinus presence was significantly associated with lower pH values in WBs (odds ratio: 0.2, 95% confidence interval 0.1-0.4). A total of 0.2% (6/2360) of collected Bulinus were shedding Schistosoma cercariae. Following snail control, the number of Bulinus decreased or remained absent in 56.7% (38/67) of visits at WBs when compared with the previous visit in 2021, 54.9% (28/51) in 2022, and 33.3% (32/96) in 2023. In a total of 43.1% (22/55) of initially infested WBs, no Bulinus were found in the survey round conducted a few weeks after the first application of niclosamide. However, 25.4% (14/55) of WBs showed a pattern of recurring Bulinus presence.<br><br>CONCLUSIONS: The distribution of WBs containing Bulinus was very heterogeneous. The percentage of Bulinus with patent Schistosoma infection in our study area was extremely low. Repeated niclosamide application reduced the number of Bulinus in WBs, but snails often recurred after one or multiple treatments. While chemical mollusciciding can reduce snail numbers, to fully break the S. haematobium transmission cycle, timely diagnosis and treatment of infected humans, access to clean water, sanitation, and health communication remain of prime importance.<br><br>TRIAL REGISTRATION: ISRCTN, ISRCTN91431493. Registered 11 February. 2020, https://www.isrctn.com/ISRCTN91431493.},
}
@article {pmid39578650,
year = {2024},
author = {Berriel Diaz, M and Rohm, M and Herzig, S},
title = {Cancer cachexia: multilevel metabolic dysfunction.},
journal = {Nature metabolism},
volume = {6},
number = {12},
pages = {2222-2245},
pmid = {39578650},
issn = {2522-5812},
support = {949017//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; },
mesh = {Animals ; Humans ; *Cachexia/metabolism/etiology ; *Energy Metabolism ; Metabolic Diseases/etiology/metabolism ; *Neoplasms/complications/metabolism ; },
abstract = {Cancer cachexia is a complex metabolic disorder marked by unintentional body weight loss or 'wasting' of body mass, driven by multiple aetiological factors operating at various levels. It is associated with many malignancies and significantly contributes to cancer-related morbidity and mortality. With emerging recognition of cancer as a systemic disease, there is increasing awareness that understanding and treatment of cancer cachexia may represent a crucial cornerstone for improved management of cancer. Here, we describe the metabolic changes contributing to body wasting in cachexia and explain how the entangled action of both tumour-derived and host-amplified processes induces these metabolic changes. We discuss energy homeostasis and possible ways that the presence of a tumour interferes with or hijacks physiological energy conservation pathways. In that context, we highlight the role played by metabolic cross-talk mechanisms in cachexia pathogenesis. Lastly, we elaborate on the challenges and opportunities in the treatment of this devastating paraneoplastic phenomenon that arise from the complex and multifaceted metabolic cross-talk mechanisms and provide a status on current and emerging therapeutic approaches.},
}
@article {pmid39567714,
year = {2024},
author = {Khan, B and Qahwaji, R and Alfaifi, MS and Athar, T and Khan, A and Mobashir, M and Ashankyty, I and Imtiyaz, K and Alahmadi, A and Rizvi, MMA},
title = {Deciphering molecular landscape of breast cancer progression and insights from functional genomics and therapeutic explorations followed by in vitro validation.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {28794},
pmid = {39567714},
issn = {2045-2322},
mesh = {Humans ; *Breast Neoplasms/genetics/pathology/drug therapy ; Female ; *Gene Expression Regulation, Neoplastic ; Genomics/methods ; Gene Regulatory Networks ; Disease Progression ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology/drug therapy ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/drug therapy ; Molecular Docking Simulation ; Gene Expression Profiling ; Prognosis ; Cell Line, Tumor ; },
abstract = {Breast cancer is caused by aberrant breast cells that proliferate and develop into tumors. Tumors have the potential to spread throughout the body and become lethal if ignored. Metastasis is the process by which invasive tumors move to neighboring lymph nodes or other organs. Metastasis can be lethal and perhaps fatal. The objective of our study was to elucidate the molecular mechanisms underlying the transition of Ductal Carcinoma In Situ (DCIS) to Invasive Ductal Carcinoma (IDC), with a particular focus on hub genes and potential therapeutic agents. Using Weighted Gene Co-expression Network Analysis (WGCNA), we built a comprehensive network combining clinical and phenotypic data from both DCIS and IDC. Modules within this network, correlated with specific phenotypic traits, were identified, and hub genes were identified as critical markers. Receiver Operating Characteristic (ROC) analysis assessed their potential as biomarkers, while survival curve analysis gauged their prognostic value. Furthermore, molecular docking predicted interactions with potential therapeutic agents. Ten hub genes-CDK1, KIF11, NUF2, ASPM, CDCA8, CENPF, DTL, EXO1, KIF2C, and ZWINT-emerged as pivotal fibroblast-specific genes potentially involved in the DCIS to IDC transition. These genes exhibited pronounced positive correlations with key pathways like the cell cycle and DNA repair, Molecular docking revealed Fisetin, an anti-inflammatory compound, effectively binding to both CDK1 and DTL underscoring their role in orchestrating cellular transformation. CDK1 and DTL were selected for molecular docking with CDK1 inhibitors, revealing effective binding of Fisetin, an anti-inflammatory compound, to both. Of the identified hub genes, DTL-an E3 ubiquitin ligase linked to the CRL4 complex-plays a central role in cancer progression, impacting tumor growth, invasion, and metastasis, as well as cell cycle regulation and epithelial-mesenchymal transition (EMT). CDK1, another hub gene, is pivotal in cell cycle progression and associated with various biological processes. In conclusion, our study offers insights into the complex mechanisms driving the transition from DCIS to IDC. It underscores the importance of hub genes and their potential interactions with therapeutic agents, particularly Fisetin. By shedding light on the interplay between CDK1 and DTL expression, our findings contribute to understanding the regulatory landscape of invasive ductal carcinoma and pave the way for future investigations and novel therapeutic avenues.},
}
@article {pmid39560723,
year = {2024},
author = {Cendrowski, J and Wrobel, M and Mazur, M and Jary, B and Maurya, R and Wang, S and Korostynski, M and Dziewulska, A and Rohm, M and Kuropka, P and Pudelko-Malik, N and Mlynarz, P and Dobrzyn, A and Zeigerer, A and Miaczynska, M},
title = {NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {81},
number = {1},
pages = {458},
pmid = {39560723},
issn = {1420-9071},
support = {POIR.04.04.00-00-1C54/16-00//Fundacja na rzecz Nauki Polskiej/ ; POIR.04.04.00-00-20CE/16-00//Fundacja na rzecz Nauki Polskiej/ ; },
mesh = {*Endosomal Sorting Complexes Required for Transport/metabolism/genetics ; Humans ; *NF-kappa B/metabolism ; *Glycolysis/genetics ; Lysosomes/metabolism ; MAP Kinase Signaling System ; Mitochondria/metabolism ; Adaptation, Physiological/genetics ; Transcription Factors/metabolism/genetics ; Glucose/metabolism ; DNA-Binding Proteins ; },
abstract = {Endosomal Sorting Complexes Required for Transport (ESCRTs) are crucial for delivering membrane receptors or intracellular organelles for lysosomal degradation which provides the cell with lysosome-derived nutrients. Yet, how ESCRT dysfunction affects cell metabolism remained elusive. To address this, we analyzed transcriptomes of cells lacking TSG101 or VPS28 proteins, components of ESCRT-I subcomplex. ESCRT-I deficiency reduced the expression of genes encoding enzymes involved in oxidation of fatty acids and amino acids, such as branched-chain amino acids, and increased the expression of genes encoding glycolytic enzymes. The changes in metabolic gene expression were associated with Warburg effect-like metabolic reprogramming that included intracellular accumulation of lipids, increased glucose/glutamine consumption and lactate production. Moreover, depletion of ESCRT-I components led to expansion of the ER and accumulation of small mitochondria, most of which retained proper potential and performed ATP-linked respiration. Mechanistically, the observed transcriptional reprogramming towards glycolysis in the absence of ESCRT-I occurred due to activation of the canonical NFκB and JNK signaling pathways and at least in part by perturbed lysosomal degradation. We propose that by activating the stress signaling pathways ESCRT-I deficiency leads to preferential usage of extracellular nutrients, like glucose and glutamine, for energy production instead of lysosome-derived nutrients, such as fatty acids and branched-chain amino acids.},
}
@article {pmid39557919,
year = {2024},
author = {Rusak, A and Kątnik, E and Górnicki, T and Schmuttermaier, C and Kujawa, K and Piotrowska, A and Ratajczak-Wielgomas, K and Kmiecik, A and Wojnar, A and Dzięgiel, P and Kzhyshkowska, J},
title = {New insights into the role of the CHI3L2 protein in invasive ductal breast carcinoma.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {28529},
pmid = {39557919},
issn = {2045-2322},
support = {2021/05/X/NZ2/01698//National Science Center, Poland (NCN)/ ; },
mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism/pathology/genetics ; *Breast Neoplasms/metabolism/pathology/genetics ; Middle Aged ; STAT3 Transcription Factor/metabolism ; Cell Line, Tumor ; Phosphorylation ; Chitinase-3-Like Protein 1/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; Adult ; Macrophages/metabolism ; Aged ; MAP Kinase Signaling System ; Chitinases ; },
abstract = {Chitinase-like proteins have multiple biological functions that promote tumor growth, angiogenesis and metastasis. Expression of CHI3L2, which is similar in structure to CHI3L1, is detected in glioma cells and tumor-associated macrophages (TAMs) in glioma and breast cancer. However, its exact role remains unclear. We analyzed the expression of CHI3L2 in 74 invasive ductal breast carcinoma (IDC) tumors, breast cancer and macrophages cell cultures using immunohistochemistry, immunofluorescence, Western blot and PCR methods. Clinicopathologic data were included in the analysis. The results obtained show that CHI3L2 expression decreases with increasing degree of tumor grade and negative status of estrogen (ER) and progesterone receptors (PR). Furthermore, CHI3L2 is significantly and positively correlated with phosphorylation of STAT-3 and ERK1/2 signaling pathways, but negatively correlated with macrophage infiltration. CHI3L2 is expressed both in the cytoplasm of cancer cells and in macrophages and may regulate STAT-3 and ERK1/2 phosphorylation in breast cancer cell lines. Analysis of the clinicopathologic data revealed that CHI3L2 levels had no effect on patient survival. CHI3L2 expression may be specific for cancer cells in IDC and involved in cross-talk with the tumor microenvironment. Our study has shown that IDC cancer cells express the CHI3L2 protein, possibly indicating a novel function of this protein.},
}
@article {pmid39541956,
year = {2025},
author = {Abdelwahab, RM and Aghazadeh Mohandesi, N and Sturgis, CD and Alavi, A},
title = {Squamous Metaplasia of Lactiferous Ducts (Zuska's Disease) of the Breast: Clinical and Histopathologic Manifestations.},
journal = {Dermatology (Basel, Switzerland)},
volume = {241},
number = {2},
pages = {210-215},
doi = {10.1159/000542622},
pmid = {39541956},
issn = {1421-9832},
mesh = {Humans ; Female ; Middle Aged ; Adult ; Metaplasia/pathology ; Retrospective Studies ; Aged ; *Breast Diseases/pathology ; Aged, 80 and over ; Smoking/adverse effects ; *Breast/pathology ; *Mammary Glands, Human/pathology ; },
abstract = {INTRODUCTION: Squamous metaplasia of lactiferous duct (SMOLD), also known as Zuska's disease, is an uncommon, recurrent inflammatory fistulizing disease of the breast that strongly correlates with smoking in premenopausal patients. Clinical and imaging findings may overlap with other breast conditions. SMOLD is well recognized by breast pathologists; however, the dermatology literature on this condition remains scarce.<br><br>METHODS: In this retrospective study, we reviewed 29 patients with SMOLD diagnosed at Mayo Clinic.<br><br>RESULTS: The mean age of the patient cohort is 50.3 with a range of 30 to 81 years. One patient (3.7%) had hidradenitis suppurativa of the retroareolar area. Patient smoking history demonstrated prior/current smokers of 37.9% (11/29), lifetime nonsmokers with significant secondhand exposure 6.9% (2/29), and unknown smoking status 3.4% (1/29). One patient had a personal history of invasive ductal carcinoma, and 10.3% (3/29) had a history of breast cancer in a first-degree relative. The clinical presentation of the patient cohort includes areolar papules, nodules, and draining tract/fistula 13.7% (4/29); pustular cyst/abscess on the breast 13.7% (4/29); breast mass 3.4% (1/29); pain breast discomfort/pain 13.7% (4/29); nipple retraction 3.4% (1/29); and asymptomatic with nipple calcifications on mammogram 3.4% (1/29). A total of 77.8% (7/9) of patients with bacterial cultures demonstrated polymicrobial growth. Overall, 37.9% (11/29) of patients received at least one round of antibiotic therapy. In total, 27.6% (8/29) of patients underwent invasive intervention. Staphylococcus, Streptococcus, and Cutibacterium species were the most frequent causes of infection in our patient cohort.<br><br>CONCLUSIONS: We confirm previous findings of strong association between SMOLD and current/former smoking status and a potential, novel correlation between extensive secondhand exposure and SMOLD development. While both medical and surgical interventions are employed in patient management, many patients ultimately require complete excision of the involved duct(s). Dermatologists should consider SMOLD in the differential diagnosis of patients presenting with breast abscess, fistulizing tracts with mass, and breast pain.},
}
@article {pmid39520846,
year = {2024},
author = {Turk, A and Metin, TO and Kuloglu, T and Yilmaz, M and Artas, G and Ozercan, IH and Hancer, S},
title = {Isthmin-1 and spexin as promising novel biomarker candidates for invasive ductal breast carcinoma.},
journal = {Tissue &amp; cell},
volume = {91},
number = {},
pages = {102601},
doi = {10.1016/j.tice.2024.102601},
pmid = {39520846},
issn = {1532-3072},
mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism/pathology ; *Biomarkers, Tumor/metabolism ; *Breast Neoplasms/metabolism/pathology ; Middle Aged ; *Peptide Hormones/metabolism ; Adult ; Aged ; Blood Proteins/metabolism ; Neoplasm Invasiveness ; },
abstract = {INTRODUCTION: Breast cancer is one of the most common malignant tumors and a leading cause of cancer-related death in women. Research is focusing on biomarkers linked to breast cancer, particularly two novel proteins: isthmin-1 (ISM-1) and spexin (SPX), which require further investigation.<br><br>MATERIAL AND METHODS: The study involved 20 healthy controls and 60 patients with invasive ductal carcinoma, categorized into three groups: Grade I (n=20), Grade II (n=20), and Grade III (n=20). Levels of ISM-1 and SPX in tissue were analyzed using immunohistochemistry alongside the clinicopathologic data of patients.<br><br>RESULTS: There were no statistically significant differences in age, menopausal status, ER, PR, and Cerb-B2 values across grades (p>0.05). Tumor diameters showed a significant increase in Grade I compared to Grade II (p<0.05), while no significant difference was noted between Grade II and Grade III, although diameters were larger in Grade III compared to Grade I (p<0.05). Notably, ISM-1 immunoreactivity decreased, and SPX immunoreactivity increased significantly across all grades compared to normal tissue (p<0.05), with no significant differences between tumor grades for these markers (p>0.05).<br><br>CONCLUSIONS: This study presents new findings on ISM-1 and SPX expression in invasive ductal breast carcinoma. The decrease in ISM-1 and increase in SPX suggest a need for further research into the relationship between adipokines and tumor development in breast cancer.},
}
@article {pmid39519098,
year = {2024},
author = {Kim, YJ and Nanda, SS and Jiang, F and Pyo, SY and Han, JY and Koh, SS and Kang, TH},
title = {Pancreatic Adenocarcinoma Up-Regulated Factor (PAUF) Transforms Human Monocytes into Alternative M2 Macrophages with Immunosuppressive Action.},
journal = {International journal of molecular sciences},
volume = {25},
number = {21},
pages = {},
pmid = {39519098},
issn = {1422-0067},
mesh = {Humans ; *Pancreatic Neoplasms/pathology/metabolism/immunology ; *Monocytes/metabolism/immunology ; *Cell Differentiation ; *Macrophages/metabolism/immunology ; *Tumor Microenvironment/immunology ; Toll-Like Receptor 2/metabolism ; Tumor-Associated Macrophages/metabolism/immunology ; Cell Proliferation ; Adenocarcinoma/pathology/metabolism/immunology ; Cell Line, Tumor ; Intercellular Signaling Peptides and Proteins ; },
abstract = {Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) promote immune evasion, cancer cell proliferation, and metastasis. Ongoing research is focused on finding ways to prevent tumor growth by inhibiting TAM polarization, which has shown a correlation with unfavorable prognosis in clinical studies. Pancreatic adenocarcinoma up-regulated factor (PAUF) is a protein secreted from pancreatic cancer (PC) and acts as a TME modulator that affects the TME by acting on not only cancer cells but also stromal cells and immune cells. Tumor cells can evade the immune system by PAUF binding to Toll-like receptor (TLR) in monocytes, as this research shows. In this study, the examination centered around the recruitment of human monocytes by PAUF and the subsequent differentiation into macrophages. In an in vitro chemotaxis assay, PAUF induced chemotactic migration of TLR2-mediated monocytes. In addition, PAUF induced differentiation of monocytes into M2 macrophages, which was verified based on expressing surface markers and cytokines and morphological analysis. The inhibition of T cell proliferation and function was observed in differentiated M2 macrophages. To conclude, these findings indicate that PAUF functions as a promoter of cancer progression by regulating the recruitment and differentiation of macrophages within TMEs, ultimately causing immunosuppression.},
}
@article {pmid39519012,
year = {2024},
author = {Newman, NA and Burke, MA},
title = {Dilated Cardiomyopathy: A Genetic Journey from Past to Future.},
journal = {International journal of molecular sciences},
volume = {25},
number = {21},
pages = {},
pmid = {39519012},
issn = {1422-0067},
mesh = {Humans ; *Cardiomyopathy, Dilated/genetics ; *Genetic Predisposition to Disease ; Genetic Testing ; },
abstract = {Dilated cardiomyopathy (DCM) is characterized by reduced systolic function and cardiac dilation. Cases without an identified secondary cause are classified as idiopathic dilated cardiomyopathy (IDC). Over the last 35 years, many cases of IDC have increasingly been recognized to be genetic in etiology with a core set of definitively causal genes in up to 40% of cases. While over 200 genes have been associated with DCM, the evidence supporting pathogenicity for most remains limited. Further, rapid advances in sequencing and bioinformatics have recently revealed a complex genetic spectrum ranging from monogenic to polygenic in DCM. These advances have also led to the discovery of causal and modifier genetic variants in secondary forms of DCM (e.g., alcohol-induced cardiomyopathy). Current guidelines recommend genetic counseling and screening, as well as endorsing a handful of genotype-specific therapies (e.g., device placement in LMNA cardiomyopathy). The future of genetics in DCM will likely involve polygenic risk scores, direct-to-consumer testing, and pharmacogenetics, requiring providers to have a thorough understanding of this rapidly developing field. Herein we outline three decades of genetics in DCM, summarize recent advances, and project possible future avenues for the field.},
}
@article {pmid39513960,
year = {2025},
author = {Huang, H and Couch, RE and Karam, R and Hu, C and Boddicker, N and Polley, EC and Na, J and Ambrosone, CB and Yao, S and Trentham-Dietz, A and Eliassen, AH and Penney, K and Brantley, K and Bodelon, C and Teras, LR and Hodge, J and Patel, A and Haiman, CA and John, EM and Neuhausen, SL and Martinez, E and Lacey, JV and O'Brien, KM and Sandler, DP and Weinberg, CR and Palmer, JR and Bertrand, KA and Vachon, CM and Olson, JE and Ruddy, KE and Anton-Culver, H and Ziogas, A and Goldgar, DE and Nathanson, KL and Domchek, SM and Weitzel, JN and Kraft, P and Dolinsky, JS and Pesaran, T and Richardson, ME and Yadav, S and Couch, FJ},
title = {Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In Situ of the Breast.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {31},
number = {1},
pages = {130-138},
pmid = {39513960},
issn = {1557-3265},
support = {R01 CA225662/CA/NCI NIH HHS/United States ; R35CA253187//National Cancer Institute (NCI)/ ; //Breast Cancer Research Foundation (BCRF)/ ; P50CA116201//National Cancer Institute (NCI)/ ; U01 CA164974/CA/NCI NIH HHS/United States ; K12 CA090628/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; R01CA225662//National Cancer Institute (NCI)/ ; P30 CA062203/CA/NCI NIH HHS/United States ; K12CA090628//National Cancer Institute (NCI)/ ; R35 CA253187/CA/NCI NIH HHS/United States ; T32 CA009001/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Genetic Predisposition to Disease ; *Breast Neoplasms/genetics/pathology/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/epidemiology ; Middle Aged ; Adult ; *Germ-Line Mutation ; Aged ; Carcinoma, Ductal, Breast/genetics/pathology/epidemiology ; },
abstract = {PURPOSE: To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).<br><br>EXPERIMENTAL DESIGN: Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls and between DCIS and invasive ductal breast cancer (IDC) cases from a clinical testing cohort (n = 9,887), a population-based cohort (n = 3,876), and the UK Biobank (n = 2,421). The risk of contralateral breast cancer (CBC) for DCIS cases with PV was estimated in the population-based cohort.<br><br>RESULTS: Germline PV were observed in 6.5% and 4.6% of women with DCIS in the clinical testing and population-based cohorts, respectively. BRCA1, BRCA2, and PALB2 PV frequencies were significantly lower among women with DCIS than those with IDC (clinical cohort: 2.8% vs. 5.7%; population-based cohort: 1.7% vs. 3.7%), whereas the PV frequencies for ATM and CHEK2 were similar. ATM, BRCA1, BRCA2, CHEK2, and PALB2 PV were significantly associated with an increased risk of DCIS (OR > 2.0), but only BRCA2 PV were associated with high risk (OR > 4) in both cohorts. The cumulative incidence of CBC among carriers of PV in high-penetrance genes with DCIS was 23% over 15 years.<br><br>CONCLUSIONS: The enrichment of PV in ATM, BRCA1, BRCA2, CHEK2, and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of CBC in carriers of PV in high-penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.},
}
@article {pmid39512981,
year = {2024},
author = {Eshaqi, MJ and Al Shamsi, SA and Al Saidi, AM and Mahesh, S},
title = {Clinical Insights Into Ductal Carcinoma In Situ in Males: A Report of Two Cases From the Sultanate of Oman.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e71071},
pmid = {39512981},
issn = {2168-8184},
abstract = {Breast cancer is a disease that predominantly affects the female population; however, rarely it can manifest in males, yet its etiology remains poorly elucidated. The scarcity of literature reviews and case reports done on male breast cancer in comparison to the female counterpart makes it difficult to understand the risk factors, treatment options, and extension of the disease. Moreover, high-grade ductal carcinoma in situ (DCIS) is exceptionally uncommon among male patients. The prognosis for male patients diagnosed with DCIS is similar to that of females at the same disease stage making early recognition and diagnosis significant. However, more efforts are being made to understand the clinical presentation, increase awareness, and acknowledge the etiology of this disease. This study addresses this gap by presenting two distinctive cases of invasive ductal carcinoma in males from the Sultanate of Oman. The aim of this study is to contribute to the growing efforts in comprehending the unclear landscape of male breast cancer, fostering awareness, and advancing knowledge of its etiology.},
}
@article {pmid39506855,
year = {2024},
author = {Kook, Y and Lee, YJ and Chu, C and Jang, JS and Baek, SH and Bae, SJ and Cha, YJ and Gong, G and Jeong, J and Lee, SB and Ahn, SG},
title = {Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 h + HER2- breast cancer: a retrospective analysis.},
journal = {Breast cancer research : BCR},
volume = {26},
number = {1},
pages = {154},
pmid = {39506855},
issn = {1465-542X},
support = {2021M3H9A2096954//National Research Foundation of Korea/ ; RS-2024-00343001//Korean government/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality/drug therapy ; *Receptor, ErbB-2/genetics/metabolism ; Retrospective Studies ; Middle Aged ; *Biomarkers, Tumor/genetics ; Adult ; Aged ; Gene Expression Profiling ; Immunohistochemistry ; Prognosis ; },
abstract = {BACKGROUND: HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay.<br><br>METHODS: A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX[&#xae;] test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS)&#x2009;>&#x2009;25. Multivariable binary logistic-regression analysis was performed.<br><br>RESULTS: Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value&#x2009;<&#x2009;0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p&#x2009;=&#x2009;0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p&#x2009;<&#x2009;0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups.<br><br>CONCLUSION: Within HR&#x2009;+&#x2009;HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR&#x2009;+&#x2009;HER2- breast cancer remains as an area that requires further study.},
}
@article {pmid39505971,
year = {2024},
author = {Olbromski, M and Mrozowska, M and Smolarz, B and Romanowicz, H and Rusak, A and Piotrowska, A},
title = {ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {26935},
pmid = {39505971},
issn = {2045-2322},
mesh = {Humans ; Female ; *Estrogen Receptor alpha/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism/genetics ; *Histone Acetyltransferases/metabolism/genetics ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Middle Aged ; Gene Expression Regulation, Neoplastic ; Adult ; Histone Deacetylases/metabolism/genetics ; MCF-7 Cells ; Aged ; Lysine/metabolism ; },
abstract = {Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 - ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6ANUC vs. ER r = 0.2373 and KAT6BNUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.},
}
@article {pmid39500528,
year = {2024},
author = {Degavre, C and Lepez, A and Ibanez, S and François, C and Głowacka, K and Guilbaud, C and Laloux-Morris, F and Esfahani, H and Brusa, D and Bouzin, C and Feron, O},
title = {In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis.},
journal = {Journal for immunotherapy of cancer},
volume = {12},
number = {11},
pages = {},
pmid = {39500528},
issn = {2051-1426},
mesh = {*Photochemotherapy/methods ; Animals ; Mice ; *Peritoneal Neoplasms/immunology/therapy/secondary ; *Dendritic Cells/immunology ; Humans ; Female ; Cancer Vaccines/therapeutic use/pharmacology/immunology ; Photosensitizing Agents/pharmacology/therapeutic use ; Cell Line, Tumor ; Vaccination/methods ; },
abstract = {BACKGROUND: Immunogenic cell death (ICD) and ferroptosis have recently emerged as key factors in the anticancer immune response. Among the treatments able to induce ICD and the associated release of danger signals is photodynamic therapy (PDT). Ferroptosis for its part results from lipid peroxidation and is induced by CD8[+] T cells to kill nearby cancer cells on IFN-γ production. We aimed to combine the two concepts, that is, to evaluate whether the strong pro-oxidant effects of PDT may promote ferroptosis and antigen release and to develop a procedure for in situ PDT to prepare the soil for highly endocytotic immature dendritic cell (iDC) adoptive transfer. This approach was implemented for managing peritoneal carcinomatosis, a lesion often associated with poor outcomes.<br><br>METHODS: We used three-dimensional (3D) heterotypic spheroids made of cancer cells, exposed them to a white light-activated OR141 photosensitizer (PS), and subsequently complexified them by adding iDC and naive lymphocytes. We next used a model of mouse peritoneal carcinomatosis and administered PDT using laparoscopy to locally induce photoactivation using the endoscope light. The immune response following adoptive transfer of iDC was tracked both in vivo and ex vivo using isolated immune cells from in situ vaccinated mice.<br><br>RESULTS: Cancer cells undergoing PDT-induced cell death significantly increased ICD markers and the infiltration of iDCs in spheroids, relying on ferroptosis. These actions induced the sequential activation of CD8[+] and CD4[+] T cells as revealed by a significant spheroid 3D structure deterioration and, remarkably, were not recapitulated by conventional ferroptosis inducer RSL3. Using LED light from an endoscope for in situ photoactivation of PS enabled us to apply the vaccination modality in mice with peritoneal tumors. Consecutive intraperitoneal injection of iDCs resulted in delayed tumor growth, increased survival rates, and prevented tumor relapse on rechallenge. CD8[+] T cell response was supported by depletion experiments, nodal detection of early activated T cells, and ex vivo T cell-induced cytotoxicity toward spheroids.<br><br>CONCLUSIONS: The combination of in situ PDT locally delivered by an endoscope light and iDC administration induces a durable memory immune response against peritoneal carcinomatosis thereby opening new perspectives for the treatment of a life-threatening condition.},
}
@article {pmid39477690,
year = {2025},
author = {Borger, J and Zweck, E and Moos, C and Horn, P and Voß, F and Schultheiss, HP and Møller, JE and Boeken, U and Aubin, H and Lichtenberg, A and Kelm, M and Roden, M and Polzin, A and Westenfeld, R and Szendroedi, J and Scheiber, D},
title = {Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy.},
journal = {ESC heart failure},
volume = {12},
number = {2},
pages = {1246-1255},
pmid = {39477690},
issn = {2055-5822},
support = {236177352//German Research Foundation/ ; 527448911//German Research Foundation/ ; 493659010//German Research Foundation/ ; //Medical Faculty, Heinrich-Heine-University/ ; //German Heart Research Foundation/ ; //German Center for Diabetes Research/ ; //German Diabetes Center/ ; //Federal Ministry of Health/ ; //Ministry of Innovation, Science, Research and Technology of the state North-Rhine Westphalia/ ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; *Myocardial Ischemia/metabolism/complications ; *Mitochondria, Heart/metabolism ; *Cardiomyopathy, Dilated/metabolism ; *Oxidative Stress/physiology ; *Myocarditis/metabolism/etiology ; Aged ; Inflammation/metabolism ; Energy Metabolism ; },
abstract = {AIMS: Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non-ischaemic HF.<br><br>METHODS: We included 81 patients with stage D HF (ICM, n&#xa0;=&#xa0;44; DCM, n&#xa0;=&#xa0;37) undergoing left ventricular assist device implantation (n&#xa0;=&#xa0;59) or heart transplantation (n&#xa0;=&#xa0;22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3[+] cells/mm[2] relevant inflammation.<br><br>RESULTS: Patients with ICM or DCM did not differ regarding age (61.5&#xa0;&#xb1;&#xa0;5.7 vs. 56.5&#xa0;&#xb1;&#xa0;12.7&#xa0;years, P&#xa0;=&#xa0;0.164), sex (86% vs. 84% male, P&#xa0;=&#xa0;0.725), type 2 diabetes mellitus (34% vs. 18%, P&#xa0;=&#xa0;0.126) or chronic kidney disease (8% vs. 11%, P&#xa0;=&#xa0;0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6&#xa0;&#xb1;&#xa0;41.4 vs. 141.9&#xa0;&#xb1;&#xa0;59.9&#xa0;pmol/(s*mg), P&#xa0;=&#xa0;0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59&#xa0;&#xb1;&#xa0;0.28 vs. 0.69&#xa0;&#xb1;&#xa0;0.36&#xa0;pmol/(s*ml), P&#xa0;=&#xa0;0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6&#xa0;&#xb1;&#xa0;164.1 vs. 503.0&#xa0;&#xb1;&#xa0;198.5&#xa0;nmol/min/mg protein, P&#xa0;=&#xa0;0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P&#xa0;=&#xa0;0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r&#xa0;=&#xa0;-0.296, P&#xa0;=&#xa0;0.019). Fibrosis was more prevalent in ICM (20.9&#xa0;&#xb1;&#xa0;21.2 vs. 7.2&#xa0;&#xb1;&#xa0;5.6% of area, P&#xa0;=&#xa0;0.002), but not associated with oxidative capacity (r&#xa0;=&#xa0;-0.13, P&#xa0;=&#xa0;0.327).<br><br>CONCLUSIONS: More than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM.},
}
@article {pmid39445545,
year = {2025},
author = {Wu, B and Gao, A and He, B and Chen, Y and Kong, X and Wen, F and Gao, H},
title = {RNA-seq analysis of mitochondria-related genes regulated by AMPK in the human trophoblast cell line BeWo.},
journal = {Animal models and experimental medicine},
volume = {8},
number = {4},
pages = {649-661},
pmid = {39445545},
issn = {2576-2095},
support = {R16 HD116702/HD/NICHD NIH HHS/United States ; RCMI/IDC Award U54MD007597//National Center on Minority Health and Health Disparities/ ; R16HD116702//National Institute of Child Health and Human Development/ ; U54 MD007597/MD/NIMHD NIH HHS/United States ; R03HD095417//National Institute of Child Health and Human Development/ ; Bridge Fund/Pilot Study Award//Dean's Office Howard University College of Medicine/ ; },
mesh = {Humans ; *Trophoblasts/metabolism ; *Mitochondria/genetics/metabolism ; *AMP-Activated Protein Kinases/metabolism/genetics ; RNA-Seq ; Adenosine Triphosphate/metabolism ; Cell Line ; Gene Expression Regulation ; Protein Interaction Maps ; Signal Transduction ; Pregnancy ; Female ; Gene Expression Profiling ; },
abstract = {BACKGROUND: How AMP activated protein kinase (AMPK) signaling regulates mitochondrial functions and mitophagy in human trophoblast cells remains unclear. This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.<br><br>METHODS: We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2 (PRKAA1/2) knockdown (AKD) and control BeWo cells using the Seahorse real-time ATP rate test, then analyzed gene expression profiling by RNA-seq. Differentially expressed genes (DEG) were examined by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then protein-protein interactions (PPI) among mitochondria related genes were further analyzed using Metascape and Ingenuity Pathway Analysis (IPA) software.<br><br>RESULTS: Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells (CT), with a greater reduction of mitochondrial ATP production. A total of 1092 DEGs were identified, with 405 upregulated and 687 downregulated. GO analysis identified 60 genes associated with the term 'mitochondrion' in the cellular component domain. PPI analysis identified three clusters of mitochondria related genes, including aldo-keto reductase family 1 member B10 and B15 (AKR1B10, AKR1B15), alanyl-tRNA synthetase 1 (AARS1), mitochondrial ribosomal protein S6 (MRPS6), mitochondrial calcium uniporter dominant negative subunit beta (MCUB) and dihydrolipoamide branched chain transacylase E2 (DBT).<br><br>CONCLUSIONS: In summary, this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells, and among them, three clusters of genes may potentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.},
}
@article {pmid39445528,
year = {2024},
author = {Zhao, Z and Li, L and He, M and Li, Y and Ma, X and Zhao, B},
title = {Prognostic and Predictive Markers for Early Stage Triple-Negative Breast Cancer Treated With Platinum-Based Neoadjuvant Chemotherapy.},
journal = {Cancer medicine},
volume = {13},
number = {20},
pages = {e70336},
pmid = {39445528},
issn = {2045-7634},
support = {2019D01C258//The Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; },
mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/genetics/mortality/pathology ; Female ; *Neoadjuvant Therapy/methods ; Middle Aged ; *Polymorphism, Single Nucleotide ; Prognosis ; *BRCA1 Protein/genetics ; *Biomarkers, Tumor/genetics ; Adult ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neoplasm Staging ; BRCA2 Protein/genetics ; Aged ; X-ray Repair Cross Complementing Protein 1/genetics ; Prospective Studies ; Treatment Outcome ; },
abstract = {BACKGROUND: Emerging evidence has indicated possible efficacy benefit of platinum-based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple-negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results.<br><br>MATERIALS AND METHODS: Present study aims to investigate predictive and prognostic roles concerning single nucleotide polymorphisms (SNPs) in XRCC1 and BRCA1, BRCA2 genes for early stage TNBC patients that received platinum-based neoadjuvant treatment. We prospectively enrolled women with stage IIB-IIIB TNBC that had progressed on neoadjuvant taxane and anthracycline-based chemotherapy at Xinjiang Medical University Affiliated Cancer Hospital. Tumor response and pathological complete response (pCR) rate were assessed. Invasive disease-free survival (iDFS) and overall survival (OS) were analyzed. Patients' blood samples were subject to Sanger sequencing to genotype XRCC1 Arg194Trp and Arg399Gln, BRCA1 s1799949, and BRCA2 rs206115. Univariate and multivariate logistic regressions were employed to investigate associations between SNPs and clinical characteristics with treatment response and pCR. A total of 45 patients were enrolled.<br><br>RESULTS: The cohort showcased ORR of 44.4%, pCR of 28.9%, median iDFS of 22&#x2009;months, and a 3-year OS of 73.3%. The A/G and G/G genotypes of BRCA1 rs1799949, and the T/T genotype of BRCA2 rs206115 were associated with higher responsive rate. Histologic grade of III and Ki67 expression >&#x2009;65% were associated with low responsive rate. Moreover, the A/G genotype of BRCA1 rs1799949 and T/T genotype of BRCA2 rs206115 correlated to high pCR. The histologic III and T4 stage correlated to inferior iDFS. Carrier of BRCA1 rs1799949 G/G had the most favorable OS, carriers of A/A showed the poorest OS, and those with A/G genotype showed an intermediate OS.<br><br>CONCLUSIONS: Platinum-based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline- and taxane-based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers.},
}
@article {pmid39443384,
year = {2025},
author = {João, D and Feltri, M and Klubickova, N and Michal, M and Kacerovská, D and Skálová, A},
title = {Apocrine variant of intraductal carcinoma of the parotid gland with sebaceous-like differentiation: expanding morphological and molecular spectrum of an enigmatic entity.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {487},
number = {1},
pages = {215-219},
pmid = {39443384},
issn = {1432-2307},
mesh = {Humans ; Male ; Middle Aged ; *Parotid Neoplasms/pathology/genetics ; Cell Differentiation ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Sebaceous Glands/pathology ; Mutation ; Biomarkers, Tumor/analysis/genetics ; *Carcinoma, Ductal/pathology/genetics ; *Apocrine Glands/pathology ; },
abstract = {Intraductal carcinoma (IDC) is a rare tumor of the salivary glands. Here, we report a unique case of apocrine IDC of the parotid gland of a 60-year-old male, exhibiting a striking sebaceous-like differentiation. Microscopically, the tumor displayed a papillary growth pattern with apocrine cells (AR-positive; S100/SOX10-negative) and distinct areas harboring clear, vacuolated cells resembling sebaceous cells (CK7/S100/SOX10-positive; AR negative). Molecular genetic analysis revealed mutations in AKT1 and BRAF genes. An AKT1 gene mutation has earlier been described in sclerosing polycystic adenoma (SPA), suggesting a possible link between IDC and SPA, while BRAF V600E mutations were reported in an oncocytic subtype of IDC, but not in the apocrine one. Since IDC is an indolent disease, its recognition is a key to prevent unwarranted overtreatment. Further evidence is needed to determine whether apocrine IDC with sebaceous-like differentiation represents a novel morphological variant of the apocrine subtype of IDC or a novel salivary gland entity.},
}
@article {pmid39435217,
year = {2024},
author = {Kumaravel, A and Esakki, M},
title = {Comparing CD10 Expression With the Clinicopathological Features and Hormone Status of Invasive Breast Cancer.},
journal = {Cureus},
volume = {16},
number = {9},
pages = {e69836},
pmid = {39435217},
issn = {2168-8184},
abstract = {Background Worldwide, female breast cancer is the most common cancer (11.7%), followed by lung (11.4%), colorectal, prostate, and stomach. Breast cancer is the fifth most common cause of cancer-related mortality, with lung cancer being the leading cause. In India, breast and cervical cancers are the two most common cancers among women. This study was undertaken to analyse the expression of CD10 in invasive duct cancer (IDC) and its correlation with the various clinicopathological features and hormone status. Materials and methods This study was conducted in the Department of Pathology, Saveetha Medical College and Hospital on 42 cases of invasive ductal carcinoma - no special type (IDC NST). The clinical and histopathologic parameters such as age, tumor site, tumor size, histologic type, histologic grade, lymph node metastases, lymphovascular invasion, and perineural invasion were assessed in hematoxylin and eosin-stained sections of the tumor tissue along with the hormone status of positivity for ER, PR and Her2Neu. These parameters were subsequently compared with the expression of CD10 in the corresponding slides and statsitical correlation was done using the chi square test. Results The most common age group was more than 40 years, with 41-50 years, and 51-60 years in particular. CD10 was positive in 93% of cases. There was a positive correlation between CD 10 expression and lymphovascular invasion in the study (p-0.006). There was no significant relationship between hormone status and CD10 expression. Conclusion A significant association was seen between CD10 expression and lymphovascular invasion. No relation was found between CD10 and the other parameters such as tumour grade, lymph node metastases, lymphovascular invasion, perineural invasion and hormone status. Further studies are required to explore the potential of CD10 as a prognostic marker for IDC.},
}
@article {pmid39418320,
year = {2025},
author = {Schwarz, D and Le Marois, M and Sturm, V and Peters, AS and Longuespée, R and Helm, D and Schneider, M and Eichmüller, B and Hidmark, AS and Fischer, M and Kender, Z and Schwab, C and Hausser, I and Weis, J and Dihlmann, S and Böckler, D and Bendszus, M and Heiland, S and Herzig, S and Nawroth, PP and Szendroedi, J and Fleming, T},
title = {Exploring Structural and Molecular Features of Sciatic Nerve Lesions in Diabetic Neuropathy: Unveiling Pathogenic Pathways and Targets.},
journal = {Diabetes},
volume = {74},
number = {1},
pages = {65-74},
pmid = {39418320},
issn = {1939-327X},
support = {GRK 1874/2//DFG/ ; //Deutsche Forschungsgemeinschaft/ ; //German Centre for Diabetes Research/ ; },
mesh = {*Diabetic Neuropathies/metabolism/pathology ; Humans ; *Sciatic Nerve/metabolism/pathology ; Male ; *Diabetes Mellitus, Type 2/metabolism/complications ; Middle Aged ; *Proteomics ; Female ; Aged ; Blood-Nerve Barrier/metabolism ; Magnetic Resonance Imaging ; Adult ; },
abstract = {Lesioned fascicles (LFs) in the sciatic nerves of individuals with diabetic neuropathy (DN) correlate with clinical symptom severity. This study aimed to characterize the structural and molecular composition of these lesions to better understand DN pathogenesis. Sciatic nerves from amputees with and without type 2 diabetes (T2D) were examined using ex vivo magnetic resonance neurography, in vitro imaging, and proteomic analysis. Lesions were only found in T2D donors and exhibited significant structural abnormalities, including axonal degeneration, demyelination, and impaired blood-nerve barrier (BNB). Although non-LFs from T2D donors showed activation of neuroprotective pathways, LFs lacked this response and instead displayed increased complement activation via the classical pathway. The detection of liver-derived acute-phase proteins suggests that BNB disruption facilitates harmful interorgan communication between the liver and nerves. These findings reveal key molecular mechanisms contributing to DN and highlight potential targets for therapeutic intervention.},
}
@article {pmid39393363,
year = {2025},
author = {Xu, J and Accola, MA and Rehrauer, WM and Weisman, PS},
title = {Pilomatrix-like breast carcinoma: A mammary analog of pilomatrix-like high-grade endometrioid carcinoma (PiMHEC).},
journal = {American journal of clinical pathology},
volume = {163},
number = {3},
pages = {388-394},
doi = {10.1093/ajcp/aqae132},
pmid = {39393363},
issn = {1943-7722},
support = {//University of Wisconsin-Madison/ ; //School of Medicine and Public Health/ ; //Department of Pathology and Laboratory Medicine/ ; },
mesh = {Female ; Humans ; beta Catenin/genetics ; Biomarkers, Tumor/metabolism/analysis ; *Breast Neoplasms/pathology/genetics ; *Carcinoma, Endometrioid/pathology/genetics/metabolism ; Mutation ; *Pilomatrixoma/pathology/genetics ; *Triple Negative Breast Neoplasms/pathology/genetics/metabolism ; Aged ; },
abstract = {OBJECTIVES: To describe what is, to our knowledge, the first recognized case of a triple-negative breast carcinoma (TNBC) with a PiMHEC-like phenotype. Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is a high-grade carcinoma with divergent differentiation resembling cutaneous pilomatrix carcinoma that was recently described in the endometrium and ovary. For reference, pertinent features of PiMHEC include (1) high-grade basaloid to squamoid morphology with the presence of ghost cells; (2) only focal p63 and/or p40 expression despite a squamoid appearance; (3) CTNNB1 mutation, accompanied by diffusely aberrant β-catenin expression and LEF1 and/or CDX2 expression; and (4) loss of site-specific markers (ie, PAX8, ER).<br><br>METHODS: Here we report the histologic, immunophenotypic and molecular genetic features of a case of a triple-negative breast carcinoma (TNBC) with a PiMHEC-like phenotype.<br><br>RESULTS: The tumor developed immediately adjacent to a HER2+, androgen receptor (AR)+, GATA3+ conventional grade 3 invasive ductal carcinoma (IDC) with only membranous &#x3b2;-catenin expression. The PiMHEC-like component had all of the above-noted morphologic and immunophenotypic features of endometrial PiMHEC but with loss of GATA3 and AR rather than PAX8 and ER. Molecular analysis performed on both tumor components demonstrated a shared TP53 point mutation and an exon 3 CTNNB1 mutation restricted to the PiMHEC-like component, implying a clonal relationship with secondary acquisition of CTNNB1. Following neoadjuvant chemotherapy, the HER2+ conventional component had completely resolved, but the PiMHEC-like component had very little response.<br><br>CONCLUSIONS: This case demonstrates that a PiMHEC-like phenotype may be seen as a form of TNBC that can develop from conventional IDC, with loss of site-specific biomarkers, acquisition of CTNNB1 mutation, and resistance to conventional chemotherapy.},
}
@article {pmid39392173,
year = {2024},
author = {Huang, YJ and Lin, JA and Chen, WM and Shia, BC and Wu, SY},
title = {Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.},
journal = {Journal of the American Heart Association},
volume = {13},
number = {20},
pages = {e036411},
pmid = {39392173},
issn = {2047-9980},
mesh = {Humans ; Female ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Middle Aged ; Retrospective Studies ; *Cardiotoxicity ; Radiotherapy, Adjuvant/adverse effects ; Taiwan/epidemiology ; Aged ; Breast Neoplasms/radiotherapy ; Incidence ; Mastectomy, Segmental ; Registries ; Risk Assessment ; Radiation Injuries/epidemiology/prevention &amp; control/etiology ; Adult ; Carcinoma, Ductal, Breast/radiotherapy ; Risk Factors ; Treatment Outcome ; },
abstract = {BACKGROUND: To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy.<br><br>METHODS AND RESULTS: A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left-sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast-conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25-0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose-response relationship. The 5-year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%).<br><br>CONCLUSIONS: Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.},
}
@article {pmid39382167,
year = {2024},
author = {Koumantou, D and Adiko, AC and Bourdely, P and Nugue, M and Boedec, E and El-Benna, J and Monteiro, R and Saveanu, C and Laffargue, M and Wymann, MP and Dalod, M and Guermonprez, P and Saveanu, L},
title = {Specific Requirement of the p84/p110γ Complex of PI3Kγ for Antibody-Activated, Inducible Cross-Presentation in Murine Type 2 DCs.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {11},
number = {44},
pages = {e2401179},
pmid = {39382167},
issn = {2198-3844},
support = {ANR-11-IDEX-0005-02//Agence Nationale de la Recherche/ ; ANR-15-CE15-0005//Agence Nationale de la Recherche/ ; ANR-17-CE11-0001//Agence Nationale de la Recherche/ ; //Fondation pour la Recherche Medicale/ ; ANR-10-EQPX-03//ICGex NGS platform of the Institut Curie/ ; ANR-10-INBS-09-08//ICGex NGS platform of the Institut Curie/ ; INCa-DGOS-465//SiRIC-Curie program/ ; INCa-DGOS- Inserm_12554//SiRIC-Curie program/ ; SNF-310030-189065/SNSF_/Swiss National Science Foundation/Switzerland ; },
mesh = {Animals ; Mice ; *Dendritic Cells/immunology/metabolism ; *Cross-Priming/immunology ; *Mice, Inbred C57BL ; Class Ib Phosphatidylinositol 3-Kinase/metabolism/immunology/genetics ; Antigen Presentation/immunology ; },
abstract = {Cross-presentation by MHCI is optimally efficient in type 1 dendritic cells (DC) due to their high capacity for antigen processing. However, through specific pathways, other DCs, such as type 2 DCs and inflammatory DCs (iDCs) can also cross-present antigens. FcγR-mediated uptake by type 2 DC and iDC subsets mediates antibody-dependent cross-presentation and activation of CD8[+] T cell responses. Here, an important role for the p84 regulatory subunit of PI3Kγ in mediating efficient cross-presentation of exogenous antigens in otherwise inefficient cross-presenting cells, such as type 2 DCs and GM-CSF-derived iDCs is identified. FcγR-mediated cross-presentation is shown in type 2 and iDCs depend on the enzymatic activity of the p84/p110γ complex of PI3Kγ, which controls the activity of the NADPH oxidase NOX2 and ROS production in murine spleen type 2 DCs and GM-CSF-derived iDCs. In contrast, p84/p110γ is largely dispensable for cross-presentation by type 1 DCs. These findings suggest that PI3Kγ-targeted therapies, currently considered for oncological practice, may interfere with the ability of type 2 DCs and iDCs to cross-present antigens contained in immune complexes.},
}
@article {pmid39365417,
year = {2025},
author = {Taira, S and Kawagoe, M and Anzai, H and Yasukawa, M and Asakawa, S and Arai, S and Yamazaki, O and Tamura, Y and Oshima, Y and Numakura, S and Ohashi, R and Shibata, S and Fujigaki, Y},
title = {Immunoglobulin A-dominant membranoproliferative glomerulonephritis-like pattern of injury as a possible paraneoplastic nephropathy in a breast cancer patient.},
journal = {CEN case reports},
volume = {14},
number = {2},
pages = {217-223},
pmid = {39365417},
issn = {2192-4449},
mesh = {Humans ; Female ; *Breast Neoplasms/complications/therapy/pathology ; *Glomerulonephritis, Membranoproliferative/diagnosis/pathology/etiology ; Middle Aged ; *Immunoglobulin A ; *Paraneoplastic Syndromes/diagnosis/pathology/etiology ; Hematuria/etiology ; *Glomerulonephritis, IGA/diagnosis/pathology ; Proteinuria/etiology ; *Carcinoma, Ductal, Breast/complications/therapy/pathology ; Biopsy ; Kidney/pathology ; },
abstract = {A middle-aged woman was found to have proteinuria during a health check-up. About sixteen months later, she was diagnosed with stage IIA invasive ductal carcinoma of the right breast. Her proteinuria progressed to nephrotic syndrome with significant hematuria. Hormone therapy was initiated for her estrogen and progesterone receptor-positive breast cancer. A kidney biopsy performed 47 days after starting the therapy revealed an IgA-dominant membranoproliferative glomerulonephritis-like pattern of injury. Electron microscopy showed subendothelial-dominant electron-dense deposits (EDD), with small amounts of mesangial EDD and a single occurrence of subepithelial hump-like EDD, along with occasional mesangial interpositions. Similar pathology can be caused by IgA vasculitis with nephritis, IgA-dominant infection-associated glomerulonephritis, and liver disease-associated glomerulopathy, but all of these were ruled out. The deposited IgA was found to be galactose-deficient IgA1. Thus, IgA nephropathy with glomerular capillary IgA deposition was considered. She underwent a right partial mastectomy and sentinel lymph node biopsy in the right axilla 75 days after starting hormone therapy, followed by adjuvant radiation. Proteinuria and hematuria tended to decrease after the treatment, and this trend continued even after corticosteroid therapy for glomerulonephritis, which was administered 156 days after starting hormone therapy. Approximately 15 months after starting hormone therapy, her proteinuria had reduced to around 1.0 g/g of creatinine, and her hematuria was negative. IgA nephropathy with glomerular capillary IgA deposition is known to be resistant to corticosteroid therapy. The favorable clinical course of the rare glomerulopathy following breast cancer treatment suggested a diagnosis of paraneoplastic glomerulopathy secondary to breast cancer in our patient.},
}
@article {pmid39363164,
year = {2024},
author = {Sun, Y and Pan, Z and Wang, Z and Wang, H and Wei, L and Cui, F and Zou, Q and Zhang, Z},
title = {Single-cell transcriptome analysis reveals immune microenvironment changes and insights into the transition from DCIS to IDC with associated prognostic genes.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {894},
pmid = {39363164},
issn = {1479-5876},
support = {62102064//National Natural Science Foundation of China/ ; 62261018//National Natural Science Foundation of China/ ; 62262015//National Natural Science Foundation of China/ ; ZDYF2024GXJS01//Science and Technology special fund of Hainan Province/ ; 324MS009//Hainan Provincial Natural Science Foundation of China/ ; },
mesh = {Humans ; *Single-Cell Analysis ; Female ; *Tumor Microenvironment/genetics/immunology ; *Gene Expression Profiling ; Prognosis ; *Carcinoma, Intraductal, Noninfiltrating/genetics/immunology/pathology ; *Breast Neoplasms/genetics/immunology/pathology ; *Gene Expression Regulation, Neoplastic ; *Carcinoma, Ductal, Breast/genetics/pathology/immunology ; *Disease Progression ; Transcriptome/genetics ; Single-Cell Gene Expression Analysis ; },
abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood.<br><br>RESULTS: We identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers.<br><br>CONCLUSIONS: We identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.},
}
@article {pmid39341718,
year = {2024},
author = {Drake, MJ and Clavica, F and Murphy, C and Fader, MJ},
title = {Innovating Indwelling Catheter Design to Counteract Urinary Tract Infection.},
journal = {European urology focus},
volume = {10},
number = {5},
pages = {713-719},
doi = {10.1016/j.euf.2024.09.015},
pmid = {39341718},
issn = {2405-4569},
mesh = {Humans ; *Catheters, Indwelling/adverse effects/microbiology ; *Urinary Tract Infections/prevention &amp; control ; *Equipment Design ; Urinary Catheters/adverse effects ; Catheter-Related Infections/prevention &amp; control ; Urinary Catheterization/adverse effects ; Stents/adverse effects ; Biofilms ; Bacteriuria/prevention &amp; control ; },
abstract = {BACKGROUND AND OBJECTIVE: Bacteriuria is anticipated in long-term indwelling catheter (IDC) use, and urinary tract infections (UTIs) and related issues are common. Defence mechanisms against infection are undermined by the presence of a Foley catheter, and adjustments to design could influence UTI risk.<br><br>METHODS: We reviewed the various aspects of IDCs and ureteric stent designs to discuss potential impact on UTI risk.<br><br>KEY FINDINGS AND LIMITATIONS: Design adaptations have focussed on reducing the sump of undrained urine, potential urinary tract trauma, and bacterial adherence. Experimental and computational studies on ureteral stents found an interplay between urine flow, bacterial microcolony formation, and accumulation of encrusting particles. The most critical regions for biofilm and crystal accumulation are associated with low shear stress. The full drainage system is the functioning unit, not just the IDC in isolation. This means reliably keeping the drainage system closed and considering whether a valve is preferred to a collection bag. Other developments may include one-way valves, obstacles to "bacterial swimming", and ultrasound techniques. Preventing or clearing IDC blockage can exploit access via the lumen or retaining balloon. Progress in computational fluid dynamics, energy delivery, and soft robotics may increase future options. Clinical data on the effectiveness of IDC design features are lacking, which is partly due to reliance on proxy measures and the challenges of undertaking trials.<br><br>Design changes are legitimate lines of development, but are only indirect for UTI prevention. Modifications may be advantageous, but might potentially bring problems in other ways. Education of health care professionals can improve UTIs and should be prioritised.<br><br>PATIENT SUMMARY: Catheters used to help bladder drainage can cause urinary infections, and improvements in design might reduce the risk. Several approaches are described in this review. However, proving that these approaches work is a challenge. Training professionals in the key aspects of catheter care is important.},
}
@article {pmid39341603,
year = {2024},
author = {Pereira, LHS and Alves, ADC and Lopes, GFM and da Silva, BF and Vieira, MS and Lopes, DO and Ferreira, JMS and Lara Dos Santos, L},
title = {Soluble isoforms of the DC-SIGN receptor can increase the dengue virus infection in immature dendritic cells.},
journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases},
volume = {28},
number = {6},
pages = {103873},
pmid = {39341603},
issn = {1678-4391},
mesh = {*Cell Adhesion Molecules/metabolism ; *Receptors, Cell Surface/metabolism ; *Lectins, C-Type/metabolism ; *Dengue Virus/immunology ; *Dendritic Cells/virology/immunology ; Humans ; Animals ; *Protein Isoforms ; Viral Load ; Dengue/immunology ; Aedes/virology ; },
abstract = {Dengue is a disease with a high-impact on public health worldwide. Many researches have focused on the cell receptors involved in its pathogenesis. The role of soluble isoforms of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin) receptor in the process of Dengue Virus (DENV) infection is not well understood. This work proposes to evaluate changes in the infection process of Immature Dendritic Cells (iDCs) by DENV in the presence of DC-SIGN recombinant soluble isoforms 8, 10, and 12. The recombinant isoforms were built by heterologous expression, the DENV-2 was multiplied in the Aedes albopictus C6/36 cells and quantified in BHK-21 cells, and the iDCs were produced from the THP-1 strain. Infection assays were performed in the presence of iDCs, DENV-2, and isoforms 8, 10, and 12 separately at 25, 50 and 100 ng/mL. The final viral load was estimated by qPCR and statistical analysis was performed by Kruskal-Wallis and ANOVA tests. The iDC profile was confirmed by increasing expression of CD11c, CD86, and CD209 surface markers and maintaining CD14 expression. Infection assays demonstrated a 23-fold increase in DENV viral load in the presence of isoforms 8 and 10 at 100 ng/mL compared to the viral control (p < 0.05), while isoform 12 did not alter the viral load. It was possible to conclude that at 100 ng/mL isoforms (8 and 10) can interact with DENV, increasing viral infection, and potentially acting as opsonins.},
}
@article {pmid39331289,
year = {2024},
author = {Vasigh, M and Mohamed, A and Jacobs, L and Lange, J and Camp, M and Sun, B and Wright, P and O'Donnell, M and Tran, HT and Sogunro, O and Habibi, M and Johnston, F and Euhus, D},
title = {The Association Between Breast Cancer Predisposing Genetic Variants and Multifocal, Multicentric Breast Cancer.},
journal = {Annals of surgical oncology},
volume = {31},
number = {13},
pages = {8891-8899},
pmid = {39331289},
issn = {1534-4681},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Retrospective Studies ; Middle Aged ; *Genetic Predisposition to Disease ; Adult ; Prognosis ; Follow-Up Studies ; Carcinoma, Ductal, Breast/genetics/pathology ; Aged ; Biomarkers, Tumor/genetics ; Genetic Variation ; },
abstract = {BACKGROUND: Breast-conserving surgery is often discouraged in BRCA gene carriers with early onset breast cancer. The genetic variant carrier breast cancers are more likely to be multifocal or multicentric (MFMC).<br><br>PATIENTS AND METHOD: This retrospective study includes newly diagnosed patients with breast cancer undergoing genetic testing between 2010 and 2021 within the Johns Hopkins Regional Health System. After excluding patients who received neoadjuvant chemotherapy or stage IV breast cancers, patients were divided into two groups: those who tested positive for a variant recognized by the National Comprehensive Cancer Network as predisposing the patient to breast cancer (ATM, BRCA1, BRCA2, CHEK2, NF1, PALB2, RAD51C, RAD51D, and TP53) and those who tested negative. Pathologic features of the tumors were compared, focusing on evidence for MFMC disease, defined as more than one malignant foci more than 5&#xa0;mm apart.<br><br>RESULTS: Among the 282 eligible cases, 69 (24%) were positive for a genetic variant. The variant carriers were younger at diagnosis (p&#x2009;<&#x2009;0.001), more likely to have invasive ductal carcinoma (p&#x2009;=&#x2009;0.03), more likely to have undergone mastectomy (p&#x2009;=&#x2009;0.03), and more likely to have a grade 3 cancer (p&#x2009;=&#x2009;0.003). Variant carriers were not more likely to have MFMC disease (28% vs. 22%, p&#x2009;=&#x2009;0.4). A positive genetic variant was not a predictor of MFMC within the entire cohort [odds ratio (OR):1.3, 95% confidence interval (CI) 0.6-2.6, p&#x2009;=&#x2009;0.5).<br><br>CONCLUSION: Genetic variant carrier cancers are not more likely to be MCMF than sporadic cancers.},
}
@article {pmid39328281,
year = {2024},
author = {Shrestha, P and Hsieh, MC and Ferguson, T and Peters, ES and Trapido, E and Yu, Q and Chu, QD and Wu, XC},
title = {Higher 10-Year Survival with Breast-Conserving Therapy over Mastectomy for Women with Early-Stage (I-II) Breast Cancer: Analysis of the CDC Patterns of Care Data Base.},
journal = {Breast cancer : basic and clinical research},
volume = {18},
number = {},
pages = {11782234241273666},
pmid = {39328281},
issn = {1178-2234},
abstract = {BACKGROUND: Studies in the United States are scarce that assess the survival differences between breast-conserving surgery plus radiation (Breast-Conserving Therapy; BCT) and mastectomy groups using population-based data while accounting for sociodemographic and clinical factors that affect the survival of women with early-stage breast cancer (ESBC).<br><br>OBJECTIVE: To assess whether BCT provides superior long-term overall survival (OS) and breast cancer-specific survival (BCSS) compared with mastectomy in women with ESBC, while considering key factors that impact survival.<br><br>DESIGN: Cohort study.<br><br>METHODS: We analyzed data on women aged 20&#x2009;years and older diagnosed with stage I-II breast cancer (BC) in 2004 who received either BCT or mastectomy. The data were collected by 5 state cancer registries through the Centers for Disease Control and Prevention-funded Patterns of Care study. Multivariable Cox proportional hazard models, accounting for sociodemographic and clinical factors, were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity analysis involved optimal caliper propensity score (PS) matching to address residual confounding.<br><br>RESULTS: Of the 3495 women, 41.5% underwent mastectomy. The 10-year OS and BCSS were 82.7% and 91.1% for BCT and 72.3% and 85.7% for mastectomy, respectively. Adjusted models showed that mastectomy recipients had a 22% higher risk of all-cause deaths (ACD) (HR&#x2009;=&#x2009;1.22, 95% CI&#x2009;=&#x2009;[1.06, 1.41]) and a 26% higher risk of breast cancer-specific deaths (BCD) (HR&#x2009;=&#x2009;1.26, 95% CI&#x2009;=&#x2009;[1.02, 1.55]) than BCT recipients. Sensitivity analysis demonstrated that mastectomy was associated with a higher risk of ACD (P&#x2009;<&#x2009;.05) but did not exhibit a statistically significant risk for BCD. Women with HR+/HER2+ (luminal B) or invasive ductal carcinoma BC who underwent mastectomy had higher risks of ACD and BCD compared with BCT recipients, while the hazards for ACD in triple-negative BC did not remain significant after adjusting for covariates.<br><br>CONCLUSION: ESBC BCT recipients demonstrate superior OS and BCSS compared with mastectomy recipients.},
}
@article {pmid39320077,
year = {2024},
author = {Hadad, Z and Wahid, W and Afzelius, P},
title = {[Not Available].},
journal = {Ugeskrift for laeger},
volume = {186},
number = {36},
pages = {},
doi = {10.61409/V01240024},
pmid = {39320077},
issn = {1603-6824},
mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/secondary/pathology/diagnostic imaging ; *Liver Neoplasms/secondary/diagnostic imaging ; *Lymphatic Metastasis/diagnostic imaging ; *Neoplasm Recurrence, Local/pathology ; },
abstract = {Breast cancer usually metastasizes by haematogenous spread. This is a case report of a woman with unusual liver metastases from a recurrent invasive ductal carcinoma via a lymphatic route draining the outer part of the breast to the liver running parallelly with the right rectus abdominis muscle, depicted by preoperative sentinel node lymphoscintigraphy. Realizing this route of metastasis can impact survival, as it has a favourable prognosis compared with haematogenous metastasis, we want to draw attention to this.},
}
@article {pmid39317017,
year = {2024},
author = {Louis, M and Fang, J and Grabill, N and Singh, H and Strom, P},
title = {Her2-positive breast cancer in a young patient with Li-Fraumeni syndrome: A comprehensive case study.},
journal = {International journal of surgery case reports},
volume = {124},
number = {},
pages = {110323},
pmid = {39317017},
issn = {2210-2612},
abstract = {INTRODUCTION AND IMPORTANCE: Li-Fraumeni syndrome (LFS) is a rare hereditary disorder caused by mutations in the TP53 gene, leading to a significantly increased risk of developing various cancers at a young age, including breast cancer.<br><br>CLINICAL PRESENTATION: This case report details the clinical journey of a 21-year-old female diagnosed with Grade 3 invasive ductal carcinoma, which was estrogen receptor low positive and progesterone receptor negative but positive for Her2 (3+) with a high Ki67 proliferation index.<br><br>CLINICAL DISCUSSION: Genetic testing confirmed a TP53 mutation, establishing the diagnosis of LFS. The patient underwent neoadjuvant chemotherapy with TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab), resulting in a complete clinical response. This was followed by bilateral skin-sparing and nipple-sparing mastectomy with sentinel lymph node biopsy and immediate reconstruction. Postoperative pathology confirmed a complete response to neoadjuvant therapy. The patient's treatment plan includes 12&#xa0;cycles of trastuzumab and pertuzumab, with regular echocardiograms to monitor cardiac function and fertility preservation strategies involving monthly Lupron injections. Given the association of LFS with a high risk of multiple primary cancers, a rigorous surveillance strategy is essential. The psychological impact of a cancer diagnosis and the burden of living with a hereditary cancer syndrome were significant, necessitating comprehensive psychosocial support.<br><br>CONCLUSION: Managing Li-Fraumeni syndrome (LFS) and its associated cancers, particularly in young patients, necessitates a comprehensive and multidisciplinary approach. Early genetic testing for TP53 mutations is crucial in identifying LFS, enabling personalized treatment plans and proactive surveillance strategies.},
}
@article {pmid39315404,
year = {2024},
author = {Liu, Y and Lin, D and Najam, SS and Huang, S and Song, M and Sirakawin, C and Zhao, C and Jiang, H and Konopka, W and Herzig, S and Vinnikov, IA},
title = {Functional redundancy between glucocorticoid and mineralocorticoid receptors in mature corticotropin-releasing hormone neurons protects from obesity.},
journal = {Obesity (Silver Spring, Md.)},
volume = {32},
number = {10},
pages = {1885-1896},
doi = {10.1002/oby.24116},
pmid = {39315404},
issn = {1930-739X},
support = {31771433//National Natural Science Foundation of China/ ; 32241020//National Natural Science Foundation of China/ ; 32350610254//National Natural Science Foundation of China/ ; },
mesh = {Animals ; Male ; Mice ; *Corticosterone/blood/metabolism ; *Corticotropin-Releasing Hormone/metabolism ; *Energy Metabolism ; Insulin Resistance ; Mice, Inbred C57BL ; *Mice, Knockout ; *Neurons/metabolism ; *Obesity/metabolism ; Paraventricular Hypothalamic Nucleus/metabolism ; *Receptors, Glucocorticoid/metabolism/genetics ; *Receptors, Mineralocorticoid/metabolism/genetics ; Female ; },
abstract = {OBJECTIVE: Here, we aimed to investigate the role of glucocorticoid and mineralocorticoid receptors (GRs and MRs, respectively) in the regulation of energy homeostasis.<br><br>METHODS: We used three mouse models with simultaneous deletion of GRs and MRs in either forebrain neurons, the paraventricular nucleus, or corticotropin-releasing hormone (CRH) neurons and compared them with wild-type controls or isolated knockout groups. In addition to body weight, food intake, energy expenditure, insulin sensitivity, fat/lean mass distribution, and plasma corticosterone levels, we also performed transcriptomic analysis of CRH neurons and assessed their response to melanocortinergic stimulation.<br><br>RESULTS: Similar to global double-knockout models, deletion of GRs and MRs specifically in mature CRH neurons resulted in obesity. Importantly, the latter was accompanied by insulin resistance, but not increased plasma corticosterone levels. Transcriptomic analysis of these neurons revealed upregulation of several genes involved in postsynaptic signal transduction, including the Ptk2b gene, which encodes proline-rich tyrosine kinase 2. Knockout of both nuclear receptors leads to upregulation of Ptk2b in CRH neurons, which results in their diminished responsiveness to melanocortinergic stimulation.<br><br>CONCLUSIONS: Our data demonstrate the functional redundancy of GRs and MRs in CRH neurons to maintain energy homeostasis and prevent obesity. Simultaneous targeting of both receptors might represent an unprecedented approach to counteract obesity.},
}
@article {pmid39302353,
year = {2024},
author = {Ben Kridis, W and Lajnef, M and Khanfir, A},
title = {Synchronous primary breast angiosarcoma with invasive ductal carcinoma.},
journal = {Breast disease},
volume = {43},
number = {1},
pages = {271-274},
pmid = {39302353},
issn = {1558-1551},
mesh = {Humans ; Female ; *Hemangiosarcoma/secondary/pathology ; *Breast Neoplasms/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/pathology/secondary ; *Neoplasms, Multiple Primary/pathology ; Ovarian Neoplasms/pathology/secondary ; },
abstract = {Primary angiosarcoma (PAS) of the breast is an extremely uncommon variant of breast malignancies. Highly aggressiveness and dismal prognosis characterize this endothelial neoplasm. We report here an unusual case of PAS of the breast occurring in a 46-year-old woman associated with concurrent bilateral invasive ductal carcinoma and ovarian metastases.},
}
@article {pmid39296436,
year = {2024},
author = {Mihai, AM and Ianculescu, LM and Suciu, N},
title = {MiRNAs as potential biomarkers in early breast cancer detection: a systematic review.},
journal = {Journal of medicine and life},
volume = {17},
number = {6},
pages = {549-554},
pmid = {39296436},
issn = {1844-3117},
mesh = {Female ; Humans ; *Biomarkers, Tumor/blood/genetics ; *Breast Neoplasms/blood/diagnosis/genetics ; *Early Detection of Cancer/methods ; *Circulating MicroRNA/blood/genetics ; },
abstract = {Breast cancer remains a significant global health challenge, with high incidence and mortality rates. While mammography has contributed to declining mortality, its limitations in sensitivity and specificity for early detection, particularly in distinguishing between pure atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC), highlight the need for more precise tools. Even with core needle biopsy (CNB), conclusive diagnoses often require surgical excision. This underscores the urgency for non-invasive biomarkers to improve early detection and differentiation, potentially reducing invasive procedures. Recent research has shifted focus from mRNA to microRNAs (miRNAs) as promising biomarkers for breast cancer screening. These small non-coding RNAs, which exhibit abnormal expression patterns in breast cancer patients' tissue and serum/plasma, play crucial roles in early breast cancer development by modulating proto-oncogenes or tumor suppressor genes at the post-transcriptional level. Notably, miRNAs such as miR-21, miR-155, and miR-200c are key regulators of cell proliferation and apoptosis, with the potential to distinguish between normal tissue and various stages of breast lesions, including ADH, DCIS, and IDC. Additionally, miRNAs in serum and plasma offer a non-invasive method to differentiate breast cancer stages. This review aims to consolidate current knowledge on early breast lesions and explore the potential of miRNAs as biomarkers for early breast cancer detection, which could enhance risk prediction and reduce reliance on invasive diagnostic procedures.},
}
@article {pmid39284909,
year = {2024},
author = {Brunetta, HS and Jung, AS and Valdivieso-Rivera, F and de Campos Zani, SC and Guerra, J and Furino, VO and Francisco, A and Berçot, M and Moraes-Vieira, PM and Keipert, S and Jastroch, M and Martinez, LO and Sponton, CH and Castilho, RF and Mori, MA and Bartelt, A},
title = {IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.},
journal = {The EMBO journal},
volume = {43},
number = {21},
pages = {4870-4891},
pmid = {39284909},
issn = {1460-2075},
support = {2022/00358-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo (FAPESP)/ ; 852742//EC | European Research Council (ERC)/ ; BA4925/2-1//Deutsche Forschungsgemeinschaft (DFG)/ ; 81X3600212//Deutsches Zentrum f&#xfc;r Herz-Kreislaufforschung (DZHK)/ ; 310287/2018-9//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico (CNPq)/ ; 88881.143924/2017-01//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior (CAPES)/ ; },
mesh = {Animals ; *Thermogenesis/genetics ; Mice ; *Adipose Tissue, Brown/metabolism ; *Cold Temperature ; *ATPase Inhibitory Protein ; *Mitochondrial Proton-Translocating ATPases/metabolism/genetics ; Hydrolysis ; Mitochondria/metabolism ; Mice, Inbred C57BL ; Male ; Adipocytes, Brown/metabolism ; Membrane Potential, Mitochondrial ; Energy Metabolism ; },
abstract = {While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether F1Fo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called "reverse mode" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.},
}
@article {pmid39283254,
year = {2024},
author = {Cai, F and Li, Y and Liu, H and Luo, J},
title = {Single-cell and Spatial Transcriptomic Analyses Implicate Formation of the Immunosuppressive Microenvironment during Breast Tumor Progression.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {213},
number = {9},
pages = {1392-1401},
doi = {10.4049/jimmunol.2400025},
pmid = {39283254},
issn = {1550-6606},
support = {62072058//MOST | National Natural Science Foundation of China (NSFC)/ ; 82073339//MOST | National Natural Science Foundation of China (NSFC)/ ; BK20231271//JST | Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)/ ; },
mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; *Breast Neoplasms/immunology/genetics/pathology ; Female ; *Single-Cell Analysis ; *Disease Progression ; *Transcriptome ; Gene Expression Profiling ; Carcinoma, Intraductal, Noninfiltrating/immunology/genetics/pathology ; Carcinoma, Ductal, Breast/immunology/genetics/pathology ; Gene Expression Regulation, Neoplastic/immunology ; },
abstract = {Ductal carcinoma in situ and invasive ductal carcinoma represent two stages of breast cancer progression. A multitude of studies have shown that genomic instability increases during tumor development, as manifested by higher mutation and copy number variation rates. The advent of single-cell and spatial transcriptomics has enabled the investigation of the subtle differences in cellular states during the tumor progression at single-cell level, thereby providing more nuanced understanding of the intercellular interactions within the solid tumor. However, the evolutionary trajectory of tumor cells and the establishment of the immunosuppressive microenvironment during breast cancer progression remain unclear. In this study, we performed an exploratory analysis of the single-cell sequencing dataset of 13 ductal carcinoma in situ and invasive ductal carcinoma samples. We revealed that tumor cells became more malignant and aggressive during their progression, and T cells transited to an exhausted state. The tumor cells expressed various coinhibitory ligands that interacted with the receptors of immune cells to create an immunosuppressive tumor microenvironment. Furthermore, spatial transcriptomics data confirmed the spatial colocalization of tumor and immune cells, as well as the expression of the coinhibitory ligand-receptor pairs. Our analysis provides insights into the cellular and molecular mechanism underlying the formation of the immunosuppressive landscape during two typical stages of breast cancer progression.},
}
@article {pmid39280872,
year = {2024},
author = {Jackson, I and Isern, R and Jesina, S and Velagapudi, M and Pruett, W},
title = {Pneumocystis jirovecii Pneumonia in Patients Treated for Solid Organ Malignancy.},
journal = {Ochsner journal},
volume = {24},
number = {3},
pages = {225-228},
pmid = {39280872},
issn = {1524-5012},
abstract = {Background: Pneumocystis jirovecii is a fungal pathogen that can present as an opportunistic cause of pneumonia and can occur in individuals with various causes of immunosuppression, including malignancy and treatments for malignancy that confer increased risk. Although the guidelines for use of Pneumocystis prophylaxis in certain populations are clear, the rapid development of novel cancer therapies elicits the need to accurately assess the degree of immunosuppression conferred by these regimens and to determine if patients receiving these therapies warrant Pneumocystis prophylaxis. Case Series: We present 2 cases of Pneumocystis jirovecii pneumonia in patients with invasive ductal carcinoma of the breast treated with a dose-dense chemotherapy regimen consisting of doxorubicin, cyclophosphamide, and paclitaxel. Conclusion: The use of a dose-dense regimen, in which the interval between doses is shortened compared to a standard regimen, has become a common therapy for patients diagnosed with early breast cancer. Although this approach leads to improved disease-free and overall survival, it has also been associated with an increased risk of developing Pneumocystis jirovecii pneumonia. Further research involving patients receiving dose-dense chemotherapy regimens is needed to determine their risk of developing opportunistic infections and whether that risk warrants changes in clinical management.},
}
@article {pmid39256827,
year = {2024},
author = {Phung, AT and Shah, JR and Dong, T and Reid, T and Larson, C and Sanchez, AB and Oronsky, B and Trogler, WC and Kummel, AC and Aisagbonhi, O and Blair, SL},
title = {CAR expression in invasive breast carcinoma and its effect on adenovirus transduction efficiency.},
journal = {Breast cancer research : BCR},
volume = {26},
number = {1},
pages = {131},
pmid = {39256827},
issn = {1465-542X},
mesh = {Humans ; Female ; *Breast Neoplasms/therapy/genetics/metabolism/pathology ; *Adenoviridae/genetics ; *Transduction, Genetic ; *Coxsackie and Adenovirus Receptor-Like Membrane Protein/metabolism/genetics ; Cell Line, Tumor ; Carcinoma, Lobular/metabolism/therapy/genetics/pathology ; Carcinoma, Ductal, Breast/metabolism/genetics/pathology/therapy ; Cadherins/metabolism/genetics ; Genetic Vectors/genetics/administration &amp; dosage ; Liposomes ; },
abstract = {BACKGROUND: Breast cancer is the second leading cause of death in women, with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) as the two most common forms of invasive breast cancer. While estrogen receptor positive (ER+) IDC and ILC are treated similarly, the multifocality of ILC presents challenges in detection and treatment, worsening long-term clinical outcomes in patients. With increasing documentation of chemoresistance in ILC, additional treatment options are needed. Oncolytic adenoviral therapy may be a promising option, but cancer cells must express the coxsackievirus &amp; adenovirus receptor (CAR) for adenoviral therapy to be effective. The present study aims to evaluate the extent to which CAR expression is observed in ILC in comparison to IDC, and how the levels of CAR expression correlate with adenovirus transduction efficiency. The effect of liposome encapsulation on transduction efficiency is also assessed.<br><br>METHODS: To characterize CAR expression in invasive breast carcinoma, 36 formalin-fixed paraffin-embedded (FFPE) human breast tumor samples were assayed by CAR immunohistochemistry (IHC). Localization of CAR in comparison to other junctional proteins was performed using a multiplex immunofluorescence panel consisting of CAR, p120-catenin, and E-cadherin. ILC and IDC primary tumors and cell lines were transduced with E1- and E3-deleted adenovirus type 5 inserted with a GFP transgene (Ad-GFP) and DOTAP liposome encapsulated Ad-GFP (DfAd-GFP) at various multiplicities of infection (MOIs). Transduction efficiency was measured using a fluorescence plate reader. CAR expression in the human primary breast carcinomas and cell lines was also evaluated by IHC.<br><br>RESULTS: We observed membranous CAR, p120-catenin and E-cadherin expression in IDC. In ILC, we observed cytoplasmic expression of CAR and p120-catenin, with absent E-cadherin. Adenovirus effectively transduced high-CAR IDC cell lines, at MOIs as low as 12.5. Ad-GFP showed similar transduction as DfAd-GFP in high-CAR IDC cell lines. Conversely, Ad-GFP transduction of ILC cell lines was observed only at MOIs of 50 and 100. Furthermore, Ad-GFP did not transduce CAR-negative IDC cell lines even at MOIs greater than 100. Liposome encapsulation (DfAd-GFP) improved transduction efficiency 4-fold in ILC and 17-fold in CAR-negative IDC cell lines.<br><br>CONCLUSION: The present study demonstrates that oncolytic adenoviral therapy is less effective in ILC than IDC due to differences in spatial CAR expression. Liposome-enhanced delivery may be beneficial for patients with ILC and tumors with low or negative CAR expression to improve adenoviral therapeutic effectiveness.},
}
@article {pmid39241490,
year = {2024},
author = {Vanni, G and Pellicciaro, M and Materazzo, M and Berretta, M and Meucci, R and Perretta, T and Portarena, I and Pistolese, CA and Buonomo, OC},
title = {Radiological and pathological predictors of post-operative upstaging of breast ductal carcinoma in situ (DCIS) to invasive ductal carcinoma and lymph-nodes metastasis; a potential algorithm for node surgical de-escalation.},
journal = {Surgical oncology},
volume = {56},
number = {},
pages = {102128},
doi = {10.1016/j.suronc.2024.102128},
pmid = {39241490},
issn = {1879-3320},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery ; Retrospective Studies ; Middle Aged ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology/secondary ; *Lymphatic Metastasis ; *Carcinoma, Ductal, Breast/surgery/pathology/secondary ; *Algorithms ; Adult ; Aged ; Sentinel Lymph Node Biopsy/methods ; Prognosis ; Follow-Up Studies ; Mammography ; Mastectomy ; Neoplasm Staging ; },
abstract = {BACKGROUND/AIM: Ductal carcinoma in situ is considered a local disease with no metastatic potential, thus sentinel lymph node biopsy (SLNB) may be deemed an overtreatment. SLNB should be reserved for patients with invasive cancer, even though the risk of upstaging rises to 25 %. We aimed to identify clinicopathological predictors of post-operative upstaging in invasive carcinoma.<br><br>METHODS: We retrospectively analyzed patients with a pre-operative diagnosis of DCIS subjected to breast surgery between January 2017 to December 2021, and evaluated at the Breast Unit of PTV (Policlinico Tor Vergata, Rome).<br><br>RESULTS: Out of 267 patients diagnosed with DCIS, 33(12.4&#xa0;%) received a diagnosis upstaging and 9(3.37&#xa0;%) patients presented with sentinel lymph node (SLN) metastasis. In multivariate analysis, grade 3 tumor (OR 1.9; 95&#xa0;% CI 1.2-5.6), dense nodule at mammography (OR 1.3; 95&#xa0;% CI 1.1-2.6) and presence of a solid nodule at ultrasonography (OR 1.5; 95&#xa0;% CI 1.2-2.6) were independent upstaging predictors. Differently, the independent predictors for SLNB metastasis were: upstaging (OR 2.1.; 95&#xa0;% CI 1.2-4.6; p&#xa0;=&#xa0;0.0079) and age between 40 and 60yrs (OR 1.4; 95&#xa0;% CI 1.4-2.7; p&#xa0;=&#xa0;0.027). All 9 patients with SLN metastasis received a diagnosis upstaging and were aged between 40 and 60 years old.<br><br>CONCLUSION: We identified pre-operative independent predictors of upstaging to invasive ductal carcinoma. The combined use of different predictors in an algorithm for surgical treatments of DCIS could reduce the numbers of unnecessary SLNB.},
}
@article {pmid39226766,
year = {2024},
author = {Madrigal, JM and Pruitt, CN and Fisher, JA and Liao, LM and Graubard, BI and Gierach, GL and Silverman, DT and Ward, MH and Jones, RR},
title = {Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study.},
journal = {Environment international},
volume = {191},
number = {},
pages = {108985},
pmid = {39226766},
issn = {1873-6750},
support = {Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; ZIA CP010125/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/chemically induced ; *Postmenopause ; Middle Aged ; United States/epidemiology ; Aged ; *Air Pollution/statistics &amp; numerical data ; Air Pollutants/analysis ; Prospective Studies ; Carcinogens/analysis ; Risk Factors ; National Institutes of Health (U.S.) ; Environmental Exposure/statistics &amp; numerical data ; Benzene/analysis ; },
abstract = {BACKGROUND: Chemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S.<br><br>METHODS: We used the U.S. Environmental Protection Agency's Toxics Release Inventory to estimate historical airborne emissions (1987-1995) of 19 known and probable carcinogens for participants enrolled (1995-1996) in the NIH-AARP Diet and Health Study. Among 170,402 women, 15,124 breast cancers were diagnosed through 2018. We constructed inverse distance- and wind-weighted average emissions metrics within 1, 2, 5, and 10&#xa0;km of the enrollment address for each chemical. We estimated multivariable adjusted HRs and 95&#xa0;% CIs for categories (quartiles, tertiles, medians) of each chemical in association with breast cancer overall and separately by type (invasive, ductal carcinoma in situ) and estrogen receptor (ER) status.<br><br>RESULTS: We observed an association between benzene emissions and breast cancer risk that was strongest at 1&#xa0;km (HRQ4 vs. non-exposed&#xa0;=&#xa0;2.06, 95&#xa0;%CI: 1.34-3.17; p-trend&#xa0;=&#xa0;0.001). The magnitude of the association weakened with increasing distance (2&#xa0;km HRQ4 vs. non-exposed&#xa0;=&#xa0;1.17, 95&#xa0;%CI=0.92-1.49; p-trend&#xa0;=&#xa0;0.19; 5&#xa0;km HRQ4 vs. non-exposed&#xa0;=&#xa0;1.05, 95&#xa0;%CI=0.94-1.16; p-trend&#xa0;=&#xa0;0.37; 10&#xa0;km HRQ4 vs. non-exposed&#xa0;=&#xa0;0.95, 95&#xa0;%CI=0.89-1.02; p-trend&#xa0;=&#xa0;0.19) and appeared to be most relevant for invasive rather than intraductal disease. Overall risk was also elevated for vinyl chloride at 5&#xa0;km (HR&#x2265;median vs. non-exposed&#xa0;=&#xa0;1.20, 95&#xa0;%CI=1.01-1.43; p-trend&#xa0;=&#xa0;0.04), but not 2&#xa0;km or 10&#xa0;km. We observed suggestive associations for asbestos, trichloroethylene, and styrene in different subgroup analyses, but risk patterns were not clear across distances. Associations with other chemicals were generally null, with limited evidence of heterogeneity by disease type or ER status.<br><br>CONCLUSIONS: An increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.},
}
@article {pmid39219256,
year = {2024},
author = {Lu, N and Zhang, M and Lu, L and Liu, YZ and Zhang, HH and Liu, XD},
title = {[Retracted] miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.},
journal = {Oncology reports},
volume = {52},
number = {5},
pages = {},
doi = {10.3892/or.2024.8802},
pmid = {39219256},
issn = {1791-2431},
abstract = {Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blotting data shown in Fig. 2D, the cell migration and invasion assay data in Fig. 3C, the mouse imaging pictures in Fig. 4C and D, and the H&amp;E‑stained images in Fig. 4E and F were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been submitted or published elsewhere prior to the submission of this paper to Oncology Reports. Given that the abovementioned data had already apparently been submitted or published prior to the receipt of this paper at Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 706‑716, 2021; DOI: 10.3892/or.2020.7880].},
}
@article {pmid39215495,
year = {2024},
author = {Islam, T and Hoque, ME and Ullah, M and Islam, T and Nishu, NA and Islam, R},
title = {CNN-based deep learning approach for classification of invasive ductal and metastasis types of breast carcinoma.},
journal = {Cancer medicine},
volume = {13},
number = {16},
pages = {e70069},
pmid = {39215495},
issn = {2045-7634},
mesh = {Humans ; Female ; *Deep Learning ; *Breast Neoplasms/pathology/classification/diagnostic imaging ; *Neural Networks, Computer ; *Carcinoma, Ductal, Breast/pathology/classification/diagnostic imaging/secondary ; Neoplasm Metastasis ; },
abstract = {OBJECTIVE: Breast cancer is one of the leading cancer causes among women worldwide. It can be classified as invasive ductal carcinoma (IDC) or metastatic cancer. Early detection of breast cancer is challenging due to the lack of early warning signs. Generally, a mammogram is recommended by specialists for screening. Existing approaches are not accurate enough for real-time diagnostic applications and thus require better and smarter cancer diagnostic approaches. This study aims to develop a customized machine-learning framework that will give more accurate predictions for IDC and metastasis cancer classification.<br><br>METHODS: This work proposes a convolutional neural network (CNN) model for classifying IDC and metastatic breast cancer. The study utilized a large-scale dataset of microscopic histopathological images to automatically perceive a hierarchical manner of learning and understanding.<br><br>RESULTS: It is evident that using machine learning techniques significantly (15%-25%) boost the effectiveness of determining cancer vulnerability, malignancy, and demise. The results demonstrate an excellent performance ensuring an average of 95% accuracy in classifying metastatic cells against benign ones and 89% accuracy was obtained in terms of detecting IDC.<br><br>CONCLUSIONS: The results suggest that the proposed model improves classification accuracy. Therefore, it could be applied effectively in classifying IDC and metastatic cancer in comparison to other state-of-the-art models.},
}
@article {pmid39207954,
year = {2024},
author = {Yates, ME and Waltermire, H and Mori, K and Li, Z and Li, Y and Guzolik, H and Wang, X and Liu, T and Atkinson, JM and Hooda, J and Lee, AV and Oesterreich, S},
title = {ESR1 Fusions Invoke Breast Cancer Subtype-Dependent Enrichment of Ligand-Independent Oncogenic Signatures and Phenotypes.},
journal = {Endocrinology},
volume = {165},
number = {10},
pages = {},
pmid = {39207954},
issn = {1945-7170},
support = {R01 CA181368/CA/NCI NIH HHS/United States ; R01 CA183976/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; S10OD028483/NH/NIH HHS/United States ; S10 OD028483/OD/NIH HHS/United States ; F30CA250167/CA/NCI NIH HHS/United States ; R01 CA256161/CA/NCI NIH HHS/United States ; //The Breasties/ ; P30CA047904-31//UPMC Hillman Cancer Biology Program/ ; //Hillman Foundation/ ; //Breast Cancer Alliance/ ; //Shear Family Foundation/ ; //Pennsylvania Department of Health/ ; R21 CA237964/CA/NCI NIH HHS/United States ; //PA Breast Cancer Coalition/ ; F30 CA250167/CA/NCI NIH HHS/United States ; RRID:SCR_022735//University of Pittsburgh/ ; },
mesh = {Humans ; *Breast Neoplasms/genetics/pathology/metabolism ; Female ; *Estrogen Receptor alpha/genetics/metabolism ; Cell Line, Tumor ; Phenotype ; YAP-Signaling Proteins/genetics/metabolism ; SOX9 Transcription Factor/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Oncogene Proteins, Fusion/genetics/metabolism ; Signal Transduction/genetics ; Carcinoma, Lobular/genetics/metabolism/pathology ; Transcription Factors/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; Ligands ; Cell Proliferation/genetics ; },
abstract = {Breast cancer is a leading cause of female mortality and despite advancements in personalized therapeutics, metastatic disease largely remains incurable due to drug resistance. The estrogen receptor (ER, ESR1) is expressed in two-thirds of all breast cancer, and under endocrine stress, somatic ESR1 mutations arise in approximately 30% of cases that result in endocrine resistance. We and others reported ESR1 fusions as a mechanism of ER-mediated endocrine resistance. ER fusions, which retain the activation function 1- and DNA-binding domains, harbor ESR1 exons 1 to 6 fused to an in-frame gene partner resulting in loss of the ER ligand-binding domain (LBD). We demonstrate that in a no-special type (invasive ductal carcinoma [IDC]-NST) and an invasive lobular carcinoma (ILC) cell line, ER fusions exhibit robust hyperactivation of canonical ER signaling pathways independent of estradiol or antiendocrine therapies. We employ cell line models stably overexpressing ER fusions with concurrent endogenous ER knockdown to minimize endogenous ER influence. Cell lines exhibited shared transcriptomic enrichment in pathways known to be drivers of metastatic disease, notably MYC signaling. Cells expressing the 3' fusion partners SOX9 and YAP1 consistently demonstrated enhanced growth and cell survival. ILC cells expressing the DAB2 fusion led to enhanced growth, survival, and migration, phenotypes not appreciated in the IDC-NST DAB2 model. Herein, we report that cell line activity is subtype-, fusion-, and assay-specific, suggesting that LBD loss, the fusion partner, and the cellular landscape all influence fusion activities. Therefore, it will be critical to assess fusion frequency in the context of the clinicopathology.},
}
@article {pmid39195215,
year = {2024},
author = {Zavaglio, F and Cassaniti, I and d'Angelo, P and Zelini, P and Comolli, G and Gregorini, M and Rampino, T and Del Frate, L and Meloni, F and Pellegrini, C and Abelli, M and Ticozzelli, E and Lilleri, D and Baldanti, F},
title = {Immune Control of Human Cytomegalovirus (HCMV) Infection in HCMV-Seropositive Solid Organ Transplant Recipients: The Predictive Role of Different Immunological Assays.},
journal = {Cells},
volume = {13},
number = {16},
pages = {},
pmid = {39195215},
issn = {2073-4409},
support = {FRRB 2015-043//Fondazione Regionale per la ricerca Biomedica/ ; PE 2016-02362470//Ministero della salute Ricerca Finalizzata/ ; 1032-rcr2023-43//Ministero della salute Ricerca Corrente/ ; 20179JHAM//Ministero dell'Universit&#xe0; e della Ricerca, PRIN/ ; },
mesh = {Humans ; *Cytomegalovirus Infections/immunology/virology ; *Cytomegalovirus/immunology ; Female ; Male ; Middle Aged ; *Transplant Recipients ; Adult ; Organ Transplantation/adverse effects ; CD8-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Aged ; DNA, Viral ; Dendritic Cells/immunology ; Enzyme-Linked Immunospot Assay ; Immunologic Tests/methods ; Cytokines/metabolism ; },
abstract = {Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4[+] T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8[+] T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4[+] CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4[+] and CD8[+] T cell responses and could be used in daily clinical practice.},
}
@article {pmid39187318,
year = {2024},
author = {Kolia, A and Frountzas, M and Liatsou, E and Samelis, G and Zagouri, F and Zografos, GC and Gazouli, M and Michalopoulos, NV},
title = {The Role of Serum Nestin in Diagnosis and Prognosis of Breast Cancer: A Prospective Observational Study.},
journal = {In vivo (Athens, Greece)},
volume = {38},
number = {5},
pages = {2399-2403},
pmid = {39187318},
issn = {1791-7549},
mesh = {Humans ; *Breast Neoplasms/blood/diagnosis/pathology/metabolism ; Female ; *Nestin/metabolism/blood ; Middle Aged ; Prognosis ; *Biomarkers, Tumor/blood ; Aged ; Adult ; Prospective Studies ; Neoplasm Staging ; Receptor, ErbB-2/metabolism/genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Aged, 80 and over ; },
abstract = {BACKGROUND/AIM: The molecular classification of breast cancer has enabled targeted therapy for specific molecular subtypes. Nestin, which has been studied for its role in oncogenesis, could contribute to this direction. This study aimed to investigate the differences between serum nestin levels and molecular profiling, as well as histopathological tumor types, in women who underwent surgery for breast cancer.<br><br>PATIENTS AND METHODS: Women who underwent surgery for breast cancer at the Breast Unit of the 1[st] Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens were prospectively included. Patients' demographic data were recorded and serum nestin levels were measured. Molecular biomarker analysis was performed, as well as histopathologic assessment.<br><br>RESULTS: Seventy patients were included in the analysis. Among patients with breast cancer, 93% were estrogen receptor (ER) positive, 91% were progesterone receptor (PR) positive, and 43% were human epidermal growth factor receptor 2 (HER2) positive. Ki67 was expressed in 16% of patients and p53 was expressed in 32% of patients. Invasive ductal carcinoma was diagnosed in 80% of patients, with 44% of tumors classified as T1 and 46% as T2. Additionally, 43% were G1 and 56% were N0, while 34% were N1. No statistically significant difference was observed between serum nestin levels and ER, PR, HER2, Ki67, and p53 expression. Furthermore, no difference was observed between serum nestin levels and breast cancer histological type, size, N-stage, and grading.<br><br>CONCLUSION: The diagnostic and prognostic role of circulating nestin for breast cancer was not confirmed and no correlation with immunohistochemistry results was observed. Thus, the necessity of larger prospective studies is enhanced.},
}
@article {pmid39148033,
year = {2024},
author = {Chen, JH and Addanki, S and Roy, D and Bassett, R and Kalashnikova, E and Spickard, E and Kuerer, HM and Meas, S and Sarli, VN and Korkut, A and White, JB and Rauch, GM and Tripathy, D and Arun, BK and Barcenas, CH and Yam, C and Sethi, H and Rodriguez, AA and Liu, MC and Moulder, SL and Lucci, A},
title = {Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {1016},
pmid = {39148033},
issn = {1471-2407},
support = {T32 CA009599/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/blood/mortality/genetics/pathology ; *Circulating Tumor DNA/blood/genetics ; Female ; *Neoadjuvant Therapy/methods ; Middle Aged ; Adult ; *Neoplastic Cells, Circulating/pathology/metabolism ; Biomarkers, Tumor/blood ; Aged ; Prognosis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; },
abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC).<br><br>METHODS: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (Signatera[TM], Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher's exact tests were used for comparisons between groups and Kaplan-Meier analysis used for survival outcomes.<br><br>RESULTS: In total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p&#x2009;=&#x2009;0.02), whereas CTC clearance was not (p&#x2009;=&#x2009;0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p&#x2009;=&#x2009;0.0002 and p&#x2009;=&#x2009;0.0034, respectively).<br><br>CONCLUSIONS: Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.},
}
@article {pmid39142851,
year = {2024},
author = {Kosáč, P and Zábojníková, M and Vážan, P and Petrů, V and Ratajský, M and Lajmar, K and Dudešek, B and Kudlová, P and Duben, J and Podrazká, L and Gatěk, J},
title = {Breast cancer in 80+ year olds.},
journal = {Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti},
volume = {103},
number = {7},
pages = {258-262},
doi = {10.48095/ccrvch2024258},
pmid = {39142851},
issn = {0035-9351},
mesh = {Humans ; Aged, 80 and over ; *Breast Neoplasms/pathology/surgery ; Female ; Retrospective Studies ; Male ; Axilla ; Breast Neoplasms, Male/pathology/surgery ; Lymph Node Excision ; Carcinoma, Ductal, Breast/surgery/pathology/mortality ; Sentinel Lymph Node Biopsy ; Chemotherapy, Adjuvant ; Radiotherapy, Adjuvant ; Mastectomy, Segmental ; },
abstract = {INTRODUCTION: The risk of breast cancer increases with increasing age. The aim of our retrospective study was to determine the extent of breast and axillary surgery, including subsequent adjuvant therapy, in 80-year and older patients.<br><br>METHODS: Between 2017 and 2021, 834 breast cancer patients were operated in the Surgical Department of the EUC Clinic. Ninety-eight women (2&#xd7; with bilateral cancer) and 2 men were included in this retrospective study. A total of 102 breast cancer cases in patients older than 80 years were analyzed. The surgical procedure corresponded to the stage of the disease and the general condition of the patient. Adjuvant systemic therapy was indicated according to the same principles.<br><br>RESULTS: At the time of surgery, the patients were more than 80 years old (80-96 years). The predominant type of invasive ductal carcinoma was diagnosed 83&#xd7;, lobular carcinoma 6&#xd7;, mucinous 6&#xd7;, papillary carcinoma 4&#xd7;, other 3&#xd7;, with luminal A, B predominating (89&#xd7;). The breast-conserving procedures were performed 63&#xd7;. Sentinel node biopsy was performed 65&#xd7;, supplemented by axillary lymph node dissection 13&#xd7;. Primary axillary lymph node dissection was performed 15&#xd7;. No axillary procedure was performed 23&#xd7;. Radiotherapy was given 49&#xd7;, chemotherapy 9&#xd7; and hormonal therapy 82&#xd7;. Local and regional recurrences were each observed 2&#xd7;. A total of 37 patients died, 10 of them from breast cancer.<br><br>CONCLUSION: The most common cause of death in patients aged 80+ years is a cardiovascular disease, not breast cancer itself. This fact should be taken into account when determining the treatment plan.},
}
@article {pmid39138514,
year = {2024},
author = {Moragas, N and Fernandez-Nogueira, P and Recalde-Percaz, L and Inman, JL and López-Plana, A and Bergholtz, H and Noguera-Castells, A and Del Burgo, PJ and Chen, X and Sorlie, T and Gascón, P and Bragado, P and Bissell, M and Carbó, N and Fuster, G},
title = {The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma.},
journal = {Breast cancer research : BCR},
volume = {26},
number = {1},
pages = {122},
pmid = {39138514},
issn = {1465-542X},
support = {Juan de la Cierva//Agencia Estatal de Investigaci&#xf3;n,Spain/ ; Postdoctoral grant//Asociaci&#xf3;n Espa&#xf1;ola contra el c&#xe1;ncer (AECC)/ ; 201915-30-31//La Marat&#xf3; TV3/ ; FPU//Spanish Ministry of Education/ ; PREDOCS-UB fellowship//Universitat de Barcelona (UB)/ ; PID2019-104991RB-I00//Spanish Ministry of Economy and Competitiveness/ ; BBM-TRA-0041//Becas Leonardo 2018/ ; },
mesh = {Humans ; *Neuropilin-1/metabolism/genetics ; Female ; *Breast Neoplasms/pathology/metabolism/genetics ; *Neuropilin-2/metabolism/genetics ; *Neoplasm Invasiveness ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology/genetics ; Cell Line, Tumor ; *Nerve Tissue Proteins/metabolism/genetics ; Epithelial-Mesenchymal Transition/genetics ; Animals ; Membrane Proteins/metabolism/genetics ; Mice ; Carcinoma, Ductal, Breast/pathology/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; Signal Transduction ; },
abstract = {BACKGROUND: A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells.<br><br>METHODS: We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results.<br><br>RESULTS: We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown.<br><br>CONCLUSIONS: Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.},
}
@article {pmid39123374,
year = {2024},
author = {Muñoz-Casares, FC and Martín-Broto, J and Cascales-Campos, P and Torres-Melero, J and López-Rojo, I and Gómez-Barbadillo, J and González-Bayón, L and Sebio, A and Serrano, C and Carvalhal, S and Abreu de Souza, J and Souza, A and Flores-Ayala, G and Palacios Fuenmayor, LJ and Lopes-Bras, R and González-López, JA and Vasques, H and Asencio-Pascual, JM},
title = {Ibero-American Consensus for the Management of Peritoneal Sarcomatosis: Updated Review and Clinical Recommendations.},
journal = {Cancers},
volume = {16},
number = {15},
pages = {},
pmid = {39123374},
issn = {2072-6694},
abstract = {Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts' voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas.},
}
@article {pmid39103259,
year = {2024},
author = {Wang, DH and Yin, WL and Pan, XY and Zhang, MN and Nie, L and Chen, XQ and Zeng, H and Zhou, Q and Chen, N},
title = {[Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis].},
journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology},
volume = {53},
number = {8},
pages = {789-796},
doi = {10.3760/cma.j.cn112151-20240402-00216},
pmid = {39103259},
issn = {0529-5807},
support = {82273047, 82273073, 82203280//National Natural Science Foundation of China/ ; 24SYSX0223, 2022YFS0305//Foundation of Science and Technology Department of Sichuan Province/ ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology ; *BRCA2 Protein/genetics ; Aged ; Retrospective Studies ; Middle Aged ; *Mutation ; Prognosis ; Aged, 80 and over ; Bone Neoplasms/genetics/secondary/pathology ; },
abstract = {Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.},
}
@article {pmid39101021,
year = {2024},
author = {Sood, A and Mishra, G and Khandelwal, S and Bhoyar, M and Manuja, N},
title = {Tumour thrombosis of the left axillary vein due to infiltrative ductal carcinoma causing superior vena cava obstruction.},
journal = {Radiology case reports},
volume = {19},
number = {10},
pages = {4195-4200},
pmid = {39101021},
issn = {1930-0433},
abstract = {Invasive ductal carcinoma is the most common type of breast cancer and can affect any age group, predominantly females older than 55 years of age. We present a case of a female in her mid-30s complaining of a fungating mass in the upper outer quadrant of the left anterior chest wall. On workup of the patient, it was histopathologically found that the patient was affected by infiltrating ductal carcinoma of the left breast, which was causing tumoral thrombosis of the left axillary vein. Also, thrombosis of the right axillary vein, bilateral brachiocephalic veins, and superior vena cava with a focal hepatic hotspot sign were appreciated on contrast-enhanced computed tomography scan. No such case of tumoral thrombosis of the axillary vein causing superior vena cava obstruction has been reported in recent literature.},
}
@article {pmid39097872,
year = {2024},
author = {Gilani, N and Ozaslan, M},
title = {Association of XRCC2 with breast cancer, a multi-omics analysis at genomic, transcriptomic, and epigenomic level.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
volume = {70},
number = {7},
pages = {252-259},
doi = {10.14715/cmb/2024.70.7.36},
pmid = {39097872},
issn = {1165-158X},
mesh = {Adult ; Female ; Humans ; Middle Aged ; *Breast Neoplasms/genetics/pathology ; *DNA Methylation/genetics ; *DNA-Binding Proteins/genetics/metabolism ; Epigenomics/methods ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Genomics/methods ; *Multiomics/methods ; Transcriptome/genetics ; },
abstract = {One of the main causes of cancer-related mortality for women worldwide is breast cancer (BC). The XRCC2 gene, essential for DNA repair, has been implicated in cancer susceptibility. This study aims to evaluate the association between XRCC2 and BC risk. The study was conducted at Zheen International Hospital in Erbil, Iraq, between 2021 and 2024 with a total of 88 samples, including 44 paired normal and cancer tissue samples. Mutation analysis was performed using Next-Generation Sequencing, coupled with in silico tools for variant impact prediction. Expression levels were assessed through RT-PCR, and methylation status was determined using methylation-sensitive restriction enzyme digestion PCR. The study identified seven inherited germline variants in the XRCC2 gene, with five of these mutations being Uncertain Significance, one being Likely Pathogenic, and one being Likely benign. RNA purity was found high with mean A260/280 ratios of 1.986 ± 0.097 in normal (N) and 1.963 ± 0.092 in tumor (T) samples. Tumor samples exhibited a higher RNA concentration (78.56 ± 40.87 ng/µL) than normal samples (71.44 ± 40.79 ng/µL). XRCC2 gene expression was significantly upregulated in tumor tissue, with marked increases in patients aged 40-55 and >56 years and in higher cancer grades (II and III) and invasive ductal carcinoma (p-values ranging from <0.0001 to 0.0392). DNA methylation rates in tumor tissues were low (7%), suggesting limited regulation by methylation. The study suggests that XRCC2 can be classified as an oncogene and that its structural investigation by targeted NGS and expression evaluation can be used as a potential biomarker in BC.},
}
@article {pmid39090623,
year = {2024},
author = {Phongpreecha, T and Mathi, K and Cholerton, B and Fox, EJ and Sigal, N and Espinosa, C and Reincke, M and Chung, P and Hwang, LJ and Gajera, CR and Berson, E and Perna, A and Xie, F and Shu, CH and Hazra, D and Channappa, D and Dunn, JE and Kipp, LB and Poston, KL and Montine, KS and Maecker, HT and Aghaeepour, N and Montine, TJ},
title = {Single-cell peripheral immunoprofiling of lewy body and Parkinson's disease in a multi-site cohort.},
journal = {Molecular neurodegeneration},
volume = {19},
number = {1},
pages = {59},
pmid = {39090623},
issn = {1750-1326},
mesh = {Humans ; *Parkinson Disease/immunology/metabolism ; *Lewy Body Disease/immunology ; Male ; Female ; Aged ; Case-Control Studies ; *Leukocytes, Mononuclear/metabolism/immunology ; Biomarkers/metabolism ; Middle Aged ; Cohort Studies ; Aged, 80 and over ; Lewy Bodies/pathology/metabolism ; Single-Cell Analysis/methods ; },
abstract = {BACKGROUND: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans.<br><br>METHODS: In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n&#x2009;=&#x2009;159), LBD (n&#x2009;=&#x2009;110), Alzheimer's disease dementia (ADD, n&#x2009;=&#x2009;97), other neurodegenerative disease controls (NDC, n&#x2009;=&#x2009;19), and immune disease controls (IDC, n&#x2009;=&#x2009;14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating.<br><br>RESULTS: The model classified LBD from HC with an AUROC of 0.87&#x2009;&#xb1;&#x2009;0.06 and AUPRC of 0.80&#x2009;&#xb1;&#x2009;0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLC&#x3b3;2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes.<br><br>CONCLUSIONS AND RELEVANCE: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.},
}
@article {pmid39072314,
year = {2024},
author = {Habanjar, O and Nehme, R and Goncalves-Mendes, N and Cueff, G and Blavignac, C and Aoun, J and Decombat, C and Auxenfans, C and Diab-Assaf, M and Caldefie-Chézet, F and Delort, L},
title = {The obese inflammatory microenvironment may promote breast DCIS progression.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1384354},
pmid = {39072314},
issn = {1664-3224},
mesh = {Humans ; Female ; *Obesity/metabolism/pathology ; *Breast Neoplasms/pathology/immunology/metabolism ; *Tumor Microenvironment/immunology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/metabolism/immunology ; *Disease Progression ; *Coculture Techniques ; *Macrophages/immunology/metabolism ; Inflammation/pathology/metabolism ; Adipocytes/metabolism/pathology ; Adipose Tissue/pathology/metabolism ; Cell Line, Tumor ; },
abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS), characterized by a proliferation of neoplastic cells confined within the mammary ducts, is distinctly isolated from the surrounding stroma by an almost uninterrupted layer of myoepithelial cells (MECs) and by the basement membrane. Heightened interactions within the adipose microenvironment, particularly in obese patients, may play a key role in the transition from DCIS to invasive ductal carcinoma (IDC), which is attracting growing interest in scientific research. Adipose tissue undergoes metabolic changes in obesity, impacting adipokine secretion and promoting chronic inflammation. This study aimed to assess the interactions between DCIS, including in situ cancer cells and MECs, and the various components of its inflammatory adipose microenvironment (adipocytes and macrophages).<br><br>METHODS: To this end, a 3D co-culture model was developed using bicellular bi-fluorescent DCIS-like tumoroids, adipose cells, and macrophages to investigate the influence of the inflammatory adipose microenvironment on DCIS progression.<br><br>RESULTS: The 3D co-culture model demonstrated an inhibition of the expression of genes involved in apoptosis (BAX, BAG1, BCL2, CASP3, CASP8, and CASP9), and an increase in genes related to cell survival (TP53, JUN, and TGFB1), inflammation (TNF-&#x3b1;, PTGS2, IL-6R), invasion and metastasis (TIMP1 and MMP-9) in cancer cells of the tumoroids under inflammatory conditions versus a non-inflammatory microenvironment. On the contrary, it confirmed the compromised functionality of MECs, resulting in the loss of their protective effects against cancer cells. Adipocytes from obese women showed a significant increase in the expression of all studied myofibroblast-associated genes (myoCAFs), such as FAP and &#x3b1;-SMA. In contrast, adipocytes from normal-weight women expressed markers of inflammatory fibroblast phenotypes (iCAF) characterized by a significant increase in the expression of LIF and inflammatory cytokines such as TNF-&#x3b1;, IL-1&#x3b2;, IL-8, and CXCL-10. These changes also influenced macrophage polarization, leading to a pro-inflammatory M1 phenotype. In contrast, myoCAF-associated adipocytes, and the cancer-promoting microenvironment polarized macrophages towards an M2 phenotype, characterized by high CD163 receptor expression and IL-10 and TGF-&#x3b2; secretion.<br><br>DISCUSSION: Reciprocal interactions between the tumoroid and its microenvironment, particularly in obesity, led to transcriptomic changes in adipocytes and macrophages, may participate in breast cancer progression while disrupting the integrity of the MEC layer. These results underlined the importance of adipose tissue in cancer progression.},
}
@article {pmid39069624,
year = {2024},
author = {Imamura, T and Komatsu, S and Nishibeppu, K and Kiuchi, J and Ohashi, T and Konishi, H and Shiozaki, A and Yamamoto, Y and Moriumura, R and Ikoma, H and Ochiai, T and Otsuji, E},
title = {Urinary microRNA-210-3p as a novel and non-invasive biomarker for the detection of pancreatic cancer, including intraductal papillary mucinous carcinoma.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {907},
pmid = {39069624},
issn = {1471-2407},
mesh = {Humans ; *MicroRNAs/urine/blood/genetics ; Female ; Male ; *Biomarkers, Tumor/urine/genetics/blood ; *Pancreatic Neoplasms/urine/genetics/diagnosis/blood ; Middle Aged ; Aged ; Adenocarcinoma, Mucinous/urine/genetics/diagnosis ; ROC Curve ; Case-Control Studies ; Gene Expression Regulation, Neoplastic ; Adult ; Carcinoma, Pancreatic Ductal/urine/genetics/diagnosis/blood ; },
abstract = {BACKGROUND: This study aims to explore novel microRNAs in urine for screening and predicting clinical characteristics in pancreatic cancer (PC) patients using a microRNA array-based approach.<br><br>METHODS: We used the Toray[&#xae;] 3D-Gene microRNA array-based approach to compare urinary levels between PC patients and healthy volunteers.<br><br>RESULTS: (1) Four oncogenic microRNAs (miR-744-5p, miR-572, miR-210-3p, and miR-575) that were highly upregulated in the urine of PC patients compared to healthy individuals were identified by comprehensive microRNA array analysis. (2) Test-scale analysis by quantitative RT-PCR for each group of 20 cases showed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P&#x2009;=&#x2009;0.009). (3) Validation analysis (58 PC patients and 35 healthy individuals) confirmed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P&#x2009;<&#x2009;0.001, area under the receiver operating characteristic curve&#x2009;=&#x2009;0.79, sensitivity: 0.828, specificity: 0.743). We differentiated PC patients into invasive ductal carcinoma (IDCa) and intraductal papillary mucinous carcinoma (IPMC) groups. In addition to urinary miR-210-3p levels being upregulated in IDCa over healthy individuals (P&#x2009;=&#x2009;0.009), urinary miR-210-3p levels were also elevated in IPMC over healthy individuals (P&#x2009;=&#x2009;0.0018). Urinary miR-210-3p can differentiate IPMC from healthy individuals by a cutoff of 8.02 with an AUC value of 0.762, sensitivity of 94%, and specificity of 63%. (4) To test whether urinary miR210-3p levels reflected plasma miR-210-3p levels, we examined the correlation between urinary and plasma levels. Spearman's correlation analysis showed a moderate positive correlation (&#x3c1;&#x2009;=&#x2009;0.64, P&#x2009;=&#x2009;0.005) between miR-210-3p expression in plasma and urine.<br><br>CONCLUSIONS: Urinary miR-210-3p is a promising, non-invasive diagnostic biomarker of PC, including IPMC.<br><br>TRIAL REGISTRATION: Not applicable.},
}
@article {pmid39062707,
year = {2024},
author = {Corrêa, TS and Asprino, PF and de Oliveira, ESC and Leite, ACR and Weis, L and Achatz, MI and de Oliveira, CP and Sandoval, RL and Barroso-Sousa, R},
title = {TP53 p.R337H Germline Variant among Women at Risk of Hereditary Breast Cancer in a Public Health System of Midwest Brazil.},
journal = {Genes},
volume = {15},
number = {7},
pages = {},
pmid = {39062707},
issn = {2073-4425},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/epidemiology ; Brazil/epidemiology ; *Germ-Line Mutation ; Adult ; *Tumor Suppressor Protein p53/genetics ; Middle Aged ; *Genetic Predisposition to Disease ; Genetic Testing/methods ; Public Health ; Li-Fraumeni Syndrome/genetics/epidemiology ; Aged ; },
abstract = {Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of TP53 p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil. A total of 180 patients who met at least one of the NCCN criteria for HBC underwent germline testing; 44.4% performed out-of-pocket germline multigene panel testing, and 55.6% were tested for the p.R337H variant by allelic discrimination PCR. The median age at BC diagnosis was 43.5 years, 93% had invasive ductal carcinoma, 50% had estrogen receptor-positive/HER2 negative tumors, and 41% and 11% were diagnosed respectively at stage III and IV. Two patients (1.11%) harbored the p.R337H variant, and cascade family testing identified 20 additional carriers. The TP53 p.R337H detection rate was lower than that reported in other studies from south/southeast Brazil. Nonetheless, identifying TP53 PV carriers through genetic testing in the Brazilian public health system could guide cancer treatment and prevention.},
}
@article {pmid39051633,
year = {2024},
author = {Liu, T and Jin, D and Le, SB and Chen, D and Sebastian, M and Riva, A and Liu, R and Tran, DD},
title = {Machine Learning-Directed Conversion of Glioblastoma Cells to Dendritic Cell-Like Antigen-Presenting Cells as Cancer Immunotherapy.},
journal = {Cancer immunology research},
volume = {12},
number = {10},
pages = {1340-1360},
pmid = {39051633},
issn = {2326-6074},
support = {P30CA014089//USC Norris Comprehensive Cancer Center (USC Norris)/ ; R42 CA228875/CA/NCI NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; F30 CA232641/CA/NCI NIH HHS/United States ; R42CA228875//National Cancer Institute (NCI)/ ; 6BC04//Florida Department of Health (DOH)/ ; F30CA232641//National Cancer Institute (NCI)/ ; K08 CA160824/CA/NCI NIH HHS/United States ; },
mesh = {*Glioblastoma/immunology/therapy/pathology ; Animals ; *Dendritic Cells/immunology ; Humans ; Mice ; *Machine Learning ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; Brain Neoplasms/immunology/therapy/pathology ; Antigen-Presenting Cells/immunology ; Cell Line, Tumor ; Mice, Inbred C57BL ; },
abstract = {Immunotherapy has limited efficacy in glioblastoma (GBM) due to the blood-brain barrier and the immunosuppressed or "cold" tumor microenvironment (TME) of GBM, which is dominated by immune-inhibitory cells and depleted of CTL and dendritic cells (DC). Here, we report the development and application of a machine learning precision method to identify cell fate determinants (CFD) that specifically reprogram GBM cells into induced antigen-presenting cells with DC-like functions (iDC-APC). In murine GBM models, iDC-APCs acquired DC-like morphology, regulatory gene expression profile, and functions comparable to natural DCs. Among these acquired functions were phagocytosis, direct presentation of endogenous antigens, and cross-presentation of exogenous antigens. The latter endowed the iDC-APCs with the ability to prime naïve CD8+ CTLs, a hallmark DC function critical for antitumor immunity. Intratumor iDC-APCs reduced tumor growth and improved survival only in immunocompetent animals, which coincided with extensive infiltration of CD4+ T cells and activated CD8+ CTLs in the TME. The reactivated TME synergized with an intratumor soluble PD1 decoy immunotherapy and a DC-based GBM vaccine, resulting in robust killing of highly resistant GBM cells by tumor-specific CD8+ CTLs and significantly extended survival. Lastly, we defined a unique CFD combination specifically for the human GBM to iDC-APC conversion of both glioma stem-like cells and non-stem-like cell GBM cells, confirming the clinical utility of a computationally directed, tumor-specific conversion immunotherapy for GBM and potentially other solid tumors.},
}
@article {pmid39044875,
year = {2024},
author = {Kocaman, N and Onat, E and Balta, H and Üçer, &#xd6;},
title = {Are Meteorin-Like Peptide and Asprosin Important in the Diagnosis of Breast Tumors?.},
journal = {Cureus},
volume = {16},
number = {6},
pages = {e62979},
pmid = {39044875},
issn = {2168-8184},
abstract = {INTRODUCTION: Breast cancer (BC) is one of the most common and leading causes of death in women. Therefore, early and accurate diagnosis is vital. In this study, meteorin-like (METRNL) peptide and asprosin levels were examined in breast tissue in invasive ductal carcinoma (IDC) of the breast, and the roles of these molecules in the diagnosis of BC were investigated.<br><br>METHODS: In this retrospective study, tissues from patients with BC in the Pathology Department Laboratory of F&#x131;rat University Faculty of Medicine,&#xa0;Elaz&#x131;&#x11f;, Turkey, were used. Samples from 30 patients were used. The control group consisted of healthy breast tissues from the same patients. The pathology group consisted of breast tissues with IDC from the same patients.&#xa0;Breast tissue samples from both groups were evaluated immunohistochemically for METRNL and asprosin.<br><br>RESULTS: Statistically significant differences were observed between both groups in terms of METRNL and asprosin. It was observed that METRNL and asprosin immunoreactivities were higher in breast tissues with IDC than in healthy breast tissues (p<0.001).<br><br>CONCLUSION: When the study results were evaluated, it was seen that there was a significant relationship between healthy breast tissues&#xa0;and the ones with IDC in terms of METRNL and asprosin. It is thought that both METRNL and asprosin may be really important in the future for the early diagnosis and treatment of BC.},
}
@article {pmid39039278,
year = {2024},
author = {Das, M and Semple, JI and Haemmerli, A and Volodkina, V and Scotton, J and Gitchev, T and Annan, A and Campos, J and Statzer, C and Dakhovnik, A and Ewald, CY and Mozziconacci, J and Meister, P},
title = {Condensin I folds the Caenorhabditis elegans genome.},
journal = {Nature genetics},
volume = {56},
number = {8},
pages = {1737-1749},
pmid = {39039278},
issn = {1546-1718},
support = {31003A_176226/PP00P3_159320//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; },
mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Adenosine Triphosphatases/genetics/metabolism ; *Multiprotein Complexes/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *Caenorhabditis elegans Proteins/genetics/metabolism ; *X Chromosome/genetics ; Chromosomal Proteins, Non-Histone/metabolism/genetics ; Cohesins ; Cell Cycle Proteins/metabolism/genetics ; Interphase/genetics ; Genome, Helminth ; Genes, X-Linked ; Chromosomes/genetics ; },
abstract = {The structural maintenance of chromosome (SMC) complexes-cohesin and condensins-are crucial for chromosome separation and compaction during cell division. During the interphase, mammalian cohesins additionally fold the genome into loops and domains. Here we show that, in Caenorhabditis elegans, a species with holocentric chromosomes, condensin I is the primary, long-range loop extruder. The loss of condensin I and its X-specific variant, condensin I[DC], leads to genome-wide decompaction, chromosome mixing and disappearance of X-specific topologically associating domains, while reinforcing fine-scale epigenomic compartments. In addition, condensin I/I[DC] inactivation led to the upregulation of X-linked genes and unveiled nuclear bodies grouping together binding sites for the X-targeting loading complex of condensin I[DC]. C. elegans condensin I/I[DC] thus uniquely organizes holocentric interphase chromosomes, akin to cohesin in mammals, as well as regulates X-chromosome gene expression.},
}
@article {pmid39038425,
year = {2024},
author = {Bar, Y and Bar, K and Feldman, D and Dror, JB and Shahoha, M and Lerner, S and Shachar, SS and Weiss-Meilik, A and Dershowitz, N and Wolf, I and Sonnenblick, A},
title = {The impact of extensive intraductal component (EIC) on the genomic risk of recurrence in early hormone receptor positive breast cancer.},
journal = {Breast (Edinburgh, Scotland)},
volume = {77},
number = {},
pages = {103777},
pmid = {39038425},
issn = {1532-3080},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/surgery ; Middle Aged ; *Neoplasm Recurrence, Local/genetics ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology/surgery ; Aged ; Adult ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/metabolism/analysis ; Receptors, Progesterone/metabolism ; Risk Assessment ; Retrospective Studies ; Genomics ; Risk Factors ; },
abstract = {BACKGROUND: Early invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component, while about 5 % of cases present with an extensive (>25 %) intraductal component (EIC). The impact of EIC on the genomic risk of recurrence is unclear.<br><br>METHODS: Patients with early hormone receptor-positive HER2neu-negative (HR&#xa0;+&#xa0;HER2-) IDC breast cancer and a known OncotypeDX Breast Recurrence Score&#xae; (RS) who underwent breast surgery at our institute were included. Using a rule-based text-analysis algorithm, we analyzed pathological reports and categorized patients into three groups: EIC, non-extensive DCIS (DCIS-L), and pure-IDC (NO-DCIS). Genomic risk was determined using OncotypeDX RS.<br><br>RESULTS: A total of 33 (4.6&#xa0;%) EIC cases, 377 (57.2&#xa0;%) DCIS-L cases and 307 (42.8&#xa0;%) NO-DCIS cases were identified. Patients in the EIC group were younger and had lower tumor grades than other groups. The distribution of genomic risk varied between the groups, with EIC tumors significantly less likely to have a high RS (>25) compared to DCIS-L and No-DCIS tumors (3&#xa0;% vs 20&#xa0;% and 20&#xa0;%, respectively; p&#xa0;=&#xa0;0.03). When adjusted to age, tumor size, grade and LNs involvement, both DCIS-L and NO-DCIS groups were significantly correlated with a higher probability of high RS compared to the EIC group (OR 12.3 and OR 13.1, respectively; p&#xa0;<&#xa0;0.02). Moreover, patients with EIC had a lower likelihood for adjuvant chemotherapy recommendation.<br><br>CONCLUSIONS: In early HR&#xa0;+&#xa0;HER2- IDC, an EIC correlates with a reduced genomic recurrence risk. The impact on genomic risk seems to be influenced by the extent, not merely the presence, of DCIS.},
}
@article {pmid39032239,
year = {2024},
author = {Davies, LSC and McDaid, L and Anandadas, C and Amaro, PF and Chuter, R and Woolf, D and Eccles, CL},
title = {Does the presence of Magtrace preclude adaptive breast radiotherapy on an MR-Linac?.},
journal = {Journal of medical imaging and radiation sciences},
volume = {55},
number = {4},
pages = {101716},
doi = {10.1016/j.jmir.2024.101716},
pmid = {39032239},
issn = {1876-7982},
mesh = {Female ; Humans ; Artifacts ; *Breast Neoplasms/radiotherapy/diagnostic imaging ; Carcinoma, Ductal, Breast/radiotherapy/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Particle Accelerators ; *Radiotherapy, Image-Guided/methods ; },
abstract = {INTRODUCTION: This work reports on an unusual finding observed during image quality assessment in the preparation for the clinical implementation of breast magnetic resonance image-guided radiotherapy (MRIgRT) on a 1.5 Tesla (T) magnetic resonance linear accelerator (MR-Linac) (Elekta AB, Stockholm, Sweden).<br><br>CASE AND OUTCOMES: A patient with T2 N0 M0 right breast invasive ductal carcinoma, receiving adjuvant radiotherapy, underwent two imaging sessions on the MR-Linac. The imaging protocol included T1- and T2-weighted (W) turbo spin echo (TSE) sequences, a T1W mDixon, and a T2W TSE navigated sequence acquired on end-expiration. All images were reconstructed in the axial plane. Images were assessed for image quality and appropriateness for use within the treatment pathway using visual grading analysis (VGA). An artefact in the right breast was noted independently by all observers. The patient's skin and medical notes were reviewed for possible explanation. The findings were discussed with the patient's responsible clinician, and subsequent referral to the local multi-disciplinary team (MDT) for radiologist review was made. On further investigation, the patient's images demonstrated a signal void in the subareolar region of the right breast coinciding with the surgical site. This was distal from the tumour bed and deemed unlikely to be related to a Magseed marker or intraoperative clips. The patient reported no history of nipple tattoo or piercing. There was nothing on clothing that this could be attributed to.<br><br>DISCUSSION: Following MDT review, where all potential sources of signal void were considered, it was concluded that the cause was Magtrace, a superparamagnetic iron oxide tracer, recommended for sentinel lymph node localisation in patients with breast cancer in the United Kingdom. The artefact was characteristic of a magnetic susceptibility artefact. These can arise from local magnetic field inhomogeneities caused by the presence of the metal compounds in MagTrace. For breast MRIgRT on the MR-Linac, treatment verification and the possibility of real-time replanning is a critical aspect. The magnetic susceptibility artefact significantly inhibited plan adaption and confidence in the online image registration process making the patient ineligible for treatment on the MR-Linac.<br><br>CONCLUSION: As part of ongoing work-up for breast MRIgRT, the screening of patients for Magtrace is now included. Optimisation of MR imaging sequences for radiotherapy planning and image review to minimise distortion are being developed.},
}
@article {pmid39031014,
year = {2024},
author = {Chen, C and Tseng, J and Amersi, F and Silberman, AW},
title = {Second primary malignancies in women with breast cancer.},
journal = {Journal of surgical oncology},
volume = {130},
number = {3},
pages = {355-359},
doi = {10.1002/jso.27785},
pmid = {39031014},
issn = {1096-9098},
support = {//Gottlieb, Buss, and Snyder Endowments in Surgical Oncology/ ; },
mesh = {Humans ; Female ; *Neoplasms, Second Primary/epidemiology/pathology ; Middle Aged ; *Breast Neoplasms/pathology/therapy/genetics ; Adult ; Aged ; Aged, 80 and over ; Retrospective Studies ; Young Adult ; Carcinoma, Ductal, Breast/pathology/therapy/epidemiology/genetics ; Prospective Studies ; Follow-Up Studies ; Risk Factors ; },
abstract = {BACKGROUND: Increased screening and treatment advancements have resulted in improved survival rates in women with breast cancer (BC). However, recent data suggests these women have elevated risk of developing a second primary malignancy (SPM) compared to the general population. Limited data exists on factors associated with BC patients developing a SPM.<br><br>METHOD: A retrospective review of a prospective single institution database (1990-2016) identified 782 patients with a history of BC. One hundred and ninety-four BC patients developed a SPM. Clinicopathologic and treatment characteristics were analyzed.<br><br>RESULTS: Of the 194 patients (24.8%) who developed a SPM, 56 (28.9%) BC patients were <50 years old (range: 24-87 years). Two-thirds (64.9%) had at least one first or second degree relative with a malignancy (no relatives-35.1%; &#x2265;1 relative-62.9%). Most patients had invasive ductal carcinoma (n&#x2009;=&#x2009;117, 60.3%) or ductal carcinoma in situ (n&#x2009;=&#x2009;39, 20.1%). Twenty-two patients (11.3%) had pathogenic genetic mutations. Mean time to developing a SPM was 8.9 years (range: 4 months-50 years). Eighty (47.6%) patients received chemotherapy with 91 (54.5%) completing radiation. The most common SPMs were breast (22%), melanoma (17.8%), gynecologic (14.1%), colorectal (12.6%), hematologic (8.9%), and sarcoma (6.5%). Most breast tumors were estrogen receptor (ER) (n&#x2009;=&#x2009;99, 78.0%) or progesterone receptor (PR) positive (n&#x2009;=&#x2009;87, 73.1%) but not HER2-neu positive (n&#x2009;=&#x2009;13, 14.0%).<br><br>CONCLUSION: Most BC patients who developed a SPM had ER/PR positive tumors and a family history of malignancy, with most <50 years old. Although chemotherapy and radiation increase cancer risk, there were an equal number of patients with SPMs who did or did not receive either treatment. Most SPMs were breast, soft tissue, gynecologic, hematologic, or colorectal. BC patients should be followed closely given an elevated propensity for developing SPMs.},
}
@article {pmid39012819,
year = {2024},
author = {Zin, I and China, A and Khan, K and Nag, JK and Vasu, K and Deshpande, GM and Ghosh, PK and Khan, D and Ramachandiran, I and Ganguly, S and Tamagno, I and Willard, B and Gogonea, V and Fox, PL},
title = {AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {30},
pages = {e2303642121},
pmid = {39012819},
issn = {1091-6490},
support = {R01 AG067146/AG/NIA NIH HHS/United States ; R01 NS124547/NS/NINDS NIH HHS/United States ; R01 DK123236/DK/NIDDK NIH HHS/United States ; R01 DK124203/DK/NIDDK NIH HHS/United States ; R01 NS124581/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Breast Neoplasms/metabolism/genetics/pathology ; Female ; *Poly (ADP-Ribose) Polymerase-1/metabolism/genetics ; *Cell Nucleus/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Cell Line, Tumor ; PTEN Phosphohydrolase/metabolism/genetics ; Amino Acyl-tRNA Synthetases/metabolism/genetics ; Active Transport, Cell Nucleus ; Nuclear Localization Signals/metabolism ; },
abstract = {Glutamyl-prolyl-tRNA synthetase (EPRS1) is a bifunctional aminoacyl-tRNA-synthetase (aaRS) essential for decoding the genetic code. EPRS1 resides, with seven other aaRSs and three noncatalytic proteins, in the cytoplasmic multi-tRNA synthetase complex (MSC). Multiple MSC-resident aaRSs, including EPRS1, exhibit stimulus-dependent release from the MSC to perform noncanonical activities distinct from their primary function in protein synthesis. Here, we show EPRS1 is present in both cytoplasm and nucleus of breast cancer cells with constitutively low phosphatase and tensin homolog (PTEN) expression. EPRS1 is primarily cytosolic in PTEN-expressing cells, but chemical or genetic inhibition of PTEN, or chemical or stress-mediated activation of its target, AKT, induces EPRS1 nuclear localization. Likewise, preferential nuclear localization of EPRS1 was observed in invasive ductal carcinoma that were also P-Ser[473]-AKT[+]. EPRS1 nuclear transport requires a nuclear localization signal (NLS) within the linker region that joins the catalytic glutamyl-tRNA synthetase and prolyl-tRNA synthetase domains. Nuclear EPRS1 interacts with poly(ADP-ribose) polymerase 1 (PARP1), a DNA-damage sensor that directs poly(ADP-ribosyl)ation (PARylation) of proteins. EPRS1 is a critical regulator of PARP1 activity as shown by markedly reduced ADP-ribosylation in EPRS1 knockdown cells. Moreover, EPRS1 and PARP1 knockdown comparably alter the expression of multiple tumor-related genes, inhibit DNA-damage repair, reduce tumor cell survival, and diminish tumor sphere formation by breast cancer cells. EPRS1-mediated regulation of PARP1 activity provides a mechanistic link between PTEN loss in breast cancer cells, PARP1 activation, and cell survival and tumor growth. Targeting the noncanonical activity of EPRS1, without inhibiting canonical tRNA ligase activity, provides a therapeutic approach potentially supplementing existing PARP1 inhibitors.},
}
@article {pmid39005669,
year = {2024},
author = {Olbromski, M and Mrozowska, M and Piotrowska, A and Kmiecik, A and Smolarz, B and Romanowicz, H and Blasiak, P and Maciejczyk, A and Wojnar, A and Dziegiel, P},
title = {Prognostic significance of alpha-2-macrglobulin and low-density lipoprotein receptor-related protein-1 in various cancers.},
journal = {American journal of cancer research},
volume = {14},
number = {6},
pages = {3036-3058},
pmid = {39005669},
issn = {2156-6976},
abstract = {Cancer is the leading cause of death worldwide. The World Health Organization (WHO) estimates that 10 million fatalities occurred in 2023. Breast cancer (BC) ranked first among malignancies with 2.26 million cases, lung cancer (LC) second with 2.21 million cases, and colon and rectum cancers (CC, CRC) third with 1.93 million cases. These results highlight the importance of investigating novel cancer prognoses and anti-cancer markers. In this study, we investigated the potential effects of alpha-2 macroglobulin and its receptor, LRP1, on the outcomes of breast, lung, and colorectal malignancies. Immunohistochemical staining was used to analyze the expression patterns of A2M and LRP1 in 545 cases of invasive ductal breast carcinoma (IDC) and 51 cases of mastopathies/fibrocystic breast disease (FBD); 256 cases of non-small cell lung carcinomas (NSCLCs) and 45 cases of non-malignant lung tissue (NMLT); and 108 cases of CRC and 25 cases of non-malignant colorectal tissue (NMCT). A2M and LRP1 expression levels were also investigated in breast (MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2), lung (NCI-H1703, NCI-H522, and A549), and colon (LS 180, Caco-2, HT-29, and LoVo) cancer cell lines. Based on our findings, A2M and LRP1 exhibited various expression patterns in the examined malignancies, which were related to one another. Additionally, the stroma of lung and colorectal cancer has increased levels of A2M/LRP1 areas, which explains the significance of the stroma in the development and maintenance of tumor homeostasis. A2M expression was shown to be downregulated in all types of malignancies under study and was positively linked with an increase in cell line aggressiveness. Although more invasive cells had higher levels of A2M expression, an IHC analysis showed the opposite results. This might be because exogenous alpha-2-macroglobulin is present, which has an inhibitory effect on several cancerous enzymes and receptor-dependent signaling pathways. Additionally, siRNA-induced suppression of the transcripts for A2M and LRPP1 revealed their connection, which provides fresh information on the function of the LRP1 receptor in A2M recurrence in cancer. Further studies on different forms of cancer may corroborate the fact that both A2M and LRP1 have high potential as innovative therapeutic agents.},
}
@article {pmid38994984,
year = {2024},
author = {Nascimento, KCG and São Marcos, BF and Fontes, PHB and Isídio, BEO and Leão, SL and da Silva, GRP and Lussón, DB and Dos Santos, DL and Leal, LRS and Espinoza, BCF and de Macêdo, LS and de França Neto, PL and Silva, AJD and Silva Neto, JC and Santos, VEP and de Freitas, AC},
title = {HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.},
journal = {Cells},
volume = {13},
number = {13},
pages = {},
pmid = {38994984},
issn = {2073-4409},
support = {444606/2023-8//National Council for Scientific and Technological Development/ ; 444156/2023-2//National Council for Scientific and Technological Development/ ; 308684/2023-0//National Council for Scientific and Technological Development/ ; },
mesh = {Humans ; Brazil/epidemiology ; Female ; Middle Aged ; Risk Factors ; *Breast Neoplasms/virology ; *Papillomavirus Infections/virology/complications/epidemiology ; Adult ; Aged ; Papillomaviridae ; Viral Load ; },
abstract = {Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.},
}
@article {pmid38992932,
year = {2024},
author = {Jamjoum, G and Arab, FS and Tayeb, R and Samkari, A and Johari, AA and Ashkar, L and Akbar, J},
title = {Cutaneous Metastasis in Breast Cancer: A Case Report.},
journal = {The American journal of case reports},
volume = {25},
number = {},
pages = {e943999},
pmid = {38992932},
issn = {1941-5923},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Adult ; *Skin Neoplasms/secondary/pathology ; Carcinoma, Ductal, Breast/secondary ; Lung Neoplasms/secondary/pathology ; },
abstract = {BACKGROUND Breast cancer (BC) is the most common malignant disease in females and one of the leading causes of death worldwide. Its treatment plan includes a long-term follow-up and close surveillance, as recurrence is a well-acknowledged concern. BC can recur either locally or as a metastasis, and skin metastasis is a common complication in advanced breast cancer patients. It can present as a skin nodule, plaque, or erythematous lesion, and can be difficult to distinguish from benign skin conditions. The risk of skin metastasis is higher in patients with inflammatory BC. Treatment of such a complex condition is even more challenging, with poor prognosis. Here, we report a case of a 42-year-old woman with stage 4 luminal A BC who had soft tissue recurrence. CASE REPORT A 42-year-old woman with a history of left-sided BC diagnosed and treated 10 years ago presented with multiple soft tissue masses mimicking abscesses at the right lower middle of the back, bilateral thighs, and back of the neck, in the last 6 months, the largest measuring 8×10 cm. The masses were found to be metastatic BC that had spread to the skin and lungs. Because it was invasive ductal carcinoma with positive ER and PR receptors, she was started on hormonal treatment and chemotherapy. CONCLUSIONS This case report highlights the importance of follow-up in patients with a history of BC, as the cancer can recur and spread many years after treatment.},
}
@article {pmid38985057,
year = {2024},
author = {Uppal, R and Saeed, U and Uppal, MR and Khan, AA and Ahmad, M and Piracha, ZZ},
title = {SARS-CoV-2 clearance in term of Cycle Threshold (Ct) during first two waves of COVID-19 in Pakistan: a phenomenon of delayed viral clearance post-corticosteroid treatment.},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {84},
number = {},
pages = {e271452},
doi = {10.1590/1519-6984.271452},
pmid = {38985057},
issn = {1678-4375},
mesh = {Humans ; *COVID-19 ; Pakistan/epidemiology ; *Viral Load/drug effects ; *SARS-CoV-2 ; Male ; Female ; COVID-19 Drug Treatment ; Adult ; RNA, Viral/analysis ; Middle Aged ; Time Factors ; Adrenal Cortex Hormones/therapeutic use ; Young Adult ; Pandemics ; Adolescent ; Real-Time Polymerase Chain Reaction ; COVID-19 Nucleic Acid Testing ; },
abstract = {SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.},
}
@article {pmid38977136,
year = {2025},
author = {Kwon, Y and Gottmann, P and Wang, S and Tissink, J and Motzler, K and Sekar, R and Albrecht, W and Cadenas, C and Hengstler, JG and Schürmann, A and Zeigerer, A},
title = {Induction of steatosis in primary human hepatocytes recapitulates key pathophysiological aspects of metabolic dysfunction-associated steatotic liver disease.},
journal = {Journal of hepatology},
volume = {82},
number = {1},
pages = {18-27},
doi = {10.1016/j.jhep.2024.06.040},
pmid = {38977136},
issn = {1600-0641},
mesh = {Humans ; *Hepatocytes/metabolism/pathology ; *Fatty Liver/metabolism/pathology/etiology ; Male ; Female ; Insulin Resistance ; Cells, Cultured ; },
abstract = {BACKGROUND &amp; AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Owing to limited available treatment options, novel pre-clinical models for target selection and drug validation are warranted. We have established and extensively characterized a primary human steatotic hepatocyte in vitro model system that could guide the development of treatment strategies for MASLD.<br><br>METHODS: Cryopreserved primary human hepatocytes from five donors varying in sex and ethnicity were cultured with free fatty acids in a 3D collagen sandwich for 7 days and the development of MASLD was followed by assessing classical hepatocellular functions. As proof of concept, the effects of the drug firsocostat (GS-0976) on in&#xa0;vitro MASLD phenotypes were evaluated.<br><br>RESULTS: Incubation with free fatty acids induced steatosis, insulin resistance, mitochondrial dysfunction, inflammation, and alterations in prominent human gene signatures similar to patients with MASLD, indicating the recapitulation of human MASLD in this system. The application of firsocostat rescued clinically observed fatty liver disease pathologies, highlighting the ability of the in&#xa0;vitro system to test the efficacy and potentially characterize the mode of action of drug candidates.<br><br>CONCLUSIONS: Altogether, our human MASLD in&#xa0;vitro model system could guide the development and validation of novel targets and drugs for the treatment of MASLD.<br><br>IMPACT AND IMPLICATIONS: Due to low drug efficacy and high toxicity, clinical treatment options for metabolic dysfunction-associated steatotic liver disease (MASLD) are currently limited. To facilitate earlier stop-go decisions in drug development, we have established a primary human steatotic hepatocyte in&#xa0;vitro model. As the model recapitulates clinically relevant MASLD characteristics at high phenotypic resolution, it can serve as a pre-screening platform and guide target identification and validation in MASLD therapy.},
}
@article {pmid38968480,
year = {2024},
author = {Zhang, Z and Huang, C and Wu, J and Cheng, Q and Wang, S},
title = {TICRR as a potential prognostic biomarker for lung adenocarcinoma: A comprehensive analysis using TCGA database.},
journal = {Medicine},
volume = {103},
number = {27},
pages = {e38660},
pmid = {38968480},
issn = {1536-5964},
mesh = {Humans ; *Adenocarcinoma of Lung/genetics/mortality/pathology ; Male ; *Biomarkers, Tumor/genetics/metabolism ; Female ; Prognosis ; *Lung Neoplasms/genetics/mortality/pathology ; Middle Aged ; Nomograms ; Kaplan-Meier Estimate ; Aged ; ROC Curve ; Neoplasm Staging ; Databases, Genetic ; },
abstract = {To investigate the role of TopBP1-interacting checkpoint and replication regulator (TICRR) in the tumorigenesis and prognosis of lung adenocarcinoma (LUAD) patients. Wilcoxon signed-rank test and logistic regression were utilized to analyze the relationship between clinical characteristics and TICRR expression in LUAD from TCGA dataset. Kaplan-Meier plots and Cox regressions were used to assess the impact of TICRR impact on prognosis. ROC curves and nomograms were generated to further evaluate the relationship between TICRR expression and the risk of LUAD. Gene set enrichment analysis (GSEA) was conducted on TCGA dataset, and ssGSEA was employed to investigate the association between TICRR and immune infiltrates. The results showed that high TICRR expression was significantly associated with various clinical factors including gender, age, pathological stage, T stage, N stage, M stage, outcome of primary therapy and smoking status. ROC curves also demonstrated that TICRR was a promising biomarker for molecular pathology diagnosis in LUAD patients (AUC = 0.952). Further analysis using gene ontology (GO) term enrichment and GSEA revealed an abnormal correlation between TICRR expression and cell division. Interestingly, ssGSEA analysis showed that TICRR expression correlated with multiple immune cell types, such as Th2 cell, TFH cell, mast cell, iDC, eosinophils, and dendritic cell. Lastly, the KM-plotters indicated that LUAD patients with high TICRR expression obtained worse life expectancy (P < .001). TICRR has proven to be a valuable tool in predicting disease progression and prognosis in patients with LUAD, thereby establishing itself as a fitting biomarker for forecasting overall survival (OS) of LUAD patients.},
}
@article {pmid38964999,
year = {2024},
author = {Yan, X and Yang, L and Ye, X and Chen, J and Wang, T and Du, M},
title = {Unpacking the hazards: An analytic study of injury patterns and risk factors in urban instant delivery.},
journal = {Injury},
volume = {55},
number = {9},
pages = {111706},
doi = {10.1016/j.injury.2024.111706},
pmid = {38964999},
issn = {1879-0267},
mesh = {Humans ; Female ; Risk Factors ; Male ; China/epidemiology ; *Accidents, Traffic/statistics &amp; numerical data ; *Wounds and Injuries/epidemiology ; Middle Aged ; Adult ; Risk-Taking ; Urban Population/statistics &amp; numerical data ; Young Adult ; },
abstract = {The rapid growth of urban instant delivery, facilitated by digital platforms and characterized by on-demand, short-term, task-based labor, has raised concerns about safety, particularly with the increasing frequency of instant delivery crashes (IDCs). This study addresses knowledge gaps in understanding injury patterns and risk factors associated with IDCs. Utilizing data extracted from judicial verdicts on IDC disputes in China, encompassing demographic, contextual, crash, and injury information, the research employs ordered logit regression to identify significant factors affecting injury patterns, the number of injuries per person (IPP), and injury severity. Overall, traffic injuries related to instant delivery services have gradually improved since 2020, as evidenced by the severity of individual accidents, the number of injuries, and the economic losses. Analysis of 648 injuries among 448 non-fatal victims reveals a prevalence of lower extremity injuries, followed by external, upper extremity, and head injuries. While the majority of victims suffered a single injury, approximately 22 % experienced major injuries. Female delivery riders exhibited higher injury ratios across various body regions. Rider risk behavior, type of delivery vehicles, and the mode of transport of non-delivery travelers emerged as significant influencers of injury patterns. Notably, functional and physical intersection areas exhibited the highest injury ratios among facility types. Contrary to conventional wisdom, older riders and travelers aged above 50 were associated with higher injury severity, challenging the perception of young age as the primary risk factor. The prominence of lower extremity injuries underscores the necessity for heightened protective measures for delivery riders. Major injuries among victims emphasize potential long-term consequences and associated costs. The significance of gender, age, and risk behavior as determining factors highlights the need for targeted safety interventions. These findings offer crucial insights for stakeholders, guiding the formulation of precise safety measures and informed policy initiatives within the dynamic landscape of instant delivery safety.},
}
@article {pmid38951766,
year = {2024},
author = {Nisar, MI and Kabole, I and Khanam, R and Shahid, S and Bakari, BA and Chowdhury, NH and Qazi, MF and Dutta, A and Rahman, S and Khalid, J and Dhingra, U and Hasan, T and Ansari, N and Deb, S and Mitra, DK and Mehmood, U and Aftab, F and Ahmed, S and Khan, S and Ali, SM and Ahmed, S and Manu, A and Yoshida, S and Bahl, R and Baqui, AH and Sazawal, S and Jehan, F},
title = {Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa.},
journal = {BMC pregnancy and childbirth},
volume = {24},
number = {1},
pages = {451},
pmid = {38951766},
issn = {1471-2393},
support = {001/WHO_/World Health Organization/International ; I64438//Bill and Melinda Gates Foundation/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Premature Birth/epidemiology ; *Stillbirth/epidemiology ; Adult ; *Hypertension, Pregnancy-Induced/diagnosis/epidemiology ; *Practice Guidelines as Topic ; United States/epidemiology ; Pakistan/epidemiology ; Cohort Studies ; American Heart Association ; Bangladesh/epidemiology ; Tanzania/epidemiology ; Young Adult ; Blood Pressure ; Infant, Newborn ; Asia, Southern ; },
abstract = {BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes.<br><br>METHODS: We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP)&#x2009;<&#x2009;120&#xa0;mm Hg and diastolic blood pressure (dBP)&#x2009;<&#x2009;80&#xa0;mm Hg), elevated blood pressure (sBP 120-129 and dBP&#x2009;<&#x2009;80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP&#x2009;&#x2265;&#x2009;140 or dBP&#x2009;&#x2265;&#x2009;90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (&#x2265;&#x2009;140/90) and revised ACC/AHA (&#x2265;&#x2009;130/80) thresholds using normal blood pressure as reference group.<br><br>RESULTS: From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8,&#xa0;95%&#xa0;CI 1.4,&#xa0;2.3). The JNC 7 hypertension cut-off of &#x2265;&#x2009;140/90 was significantly associated with a higher risk of preterm births (RR 1.6,&#xa0;95%&#xa0;CI 1.2,&#xa0;2.2) and stillbirths (RR&#xa0;3.6,&#xa0;95%&#xa0;CI 2.5,&#xa0;5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7&#xa0;and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes.<br><br>CONCLUSION: The ACC/AHA criteria (&#x2265;&#x2009;130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.},
}
@article {pmid38944914,
year = {2024},
author = {Bogaard, M and Strømme, JM and Kidd, SG and Johannessen, B and Bakken, AC and Lothe, RA and Axcrona, K and Skotheim, RI and Axcrona, U},
title = {GRIN3A: A biomarker associated with a cribriform pattern and poor prognosis in prostate cancer.},
journal = {Neoplasia (New York, N.Y.)},
volume = {55},
number = {},
pages = {101023},
pmid = {38944914},
issn = {1476-5586},
mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology/metabolism/surgery ; *Biomarkers, Tumor/genetics/metabolism ; Prognosis ; *Neoplasm Grading ; Middle Aged ; Aged ; Gene Expression Regulation, Neoplastic ; Prostatectomy ; Gene Expression Profiling ; },
abstract = {Prostate cancer with a cribriform pattern, including invasive cribriform carcinoma (ICC) and/or intraductal carcinoma (IDC) is associated with a poor prognosis, and the underlying mechanisms are unclear. Therefore, we aimed to identify biomarkers for this feature. Using a radical prostatectomy cohort, we performed within-patient differential expression analyses with RNA sequencing data to compare samples with a cribriform pattern to those with non-cribriform Gleason pattern 4 (NcGP4; n=13). ACSM1, GRIN3A, PCDHB2, and REG4 were identified as differentially expressed, and validation was performed using real-time reverse transcription polymerase chain reaction (n=99; 321 RNA samples) and RNA in situ hybridization on tissue microarrays (n=479; 2047 tissue cores). GRIN3A was significantly higher expressed in cribriform pattern vs. NcGP4, when assessed within the same patient (n=27; p=0.005) and between different patients (n=83; p=0.001). Tissue cores with IDC more often expressed GRIN3A compared to ICC, NcGP4, and benign tissue (52 % vs. ≤ 32 %). When IDC and NcGP4 was compared within the same patient (173 pairs of tissue cores; 54 patients), 38 (22 %) of the tissue microarray core pairs had GRIN3A expression in only IDC, 33 (19 %) had expression in both IDC and NcGP4, 14 (8 %) in only NcGP4 and 88 (51 %) were negative in both entities (p=0.001). GRIN3A was as well associated with biochemical recurrence (log-rank, p=0.002). In conclusion, ectopic GRIN3A expression is an RNA-based biomarker for the presence of cribriform prostate cancer, particularly for IDC.},
}
@article {pmid38942922,
year = {2024},
author = {Pantazi, V and Miklós, V and Smith, P and Oláh-Németh, O and Pankotai-Bodó, G and Teja Dondapati, D and Ayaydin, F and D'Angiolella, V and Pankotai, T},
title = {Prognostic potential of CUL3 ligase with differential roles in luminal A and basal type breast cancer tumors.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {14912},
pmid = {38942922},
issn = {2045-2322},
support = {MR/X006980/1/MRC_/Medical Research Council/United Kingdom ; National Research, Development and Innovation Office under NKFI-FK 13208//Tibor Pankotai/ ; Medical Research Council (MRC) grant MR/X006980/1//Vincenzo D'Angiolella/ ; },
mesh = {Humans ; *Cullin Proteins/metabolism/genetics ; Female ; Prognosis ; *Breast Neoplasms/pathology/genetics/metabolism ; *Biomarkers, Tumor/metabolism/genetics ; *Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Gene Expression Profiling ; MCF-7 Cells ; Triple Negative Breast Neoplasms/genetics/pathology/metabolism ; },
abstract = {Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into non-invasive ductal or lobular carcinoma (DCIS) and invasive carcinoma (ILC or IDC) underscores its heterogeneity. The ubiquitin-proteasome system plays a crucial role in breast cancer, with inhibitors targeting the 26S proteasome showing promise in clinical treatment. The Cullin-RING ubiquitin ligases, including CUL3, have direct links to breast cancer. This study focuses on CUL3 as a potential biomarker, leveraging high-throughput sequencing, gene expression profiling, experimental and data analysis tools. Through comprehensive analysis using databases like GEPIA2 and UALCAN, as well as TCGA datasets, CUL3's expression and its association with prognostic values were assessed. Additionally, the impact of CUL3 overexpression was explored in MCF-7 and MDA-MB-231 breast cancer cell lines, revealing distinct differences in molecular and phenotypic characteristics. We further profiled its expression and localization in breast cancer tissues identifying prominent differences between luminal A and TNBC tumors. Conclusively, CUL3 was found to be associated with cell cycle progression, and DNA damage response, exhibiting diverse roles depending on the tumor's molecular type. It exhibits a tendency to act as an oncogene in triple-negative tumors and as a tumor suppressor in luminal A types, suggesting a potential significance in breast cancer progression and therapeutic directions.},
}
@article {pmid38935197,
year = {2024},
author = {Delfin, L and Doff, JJ and Gagan, J and Flack, A and Krane, JF and Jo, VY and Torell, AG and Palsgrove, D and Bishop, JA},
title = {Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.},
journal = {Head and neck pathology},
volume = {18},
number = {1},
pages = {58},
pmid = {38935197},
issn = {1936-0568},
mesh = {Humans ; Male ; Middle Aged ; Aged ; Female ; *Salivary Gland Neoplasms/pathology/genetics ; Aged, 80 and over ; Carcinoma, Intraductal, Noninfiltrating/pathology/genetics ; Biomarkers, Tumor/analysis/genetics ; Adult ; Carcinoma, Ductal/pathology/genetics ; },
abstract = {BACKGROUND: Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested.<br><br>METHODS: IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed.<br><br>RESULTS: Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma.<br><br>CONCLUSIONS: Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.},
}
@article {pmid38929597,
year = {2024},
author = {Yoo, KC and Kim, DH and Park, S and Yun, H and Ryu, DH and Lee, J and Son, SM},
title = {Gastric Metastasis Mimicking Early Gastric Cancer from Invasive Ductal Carcinoma of the Breast: Case Report and Literature Review.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {6},
pages = {},
pmid = {38929597},
issn = {1648-9144},
mesh = {Humans ; Female ; *Stomach Neoplasms/pathology/diagnosis ; Aged ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/secondary/diagnosis ; *Gastrectomy/methods ; Diagnosis, Differential ; Lymphatic Metastasis ; },
abstract = {Backgound and Objectives: Gastric metastasis from invasive ductal breast cancer (BC) is rare. It mainly occurs in patients with lobular BC. The occurrence of multiple metastases is typically observed several years after the primary diagnosis. Endoscopic findings of gastric metastasis of the BC were usually the linitis plastic type. Case presentation: A 72-year-old women who underwent right modified radical mastectomy (MRM) 10 month ago was referred after being diagnosed with early gastric cancer (EGC) during systemic chemotherapy. EGC type I was found at gastric fundus, and pathologic finding showed poorly differentiated adenocarcinoma. Metachronous double primary tumor EGC was considered. Management and Outcome: A laparoscopic total gastrectomy was performed, and postoperative pathology revealed submucosa invasion and two lymph node metastases. A pathologic review that focused on immunohistochemical studies of selected antibodies such as GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7) was performed again, comparing previous results. As a result, gastric metastasis from BC was diagnosed. After totally laparoscopic total gastrectomy, palliative first-line chemotherapy with paclitaxel/CDDP was performed. Two months after gastrectomy, she was diagnosed with para-aortic lymph node metastasis and multiple bone metastases. She expired six months after gastrectomy. Conclusions: Gastric metastasis from invasive ductal carcinoma of the breast, which is clinically manifested as EGC, is a very rare condition. If there is a history of BC, careful pathological review will be required.},
}
@article {pmid38927753,
year = {2024},
author = {Markalunas, EG and Arnold, DH and Funkhouser, AT and Martin, JC and Shtutman, M and Edenfield, WJ and Blenda, AV},
title = {Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients.},
journal = {Genes},
volume = {15},
number = {6},
pages = {},
pmid = {38927753},
issn = {2073-4425},
support = {P20 GM109091/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Breast Neoplasms/genetics/blood/pathology ; Female ; *Galectins/genetics/blood ; *Mutation ; *Biomarkers, Tumor/genetics/blood ; Galectin 1/genetics/blood ; Middle Aged ; Galectin 3/genetics/blood ; Adult ; Blood Proteins ; },
abstract = {Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.},
}
@article {pmid38926485,
year = {2024},
author = {Baranová, I and Samec, M and Dvorská, D and Šťastný, I and Janíková, K and Kašubová, I and Hornáková, A and Lukáčová, E and Kapinová, A and Biringer, K and Halašová, E and Danková, Z},
title = {Droplet digital PCR analysis of CDH13 methylation status in Slovak women with invasive ductal breast cancer.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {14700},
pmid = {38926485},
issn = {2045-2322},
support = {1/0286/22//Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences/ ; },
mesh = {Humans ; *Cadherins/genetics ; Female ; *DNA Methylation ; *Breast Neoplasms/genetics/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Aged ; *Promoter Regions, Genetic ; Slovakia ; Biomarkers, Tumor/genetics ; Adult ; Polymerase Chain Reaction/methods ; },
abstract = {Identifying novel epigenetic biomarkers is a promising way to improve the clinical management of patients with breast cancer. Our study aimed to determine the methylation pattern of 25 tumor suppressor genes (TSG) and select the best methylation biomarker associated with clinicopathological features in the cohort of Slovak patients diagnosed with invasive ductal carcinoma (IDC). Overall, 166 formalin-fixed, paraffin-embedded (FFPE) tissues obtained from patients with IDC were included in the study. The methylation status of the promoter regions of 25 TSG was analyzed using semiquantitative methylation-specific MLPA (MS-MLPA). We identified CDH13 as the most frequently methylated gene in our cohort of patients. Further analysis by ddPCR confirmed an increased level of methylation in the promoter region of CDH13. A significant difference in CDH13 methylation levels was observed between IDC molecular subtypes LUM A versus HER2 (P = 0.0116) and HER2 versus TNBC (P = 0.0234). In addition, significantly higher methylation was detected in HER2+ versus HER2- tumors (P = 0.0004) and PR- versus PR+ tumors (P = 0.0421). Our results provide evidence that alteration in CDH13 methylation is associated with clinicopathological features in the cohort of Slovak patients with IDC. In addition, using ddPCR as a methylation-sensitive method represents a promising approach characterized by higher precision and technical simplicity to measure the methylation of target CpGs in CDH13 compared to other conventional methods such as MS-MLPA.},
}
@article {pmid38923054,
year = {2024},
author = {Sendag, S and Koca, D and Arslan, T and Schuler, G and Wehrend, A},
title = {Oestrogen and progesterone concentrations in intrapartum cows with insufficient cervix dilation.},
journal = {Reproduction in domestic animals = Zuchthygiene},
volume = {59},
number = {6},
pages = {e14656},
doi = {10.1111/rda.14656},
pmid = {38923054},
issn = {1439-0531},
mesh = {Animals ; Female ; Cattle ; *Progesterone/blood ; Pregnancy ; *Cervix Uteri ; *Estrogens/blood ; Dystocia/veterinary ; Estradiol/blood ; Cattle Diseases/blood ; },
abstract = {The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the cervix (IDC) is a frequent cause of dystocia in cattle. The mechanisms underlying cervical opening and the pathogenesis of IDC are still widely unclear. Systematic studies on the relationship between IDC and steroid hormones have been limited and have yielded inconsistent findings. This study aimed to measure oestrogen and progesterone (P4) concentrations in intrapartum cows presented with dystocia due to IDC and in a comparison (C) group of cows with eutocic delivery. Before any obstetrical procedures, and right after the initial evaluation, blood samples were taken from IDC and C animals. Concentrations of P4, oestradiol-17β (E2), free total oestrogens (FTE) and conjugated total oestrogens (CTE) were measured by established radioimmunoassays. Concentrations of P4 (p = .538), FTE (p = .065) and CTE (p = .605) were not statistically different between C and IDC groups. However, E2 levels in group C were significantly lower when compared to those in the IDC group (p = .013), which is inconsistent with the function of oestrogens in cervical dilatation. The correlation analysis demonstrated significant positive correlations between the pairs P4 versus FTE, P4 versus E2 and FTE versus E2 in group C and between the pair FTE versus E2 in group IDC. In conclusion, the results suggest that local activities of steroids relevant to the aetiology of IDC are not reflected by concentrations in the systemic circulation or that other factors are clearly more important.},
}
@article {pmid38908072,
year = {2024},
author = {Berndt, C and Alborzinia, H and Amen, VS and Ayton, S and Barayeu, U and Bartelt, A and Bayir, H and Bebber, CM and Birsoy, K and Böttcher, JP and Brabletz, S and Brabletz, T and Brown, AR and Brüne, B and Bulli, G and Bruneau, A and Chen, Q and DeNicola, GM and Dick, TP and Distéfano, A and Dixon, SJ and Engler, JB and Esser-von Bieren, J and Fedorova, M and Friedmann Angeli, JP and Friese, MA and Fuhrmann, DC and García-Sáez, AJ and Garbowicz, K and Götz, M and Gu, W and Hammerich, L and Hassannia, B and Jiang, X and Jeridi, A and Kang, YP and Kagan, VE and Konrad, DB and Kotschi, S and Lei, P and Le Tertre, M and Lev, S and Liang, D and Linkermann, A and Lohr, C and Lorenz, S and Luedde, T and Methner, A and Michalke, B and Milton, AV and Min, J and Mishima, E and Müller, S and Motohashi, H and Muckenthaler, MU and Murakami, S and Olzmann, JA and Pagnussat, G and Pan, Z and Papagiannakopoulos, T and Pedrera Puentes, L and Pratt, DA and Proneth, B and Ramsauer, L and Rodriguez, R and Saito, Y and Schmidt, F and Schmitt, C and Schulze, A and Schwab, A and Schwantes, A and Soula, M and Spitzlberger, B and Stockwell, BR and Thewes, L and Thorn-Seshold, O and Toyokuni, S and Tonnus, W and Trumpp, A and Vandenabeele, P and Vanden Berghe, T and Venkataramani, V and Vogel, FCE and von Karstedt, S and Wang, F and Westermann, F and Wientjens, C and Wilhelm, C and Wölk, M and Wu, K and Yang, X and Yu, F and Zou, Y and Conrad, M},
title = {Ferroptosis in health and disease.},
journal = {Redox biology},
volume = {75},
number = {},
pages = {103211},
pmid = {38908072},
issn = {2213-2317},
support = {R01 CA165065/CA/NCI NIH HHS/United States ; R01 CA254970/CA/NCI NIH HHS/United States ; U01 AI156924/AI/NIAID NIH HHS/United States ; R01 NS076511/NS/NINDS NIH HHS/United States ; R01 AI145406/AI/NIAID NIH HHS/United States ; R01 NS061817/NS/NINDS NIH HHS/United States ; R01 CA243142/CA/NCI NIH HHS/United States ; P01 HL114453/HL/NHLBI NIH HHS/United States ; R35 CA253059/CA/NCI NIH HHS/United States ; R01 GM112948/GM/NIGMS NIH HHS/United States ; R01 CA258390/CA/NCI NIH HHS/United States ; R37 NS061817/NS/NINDS NIH HHS/United States ; R01 CA266342/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U01 AI156923/AI/NIAID NIH HHS/United States ; },
mesh = {*Ferroptosis ; Humans ; Animals ; Iron/metabolism ; Neoplasms/metabolism/drug therapy/pathology ; Lipid Peroxidation ; Oxidation-Reduction ; Disease Susceptibility ; },
abstract = {Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells' susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with - or caused by - ferroptosis.},
}
@article {pmid38897820,
year = {2024},
author = {Corso, G and Fusco, N and Guerini-Rocco, E and Leonardi, MC and Criscitiello, C and Zagami, P and Nicolò, E and Mazzarol, G and La Vecchia, C and Pesapane, F and Zanzottera, C and Tarantino, P and Petitto, S and Bianchi, B and Massari, G and Boato, A and Sibilio, A and Polizzi, A and Curigliano, G and De Scalzi, AM and Lauria, F and Bonanni, B and Marabelli, M and Rotili, A and Nicosia, L and Albini, A and Calvello, M and Mukhtar, RA and Robson, ME and Sacchini, V and Rennert, G and Galimberti, V and Veronesi, P and Magnoni, F},
title = {Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.},
journal = {Seminars in oncology},
volume = {51},
number = {3-4},
pages = {106-122},
doi = {10.1053/j.seminoncol.2024.05.001},
pmid = {38897820},
issn = {1532-8708},
mesh = {Humans ; *Breast Neoplasms/diagnosis/genetics/therapy/pathology/prevention &amp; control ; Female ; *Carcinoma, Lobular/diagnosis/therapy/genetics/pathology ; },
abstract = {Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.},
}
@article {pmid38894870,
year = {2024},
author = {Ramamoorthy, P and Ramakantha Reddy, BR and Askar, SS and Abouhawwash, M},
title = {Histopathology-based breast cancer prediction using deep learning methods for healthcare applications.},
journal = {Frontiers in oncology},
volume = {14},
number = {},
pages = {1300997},
pmid = {38894870},
issn = {2234-943X},
abstract = {Breast cancer (BC) is the leading cause of female cancer mortality and is a type of cancer that is a major threat to women's health. Deep learning methods have been used extensively in many medical domains recently, especially in detection and classification applications. Studying histological images for the automatic diagnosis of BC is important for patients and their prognosis. Owing to the complication and variety of histology images, manual examination can be difficult and susceptible to errors and thus needs the services of experienced pathologists. Therefore, publicly accessible datasets called BreakHis and invasive ductal carcinoma (IDC) are used in this study to analyze histopathological images of BC. Next, using super-resolution generative adversarial networks (SRGANs), which create high-resolution images from low-quality images, the gathered images from BreakHis and IDC are pre-processed to provide useful results in the prediction stage. The components of conventional generative adversarial network (GAN) loss functions and effective sub-pixel nets were combined to create the concept of SRGAN. Next, the high-quality images are sent to the data augmentation stage, where new data points are created by making small adjustments to the dataset using rotation, random cropping, mirroring, and color-shifting. Next, patch-based feature extraction using Inception V3 and Resnet-50 (PFE-INC-RES) is employed to extract the features from the augmentation. After the features have been extracted, the next step involves processing them and applying transductive long short-term memory (TLSTM) to improve classification accuracy by decreasing the number of false positives. The results of suggested PFE-INC-RES is evaluated using existing methods on the BreakHis dataset, with respect to accuracy (99.84%), specificity (99.71%), sensitivity (99.78%), and F1-score (99.80%), while the suggested PFE-INC-RES performed better in the IDC dataset based on F1-score (99.08%), accuracy (99.79%), specificity (98.97%), and sensitivity (99.17%).},
}
@article {pmid38839260,
year = {2025},
author = {Sun, T and Golestani, R and Zhan, H and Krishnamurti, U and Harigopal, M and Zhong, M and Liang, Y},
title = {Clinicopathologic Characteristics of MYC Copy Number Amplification in Breast Cancer.},
journal = {International journal of surgical pathology},
volume = {33},
number = {1},
pages = {59-64},
doi = {10.1177/10668969241256109},
pmid = {38839260},
issn = {1940-2465},
mesh = {Humans ; Female ; Middle Aged ; Gene Amplification ; *Breast Neoplasms/genetics/pathology/mortality ; Adult ; Aged ; *Proto-Oncogene Proteins c-myc/genetics/analysis ; *Biomarkers, Tumor/genetics/analysis ; Gene Dosage ; Prognosis ; Aged, 80 and over ; *Carcinoma, Ductal, Breast/genetics/pathology/mortality ; High-Throughput Nucleotide Sequencing ; Immunohistochemistry ; Breast/pathology ; },
abstract = {INTRODUCTION: MYC overexpression is a known phenomenon in breast cancer. This study investigates the correlation of MYC gene copy number amplification and MYC protein overexpression with coexisting genetic abnormalities and associated clinicopathologic features in breast cancer patients.<br><br>METHODS: The study analyzed data from 81 patients with localized or metastatic breast cancers using targeted next-generation sequencing and MYC immunohistochemical studies, along with pathological and clinical data.<br><br>RESULTS: Applying the criteria of MYC/chromosome 8 ratio &#x2265;5, MYC copy number amplified tumors (n&#x2009;=&#x2009;11, 14%) were associated with invasive ductal carcinoma (91% vs 68%, P&#x2009;=&#x2009;.048), poorly differentiated (grade 3, 64% vs 30%, P&#x2009;=&#x2009;.032), mitotically active (Nottingham mitotic score 3, 71% vs 20%, P&#x2009;=&#x2009;.004), estrogen receptor (ER)-negative (45% vs 12%, P&#x2009;=&#x2009;.008), and triple-negative (56% vs 12%, P&#x2009;=&#x2009;.013) compared to MYC non-amplified tumors. Among MYC-amplified breast cancer patients, those with triple-negative status showed significantly shorter disease-free survival time than non-triple negative MYC-amplified patients (median survival month: 25.5 vs 127.6, P&#x2009;=&#x2009;.049). MYC amplification is significantly associated with TP53 mutation (P&#x2009;=&#x2009;.007). The majority (10 of 11; 91%) of MYC-amplified tumors showed positive c-MYC immunostaining.<br><br>CONCLUSION: Breast cancers with MYC copy number amplication display distinct clinicopathologic characteristics indicative of more aggressive behavior.},
}
@article {pmid38838211,
year = {2024},
author = {Wang, Y and Li, G and Chen, B and Shakir, G and Volz, M and van der Vorst, EPC and Maas, SL and Geiger, M and Jethwa, C and Bartelt, A and Li, Z and Wettich, J and Sachs, N and Maegdefessel, L and Nazari Jahantigh, M and Hristov, M and Lacy, M and Lutz, B and Weber, C and Herzig, S and Guillamat Prats, R and Steffens, S},
title = {Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner.},
journal = {Cardiovascular research},
volume = {120},
number = {12},
pages = {1411-1426},
pmid = {38838211},
issn = {1755-3245},
support = {STE1053/6-1//Deutsche Forschungsgemeinschaft/ ; 81Z0600205//German Ministry of Research and Education/ ; 1061//LMU Medical Faculty F&#xf6;FoLe program/ ; //Interdisciplinary Center for Clinical Research/ ; //RWTH Aachen University/ ; 10.20.2.043MN//Fritz Thyssen Stiftung/ ; 201908080123//Chinese Scholar Council/ ; },
mesh = {Animals ; Female ; Humans ; Male ; Aortic Diseases/genetics/pathology/prevention &amp; control/metabolism/enzymology ; *Atherosclerosis/genetics/pathology/metabolism/prevention &amp; control/enzymology ; Carotid Artery Diseases/genetics/pathology/metabolism/prevention &amp; control ; *Cell Proliferation ; *Disease Models, Animal ; Estradiol/pharmacology ; Estrogen Receptor alpha/metabolism/genetics/deficiency ; *Macrophages/metabolism/pathology ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; *Plaque, Atherosclerotic ; *Receptor, Cannabinoid, CB1/metabolism/genetics ; Sex Factors ; *Signal Transduction ; Tumor Suppressor Protein p53/metabolism/genetics/deficiency ; },
abstract = {AIMS: Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cell-specific effects in this disease are not well understood. To address this, we generated a transgenic mouse model to study the role of myeloid CB1 signalling in atherosclerosis.<br><br>METHODS AND RESULTS: Here, we report that male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. Male Cnr1-deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sex-specific differences in proliferation were dependent on oestrogen receptor (ER)&#x3b1;-oestradiol signalling. Kinase activity profiling identified a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further revealed chromatin modifications, mRNA processing, and mitochondrial respiration among the key processes affected by CB1 signalling, which was supported by metabolic flux assays. Chronic administration of the peripherally restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally, CNR1 expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism, and inflammatory markers, suggesting a possible implication of CB1-dependent regulation in human pathophysiology.<br><br>CONCLUSION: Impaired macrophage CB1 signalling is atheroprotective by limiting their arterial recruitment, proliferation, and inflammatory reprogramming in male mice. The importance of macrophage CB1 signalling appears to be sex-dependent.},
}
@article {pmid38837365,
year = {2024},
author = {Voloch, L and Icht, M and Ben-David, BM and Carmel Neiderman, NN and Levenberg, G and Manor, Y and Shpunt, D and Oestreicher-Kedem, Y},
title = {Seven Days of Voice Rest Post-phonosurgery Is Not Better than 3 days: A Prospective Randomized Short-term Outcome Study.},
journal = {The Laryngoscope},
volume = {134},
number = {11},
pages = {4661-4666},
doi = {10.1002/lary.31556},
pmid = {38837365},
issn = {1531-4995},
mesh = {Humans ; Female ; Male ; Prospective Studies ; Adult ; *Vocal Cords/surgery/physiopathology ; *Voice Quality ; Time Factors ; Treatment Outcome ; Middle Aged ; *Laryngeal Diseases/surgery/physiopathology ; Rest/physiology ; Voice Disorders/etiology/surgery/physiopathology ; Phonation/physiology ; Postoperative Period ; Postoperative Care/methods ; },
abstract = {OBJECTIVE: The aim of the study is to compare the short-term effect of 7 versus 3 days of voice rest (VR) on objective vocal (acoustic) parameters following phonosurgery.<br><br>METHODS: A prospective randomized study conducted at a tertiary referral medical center. Patients with vocal fold nodules, polyps, or cysts and scheduled for phonosurgery were recruited from the Voice Clinic. They were randomized into groups of 7- or 3-day postoperative VR periods and their voices were recorded preoperatively and at 4-week postoperatively. A mixed linear model statistical analysis (MLMSA) was used to compare pre- and postoperative jitter, shimmer, harmonic-to-noise ratio, and maximum phonation time between the two groups.<br><br>RESULTS: Sixty-five patients were recruited, but only 34 fully complied with the study protocol, and their data were included in the final analysis (19 males, 20 females; mean age: 40.6&#x2009;years; 17 patients in the 7-day VR group and 16 in the 3-day VR group). The groups were comparable in age, sex, and type of vocal lesion distribution. The preoperative MLMSA showed no significant group differences in the tested vocal parameters. Both groups exhibited significant (p&#x2009;<&#x2009;0.05) and comparable improvement in all vocal parameters at postoperative week 4.<br><br>CONCLUSIONS: A VR duration of 7&#x2009;days showed no greater benefit on the examined vocal parameters than the 3-day protocol 4-week postoperatively. Our results suggest that a 3-day VR regimen can be followed by patients who undergo phonosurgery without compromising the vocal results. Larger-scale and longer-duration studies are needed to confirm our findings.<br><br>LEVEL OF EVIDENCE: 2 Laryngoscope, 134:4661-4666, 2024.},
}
@article {pmid38837155,
year = {2024},
author = {Wang, WE and Ho, CC and Chang, CH},
title = {Taxane-Induced Cutaneous Toxic Effects.},
journal = {JAMA dermatology},
volume = {160},
number = {7},
pages = {771-772},
doi = {10.1001/jamadermatol.2024.1204},
pmid = {38837155},
issn = {2168-6084},
mesh = {Humans ; *Taxoids/adverse effects ; Female ; Drug Eruptions/etiology/pathology ; Antineoplastic Agents/adverse effects ; Middle Aged ; },
}
@article {pmid38833720,
year = {2025},
author = {Wang, L and Vasudevaraja, V and Tran, I and Sukhadia, P and Reuter, VE and Abu-Rustum, NR and Rubinstein, MM and Gopalan, A and Ross, D and Snuderl, M and Chiang, S},
title = {Novel Androgen Receptor Splice Variant 7 in Gynecologic Tumors.},
journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists},
volume = {44},
number = {1},
pages = {88-93},
doi = {10.1097/PGP.0000000000001029},
pmid = {38833720},
issn = {1538-7151},
mesh = {Female ; Humans ; Middle Aged ; Biomarkers, Tumor/genetics ; DNA Methylation ; Genital Neoplasms, Female/genetics/pathology ; Ovarian Neoplasms/pathology/genetics ; *Receptors, Androgen/genetics ; Uterine Neoplasms/genetics/pathology ; },
abstract = {Androgen receptor splicing variant 7 (AR-V7) is a truncated variant of the AR mRNA that may be a predictive biomarker for AR-targeted therapy. AR-V7 has been described in prostate, breast, salivary duct, and hepatocellular carcinomas as well as mammary and extra-mammary Paget disease. We report 2 gynecologic cancers occurring in the lower uterine segment and ovary and both harboring AR-V7 by targeted RNA sequencing. The uterine tumor was an undifferentiated carcinoma consisting of epithelioid cells and focally spindled cells arranged in sheets, nests, and cords associated with brisk mitotic activity and tumor necrosis. The ovarian tumor consisted of glands with cribriform and solid architecture and uniform cytologic atypia. ER and PR were positive in the ovarian tumor and negative in the uterine tumor. Both were positive for AR and negative for HER2, GATA3, and NKX3.1. DNA methylation profiling showed epigenetic similarity of the AR-V7-positive gynecologic cancers to AR-V7-positive breast cancers rather than to prostate cancers. AR-V7 may underpin rare gynecologic carcinomas with undifferentiated histology or cribriform growth reminiscent of prostatic adenocarcinoma and breast invasive ductal carcinoma.},
}
@article {pmid38831458,
year = {2024},
author = {Morla-Barcelo, PM and Laguna-Macarrilla, D and Cordoba, O and Matheu, G and Oliver, J and Roca, P and Nadal-Serrano, M and Sastre-Serra, J},
title = {Unraveling malignant phenotype of peritumoral tissue: transcriptomic insights into early-stage breast cancer.},
journal = {Breast cancer research : BCR},
volume = {26},
number = {1},
pages = {89},
pmid = {38831458},
issn = {1465-542X},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality/metabolism ; *Gene Expression Profiling ; *Transcriptome ; *Gene Expression Regulation, Neoplastic ; *Neoplasm Staging ; Prognosis ; *Protein Interaction Maps/genetics ; Middle Aged ; Biomarkers, Tumor/genetics ; Gene Regulatory Networks ; Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Phenotype ; Neoplasm Recurrence, Local/genetics/pathology ; Aged ; Adult ; },
abstract = {BACKGROUND: Early-stage invasive ductal carcinoma displays high survival rates due to early detection and treatments. However, there is still a chance of relapse of 3-15% after treatment. The aim of this study was to uncover the distinctive transcriptomic characteristics and monitoring prognosis potential of peritumoral tissue in early-stage cases.<br><br>METHODS: RNA was isolated from tumoral, peritumoral, and non-tumoral breast tissue from surgical resection of 10 luminal early-stage invasive ductal carcinoma patients. Transcriptome expression profiling for differentially expressed genes (DEGs) identification was carried out through microarray analysis. Gene Ontology and KEGG pathways enrichment analysis were explored for functional characterization of identified DEGs. Protein-Protein Interactions (PPI) networks analysis was performed to identify hub nodes of peritumoral tissue alterations and correlated with Overall Survival and Relapse Free Survival.<br><br>RESULTS: DEGs closely related with cell migration, extracellular matrix organization, and cell cycle were upregulated in peritumoral tissue compared to non-tumoral. Analyzing PPI networks, we observed that the proximity to tumor leads to the alteration of gene modules involved in cell proliferation and differentiation signaling pathways. In fact, in the peritumoral area were identified the top ten upregulated hub nodes including CDK1, ESR1, NOP58, PCNA, EZH2, PPP1CA, BUB1, TGFBR1, CXCR4, and CCND1. A signature performed by four of these hub nodes (CDK1, PCNA, EZH2, and BUB1) was associated with relapse events in untreated luminal breast cancer patients.<br><br>CONCLUSIONS: In conclusion, our study characterizes in depth breast peritumoral tissue providing clues on the changes that tumor signaling could cause in patients with early-stage breast cancer. We propose that the use of a four gene signature could help to predict local relapse. Overall, our results highlight the value of peritumoral tissue as a potential source of new biomarkers for early detection of relapse and improvement in invasive ductal carcinoma patient's prognosis.},
}
@article {pmid38830849,
year = {2024},
author = {Wearn, A and Tremblay, SA and Tardif, CL and Leppert, IR and Gauthier, CJ and Baracchini, G and Hughes, C and Hewan, P and Tremblay-Mercier, J and Rosa-Neto, P and Poirier, J and Villeneuve, S and Schmitz, TW and Turner, GR and Spreng, RN and , },
title = {Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4706},
pmid = {38830849},
issn = {2041-1723},
support = {R01 AG068563/AG/NIA NIH HHS/United States ; NIA R01 AG068563//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AARG-22-927100/ALZ/Alzheimer's Association/United States ; },
mesh = {Humans ; *White Matter/diagnostic imaging/pathology/metabolism ; Female ; Male ; Aged ; Middle Aged ; *Alzheimer Disease/genetics/pathology/cerebrospinal fluid/metabolism/diagnostic imaging ; *Tauopathies/diagnostic imaging/metabolism/pathology/genetics/cerebrospinal fluid ; *tau Proteins/metabolism/cerebrospinal fluid ; *Magnetic Resonance Imaging ; Brain/pathology/diagnostic imaging/metabolism ; Apolipoproteins E/genetics/metabolism ; Apolipoprotein E4/genetics/metabolism ; Neurites/metabolism/pathology ; },
abstract = {The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.},
}
@article {pmid38795111,
year = {2024},
author = {Voß, F and Zweck, E and Ipek, R and Schultheiss, HP and Roden, M and Kelm, M and Szendroedi, J and Polzin, A and Westenfeld, R and Scheiber, D},
title = {Myocardial Mitochondrial Function Is Impaired in Cardiac Light-Chain Amyloidosis Compared to Transthyretin Amyloidosis.},
journal = {JACC. Heart failure},
volume = {12},
number = {10},
pages = {1778-1780},
doi = {10.1016/j.jchf.2024.03.012},
pmid = {38795111},
issn = {2213-1787},
mesh = {Humans ; *Amyloid Neuropathies, Familial/metabolism/physiopathology/complications ; *Cardiomyopathies/etiology/physiopathology/metabolism ; Mitochondria, Heart/metabolism ; Male ; Female ; Immunoglobulin Light-chain Amyloidosis ; Aged ; Middle Aged ; Myocardium/pathology/metabolism ; },
}
@article {pmid38784039,
year = {2024},
author = {Ahmad, H and Ali, A and Khalil, AT and Ali, R and Khan, I and Khan, MM and Ahmed, I and Basharat, Z and Alorini, M and Mehmood, A},
title = {Clinico-genomic findings, molecular docking, and mutational spectrum in an understudied population with breast cancer patients from KP, Pakistan.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1383284},
pmid = {38784039},
issn = {1664-8021},
abstract = {In this study, we report the mutational profiles, pathogenicity, and their association with different clinicopathologic and sociogenetic factors in patients with Pashtun ethnicity for the first time. A total of 19 FFPE blocks of invasive ductal carcinoma (IDC) from the Breast Cancer (BC) tissue and 6 normal FFPE blocks were analyzed by whole-exome sequencing (WES). Various somatic and germline mutations were identified in cancer-related genes, i.e., ATM, CHEK2, PALB2, and XRCC2. Among a total of 18 mutations, 14 mutations were somatic and 4 were germline. The ATM gene exhibited the maximum number of mutations (11/18), followed by CHEK2 (3/18), PALB2 (3/18), and XRCC2 (1/18). Except one frameshift deletion, all other 17 mutations were nonsynonymous single-nucleotide variants (SNVs). SIFT prediction revealed 7/18 (38.8%) mutations as deleterious. PolyPhen-2 and MutationTaster identified 5/18 (27.7%) mutations as probably damaging and 10/18 (55.5%) mutations as disease-causing, respectively. Mutations like PALB2 p.Q559R (6/19; 31.5%), XRCC2 p.R188H (5/19; 26.31%), and ATM p.D1853N (4/19; 21.05%) were recurrent mutations and proposed to have a biomarker potential. The protein network prediction was performed using GeneMANIA and STRING. ISPRED-SEQ indicated three interaction site mutations which were further used for molecular dynamic simulation. An average increase in the radius of gyration was observed in all three mutated proteins revealing their perturbed folding behavior. Obtained SNVs were further correlated with various parameters related to the clinicopathological status of the tumors. Three mutation positions (ATM p. D1853N, CHEK2 p.M314I, and PALB2 p.T1029S) were found to be highly conserved. Finally, the wild- and mutant-type proteins were screened for two drugs: elagolix (DrugBank ID: DB11979) and LTS0102038 (a triterpenoid, isolated from the anticancer medicinal plant Fagonia indica). Comparatively, a higher number of interactions were noted for normal ATM with both compounds, as compared to mutants.},
}
@article {pmid38751260,
year = {2024},
author = {Shirazi, B and Niaz, M and Khan, MA},
title = {The characteristics and risk factors of breast cancer patients trend distinctive regional differences: a cross-sectional study.},
journal = {JPMA. The Journal of the Pakistan Medical Association},
volume = {74},
number = {4},
pages = {672-676},
doi = {10.47391/JPMA.9360},
pmid = {38751260},
issn = {0030-9982},
mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/pathology ; Cross-Sectional Studies ; Pakistan/epidemiology ; Middle Aged ; Risk Factors ; Adult ; Retrospective Studies ; Male ; Neoplasm Staging ; Breast Neoplasms, Male/epidemiology/pathology ; Breast Feeding/statistics &amp; numerical data ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Parity ; Aged ; Neoplasm Grading ; Marital Status ; },
abstract = {OBJECTIVE: To determine the characteristics and risk factors of breast cancer patients in a tertiary care setting.<br><br>METHODS: The retrospective, cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, and comprised data of all patients diagnosed with breast cancer from March 2017 to December 2021. Demographic characteristics, clinical presentation, stage of the disease and histopathological characteristics were noted. Data related to all the variables was not available in all cases. Data was analysed using SPSS 23.<br><br>RESULTS: Of the 690 patients, 683(99%) were females and 7(1%) were males. The mean age at presentation was 49.3&#xb1;13.5 years, while the mean duration of symptoms was 10.24&#xb1;17.64) months. Most of the females were married 642(93%) and multiparous 484(70.9%), while 293(42.5%) had breastfed their children for >1 year, and 412(59.7%) had no history of contraception use. The most common stage at presentation was stage II (48.6%), and most patients had grade II 395(57.2%) invasive ductal carcinoma, with Luminal A molecular subtype noted in 287(41.6%) cases.<br><br>CONCLUSIONS: The characteristics of breast cancer in the sample had certain distinctions compared to other populations. It is important to integrate all datasets and develop guidelines appropriate to Pakistani population.},
}
@article {pmid38747597,
year = {2024},
author = {Stindt, KR and McClean, MN},
title = {Tuning interdomain conjugation to enable in situ population modification in yeasts.},
journal = {mSystems},
volume = {9},
number = {6},
pages = {e0005024},
pmid = {38747597},
issn = {2379-5077},
support = {R01 AI154940/AI/NIAID NIH HHS/United States ; P30CA014520//University of Wisconsin Carbone Cancer Center (UWCCC)/ ; P30 CA014520/CA/NCI NIH HHS/United States ; R35 GM128873/GM/NIGMS NIH HHS/United States ; 135AAI9593//Wisconsin Alumni Research Foundation (WARF)/ ; R35GM128873//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32 GM130550/GM/NIGMS NIH HHS/United States ; T32GM130550//Molecular Biophysics Training Grant/ ; R01AI154940//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {*Saccharomyces cerevisiae/genetics ; *Escherichia coli/genetics/metabolism ; Conjugation, Genetic ; },
abstract = {The ability to modify and control natural and engineered microbiomes is essential for biotechnology and biomedicine. Fungi are critical members of most microbiomes, yet technology for modifying the fungal members of a microbiome has lagged far behind that for bacteria. Interdomain conjugation (IDC) is a promising approach, as DNA transfer from bacterial cells to yeast enables in situ modification. While such genetic transfers have been known to naturally occur in a wide range of eukaryotes and are thought to contribute to their evolution, IDC has been understudied as a technique to control fungal or fungal-bacterial consortia. One major obstacle to the widespread use of IDC is its limited efficiency. In this work, we manipulated metabolic and physical interactions between genetically tractable Escherichia coli and Saccharomyces cerevisiae to control the incidence of IDC. We test the landscape of population interactions between the bacterial donors and yeast recipients to find that bacterial commensalism leads to maximized IDC, both in culture and in mixed colonies. We demonstrate the capacity of cell-to-cell binding via mannoproteins to assist both IDC incidence and bacterial commensalism in culture and model how these tunable controls can predictably yield a range of IDC outcomes. Furthermore, we demonstrate that these controls can be utilized to irreversibly alter a recipient yeast population, by both "rescuing" a poor-growing recipient population and collapsing a stable population via a novel IDC-mediated CRISPR/Cas9 system.IMPORTANCEFungi are important but often unaddressed members of most natural and synthetic microbial communities. This work highlights opportunities for modifying yeast microbiome populations through bacterial conjugation. While conjugation has been recognized for its capacity to deliver engineerable DNA to a range of cells, its dependence on cell contact has limited its efficiency. Here, we find "knobs" to control DNA transfer, by engineering the metabolic dependence between bacterial donors and yeast recipients and by changing their ability to physically adhere to each other. Importantly, we functionally validate these "knobs" by irreversibly altering yeast populations. We use these controls to "rescue" a failing yeast population, demonstrate the capacity of conjugated CRISPR/Cas9 to depress or collapse populations, and show that conjugation can be easily interrupted by disrupting cell-to-cell binding. These results offer building blocks toward in situ mycobiome editing, with significant implications for clinical treatments of fungal pathogens and other fungal system engineering.},
}
@article {pmid38741627,
year = {2024},
author = {Ahuja, S and G, K and Zaheer, S},
title = {Evaluation of Histomorphological Changes in Breast Cancer Post-Neoadjuvant Chemotherapy.},
journal = {Indian journal of surgical oncology},
volume = {15},
number = {2},
pages = {236-240},
pmid = {38741627},
issn = {0975-7651},
abstract = {Breast cancer, a leading cause of global female mortality, demands comprehensive diagnostic and therapeutic strategies. This study delves into the nuanced realm of post-neoadjuvant chemotherapy breast cancer specimens, emphasizing the imperative need for pathologists to discern stromal and nuclear alterations adeptly. The investigation, encompassing 100 female patients with a mean age of 47.5 years, elucidates the demographic and clinicopathological parameters. Predominantly presenting as palpable lumps (85%), invasive ductal carcinoma emerged as the predominant histological type (98%). The primary focus of the study revolves around the morphological changes post-neoadjuvant chemotherapy, with a meticulous qualitative analysis encompassing stromal elements (fibrosis, elastosis, calcification) and nuclear features (pyknosis, hyperchromasia). Notably, the response to chemotherapy, classified by the International Union against Cancer criteria, delineates a substantial pathological complete response (55%), partial response (35%), and limited non-response (10%). The therapeutic landscape includes a majority of cases undergoing extensive chemotherapy cycles, primarily featuring the cyclophosphamide, doxorubicin, and paclitaxel regimen. Remarkably, this investigation unveils fibrosis (63%) and elastosis/collagenization (51%) as prevalent stromal changes, while pyknosis (58%) and hyperchromasia (48%) dominate nuclear alterations. In conclusion, this retrospective study provides a comprehensive overview of post-neoadjuvant chemotherapy breast cancer specimens, shedding light on the intricate interplay of clinical parameters, treatment responses, and histopathological changes. The findings underscore the pivotal role of pathologists in accurately diagnosing and grading tumors in the evolving landscape of breast cancer management.},
}
@article {pmid38734990,
year = {2024},
author = {Greenland, NY and Cooperberg, MR and Carroll, PR and Cowan, JE and Simko, JP and Stohr, BA and Chan, E},
title = {Morphologic patterns observed in prostate biopsy cases with discrepant grade group and molecular risk classification.},
journal = {The Prostate},
volume = {84},
number = {11},
pages = {1076-1085},
doi = {10.1002/pros.24725},
pmid = {38734990},
issn = {1097-0045},
mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/genetics ; *Neoplasm Grading ; *Prostate/pathology ; Biopsy ; Middle Aged ; Aged ; Biomarkers, Tumor/genetics ; Risk Assessment ; Prostatectomy ; },
abstract = {BACKGROUND: Molecular-based risk classifier tests are increasingly being utilized by urologists and radiation oncologists to guide clinical decision making. The Decipher prostate biopsy test is a 22-gene RNA biomarker assay designed to predict likelihood of high-grade disease at radical prostatectomy and risk of metastasis and mortality. The test provides a risk category of low, intermediate, or high. We investigated histologic features of biopsies in which the Grade Group (GG) and Decipher risk category (molecular risk) were discrepant.<br><br>METHODS: Our institutional urologic outcomes database was searched for men who underwent prostate biopsies with subsequent Decipher testing from 2016 to 2020. We defined discrepant GG and molecular risk as either GG1-2 with high Decipher risk category or GG&#x2009;&#x2265;&#x2009;3 with low Decipher risk category. The biopsy slide on which Decipher testing was performed was re-reviewed for GG and various histologic features, including % Gleason pattern 4, types of Gleason pattern 4 and 5, other "high risk" features (e.g., complex papillary, ductal carcinoma, intraductal carcinoma [IDC]), and other unusual and often "difficult to grade" patterns (e.g., atrophic carcinoma, mucin rupture, pseudohyperplastic carcinoma, collagenous fibroplasia, foamy gland carcinoma, carcinoma with basal cell marker expression, carcinoma with prominent vacuoles, and stromal reaction). Follow-up data was also obtained from the electronic medical record.<br><br>RESULTS: Of 178 men who underwent prostate biopsies and had Decipher testing performed, 41 (23%) had discrepant GG and molecular risk. Slides were available for review for 33/41 (80%). Of these 33 patients, 23 (70%) had GG1-2 (GG1 n&#x2009;=&#x2009;5, GG2 n&#x2009;=&#x2009;18) with high Decipher risk, and 10 (30%) had GG&#x2009;&#x2265;&#x2009;3 with low Decipher risk. Of the 5 GG1 cases, one case was considered GG2 on re-review; no other high risk features were identified but each case showed at least one of the following "difficult to grade" patterns: 3 atrophic carcinoma, 1 collagenous fibroplasia, 1 carcinoma with mucin rupture, and 1 carcinoma with basal cell marker expression. Of the 18 GG2 high Decipher risk cases, 2 showed GG3 on re-review, 5 showed large cribriform and/or other high risk features, and 10 showed a "difficult to grade" pattern. Of the 10 GG&#x2009;&#x2265;&#x2009;3 low Decipher risk cases, 5 had known high risk features including 2 with large cribriform, 1 with IDC, and 1 with Gleason pattern 5.<br><br>CONCLUSIONS: In GG1-2 high Decipher risk cases, difficult to grade patterns were frequently seen in the absence of other known high risk morphologic features; whether these constitute true high risk cases requires further study. In the GG&#x2009;&#x2265;&#x2009;3 low Decipher risk cases, aggressive histologic patterns such as large cribriform and IDC were observed in half (50%) of cases; therefore, the molecular classifier may not capture all high risk histologic patterns.},
}
@article {pmid38734115,
year = {2024},
author = {Clark, AB and Conzen, SD},
title = {Glucocorticoid receptor-mediated oncogenic activity is dependent on breast cancer subtype.},
journal = {The Journal of steroid biochemistry and molecular biology},
volume = {243},
number = {},
pages = {106518},
doi = {10.1016/j.jsbmb.2024.106518},
pmid = {38734115},
issn = {1879-1220},
support = {R01 CA238519/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Receptors, Glucocorticoid/metabolism/genetics ; Female ; *Breast Neoplasms/pathology/metabolism/genetics ; Receptors, Estrogen/metabolism/genetics ; Signal Transduction ; Gene Expression Regulation, Neoplastic ; Triple Negative Breast Neoplasms/genetics/pathology/metabolism/classification ; Animals ; Carcinogenesis/genetics/metabolism ; },
abstract = {Breast cancer incidence has been steadily rising and is the leading cause of cancer death in women due to its high metastatic potential. Individual breast cancer subtypes are classified by both cell type of origin and receptor expression, namely estrogen, progesterone and human epidermal growth factor receptors (ER, PR and HER2). Recently, the importance and context-dependent role of glucocorticoid receptor (GR) expression in the natural history and prognosis of breast cancer subtypes have been uncovered. In ER-positive breast cancer, GR expression is associated with a better prognosis as a result of ER-GR crosstalk. GR appears to modulate ER-mediated gene expression resulting in decreased tumor cell proliferation and a more indolent cancer phenotype. In ER-negative breast cancer, including GR-positive triple-negative breast cancer (TNBC), GR expression enhances migration, chemotherapy resistance and cell survival. In invasive lobular carcinoma, GR function is relatively understudied, and more work is required to determine whether lobular subtypes behave similarly to their invasive ductal carcinoma counterparts. Importantly, understanding GR signaling in individual breast cancer subtypes has potential clinical implications because of the recent development of highly selective GR non-steroidal ligands, which represent a therapeutic approach for modulating GR activity systemically.},
}
@article {pmid38699697,
year = {2024},
author = {Geng, J and Jinli, S and Guo, W and Li, H and Dan, Y and Gao, Y},
title = {Expression and clinical significance of CA125, CA153 and CEA in nipple discharge of breast cancer patients.},
journal = {Journal of medical biochemistry},
volume = {43},
number = {2},
pages = {234-242},
pmid = {38699697},
issn = {1452-8258},
abstract = {BACKGROUND: It is an important clinical means to identify benign and malignant breast diseases caused by nipple discharge through the detection and analysis of components in nipple discharge. This study was aimed to test the expression and clinical significance of carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carcinoembryonic antigen (CEA) in nipple discharge of breast cancer patients.<br><br>METHODS: From January 2017 to December 2018, 86 patients with invasive ductal carcinoma of the breast with nipple discharge (breast cancer group) and 50 patients with ordinary breast duct hyperplasia with nipple discharge (benign control group) were selected, and the levels of CA125, CA153 and CEA in nipple discharge and serum were detected by electrochemiluminescence immunoassay.},
}
@article {pmid38695948,
year = {2024},
author = {Agreda-Castañeda, F and Freixa-Sala, R and Franco, M and Bultó-Gonzalvo, R and Areal-Calama, J},
title = {Predictive factors of post-HoLEP incontinence: differences between stress and urgency urinary incontinence.},
journal = {World journal of urology},
volume = {42},
number = {1},
pages = {281},
pmid = {38695948},
issn = {1433-8726},
mesh = {Humans ; Male ; *Urinary Incontinence, Stress/surgery/epidemiology ; *Urinary Incontinence, Urge/epidemiology/etiology ; Aged ; Middle Aged ; *Prostatectomy/methods ; Postoperative Complications/epidemiology/etiology ; Retrospective Studies ; Risk Factors ; Prostatic Hyperplasia/surgery/complications ; Urodynamics/physiology ; Age Factors ; },
abstract = {INTRODUCTION: The analysis of post-HoLEP urinary incontinence (UI) has traditionally focused on stress UI. Our aim is to evaluate the factors associated with stress and urgency UI in the first month after the surgery.<br><br>METHODS: Data were obtained from patients who underwent HoLEP by the same experienced surgeon. UI was evaluated at one month and at 6 months after the surgery. Three groups were defined: continent patients, patients with pure urgency UI and patients with stress or mixed UI. Preoperative, intraoperative, urodynamic and clinical variables were analyzed and compared between the three groups.<br><br>RESULTS: In total, 235 subjects were included. One month after the surgery, 156 (66.5%) were continent (group 1), 49 (20.8%) reported pure urgency UI (group 2), and 30 (12.7%) reported some level of stress UI (group 3). In Group 2, the factors associated with urgency UI in the univariate analysis were age, presurgical urgency UI, having diabetes or hypertension. In Group 3, age, prostatic volume, preoperative PSA, time of enucleation, weight of the resection in grams, having an IDC or being diabetic were significant in the univariate analysis. In the multivariate analysis, age predicts both types of UI, while prostatic volume and having an IDC predict stress or mixed UI.<br><br>CONCLUSION: In the first month post-HoLEP, age is a predictive factor of urgency UI and stress UI. In addition, prostatic volume and the presence of an indwelling urinary catheter are predictive factors of stress UI.},
}
@article {pmid38695332,
year = {2024},
author = {Iradukunda, Y and Kang, JY and Zhao, XB and Fu, XK and Nsanzamahoro, S and Ha, W and Shi, YP},
title = {Triple Sensing Modes for Triggered β-Galactosidase Activity Assays Based on Kaempferol-Deduced Silicon Nanoparticles and Biological Imaging of MCF-7 Breast Cancer Cells.},
journal = {ACS applied bio materials},
volume = {7},
number = {5},
pages = {3154-3163},
doi = {10.1021/acsabm.4c00185},
pmid = {38695332},
issn = {2576-6422},
mesh = {Female ; Humans ; *beta-Galactosidase/metabolism ; Biocompatible Materials/chemistry/pharmacology/chemical synthesis ; *Breast Neoplasms/diagnosis/pathology ; Colorimetry ; *Kaempferols/chemistry/pharmacology ; MCF-7 Cells ; Molecular Structure ; *Nanoparticles/chemistry ; Particle Size ; *Silicon/chemistry ; },
abstract = {β-Galactosidase (β-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor β-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine β-Gala activity effectively. Via the sensing performance, the catalytic activity of β-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-β-d-galactopyranoside (KOβDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing β-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of β-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.},
}
@article {pmid38684889,
year = {2024},
author = {Khani, S and Topel, H and Kardinal, R and Tavanez, AR and Josephrajan, A and Larsen, BDM and Gaudry, MJ and Leyendecker, P and Egedal, NM and Güller, AS and Stanic, N and Ruppert, PMM and Gaziano, I and Hansmeier, NR and Schmidt, E and Klemm, P and Vagliano, LM and Stahl, R and Duthie, F and Krause, JH and Bici, A and Engelhard, CA and Gohlke, S and Frommolt, P and Gnad, T and Rada-Iglesias, A and Pradas-Juni, M and Schulz, TJ and Wunderlich, FT and Pfeifer, A and Bartelt, A and Jastroch, M and Wachten, D and Kornfeld, JW},
title = {Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.},
journal = {Nature metabolism},
volume = {6},
number = {6},
pages = {1053-1075},
pmid = {38684889},
issn = {2522-5812},
support = {675014//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; PROTEOFIT//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; 33444//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 28416//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; A/12/97620//Deutscher Akademischer Austauschdienst (German Academic Exchange Service)/ ; TRR333/1 (450149205)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 1454 (432325352)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; TRR83//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SPP1926//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SPP1726//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; FOR2743//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB1123-B10//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 676-2021//European Molecular Biology Organization (EMBO)/ ; },
mesh = {*Adenylyl Cyclases/metabolism/genetics ; *Adipose Tissue, Brown/metabolism ; Animals ; Mice ; *Cold Temperature ; Male ; Humans ; Thermogenesis/genetics ; Energy Metabolism ; Cyclic AMP/metabolism ; Mice, Knockout ; },
abstract = {Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5' truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.},
}
@article {pmid38684702,
year = {2024},
author = {de Oliveira, RM and Paiva, MUB and Picossi, CRC and Paiva, DVN and Ricart, CAO and Ruperez, FJ and Barbas, C and Atik, FA and Martins, AMA},
title = {Metabolomic insights in advanced cardiomyopathy of chronic chagasic and idiopathic patients that underwent heart transplant.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {9810},
pmid = {38684702},
issn = {2045-2322},
support = {EADS CASA 002/DCTA-COPAC/2014//Airbus Spain/ ; },
mesh = {Humans ; *Heart Transplantation ; Male ; Female ; Middle Aged ; *Chagas Cardiomyopathy/metabolism/blood ; *Metabolomics/methods ; *Cardiomyopathy, Dilated/metabolism/surgery/blood ; Adult ; Metabolome ; Heart Failure/metabolism/etiology ; Aged ; Chronic Disease ; Gas Chromatography-Mass Spectrometry ; },
abstract = {Heart failure (HF) studies typically focus on ischemic and idiopathic heart diseases. Chronic chagasic cardiomyopathy (CCC) is a progressive degenerative inflammatory condition highly prevalent in Latin America that leads to a disturbance of cardiac conduction system. Despite its clinical and epidemiological importance, CCC molecular pathogenesis is poorly understood. Here we characterize and discriminate the plasma metabolomic profile of 15 patients with advanced HF referred for heart transplantation - 8 patients with CCC and 7 with idiopathic dilated cardiomyopathy (IDC) - using gas chromatography/quadrupole time-of-flight mass spectrometry. Compared to the 12 heart donor individuals, also included to represent the control (CTRL) scenario, patients with advanced HF exhibited a metabolic imbalance with 21 discriminating metabolites, mostly indicative of accumulation of fatty acids, amino acids and important components of the tricarboxylic acid (TCA) cycle. CCC vs. IDC analyses revealed a metabolic disparity between conditions, with 12 CCC distinctive metabolites vs. 11 IDC representative metabolites. Disturbances were mainly related to amino acid metabolism profile. Although mitochondrial dysfunction and loss of metabolic flexibility may be a central mechanistic event in advanced HF, metabolic imbalance differs between CCC and IDC populations, possibly explaining the dissimilar clinical course of Chagas' patients.},
}
@article {pmid38680708,
year = {2024},
author = {Shaghaghi Torkdari, Z and Khalaj-Kondori, M and Hosseinpour Feizi, MA},
title = {Plasma Circulating Terminal Differentiation-Induced Non-Coding RNA Serves as a Biomarker in Breast Cancer.},
journal = {International journal of hematology-oncology and stem cell research},
volume = {18},
number = {1},
pages = {1-6},
pmid = {38680708},
issn = {2008-3009},
abstract = {Background: Breast cancer is identified as the most common malignancy and cause of cancer-related death worldwide. Compared with healthy controls, this study evaluated the expression level and diagnostic power of lncRNA plasma TINCR in breast cancer patients. Materials and Methods: Fifty-eight women diagnosed with invasive ductal carcinoma and fifty healthy age- matched controls were included in the study. TRIzol[®] LS regent was used to isolate the total RNA from the whole plasma. Total RNA was converted to cDNA using Prime Script[TM] RT reagent kit and the expression levels of TINCR were quantified by qRT-PCR. Results: Low levels of TINCR lncRNA were observed in the plasma of breast cancer patients compared with control subjects. Plasma TINCR level was also positively correlated with the diagnostic age of breast cancer patients. Conclusion: A low level of plasma TINCR could discriminate breast cancer patients from healthy control subjects.},
}
@article {pmid38678597,
year = {2024},
author = {Rostami, B and Kahrizi, S and Ghorbani Yekta, B and Ghadyani, R and Keramatinia, A and Hoseini, SJ and Karima, S and Nikzamir, AR and Mansouri, N and Chen, M and Movafagh, A},
title = {Correlation of IDH1 gene expression error in breast tumor biopsy in patients with invasive ductal carcinoma.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
volume = {70},
number = {4},
pages = {242-247},
doi = {10.14715/cmb/2024.70.4.38},
pmid = {38678597},
issn = {1165-158X},
mesh = {Humans ; *Isocitrate Dehydrogenase/genetics ; Female ; *Breast Neoplasms/genetics/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Gene Expression Regulation, Neoplastic ; Adult ; Biopsy ; RNA, Messenger/genetics/metabolism ; Aged ; },
abstract = {One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000). This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.},
}
@article {pmid38677859,
year = {2024},
author = {de Souza, IC and Langer, FW},
title = {Post-radiation angiosarcoma of the breast in a patient with a history of invasive ductal carcinoma.},
journal = {Lancet (London, England)},
volume = {403},
number = {10437},
pages = {1681-1682},
doi = {10.1016/S0140-6736(24)00688-3},
pmid = {38677859},
issn = {1474-547X},
mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/radiotherapy ; *Carcinoma, Ductal, Breast/radiotherapy ; *Hemangiosarcoma/etiology ; *Neoplasms, Radiation-Induced/etiology ; Neoplasms, Second Primary/etiology ; },
}
@article {pmid38672600,
year = {2024},
author = {Yousef, YA and Mohammad, M and Khalil, H and Khouri, T and Alsweiti, R and Khzouz, J and Abu Laban, D and Jaradat, I and Ibrahimi, AK and Al-Ibraheem, A and Masri, MA and AlNawiaseh, I and Abdel-Razeq, H},
title = {Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome.},
journal = {Cancers},
volume = {16},
number = {8},
pages = {},
pmid = {38672600},
issn = {2072-6694},
abstract = {BACKGROUND: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients.<br><br>METHODS: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed.<br><br>RESULTS: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis.<br><br>CONCLUSIONS: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis.},
}
@article {pmid38656713,
year = {2024},
author = {Kikuchi, M and Miyabe, R and Matsushima, H and Kita, H and Kobayashi, J and Ando, T and Atsuta, K and Shintani, T},
title = {Tumor lysis syndrome following letrozole for locally advanced breast cancer: a case report.},
journal = {Surgical case reports},
volume = {10},
number = {1},
pages = {100},
pmid = {38656713},
issn = {2198-7793},
abstract = {BACKGROUND: Letrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole.<br><br>CASE PRESENTATION: An 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died.<br><br>CONCLUSIONS: Although TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution.},
}
@article {pmid38644311,
year = {2024},
author = {Satoh, E and Innami, Y and Uehira, D and Yonekura, K and Murakata, A and Ohinata, R and Toyofuku, Y and Tanami, H and Osanai, T and Sugano, N and Sakoma, T},
title = {[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {51},
number = {4},
pages = {427-429},
pmid = {38644311},
issn = {0385-0684},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy ; *Lung Neoplasms/secondary/drug therapy ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Time Factors ; Carcinoma, Ductal, Breast/secondary/therapy/drug therapy ; Mastectomy ; },
abstract = {We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer(invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).},
}
@article {pmid38638844,
year = {2024},
author = {Zhou, H and Liu, D and Chen, L and Zhang, Y and Zhao, X and Ge, Y and Liu, M and Kong, T},
title = {Metastasis to the bladder from primary breast cancer: A case report and literature review.},
journal = {Oncology letters},
volume = {27},
number = {6},
pages = {249},
pmid = {38638844},
issn = {1792-1082},
abstract = {Breast cancer is the most prevalent malignant tumor affecting women and represents the leading cause of female cancer-related mortality worldwide. Although distant organ metastasis accounts for the majority of breast cancer-related deaths, reports on bladder metastasis are limited in the existing literature. The present study describes the case of a patient with bladder metastasis originating from breast cancer. In addition, the present study also provides a review of 54 cases of similar disease that have been documented in the currently available literature. The literature review aims to elucidate the clinicopathological characteristics and therapeutic approaches for such conditions. The median time from breast cancer diagnosis to bladder metastasis was found to be 5.6 years (range, 0-28 years). The origin of the bladder metastases was predominantly invasive ductal carcinoma (IDC) accounting for 52.3% of cases, followed by invasive lobular carcinoma, accounting for 40.9% of cases. The pathology in the primary tumor was the same as the pathology of the bladder metastases in all cases. There was an 88.9% concordance rate for estrogen receptor status, while the progesterone receptor status was 83.3% and the human epidermal growth factor receptor 2 expression status was 100%. The primary initial symptoms included urinary system manifestations, such as increased frequency, urgency, dysuria, urinary incontinence, nocturia and gross hematuria. For the cystoscopic examination, the predominant findings were bladder wall thickening or masses, along with ureteral orifice masses. Overall, the present study demonstrated that the occurrence of bladder metastasis often follows the metastasis of other organs, with IDC being the most prevalent subtype. The pathological characteristics between the primary tumor and bladder metastasis exhibit a high degree of concordance.},
}
@article {pmid38624259,
year = {2024},
author = {Petrakis, IL and Meshberg-Cohen, S and Nich, C and Kelly, MM and Claudio, T and Jane, JS and Pisani, E and Ralevski, E},
title = {Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine.},
journal = {The American journal on addictions},
volume = {33},
number = {5},
pages = {525-533},
doi = {10.1111/ajad.13557},
pmid = {38624259},
issn = {1521-0391},
support = {1 I01 CX001517-01//VA MERIT grant, Division of Clinical Science Research and Development/ ; },
mesh = {Humans ; *Stress Disorders, Post-Traumatic/therapy/drug therapy/psychology/complications ; *Buprenorphine/therapeutic use ; *Veterans/psychology ; Male ; *Opioid-Related Disorders/drug therapy/therapy/psychology/complications ; *Cognitive Behavioral Therapy/methods ; *Opiate Substitution Treatment/methods ; Middle Aged ; Female ; Counseling/methods ; Adult ; Narcotic Antagonists/therapeutic use ; },
abstract = {BACKGROUND AND OBJECTIVES: There are high rates of comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD). Evidence-based trauma-focused psychotherapies such as Cognitive Processing Therapy (CPT) are a first-line treatment for PTSD. Veterans with OUD are treated primarily in substance use disorder (SUD) clinics where the standard of care is drug counseling; they often do not have access to first-line PTSD treatments. This study tested whether CPT can be conducted safely and effectively in veterans with comorbid OUD treated with buprenorphine.<br><br>METHODS: This 12-week, 2-site, randomized clinical trial (RCT) included open-label randomization to two groups: (a) CPT versus (b) Individual Drug Counselling (IDC) in veterans with PTSD and comorbid OUD who were maintained on buprenorphine (N&#x2009;=&#x2009;38).<br><br>RESULTS: Veterans randomized to either IDC (n&#x2009;=&#x2009;18) or CPT (n&#x2009;=&#x2009;20) showed a significant reduction in self-reported PTSD symptoms over time as measured by the PTSD checklist (PCL-5) but there were no treatment group differences; there was some indication that reduction in PTSD symptoms in the CPT group were sustained in contrast to the IDC group. Recruitment was significantly impacted by COVID-19 pandemic, so this study serves as a proof-of-concept pilot study.<br><br>DISCUSSION AND CONCLUSIONS: Veterans with OUD and PTSD can safely and effectively participate in evidence-based therapy for PTSD; further work should confirm that trauma-focused treatment may be more effective in leading to sustained remission of PTSD symptoms than drug counseling.<br><br>SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate CPT for PTSD in the context of buprenorphine treatment for OUD.},
}
@article {pmid38621672,
year = {2024},
author = {Sánchez-Dávila, JN and Verástegui, EL and Peña-Nieves, A and Allende-Pérez, SR},
title = {Integration of the geriatric palliative care in oncological care of elderly patient with cancer.},
journal = {Palliative &amp; supportive care},
volume = {22},
number = {4},
pages = {792-800},
doi = {10.1017/S1478951524000294},
pmid = {38621672},
issn = {1478-9523},
mesh = {Humans ; Aged ; *Palliative Care/methods/standards ; Aged, 80 and over ; Female ; Male ; *Neoplasms/complications/therapy ; *Geriatrics/methods ; Geriatric Assessment/methods ; },
abstract = {OBJECTIVES: The objective of this article is to describe the profile of the population attended to by the palliative geriatrics clinic and to evaluate the symptomatic control derived from the care provided.<br><br>METHODS: During 2017 a model based on a holistic approach was implemented, in this model the team geriatric palliative care plays a fundamental role by being part of the palliative care team and functioning as a liaison with the oncology team and other required services. We outlined the profile of 100 patients aged 70 and older seen between 2017 and 2019 at our geriatric palliative care clinic. Descriptive statistics were used. In addition, the symptoms and the care clinic model effect on the symptomatic control were analyzed, as well as the complexity of patients in palliative care with IDC-Pal.<br><br>RESULTS: The patients median age was 83.5 years. Patients were classified by type of management: 47% within the supportive care group and 53% with palliative care only; 58% had metastatic disease and 84% presented at least 1 comorbidity. Frailty was observed in 78% and a Karnofsky scale of 60 or less was observed in 59% of the overall population.<br><br>SIGNIFICANCE OF RESULTS: Elderly cancer patients have a complex profile and may have multiple needs. Integrating geriatric palliative care can help to provide better and personalized care along with symptomatic control. Further studies are required to establish the ideal care model for these patients. Importantly, a personalized treatment with a geriatric palliative care specialist is a key element.},
}
@article {pmid38592540,
year = {2024},
author = {Rukhsana, and Supty, AT and Hussain, M and Lee, Y},
title = {STK3 higher expression association with clinical characteristics in intrinsic subtypes of breast cancer invasive ductal carcinoma patients.},
journal = {Breast cancer research and treatment},
volume = {206},
number = {1},
pages = {119-129},
pmid = {38592540},
issn = {1573-7217},
support = {2022R1F1A1069631//National Research Foundation of Korea/ ; },
mesh = {Aged ; Female ; Humans ; Middle Aged ; *Biomarkers, Tumor/genetics ; *Breast Neoplasms/genetics/pathology/mortality/metabolism ; *Carcinoma, Ductal, Breast/genetics/pathology/mortality/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Kaplan-Meier Estimate ; Neoplasm Staging ; Prognosis ; Protein Serine-Threonine Kinases/genetics/metabolism ; *Serine-Threonine Kinase 3/analysis/genetics ; },
abstract = {PURPOSE: STK3 has a central role in maintaining cell homeostasis, proliferation, growth, and apoptosis. Previously, we investigated the functional link between STK3/MST2, and estrogen receptor in MCF-7 breast cancer cells. To expand the investigation, this study evaluated STK3's higher expression and associated genes in breast cancer intrinsic subtypes using publicly available data.<br><br>METHODS: The relationship between clinical pathologic features and STK3 high expression was analyzed using descriptive and multivariate analysis.<br><br>RESULTS: Increased STK3 expression in breast cancer was significantly associated with higher pathological cancer stages, and a different expression level was observed in the intrinsic subtypes of breast cancer. Kaplan-Meier analysis showed that breast cancer with high STK3 had a lower survival rate in IDC patients than that with low STK3 expression (p&#x2009;<&#x2009;0.05). The multivariate analysis unveiled a strong&#xa0;correlation between STK3 expression and the survival rate among IDC patients, demonstrating hazard ratios for lower expression. In the TCGA dataset, the hazard ratio was 0.56 (95% CI 0.34-0.94, p&#x2009;=&#x2009;0.029) for patients deceased with tumor, and 0.62 (95% CI 0.42-0.92, p&#x2009;=&#x2009;0.017) for all deceased patients. Additionally, in the METABRIC dataset, the hazard ratio was 0.76 (95% CI 0.64-0.91, p&#x2009;=&#x2009;0.003) for those deceased with tumor. From GSEA outcomes 7 gene sets were selected based on statistical significance (FDR&#x2009;<&#x2009;0.25 and p&#x2009;<&#x2009;0.05). Weighted Sum model (WSM) derived top 5% genes also have higher expression in basal and lower in luminal A in association with STK3.<br><br>CONCLUSION: By introducing a novel bioinformatics approach that combines GSEA and WSM, the study successfully identified the top 5% of genes associated with higher expression of STK3.},
}
@article {pmid38578876,
year = {2024},
author = {Rodriguez, GF and Shah, A and Maderal, AD},
title = {Telangiectasias induced by combination tucatinib and ado-trastuzumab emtansine in a patient with metastatic breast cancer.},
journal = {Breast disease},
volume = {43},
number = {1},
pages = {61-64},
pmid = {38578876},
issn = {1558-1551},
mesh = {Female ; Humans ; Aged ; Ado-Trastuzumab Emtansine/therapeutic use ; *Breast Neoplasms/pathology ; Trastuzumab/adverse effects ; Quinazolines/therapeutic use ; Receptor, ErbB-2/genetics/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Oxazoles ; *Pyridines ; },
abstract = {BACKGROUND: Tucatinib is a tyrosine kinase inhibitor currently used in salvage therapy for human epidermal growth factor receptor 2 (HER2)-positive breast and colorectal cancer. The use of tucatinib alone or in combination with ado-trastuzumab emtansine (T-DM1) in the treatment of advanced HER2-positive cancers is rapidly expanding.<br><br>OBJECTIVE/METHODS: We report the case of a 66-year-old female who presented to the dermatology clinic with a one-year history of widespread telangiectasias that began after initiation of combination chemotherapy with tucatinib and T-DM1 for metastatic HER2-positive invasive ductal carcinoma.<br><br>RESULTS: The patient's lesions regressed upon cessation of combination therapy and reappeared in the setting of tucatinib re-initiation, with gradual improvement over the following four months following electrocautery to the affected regions.<br><br>CONCLUSIONS: We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.},
}
@article {pmid38577141,
year = {2024},
author = {Sukhija, S and Purohit, P and Pareek, P and Garg, PK and Vishnoi, JR and Elhence, PA and Varthya, SB and Sharma, P and Ambwani, S and Charan, J},
title = {Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.},
journal = {Indian journal of clinical biochemistry : IJCB},
volume = {39},
number = {2},
pages = {214-220},
pmid = {38577141},
issn = {0970-1915},
abstract = {Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m[2]), Cyclophosphamide (600 mg/m[2]) with or without Taxane (75-175 mg/m[2]) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.},
}
@article {pmid38576929,
year = {2024},
author = {Jamal, O and Makhchoune, M and Laidi, A and Misbahi, T and Haouas, MY and Chellaoui, A and Bertal, A and Hilmani, S and Ibahiouine, K and Naja, A and Lakhder, A},
title = {Rupture of a dermoid cyst in the subarachnoid space: a case report.},
journal = {Annals of medicine and surgery (2012)},
volume = {86},
number = {4},
pages = {2366-2369},
pmid = {38576929},
issn = {2049-0801},
abstract = {INTRODUCTION AND IMPORTANCE: Intracranial dermoid cysts (IDC) are defined as rare, slow-growing cystic congenital neoplasms. Rupture of an intracranial dermoid cyst occurs rarely and most often spontaneously and results in potentially serious symptoms.<br><br>CASE PRESENTATION: A39-year-old female, with mechanical prosthetic heart valve presented with history of headache for 10 months and generalized tonicoclonic seizures. On the admission, the patient had a normal neurological and cranial nerve exam. The authors performed a computed tomography of the brain, The MRI could not be performed because of the presence of the prosthetic valve, revealed rupture of the dermoid cyst in the bilateral subarachnoid spaces. The patient underwent a large temporal craniotomy and the tumour was well exposed and completely removed without incident, the histopathological examination concludes to dermoid cyst, the patient recovered well from surgery.<br><br>CLINICAL DISCUSSION: Rupture is a very rare phenomenon. there are about 60 cases reported in the literature. the contents of the cyst disseminate into the subarachnoid and ventricular spaces in the event of rupture. A variety of clinical symptoms is usually caused. The mechanism of spontaneous rupture of the dermoid cyst is unclear. Among the proposed mechanisms is a rapid expansion of the cyst. Complete surgical resection of dermoid cysts is the only effective treatment for the prevention of recurrences and/or complications.<br><br>CONCLUSION: Rupture of an intracranial dermoid cyst is associated with significant morbidity and mortality, although it remains a rare phenomenon. Surgical excision should be considered as soon as the diagnosis is made in order to prevent more severe intracranial complication.},
}
@article {pmid38571894,
year = {2024},
author = {Maiti, S and Nayak, S and Hebbar, KD and Pendem, S},
title = {Differentiation of invasive ductal and lobular carcinoma of the breast using MRI radiomic features: a pilot study.},
journal = {F1000Research},
volume = {13},
number = {},
pages = {91},
pmid = {38571894},
issn = {2046-1402},
mesh = {Female ; Humans ; *Carcinoma, Lobular/diagnostic imaging/pathology ; Pilot Projects ; Retrospective Studies ; Radiomics ; *Breast Neoplasms/diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; },
abstract = {BACKGROUND: Breast cancer (BC) is one of the main causes of cancer-related mortality among women. For clinical management to help patients survive longer and spend less time on treatment, early and precise cancer identification and differentiation of breast lesions are crucial. To investigate the accuracy of radiomic features (RF) extracted from dynamic contrast-enhanced Magnetic Resonance Imaging (DCE MRI) for differentiating invasive ductal carcinoma (IDC) from invasive lobular carcinoma (ILC).<br><br>METHODS: This is a retrospective study. The IDC of 30 and ILC of 28 patients from Dukes breast cancer MRI data set of The Cancer Imaging Archive (TCIA), were included. The RF categories such as shape based, Gray level dependence matrix (GLDM), Gray level co-occurrence matrix (GLCM), First order, Gray level run length matrix (GLRLM), Gray level size zone matrix (GLSZM), NGTDM (Neighbouring gray tone difference matrix) were extracted from the DCE-MRI sequence using a 3D slicer. The maximum relevance and minimum redundancy (mRMR) was applied using Google Colab for identifying the top fifteen relevant radiomic features. The Mann-Whitney U test was performed to identify significant RF for differentiating IDC and ILC. Receiver Operating Characteristic (ROC) curve analysis was performed to ascertain the accuracy of RF in distinguishing between IDC and ILC.<br><br>RESULTS: Ten DCE MRI-based RFs used in our study showed a significant difference (p <0.001) between IDC and ILC. We noticed that DCE RF, such as Gray level run length matrix (GLRLM) gray level variance (sensitivity (SN) 97.21%, specificity (SP) 96.2%, area under curve (AUC) 0.998), Gray level co-occurrence matrix (GLCM) difference average (SN 95.72%, SP 96.34%, AUC 0.983), GLCM interquartile range (SN 95.24%, SP 97.31%, AUC 0.968), had the strongest ability to differentiate IDC and ILC.<br><br>CONCLUSIONS: MRI-based RF derived from DCE sequences can be used in clinical settings to differentiate malignant lesions of the breast, such as IDC and ILC, without requiring intrusive procedures.},
}
@article {pmid38570490,
year = {2024},
author = {Wang, J and Li, B and Luo, M and Huang, J and Zhang, K and Zheng, S and Zhang, S and Zhou, J},
title = {Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance.},
journal = {Signal transduction and targeted therapy},
volume = {9},
number = {1},
pages = {83},
pmid = {38570490},
issn = {2059-3635},
support = {82172344//National Natural Science Foundation of China (National Science Foundation of China)/ ; LY21H160039//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LGF21H030010//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; },
mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; *Breast Neoplasms/pathology ; Clinical Relevance ; Artificial Intelligence ; Gene Expression Profiling ; Tumor Microenvironment/genetics ; },
abstract = {Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.},
}
@article {pmid38554305,
year = {2024},
author = {Dogan, I and Khanmammadov, N and Ozkurt, S and Aydiner, A and Saip, P},
title = {Outcomes of the patients with metastatic male breast cancer.},
journal = {Journal of cancer research and therapeutics},
volume = {20},
number = {1},
pages = {98-102},
doi = {10.4103/jcrt.jcrt_1829_22},
pmid = {38554305},
issn = {1998-4138},
mesh = {Humans ; Male ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Breast Neoplasms, Male/drug therapy ; Retrospective Studies ; Receptor, ErbB-2 ; Disease-Free Survival ; *Breast Neoplasms/pathology ; Trastuzumab/therapeutic use ; Prognosis ; *Brain Neoplasms/drug therapy/secondary ; Kaplan-Meier Estimate ; },
abstract = {BACKGROUND: The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC).<br><br>METHODS: A retrospective analysis of the data of 28 patients was conducted. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognostic variables.<br><br>RESULTS: At the time of diagnosis, the median age was 57 years (range 26-86). The most prevalent pathological subtype was invasive ductal carcinoma (92.6%). HER2 positivity was 21.6% in patients, with estrogen and progesterone receptor positivity at 96.4% and 71.4%, respectively. Bone-75%, lung-39.3%, brain-21.4%, and adrenal gland-10.7% were the most prevalent metastatic sites. Trastuzumab-based chemotherapy was given to six patients. During the study period, 14 patients (or half) died. All patients had a median OS of 42.6 months (range: 21.6-63.7). The OS rates after 1, 3, and 5 years were 95.7%, 54.2%, and 36.6%, respectively. The number of metastatic locations (P = 0.045), brain metastasis (P = 0.033), and a history of regular alcohol intake (P = 0.008) were all shown to be statistically significant factors affecting OS in univariate analysis. However, multivariate analysis did not support the findings. In addition, we discovered that trastuzumab-based therapy and de-novo metastatic disease had no effect on OS for mMBC.<br><br>CONCLUSIONS: The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.},
}
@article {pmid38553788,
year = {2024},
author = {Dreindl, R and Bolsa-Ferruz, M and Fayos-Sola, R and Padilla Cabal, F and Scheuchenpflug, L and Elia, A and Amico, A and Carlino, A and Stock, M and Grevillot, L},
title = {Commissioning and clinical implementation of an independent dose calculation system for scanned proton beams.},
journal = {Journal of applied clinical medical physics},
volume = {25},
number = {5},
pages = {e14328},
pmid = {38553788},
issn = {1526-9914},
mesh = {Humans ; *Proton Therapy/methods ; *Radiotherapy Dosage ; *Radiotherapy Planning, Computer-Assisted/methods ; *Software ; *Organs at Risk/radiation effects ; Quality Assurance, Health Care/standards ; Phantoms, Imaging ; Radiotherapy, Intensity-Modulated/methods ; Calibration ; Neoplasms/radiotherapy ; Tomography, X-Ray Computed/methods ; Algorithms ; },
abstract = {PURPOSE: Experimental patient-specific QA (PSQA) is a time and resource-intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center.<br><br>METHODS: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined.<br><br>RESULTS: Beam model validation showed agreement of ranges within&#xa0;&#xb1;&#xa0;0.2&#xa0;mm, Bragg-Peak widths within&#xa0;&#xb1;&#xa0;0.1&#xa0;mm, and spot sizes at various air gaps within&#xa0;&#xb1;&#xa0;5% compared to physical measurements. Simulated dose in 2D reference fields deviated by&#xa0;-0.3%&#xa0;&#xb1;&#xa0;0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4&#xa0;&#xb1;&#xa0;0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2&#xa0;mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3&#xa0;mm. Root causes of GPR outliers, for example, implants were identified and evaluated.<br><br>CONCLUSION: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year.},
}
@article {pmid38539179,
year = {2024},
author = {Esmat, E and Haidary, AM and Saadaat, R and Rizvi, SN and Aleena, S and Haidari, M and Hofiani, SMS and Hussaini, N and Hakimi, A and Khairy, A and Abdul-Ghafar, J},
title = {Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {388},
pmid = {38539179},
issn = {1471-2407},
mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Afghanistan/epidemiology ; Biomarkers, Tumor/metabolism ; *Breast Neoplasms/epidemiology/genetics/metabolism ; Cross-Sectional Studies ; Hormones ; *Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Tertiary Care Centers ; },
abstract = {BACKGROUND: Breast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation.<br><br>METHODOLOGY: A cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years.<br><br>RESULTS: One hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58&#x2009;&#xb1;&#x2009;11.16&#xa0;years. Out of the total patients, 68 (56.7%) were above 40&#xa0;years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40-50&#xa0;years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases.<br><br>CONCLUSION: In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.},
}
@article {pmid38525191,
year = {2024},
author = {Lopez-Vazquez, P and Fernandez-Caggiano, M and Barge-Caballero, E and Barge-Caballero, G and Couto-Mallon, D and Grille-Cancela, Z and Blanco-Canosa, P and Paniagua-Martin, MJ and Enriquez-Vazquez, D and Vazquez-Rodriguez, JM and Domenech, N and Crespo-Leiro, MG},
title = {Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.},
journal = {Frontiers in cardiovascular medicine},
volume = {11},
number = {},
pages = {1349417},
pmid = {38525191},
issn = {2297-055X},
abstract = {INTRODUCTION AND OBJECTIVES: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies.<br><br>METHODS: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.<br><br>RESULTS: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.<br><br>CONCLUSION: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.},
}
@article {pmid38523415,
year = {2024},
author = {Seth, A and Slama, EM},
title = {Delayed Diagnosis of Inflammatory Breast Cancer Presenting as Acute Mastitis in a Patient One Month Postpartum.},
journal = {The American surgeon},
volume = {90},
number = {7},
pages = {1925-1927},
doi = {10.1177/00031348241241736},
pmid = {38523415},
issn = {1555-9823},
mesh = {Humans ; Female ; Adult ; *Mastitis/diagnosis/etiology ; *Inflammatory Breast Neoplasms/diagnosis ; *Delayed Diagnosis ; *Postpartum Period ; Diagnosis, Differential ; Acute Disease ; },
abstract = {Inflammatory breast cancer (IBC) is a rare yet aggressive form of invasive ductal carcinoma, with a poor prognosis and decreased 5-year survival rates. Characteristic findings for IBC include rapid onset of breast edema, peau d'orange appearance, and involvement of the breast skin. Additionally, diagnosis is confirmed with a skin punch biopsy. With such nonspecific features, IBC can be mistaken for benign etiologies, causing delays in diagnosis and treatment. This patient is a 44-year-old woman presenting with left breast swelling while concurrently breastfeeding. Following antibiotic treatment but no symptom resolution, the patient was referred out for further follow-up. Despite multiple imaging studies, suggesting benign findings, clinical suspicion prompted continued evaluation and finally diagnosis of triple-negative inflammatory breast cancer with distant metastases. Further awareness of the presentation of IBC and its mimicking of other disease processes such as mastitis is paramount to earlier detection and improved outcomes in future patients.},
}
@article {pmid38523303,
year = {2024},
author = {Yanase, Y and Bando, H and Sato, R and Matsuo, T and Ueda, A and Okazaki, M and Hashimoto, S and Iguchi-Manaka, A and Hara, H},
title = {Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.},
journal = {Journal of medical case reports},
volume = {18},
number = {1},
pages = {150},
pmid = {38523303},
issn = {1752-1947},
mesh = {Female ; Humans ; Adult ; Aged ; *Breast Neoplasms/drug therapy/pathology ; *Hypocalcemia/chemically induced ; Lapatinib/adverse effects ; Denosumab/adverse effects ; Calcium/therapeutic use ; *Bone Neoplasms/secondary ; },
abstract = {BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements.<br><br>CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole&#x2009;+&#x2009;lapatinib, trastuzumab emtansine, and lapatinib&#x2009;+&#x2009;capecitabine.<br><br>CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.},
}
@article {pmid38485913,
year = {2024},
author = {Heidari, N and Abbasi-Kenarsari, H and Niknam, B and Asadirad, A and Amani, D and Mirsanei, Z and Hashemi, SM},
title = {Exosomes Derived from Heat-shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells.},
journal = {Iranian journal of allergy, asthma, and immunology},
volume = {23},
number = {1},
pages = {97-106},
doi = {10.18502/ijaai.v23i1.14957},
pmid = {38485913},
issn = {1735-5249},
mesh = {*Exosomes ; Dendritic Cells ; Bone Marrow ; T-Lymphocytes ; Coculture Techniques ; Cell Differentiation ; },
abstract = {Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways. Exosomes derived from heat-shocked tumor cells (HS-TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS-TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS-TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that DCs treated with HS-TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS-TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS-TEXs could be used as a strategy to improve DC maturation and activation.},
}
@article {pmid38485644,
year = {2024},
author = {Shi, Y and Wang, H and Golijanin, B and Amin, A and Lee, J and Sikov, M and Hyams, E and Pareek, G and Carneiro, BA and Mega, AE and Lagos, GG and Wang, L and Wang, Z and Cheng, L},
title = {Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.},
journal = {Urologic oncology},
volume = {42},
number = {5},
pages = {144-154},
doi = {10.1016/j.urolonc.2024.01.037},
pmid = {38485644},
issn = {1873-2496},
mesh = {Male ; Humans ; Prostate/pathology ; *Adenocarcinoma/pathology ; *Prostatic Neoplasms/genetics/therapy/pathology ; Cell Proliferation ; },
abstract = {Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.},
}
@article {pmid38471320,
year = {2024},
author = {Niu, Q and Li, H and Du, L and Wang, R and Lin, J and Chen, A and Jia, C and Jin, L and Li, F},
title = {Development of a Multi-Parametric ultrasonography nomogram for prediction of invasiveness in ductal carcinoma in situ.},
journal = {European journal of radiology},
volume = {175},
number = {},
pages = {111415},
doi = {10.1016/j.ejrad.2024.111415},
pmid = {38471320},
issn = {1872-7727},
mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/pathology ; *Nomograms ; *Neoplasm Invasiveness/diagnostic imaging ; *Ultrasonography, Mammary/methods ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Aged ; *Elasticity Imaging Techniques/methods ; Adult ; Prospective Studies ; Contrast Media ; Risk Factors ; Predictive Value of Tests ; Sensitivity and Specificity ; Risk Assessment ; },
abstract = {OBJECTIVE: To investigate the independent risk variables associated with the potential invasiveness of ductal carcinoma in situ (DCIS) on multi-parametric ultrasonography, and further construct a nomogram for risk assessment.<br><br>METHODS: Consecutive patients from January 2017 to December 2022 who were suspected of having ductal carcinoma in situ (DCIS) based on magnetic resonance imaging or mammography were prospectively enrolled. Histopathological findings after surgical resection served as the gold standard. Grayscale ultrasound, Doppler ultrasound, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) examinations were preoperative performed. Binary logistic regression was used for multifactorial analysis to identify independent risk factors from multi-parametric ultrasonography. The correlation between independent risk factors and pathological prognostic markers was analyzed. The predictive efficacy of DCIS associated with invasiveness was assessed by logistic analysis, and a nomogram was established.<br><br>RESULTS: A total of 250 DCIS lesions were enrolled from 249 patients, comprising 85 pure DCIS and 165 DCIS with invasion (DCIS-IDC), of which 41 exhibited micro-invasion. The multivariate analysis identified independent risk factors for DCIS with invasion on multi-parametric ultrasonography, including image size (>2cm), Doppler ultrasound RI (&#x2265;0.72), SWE's Emax (&#x2265;66.4&#xa0;kPa), hyper-enhancement, centripetal enhancement, increased surrounding vessel, and no contrast agent retention on CEUS. These factors correlated with histological grade, Ki-67, and human epidermal growth factor receptor 2 (HER2) (P&#xa0;<&#xa0;0.1). The multi-parametric ultrasound approach demonstrated good predictive performance (sensitivity 89.7&#xa0;%, specificity 73.8&#xa0;%, AUC 0.903), surpassing single US modality or combinations with SWE or CEUS modalities. Utilizing these factors, a predictive nomogram achieved a respectable performance (AUC of 0.889) for predicting DCIS with invasion. Additionally, a separate nomogram for predicting DCIS with micro-invasion, incorporating independent risk factors such as RI (&#x2265;0.72), SWE's Emax (&#x2265;65.2&#xa0;kPa), and centripetal enhancement, demonstrated an AUC of 0.867.<br><br>CONCLUSION: Multi-parametric ultrasonography demonstrates good discriminatory ability in predicting both DCIS with invasion and micro-invasion through the analysis of lesion morphology, stiffness, neovascular architecture, and perfusion. The use of a nomogram based on ultrasonographic images offers an intuitive and effective method for assessing the risk of invasion in DCIS. Although the nomogram is not currently considered a clinically applicable diagnostic tool due to its AUC being below the threshold of 0.9, further research and development are anticipated to yield positive outcomes and enhance its viability for clinical utilization.},
}
@article {pmid38461375,
year = {2024},
author = {Turhan, &#x15e; and Sultan, DAO and Altuner, EM and Kurnaz, A and Bakır, TK and Altamemi, RAA},
title = {Determination of radon concentrations and physicochemical parameters of non-alcoholic carbonated beverages consumed in Türkiye and assessment of radiological health risk.},
journal = {International journal of environmental health research},
volume = {34},
number = {11},
pages = {3836-3846},
doi = {10.1080/09603123.2024.2327530},
pmid = {38461375},
issn = {1369-1619},
mesh = {*Radon/analysis ; Humans ; *Carbonated Beverages/analysis ; Risk Assessment ; Turkey ; },
abstract = {The strategy for controlling the existence of radionuclides in drinking water depends upon an individual dose criterion (IDC) of 0.1 mSv/y, which represents a very low level of risk that is not expected to cause any identified adverse health effects. Radon gas, considered a carcinogenic radionuclide, can dissolve and accumulate in drinking water. Non-alcoholic carbonated beverages (NACBs), which mainly contain drinking water, phosphoric acid, citric acid, caffeine, and sugar, represent one of the most consumed groups worldwide and in Türkiye. In this study, the radon activity concentration and some physicochemical characteristics of 45 NACB samples from 24 most preferred commercial brands in Türkiye were determined to assess the radiological health risk associated with the ingestion of these samples. Radon activity concentrations measured in NACB samples using the AlphaGUARD radon analyzer ranged from 22.8 ± 0.7 to 54.9 ± 1.7 mBq/L. The pH, conductivity, total dissolved solids, and brix values in NACB samples ranged from 2.31 to 7.29, 401 to 3281 μSv/cm, 355 to 2453 mg/L, and 0.10 to 12.95%, respectively. Total (ingestion and inhalation) annual effective doses and the corresponding excess lifetime cancer risks estimated for adults to assess the radiological health risk are significantly below the IDC and advised safety limit (10[-3]), respectively.},
}
@article {pmid38451627,
year = {2024},
author = {Saeed, U and Uppal, R and Khan, AA and Uppal, MR and Piracha, ZZ and Uppal, SR},
title = {Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {84},
number = {},
pages = {e265550},
doi = {10.1590/1519-6984.265550},
pmid = {38451627},
issn = {1678-4375},
mesh = {Humans ; *COVID-19/diagnosis ; Cross-Sectional Studies ; Nasopharynx/virology ; Pakistan ; Pandemics ; *SARS-CoV-2/genetics ; *Reagent Kits, Diagnostic ; Sensitivity and Specificity ; },
abstract = {Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.},
}
@article {pmid38432595,
year = {2024},
author = {Chuang, ML},
title = {Analyzing key elements of breathing patterns, deriving remaining variables, and identifying cutoff values in individuals with chronic respiratory disease and healthy subjects.},
journal = {Respiratory physiology &amp; neurobiology},
volume = {324},
number = {},
pages = {104242},
doi = {10.1016/j.resp.2024.104242},
pmid = {38432595},
issn = {1878-1519},
mesh = {Humans ; Healthy Volunteers ; Respiration ; Exhalation ; *Respiration Disorders ; *Pulmonary Disease, Chronic Obstructive ; *Lung Diseases, Interstitial ; },
abstract = {BACKGROUND: Pulmonary physiology encompasses intricate breathing patterns (BPs), characterized by breathing frequency (Bf), volumes, and flows. The complexities intensify in the presence of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), especially during exercise. This study seeks to identify pivotal factors driving changes among these variables and establish cutoff values, comparing their efficacy in differentiating BPs to traditional methods, specifically a breathing reserve (BR) of 30% and a Bf of 50 bpm.<br><br>METHODS: Screening 267 subjects revealed 23 with ILD, 126 with COPD, 33 healthy individuals, and the exclusion of 85 subjects. Lung function tests and ramp-pattern cardiopulmonary exercise testing (CPET) were conducted, identifying crucial BP elements. Changes were compared between groups at peak exercise. The area under the receiver operating characteristic curve (AUC) analysis determined cutoff values.<br><br>RESULTS: Inspiratory time (TI) remained constant at peak exercise for all subjects (two-group comparisons, all p=NS). Given known differences in expiratory time (TE) and tidal volume (VT) among ILD, COPD, and healthy states, constant TI could infer patterns for Bf, total breathing cycle time (TTOT=60/Bf), I:E ratio, inspiratory duty cycle (IDC, TI/TTOT), rapid shallow breathing index (Bf/VT), tidal inspiratory and expiratory flows (VT/TI and VT/TE), and minute ventilation (V&#x307;E=Bf&#xd7;VT) across conditions. These inferences aligned with measurements, with potential type II errors causing inconsistencies. RSBI of 23 bpm/L and VT/TI of 104&#x202f;L/min may differentiate ILD from control, while V&#x307;E of 54&#x202f;L/min, BR of 30%, and VT/TE of 108 may differentiate COPD from control. BR of 21%, TE of 0.99&#x202f;s, and IDC of .45 may differentiate ILD from COPD. The algorithm outperformed traditional methods (AUC 0.84-0.91 versus 0.59-0.90).<br><br>CONCLUSION: The quasi-fixed TI, in conjunction with TE and VT, proves effective in inferring time-related variables of BPs. The findings have the potential to significantly enhance medical education in interpreting cardiopulmonary exercise testing. Moreover, the study introduces a novel algorithm for distinguishing BPs among individuals with ILD, COPD, and those who are healthy.},
}
@article {pmid38417222,
year = {2024},
author = {Hu, J and Chen, X and Sun, F and Liu, L and Liu, L and Yang, Z and Zhang, H and Yu, Z and Zhao, R and Wang, Y and Liu, H and Yang, X and Sun, F and Han, B},
title = {Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.},
journal = {Neoplasia (New York, N.Y.)},
volume = {50},
number = {},
pages = {100983},
pmid = {38417222},
issn = {1476-5586},
mesh = {Humans ; Male ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; China ; Mutation ; Prostate/pathology ; *Prostatic Neoplasms/genetics/pathology ; *Proto-Oncogene Proteins B-raf/genetics ; },
abstract = {While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAF[K601E] and BRAF[L597R] exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.},
}
@article {pmid38416170,
year = {2024},
author = {Maggi, G and Loayza, F and Vitale, C and Santangelo, G and Obeso, I},
title = {Anatomical correlates of apathy and impulsivity co-occurrence in early Parkinson's disease.},
journal = {Journal of neurology},
volume = {271},
number = {5},
pages = {2798-2809},
pmid = {38416170},
issn = {1432-1459},
mesh = {Humans ; *Parkinson Disease/complications/pathology/diagnostic imaging/physiopathology ; *Apathy/physiology ; Male ; Female ; Middle Aged ; Aged ; *Magnetic Resonance Imaging ; *Gray Matter/diagnostic imaging/pathology ; *Disruptive, Impulse Control, and Conduct Disorders/etiology/physiopathology/diagnostic imaging/pathology ; Longitudinal Studies ; Impulsive Behavior/physiology ; },
abstract = {BACKGROUND: Although apathy and impulse control disorders (ICDs) are considered to represent opposite extremes of a continuum of motivated behavior (i.e., hypo- and hyperdopaminergic behaviors), they may also co-occur in Parkinson's disease (PD).<br><br>OBJECTIVES: We aimed to explore the co-occurrence of ICDs and apathy and its neural correlates analyzing gray matter (GM) changes in early untreated PD patients. Moreover, we aimed to investigate the possible longitudinal relationship between ICDs and apathy and their putative impact on cognition during the first five years of PD.<br><br>METHODS: We used the Parkinson's Progression Markers Initiative (PPMI) database to identify the co-occurrence of apathy and ICDs in 423 early drug-na&#xef;ve PD patients at baseline and at 5-year follow-up. Baseline MRI volumes and gray matter changes were analyzed between groups using voxel-based morphometry. Multi-level models assessed the longitudinal relationship (across five&#xa0;years) between apathy and ICDs and cognitive functioning.<br><br>RESULTS: At baseline, co-occurrence of apathy and ICDs was observed in 23 patients (5.4%). This finding was related to anatomical GM reduction along&#xa0;the cortical regions involved in the limbic circuit and cognitive control systems. Longitudinal analyses indicated that apathy and ICDs were related to each other as well as to&#xa0;the combined use of levodopa and dopamine agonists. Worse apathetic and ICDs states were associated with poorer executive functions.<br><br>CONCLUSIONS: Apathy and ICDs are joint non-exclusive neuropsychiatric disorders also in the early stages of PD and their co-occurrence was associated with GM decrease in several cortical regions of the limbic circuit and cognitive control systems.},
}
@article {pmid38414161,
year = {2024},
author = {Geppert, J and Rohm, M},
title = {Cancer cachexia: biomarkers and the influence of age.},
journal = {Molecular oncology},
volume = {18},
number = {9},
pages = {2070-2086},
pmid = {38414161},
issn = {1878-0261},
support = {//Helmholtz-Gemeinschaft/ ; 949017//European Commission/ ; },
mesh = {*Cachexia/metabolism/diagnosis ; Humans ; *Neoplasms/complications/metabolism ; *Aging/metabolism ; Animals ; Biomarkers/metabolism ; Biomarkers, Tumor/metabolism ; Inflammation/metabolism ; },
abstract = {Cancer cachexia (Ccx) is a complex metabolic condition characterized by pronounced muscle and fat wasting, systemic inflammation, weakness and fatigue. Up to 30% of cancer patients succumb directly to Ccx, yet therapies that effectively address this perturbed metabolic state are rare. In recent decades, several characteristics of Ccx have been established in mice and humans, of which we here highlight adipose tissue dysfunction, muscle wasting and systemic inflammation, as they are directly linked to biomarker discovery. To counteract cachexia pathogenesis as early as possible and mitigate its detrimental impact on anti-cancer treatments, identification and validation of clinically endorsed biomarkers assume paramount importance. Ageing was recently shown to affect both the validity of Ccx biomarkers and Ccx development, but the underlying mechanisms are still unknown. Thus, unravelling the intricate interplay between ageing and Ccx can help to counteract Ccx pathogenesis and tailor diagnostic and treatment strategies to individual needs.},
}
@article {pmid38409747,
year = {2024},
author = {Ruan, GJ and Zanwar, S and Ravindran, A and Schram, S and Abeykoon, JP and Hazim, A and Young, JR and Shah, MV and Bennani, NN and Jiang, L and Morlote, D and Rech, KL and Goyal, G and Go, RS and , },
title = {Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.},
journal = {American journal of hematology},
volume = {99},
number = {5},
pages = {871-879},
pmid = {38409747},
issn = {1096-8652},
support = {K12 CA090628/CA/NCI NIH HHS/United States ; P50 CA097274/CA/NCI NIH HHS/United States ; R01 CA262613/CA/NCI NIH HHS/United States ; R21 CA097422/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Histiocytic Sarcoma/genetics/therapy/pathology ; Macrophages/pathology ; Bone Marrow/pathology ; Prognosis ; Liver/pathology ; },
abstract = {Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.},
}
@article {pmid38406950,
year = {2023},
author = {Asad, S and Khan, SA and Khan, FA and Jalal-Ud-Din, M and Bhatti, G and Kamran, H},
title = {Pattern Of Breast Cancer: Experience At Ayub Teaching Hospital, Abbottabad.},
journal = {Journal of Ayub Medical College, Abbottabad : JAMC},
volume = {35},
number = {4},
pages = {629-632},
doi = {10.55519/JAMC-04-12089},
pmid = {38406950},
issn = {1819-2718},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Lymph Nodes/pathology ; Hospitals, Teaching ; Biopsy ; Axilla/pathology ; },
abstract = {BACKGROUND: Breast cancer is the most common malignancy found in females all over the world and the second leading cause of cancer death in European countries. The purpose of this study was to find out the pattern of disease presentation in our region where a proper tumour registry system is lacking.<br><br>METHODS: This descriptive study was carried out in the Department of Surgery, Ayub Teaching Hospital Abbottabad, from July 2021 to June 2022. All female patients with biopsy-proven breast cancer were included in the study: benign lumps, refused to enrol, and those who were lost to follow-up were excluded.<br><br>RESULTS: A total of 87 patients with carcinoma breast were included: 92 % (n=80) had invasive ductal carcinoma. Axillary lymph nodes were involved in 88.5% (n=77), 75.8% of the tumours, (n=66), were Grade 2, 34.5% (n=30) were in the 40-49 years age group, and 30 % (n=27) of the disease was categorized as Stage III or IV. In 55 % (n=48), the tumour was on the right side and in 39% (n=34), the upper outer quadrant was involved. Most of the patients, 90.8% (n=79), were married and had used contraceptive measures. Only 19.5% of patients (n=17), had a history of nipple discharge and 56% (n=49) had a positive family history: 71% (n=62) had nipple retraction, and 54% (n=47), proved to be ER PR positive.<br><br>CONCLUSIONS: Our patients presented late: axilla was commonly involved and a third had advanced disease. Screening and community awareness programs may help in early detection. Hormone use for contraception needs to be weighed carefully. Better data collection may help in designing screening and care programs.},
}
@article {pmid38406898,
year = {2023},
author = {, and Haider, G and Shaikh, Z and Memon, P and Shahid, A and Rahul, R and Kumar, P and Beg, S and Parkash, J},
title = {Significance of ca15-3 in carcinoma of the breast with Visceral metastases.},
journal = {Journal of Ayub Medical College, Abbottabad : JAMC},
volume = {35(Suppl 1)},
number = {4},
pages = {S710-S714},
doi = {10.55519/JAMC-S4-7329},
pmid = {38406898},
issn = {1819-2718},
mesh = {Female ; Humans ; Middle Aged ; Cross-Sectional Studies ; Mucin-1 ; Biomarkers, Tumor ; *Breast Neoplasms/diagnosis ; *Carcinoma ; Prognosis ; },
abstract = {BACKGROUND: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi.<br><br>METHODS: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data.<br><br>RESULTS: A total of 139 females were included in the study. The mean age &amp; BMI of the patients were reported as 46.5 years &amp; 26.69 kg/m2. In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L).<br><br>CONCLUSION: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients.},
}
@article {pmid38399000,
year = {2024},
author = {Khan, MRR},
title = {Development of a Battery-Free, Chipless, and Highly Sensitive Radio Frequency Glucose Biosensor.},
journal = {Micromachines},
volume = {15},
number = {2},
pages = {},
pmid = {38399000},
issn = {2072-666X},
abstract = {In our study, we designed and developed a glucose biosensor that operates without a battery or chip. This biosensor utilizes the principles of radio frequency (RF) to operate. For the construction of a glucose-sensitive interdigitated capacitor (IDC), a famous glucose-sensitive substance called phenylboronic acid (PBA) is combined with a polyvinyl chloride (PVC) and n,n-dimethylacetamide (DMAC) solution. According to the theory of radio frequency sensing, the resonance frequency shifts whenever there is a change in the capacitance of the glucose-sensitive IDC. This change is caused by the fluctuations in glucose concentrations. As far as we are aware, this is the first glucose sensor that employs the RF principle to detect changes in glucose solution concentrations using PBA as the principal glucose-sensitive material. The sensor can detect glucose levels with remarkable sensitivity, around 40.89 kHz/decade, and a broad dynamic range covering 10 μM to 1 M. Additionally, the designed biosensor has excellent linearity performance, with a value of around 0.988. The proposed glucose biosensor has several benefits: lightweight, inexpensive, easy to build, and an acceptable selectivity response. Our study concludes by comparing the proposed RF sensor's effectiveness to that of existing glucose sensors, which it outperforms.},
}
@article {pmid38396137,
year = {2024},
author = {Matsumoto, T and Tanaka, G and Mori, S and Niki, M and Sato, S and Shiraki, T and Iso, Y and Nagashima, K and Irisawa, A and Nozawa, Y and Takada-Owada, A and Ishida, K and Aoki, T},
title = {A resected case of pancreatic head cancer developing 40 years after lateral pancreaticojejunostomy for chronic pancreatitis.},
journal = {Clinical journal of gastroenterology},
volume = {17},
number = {3},
pages = {537-542},
pmid = {38396137},
issn = {1865-7265},
mesh = {Humans ; Male ; *Pancreaticojejunostomy ; Aged ; *Pancreatic Neoplasms/surgery ; *Pancreatitis, Chronic/surgery/complications/etiology ; Pancreaticoduodenectomy/adverse effects ; Carcinoma, Pancreatic Ductal/surgery ; Postoperative Complications/etiology ; Tomography, X-Ray Computed ; },
abstract = {A 72-year-old male patient presented to our department complaining of with upper abdominal pain and jaundice. He had a history of a side-to-side pancreaticojejunostomy performed 40 years previously for chronic pancreatitis. A diagnostic workup revealed a tumor 3 cm in size in the pancreatic head as the etiology of the jaundice. Subsequently, the patient was diagnosed with resectable pancreatic cancer. Following two cycles of neoadjuvant chemotherapy, an extended pancreatoduodenectomy was performed because of tumor invasion at the previous pancreaticojejunostomy site. Concurrent portal vein resection and reconstruction were performed. Pathological examination confirmed invasive ductal carcinoma (T2N1M0, Stage IIB). This case highlights the clinical challenges in pancreatic head carcinoma following a side-to-side pancreaticojejunostomy. Although pancreaticojejunostomy is believed to reduce the risk of pancreatic cancer in patients with chronic pancreatitis, clinicians should be aware that, even after this surgery, there is still a chance of developing pancreatic cancer during long-term follow-up.},
}
@article {pmid38379333,
year = {2024},
author = {Zhu, S and Xu, N and Zeng, H},
title = {Molecular complexity of intraductal carcinoma of the prostate.},
journal = {Cancer medicine},
volume = {13},
number = {2},
pages = {e6939},
pmid = {38379333},
issn = {2045-7634},
support = {NSFC 82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; 2022-I2M-C&amp;T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Medical Sciences/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; X-J-2020-016//Bethune Foundation, Oncology Basic Research Program/ ; ZYJC21020//West China Hospital, Sichuan University/ ; ZYGD22004//West China Hospital, Sichuan University/ ; mnzl202002//Bethune Foundation, Urological Oncology Special Research Fund/ ; mnzl202007//Bethune Foundation, Urological Oncology Special Research Fund/ ; },
mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; Prognosis ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.},
}
@article {pmid38379091,
year = {2024},
author = {Bufman, H and Faermann, R and Halshtok-Neiman, O and Shalmon, A and Gotlieb, M and Samoocha, D and Yagil, Y and Feldman, DM and Friedman, E and Sklair-Levy, M},
title = {Breast cancer diagnosed after age 70 years in Israeli BRCA1/BRCA2 pathogenic sequence variant carriers: a single institution experience.},
journal = {Breast cancer research and treatment},
volume = {205},
number = {2},
pages = {281-285},
pmid = {38379091},
issn = {1573-7217},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/diagnosis/epidemiology ; Aged ; Israel/epidemiology ; Aged, 80 and over ; *BRCA1 Protein/genetics ; *BRCA2 Protein/genetics ; Heterozygote ; Genetic Predisposition to Disease ; Early Detection of Cancer/methods ; Mutation ; },
abstract = {PURPOSE: A semi-annual surveillance scheme from age 25 to 30 years is offered to BRCA1/BRCA2 pathogenic sequence variants (PSVs) carriers for early detection of breast cancer (BC). There is a paucity of data on the yield of adhering to this scheme beyond 70 years of age.<br><br>METHODS: Female BRCA1/BRCA2 PSV carriers followed at the Meirav high-risk clinic, Sheba Medical center, Israel were eligible. Type and frequencies if use of Imaging modalities, breast biopsies and histological outcomes for participants after age 70 years were retrieved and analyzed.<br><br>RESULTS: Overall, the study encompassed 88 consenting participants (46 BRCA1 carriers) mean age&#x2009;&#xb1;&#x2009;SD 73.7&#x2009;&#xb1;&#x2009;3.3 years (range 70-90 years), followed for an average of 3.8 years (range 1-11 years). Ten carriers (11.3%) were diagnosed with BC after age 70 years (mean age at diagnosis 72&#x2009;&#xb1;&#x2009;2 years) and an additional case was diagnosed with breast lymphoma. The imaging modality that has led to most diagnoses was MRI (8/11 cases). Eight of these ten cases were previously diagnosed with BC prior to age 70 and in six, BC past 70 years was in the contralateral breast. The lesions size averaged 1.29&#x2009;&#xb1;&#x2009;0.75&#xa0;cm, with IDC and DCIS diagnosed in five cases each, and none had lymph node involvement.<br><br>CONCLUSION: In ~10% of BRCA1/BRCA2 PSV carriers BC is diagnosed by breast imaging after age 70 years. If these results are validated in a larger study, the guidelines for the maximum age for BC surveillance in high risk women should be revisited and set at 75 years.},
}
@article {pmid38378247,
year = {2025},
author = {Nguyen, NJ and Liu, K and Lajkosz, K and Iczkowski, KA and van der Kwast, TH and Downes, MR},
title = {Addition of cribriform pattern 4 and intraductal prostatic carcinoma into the CAPRA-S tool improves post-radical prostatectomy patient stratification in a multi-institutional cohort.},
journal = {Journal of clinical pathology},
volume = {78},
number = {12},
pages = {805-813},
doi = {10.1136/jcp-2023-209222},
pmid = {38378247},
issn = {1472-4146},
mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/surgery/mortality ; *Prostatectomy ; Retrospective Studies ; Aged ; Middle Aged ; Risk Assessment/methods ; Prognosis ; Neoplasm Grading ; Disease-Free Survival ; Risk Factors ; },
abstract = {AIMS: Pre-surgical risk classification tools for prostate cancer have shown better patient stratification with the addition of cribriform pattern 4 (CC) and intraductal prostatic carcinoma (IDC) identified in biopsies. Here, we analyse the additional prognostic impact of CC/IDC observed in prostatectomies using Cancer of Prostate Risk Assessment post-surgical (CAPRA-S) stratification.<br><br>METHODS: A retrospective cohort of treatment-na&#xef;ve radical prostatectomy specimens from three North American academic institutions (2010-2018) was assessed for the presence of CC/IDC. Patients were classified, after calculating the CAPRA-S scores, into low-risk (0-2), intermediate-risk (3-5) and high-risk (6-12) groups. Kaplan-Meier curves were created to estimate biochemical recurrence (BCR)-free survival. Prognostic performance was examined using Harrell's concordance index, and the effects of CC/IDC within each risk group were evaluated using the Cox proportional hazards models.<br><br>RESULTS: Our cohort included 825 prostatectomies (grade group (GG)1, n=94; GG2, n=475; GG3, n=185; GG4, n=13; GG5, n=58). CC/IDC was present in 341 (41%) prostatectomies. With a median follow-up of 4.2 years (range 2.9-6.4), 166 (20%) patients experienced BCR. The CAPRA-S low-risk, intermediate-risk and high-risk groups comprised 357 (43%), 328 (40%) and 140 (17%) patients, and discriminated for BCR-free survival (p<0.0001). For CAPRA-S scores 3-5, the addition of CC/IDC status improved stratification for BCR (HR 2.27, 95%&#x2009;CI 1.41 to 3.66, p<0.001) and improved the overall c-index (0.689 vs 0.667, analysis of variance p<0.001).<br><br>CONCLUSION: The addition of CC/IDC into the CAPRA-S classification significantly improved post-radical prostatectomy patient stratification for BCR among the intermediate-risk group (CAPRA-S scores 3-5). The reporting of CC and IDC should be included in future prostate cancer stratification tools for improved outcome prediction.},
}
@article {pmid38376291,
year = {2023},
author = {Piracha, ZZ and Saeed, U},
title = {Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer.},
journal = {Journal of cancer research and therapeutics},
volume = {19},
number = {7},
pages = {1870-1879},
pmid = {38376291},
issn = {1998-4138},
mesh = {Female ; Humans ; beta Catenin ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal ; *Fibroadenoma/genetics ; Glycogen Synthase Kinase 3 ; Immunoglobulin Domains ; Leucine ; *Membrane Glycoproteins/genetics ; Prognosis ; Proto-Oncogene Proteins c-akt ; },
abstract = {BACKGROUND: LRIG1 belongs to the family of transmembrane proteins containing leucine-rich repeats. LRIGs are considered as tumor suppressors as they negatively regulate receptor tyrosine kinases. The role of LRIG1 as an EGFR regulator makes it an important marker to be studied in various epithelial-derived cancers.<br><br>METHODS: LRIG1 expression was determined in Erbb2 + cell lines by western blotting, and cell motility was examined by cell migration assay. The AKT/GSK3-&#x3b2;/&#x3b2;-catenin pathway was determined in the presence of LRIG1 and Erbb2 by using western blotting.<br><br>RESULTS: So far, no study has reported the expression of LRIG1 in benign forms of tumor such as fibroadenoma. The current study aims to analyze LRIG1 expression in fibroadenoma and invasive ductal carcinoma (IDC) tissues. In this study, we compared the LRIG1 expression with different clinicopathological parameters of patients having IDC or fibroadenoma. LRIG1 expression was low in Erbb2+ cell lines, and more cell motility was observed. The AKT/GSK3-&#x3b2;/&#x3b2;-catenin pathway was activated when LRIG1 was downregulated; consequently, Erbb2 was upregulated. Our results indicated that LRIG1 expression can be significantly correlated with age, Nottingham index, and Her2/neu status of cancer. The expression of LRIG1 in IDC and fibroadenoma were found to be significantly different.<br><br>CONCLUSION: The fibroadenoma tissue sections were found to express LRIG1 more intensely as compared to the IDC sections, which are in line with the studies reporting reduced copy number of the gene either due to gene deletion or transcriptional inhibition. This further supports that the downregulation of LRIG1 may lead to malignant tumor acting as a tumor suppressor.},
}
@article {pmid38369589,
year = {2024},
author = {Liu, XS and Chen, YX and Wan, HB and Wang, YL and Wang, YY and Gao, Y and Wu, LB and Pei, ZJ},
title = {TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {4042},
pmid = {38369589},
issn = {2045-2322},
mesh = {Humans ; *Adaptor Proteins, Signal Transducing/genetics/metabolism ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; Glycolysis ; *LIM Domain Proteins/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; *Transcription Factors/genetics/metabolism ; },
abstract = {Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.},
}
@article {pmid38368669,
year = {2024},
author = {Gomez, D and Seneviratne, S},
title = {Invasive breast carcinoma with ipsilateral axillary squamous carcinoma of unknown primary: A case report.},
journal = {International journal of surgery case reports},
volume = {116},
number = {},
pages = {109397},
pmid = {38368669},
issn = {2210-2612},
abstract = {INTRODUCTION &amp; IMPORTANCE: Invasive ductal carcinoma is the commonest primary breast carcinoma to metastasize to the axillary nodes. Squamous carcinoma (SCC) of the breast is seen rarely as a primary breast malignancy. Breast SCC with coexistent invasive ductal/lobular carcinoma as a 'collision tumour' is rare.<br><br>CASE PRESENTATION: A 52-year-old Sri Lankan female presented with a right sided breast lump and ipsilateral cystic axillary mass. She was diagnosed with locally advanced invasive breast carcinoma and underwent neoadjuvant chemotherapy followed by mastectomy and axillary clearance where tumour infiltration of the brachial plexus was observed. Histology revealed two separate carcinomas; an invasive carcinoma of the breast and squamous carcinoma in the axilla. A squamous primary was not found despite evaluation. The patient developed recurrent axillary ulceration due to residual tumour and was transferred for oncological care.<br><br>CLINICAL DISCUSSION: This patient had a biopsy-proven invasive breast carcinoma with a cystic axillary mass with lymphadenopathy. This was concluded as locally advanced breast cancer. Pathological examination of the specimen indicated the presence of two separate malignancies of the breast and axilla. No evidence of squamous metaplasia or carcinoma of the breast was seen on histology, neither was a squamous primary identified on imaging or endoscopy. Neoadjuvant therapy may have caused resolution of the squamous component.<br><br>CONCLUSION: The presence of two separate cancers of varied histology in the breast and ipsilateral axilla in close proximity to each other is a rare phenomenon. Clinicians must be cautious not to misinterpret it as evidence of lymphatic spread.},
}
@article {pmid38348593,
year = {2024},
author = {Schweiger, M and Arredondo-Lasso, MN and Friano, ME and Gil-Lozano, M and Herzig, S and Uhlenhaut, NH},
title = {Lipid sensing nuclear receptors involved in the pathogenesis of fatty liver disease.},
journal = {FEBS letters},
volume = {598},
number = {23},
pages = {2854-2855},
pmid = {38348593},
issn = {1873-3468},
support = {UH 275/6-1-ID 457050056//German Research Foundation DFG/ ; TRR333 BATEnergy ID 450149205//German Research Foundation DFG/ ; TRR205 Adrenal Gland ID 314061271//German Research Foundation DFG/ ; CRC1064 Chromatin Dynamics ID 213249687//German Research Foundation DFG/ ; 457050056//German Research Foundation/ ; 450149205//TRR333 BAT-Energy/ ; },
mesh = {Humans ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Animals ; *Lipid Metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism/pathology/genetics ; Fatty Liver/metabolism/pathology/genetics ; },
abstract = {Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation and progresses toward inflammation and fibrosis. Nuclear receptors (NRs), like the Peroxisome Proliferator-Activated Receptors alpha and gamma (PPARα and PPARy), the Farnesoid X Receptor (FXR), and the Liver X receptor (LXR), regulate genes by heterodimerizing with Retinoid X receptor (RXR). These receptors are emerging targets for pharmaceutical intervention for metabolic diseases.},
}
@article {pmid38343885,
year = {2023},
author = {Santos, MM and Baerga, CG and Lamsal, S and Engel, C and Ozdemir, S},
title = {Breast cancer in a Hispanic patient with Werner syndrome.},
journal = {Journal of radiology case reports},
volume = {17},
number = {10},
pages = {21-31},
pmid = {38343885},
issn = {1943-0922},
mesh = {Adult ; Female ; Humans ; *Breast Neoplasms/diagnostic imaging/genetics ; Hispanic or Latino ; Mastectomy ; Mutation ; *Werner Syndrome/complications/diagnostic imaging/genetics ; Werner Syndrome Helicase/genetics ; },
abstract = {Werner Syndrome is a rare autosomal recessive condition characterized by premature aging and increased risk of malignancies due to gene mutations associated with DNA stability. We present the first case report of a 29-year-old Hispanic female with WS diagnosed with breast cancer. Diagnostic mammography and ultrasound, breast MRI and PET examinations revealed two lesions biopsy proven as invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy and radical mastectomy. Recurrence occurred 10 months postoperatively with molecular analysis demonstrating TP53 mutations. The multifactorial assessment of breast cancer in this case study is crucial towards optimizing screening, diagnosis and management of this disease in patients with WS.},
}
@article {pmid38336663,
year = {2024},
author = {Ye, C and Shi, M and Xie, D and Wu, H and Chen, Q and Yang, L},
title = {A rare case of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament in a child: a case report and literature review.},
journal = {BMC musculoskeletal disorders},
volume = {25},
number = {1},
pages = {118},
pmid = {38336663},
issn = {1471-2474},
support = {82372431//National Natural Science Foundation of China/ ; 2022LJ007//Shanghai Municipal Health Commission Health Leading Talents Program/ ; 22ZR1476700//the Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality/ ; 201409003200//the Science and Technology Innovation Action Plan of the Science and Technology Commission of Shanghai Municipality/ ; 0906//the Fifth Round Innovation Team of Shanghai Changning District, the Pyramid Talent Project of Shanghai Changzheng Hospital in 2020/ ; 2021X002//the Discipline Team Support Project of No. 905 Hospital of PLA Navy/ ; },
mesh = {Humans ; Child ; Longitudinal Ligaments/diagnostic imaging ; Osteogenesis ; *Intervertebral Disc Degeneration/complications/diagnostic imaging ; *Ossification of Posterior Longitudinal Ligament/complications/diagnostic imaging/therapy ; *Calcinosis/complications/diagnostic imaging/therapy ; *Chondrocalcinosis/complications ; Cervical Vertebrae/diagnostic imaging ; *Intervertebral Disc/diagnostic imaging ; },
abstract = {BACKGROUND: Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition.<br><br>CASE PRESENTATION: We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion.<br><br>CONCLUSIONS: We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.},
}
@article {pmid38329829,
year = {2024},
author = {Fang, L and Simman, R and Workman, L and Ayoub, S and Bratton, C},
title = {Malignant wound aetiology, diagnosis and management: a case series and literature review.},
journal = {Journal of wound care},
volume = {33},
number = {2},
pages = {102-117},
doi = {10.12968/jowc.2024.33.2.102},
pmid = {38329829},
issn = {0969-0700},
mesh = {Aged ; Humans ; *Carcinoma, Squamous Cell/diagnosis/therapy/complications ; *Melanoma/diagnosis/therapy ; Neoplasm Recurrence, Local ; Skin/pathology ; *Skin Neoplasms/diagnosis/therapy ; },
abstract = {OBJECTIVE: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy.<br><br>METHOD: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles.<br><br>RESULTS: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC.<br><br>CONCLUSION: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort.},
}
@article {pmid38326829,
year = {2024},
author = {Verma, VK and Beevi, SS and Nair, RA and Kumar, A and Kiran, R and Alexander, LE and Dinesh Kumar, L},
title = {MicroRNA signatures differentiate types, grades, and stages of breast invasive ductal carcinoma (IDC): miRNA-target interacting signaling pathways.},
journal = {Cell communication and signaling : CCS},
volume = {22},
number = {1},
pages = {100},
pmid = {38326829},
issn = {1478-811X},
mesh = {Animals ; Female ; Mice ; Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *MicroRNAs/genetics/metabolism ; Signal Transduction ; },
abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most common form of breast cancer which accounts for 85% of all breast cancer diagnoses. Non-invasive and early stages have a better prognosis than late-stage invasive cancer that has spread to lymph nodes. The involvement of microRNAs (miRNAs) in the initiation and progression of breast cancer holds great promise for the development of molecular tools for early diagnosis and prognosis. Therefore, developing a cost effective, quick and robust early detection protocol using miRNAs for breast cancer diagnosis is an imminent need that could strengthen the health care system to tackle this disease around the world.<br><br>METHODS: We have analyzed putative miRNAs signatures in 100 breast cancer samples using two independent high fidelity array systems. Unique and common miRNA signatures from both array systems were validated using stringent double-blind individual TaqMan assays and their expression pattern was confirmed with tissue microarrays and northern analysis. In silico analysis were carried out to find miRNA targets and were validated with q-PCR and immunoblotting. In addition, functional validation using antibody arrays was also carried out to confirm the oncotargets and their networking in different pathways. Similar profiling was carried out in Brca2/p53 double knock out mice models using rodent miRNA microarrays that revealed common signatures with human arrays which could be used for future in vivo functional validation.<br><br>RESULTS: Expression profile revealed 85% downregulated and 15% upregulated microRNAs in the patient samples of IDC. Among them, 439 miRNAs were associated with breast cancer, out of which 107 miRNAs qualified to be potential biomarkers for the stratification of different types, grades and stages of IDC after stringent validation. Functional validation of their putative targets revealed extensive miRNA network in different oncogenic pathways thus contributing to epithelial-mesenchymal transition (EMT) and cellular plasticity.<br><br>CONCLUSION: This study revealed potential biomarkers for the robust classification as well as rapid, cost effective and early detection of IDC of breast cancer. It not only confirmed the role of these miRNAs in cancer development but also revealed the oncogenic pathways involved in different progressive grades and stages thus suggesting a role in EMT and cellular plasticity during breast tumorigenesis per se and IDC in particular. Thus, our findings have provided newer insights into the miRNA signatures for the classification and early detection of IDC.},
}
@article {pmid38318566,
year = {2024},
author = {Youh, J and Yamaguchi, Y and Hiraguchi, E},
title = {Centrifugally Spreading Annular Erythema as a Dermatological Indicator of Metastatic Breast Carcinoma.},
journal = {Cureus},
volume = {16},
number = {1},
pages = {e51641},
pmid = {38318566},
issn = {2168-8184},
abstract = {Breast cancer is the leading cause of skin metastasis in women with internal malignancies. This report highlights an atypical case of cutaneous metastasis of breast cancer (CMBC) in a 66-year-old woman. Starting four months before her dermatology consultation, the patient underwent a chemotherapy regimen comprising pertuzumab, trastuzumab, and vinorelbine for right breast cancer, right axillary lymph node enlargement, and bone metastases. After commencing chemotherapy, erythematous macules appeared around her right nipple. Subsequently, the cutaneous lesions developed into annular erythematous patches around her right nipple and began to coalesce and expand to the contralateral breast. A skin biopsy revealed dysplastic cells indicative of metastasis from invasive ductal carcinoma. In addition, lymphovascular tumor cell invasion was noted in the reticular dermis. Based on these clinical progressions and histopathologic findings, a diagnosis of CMBC was made, specifically considering the possibility of inflammatory breast cancer (IBC). The patient continued the same chemotherapy regimen for 17 cycles, which improved the skin lesions, but she succumbed to breast cancer two years later. This case emphasizes the importance of considering CMBC in breast cancer patients with expanding, treatment-resistant thoracic cutaneous lesions, especially in aggressive subtypes like IBC. The diverse presentations of CMBC require thorough histopathological evaluation.},
}
@article {pmid38308423,
year = {2024},
author = {Agaoglu, NB and Unal, B and Hayes, CP and Walker, M and Ng, OH and Doganay, L and Can, ND and Rana, HQ and Ghazani, AA},
title = {Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients.},
journal = {Cancer medicine},
volume = {13},
number = {3},
pages = {e6852},
pmid = {38308423},
issn = {2045-7634},
support = {Number YNY2016/144//The Istanbul Development Agency (ISTKA)/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; *Carcinoma, Lobular ; Genomics ; *Carcinoma, Ductal, Breast ; Oncogenes ; },
abstract = {OBJECTIVE: Turkish genome is underrepresented in large genomic databases. This study aims to evaluate the effect of allele frequency in the Turkish population in determining the clinical utility of germline findings in breast cancer, including invasive lobular carcinoma (ILC), mixed invasive ductal and lobular carcinoma (IDC-L), and ductal carcinoma (DC).<br><br>METHODS: Two clinic-based cohorts from the Umraniye Research and Training Hospital (URTH) were used in this study: a cohort consisting of 132 women with breast cancer and a non-cancer cohort consisting of 492 participants. The evaluation of the germline landscape was performed by analysis of 27 cancer genes. The frequency and type of variants in the breast cancer cohort were compared to those in the non-cancer cohort to investigate the effect of population genetics. The variant allele frequencies in Turkish Variome and gnomAD were statistically evaluated.<br><br>RESULTS: The genetic analysis identified 121 variants in the breast cancer cohort (actionable&#x2009;=&#x2009;32, VUS&#x2009;=&#x2009;89) and 223 variants in the non-cancer cohort (actionable&#x2009;=&#x2009;25, VUS&#x2009;=&#x2009;188). The occurrence of 21 variants in both suggested a possible genetic population effect. Evaluation of allele frequency of 121 variants from the breast cancer cohort showed 22% had a significantly higher value in Turkish Variome compared to gnomAD (p&#x2009;<&#x2009;0.0001, 95% CI) with a mean difference of 60 times (ranging from 1.37-354.4). After adjusting for variant allele frequency using the ancestry-appropriate database, 6.7% (5/75) of VUS was reclassified to likely benign.<br><br>CONCLUSION: To our knowledge, this is the first study of population genetic effects in breast cancer subtypes in Turkish women. Our findings underscore the need for a large genomic database representing Turkish population-specific variants. It further highlights the significance of the ancestry-appropriate population database for accurate variant assessment in clinical settings.},
}
@article {pmid38307851,
year = {2024},
author = {Coria, LM and Rodriguez, JM and Demaria, A and Bruno, LA and Medrano, MR and Castro, CP and Castro, EF and Del Priore, SA and Hernando Insua, AC and Kaufmann, IG and Saposnik, LM and Stone, WB and Prado, L and Notaro, US and Amweg, AN and Diaz, PU and Avaro, M and Ortega, H and Ceballos, A and Krum, V and Zurvarra, FM and Sidabra, JE and Drehe, I and Baqué, JA and Li Causi, M and De Nichilo, AV and Payes, CJ and Southard, T and Vega, JC and Auguste, AJ and Álvarez, DE and Flo, JM and Pasquevich, KA and Cassataro, J},
title = {A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {997},
pmid = {38307851},
issn = {2041-1723},
support = {R01 AI153433/AI/NIAID NIH HHS/United States ; },
mesh = {Animals ; Mice ; Humans ; *SARS-CoV-2 ; Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; *COVID-19/prevention &amp; control ; Vaccines, Subunit ; Adjuvants, Immunologic ; Epitopes, B-Lymphocyte ; Antibodies, Viral ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus/genetics ; },
abstract = {In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.},
}
@article {pmid38305220,
year = {2024},
author = {Tsilingiris, D and Schimpfle, L and Κender, Z and Sulaj, A and von Rauchhaupt, E and Herzig, S and Szendroedi, J and Kopf, S},
title = {Utility of bioelectrical phase angle for cardiovascular risk assessment among individuals with and without diabetes mellitus.},
journal = {Diabetes &amp; vascular disease research},
volume = {21},
number = {1},
pages = {14791641231223701},
pmid = {38305220},
issn = {1752-8984},
mesh = {Adult ; Humans ; Male ; Female ; *Cardiovascular Diseases/diagnosis/etiology ; Carotid Intima-Media Thickness ; Pulse Wave Analysis ; *Diabetes Mellitus, Type 1 ; Risk Factors ; Heart Disease Risk Factors ; *Diabetes Mellitus, Type 2 ; Natriuretic Peptide, Brain ; Peptide Fragments ; Biomarkers ; },
abstract = {PURPOSE: Low values of bioimpedance-derived phase angle (PA) have been associated with various adverse outcomes. We investigated the association of PA with cardiovascular markers in individuals with and without diabetes mellitus (DM).<br><br>METHODS: PA was measured in 452 adults (without DM n = 153, T1DM n = 67, T2DM n = 232). Carotid intima-media thickness (IMT), renal resistive index (RRI), ankle-brachial index (ABI) and carotid-femoral Pulse Wave Velocity (cfPWV) were estimated. Furthermore, the levels of high-sensitive Troponin-T [hsTnT], N-terminal brain natriuretic peptide [NT-pro-BNP]) were measured.<br><br>RESULTS: PA values were lower in DM independently of age, gender, and BMI (estimated marginal means 6.21, 5.83, 5.95 for controls, T1DM, T2DM p < .05), a finding which persisted after propensity score matching. PA correlated negatively with IMT (r = -0.181), RRI (r = -0.374), cfPWV (r = -0.358), hsTnT (r = -0.238) and NT-pro-BNP (r = -0.318) (all p < .001). In multivariable analysis, the associations with RRI, cfPWV, hsTnT and NT-pro-BNP remained unchanged. PA values 6.0-6.5&#xb0; for males and 5.2-5.8&#xb0; for females were predictive of commonly used cutoffs. The combination of &#x391;CC/AHA ASCVD Score with PA outperformed either factor in predicting cfPWV, RRI for males and hsTnT, BNP for both genders.<br><br>CONCLUSIONS: PA exhibits independent correlations with various parameters pertinent to cardiovascular risk and may be useful for cardiovascular assessment.},
}
@article {pmid38303308,
year = {2023},
author = {Aoyagi, T and Namura, M and Sakata, H and Tamanuki, T and Iwai, M and Iwata, K and Takahashi, H and Matsuzaki, H},
title = {[A Case of Recurrent Breast Cancer That Was BRCA1 Pathogenic Variant-Positive Successfully Treated with PARP Inhibitor].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {50},
number = {13},
pages = {1462-1464},
pmid = {38303308},
issn = {0385-0684},
mesh = {Female ; Humans ; Aged ; Middle Aged ; *Breast Neoplasms/drug therapy/genetics/surgery ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Mastectomy ; Neoplasm Recurrence, Local/drug therapy/surgery ; *Antineoplastic Agents/therapeutic use ; BRCA1 Protein/genetics ; },
abstract = {The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.},
}
@article {pmid38303174,
year = {2023},
author = {Takeda, Y and Ohmura, Y and Katsura, Y and Shinke, G and Kinoshita, M and Aoyama, S and Kihara, Y and Yanagisawa, K and Katsuyama, S and Ikeshima, R and Hiraki, M and Sugimura, K and Masuzawa, T and Hata, T and Murata, K},
title = {[Robotic and Laparoscopic Pancreaticoduodenectomy for the Elderly Patients-A Single Institutional Experience].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {50},
number = {13},
pages = {1688-1690},
pmid = {38303174},
issn = {0385-0684},
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; Pancreaticoduodenectomy/adverse effects ; *Pancreatic Neoplasms/surgery/complications ; Pancreatic Fistula/etiology ; *Robotic Surgical Procedures/adverse effects ; Retrospective Studies ; *Laparoscopy/adverse effects ; Postoperative Complications/epidemiology/etiology ; Length of Stay ; *Carcinoma, Ductal/complications ; },
abstract = {INTRODUCTION: Laparoscopic pancreaticoduodenectomy(LPD)has been covered by insurance since 2016 in Japan. Advance LPD and robotic pancreaticoduodenectomy(RPD)has been also covered by insurance since 2020 in Japan. The aim of this study was to analyze the perioperative results and outcomes of RPD and LPD for the elderly patients and to compare to the non-elderly patients.<br><br>PATIENTS AND METHOD: Between July 2020 and April 2023, 67 patients underwent RPD and between May 2012 and February 2021, 63 patients underwent LPD at Kansai Rosai Hospital. Sixty-seven RPD and 62 LPD patients without extended resection were divided into 2 groups those who were over 75 years old(R/LPD E)(n=55)and under 74 years old(R/LPD non-E)(n=74). Control patients who received open pancreaticoduodenectomy(OPD)without extended resection between April 2010 and April 2023 were also divided into 2 groups those who were over 75 years old(OPD E)(n =60)and under 74 years old(OPD non-E)(n=78). The patient age was 79.0 and 60.5 years, the male to female ratio was 35/20 and 45/29, disease ratio(invasive ductal carcinoma or not)was 7/48 and 9/65 in R/LPD E and R/LPD non-E groups, respectively. The patient age was 79.0 and 79.5 years, the male to female ratio was 35/20 and 31/29, disease ratio (invasive ductal carcinoma or not)was 7/48 and 30/30(p<0.0001)in R/LPD E and OPD E groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2001019).<br><br>RESULTS: The average operation time was 644.6 and 675.2 minutes, an estimated blood loss was 220.8 and 134.4 g, postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 28/25/21/0, delayed gastric emptying(ISGPS 2007, [-]/Grade A/B/C)was 48/0/4/3 and 61/2/6/5 and postoperative hospital stay was 27.9 and 25.9 and in R/LPD E and R/LPD non-E groups, respectively. No significant differences were noted between the groups, However, postoperative complication over &#x2162;a Clavien-Dindo classification was 8(15.7%)and 3(4.4%)cases(p=0.0319)in R/LPD E and R/ LPD non-E groups. The average operation time was 644.6 and 492.1 minutes(p<0.0001), an estimated blood loss was 220.8 and 534.8 g(p=0.0004), postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 27/8/24/1(p=0.0442), postoperative hospital stay was 27.9 and 42.0(p=0.0490)in R/LPD E and OPD E groups, respectively.<br><br>CONCLUSION: The R/LPD was undergone in safety, even for the over 75 years old patients.},
}
@article {pmid38285770,
year = {2024},
author = {Younas, H and Shahid, M and Khan, Z and Fatima, K and Tasadduq, R},
title = {Investigating the association of Angiotensin II Type I Receptor A1166C Polymorphism with Breast Cancer Risk in the Pakistani Population.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {25},
number = {1},
pages = {79-85},
pmid = {38285770},
issn = {2476-762X},
mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; Angiotensin II/genetics ; Pakistan/epidemiology ; Polymorphism, Genetic ; Renin-Angiotensin System/genetics ; Genotype ; Genetic Predisposition to Disease ; },
abstract = {The polymorphisms of the Renin-Angiotensin System are related to many disorders like diabetes, cardiovascular disease, and different types of cancer. Among all the polymorphisms related to AGTR1, A1166C has been associated with several disorders, including cardiovascular diseases and breast cancer. This study was conducted to discover the association of AGTR1 polymorphism (A1166C) Renin-Angiotensin and its effect on the development and progression of breast cancer in the Pakistani population. One hundred forty participants, including seventy diagnosed breast cancer patients and seventy healthy individuals, were included in this study and genotyped with an allele-specific polymerase chain reaction. The most frequent genotype in healthy participants and breast cancer patients was CC. An insignificant (p value>0.05) risk of breast cancer was found with A1166C polymorphism in codominant (CC vs. AA OR=1.200 [0.256-5.631] and AC vs. AA 0.941 [OR=0.223-3.976]), dominant (OR=1.00 [0.240-4.167]), recessive (OR=1.230 [0.593-2.552]) and additive models (OR=1.028 [0.533-1.983]) of general population genotypes. Nonetheless, when the AA genotype was considered a reference group, a significant association was found between AC and CC genotypes and invasive ductal and ductal carcinoma development in breast cancer patients. In conclusion, this study demonstrated no significant association between AGTR1 (A1166C) polymorphism and breast cancer risk.},
}
@article {pmid38284471,
year = {2024},
author = {Shoshani, A and Kor, A and Farbstein-Yavin, S and Gvion, Y},
title = {Risk and protective factors for substance use and media addictive behaviors in adolescents during the COVID-19 pandemic.},
journal = {Journal of adolescence},
volume = {96},
number = {4},
pages = {746-759},
doi = {10.1002/jad.12295},
pmid = {38284471},
issn = {1095-9254},
mesh = {Humans ; Adolescent ; *COVID-19/epidemiology/psychology/prevention &amp; control ; Male ; Female ; Israel/epidemiology ; *Substance-Related Disorders/epidemiology/psychology ; *Behavior, Addictive/psychology/epidemiology ; Risk Factors ; *Protective Factors ; *Social Media/statistics &amp; numerical data ; Longitudinal Studies ; Child ; Adolescent Behavior/psychology ; Internet Addiction Disorder/epidemiology/psychology ; SARS-CoV-2 ; Surveys and Questionnaires ; Screen Time ; },
abstract = {OBJECTIVE: This study examined the long-term effects of the COVID-19 pandemic on adolescents' substance use, digital media use, and symptoms of internet, gaming, and social media addiction.<br><br>METHOD: A nationally representative longitudinal cohort of 1665 Israeli teens and preteens, aged 9-16, completed questionnaires assessing substance use prevalence, daily screen time, symptoms of media addiction, and potential risk and protective factors. Data were collected before the pandemic (October 2019), after the second wave lockdown (November 2020), and after the fifth wave (April 2022) in Israel.<br><br>RESULTS: The analysis documented significant increases in substance use, daily screen time, and social media addiction indices over time. Gratitude, life satisfaction, positive emotions, future orientation, grit, and secure attachment emerged as significant protective factors. Sensation-seeking, negative emotions, and mental health symptoms were identified as risk factors.<br><br>CONCLUSIONS: These findings highlight the importance of educational and public mental health services in addressing the pandemic's long-term impact on the mental health and addictive behaviors of adolescents. They also emphasize the significance of enhancing protective factors and reducing risk factors to effectively mitigate substance and digital media abuse among adolescents.},
}
@article {pmid38281565,
year = {2024},
author = {Dimitrov, G and Shousha, S and Troianova, P},
title = {CD10 expression as a potential predictor of pathological complete response in ER-negative and triple-negative breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.},
journal = {Experimental and molecular pathology},
volume = {135},
number = {},
pages = {104885},
doi = {10.1016/j.yexmp.2024.104885},
pmid = {38281565},
issn = {1096-0945},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *Triple Negative Breast Neoplasms/drug therapy/genetics ; Anthracyclines/therapeutic use ; Retrospective Studies ; Receptor, ErbB-2/metabolism ; Neoadjuvant Therapy ; Antibiotics, Antineoplastic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; Biomarkers, Tumor/metabolism ; },
abstract = {BACKGROUND: Neoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which patients will achieve pCR remains a challenge. CD10, a myoepithelial marker, has shown diagnostic and prognostic value in metastatic tumors. Its potential as a predictor of chemosensitivity to anthracycline-based NCT in breast cancer is unknown.<br><br>AIM: This retrospective study aimed to investigate the potential of CD10 cancer cell expression as a predictive marker of chemosensitivity in breast cancers treated with anthracycline-based neoadjuvant chemotherapy.<br><br>METHODS: We analyzed 130 patients with invasive ductal carcinoma who received anthracycline-based NCT. CD10 expression was assessed by immunohistochemistry on pre-treatment biopsies. Statistical analysis evaluated the association between CD10 expression and pCR rates.<br><br>RESULTS: Univariate analysis revealed that ER-positive and CD10-negative tumors had lower pCR rates [OR 7.4830 (95% CI 2.7762-20.1699); p&#xa0;=&#xa0;0.0001]. Multivariate analysis confirmed ER status as a strong predictor of poor response [OR 0.085 (95% CI 0.024-0.30); p&#xa0;<&#xa0;0.001] and CD10 expression as a predictor of a favourable response [OR 0.11 (0.8-0.19); p&#xa0;=&#xa0;0.049]. CD10 expression significantly predicted pCR in ER-negative cases [OR 0.1098 (0.0268-0.4503); p&#xa0;=&#xa0;0.0022] and triple-negative breast cancer [OR 0.0966 (95% CI 0.0270-0.3462); p&#xa0;=&#xa0;0.0003]. Concordance was observed between core biopsies and excised samples.<br><br>CONCLUSION: Positive CD10 cancer cell expression may predict increased response to anthracycline-based neoadjuvant chemotherapy in ER-negative and triple-negative breast cancer cases. Further research is needed to validate these findings in larger cohorts and determine the clinical utility of CD10 as a predictive marker.},
}
@article {pmid38278448,
year = {2024},
author = {Mahlow, J and Barry, M and Albertson, DJ and Jo, YJ and Balatico, M and Seasor, T and Gebrael, G and Kumar, SA and Sayegh, N and Tripathi, N and Agarwal, N and Swami, U and Sirohi, D},
title = {Histologic patterns in prostatic adenocarcinoma are not predictive of mutations in the homologous recombination repair pathway.},
journal = {Human pathology},
volume = {144},
number = {},
pages = {28-33},
doi = {10.1016/j.humpath.2024.01.005},
pmid = {38278448},
issn = {1532-8392},
mesh = {Male ; Humans ; Recombinational DNA Repair ; BRCA1 Protein/genetics ; *Carcinoma, Lobular ; BRCA2 Protein/genetics ; Mutation ; *Prostatic Neoplasms/genetics ; },
abstract = {Somatic or germline homologous recombination repair (HRR) pathway gene mutations are commonly detected in prostate cancer, especially in advanced disease, and are associated with response to poly (ADP-ribose) polymerase (PARP) inhibitors. In this study, we evaluated whether histological patterns are predictive of HRR pathway gene mutations. The study population comprised 130 patients with advanced prostate carcinoma who underwent comprehensive genomic profiling (CGP) of tumor tissue at a CLIA-certified laboratory. HRR genes in the study included BRCA1, BRCA2, ATM, BARD1, BRIP, CHEK2, MRE11A, NBN, PALB2, RAD51C, RAD51D, EMSY, ATR, CHEK1, and FAM175A. Overall, 38 patients had mutations in BRCA1/2, 36 in other HRR genes, and 56 were negative for HRR mutations. All cases were re-reviewed and quantified by two genitourinary pathologists blinded to mutational status for the following histological patterns of prostate carcinoma: cribriform, ductal, intraductal carcinoma (IDC), small cell carcinoma, signet ring-like pattern, and lobular carcinoma-like pattern. Discordances were resolved by consensus review. Histologic patterns were analyzed for any correlation with mutations in HRR pathway genes (grouped as BRCA1/2 mutated or non-BRCA1/2 mutated) compared to tumors without mutations in HRR genes by Chi-square testing. Patterns with >20 % and >30 % of tumor volume were additionally evaluated for correlation with mutational status. We found no significant association between HRR pathway mutations and cribriform pattern, IDC, ductal carcinoma, small cell carcinoma, signet ring-like pattern, or lobular carcinoma-like patterns. Tumors with >20 % or >30 % histologic patterns by volume also demonstrated no significant association with mutational status. This study suggests that histopathologic examination alone is insufficient to distinguish prostate cancer with germline or somatic mutations in HRR pathway genes, highlighting the continuing importance of ancillary molecular diagnostics in guiding therapy selection for prostate cancer patients who may benefit from PARP inhibitors.},
}
@article {pmid38273267,
year = {2024},
author = {Yang, ZJ and Xin, F and Chen, ZJ and Yu, Y and Wang, X and Cao, XC},
title = {Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {134},
pmid = {38273267},
issn = {1471-2407},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/metabolism ; Neoadjuvant Therapy ; Treatment Outcome ; Receptor, ErbB-2/metabolism ; Ki-67 Antigen ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {BACKGROUND: Neoadjuvant chemotherapy with dual-targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)-positive breast cancer. Although the dual-targeted therapy has significantly improved the pathological complete response (pCR) rate, further investigation is needed to identify biomarkers that predict the response to neoadjuvant therapy.<br><br>METHODS: This retrospective study analyzed 353 patients with HER2-positive breast invasive ductal carcinoma. The correlation between clinicopathological factors and pCR rate was evaluated. A nomogram was constructed based on the results of the multivariate logistic regression analysis to predict the probability of pCR.<br><br>RESULTS: The breast pCR (b-pCR) rate was 56.1% (198/353) and the total pCR (t-pCR) rate was 52.7% (186/353). Multivariate analysis identified ER status, PR status, HER2 status, Ki-67 index, and neoadjuvant chemotherapy regimens as independent indicators for both b-pCR and t-pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI: 0.68-0.78). According to the nomogram, the t- pCR rate was highest in the ER-PR- HER2-positive patients (131/208) and lowest in the ER&#x2009;+&#x2009;PR&#x2009;+&#x2009;HER2-positive patients (19/73). The subgroup analyses showed that there was no significant difference in pCR rate among the neoadjuvant chemotherapy regimens in ER positive, PR positive, HER2 IHC 2&#x2009;+&#x2009;, Ki67 index&#x2009;<&#x2009;30% population. However, for ER-PR-HER2-positive patients, the neoadjuvant chemotherapy regimen has a great influence on the pCR rates.<br><br>CONCLUSIONS: Patients with ER-negative, PR-negative, HER2 3&#x2009;+&#x2009;and high KI-67 index were more likely to achieve pCR. THP may be used as an alternative to AC-THP or TCbHP in selected HER2-positive patients.},
}
@article {pmid38273260,
year = {2024},
author = {Saad, HA and Baz, A and Riad, M and Eraky, ME and El-Taher, A and Farid, MI and Sharaf, K and Said, HEM and Ibrahim, LA},
title = {Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.},
journal = {BMC immunology},
volume = {25},
number = {1},
pages = {9},
pmid = {38273260},
issn = {1471-2172},
mesh = {Humans ; Female ; *Breast Neoplasms/surgery ; Mastectomy ; Vimentin/therapeutic use ; *Carcinoma, Ductal, Breast/pathology/secondary/surgery ; Tumor Microenvironment ; Matrix Metalloproteinase 1/therapeutic use ; *Carcinoma, Lobular/pathology/secondary/surgery ; },
abstract = {BACKGROUND: Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences.<br><br>METHODS: This was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, &#x3b1;-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated.<br><br>RESULTS: Of the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p&#x2009;=&#x2009;0.000 and 0.021), PDGF (p&#x2009;=&#x2009;0.000 and 0.002), and CD95 (p&#x2009;=&#x2009;0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p&#x2009;=&#x2009;0.000) and &#x3b1;-SMA (p&#x2009;=&#x2009;0.000). &#x3b1;-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form.<br><br>CONCLUSIONS: While the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.},
}
@article {pmid38272241,
year = {2024},
author = {Failayev, H and Ganoth, A and Tsfadia, Y},
title = {Molecular insights on the coronavirus MERS-CoV interaction with the CD26 receptor.},
journal = {Virus research},
volume = {342},
number = {},
pages = {199330},
pmid = {38272241},
issn = {1872-7492},
mesh = {Humans ; Animals ; Dogs ; Dipeptidyl Peptidase 4/genetics ; *Middle East Respiratory Syndrome Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/genetics ; *Coronavirus Infections ; Amino Acids ; },
abstract = {The Middle East respiratory syndrome (MERS) is a severe respiratory disease with high fatality rates, caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus initiates infection by binding to the CD26 receptor (also known as dipeptidyl peptidase 4 or DPP4) via its spike protein. Although the receptor-binding domain (RBD) of the viral spike protein and the complex between RBD and the extracellular domain of CD26 have been studied using X-ray crystallography, conflicting studies exist regarding the importance of certain amino acids outside the resolved RBD-CD26 complex interaction interface. To gain atomic-level knowledge of the RBD-CD26 complex, we employed computational simulations to study the complex's dynamic behavior as it evolves from its crystal structure to a conformation stable in solution. Our study revealed previously unidentified interaction regions and interacting amino acids within the complex, determined a novel comprehensive RBD-binding domain of CD26, and by that expanded the current understanding of its structure. Additionally, we examined the impact of a single amino acid substitution, E513A, on the complex's stability. We discovered that this substitution disrupts the complex through an allosteric domino-like mechanism that affects other residues. Since MERS-CoV is a zoonotic virus, we evaluated its potential risk of human infection via animals, and suggest a low likelihood for possible infection by cats or dogs. The molecular structural information gleaned from our insights into the RBD-CD26 complex pre-dissociative states may be proved useful not only from a mechanistic view but also in assessing inter-species transmission and in developing anti-MERS-CoV antiviral therapeutics.},
}
@article {pmid38265547,
year = {2024},
author = {Dai, Q and Feng, K and Liu, G and Cheng, H and Tong, X and Wang, X and Feng, L and Wang, Y},
title = {Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China.},
journal = {Targeted oncology},
volume = {19},
number = {1},
pages = {81-93},
pmid = {38265547},
issn = {1776-260X},
support = {CIFMS//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: 2021-I2M-1-014//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: LC2022A02//Beijing Hope Run Special Fund of Cancer Foundation of China/ ; },
mesh = {Humans ; Female ; Prognosis ; *Breast Neoplasms/drug therapy/pathology ; Receptor, ErbB-2 ; Retrospective Studies ; Hormones ; },
abstract = {BACKGROUND: The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status.<br><br>OBJECTIVE: To investigate the prognostic impact of HER2-low in different HR subgroups.<br><br>PATIENTS AND METHODS: We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals-36 months, 60 months, and 120 months.<br><br>RESULTS: HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models.<br><br>CONCLUSIONS: HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients' HR status.},
}
@article {pmid38250443,
year = {2023},
author = {Wang, Y and Zhang, X and Yan, Y and Niu, T and Zhang, M and Fan, C and Liang, W and Shu, Y and Guo, C and Guo, D and Bi, Y},
title = {GmABCG5, an ATP-binding cassette G transporter gene, is involved in the iron deficiency response in soybean.},
journal = {Frontiers in plant science},
volume = {14},
number = {},
pages = {1289801},
pmid = {38250443},
issn = {1664-462X},
abstract = {Iron deficiency is a major nutritional problem causing iron deficiency chlorosis (IDC) and yield reduction in soybean, one of the most important crops. The ATP-binding cassette G subfamily plays a crucial role in substance transportation in plants. In this study, we cloned the GmABCG5 gene from soybean and verified its role in Fe homeostasis. Analysis showed that GmABCG5 belongs to the ABCG subfamily and is subcellularly localized at the cell membrane. From high to low, GmABCG5 expression was found in the stem, root, and leaf of young soybean seedlings, and the order of expression was flower, pod, seed stem, root, and leaf in mature soybean plants. The GUS assay and qRT-PCR results showed that the GmABCG5 expression was significantly induced by iron deficiency in the leaf. We obtained the GmABCG5 overexpressed and inhibitory expressed soybean hairy root complexes. Overexpression of GmABCG5 promoted, and inhibition of GmABCG5 retarded the growth of soybean hairy roots, independent of nutrient iron conditions, confirming the growth-promotion function of GmABCG5. Iron deficiency has a negative effect on the growth of soybean complexes, which was more obvious in the GmABCG5 inhibition complexes. The chlorophyll content was increased in the GmABCG5 overexpression complexes and decreased in the GmABCG5 inhibition complexes. Iron deficiency treatment widened the gap in the chlorophyll contents. FCR activity was induced by iron deficiency and showed an extraordinary increase in the GmABCG5 overexpression complexes, accompanied by the greatest Fe accumulation. Antioxidant capacity was enhanced when GmABCG5 was overexpressed and reduced when GmABCG5 was inhibited under iron deficiency. These results showed that the response mechanism to iron deficiency is more actively mobilized in GmABCG5 overexpression seedlings. Our results indicated that GmABCG5 could improve the plant's tolerance to iron deficiency, suggesting that GmABCG5 might have the function of Fe mobilization, redistribution, and/or secretion of Fe substances in plants. The findings provide new insights into the ABCG subfamily genes in the regulation of iron homeostasis in plants.},
}
@article {pmid38233262,
year = {2024},
author = {Wang, B and Fu, Y and Chen, M and Peng, S and Marra, G and Zhuang, J and Zhang, S and Guo, H and Qiu, X},
title = {The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy.},
journal = {Urologic oncology},
volume = {42},
number = {3},
pages = {67.e9-67.e15},
doi = {10.1016/j.urolonc.2023.11.018},
pmid = {38233262},
issn = {1873-2496},
mesh = {Male ; Humans ; Prostate/surgery/pathology ; *Prostatic Neoplasms/drug therapy/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Neoadjuvant Therapy ; Androgen Antagonists/therapeutic use ; Prospective Studies ; Prostatectomy ; Risk Factors ; },
abstract = {OBJECTIVE: To explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer.<br><br>METHODS: Eighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology.<br><br>RESULTS: IDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176-10.971, P&#x202f;=&#x202f;0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234-11.930, P&#x202f;=&#x202f;0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis.<br><br>CONCLUSION: IDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.},
}
@article {pmid38231374,
year = {2024},
author = {Maggi, G and Vitale, C and Giacobbe, C and Barone, A and Mastromarino, C and Iannotta, F and Amboni, M and Weintraub, D and Santangelo, G},
title = {Validation of the Italian version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) in an Italian Parkinson's disease cohort.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {45},
number = {7},
pages = {3153-3161},
pmid = {38231374},
issn = {1590-3478},
mesh = {Humans ; *Parkinson Disease/complications/psychology/diagnosis ; Female ; Male ; Italy ; *Disruptive, Impulse Control, and Conduct Disorders/diagnosis/etiology ; Aged ; Middle Aged ; *Psychiatric Status Rating Scales/standards ; Reproducibility of Results ; Cohort Studies ; Severity of Illness Index ; Surveys and Questionnaires/standards ; Psychometrics/standards ; },
abstract = {INTRODUCTION: Impulse control disorders (ICDs) frequently occur in Parkinson's disease (PD), and an early identification is essential to prevent severe psychosocial consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) has been developed to evaluate the severity of ICDs along with a range of impulsive-compulsive behaviors (ICBs) in PD; however, its Italian version has not yet been validated.<br><br>METHODS: One hundred consecutive outpatients with PD were administered an Italian version of the QUIP-RS and a brief neuropsychological assessment to evaluate global cognitive status and scales to measure depression, apathy and impulsive disorders. We evaluated the internal consistency, convergent and divergent validity, and factorial structure of QUIP-RS. We also explored the possible association between QUIP-RS scores and clinical factors and dopaminergic medication.<br><br>RESULTS: Subsyndromal ICDs manifestations were observed in 54% of&#xa0;the patients, and one in four (22%) reported two or more ICDs or related behaviors. The QUIP-RS demonstrated good internal consistency (Cronbach's alpha = 0.806) and construct validity, and its factorial structure reflected different ICDs and ICBs domains. No association emerged between QUIP-RS scores and&#xa0;the clinical aspects of PD and dopaminergic medication.<br><br>CONCLUSION: We provided, for the first time, an Italian translation of the QUIP-RS and demonstrated its feasibility in clinical and research settings. Severity of ICDs was independent of clinical factors and dopaminergic medication, underlining the need to adopt a broader perspective on their etiopathology in PD.},
}
@article {pmid38229073,
year = {2024},
author = {Ido, M and Fujii, K and Mishima, H and Kubo, A and Saito, M and Banno, H and Ito, Y and Goto, M and Ando, T and Mouri, Y and Kousaka, J and Imai, T and Nakano, S},
title = {Comprehensive genomic evaluation of advanced and recurrent breast cancer patients for tailored precision treatments.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {85},
pmid = {38229073},
issn = {1471-2407},
mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; Phosphatidylinositol 3-Kinases/genetics ; Neoplasm Recurrence, Local/drug therapy/genetics ; Genomics ; Mutation ; *Carcinoma ; High-Throughput Nucleotide Sequencing ; },
abstract = {AIM: The aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease.<br><br>PATIENTS AND METHODS: This study included 22 patients with recurrent breast cancer (n&#x2009;=&#x2009;19) and inoperable de novo stage IV breast cancer (n&#x2009;=&#x2009;3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient.<br><br>RESULTS: Median age was 62.9 years (range, 33.4-82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n&#x2009;=&#x2009;19), invasive lobular carcinoma (n&#x2009;=&#x2009;2), and invasive micropapillary carcinoma (n&#x2009;=&#x2009;1). F1CDx detected a median of 4.5 variants (range, 1-11). The most commonly altered gene were PIK3CA (n&#x2009;=&#x2009;9), followed by TP53 (n&#x2009;=&#x2009;7), MYC (n&#x2009;=&#x2009;4), PTEN (n&#x2009;=&#x2009;3), and CDH1 (n&#x2009;=&#x2009;3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment.<br><br>CONCLUSION: Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.},
}
@article {pmid38215056,
year = {2024},
author = {Schimpfle, L and Tsilingiris, D and Mooshage, CM and Kender, Z and Sulaj, A and von Rauchhaupt, E and Szendroedi, J and Herzig, S and Goepfert, J and Groener, J and Nawroth, PP and Bendszus, M and Heiland, S and Kurz, FT and Jende, JME and Kopf, S},
title = {Phase Angle of Bioelectrical Impedance Analysis as an Indicator for Diabetic Polyneuropathy in Type 2 Diabetes Mellitus.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {109},
number = {11},
pages = {e2110-e2119},
pmid = {38215056},
issn = {1945-7197},
support = {B05//Collaborative Research Council 1118/ ; A03//Collaborative Research Council 1158/ ; //Deutsches Zentrum f&#xfc;r Diabetesforschung (DZD e.V.)/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/physiopathology ; *Diabetic Neuropathies/diagnosis/physiopathology ; Female ; Male ; *Electric Impedance ; Middle Aged ; Cross-Sectional Studies ; Aged ; Neural Conduction/physiology ; Adult ; },
abstract = {CONTEXT: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routines, leading to increased morbidity and mortality.<br><br>OBJECTIVE: We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory, and physical markers of DPN to evaluate PhA as a possible diagnostic method for DPN.<br><br>MATERIALS AND METHODS: In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications, we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), among which 63 had DPN. The PhA was calculated from multifrequency BIA. Nerve conduction studies, quantitative sensory testing (QST) and diffusion-weighted magnetic resonance neurography to determine fractional anisotropy (FA) reflecting peripheral nerve integrity were performed.<br><br>RESULTS: T2D patients with DPN had lower PhA values (5.71 &#xb1; 0.10) compared to T2D patients without DPN (6.07 &#xb1; 0.08, P = .007, + 6.1%) and healthy controls (6.18 &#xb1; 0.08, P < .001, + 7.9%). Confounder-adjusted analyses showed correlations of the PhA with conduction velocities and amplitudes of the peroneal (&#x3b2;=.28; &#x3b2;=.31, P < .001) and tibial nerves (&#x3b2;=.28; &#x3b2;=.32, P < .001), Z-scores of QST (thermal detection &#x3b2;=.30, P < .05) and the FA (&#x3b2;=.60, P < .001). Receiver-operating characteristic analysis showed similar performance of PhA in comparison to the mentioned diagnostic methods.<br><br>CONCLUSION: The study shows that PhA is, in comparison to other test systems used, at least an equally good and much easier to handle investigator-independent marker for detection of DPN.},
}
@article {pmid38195987,
year = {2024},
author = {Knödlseder, N and Fábrega, MJ and Santos-Moreno, J and Manils, J and Toloza, L and Marín Vilar, M and Fernández, C and Broadbent, K and Maruotti, J and Lemenager, H and Carolis, C and Zouboulis, CC and Soler, C and Lood, R and Brüggemann, H and Güell, M},
title = {Delivery of a sebum modulator by an engineered skin microbe in mice.},
journal = {Nature biotechnology},
volume = {42},
number = {11},
pages = {1661-1666},
pmid = {38195987},
issn = {1546-1696},
support = {Marie Sk&#x142;odowska-Curie Grant Agreement 882387//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; Award N62909-18-1-2155//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/ ; - IdC 2019 PROD 00057//Government of Catalonia | Ag&#xe8;ncia de Gesti&#xf3; d'Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants)/ ; Fellowship number 8240//European Molecular Biology Organization (EMBO)/ ; Award Juan de la Cierva FJC 2018-037096-I//Ministerio de Econom&#xed;a y Competitividad (Ministry of Economy and Competitiveness)/ ; Grant Agreement 882387//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Sk&#x142;odowska-Curie Actions (H2020 Excellent Science - Marie Sk&#x142;odowska-Curie Actions)/ ; },
mesh = {*Sebum/metabolism ; Animals ; Mice ; *Skin/microbiology/metabolism ; Humans ; Propionibacteriaceae/genetics ; },
abstract = {Microorganisms can be equipped with synthetic genetic programs for the production of targeted therapeutic molecules. Cutibacterium acnes is the most abundant commensal of the human skin, making it an attractive chassis to create skin-delivered therapeutics. Here, we report the engineering of this bacterium to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin, in vivo, for the modulation of cutaneous sebum production.},
}
@article {pmid38193247,
year = {2024},
author = {Okano, K and Miyai, K and Mikoshi, A and Edo, H and Ito, K and Tsuda, H and Shinmoto, H},
title = {Histological parameters and stromal desmoplastic status affecting accurate diagnosis of extraprostatic extension of prostate cancer using multi-parametric magnetic resonance imaging.},
journal = {International journal of urology : official journal of the Japanese Urological Association},
volume = {31},
number = {5},
pages = {475-482},
doi = {10.1111/iju.15385},
pmid = {38193247},
issn = {1442-2042},
mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnostic imaging/surgery ; Aged ; Middle Aged ; *Prostatectomy ; *Multiparametric Magnetic Resonance Imaging ; Prostate/pathology/diagnostic imaging ; Cell Adhesion Molecules/analysis/metabolism ; Neoplasm Grading ; Retrospective Studies ; Magnetic Resonance Imaging ; },
abstract = {OBJECTIVE: To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer.<br><br>METHODS: One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups.<br><br>RESULTS: pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p&#x2009;<&#x2009;0.0001), anterior location (p&#x2009;=&#x2009;0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p&#x2009;=&#x2009;0.026), and high stromal periostin expression (p&#x2009;<&#x2009;0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup.<br><br>CONCLUSIONS: GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.},
}
@article {pmid38190207,
year = {2024},
author = {Elshanbary, AA and Zaazouee, MS and Nourelden, AZ and Al-Kafarna, M and Matar, SG and Elsaeidy, AS and Ragab, KM and Elhady, MM and Albadrani, GM and Altyar, AE and Kensara, OA and Abdel-Daim, MM},
title = {Risk factors of diabetes and cancer-specific mortalities in patients with infiltrating ductal carcinoma of the breast: a population-based study.},
journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)},
volume = {33},
number = {4},
pages = {321-333},
pmid = {38190207},
issn = {1473-5709},
mesh = {Humans ; Female ; *Breast Neoplasms/mortality/pathology/therapy ; Middle Aged ; Risk Factors ; *Carcinoma, Ductal, Breast/mortality/pathology/therapy/epidemiology ; *SEER Program/statistics &amp; numerical data ; Aged ; Adult ; Diabetes Mellitus/mortality/epidemiology ; Prognosis ; United States/epidemiology ; Survival Rate ; Follow-Up Studies ; Neoplasm Staging ; },
abstract = {BACKGROUND AND AIMS: Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast.<br><br>MATERIALS AND METHODS: Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software.<br><br>RESULTS: A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV.<br><br>CONCLUSION: In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.},
}
@article {pmid38180699,
year = {2024},
author = {Nakagawa, S and Miyashita, M and Maeda, I and Goda, A and Tada, H and Amari, M and Kojima, Y and Tsugawa, K and Ohi, Y and Sagara, Y and Sato, M and Ebata, A and Harada-Shoji, N and Suzuki, T and Nakanishi, M and Ohta, T and Ishida, T},
title = {Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.},
journal = {Breast cancer research and treatment},
volume = {204},
number = {3},
pages = {453-463},
pmid = {38180699},
issn = {1573-7217},
mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *Carcinoma, Lobular/pathology ; Selective Estrogen Receptor Modulators/therapeutic use ; *Carcinoma, Ductal, Breast/pathology ; Treatment Outcome ; Tumor Microenvironment ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC.<br><br>METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy.<br><br>RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P&#x2009;<&#x2009;0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P&#x2009;=&#x2009;0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P&#x2009;=&#x2009;0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P&#x2009;=&#x2009;0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis.<br><br>CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.},
}
@article {pmid38170222,
year = {2024},
author = {Li, QY and Guo, Q and Luo, WM and Luo, XY and Ji, YM and Xu, LQ and Guo, JL and Shi, RS and Li, F and Lin, CY and Zhang, J and Ke, D},
title = {Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.},
journal = {Aging},
volume = {16},
number = {1},
pages = {66-88},
pmid = {38170222},
issn = {1945-4589},
mesh = {Humans ; Cisplatin/pharmacology/therapeutic use ; *Lung Neoplasms/drug therapy/genetics/pathology ; Proto-Oncogene Proteins c-akt/metabolism ; *Adenocarcinoma of Lung/drug therapy/genetics/pathology ; Drug Resistance, Neoplasm/genetics ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Tumor Microenvironment/genetics ; },
abstract = {OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis.<br><br>METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting.<br><br>RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC.<br><br>CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.},
}
@article {pmid38157332,
year = {2023},
author = {Shinohara, T and Asoda, T and Nakano, Y and Yamada, H and Fujimori, Y},
title = {Germline BRCA2 Pathogenic Variant in Primary Breast Cancer of a Down Syndrome Individual.},
journal = {The American journal of case reports},
volume = {24},
number = {},
pages = {e942208},
pmid = {38157332},
issn = {1941-5923},
mesh = {Female ; Humans ; Adult ; *Breast Neoplasms/pathology ; Mastectomy ; *Down Syndrome/complications/surgery ; Biomarkers, Tumor ; *Carcinoma, Ductal/surgery ; Germ Cells/pathology ; BRCA2 Protein/genetics ; },
abstract = {BACKGROUND Down syndrome (DS) is the most common genetic disorder, and individuals with DS are known to have a low risk for solid tumors, including breast cancer. In contrast, Breast Cancer Susceptibility Gene (BRCA) pathogenic variant can cause breast cancer. We report a case of primary breast cancer harboring a BRCA2 pathogenic variant in a 35-year-old woman with DS. CASE REPORT A 35-year-old woman with DS presented with a palpable 2-cm mass in the upper-inner quadrant of the left breast. A biopsy confirmed an invasive ductal carcinoma of the breast. Her clinical diagnosis was cT2, N0, M0, cStageIIA. A left modified radical mastectomy with axillary node dissection was performed. Her final pathological diagnosis was invasive ductal carcinoma (T2, pN1, M0, stageIIB), positive estrogen receptors, negative progesterone receptors, negative human epidermal receptor-2 status. She was started on adjuvant hormonal therapy. Unfortunately, 23 months after the operation, multiple metastases were detected. Testing for a BRCA pathogenic variant was performed, and a BRCA2 pathogenic variant was detected. Olaparib was orally administered, and the levels of tumor markers rapidly declined; however, the levels of the tumor markers started to increase again 5 months after the initiation of olaparib. Subsequently, she developed bilateral carcinomatous lymphangiomatosis and died 59 months after the operation. CONCLUSIONS This report highlights a rare case of primary breast cancer harboring a germline BRCA2 pathogenic variant in an individual with DS. Our study highlights the importance of genetic testing as part of breast cancer management in these patients.},
}
@article {pmid38151327,
year = {2024},
author = {Kos, Z and Nielsen, TO and Laenkholm, AV},
title = {Breast Cancer Histopathology in the Age of Molecular Oncology.},
journal = {Cold Spring Harbor perspectives in medicine},
volume = {14},
number = {6},
pages = {},
pmid = {38151327},
issn = {2157-1422},
mesh = {Humans ; *Breast Neoplasms/pathology/genetics ; Female ; *Biomarkers, Tumor/genetics ; Prognosis ; Carcinoma, Ductal, Breast/pathology/genetics ; },
abstract = {For more than a century, microscopic histology has been the cornerstone for cancer diagnosis, and breast carcinoma is no exception. In recent years, clinical biomarkers, gene expression profiles, and other molecular tests have shown increasing utility for identifying the key biological features that guide prognosis and treatment of breast cancer. Indeed, the most common histologic pattern-invasive ductal carcinoma of no special type-provides relatively little guidance to management beyond triggering grading, biomarker testing, and clinical staging. However, many less common histologic patterns can be recognized by trained pathologists, which in many cases can be linked to characteristic biomarker and gene expression patterns, underlying mutations, prognosis, and therapy. Herein we describe more than a dozen such histomorphologic subtypes (including lobular, metaplastic, salivary analog, and several good prognosis special types of breast cancer) in the context of their molecular and clinical features.},
}
@article {pmid38131316,
year = {2024},
author = {Özden, A and Dalgıç, B and Demir, M and Hazırolan, G and Uzun, &#xd6; and Metan, G},
title = {Impact of a hospital sepsis management protocol on the selection of empirical antibiotics in infectious disease consultations.},
journal = {Journal of chemotherapy (Florence, Italy)},
volume = {36},
number = {3},
pages = {190-197},
doi = {10.1080/1120009X.2023.2296146},
pmid = {38131316},
issn = {1973-9478},
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Anti-Bacterial Agents/therapeutic use ; *Bacteremia/drug therapy ; beta-Lactamases ; Carbapenems ; *Communicable Diseases/drug therapy ; Escherichia coli ; *Escherichia coli Infections/drug therapy ; Hospitals ; *Klebsiella Infections/microbiology ; Piperacillin, Tazobactam Drug Combination/therapeutic use ; Referral and Consultation ; Retrospective Studies ; *Sepsis/drug therapy ; Clinical Trials as Topic ; },
abstract = {It is well-established that Infectious Diseases consultation (IDC) enhances the prognosis of bloodstream infections. However, it is unclear if adoption of an institutional sepsis protocol would lead to any further improvement in a setting where IDC and infectious diseases approval (IDA) - available throughout 7 days/24 hours -are mandatory for administering broad spectrum antibiotics. We aimed to evaluate the influence of the institutional sepsis protocol developed by Department of Infectious Diseases and Clinical Microbiology on the selection of appropriate empirical antibiotics by IDC through focusing on patients who had bloodstream infections caused by Extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, which poses a therapeutic challenge. One hundred and fifty-three adult patients (58 patients in the pre-protocol period and 95 patients in the post-protocol period), who received empirical antibiotic treatment for ESBL-producing E. coli and K. pneumoniae, in whom at least one systemic antibiotic was started either on the day blood cultures were drawn or not later than 24 hours were included in the study, retrospectively. The primary outcome was whether the empirical treatment regimen included a carbapenem that was accepted as the appropriate treatment based on the results of the MERINO trial. Secondary outcomes included empirical treatment based on pre-defined risk factors suggesting multidrug resistance (MDR), 30-day inpatient mortality, and appropriate antibacterial treatment according to antimicrobial susceptibility test (AST) results. The median age (Interquartile range) was 61 (48-70.5) years and 76 (49.7%) out of 153 patients were male. The patients in the post-protocol period were older compared to the pre-protocol period (54 years vs 64 years, p = 0.045). The Charlson Comorbidity Index was higher during the post-protocol period compared to the pre-protocol period (4 vs 5, p=0.038). At least one risk factor for MDR bacteria infection was present in 147 (96.1%) of the 153 patients. While the rate of risk factors for MDR bacteria infections did not differ significantly between the pre-protocol and post-protocol periods, the post-protocol period showed a significantly higher level of appropriate antibiotic treatment according to the presence of MDR risk factors compared to the pre-protocol period (44.8% vs 64.2%, p=0.019). There was a significant increase in the use of carbapenems in the post-protocol period compared to the pre-protocol period (34.5% vs. 56.8%, p=0.007). When the subgroup of patients who were likely to have infection caused by ESBL-producing bacteria is taken into consideration, the carbapenem use was more frequent in the post-protocol period (37.8% vs 68.9%, p=0.002). The rate of appropriate empirical treatment according to AST was not statistically different between pre-protocol and post-protocol period. The 30-day mortality rates were similar in both periods (24.1% vs 31.5, p=0.33). However, the rate of susceptibility to piperacillin-tazobactam was statistically higher in the pre-protocol period (82.6% vs 46.2%, p=0.016) when 39.7% of the patients received piperacillin-tazobactam as the empirical treatment. This study highlights the significance of using a structured protocol to attain appropriate empirical treatment for patients suspected of sepsis, even in a setting where IDC is readily available.},
}
@article {pmid38104283,
year = {2023},
author = {Maman, A and Senol, O},
title = {Evaluating Alterations in Breast Cancer Patients after Recovery Via A PET/CT-Assisted Metabolomics Approach.},
journal = {Puerto Rico health sciences journal},
volume = {42},
number = {4},
pages = {276-282},
pmid = {38104283},
issn = {2373-6011},
mesh = {Humans ; Female ; *Positron Emission Tomography Computed Tomography ; *Breast Neoplasms/pathology ; Metabolome ; Metabolomics/methods ; Biomarkers ; },
abstract = {OBJECTIVE: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery.<br><br>MATERIALS AND METHODS: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm.<br><br>RESULTS AND DISCUSSION: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient.<br><br>CONCLUSION: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.},
}
@article {pmid38091153,
year = {2024},
author = {Schwartz, CJ and Khorsandi, N and Blanco, A and Mukhtar, RA and Chen, YY and Krings, G},
title = {Clinicopathologic and genetic analysis of invasive breast carcinomas in women with germline CHEK2 variants.},
journal = {Breast cancer research and treatment},
volume = {204},
number = {1},
pages = {171-179},
pmid = {38091153},
issn = {1573-7217},
mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; *Breast Neoplasms/genetics/pathology ; Checkpoint Kinase 2/genetics ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Germ Cells ; Carrier Proteins/genetics ; },
abstract = {PURPOSE: Germline pathogenic variants in checkpoint kinase 2 (CHEK2) are associated with a moderately increased risk of breast cancer (BC). The spectrum of clinicopathologic features and genetics of these tumors has not been fully established.<br><br>METHODS: We characterized the histopathologic and clinicopathologic features of 44 CHEK2-associated BCs from 35 women, and assessed responses to neoadjuvant chemotherapy. A subset of cases (n&#x2009;=&#x2009;23) was additionally analyzed using targeted next-generation DNA sequencing (NGS).<br><br>RESULTS: Most (94%, 33/35) patients were heterozygous carriers for germline CHEK2 variants, and 40% had the c.1100delC allele. Two patients were homozygous, and five had additional germline pathogenic variants in ATM (2), PALB2 (1), RAD50 (1), or MUTYH (1). CHEK2-associated BCs occurred in younger women (median age 45&#xa0;years, range 25-75) and were often multifocal (20%) or bilateral (11%). Most (86%, 38/44) were invasive ductal carcinomas of no special type (IDC-NST). Almost all (95%, 41/43) BCs were ER&#x2009;+&#x2009;(79% ER&#x2009;+&#x2009;HER2-, 16% ER&#x2009;+&#x2009;HER2&#x2009;+&#x2009;, 5% ER-HER2&#x2009;+), and most (69%) were luminal B. Nottingham grade, proliferation index, and results of multiparametric molecular testing were heterogeneous. Biallelic CHEK2 alteration with loss of heterozygosity was identified in most BCs (57%, 13/23) by NGS. Additional recurrent alterations included GATA3 (26%), PIK3CA (226%), CCND1 (22%), FGFR1 (22%), ERBB2 (17%), ZNF703 (17%), TP53 (9%), and PPM1D (9%), among others. Responses to neoadjuvant chemotherapy were variable, but few patients (21%, 3/14) achieved pathologic complete response. Most patients (85%) were without evidence of disease at time of study (n&#x2009;=&#x2009;34). Five patients (15%) developed distant metastasis, and one (3%) died (mean follow-up 50&#xa0;months).<br><br>CONCLUSION: Almost all CHEK2-associated BCs were ER&#x2009;+&#x2009;IDC-NST, with most classified as luminal B with or without HER2 overexpression. NGS supported the luminal-like phenotype and confirmed CHEK2 as an oncogenic driver in the majority of cases. Responses to neoadjuvant chemotherapy were variable but mostly incomplete.},
}
@article {pmid38090235,
year = {2023},
author = {Adedokun, KA and Oluogun, WA and Oyenike, MA and Imodoye, SO and Yunus, LA and Lasisi, SA and Bello, IO and Kamorudeen, RT and Adekola, SA},
title = {Expression Patterns of ER, PR, HER-2/neu and p53 in Association with Nottingham Tumour Grade in Breast Cancer Patients.},
journal = {Sultan Qaboos University medical journal},
volume = {23},
number = {4},
pages = {526-533},
pmid = {38090235},
issn = {2075-0528},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53 ; Receptor, ErbB-2/genetics/metabolism ; Hormones ; },
abstract = {OBJECTIVES: Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade.<br><br>METHODS: In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53.<br><br>RESULTS: Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed.<br><br>CONCLUSION: Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER-2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.},
}
@article {pmid38076287,
year = {2023},
author = {Tractenberg, RE and Groah, SL and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH},
title = {Urinary Symptoms Among People With Neurogenic Lower Urinary Tract Dysfunction (NLUTD) Vary by Bladder Management.},
journal = {Topics in spinal cord injury rehabilitation},
volume = {29},
number = {3},
pages = {31-43},
pmid = {38076287},
issn = {1945-5763},
mesh = {Humans ; Urinary Bladder ; *Urinary Bladder, Neurogenic/therapy/diagnosis ; *Spinal Cord Injuries/complications ; Catheters, Indwelling ; Pain/complications ; },
abstract = {OBJECTIVES: To determine whether assessment and decision-making around urinary symptoms in people with neurogenic lower urinary tract dysfunction (NLUTD) should depend on bladder management.<br><br>METHODS: Three surveys of urinary symptoms associated with NLUTD (USQNBs) were designed specific to bladder management method for those who manage their bladders with indwelling catheter (IDC), intermittent catheter (IC), or voiding (V). Each was deployed one time to a national sample. Subject matter experts qualitatively assessed the wording of validated items to identify potential duplicates. Clustering by unsupervised structural learning was used to analyze duplicates. Each item was classified into mutually exclusive and exhaustive categories: clinically actionable ("fever"), bladder-specific ("suprapubic pain"), urine quality ("cloudy urine"), or constitutional ("leg pain").<br><br>RESULTS: A core of 10 "NLUTD urinary symptoms" contains three clinically actionable, bladder-specific, and urine quality items plus one constitutional item. There are 9 (IDC), 11 (IC), and 8 (V) items unique to these instruments. One decision-making protocol applies to all instruments.<br><br>CONCLUSION: Ten urinary symptoms in NLUTD are independent of bladder management, whereas a similar number depend on bladder management. We conclude that assessment of urinary symptoms for persons with NLUTD should be specific to bladder management method, like the USQNBs are.},
}
@article {pmid38070191,
year = {2024},
author = {Mouabbi, JA and Qaio, W and Shen, Y and Raghavendra, AS and Tripathy, D and Layman, RM},
title = {Efficacy of Single-Agent Chemotherapy in Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma.},
journal = {The oncologist},
volume = {29},
number = {3},
pages = {213-218},
pmid = {38070191},
issn = {1549-490X},
support = {MIRA RP170067//Cancer Prevention and Research Institute of Texas/ ; //NIH/ ; //NCI/ ; },
mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; Prospective Studies ; Receptor, ErbB-2/genetics/therapeutic use ; *Breast Neoplasms/pathology ; Capecitabine/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {BACKGROUND: Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC.<br><br>MATERIALS AND METHODS: Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic setting. We compared outcomes between 173 CAP-treated and 96 TAX-treated patients.<br><br>RESULTS: CAP-treated patients had significantly better median progression-free survival (PFS) than TAX-treated patients (8.8 vs 5.0 months, HR 0.63, P&#x2005;<&#x2005;.001). Overall survival (OS) did not differ significantly between the groups (42.7 vs 36.6 months for CAP vs TAX, respectively, HR 0.84, P&#x2005;=&#x2005;.241). Multivariate analyses for PFS and OS revealed better outcomes in subjects with fewer metastatic sites and those exposed to more lines of ET. Additionally, Black patients showed worse OS outcomes compared to White patients (HR 2.46; P&#x2005;=&#x2005;.001).<br><br>CONCLUSION: In ET-refractory HR+ HER2-negative mILC, single-agent CAP demonstrated superior PFS compared to TAX. Our findings highlight the potential benefit of CAP in this patient subset, warranting further investigation through prospective trials.},
}
@article {pmid38067216,
year = {2023},
author = {Bernhardt, M and Kristiansen, G},
title = {Molecular Alterations in Intraductal Carcinoma of the Prostate.},
journal = {Cancers},
volume = {15},
number = {23},
pages = {},
pmid = {38067216},
issn = {2072-6694},
abstract = {Intraductal carcinoma of the prostate is most commonly associated with high-grade invasive prostate cancer. However, isolated IDC-P without adjacent cancer or high-grade cancer is also well known. Common genetic alterations present in IDC-P with adjacent high-grade prostate cancer are those described in high-grade tumors, such as PTEN loss (69-84%). In addition, the rate of LOH involving TP53 and RB1 is significantly higher. IDC-P is common in the TCGA molecular subset of SPOP mutant cancers, and the presence of SPOP mutations are more likely in IDC-P bearing tumors. IDC-P without adjacent high-grade cancers are by far less common. They are less likely to have PTEN loss (47%) and rarely harbor an ERG fusion (7%). Molecular alterations that may predispose a person to the development of IDC-P include the loss of BRCA2 and PTEN as well as mutations in SPOP. However, the causative nature of these genetic alterations is yet to be validated.},
}
@article {pmid38049608,
year = {2024},
author = {Maggi, G and Giacobbe, C and Vitale, C and Amboni, M and Obeso, I and Santangelo, G},
title = {Theory of mind in mild cognitive impairment and Parkinson's disease: The role of memory impairment.},
journal = {Cognitive, affective &amp; behavioral neuroscience},
volume = {24},
number = {1},
pages = {156-170},
pmid = {38049608},
issn = {1531-135X},
mesh = {Humans ; *Parkinson Disease/complications/psychology ; *Theory of Mind ; *Cognitive Dysfunction/etiology/psychology ; Executive Function ; *Cognition Disorders ; Memory Disorders ; Neuropsychological Tests ; },
abstract = {BACKGROUND: Social cognition is impaired in Parkinson's disease (PD). Whether social cognitive impairment (iSC) is a by-product of the underlying cognitive deficits in PD or a process independent of cognitive status is unknown. To this end, the present study was designed to investigate the weight of specific cognitive deficits in social cognition, considering different mild cognitive impairment subtypes of PD (PD-MCI).<br><br>METHODS: Fifty-eight PD patients underwent a neuropsychological battery assessing executive functions, memory, language, and visuospatial domains, together with social cognitive tests focused on theory of mind (ToM). Patients were divided into subgroups according to their clinical cognitive status: amnestic PD-MCI (PD-aMCI, n = 18), non-amnestic PD-MCI (PD-naMCI, n = 16), and cognitively unimpaired (PD-CU, n = 24). Composite scores for cognitive and social domains were computed to perform mediation analyses.<br><br>RESULTS: Memory and language impairments mediated the effect of executive functioning in social cognitive deficits in PD patients. Dividing by MCI subgroups, iSC occurred more frequently in PD-aMCI (77.8%) than in PD-naMCI (18.8%) and PD-CU (8.3%). Moreover, PD-aMCI performed worse than PD-CU in all social cognitive measures, whereas PD-naMCI performed worse than PD-CU in only one subtype of the affective and cognitive ToM tests.<br><br>CONCLUSIONS: Our findings suggest that ToM impairment in PD can be explained by memory dysfunction that mediates executive control. ToM downsides in the amnesic forms of PD-MCI may suggest that subtle changes in social cognition could partly explain future transitions into dementia. Hence, the evaluation of social cognition in PD is critical to characterize a possible behavioral marker of cognitive decline.},
}
@article {pmid38047107,
year = {2023},
author = {Zhang, W and Nowotny, H and Theodoropoulou, M and Simon, J and Hemmer, CM and Bidlingmaier, M and Auer, MK and Reincke, M and Uhlenhaut, H and Reisch, N},
title = {E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1249863},
pmid = {38047107},
issn = {1664-2392},
mesh = {Animals ; Female ; Humans ; Mice ; Adrenocorticotropic Hormone/metabolism ; Cholesterol ; *Cushing Syndrome ; Dexamethasone/pharmacology ; *Glucocorticoids/pharmacology ; Hydrocortisone ; Lipid Metabolism/genetics ; Prospective Studies ; RNA, Messenger/metabolism ; },
abstract = {PURPOSE: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism.<br><br>METHODS: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47.<br><br>RESULTS: E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30&#xa0;min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission.<br><br>CONCLUSION: E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such as&#xa0;dyslipidemia.},
}
@article {pmid38046902,
year = {2023},
author = {Naeimzadeh, Y and Ilbeigi, S and Dastsooz, H and Rafiee Monjezi, M and Mansoori, Y and Tabei, SMB},
title = {Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers.},
journal = {BioMed research international},
volume = {2023},
number = {},
pages = {8236853},
pmid = {38046902},
issn = {2314-6141},
mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/pathology ; Breast/pathology ; GTPase-Activating Proteins/genetics/metabolism ; },
abstract = {Invasive duct carcinoma (IDC) is one of the most common types of breast cancer (BC) in women worldwide, with a high risk of malignancy, metastasis, recurrence, and death. So far, molecular patterns among IDC cases have not been fully defined. However, extensive evidence has shown that dysregulated Rho family small GTPases (Rho GTPases) including Rho GTPase activating proteins (RhoGAPs) have important roles in the invasive features of IDCs. In the current study, we analyzed the expression levels of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) breast cancer (BRCA) and also our 51 IDC tumors compared to their matched normal tissues using quantitative polymerase chain reaction (qPCR). Our TCGA data analysis revealed higher expression of ARHGAP11A and ARHGAP11B in various cancers comprising BCs. Also, we found correlations between these genes and other genes in TCGA-BRCA. Moreover, our methylation analysis showed that their promotor methylation had a negative correlation with their overexpression. QPCR revealed their significant upregulation in our tumor samples. Furthermore, we found that the expression level of ARHGAP11A was considerably lower in women who were breastfeeding. Moreover, it had overexpression in cases who had regular menstrual cycles and early age (younger than 14) at menarche. However, ARHGAP11B had a higher expression in HER2-positive tumors versus HER2-positive and ER-positive tumors. Our study found possible protooncogenic roles for these genes and their involvement in IDC pathogenesis and malignancy. Therefore, they can be considered novel prognostic and diagnostic biomarkers for IDC.},
}
@article {pmid38026906,
year = {2023},
author = {Günay, S and Gökçek, B and Kandemir, &#xd6; and Akan, A and Yalçın, O},
title = {Long-term results of breast cancer patients who received IOERT as boost during BCS: A single-institution retrospective analysis.},
journal = {Turkish journal of surgery},
volume = {39},
number = {2},
pages = {115-120},
pmid = {38026906},
issn = {2564-6850},
abstract = {OBJECTIVES: Intraoperative electron radiotherapy (IOERT) applied as boost to the tumor bed during breast conserving surgery is advantageous in terms of local recurrence in breast cancer patients. In addition, it has other advantages over the adjuvant boost RT such as no risk of tumor bed change, ease of sequencing radiotherapy chemotherapy, and reduced workload of the radiotherapy clinic. This study aimed to evaluate the long-term results of our patients who were treated with this method in our institution and are still being followed up.<br><br>MATERIAL AND METHODS: One hundred and three patients enrolled in this study received IOERT equivalent to 10 Gy as boost during BCS and were subsequently given adjuvant WBI according to the biological subtype of the tumor systemic therapy. These patients were analyzed using their files and hospital records. Patients were evaluated for overall survival, local recurrence, distant metastasis, and cosmetic outcome (using LENT-SOMA scale).<br><br>RESULTS: Median age was 53,5 (27-74), mean follow-up time was 75 (48-106) months. Mean pathological tumor size was 18 mm (4-30), 90 of the patients had invasive ductal carcinoma, eight of them were lobular and five of them had mixed histological structure. Ninety-three of the patients presented histological grade II, 15 grade III; 74 patients were luminal A-like, 15 luminal B-like, eight HER2 positive and six triple negative breast cancer. According to the LENT-SOMA scale, 35 had grade 0, 42 each had grade I, 23 had grade II, and two had grade III. All patients underwent whole breast irradiation after surgery, 81 received chemotherapy and 90 endocrine therapy. There was one local recurrence, distant recurrence was seen in four patients and one patient died of non-breast cancer causes. Overall survival was %99, and event free survival %96.<br><br>CONCLUSION: IOERT for breast cancer treatment during BCS is a safe option with low chronic toxicity and the cosmetic outcome gets better over time.},
}
@article {pmid38024052,
year = {2023},
author = {Prabhu, SD and Rai, HS and Nayak, R and Naik, R and Jayasheelan, S},
title = {Study of the Immunohistochemical Expression of p63 in Benign Lesions and Carcinoma of the Breast at a Tertiary Hospital in South India.},
journal = {Cureus},
volume = {15},
number = {11},
pages = {e48557},
pmid = {38024052},
issn = {2168-8184},
abstract = {BACKGROUND: Invasive breast carcinoma is among the most common female cancers worldwide, causing high morbidity and mortality. Considerable disagreement in the interpretation of diagnostically challenging breast lesions based on histology alone has been documented. One of the essential histopathological findings that help distinguish benign from malignant lesions is the presence of the myoepithelial cell layer. Myoepithelial markers such as tumor protein 63 (p63) help distinguish invasive carcinoma from benign proliferations. p63 antibody is superior to other myoepithelial markers as it selectively stains the nuclei and is negative in stromal cells.<br><br>OBJECTIVE: To study the expression of p63 in various histological subtypes and grades of breast carcinomas.<br><br>METHODS: After routine hematoxylin and eosin stain, 65 cases of breast lesions were subjected to immunohistochemistry for p63 antigen using Novacastra ready-to-use monoclonal antibody p6. All cases were analyzed for p63 expression, and its staining arrangement was interpreted.<br><br>RESULTS: In all benign lesions, immunoreactivity was noted in the myoepithelial cells, forming a continuous layer surrounding the luminal epithelial cells. The benign papillary lesions showed p63 staining in the fibrovascular core of the papillary fronds and at the periphery. A few single myoepithelial cells stained by p63 were also seen scattered discontinuously in ductal carcinoma in situ (DCIS). All invasive carcinomas and encapsulated papillary carcinomas were completely devoid of peripheral p63 staining of myoepithelial cells.<br><br>CONCLUSION: p63 is a specific nuclear marker of myoepithelial cells in the breast and can, therefore, aid in distinguishing invasive ductal carcinoma from DCIS or rare questionable hyperplastic lesions. They also play a significant role in distinguishing various papillary lesions of the breast and, hence, can be incorporated into routine reporting for definitive diagnosis and accurate treatment.},
}
@article {pmid38022397,
year = {2023},
author = {Zhu, XD and Yu, JH and Ai, FL and Wang, Y and Lv, W and Yu, GL and Cao, XK and Lin, J},
title = {Construction and Validation of a Novel Nomogram for Predicting the Risk of Metastasis in a Luminal B Type Invasive Ductal Carcinoma Population.},
journal = {World journal of oncology},
volume = {14},
number = {6},
pages = {476-487},
pmid = {38022397},
issn = {1920-454X},
abstract = {BACKGROUND: Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma.<br><br>METHODS: We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram.<br><br>RESULTS: The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis.<br><br>CONCLUSIONS: The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.},
}
@article {pmid38012767,
year = {2023},
author = {Deguchi, S and Iwakami, A and Tujigiwa, M and Otake, H and Mano, Y and Yamamoto, N and Nakazawa, Y and Misra, M and Nagai, N},
title = {Recovery from indomethacin-induced gastrointestinal bleeding by treatment with teprenone.},
journal = {Journal of pharmaceutical health care and sciences},
volume = {9},
number = {1},
pages = {44},
pmid = {38012767},
issn = {2055-0294},
abstract = {BACKGROUND: Gastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats).<br><br>METHODS: Gastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised.<br><br>RESULTS: On day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP.<br><br>CONCLUSIONS: These results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.},
}
@article {pmid38008819,
year = {2023},
author = {Jalilian, E and Abolhasani-Zadeh, F and Afgar, A and Samoudi, A and Zeinalynezhad, H and Langroudi, L},
title = {Neutralizing tumor-related inflammation and reprogramming of cancer-associated fibroblasts by Curcumin in breast cancer therapy.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {20770},
pmid = {38008819},
issn = {2045-2322},
support = {IR.KMU.REC.1398.326//Kerman University of Medical Sciences/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Cancer-Associated Fibroblasts/metabolism ; *Curcumin/pharmacology/therapeutic use/metabolism ; Cyclooxygenase 2/metabolism ; Dinoprostone/metabolism ; Fibroblasts/metabolism ; Inflammation/pathology ; Cell Line, Tumor ; Tumor Microenvironment ; },
abstract = {Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.},
}
@article {pmid38007354,
year = {2024},
author = {Miyajima, K and Sato, S and Uchida, N and Suzuki, H and Iwatani, K and Imai, Y and Aikawa, K and Yanagisawa, T and Kimura, S and Tashiro, K and Tsuzuki, S and Honda, M and Koike, Y and Miki, J and Miki, K and Shimomura, T and Yuen, S and Yamada, Y and Aoki, M and Takahashi, H and Urabe, F and Kimura, T},
title = {Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis.},
journal = {Clinical genitourinary cancer},
volume = {22},
number = {2},
pages = {149-156.e1},
doi = {10.1016/j.clgc.2023.10.005},
pmid = {38007354},
issn = {1938-0682},
mesh = {Male ; Humans ; *Brachytherapy/adverse effects ; Prostate/pathology ; Retrospective Studies ; *Carcinoma, Intraductal, Noninfiltrating/etiology ; Clinical Relevance ; *Prostatic Neoplasms/pathology ; },
abstract = {BACKGROUND: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT).<br><br>METHODS: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P.<br><br>RESULTS: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003).<br><br>CONCLUSION: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.},
}
@article {pmid38000681,
year = {2024},
author = {Boyraz, B and Ly, A},
title = {Spectrum of histopathologic findings in risk-reducing bilateral prophylactic mastectomy in patients with and without BRCA mutations.},
journal = {Human pathology},
volume = {151},
number = {},
pages = {105534},
doi = {10.1016/j.humpath.2023.11.010},
pmid = {38000681},
issn = {1532-8392},
mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Biomarkers, Tumor/genetics ; *BRCA1 Protein/genetics ; *BRCA2 Protein/genetics ; *Breast Neoplasms/genetics/pathology/prevention &amp; control/surgery ; Carcinoma, Ductal, Breast/genetics/pathology/prevention &amp; control/surgery ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery/prevention &amp; control ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Phenotype ; *Prophylactic Mastectomy ; PTEN Phosphohydrolase/genetics ; Risk Factors ; },
abstract = {Many germline mutations have been implicated in breast cancer pathogenesis and despite several studies on occult atypical lesions in prophylactic mastectomy specimens from patients with BRCA1/2 mutations, there are very limited data on other genes associated with increased breast cancer risk and the distribution of lesions in patients with hereditary breast cancer. We identified 207 patients who underwent bilateral prophylactic mastectomy due to germline mutations in BRCA1/2, PALB2, CHEK2, ATM, CDH1, PTEN, BARD1, or strong family history between 2015 and 2023. Patients with biopsy-proven past or current invasive breast carcinoma or carcinoma in-situ preoperatively were excluded. In addition to multiple benign lesions, the following atypical lesions were identified: flat epithelial atypia (16.9%), atypical ductal hyperplasia (14.0%), lobular neoplasia (14.0%), ductal carcinoma in-situ (4.3%), invasive ductal carcinoma (0.4%). Both low-grade and high-grade pathway lesions were identified in this cohort, and in a subset of patients, they co-occurred. The frequency of atypical lesions identified in patients with strong family history were comparable to those with proven germline mutation. PTEN immunohistochemistry showed loss of expression in ductal carcinoma in-situ and tubular adenomas in PTEN-mutant patients. Overall, findings from this cohort support the benefit of prophylactic mastectomy in patients with germline mutations and/or strong family history. Additionally, this is the first demonstration that PTEN immunohistochemistry may be helpful in identifying germline mutations in patients with atypical or neoplastic proliferations.},
}
@article {pmid37993256,
year = {2023},
author = {Wang, H and Ma, X and Li, S and Ni, X},
title = {SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.},
journal = {Aging},
volume = {15},
number = {22},
pages = {13150-13162},
pmid = {37993256},
issn = {1945-4589},
mesh = {Humans ; Biomarkers, Tumor/genetics ; *Carcinoma, Renal Cell/genetics/pathology ; Computational Biology/methods ; Gene Expression Profiling/methods ; Gene Regulatory Networks ; *Kidney Neoplasms/genetics ; Transcription Factors/genetics ; },
abstract = {BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear.<br><br>METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting.<br><br>RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more.<br><br>CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.},
}
@article {pmid37978324,
year = {2023},
author = {Stead, Z and Capuano, R and Di Natale, C and Pain, A},
title = {The volatilome signatures of Plasmodium falciparum parasites during the intraerythrocytic development cycle in vitro under exposure to artemisinin drug.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {20167},
pmid = {37978324},
issn = {2045-2322},
support = {BAS/1/1020-01-01//KAUST faculty baseline fund/ ; BAS/1/1020-01-01//KAUST faculty baseline fund/ ; Giunta Regionale n. G10795//Regione Lazio/ ; Giunta Regionale n. G10795//Regione Lazio/ ; },
mesh = {Humans ; Animals ; Plasmodium falciparum ; *Parasites ; *Antimalarials/pharmacology/therapeutic use ; *Volatile Organic Compounds/pharmacology ; Drug Resistance ; *Artemisinins/pharmacology/therapeutic use ; *Malaria, Falciparum/drug therapy/parasitology ; *Malaria/drug therapy ; Protozoan Proteins/pharmacology ; },
abstract = {Volatile organic compounds (VOCs) comprise a diverse range of metabolites with high vapour pressure and low boiling points. Although they have received attention, they are a largely unexplored part of the metabolome. Previous studies have shown that malaria infections produce characteristic, definitive, and detectable volatile signatures. Many transcriptional and metabolic differences are observed at different stages of the parasite Intraerythrocytic Developmental Cycle (IDC) as well as when artemisinin-resistant parasites are put under drug pressure. This prompted our research to characterize whether these responses are reflected at a volatile level in malaria during the IDC stages using gas chromatography-mass spectrometry. We investigated whether the resistant P. falciparum parasites would produce their own characteristic volatilome profile compared to near-isogenic wild-type parasite in vitro; firstly at three different stages of the IDC and secondly in the presence or absence of artemisinin drug treatment. Finally, we explored the VOC profiles from two media environments (Human serum and Albumax) of recently lab-adapted field parasite isolates, from Southeast Asia and West/East Africa, compared to long-term lab-adapted parasites. Recognizable differences were observed between IDC stages, with schizonts having the largest difference between wild type and resistant parasites, and with cyclohexanol and 2,5,5-trimethylheptane only present for resistant schizonts. Artemisinin treatment had little effect on the resistant parasite VOC profile, whilst for the wild type parasites compounds ethylbenzene and nonanal were greatly affected. Lastly, differing culturing conditions had an observable impact on parasite VOC profile and clustering patterns of parasites were specific to geographic origin. The results presented here provide the foundation for future studies on VOC based characterization of P. falciparum strains differing in abilities to tolerate artemisinin.},
}
@article {pmid37925055,
year = {2024},
author = {Derakhshan, F and Da Cruz Paula, A and Selenica, P and da Silva, EM and Grabenstetter, A and Jalali, S and Gazzo, AM and Dopeso, H and Marra, A and Brown, DN and Ross, DS and Mandelker, D and Razavi, P and Chandarlapaty, S and Wen, HY and Brogi, E and Zhang, H and Weigelt, B and Pareja, F and Reis-Filho, JS},
title = {Nonlobular Invasive Breast Carcinomas with Biallelic Pathogenic CDH1 Somatic Alterations: A Histologic, Immunophenotypic, and Genomic Characterization.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {37},
number = {2},
pages = {100375},
pmid = {37925055},
issn = {1530-0285},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA247749/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Cadherins/genetics ; Genomics ; Antigens, CD/genetics ; },
abstract = {CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, biallelic CDH1 alterations may be found in nonlobular breast carcinomas (NL-BCs). We sought to determine the clinicopathologic characteristics and repertoire of genetic alterations of NL-BCs harboring CDH1 biallelic genetic alterations. Analysis of 5842 breast cancers (BCs) subjected to clinical tumor-normal sequencing with an FDA-cleared multigene panel was conducted to identify BCs with biallelic CDH1 pathogenic/likely pathogenic somatic mutations lacking lobular features. The genomic profiles of NL-BCs with CDH1 biallelic genetic alterations were compared with those of ILCs and invasive ductal carcinomas (IDCs), matched by clinicopathologic characteristics. Of the 896 CDH1-altered BCs, 889 samples were excluded based on the diagnosis of invasive mixed ductal/lobular carcinoma or ILC or the detection of monoallelic CDH1 alterations. Only 7 of the 5842 (0.11%) BCs harbored biallelic CDH1 alterations and lacked lobular features. Of these, 4/7 (57%) cases were ER-positive/HER2-negative, 1/7 (14%) was ER-positive/HER2-positive, and 2/7 (29%) were ER-negative/HER2-negative. In total, 5/7 (71%) were of Nottingham grade 2, and 2/7 (29%) were of grade 3. The NL-BCs with CDH1 biallelic genetic alterations included a mucinous carcinoma (n = 1), IDCs with focal nested growth (n = 2), IDC with solid papillary (n = 1) or apocrine (n = 2) features, and an IDC of no special type (NST; n = 1). E-cadherin expression, as detected by immunohistochemistry, was absent (3/5) or aberrant (discontinuous membranous/cytoplasmic/granular; 2/5). However, NL-BCs with CDH1 biallelic genetic alterations displayed recurrent genetic alterations, including TP53, PIK3CA (57%, 4/7; each), FGFR1, and NCOR1 (28%, 2/7, each) alterations. Compared with CDH1 wild-type IDC-NSTs, NL-BCs less frequently harbored GATA3 mutations (0% vs 47%, P = .03), but no significant differences were detected when compared with matched ILCs. Therefore, NL-BCs with CDH1 biallelic genetic alterations are vanishingly rare, predominantly comprise IDCs with special histologic features, and have genomic features akin to luminal B ER-positive BCs.},
}
@article {pmid37922498,
year = {2024},
author = {Maggi, G and Giacobbe, C and Iannotta, F and Santangelo, G and Vitale, C},
title = {Prevalence and clinical aspects of obstructive sleep apnea in Parkinson disease: A meta-analysis.},
journal = {European journal of neurology},
volume = {31},
number = {2},
pages = {e16109},
pmid = {37922498},
issn = {1468-1331},
mesh = {Humans ; Male ; *Parkinson Disease/complications/epidemiology ; Polysomnography ; Prevalence ; *REM Sleep Behavior Disorder/etiology/complications ; *Sleep Apnea, Obstructive/epidemiology/complications ; },
abstract = {BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) frequently occurs in Parkinson Disease (PD), probably caused by upper airway dysfunctions or shared pathogenetic mechanisms. OSA may precede PD diagnosis or worsen throughout its course, but its relationship with clinical features and dopaminergic medication remains unclear. This meta-analysis aimed to provide a reliable estimate of OSA prevalence in the PD population (PD-OSA) and to clarify its clinical associated factors to help clinicians in understanding the underlying pathophysiological mechanisms.<br><br>METHODS: A systematic literature search was performed up to April 2023 using the PubMed, Scopus, and PsycINFO databases. Articles were included if they provided data on PD patients with and without OSA. Pooled prevalence for PD-OSA was calculated using the proportions of PD participants diagnosed with OSA. Demographic and clinical features associated with PD-OSA were explored by comparing PD patients with and without OSA.<br><br>RESULTS: Seventeen studies were included in the meta-analysis. Pooled OSA prevalence was 45% of a total sample of 1448 PD patients and was associated with older age, male sex, higher body mass index (BMI), more severe motor disturbances and periodic limb movements, reduced risk of rapid eye movement sleep behavior disorder, intake of dopamine agonists, and worse excessive daytime sleepiness. No relationship emerged with cognitive functioning and neuropsychiatric manifestations.<br><br>CONCLUSIONS: OSA affects nearly half of PD patients as a secondary outcome of predisposing factors such as older age and higher BMI in addition to PD-related motor impairment. Future studies should focus on determining the impact of both clinical features and dopaminergic medication on the development of PD-OSA.},
}
@article {pmid37921670,
year = {2023},
author = {Kalra, R and Lim, B and Ellis, MJ and Kavuri, SM},
title = {The uncharted role of HER2 mutant alleles in breast cancer.},
journal = {Oncotarget},
volume = {14},
number = {},
pages = {904-907},
pmid = {37921670},
issn = {1949-2553},
support = {P50 CA186784/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/genetics ; Alleles ; Receptor, ErbB-2/genetics ; },
abstract = {Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.},
}
@article {pmid37919558,
year = {2024},
author = {Avatefi, M and HadavandSiri, F and Nazari, SSH and Akbari, ME},
title = {Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.},
journal = {Cancer reports (Hoboken, N.J.)},
volume = {7},
number = {1},
pages = {e1927},
pmid = {37919558},
issn = {2573-8348},
mesh = {Female ; Humans ; *Breast Neoplasms/diagnosis/epidemiology/therapy ; Retrospective Studies ; *Neoplasms, Second Primary/diagnosis/epidemiology/etiology ; Risk Factors ; Proportional Hazards Models ; },
abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem.<br><br>AIMS: This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors.<br><br>METHODS AND RESULTS: This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6&#x2009;months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92&#x2009;years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60&#x2009;years and older were negatively associated with CBC.<br><br>CONCLUSION: This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.},
}
@article {pmid37914605,
year = {2024},
author = {Shuman, E and Goldenberg, A and Saguy, T and Halperin, E and van Zomeren, M},
title = {When Are Social Protests Effective?.},
journal = {Trends in cognitive sciences},
volume = {28},
number = {3},
pages = {252-263},
doi = {10.1016/j.tics.2023.10.003},
pmid = {37914605},
issn = {1879-307X},
abstract = {Around the world, people engage in social protests aimed at addressing major societal problems. Certain protests have led to significant progress, yet other protests have resulted in little demonstrable change. We introduce a framework for evaluating the effectiveness of social protest made up of three components: (i) what types of action are being considered; (ii) what target audience is being affected; and (iii) what outcomes are being evaluated? We then review relevant research to suggest how the framework can help synthesize conflicting findings in the literature. This synthesis points to two key conclusions: that nonviolent protests are effective at mobilizing sympathizers to support the cause, whereas more disruptive protests can motivate support for policy change among resistant individuals.},
}
@article {pmid37910521,
year = {2023},
author = {Imamichi, T and Chen, Q and Sowrirajan, B and Yang, J and Laverdure, S and Marquez, M and Mele, AR and Watkins, C and Adelsberger, JW and Higgins, J and Sui, H},
title = {Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner.},
journal = {PloS one},
volume = {18},
number = {11},
pages = {e0287829},
pmid = {37910521},
issn = {1932-6203},
support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Interleukin-27 ; *HIV Infections ; Virus Internalization ; *HIV-1 ; Interleukins/metabolism ; Monocytes ; Autophagy/genetics ; DNA/metabolism ; Dendritic Cells/metabolism ; Virus Replication ; Spectrin/metabolism ; },
abstract = {Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3% without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.},
}
@article {pmid37897648,
year = {2024},
author = {Zhao, YY and Ge, HJ and Yang, WT and Shao, ZM and Hao, S},
title = {Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.},
journal = {Breast cancer research and treatment},
volume = {203},
number = {3},
pages = {543-551},
pmid = {37897648},
issn = {1573-7217},
support = {82203789//National Natural Science Foundation of China/ ; 82102683//National Natural Science Foundation of China/ ; },
mesh = {Male ; Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnosis/genetics/therapy ; *Carcinoma, Ductal, Breast/pathology ; In Situ Hybridization, Fluorescence ; China ; Prognosis ; *Triple Negative Breast Neoplasms/pathology ; *Carcinoma ; },
abstract = {PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method.<br><br>RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46&#xa0;years (mean, 48.1&#xa0;years; range, 10-80&#xa0;years). The tumor sizes ranged from 0.3 to 6.8&#xa0;cm, with a mean of 3.5&#xa0;cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients.<br><br>CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve&#xa0;diagnosis and management in this unique subtype of breast cancer.},
}
@article {pmid37890687,
year = {2024},
author = {Liao, H and Wang, H and Zheng, R and Yu, Y and Zhang, Y and Lv, L and Zhang, B and Chen, J},
title = {LncRNA CARMN suppresses EMT through inhibiting transcription of MMP2 activated by DHX9 in breast cancer.},
journal = {Cellular signalling},
volume = {113},
number = {},
pages = {110943},
doi = {10.1016/j.cellsig.2023.110943},
pmid = {37890687},
issn = {1873-3913},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *RNA, Long Noncoding/genetics/metabolism ; Matrix Metalloproteinase 2/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Epithelial Cells/metabolism ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; *MicroRNAs/genetics ; Neoplasm Proteins/genetics/metabolism ; DEAD-box RNA Helicases/genetics/metabolism ; },
abstract = {Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.},
}
@article {pmid37879875,
year = {2023},
author = {Wang, HY and Li, SJ and Zhang, AL and Ni, XC},
title = {[Identification of lymph node metastasis related genes in prostate cancer using weighted gene co-expression network analysis].},
journal = {Zhonghua yi xue za zhi},
volume = {103},
number = {40},
pages = {3204-3210},
doi = {10.3760/cma.j.cn112137-20230531-00902},
pmid = {37879875},
issn = {0376-2491},
mesh = {Male ; Humans ; Lymphatic Metastasis ; *Nomograms ; *Prostatic Neoplasms/genetics/pathology ; Neoplasm Grading ; Risk Factors ; },
abstract = {Objective: To explore the molecular markers related to lymph node metastasis of prostate cancer (PCa) based on bioinformatics technology and carry out clinical verification. Methods: The differentially expressed genes of PCa with lymph node metastasis were screened from geo data, and the hub genes of the gene co expression network were constructed. The hub genes were incorporated into the support vector machine model to evaluate its prediction efficiency. The hub genes were verified in the TCGA data set and analyzed for immune infiltration. The clinical data of 80 patients with prostate cancer in the Fourth Hospital of Hebei Medical University from January 2019 to December 2022 were collected. The logistic risk model was used to evaluate the prediction efficiency of hub gene metastasis. Results: Five hub genes (GSK3B, TP53, PSMC6, SUMO1, PIK3CA) were identified, and the support vector machine model constructed by them had good diagnostic value (the accuracy rate was 83.87%). TCGA validation results showed that only PSMC6 was significantly differentially expressed in PCa tissues with lymph node metastasis (P<0.001). The results of immune infiltration analysis showed that the expression of PSMC6 was significantly correlated with 9 kinds of immune cells (B cells, DC, IDC, etc.). Clinical information analysis showed that the expression of PSMC6 was significantly correlated with lymph node metastasis, PSA value, T stage and Gleason score (P<0.01). Univariate logistic results showed that T stage (OR=3.230, 95%CI:1.192-8.757, P=0.021), Gleason score (OR=4.627, 95%CI:2.212-9.677, P<0.001), PSMC6 (OR=25.235, 95%CI:5.326-119.560, P<0.001) could be used as predictors of lymph node metastasis. Multivariate logistic analysis showed that PSMC6 (OR=16.537, 95%CI:2.928-93.393, P=0.001) could be used as an independent risk factor for predicting lymph node metastasis. Conclusion: PSMC6 may be used as a potential molecular marker for judging lymph node metastasis in patients with PCa.},
}
@article {pmid37874803,
year = {2023},
author = {Coskunpinar, E and Tiryakioglu, DZ and Abaci, N and Tukenmez, M and Pence, S},
title = {Investigation of the miR-637 and miR-523-5p as candidate biomarkers in breast cancer.},
journal = {Bratislavske lekarske listy},
volume = {124},
number = {11},
pages = {814-820},
doi = {10.4149/BLL_2023_125},
pmid = {37874803},
issn = {0006-9248},
mesh = {Humans ; Female ; *Fibroadenoma/diagnosis/genetics ; *Breast Neoplasms/diagnosis/genetics/pathology ; *MicroRNAs/metabolism ; Biomarkers ; *Carcinoma, Ductal ; Biomarkers, Tumor/genetics ; Gene Expression Profiling ; },
abstract = {OBJECTIVES: The distinction of benign lesions from malign tumors is crucial for the diagnosis and treatment of breast cancers.<br><br>BACKGROUND: The aim of this study was to investigate the use of miRNAs as plasma biomarkers for the discrimination of malign and benign breast tumors.<br><br>METHODS: Whole blood samples obtained from 40 individuals in 3 groups designated as invasive ductal carcinoma group, fibroadenoma group and healthy controls were included in this study. The expression levels of 372 miRNAs were determined using RT-PCR. &#xa0;Results: The comparison of fibroadenoma group with healthy controls revealed an upregulation of thirty miRNAs and downregulation of twenty-nine miRNAs. The comparison of invasive ductal carcinoma (IDC) group with controls has shown that eight miRNAs were upregulated while eleven miRNAs were downregulated. When comparing IDC and fibroadenoma groups, 15 miRNAs were found to be upregulated, while 10 miRNAs were downregulated. Further analysis of these miRNAs aimed to determine their power in distinguishing&#xa0; IDCs from fibroadenomas. Among the miRNAs analyzed, seven miRNAs have shown sufficient discriminative power, of which three miRNAs, namely miR-637, miR-523-5p and miR-490-3p, have shown a significantly high discriminative power.<br><br>CONCLUSIONS: Circulating miR-637 and miR-523-5p combination maybe used to discriminate between invasive ductal carcinomas and fibroadenomas. (Tab. 9, Fig. 4, Ref. 30).},
}
@article {pmid37873952,
year = {2024},
author = {Patel, K and Rao, DM and Sundersingh, S and Velusami, S and Rajkumar, T and Nair, B and Pandey, A and Chatterjee, A and Mani, S and Gowda, H},
title = {MicroRNA Expression Profile in Early-Stage Breast Cancers.},
journal = {MicroRNA (Shariqah, United Arab Emirates)},
volume = {13},
number = {1},
pages = {71-81},
pmid = {37873952},
issn = {2211-5374},
support = {BT/PR8152/AGR/36/739/2013//Department of Biotechnology, Govt. of India/ ; },
mesh = {Humans ; Female ; *MicroRNAs/genetics ; *Breast Neoplasms/genetics/pathology/mortality ; *Gene Expression Regulation, Neoplastic/genetics ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Middle Aged ; Neoplasm Staging ; Gene Expression Profiling ; Biomarkers, Tumor/genetics ; Transcriptome/genetics ; },
abstract = {BACKGROUND: Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples.<br><br>METHODS: We have deployed miRge for microRNA analysis, DESeq for differential expression analysis, and Cytoscape for competing endogenous RNA network investigation.<br><br>RESULTS: Here, we identified 76 miRNAs that were differentially expressed in DCIS and IDC. Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in earlystage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples.<br><br>CONCLUSION: Higher expression of miR-301a-3p is associated with poor overall survival in The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation.},
}
@article {pmid37855288,
year = {2024},
author = {Mohammed, BT and Uzodi, N and Gotimukul, A and Kokebie, R},
title = {Case Report of MPO+ ANCA Vasculitis with Pauci-immune GN Associated with Invasive Ductal Carcinoma of the Breast.},
journal = {Current rheumatology reviews},
volume = {20},
number = {2},
pages = {213-218},
doi = {10.2174/0115733971246438230924163114},
pmid = {37855288},
issn = {1875-6360},
mesh = {Female ; Humans ; Aged ; Antibodies, Antineutrophil Cytoplasmic ; *Glomerulonephritis ; Abscess ; *Breast Neoplasms/complications ; Mastectomy ; *Vasculitis ; Peroxidase ; *Carcinoma, Ductal ; },
abstract = {BACKGROUND: Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated with invasive ductal carcinoma of the breast.<br><br>CASE PRESENTATION: A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis, and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia and numbness, and deranged renal function a month after diagnosis of localized left breast invasive ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional interventional radiology-guided drainage of the abscess. We treated the patient successfully with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution of symptoms, normalization of inflammatory markers, and ANCA seroconversion.<br><br>CONCLUSION: Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation can be challenging. Individualized treatment strategy tailored to patients' acute needs is crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit the patient's clinical situation in a multidisciplinary approach.},
}
@article {pmid37847513,
year = {2024},
author = {Zhao, J and Xu, N and Zhu, S and Nie, L and Zhang, M and Zheng, L and Cai, D and Sun, X and Chen, J and Dai, J and Ni, Y and Wang, Z and Zhang, X and Liang, J and Chen, Y and Hu, X and Pan, X and Yin, X and Liu, H and Zhao, F and Zhang, B and Chen, H and Miao, J and Qin, C and Zhao, X and Yao, J and Liu, Z and Liao, B and Wei, Q and Li, X and Liu, J and Gao, AC and Huang, H and Shen, P and Chen, N and Zeng, H and Sun, G},
title = {Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.},
journal = {Cancer research},
volume = {84},
number = {1},
pages = {154-167},
doi = {10.1158/0008-5472.CAN-23-1176},
pmid = {37847513},
issn = {1538-7445},
support = {82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; ZYJC21020//1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; 2022-12M-C&amp;T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Mediccal Sciences/ ; mnzl202002//Beijing Bethune Charitable Foundation/ ; mnzl202007//Beijing Bethune Charitable Foundation/ ; 2023HXBH024//Postdoctoral Research and Development Fund of West China Hospital of Sichuan University/ ; },
mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Prostate/pathology ; *Adenocarcinoma/genetics/pathology ; *Prostatic Neoplasms/pathology ; Genomics ; Neoplasm Grading ; },
abstract = {UNLABELLED: Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P.<br><br>SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.},
}
@article {pmid37835856,
year = {2023},
author = {Khalid, A and Mehmood, A and Alabrah, A and Alkhamees, BF and Amin, F and AlSalman, H and Choi, GS},
title = {Breast Cancer Detection and Prevention Using Machine Learning.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {19},
pages = {},
pmid = {37835856},
issn = {2075-4418},
abstract = {Breast cancer is a common cause of female mortality in developing countries. Early detection and treatment are crucial for successful outcomes. Breast cancer develops from breast cells and is considered a leading cause of death in women. This disease is classified into two subtypes: invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). The advancements in artificial intelligence (AI) and machine learning (ML) techniques have made it possible to develop more accurate and reliable models for diagnosing and treating this disease. From the literature, it is evident that the incorporation of MRI and convolutional neural networks (CNNs) is helpful in breast cancer detection and prevention. In addition, the detection strategies have shown promise in identifying cancerous cells. The CNN Improvements for Breast Cancer Classification (CNNI-BCC) model helps doctors spot breast cancer using a trained deep learning neural network system to categorize breast cancer subtypes. However, they require significant computing power for imaging methods and preprocessing. Therefore, in this research, we proposed an efficient deep learning model that is capable of recognizing breast cancer in computerized mammograms of varying densities. Our research relied on three distinct modules for feature selection: the removal of low-variance features, univariate feature selection, and recursive feature elimination. The craniocaudally and medial-lateral views of mammograms are incorporated. We tested it with a large dataset of 3002 merged pictures gathered from 1501 individuals who had digital mammography performed between February 2007 and May 2015. In this paper, we applied six different categorization models for the diagnosis of breast cancer, including the random forest (RF), decision tree (DT), k-nearest neighbors (KNN), logistic regression (LR), support vector classifier (SVC), and linear support vector classifier (linear SVC). The simulation results prove that our proposed model is highly efficient, as it requires less computational power and is highly accurate.},
}
@article {pmid37828835,
year = {2023},
author = {Yang, SY and Zhang, J and Yang, ZQ and Duan, JJ and Zhang, Y and Li, MK and Wang, L and Ye, CM and Nie, JY},
title = {Advanced hormone receptor-positive/human epidermal growth factor receptor 2-positive invasive ductal carcinoma with cecal metastasis: A case report.},
journal = {Science progress},
volume = {106},
number = {4},
pages = {368504231201043},
pmid = {37828835},
issn = {2047-7163},
mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; *Breast Neoplasms/metabolism ; Receptor, ErbB-2/genetics/metabolism ; },
abstract = {The incidence of gastrointestinal metastases from breast cancer (BC) is low. We report a special case of Luminal B (Hormone Receptor positive [HR+]/Human Epidermal Growth Factor receptor 2-positive [HER-2+]) BC. The patient presented with asymptomatic brain metastases two years after radical surgery for modified breast cancer and developed right lower abdominal pain during relief therapy. Electronic gastroenteroscopy revealed inflammatory changes in the cecal mucosa. These changes were confirmed on pathology to be cecal metastasis from BC. The patient's condition was stabilised after treatment with an antibody-drug conjugate (ADC). For patients with BC who develop appendicitis-like symptoms after treatment for invasive ductal carcinoma of the breast, clinicians should be fully aware that the possibility of cecal metastasis needs to be considered, despite the very low probability of occurrence.},
}
@article {pmid37824772,
year = {2023},
author = {Dieu Vuong, L and Ngoc Nguyen, Q},
title = {ABERRANT METHYLATION OF CANCER-RELATED GENES IN VIETNAMESE BREAST CANCER PATIENTS: ASSOCIATIONS WITH CLINICOPATHOLOGICAL FEATURES.},
journal = {Experimental oncology},
volume = {45},
number = {2},
pages = {195-202},
doi = {10.15407/exp-oncology.2023.02.195},
pmid = {37824772},
issn = {2312-8852},
mesh = {Aged ; Female ; Humans ; *Breast Neoplasms/genetics/pathology ; DNA Methylation ; ErbB Receptors/genetics ; Promoter Regions, Genetic ; Southeast Asian People ; Epigenomics ; Vietnam ; },
abstract = {BACKGROUND: Epigenetic alteration is one of the most common molecular changes identified in the progression of breast cancer (BC).<br><br>AIM: To study the frequency and relation between methylation of BRCA1, MLH1, MGMT, GSTP1, APC, RASSF1A, p16, WIF, and EGFR and the clinicopathological features in Vietnamese BC patients.<br><br>MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (MS-PCR) and SPSS 20.0 software were utilized in order to identify methylated frequency as well as evaluate its relationship with the patient's clinical features.<br><br>RESULTS: In 162 BC cases, the methylation rates of the selected genes were 53.7%, 22.8%, 38.9%, 34.6%, 29.0%, 46.3%, 20.4%, 18.5%, and 28.4% respectively. In 32 cases of benign breast diseases (BBD) - 12.5%, 15.6%, 6.3%, 3.1%, 12.5%, 21.9%, 3.1%, 15.6% and 3.1%. BC samples displayed higher BRCA1, MGMT, GSTP1, APC, RASSF1A, WIF1, and p16 methylation levels than BBD samples (p < 0.001). Hypermethylation of BRCA1, GSTP1, and RASSF1A was predominant in the invasive ductal carcinoma, while hypermethylation of BRCA1, GSTP1, RASSF1A, WIF-1, and p16 was found to significantly correlate with lymph node metastasis (p < 0.05). Hypermethylation of BRCA1, MGMT, and GSTP1 was more common in stage III (p < 0.05) than in stages I/II, whereas MLH1 methylation was predominant in stage I and APC methylation was less common in stage III (p = 0.03). In addition, methylation of RASSF1A and EGFR was more frequent in younger patients (p < 0.01) than in elder patients.<br><br>CONCLUSION: These data suggest that a gene panel (BRCA1/MGMT/GSTP1) can be used to support the diagnosis and screening of Vietnamese patients' BC with a sensitivity of 70%, and a specificity of 85%.},
}
@article {pmid37800299,
year = {2023},
author = {Takashima, Y and Terasawa, R and Hirata, A and Morita, S and Kimura, K and Iwamoto, M and Hayashi, M},
title = {[A Case of COVID-19 Infection during Postoperative Chemotherapy for Breast Cancer Treated with Antibody Cocktail Therapy to Prevent Disease Aggravation].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {50},
number = {9},
pages = {1009-1011},
pmid = {37800299},
issn = {0385-0684},
mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; Combined Antibody Therapeutics ; *COVID-19 ; COVID-19 Drug Treatment ; Mastectomy ; },
abstract = {The outbreak of COVID-19 has caused a global pandemic, and it has been reported that patients with cancer are at high risk of developing complications from the disease. However, we believe that prolonged interruption of chemotherapy due to extended COVID-19 treatment is not desirable, given the intensity of cancer treatment. We report a case of COVID-19 infection during postoperative chemotherapy for breast cancer, in which antibody cocktail therapy prevented disease aggravation and delayed breast cancer treatment. The patient is a 45-year-old woman who came to our hospital with a complaint of a right mammary mass. The mass was diagnosed as invasive ductal carcinoma with an ER and PR of 0%, a HER2 score of 1+, and a Ki-67 of 90%. After preoperative chemotherapy, she underwent a right mastectomy and axillary dissection. The pathology result showed non-pCR. The administration of capecitabine was started as adjuvant therapy. On day 8 of cycle 3, she developed a fever in the 39℃ range, and on the next day, a COVID-19 POC gene test confirmed that the patient was positive for infection. On the same day, neutralizing antibody drugs(casirivimab and imdevimab)were administered as antibody cocktail therapy. Two days after treatment(day 11), a blood test showed Grade 3 neutropenia, but there was no recurrence of fever or evidence of pneumonia. After 2 weeks, capecitabine was resumed, and the patient was able to complete 8 cycles of capecitabine therapy without any major complications.},
}
@article {pmid37792368,
year = {2023},
author = {Martelli, G and Barretta, F and Vernieri, C and Folli, S and Pruneri, G and Segattini, S and Trapani, A and Carolla, C and Spatti, G and Miceli, R and Ferraris, C},
title = {Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection.},
journal = {JAMA surgery},
volume = {158},
number = {12},
pages = {1275-1284},
pmid = {37792368},
issn = {2168-6262},
mesh = {Female ; Humans ; Adult ; *Breast Neoplasms/genetics/prevention &amp; control/surgery ; Salpingo-oophorectomy ; BRCA1 Protein/genetics ; Mastectomy ; Retrospective Studies ; BRCA2 Protein/genetics ; Genes, BRCA1 ; Neoplasm Recurrence, Local/genetics ; Ovariectomy ; *Ovarian Neoplasms/genetics/prevention &amp; control ; Mutation ; },
abstract = {IMPORTANCE: Few studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death.<br><br>OBJECTIVE: To assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer.<br><br>This retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023.<br><br>EXPOSURE: Following breast surgery, some patients underwent PSO, PM, or both, whereas others did not.<br><br>MAIN OUTCOMES AND MEASURES: The primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer-specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer-specific mortality.<br><br>RESULTS: Of 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P&#x2009;<&#x2009;.001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P&#x2009;=&#x2009;.001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P&#x2009;=&#x2009;.002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P&#x2009;=&#x2009;.008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer-specific mortality.<br><br>CONCLUSIONS: The study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.},
}
@article {pmid37769530,
year = {2023},
author = {Siregar, KB and Al Anas, M},
title = {Unveiling bone metastasis: Exploring histological subtypes of breast cancer in Indonesia's tertiary referral hospital.},
journal = {Cancer treatment and research communications},
volume = {37},
number = {},
pages = {100764},
doi = {10.1016/j.ctarc.2023.100764},
pmid = {37769530},
issn = {2468-2942},
mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/secondary ; *Carcinoma, Ductal, Breast/secondary ; Retrospective Studies ; Indonesia/epidemiology ; Tertiary Care Centers ; *Bone Neoplasms ; },
abstract = {INTRODUCTION: The histological grade of a tumor is an important prognostic indicator in both primary breast cancer and metastatic. We aimed to show the distribution of bone metastasis locations across different histological subtypes of breast cancer and how they relate to each.<br><br>METHODS: The cohort retrospective study comprised 65 patients diagnosed with bone-only metastatic breast cancer, all female. The secondary statistics for 2014 to 2022 were derived from breast cancer registration data collected to determine the relationships between patterns of bone metastases sites and histopathological grading in various histological categories.<br><br>RESULTS: The average age was 44.28&#xb1;9.80 years (25-62 years), with 38 patients (58.5%) diagnosed with Invasive Ductal Carcinoma (IDC) and 27 patients (41.5%) with Invasive Lobular Carcinoma (ILC). Grade III were found in 34 patients (50.8%), Grade II in 31 patients (47.7%) and Grade I in one patient (1.5%). The most common sites of bone metastases are costae, followed by femur, vertebrae and pelvic. Vertebrae and costae metastasis are significantly correlated with histological grading and breast cancer pathology (p: 0.027 and 0.033, respectively).<br><br>CONCLUSION: There is a considerable difference between vertebrae and costae metastasis in terms of histological grading and breast cancer pathology which indicates the higher grade contains a greater variety of bone metastases sites.},
}
@article {pmid37761331,
year = {2023},
author = {Al-Refai, R and Bendari, A and Morrar, D and Sham, S and Kataw, L and Garajayev, A and Hajiyeva, S},
title = {Immunohistochemical Staining Characteristics of Low-Grade Invasive Ductal Carcinoma Using the ADH5 Cocktail (CK5/14, P63, and CK7/18): A Potential Interpretative Pitfall.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {18},
pages = {},
pmid = {37761331},
issn = {2075-4418},
abstract = {Background: In our practice, the antibody cocktail ADH5 (CK5/14, p63, and CK7/18) helps with diagnostic challenges, such as identifying microinvasion and foci of invasive carcinoma, differentiating atypical ductal hyperplasia from hyperplasia of the usual type, and distinguishing basal phenotypes in triple-negative carcinomas. However, the ADH5 cocktail does have pitfalls and caveats. Methods: We describe our experience with the ADH5 cocktail of antibodies in breast pathology. Institutional knowledge and a literature search form our data sources. Results: We analyzed 44 cases. Four out of a total of 44 cases (9.1%)-two tubular carcinomas and two low-grade invasive breast carcinomas of no special type (ductal) with tubular features-showed an expected pattern of staining for ADH5 with a loss of brown (P63, CK5/14) staining around invasive glands and diffuse red (CK7/18) expression. Forty out of 44 (90.9%) cases showed an unexpected staining pattern (mixture of cytoplasmic brown and red). All 44 cases (100%) showed negative myoepithelial staining around invasive foci when separately stained for P63 and SMMH (Smooth Muscle Myosin Heavy). Conclusions: The unexpected staining pattern of ADH5 in low-grade invasive ductal carcinomas can be challenging to interpret in these lesions with low-grade cytology. The occurrence can cause confusion among users who employ multiplex stains, and it is important for users to be aware of this potential pitfall.},
}
@article {pmid37749321,
year = {2023},
author = {Taylor, J and Uhl, L and Moll, I and Hasan, SS and Wiedmann, L and Morgenstern, J and Giaimo, BD and Friedrich, T and Alsina-Sanchis, E and De Angelis Rigotti, F and Mülfarth, R and Kaltenbach, S and Schenk, D and Nickel, F and Fleming, T and Sprinzak, D and Mogler, C and Korff, T and Billeter, AT and Müller-Stich, BP and Berriel Diaz, M and Borggrefe, T and Herzig, S and Rohm, M and Rodriguez-Vita, J and Fischer, A},
title = {Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.},
journal = {Nature cancer},
volume = {4},
number = {11},
pages = {1544-1560},
pmid = {37749321},
issn = {2662-1347},
support = {394046768 - SFB1366//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB1118-A04/S01//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BO 1639/9-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; },
mesh = {Animals ; Humans ; Male ; Mice ; *Adipose Tissue, White/pathology ; *Cachexia/pathology ; *Neoplasms/complications ; Signal Transduction ; Tretinoin ; *Receptor, Notch1/metabolism ; },
abstract = {Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.},
}
@article {pmid37747019,
year = {2023},
author = {Choi, JH and Yu, J and Jung, M and Jekal, J and Kim, KS and Jung, SU},
title = {Prognostic significance of TP53 and PIK3CA mutations analyzed by next-generation sequencing in breast cancer.},
journal = {Medicine},
volume = {102},
number = {38},
pages = {e35267},
pmid = {37747019},
issn = {1536-5964},
mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics ; Prognosis ; Mastectomy ; High-Throughput Nucleotide Sequencing ; Class I Phosphatidylinositol 3-Kinases/genetics ; Tumor Suppressor Protein p53/genetics ; },
abstract = {Breast cancer is one of the most prevalent malignant tumors affecting women globally. It is a heterogeneous disease characterized by mutations in several genes. Several gene panels have been applied to assess the risk of breast cancer and determine the appropriate treatment. As a powerful tool, Next-generation sequencing (NGS) has been widely utilized in cancer research due to its advantages, including high speed, high throughput, and high accuracy. In this study, we aim to analyze the correlation between somatic mutations in breast cancer, analyzed using NGS, and the prognosis of patients. Between May 2018 and May 2019, a total of 313 patients with breast cancer underwent surgical treatment, which included total mastectomy and breast-conserving surgery. Among these patients, 265 were diagnosed with invasive ductal carcinoma. In this study, we analyzed the NGS results, clinicopathological characteristics, and their correlation with prognosis. Using a gene panel, we examined 143 somatic mutations in solid cancers. Notably, the study population included patients who had received neoadjuvant chemotherapy. The mean age of the patients was 53.1 (±10.28) years, and the median follow-up time was 48 months (range, 8-54). Among the 265 patients, 68 had received prior systemic therapy. Of these, 203 underwent breast-conserving surgery, and 62 underwent a mastectomy. Various somatic mutations were observed in NGS, with the most frequent mutation being PIK3CA mutations, which accounted for 44% of all mutations. TP53 mutations were the second most frequent, and ERBB2 mutations were the third most frequent. TP53 mutations were associated with poor disease-free survival (P = .027), while PIK3CA mutations were associated with better disease-free survival (P = .035) than PIK3CA wild-type. In our study, we identified various somatic mutations in breast cancer. Particularly, we found that TP53 and PIK3CA mutations are potentially associated with the prognosis of breast cancer. These findings suggest that the presence of specific mutations may have implications for predicting the prognosis of breast cancer. Further research and validation are needed to gain a deeper understanding of the role of these mutations and their mechanisms in prognosis prediction.},
}
@article {pmid37743485,
year = {2023},
author = {Pourriahi, R and Omranipour, R and Alipour, S and Hajimaghsoudi, L and Mashoori, N and Kenary, AY and Motamedi, M and Tavakol, M and Mohammadzadeh, M and Hessamiazar, S and Shabani, S and Mahmoodi, F and Goodarzi, MM and Eslami, B},
title = {Clinical characteristics of breast cancer patients admitted to academic surgical wards in Tehran, Iran: an analytical cross-sectional study.},
journal = {BMC women's health},
volume = {23},
number = {1},
pages = {511},
pmid = {37743485},
issn = {1472-6874},
mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnosis/epidemiology ; Iran/epidemiology ; Cross-Sectional Studies ; Hospitalization ; Palpation ; },
abstract = {BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women. Knowledge of the clinical characteristics of BC in a population may be informative for disease prediction or diagnosis and for developing screening and diagnostic guidelines. This study aimed to evaluate the clinical characteristics of female patients with BC who were admitted to academic surgical wards in Tehran, Iran.<br><br>METHODS: In this cross-sectional study, demographic information and clinical characteristics of Iranian females with BC who had undergone breast surgery from 2017-2021 in four academic Breast Surgery Units were extracted from medical files and recorded via a pre-designed checklist.<br><br>RESULTS: A total of 1476 patients with a mean age of 48.03 (&#xb1;&#x2009;11.46) years were enrolled. Among them, 10.4% were aged less than 35. In younger patients, Triple-negative and Her2-enriched subtypes of BC were significantly higher compared to older ones. Overall, 85.7% of tumors were invasive ductal carcinoma, 43.3% were grade 2, 41.4% were located in the UOQ, and 65.2% had presented with mass palpation. The mean pathologic tumor size was 28.94 mm, and the most common subtype was luminal B.<br><br>CONCLUSIONS: Many characteristics of breast cancer in this study were similar to other countries and previous studies in Iran. However, a higher proportion of young BC compared with Western countries, and even with older studies in Iran, suggest a trend toward lower age for BC in recent years. These results indicate the need for preventive measures and screening in Iranian women at a younger age.},
}
@article {pmid37738898,
year = {2023},
author = {Peng, L and He, X and Peng, X and Li, Z and Zhang, L},
title = {STGNNks: Identifying cell types in spatial transcriptomics data based on graph neural network, denoising auto-encoder, and k-sums clustering.},
journal = {Computers in biology and medicine},
volume = {166},
number = {},
pages = {107440},
doi = {10.1016/j.compbiomed.2023.107440},
pmid = {37738898},
issn = {1879-0534},
mesh = {Humans ; Cluster Analysis ; *Transcriptome/genetics ; *Neural Networks, Computer ; Algorithms ; Gene Expression Profiling/methods ; Breast Neoplasms/genetics/pathology/metabolism ; },
abstract = {BACKGROUND: Spatial transcriptomics technologies fully utilize spatial location information, tissue morphological features, and transcriptional profiles. Integrating these data can greatly advance our understanding about cell biology in the morphological background.<br><br>METHODS: We developed an innovative spatial clustering method called STGNNks by combining graph neural network, denoising auto-encoder, and k-sums clustering. First, spatial resolved transcriptomics data are preprocessed and a hybrid adjacency matrix is constructed. Next, gene expressions and spatial context are integrated to learn spots' embedding features by a deep graph infomax-based graph convolutional network. Third, the learned features are mapped to a low-dimensional space through a zero-inflated negative binomial (ZINB)-based denoising auto-encoder. Fourth, a k-sums clustering algorithm is developed to identify spatial domains by combining k-means clustering and the ratio-cut clustering algorithms. Finally, it implements spatial trajectory inference, spatially variable gene identification, and differentially expressed gene detection based on the pseudo-space-time method on six 10x Genomics Visium datasets.<br><br>RESULTS: We compared our proposed STGNNks method with five other spatial clustering methods, CCST, Seurat, stLearn, Scanpy and SEDR. For the first time, four internal indicators in the area of machine learning, that is, silhouette coefficient, the Davies-Bouldin index, the Caliniski-Harabasz index, and the S_Dbw index, were used to measure the clustering performance of STGNNks with CCST, Seurat, stLearn, Scanpy and SEDR on five spatial transcriptomics datasets without labels (i.e., Adult Mouse Brain (FFPE), Adult Mouse Kidney (FFPE), Human Breast Cancer (Block A Section 2), Human Breast Cancer (FFPE), and Human Lymph Node). And two external indicators including adjusted Rand index (ARI) and normalized mutual information (NMI) were applied to evaluate the performance of the above six methods on Human Breast Cancer (Block A Section 1) with real labels. The comparison experiments elucidated that STGNNks obtained the smallest Davies-Bouldin and S_Dbw values and the largest Silhouette Coefficient, Caliniski-Harabasz, ARI and NMI, significantly outperforming the above five spatial transcriptomics analysis algorithms. Furthermore, we detected the top six spatially variable genes and the top five differentially expressed genes in each cluster on the above five unlabeled datasets. And the pseudo-space-time tree plot with hierarchical layout demonstrated a flow of Human Breast Cancer (Block A Section 1) progress in three clades branching from three invasive ductal carcinoma regions to multiple ductal carcinoma in situ sub-clusters.<br><br>CONCLUSION: We anticipate that STGNNks can efficiently improve spatial transcriptomics data analysis and further boost the diagnosis and therapy of related diseases. The codes are publicly available at https://github.com/plhhnu/STGNNks.},
}
@article {pmid37737015,
year = {2023},
author = {Sijnesael, T and Richard, F and Rätze, MA and Koorman, T and Bassey-Archibong, B and Rohof, C and Daniel, J and Desmedt, C and Derksen, PW},
title = {Canonical Kaiso target genes define a functional signature that associates with breast cancer survival and the invasive lobular carcinoma histological type.},
journal = {The Journal of pathology},
volume = {261},
number = {4},
pages = {477-489},
doi = {10.1002/path.6205},
pmid = {37737015},
issn = {1096-9896},
support = {2018NovPCC1297/BBC_/Breast Cancer Now/United Kingdom ; },
mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/metabolism ; Neoplasm Recurrence, Local ; Prognosis ; Cadherins/genetics/metabolism ; Transcription Factors/metabolism ; *Carcinoma, Ductal, Breast/pathology ; },
abstract = {Invasive lobular carcinoma (ILC) is a low- to intermediate-grade histological breast cancer type caused by mutational inactivation of E-cadherin function, resulting in the acquisition of anchorage independence (anoikis resistance). Most ILC cases express estrogen receptors, but options are limited in relapsed endocrine-refractory disease as ILC tends to be less responsive to standard chemotherapy. Moreover, ILC can relapse after >15 years, an event that currently cannot be predicted. E-cadherin inactivation leads to p120-catenin-dependent relief of the transcriptional repressor Kaiso (ZBTB33) and activation of canonical Kaiso target genes. Here, we examined whether an anchorage-independent and ILC-specific transcriptional program correlated with clinical parameters in breast cancer. Based on the presence of a canonical Kaiso-binding consensus sequence (cKBS) in the promoters of genes that are upregulated under anchorage-independent conditions, we defined an ILC-specific anoikis resistance transcriptome (ART). Converting the ART genes into human orthologs and adding published Kaiso target genes resulted in the Kaiso-specific ART (KART) 33-gene signature, used subsequently to study correlations with histological and clinical variables in primary breast cancer. Using publicly available data for ER[POS] Her2[NEG] breast cancer, we found that expression of KART was positively associated with the histological ILC breast cancer type (p < 2.7E-07). KART expression associated with younger patients in all invasive breast cancers and smaller tumors in invasive ductal carcinoma of no special type (IDC-NST) (<2 cm, p < 6.3E-10). We observed associations with favorable long-term prognosis in both ILC (hazard ratio [HR] = 0.51, 95% CI = 0.29-0.91, p < 3.4E-02) and IDC-NST (HR = 0.79, 95% CI = 0.66-0.93, p < 1.2E-04). Our analysis thus defines a new mRNA expression signature for human breast cancer based on canonical Kaiso target genes that are upregulated in E-cadherin deficient ILC. The KART signature may enable a deeper understanding of ILC biology and etiology. © 2023 The Authors. The Journal of Pathology published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.},
}
@article {pmid37705411,
year = {2023},
author = {McMurtry, V and Cleary, AS and Ruano, AL and Lomo, L and Gulbahce, HE},
title = {Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.},
journal = {American journal of clinical oncology},
volume = {46},
number = {12},
pages = {559-566},
doi = {10.1097/COC.0000000000001041},
pmid = {37705411},
issn = {1537-453X},
mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/genetics ; *Breast Neoplasms/genetics/epidemiology ; Proportional Hazards Models ; SEER Program ; Registries ; Prognosis ; },
abstract = {OBJECTIVES: Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC.<br><br>METHODS: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. &#x3c7; 2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD).<br><br>RESULTS: Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2&#xa0;cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC.<br><br>CONCLUSIONS: All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.},
}
@article {pmid37697863,
year = {2023},
author = {Lu, D and Li, F and Zhao, C and Ye, Y and Zhang, X and Yang, P and Zhang, X},
title = {A Remineralizing and Antibacterial Coating for Arresting Caries.},
journal = {Journal of dental research},
volume = {102},
number = {12},
pages = {1315-1325},
doi = {10.1177/00220345231189992},
pmid = {37697863},
issn = {1544-0591},
mesh = {Humans ; *Dental Caries/prevention &amp; control ; Dental Caries Susceptibility ; *Tooth Demineralization/prevention &amp; control ; Dental Enamel ; Composite Resins ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Tooth Remineralization/methods ; },
abstract = {Dental caries is a dynamic disease induced by the unbalance between demineralization of dental hard tissues caused by biofilm and remineralization of them; however, although various effective remineralization methods have been well documented, it is a challenge to reestablish the balance by enhancing remineralization alone while ignoring the antibacterial therapy. Therefore, the integration of remineralizing and antibacterial technologies offers a promising strategy to halt natural caries progression in clinical practice. Here, the conception of interrupting dental caries (IDC) was proposed based on the development of dual-functional coating with remineralizing and antibacterial properties. In this study, bovine serum albumin (BSA) loaded octenidine (OCT) successfully to form a BSA-OCT composite. Subsequently, through fast amyloid-like aggregation, the phase-transited BSA-OCT (PTB-OCT) coating can be covered on teeth, resin composite, or sealant surfaces in 30 min by a simple smearing process. The PTB-OCT coating showed satisfactory effects in promoting the remineralization of demineralized enamel and dentin in vitro. Moreover, this coating also exerted significant acid-resistance stability and anti-biofilm properties. Equally importantly, this coating exhibited promising abilities in reducing the microleakage between the tooth and resin composite in vitro and preventing primary and secondary caries in vivo. In conclusion, this novel dual-functional PTB-OCT coating could reestablish the balance between demineralization and remineralization in the process of caries, thereby potentially preventing or arresting caries.},
}
@article {pmid37683019,
year = {2023},
author = {Moon, SY and Lim, KR and Son, JS},
title = {The role of infectious disease consultations in the management of patients with fever in a long-term care facility.},
journal = {PloS one},
volume = {18},
number = {9},
pages = {e0291421},
pmid = {37683019},
issn = {1932-6203},
mesh = {Humans ; Long-Term Care ; Retrospective Studies ; Nursing Homes ; Fever ; Referral and Consultation ; Tertiary Care Centers ; *Cardiomyopathy, Dilated ; *Communicable Diseases/therapy ; },
abstract = {BACKGROUND: Infectious disease (ID) clinicians can provide essential services for febrile patients in tertiary hospitals. The aim of this study was to evaluate the role of ID consultations (IDC) in managing hospitalized patients with infections in an oriental medical hospital (OMH), which serves as a long-term care facility. To our knowledge, this is the first study on the role of IDCs in managing patients in an OMH.<br><br>METHODS: This retrospective study was conducted in an OMH in Seoul, Korea, from June 2006 to June 2013.<br><br>RESULTS: Among the 465 cases of hospital-acquired fever, 141 (30.3%) were referred for ID. The most common cause of fever was infection in both groups. The peak body temperature of the patient was higher in IDC group (38.8&#xb1;0.6&#xb0;C vs. 38.6&#xb1;0.5&#xb0;C, p<0.001). Crude mortality at 30 days (14.6% vs. 7.8%, p = 0.043) and infection-attributable mortality (15.3% vs. 6.7%, p = 0.039) were higher in the No-IDC group. Multivariable analysis showed that infection as the focus of fever (adjusted Odd ratio [aOR] 3.49, 95% confidence interval (CI) 1.64-7.44), underlying cancer (aOR 10.32, 95% CI 4.34-24.51,), and multiorgan dysfunction syndrome (aOR 15.68, 95% CI 2.06-119.08) were associated with increased 30-day mortality. Multivariate analysis showed that in patients with infectious fever, appropriate antibiotic therapy (aOR 0.19, 95% CI 0.05-0.76) was the only factor associated with decreased infection-attributable mortality while underlying cancer (aOR 7.80, 95% CI 2.555-23.807) and severe sepsis or septic shock at the onset of fever (aOR 10.15, 95% CI 1.00-102.85) were associated with increased infection-attributable mortality.<br><br>CONCLUSION: Infection was the most common cause of fever in patients hospitalized for OMH. Infection as the focus of fever, underlying cancer, and MODS was associated with increased 30-day mortality in patients with nosocomial fever. Appropriate antibiotic therapy was associated with decreased infection-attributable mortality in patients with infectious fever.},
}
@article {pmid37652705,
year = {2023},
author = {Li, X and Stitt, D and Lanzino, G and Giannini, C and Dubey, D and Carabenciov, ID},
title = {Teaching NeuroImage: Pachymeningitis and Aortitis as the Initial Presentation of Granulomatosis With Polyangiitis.},
journal = {Neurology},
volume = {101},
number = {21},
pages = {979-980},
pmid = {37652705},
issn = {1526-632X},
mesh = {Humans ; *Aortitis/complications/diagnostic imaging ; *Granulomatosis with Polyangiitis/complications/diagnostic imaging ; *Meningitis/complications/diagnostic imaging ; },
}
@article {pmid37637763,
year = {2023},
author = {Abbasi, A and Ghaffarizadeh, F and Mojdeganlou, H},
title = {Prognostic Significance of Microvessel Density in Invasive Ductal Carcinoma of Breast.},
journal = {International journal of hematology-oncology and stem cell research},
volume = {17},
number = {2},
pages = {100-105},
pmid = {37637763},
issn = {2008-3009},
abstract = {Background: Breast cancer is the most common malignant tumor and cause of death in women. Factors that play role in tumor metastasis are lymph node involvement, lack of tumor differentiation and hormone receptor expression, high proliferation rate, and angiogenesis. In the present study, we tried to evaluate the microvessel density (MVD) using Immunohistochemistry for the CD34 marker to investigate the amount of angiogenesis in breast cancer and its relationship with other histopathological parameters and compare it with normal tissue. Materials and Methods: 58 paraffin-embedded samples of breast cancer were enrolled. All blocks were sectioned and stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2(HER 2/neu), ki67, and CD34 by immunohistochemistry (IHC) method. Results: The mean age of patients in this study was 49.6 ± 10.6 years. Statistically, there was a significant relationship between the grade of the tumor (P = 0.01), absence of expression of estrogen receptor (P = 0.008), and progesterone receptor (P = 0.003) with MVD. Conclusion: Due to the association between MVD, tumor grade, and absence of ER and PR expression, this valuable marker can play an important role in the prediction of prognosis in breast cancer patients and can lead to new-targeted therapy in the future.},
}
@article {pmid37635979,
year = {2023},
author = {Barlier, A and Romanet, P and Pellegata, NS},
title = {Editorial: New insights into multiple endocrine neoplasia type 1.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1266148},
pmid = {37635979},
issn = {1664-2392},
mesh = {Humans ; *Multiple Endocrine Neoplasia Type 1/genetics ; },
}
@article {pmid37608749,
year = {2023},
author = {Ito, T and Takahara, T and Taniguchi, N and Yamamoto, Y and Satou, A and Ohashi, A and Takahashi, E and Sassa, N and Tsuzuki, T},
title = {PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients.},
journal = {Pathology international},
volume = {73},
number = {11},
pages = {542-548},
doi = {10.1111/pin.13369},
pmid = {37608749},
issn = {1440-1827},
support = {21K06933//Japan Society for the Promotion of Science/ ; 21K15392//Japan Society for the Promotion of Science/ ; },
mesh = {Male ; Humans ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Incidence ; East Asian People ; *Prostatic Neoplasms/pathology ; PTEN Phosphohydrolase/genetics/metabolism ; },
abstract = {Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.},
}
@article {pmid37559588,
year = {2023},
author = {Bai, X and Fang, C and Liu, B and Huagn, J and Chen, X and Xie, X and Zhang, Q and Liu, M and Liang, J and Guo, J and Song, L and Lan, X and Chen, L and Huang, S and Deng, W and Luo, Z and Du, C},
title = {Breast cancer metastases to the thyroid and stomach: A case report.},
journal = {Oncology letters},
volume = {26},
number = {3},
pages = {386},
pmid = {37559588},
issn = {1792-1082},
abstract = {The most common sites of metastasis for breast cancer are the soft tissues, bones, lungs, liver and brain; however, metastases to the gastrointestinal tract and thyroid gland from breast cancer rarely occur. The present study describes the case of a 30-year-old woman who developed gastric and thyroid metastases 5 years after her initial diagnosis of invasive ductal breast carcinoma. The initial pathological diagnosis when receiving modified radical mastectomy was invasive ductal carcinoma, and further immunohistochemical examination revealed the cancer to be estrogen receptor (-), progesterone receptor (-), human epidermal growth factor receptor 2 (HER2; ++) and Ki-67 (70%). Genetic testing indicated the HER2 amplification mutation, whereas BRCA1/2 testing was negative. A total of 21 months after surgery, during regular follow-up, the patient was revealed to have developed an enlarged lymph node in the left side of the neck and the first recurrence was confirmed. Approximately 5 years after surgery, the patient gradually developed multi-site metastasis, and developed metastases to the thyroid gland and stomach confirmed by pathology and imaging. Combined chemotherapy and targeted therapy were administered and exhibited good efficacy; however, the patient subsequently died due to heart failure. This case report describes the occurrence of gastric and thyroid metastases from breast cancer, and highlights the importance of distinguishing between metastatic and primary tumors. Distinguishing between a metastatic and primary tumor is crucial as treatment protocols vary significantly for these two types of tumors. For patients with a history of breast cancer it should first be considered whether they have metastasis of the primary disease or discomfort caused by treatment; however, the possibility of a second primary tumor cannot be ignored. If the patient has symptoms such as loss of appetite, nausea, vomiting, stomach pain and stomach discomfort, a gastroscopy should be performed in a timely manner.},
}
@article {pmid37558640,
year = {2023},
author = {Doi, K and Fujii, T and Hanamoto, M and Takamura, K and Nakada, T and Sato, Y and Ogura, K},
title = {[A Case of BRCA2 Mutation-Positive Intraductal Carcinoma of the Prostate].},
journal = {Hinyokika kiyo. Acta urologica Japonica},
volume = {69},
number = {7},
pages = {189-192},
doi = {10.14989/ActaUrolJap_69_7_189},
pmid = {37558640},
issn = {0018-1994},
mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Prostate-Specific Antigen ; Hematuria ; *Prostatic Neoplasms/drug therapy/genetics/pathology ; Disease Progression ; Mutation ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology ; BRCA2 Protein/genetics ; },
abstract = {A 75-year-old man presented with macroscopic hematuria and a high serum prostate-specific antigen (PSA) level. Macroscopic hematuria had subsided by the time of consultation. The PSA level was 38.590 ng/ml, which, along with rectal examination and magnetic resonance imaging findings, led to the suspicion of prostate cancer. Transrectal needle biopsy of the prostate revealed intraductal carcinoma of the prostate (IDC-P). Computed tomography and bone scintigraphy were performed, and the prostate cancer was classified as cT2cN0M0. After 6 months of combined androgen blockade therapy, a radical prostatectomy was performed; however, PSA levels continued to increase, and the patient was diagnosed with castration resistant prostate cancer. Multiple bone metastases appeared 5 months after the initiation of abiraterone therapy. Three courses of docetaxel and two courses of cabazitaxel were administered, but the disease progression continued. The IDC-P was found to be positive for the BRCA2 mutation by BRACAnalysis® performed at the start of cabazitaxel therapy. To our knowledge, no other cases of BRCA2 mutation positive IDC-P have been reported in Japan. After we started administration of Olaparib, the patient's PSA level was lowered and the disease progression stopped.},
}
@article {pmid37548682,
year = {2024},
author = {Mooshage, CM and Schimpfle, L and Kender, Z and Tsilingiris, D and Aziz-Safaie, T and Hohmann, A and Szendroedi, J and Nawroth, P and Sturm, V and Heiland, S and Bendszus, M and Kopf, S and Kurz, FT and Jende, JME},
title = {Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes : Study using Quantitative Sensory Testing and Magnetic Resonance Neurography.},
journal = {Clinical neuroradiology},
volume = {34},
number = {1},
pages = {55-66},
pmid = {37548682},
issn = {1869-1447},
mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/pathology ; Cross-Sectional Studies ; Pain/complications ; Sciatic Nerve ; Perfusion ; Magnetic Resonance Spectroscopy ; Magnetic Resonance Imaging ; },
abstract = {INTRODUCTION/AIMS: Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN.<br><br>METHODS: A&#xa0;total of 18&#xa0;patients with type&#xa0;2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10&#xa0;healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (K[trans]), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp).<br><br>RESULTS: The K[trans] (HC 0.031&#x202f;min[-1]&#x202f;&#xb1;&#x2009;0.009, T2D 0.043&#x202f;min[-1]&#x202f;&#xb1;&#x2009;0.015; p&#x202f;=&#x2009;0.033) and Ve (HC 1.2%&#x202f;&#xb1;&#x2009;1.5, T2D: 4.1%&#x202f;&#xb1;&#x2009;5.1; p&#x202f;=&#x2009;0.027) were lower in T2D patients compared to controls. In T2D patients, compound z&#x2011;scores of thermal and mechanical detection correlated with K[trans] (r&#x202f;=&#x2009;0.73; p&#x202f;=&#x2009;0.001, and r&#x202f;=&#x2009;0.57; p&#x202f;=&#x2009;0.018, respectively) and Ve (r&#x202f;=&#x2009;0.67; p&#x202f;=&#x2009;0.002, and r&#x202f;=&#x2009;0.69; p&#x202f;=&#x2009;0.003, respectively). Compound z&#x2011;scores of thermal pain and Vp (r&#x202f;=&#x2009;-0.57; p&#x202f;=&#x2009;0.015) correlated negatively.<br><br>DISCUSSION: The findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A&#xa0;reduced capillary permeability may result in a&#xa0;loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a&#xa0;gain of function.},
}
@article {pmid37536436,
year = {2023},
author = {Abdollahi, E and Mozdarani, H},
title = {Epigenetic regulation of circ-HIPK3, circ-PVT1, miR-25, and miR-149 in radiosensitivity of breast cancer.},
journal = {Experimental and molecular pathology},
volume = {132-133},
number = {},
pages = {104865},
doi = {10.1016/j.yexmp.2023.104865},
pmid = {37536436},
issn = {1096-0945},
mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics/radiotherapy ; Epigenesis, Genetic ; Leukocytes, Mononuclear ; Radiation Tolerance/genetics ; *MicroRNAs/genetics ; Cell Proliferation ; Protein Serine-Threonine Kinases ; Intracellular Signaling Peptides and Proteins ; },
abstract = {Assessing the radiosensitivity of cells before administering radiation therapy (RT) to individuals diagnosed with breast cancer (BC) can facilitate the selection of appropriate treatment regimens and minimize the incidence of adverse side effects in patients undergoing radiation exposure. In this research, blood samples were obtained from 60 women who had been diagnosed with Invasive Ductal Carcinoma (IDC) Breast Cancer. The average age of the patients was 47 ± 9.93. Additionally, the study incorporated 20 healthy women, with an average age of 44.43 ± 6.7. A standard G2 assay was conducted to predict the cellular response to radiation. Out of the 60 samples, the G2 assay identified 20 patients with breast cancer who exhibited radiosensitivity. Hence, molecular investigations were ultimately conducted on two equivalent cohorts comprising 20 subjects each, one with and the other without cellular radiosensitivity. The expression levels of miR-149, miR-25, circ-PVT1, and circ-HIPK3 in peripheral blood mononuclear cells (PBMCs) were evaluated using quantitative polymerase chain reaction (qPCR). Receiver Operating Characteristic (ROC) curves were used to evaluate the sensitivity and specificity of the RNAs. An analysis using binary logistic regression was performed to investigate the relationship between RNAs and both BC and cellular radiosensitivity (CR) in patients with BC. The findings revealed a significant upregulation of Circ-HIPK3 and circ-PVT1 in individuals diagnosed with BC. The levels of Circ-HIPK3 and Circ-PVT1 were found to be directly associated with CR in BC patients. The analysis of the ROC curve demonstrated that circ-HIPK3 and circ-PVT1 exhibit favorable specificity and sensitivity in accurately predicting both BC and CR in patients with BC. The findings from the binary logistic regression analysis demonstrated that circ-HIPK3 and circ-PVT1 were effective predictors of both BC and CR. The ROC curve and binary logistic regression analyses provide evidence that miR-25 is a reliable predictor for BC patients exclusively. Our research has demonstrated that circ-HIPK3, circ-PVT1, and miR-25 may be involved in BC regulatory processes. The circular RNAs Circ-HIPK3 and circ-PVT1, as well as miR-25, among other significant biomarkers, could potentially serve as promising biomarkers for predicting BC. Furthermore, Circ-HIPK3 and circ-PVT1 have the potential to serve as biomarkers for predicting CR in BC patients.},
}
@article {pmid37530887,
year = {2023},
author = {Kishore, A and Venkataramana, L and Prasad, DVV and Mohan, A and Jha, B},
title = {Enhancing the prediction of IDC breast cancer staging from gene expression profiles using hybrid feature selection methods and deep learning architecture.},
journal = {Medical &amp; biological engineering &amp; computing},
volume = {61},
number = {11},
pages = {2895-2919},
pmid = {37530887},
issn = {1741-0444},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; Transcriptome ; Neoplasm Staging ; *Deep Learning ; Gene Expression Profiling/methods ; },
abstract = {Prediction of the stage of cancer plays an important role in planning the course of treatment and has been largely reliant on imaging tools which do not capture molecular events that cause cancer progression. Gene-expression data-based analyses are able to identify these events, allowing RNA-sequence and microarray cancer data to be used for cancer analyses. Breast cancer is the most common cancer worldwide, and is classified into four stages - stages 1, 2, 3, and 4 [2]. While machine learning models have previously been explored to perform stage classification with limited success, multi-class stage classification has not had significant progress. There is a need for improved multi-class classification models, such as by investigating deep learning models. Gene-expression-based cancer data is characterised by the small size of available datasets, class imbalance, and high dimensionality. Class balancing methods must be applied to the dataset. Since all the genes are not necessary for stage prediction, retaining only the necessary genes can improve classification accuracy. The breast cancer samples are to be classified into 4 classes of stages 1 to 4. Invasive ductal carcinoma breast cancer samples are obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets and combined. Two class balancing techniques are explored, synthetic minority oversampling technique (SMOTE) and SMOTE followed by random undersampling. A hybrid feature selection pipeline is proposed, with three pipelines explored involving combinations of filter and embedded feature selection methods: Pipeline 1 - minimum-redundancy maximum-relevancy (mRMR) and correlation feature selection (CFS), Pipeline 2 - mRMR, mutual information (MI) and CFS, and Pipeline 3 - mRMR and support vector machine-recursive feature elimination (SVM-RFE). The classification is done using deep learning models, namely deep neural network, convolutional neural network, recurrent neural network, a modified deep neural network, and an AutoKeras generated model. Classification performance post class-balancing and various feature selection techniques show marked improvement over classification prior to feature selection. The best multiclass classification was found to be by a deep neural network post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with a Cohen-Kappa score of 0.303 and a classification accuracy of 53.1%. For binary classification into early and late-stage cancer, the best performance is obtained by a modified deep neural network (DNN) post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with an accuracy of 81.0% and a Cohen-Kappa score (CKS) of 0.280. This pipeline also showed improved multiclass classification performance on neuroblastoma cancer data, with a best area under the receiver operating characteristic (auROC) curve score of 0.872, as compared to 0.71 obtained in previous work, an improvement of 22.81%. The results and analysis reveal that feature selection techniques play a vital role in gene-expression data-based classification, and the proposed hybrid feature selection pipeline improves classification performance. Multi-class classification is possible using deep learning models, though further improvement particularly in late-stage classification is necessary and should be explored further.},
}
@article {pmid37530324,
year = {2023},
author = {Cakir, Y and Talu, CK and Trabulus, DC and Mermut, O},
title = {The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {66},
number = {3},
pages = {456-464},
doi = {10.4103/ijpm.ijpm_284_21},
pmid = {37530324},
issn = {0974-5130},
mesh = {Humans ; Female ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Galectin 3/genetics ; *Triple Negative Breast Neoplasms/pathology ; Retrospective Studies ; *Carcinoma, Ductal ; *Breast Neoplasms ; Biomarkers, Tumor/metabolism ; },
abstract = {BACKGROUND: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers.<br><br>AIM: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas.<br><br>MATERIALS AND METHODS: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs.<br><br>STATISTICAL ANALYSIS: Data was analyzed with t-tests and Chi-square tests. Kaplan-Meier and Log-rank tests were used for survival analysis.<br><br>RESULTS: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs.<br><br>CONCLUSIONS: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.},
}
@article {pmid37517027,
year = {2023},
author = {Amato, S and Ramsey, J and Ahern, TP and Rovnak, J and Barlow, J and Weaver, D and Eyasu, L and Singh, R and Cintolo-Gonzalez, J},
title = {Exploring the presence of bovine leukemia virus among breast cancer tumors in a rural state.},
journal = {Breast cancer research and treatment},
volume = {202},
number = {2},
pages = {325-334},
pmid = {37517027},
issn = {1573-7217},
mesh = {Cattle ; Humans ; Female ; Animals ; Sheep/genetics ; *Breast Neoplasms/epidemiology/genetics ; *Leukemia Virus, Bovine/genetics ; DNA, Viral/genetics ; Breast ; *Mammary Neoplasms, Animal ; },
abstract = {PURPOSE: The bovine leukemia virus (BLV) is a deltaretrovirus that causes malignant lymphoma and lymphosarcomas in cattle globally and has high prevalence among large scale U.S. dairy herds. Associations between presence of BLV DNA in human mammary tissue and human breast cancer incidence have been reported. We sought to estimate the prevalence of BLV DNA in breast cancer tissue samples in a rural state with an active dairy industry.<br><br>METHODS: We purified genomic DNA from 56 fresh-frozen breast cancer tissue samples (51 tumor samples, 5 samples representing adjacent normal breast tissue) banked between 2016 and 2019. Using nested PCR assays, multiple BLV tax sequence primers and primers for the long terminal repeat (LTR) were used to detect BLV DNA in tissue samples and known positive control samples, including the permanently infected fetal lamb kidney cell line (FLK-BLV) and blood from BLV positive cattle.<br><br>RESULTS: The median age of patients from which samples were obtained at the time of treatment was 60 (40-93) and all were female. Ninety percent of patients had invasive ductal carcinoma. The majority were poorly differentiated (60%). On PCR assay, none of the tumor samples tested positive for BLV DNA, despite having consistent signals in positive controls.<br><br>CONCLUSION: We did not find BLV DNA in fresh-frozen breast cancer tumors from patients presenting to a hospital in Vermont. Our findings suggest a low prevalence of BLV in our patient population and a need to reevaluate the association between BLV and human breast cancer.},
}
@article {pmid37513591,
year = {2023},
author = {Hardt, LM and Herrmann, HJ and Reljic, D and Jaensch, P and Zerth, J and Neurath, MF and Zopf, Y},
title = {Are Guideline Recommendations on Supportive Nutrition and Exercise Therapy for Cancer Patients Implemented in Clinical Routine? A National Survey with Real-Life Data.},
journal = {Nutrients},
volume = {15},
number = {14},
pages = {},
pmid = {37513591},
issn = {2072-6643},
support = {MED1710//Hector-Stiftung/ ; N.N.//Research Foundation for Medicine at the University Hospital Erlangen/ ; },
mesh = {Humans ; Quality of Life ; Nutritional Support ; *Malnutrition/diagnosis ; *Neoplasms/complications/therapy ; Exercise Therapy ; },
abstract = {Malnutrition and cancer cachexia are highly prevalent comorbidities of cancer, limiting patients' quality of life and being relevant to prognosis. International and national clinical guidelines recommend supportive nutrition and exercise therapy for cancer patients. However, there is little current epidemiological evidence on the implementation of these guideline recommendations in clinical routine. To close this data gap, a national survey in Germany using an online questionnaire was conducted. There were 261 of a total of 5074 contacted hospitals and medical offices who participated in the survey (5.1% response rate). The data indicated that nutrition and exercise therapy for cancer patients is so far inadequately implemented, with 59% of the respondents reporting nutrition therapy as an integral part of oncological treatment, 66.7% having a nutrition specialist/team, and 65.1% routinely conducting a screening for nutritional status. Only half of the participants stated that there are defined goals in nutrition therapy. The majority of respondents (85.8%) generally recommend exercise therapy, but only a few of them provide specific offers at their own institution (19.6%) or at cooperation partners (31.7%). In order to implement the recommended combined nutrition and exercise therapy as part of regular care, there is a need for nationwide availability of multidisciplinary nutrition teams and targeted offers of individualized exercise therapy. Health policy support would be important to create the structural, financial, and staff conditions for appropriate guideline implementation in order to achieve the optimal treatment of cancer patients.},
}
@article {pmid37500355,
year = {2023},
author = {Ding, W and Ye, D and Zhu, H and Lin, Y and Li, Z and Ruan, G},
title = {Survival Benefit of Adjuvant Chemotherapy in Node-Positive Breast Cancer With a 21-Gene Recurrence Score of 14 to 25: A Real-World Study Based on the Inverse Probability of Treatment Weighting Method.},
journal = {Clinical breast cancer},
volume = {23},
number = {7},
pages = {e441-e450},
doi = {10.1016/j.clbc.2023.07.004},
pmid = {37500355},
issn = {1938-0666},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; Retrospective Studies ; Biomarkers, Tumor ; Prognosis ; Chemotherapy, Adjuvant ; Proportional Hazards Models ; Neoplasm Recurrence, Local/pathology ; },
abstract = {INTRODUCTION: The role of recurrence score in predicting the benefits of adjuvant chemotherapy for lymph-node-positive breast cancer remains uncertain. We studied chemotherapy usage in patients with 1 to 3 positive lymph nodes and a recurrence score (RS) of 25 or lower to assess changes in clinical practice based on the RxPONDER trial.<br><br>METHODS: A retrospective study using the SEER database identified female patients diagnosed with ER-positive, HER2-negative breast cancer, 1 to 3 positive lymph nodes, and an RS of 25 or lower between 2010 and 2015. Patients were divided into nonchemotherapy and chemotherapy groups, with propensity score weighting to balance clinicopathologic factors.<br><br>RESULTS: Among 7965 patients, 5774 (72.5%) were in the nonchemotherapy group, while 2191 (27.5%) were in the chemotherapy group. Median follow-up was 39 months. Breast cancer accounted for 67 deaths, while 128 deaths were due to other causes. The weighted 5-year overall survival (OS) rates were 95.7% for the nonchemotherapy group and 97.2% for the chemotherapy group. For high-risk patients, the weighted 5-year OS rates were 95.2% and 97.0% for the nonchemotherapy and chemotherapy groups, respectively, with a significant absolute difference of 1.8% (P&#xa0;=&#xa0;.014). Multivariate analysis showed a significant difference in weighted hazard ratios for OS between the nonchemotherapy and chemotherapy groups in high-risk patients (hazard ratio: 0.64; 95% CI: 0.48-0.86). However, there were no significant differences in weighted hazard ratios for lower-risk patients, and similar results were observed for breast cancer-specific survival (BCSS).<br><br>CONCLUSION: Patients with ER-positive, HER2-negative breast cancer and 1 to 3 positive lymph nodes, assessed by a 21-gene RS of 0 to 25, exhibited heterogeneous prognosis. Adjuvant chemotherapy provided a significant survival benefit, especially for patients with RS of 14 to 25, particularly those with invasive ductal carcinoma (IDC) and 2 to 3 positive lymph nodes.},
}
@article {pmid37498719,
year = {2024},
author = {Shoshani, A},
title = {Longitudinal changes in children's and adolescents' mental health and well-being and associated protective factors during the COVID-19 pandemic.},
journal = {Psychological trauma : theory, research, practice and policy},
volume = {16},
number = {7},
pages = {1158-1168},
doi = {10.1037/tra0001556},
pmid = {37498719},
issn = {1942-969X},
mesh = {Humans ; *COVID-19/psychology/prevention &amp; control ; Child ; Adolescent ; Male ; Female ; Longitudinal Studies ; *Protective Factors ; *Social Support ; Israel ; Mental Health ; Resilience, Psychological ; Personal Satisfaction ; Depression/psychology ; },
abstract = {OBJECTIVE: The COVID-19 pandemic has heightened children's and adolescents' risk of experiencing long-term mental health problems and a decline in subjective well-being. To better understand the longitudinal impact of COVID-19, this study explored the role of demographic variables and the potential moderating effects of social support and daily routines as resilience factors.<br><br>METHOD: A nationally representative, longitudinal cohort of 5,217 Israeli children and adolescents aged 10-15 at baseline completed measures of mental health symptoms, life satisfaction, positive and negative emotions, gratitude, social support, and daily routines. Data were collected in school at four measurement points: September 2019 (before the outbreak of COVID-19; N = 5,127), May 2020 (after the first lockdown; N = 4,698), May 2021 (after the third wave lockdown; N = 4,813), and May 2022 (after the fourth and fifth waves of the pandemic; N = 4,897). The data were analyzed using multilevel mixed models.<br><br>RESULTS: Significant increases in depression, anxiety, and panic along with decreases in psychological well-being were found as a function of time. These effects were moderated by age and gender. Participants with high social support and structured daily routines reported smaller increases in mental health symptoms than students with low social support or irregular daily routines.<br><br>CONCLUSION: There is a critical need for clinical and educational interventions for young people during this period to promote the resilience factors that can moderate well-being and counter the decline in mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).},
}
@article {pmid37496230,
year = {2023},
author = {Konishi, K and Araya, J and Nagabuchi, M and Sakamoto, T and Ogino, J and Hirano, S},
title = {[A Case of Breast Carcinoma That Changed Subtype to Squamous Cell Carcinoma after Chemotherapy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {50},
number = {7},
pages = {825-827},
pmid = {37496230},
issn = {0385-0684},
mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/surgery/pathology ; Docetaxel/therapeutic use ; Mastectomy ; Quality of Life ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Carcinoma, Squamous Cell/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; Cyclophosphamide/therapeutic use ; *Liver Neoplasms/drug therapy/surgery/secondary ; },
abstract = {Metaplastic carcinoma is a rare histological malignancy, often triple-negative, and has a poor prognosis. Here, we report a case of breast cancer in which the primary lesion degenerated into squamous cell carcinoma(triple negative)after drug treatment for invasive ductal carcinoma(Luminal type). The patient was a 41-year-old woman who was diagnosed with Stage Ⅳ left breast cancer T2N2bM1(HEP)(ER 90%, PR 70%, HER2 2+, FISH-)at another hospital and participated in the PATHWAY study(tamoxifen plus goserelin plus palbociclib/placebo). Since the primary lesion and liver metastasis increased in size, the study was discontinued after 8 weeks. She was treated at our hospital thereafter, with capecitabine plus cyclophosphamide, palbociclib plus fulvestrant plus leuprorelin, paclitaxel plus bevacizumab, eribulin, EC therapy, and docetaxel. However, both the primary lesion and liver metastasis increased. In particular, the increase in primary lesion size was remarkable, and the QOL significantly reduced due to bleeding and exudation. Biopsy performed during docetaxel treatment revealed metaplastic/squamous cell carcinoma(ER-, PR-, HER2 0, Ki-67 90-100%)histopathological findings. BRCA and microsatellite instability tests were negative, and PDL1 expression was less than 1%. Although Mohs ointment was used, tumor bleeding, exudate, and stink were poorly controlled, and the patient experienced painful symptoms due to the weight of the tumor. Therefore, left mastectomy plus pectoralis major muscle resection was performed. The patient died one month after the operation.},
}
@article {pmid37495452,
year = {2023},
author = {Bódis, K and Bombrich, M and Schön, M and Knebel, B and Zaharia, OP and Bönhof, G and Karusheva, Y and Strassburger, K and Kupriyanova, Y and Kotzka, J and Guthoff, R and Schrauwen-Hinderling, V and Al-Hasani, H and Burkart, V and Szendroedi, J and Wagner, R and Markgraf, DF and Roden, M and , },
title = {Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes.},
journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD},
volume = {33},
number = {9},
pages = {1785-1796},
doi = {10.1016/j.numecd.2023.06.004},
pmid = {37495452},
issn = {1590-3729},
mesh = {Humans ; Male ; Case-Control Studies ; *Diabetes Mellitus, Type 2/diagnosis/genetics/complications ; *Insulin Resistance/genetics ; Liver/metabolism ; *Liver Neoplasms ; Membrane Proteins/genetics/metabolism ; *Non-alcoholic Fatty Liver Disease/diagnosis/genetics/complications ; Polymorphism, Single Nucleotide ; Triglycerides/metabolism ; },
abstract = {BACKGROUND AND AIMS: Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2[EK]; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.<br><br>METHODS AND RESULTS: Males with recent-onset type 2 diabetes with (TM6SF2[EK]: n&#xa0;=&#xa0;16) or without (TM6SF2[EE]: n&#xa0;=&#xa0;16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-[2]H2]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with [1]H-magnetic-resonance-spectroscopy. A subset of both groups (n&#xa0;=&#xa0;24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2[EK] had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2[EE]. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2[EE] only.<br><br>CONCLUSIONS: The TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.},
}
@article {pmid37490055,
year = {2023},
author = {Choo, ZY and Xu, AZ},
title = {Predictors and outcomes of cutaneous metastatic breast carcinoma: a retrospective, single-institution review.},
journal = {Archives of dermatological research},
volume = {315},
number = {9},
pages = {2725-2728},
pmid = {37490055},
issn = {1432-069X},
mesh = {Humans ; Female ; Retrospective Studies ; *Breast Neoplasms/therapy ; Skin/pathology ; Administration, Cutaneous ; *Carcinoma, Lobular/pathology/secondary ; },
}
@article {pmid37480503,
year = {2023},
author = {D'Iorio, A and Aiello, EN and Amboni, M and Vitale, C and Verde, F and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B and Santangelo, G},
title = {Validity and diagnostics of the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson's disease patients.},
journal = {Aging clinical and experimental research},
volume = {35},
number = {10},
pages = {2157-2163},
pmid = {37480503},
issn = {1720-8319},
mesh = {Humans ; *Parkinson Disease/complications/diagnosis ; Retrospective Studies ; Mental Status and Dementia Tests ; *Cognitive Dysfunction/diagnosis/etiology ; Language ; },
abstract = {BACKGROUND: This study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson's disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties.<br><br>METHODS: A retrospective cohort of N&#x2009;=&#x2009;237 non-demented PD patients having been administered the MoCA was addressed, of whom N&#x2009;=&#x2009;169 further underwent the Mini-Mental State Examination (MMSE) and N&#x2009;=&#x2009;68 the Parkinson's Disease Cognitive Rating Scale (PD-CRS). A subsample (N&#x2009;=&#x2009;60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score.<br><br>RESULTS: The MoCA was associated with both PD-CRS scores (p&#x2009;<&#x2009;.001) and the vast majority of second-level cognitive measures (ps&#x2009;<&#x2009;.003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and&#x2009;<&#x2009;19.015 is herewith suggested as indexing cognitive impairment in this population (AUC&#x2009;=&#x2009;.92; sensitivity&#x2009;=&#x2009;.92; specificity&#x2009;=&#x2009;.80).<br><br>DISCUSSION: The Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.},
}
@article {pmid37480256,
year = {2023},
author = {White, D and Sadough Shahmirzadi, M and Boulmay, B},
title = {Multi-Phenotypic Breast Cancer Post-Radiotherapy for Hodgkin Lymphoma: A Case of Secondary Malignancy.},
journal = {Journal of investigative medicine high impact case reports},
volume = {11},
number = {},
pages = {23247096231188251},
pmid = {37480256},
issn = {2324-7096},
mesh = {Female ; Humans ; Middle Aged ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; *Breast Neoplasms/radiotherapy ; *Hodgkin Disease/radiotherapy ; Mastectomy ; Breast/pathology ; *Neoplasms, Second Primary/etiology ; },
abstract = {Morbidity and mortality associated with radiation-induced secondary malignancies (RISMs) have shifted treatment paradigms to minimize or eliminate radiation from treatment regimens. In this case, a 48-year-old woman was diagnosed with Hodgkin lymphoma (HL) and treated with radiotherapy in 2000. In 2018, she was diagnosed with ductal carcinoma in situ (DCIS) of the right breast and treated with a mastectomy. Soon after, she developed triple-negative invasive ductal carcinoma (IDC) in her reconstructed breast. The patient underwent a left lumpectomy, and pathology showed ER-/PR-/HER2+ IDC. This patient's multi-phenotypic DCIS and IDC presentation are suspected to be RISM due to her previous HL treatment regimen.},
}
@article {pmid37479782,
year = {2023},
author = {Fond, G and Falissard, B and Nuss, P and Collin, C and Duret, S and Rabbani, M and De Chefdebien, I and Tonelli, I and Llorca, PM and Boyer, L},
title = {How can we improve the care of patients with schizophrenia in the real-world? A population-based cohort study of 456,003 patients.},
journal = {Molecular psychiatry},
volume = {28},
number = {12},
pages = {5328-5336},
pmid = {37479782},
issn = {1476-5578},
mesh = {Humans ; *Schizophrenia/drug therapy/epidemiology ; Male ; Female ; Middle Aged ; Adult ; *Antipsychotic Agents/therapeutic use ; Cohort Studies ; Aged ; Comorbidity ; Antidepressive Agents/therapeutic use ; Anticonvulsants/therapeutic use ; Adolescent ; Young Adult ; },
abstract = {An important step to improve outcomes for patients with schizophrenia is to understand treatment patterns in routine practice. The aim of the current study was to describe the long-term management of patients with schizophrenia treated with antipsychotics (APs) in real-world practice. This population-based study included adults with schizophrenia and who had received ≥3 deliveries of an AP from 2012-2017, identified using a National Health Data System. Primary endpoints were real-life prescription patterns, patient characteristics, healthcare utilization, comorbidities and mortality. Of the 456,003 patients included, 96% received oral APs, 17.5% first-generation long-acting injectable APs (LAIs), and 16.1% second generation LAIs. Persistence rates at 24 months after treatment initiation were 23.9% (oral APs), 11.5% (first-generation LAIs) and 20.8% (second-generation LAIs). Median persistence of oral APs, first-generation LAIs and second-generation LAIs was 5.0, 3.3, and 6.1 months, respectively. Overall, 62.1% of patients were administered anxiolytics, 45.7% antidepressants and 28.5% anticonvulsants, these treatments being more frequently prescribed in women and patients aged ≥50 years. Dyslipidemia was the most frequent metabolic comorbidity (16.2%) but lipid monitoring was insufficient (median of one occasion). Metabolic comorbidities were more frequent in women. Standardized patient mortality remained consistently high between 2013 and 2015 (3.3-3.7 times higher than the general French population) with a loss of life expectancy of 17 years for men and 8 years for women. Cancer (20.2%) and cardiovascular diseases (17.2%) were the main causes of mortality, and suicide was responsible for 25.4% of deaths among 18-34-year-olds. These results highlight future priorities for care of schizophrenia patients. The global persistence of APs used in this population was low, whereas rates of psychiatric hospitalization remain high. More focus on specific populations is needed, such as patients aged >50 years to prevent metabolic disturbances and 18-34-year-olds to reduce suicide rates.},
}
@article {pmid37478120,
year = {2023},
author = {Shi, K and Liu, XL and Guo, Q and Zhang, YQ and Fan, ST and Dai, L and Jiang, N and Li, D},
title = {TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma.},
journal = {PloS one},
volume = {18},
number = {7},
pages = {e0285817},
pmid = {37478120},
issn = {1932-6203},
mesh = {Female ; Humans ; Biomarkers, Tumor/genetics/metabolism ; *Endometrial Neoplasms/pathology ; Nomograms ; Prognosis ; RNA ; Tumor Microenvironment/genetics ; },
abstract = {BACKGROUND: Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression.<br><br>METHODS: The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC.<br><br>RESULTS: TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications.<br><br>CONCLUSIONS: TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.},
}
@article {pmid37474400,
year = {2024},
author = {Chappidi, MR and Sjöström, M and Greenland, NY and Cowan, JE and Baskin, AS and Shee, K and Simko, JP and Chan, E and Stohr, BA and Washington, SL and Nguyen, HG and Quigley, DA and Davicioni, E and Feng, FY and Carroll, PR and Cooperberg, MR},
title = {Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes.},
journal = {European urology oncology},
volume = {7},
number = {2},
pages = {222-230},
doi = {10.1016/j.euo.2023.06.007},
pmid = {37474400},
issn = {2588-9311},
mesh = {Male ; Humans ; *Prostate-Specific Antigen ; Retrospective Studies ; Transcriptome ; *Prostatic Neoplasms/genetics/surgery/pathology ; Gene Expression Profiling ; },
abstract = {BACKGROUND: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited.<br><br>OBJECTIVE: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival.<br><br>This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR.<br><br>Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival.<br><br>RESULTS AND LIMITATIONS: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity.<br><br>CONCLUSIONS: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments.<br><br>PATIENT SUMMARY: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.},
}
@article {pmid37470893,
year = {2023},
author = {Chen, BF and Tsai, YF and Lien, PJ and Lin, YS and Feng, CJ and Chen, YJ and Cheng, HF and Tseng, LM and Huang, CC},
title = {Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.},
journal = {Breast cancer research and treatment},
volume = {201},
number = {3},
pages = {547-560},
pmid = {37470893},
issn = {1573-7217},
support = {V110E-005-3//Taipei Veterans General Hospital/ ; V111E-006-3//Taipei Veterans General Hospital/ ; V112E-004-3//Taipei Veterans General Hospital/ ; },
mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/epidemiology/genetics/therapy ; *Carcinoma, Ductal, Breast/therapy/drug therapy ; Taiwan/epidemiology ; Mastectomy ; Neoplasm Recurrence, Local/pathology ; Treatment Outcome ; Registries ; Retrospective Studies ; },
abstract = {PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry.<br><br>METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the &#x3c7;2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model.<br><br>RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.},
}
@article {pmid37439959,
year = {2023},
author = {Tsunokake, S and Iwabuchi, E and Miki, Y and Kanai, A and Onodera, Y and Sasano, H and Ishida, T and Suzuki, T},
title = {SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.},
journal = {Breast cancer research and treatment},
volume = {201},
number = {3},
pages = {499-513},
pmid = {37439959},
issn = {1573-7217},
mesh = {Humans ; Female ; *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use ; Sodium-Glucose Transporter 2/metabolism ; Prognosis ; Vascular Endothelial Growth Factor A/metabolism ; *Breast Neoplasms/drug therapy/genetics ; Glucose/metabolism ; *Carcinoma, Ductal ; },
abstract = {PURPOSE: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained remain virtually unknown. Therefore, in this study, we explored the expression status of SGLT1 and SGLT2 in breast cancer patients and examined the effects of SGLT1 inhibitors on breast carcinoma cells in vitro.<br><br>METHODS: SGLT1 and SGLT2 were immunolocalized and we first correlated the findings with clinicopathological factors of the patients. We then administered mizagliflozin and KGA-2727, SGLT1 specific inhibitors to MCF-7 and MDA-MB-468 breast carcinoma cell lines, and their growth-inhibitory effects were examined. Protein arrays were then used to further explore their effects on the growth factors.<br><br>RESULTS: The SGLT1 high group had significantly worse clinical outcome including both overall survival and disease-free survival than low group. SGLT2 status was not significantly correlated with clinical outcome of the patients. Both mizagliflozin and KGA-2727 inhibited the growth of breast cancer cell lines. Of particular interest, mizagliflozin inhibited the proliferation of MCF-7 cells, even under very low glucose conditions. Mizagliflozin downregulated vascular endothelial growth factor receptor 2 phosphorylation.<br><br>CONCLUSION: High SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors.},
}
@article {pmid37435234,
year = {2023},
author = {Li, S and Tong, J and Li, H and Mao, C and Shen, W and Lei, Y and Hu, P},
title = {L. pneumophila Infection Diagnosed by tNGS in a Lady with Lymphadenopathy.},
journal = {Infection and drug resistance},
volume = {16},
number = {},
pages = {4435-4442},
pmid = {37435234},
issn = {1178-6973},
abstract = {We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee joint cavity effusion. Later, bilateral interstitial changes in her lungs and mediastinal lymphadenopathy were found after chest CT scanning. Empirical quinolone therapy was given although pathological examinations of blood, sputum and bronchoalveolar lavage fluid (BALF) did not find anything. Finally, Legionella pneumophila was identified by target next-generation sequencing (tNGS) detection. This case highlighted the timely use of tNGS, a new tool with fast speed, high accuracy and effective cost, could help to identify atypical infection and start an early therapy.},
}
@article {pmid37408309,
year = {2023},
author = {Ji, H and Englmaier, F and Morigny, P and Giroud, M and Gräsle, P and Brings, S and Szendrödi, J and Berriel Diaz, M and Plettenburg, O and Herzig, S and Rohm, M},
title = {Development of a peptide drug restoring AMPK and adipose tissue functionality in cancer cachexia.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {31},
number = {8},
pages = {2408-2421},
pmid = {37408309},
issn = {1525-0024},
support = {R01 GM129325/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; Adipose Tissue/metabolism ; *AMP-Activated Protein Kinases/metabolism ; Cachexia/drug therapy/etiology/metabolism ; *Neoplasms/complications/metabolism ; Peptides/pharmacology ; Pharmaceutical Preparations/metabolism ; Quality of Life ; },
abstract = {Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in adipose tissue as a key event in cachexia-related adipose tissue dysfunction and developed an adeno-associated virus (AAV)-based approach to prevent AMPK degradation and prolong cachexia-free survival. Here, we show the development and optimization of a prototypic peptide, Pen-X-ACIP, where the AMPK-stabilizing peptide ACIP is fused to the cell-penetrating peptide moiety penetratin via a propargylic glycine linker to enable late-stage functionalization using click chemistry. Pen-X-ACIP was efficiently taken up by adipocytes, inhibited lipolysis, and restored AMPK signaling. Tissue uptake assays showed a favorable uptake profile into adipose tissue upon intraperitoneal injection. Systemic delivery of Pen-X-ACIP into tumor-bearing animals prevented the progression of cancer cachexia without affecting tumor growth and preserved body weight and adipose tissue mass with no discernable side effects in other peripheral organs, thereby achieving proof of concept. As Pen-X-ACIP also exerted its anti-lipolytic activity in human adipocytes, it now provides a promising platform for further (pre)clinical development toward a novel, first-in-class approach against cancer cachexia.},
}
@article {pmid37402637,
year = {2023},
author = {Shulder, S and Tamma, PD and Fiawoo, S and Dzintars, K and Escobar, D and Livorsi, DJ and Malani, AN and Palacio, D and Spivak, ES and Zimmerman, M and Bork, JT},
title = {Infectious Diseases Consultation Associated With Reduced Mortality in Gram-Negative Bacteremia.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {77},
number = {9},
pages = {1234-1237},
doi = {10.1093/cid/ciad383},
pmid = {37402637},
issn = {1537-6591},
mesh = {Humans ; *Communicable Diseases ; Cohort Studies ; *Bacteremia ; Referral and Consultation ; Retrospective Studies ; *Gram-Negative Bacterial Infections ; },
abstract = {Gram-negative bacteremia (GN-BSI) can cause significant morbidity and mortality, but the benefit of infectious diseases consultation (IDC) is not well defined. A 24-site observational cohort study of unique hospitalized patients with 4861 GN-BSI episodes demonstrated a 40% decreased risk of 30-day mortality in patients with IDC compared to those without IDC.},
}
@article {pmid37385107,
year = {2023},
author = {Chen, J and Gao, P and Xiao, W and Cheng, G and Krishna, S and Wang, J and Wong, YK and Wang, C and Gu, L and Yang, DH and Wang, J},
title = {Multi-omics dissection of stage-specific artemisinin tolerance mechanisms in Kelch13-mutant Plasmodium falciparum.},
journal = {Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy},
volume = {70},
number = {},
pages = {100978},
doi = {10.1016/j.drup.2023.100978},
pmid = {37385107},
issn = {1532-2084},
mesh = {Humans ; Plasmodium falciparum/genetics ; Multiomics ; Drug Resistance/genetics ; Protozoan Proteins/genetics/pharmacology/therapeutic use ; *Artemisinins/pharmacology/therapeutic use ; *Antimalarials/pharmacology/therapeutic use ; *Malaria, Falciparum/drug therapy/parasitology ; Mutation ; },
abstract = {AIMS: We investigated the stage-specific mechanisms of partial resistance to artemisinin (ART, an antimalarial drug) in Plasmodium falciparum (P. falciparum) carrying the Kelch13 C580Y mutation.<br><br>METHODS: Using fluorescence labeling and activity-based protein profiling, we systematically profile the ART activation levels in P. falciparum during the entire intra-erythrocytic developmental cycle (IDC), and determined the ART-targets profile of the ART-sensitive and -resistant strains at different stages. We retrieved and integrated datasets of single-cell transcriptomics and label-free proteomics across three IDC stages of wild-type P. falciparum. We also employed lipidomics to validate lipid metabolic reprogramming in the resistant strain.<br><br>RESULTS: The activation and expression patterns of genes and proteins of ART-targets in both ART-sensitive and resistant strains varied at different stages and periods of P. falciparum development, with the late trophozoite stage harboring the largest number of ART targets. We identified and validated 36 overlapping targets, such as GAPDH, EGF-1a, and SpdSyn, during the IDC stages in both strains. We revealed the ART-insensitivity of fatty acid-associated activities in the partially resistant strain at both the early ring and early trophozoite stages.<br><br>CONCLUSIONS: Our multi-omics strategies provide novel insights into the mechanisms of ART partial resistance in Kelch13 mutant P. falciparum, demonstrating the stage-specific interaction between ART and malaria parasites.},
}
@article {pmid37371442,
year = {2023},
author = {Maggi, G and Vitale, C and Delle Curti, A and Amboni, M and Santangelo, G},
title = {Unawareness of Apathy in Parkinson's Disease: The Role of Executive Dysfunction on Symptom Recognition.},
journal = {Brain sciences},
volume = {13},
number = {6},
pages = {},
pmid = {37371442},
issn = {2076-3425},
abstract = {Altered self-awareness or anosognosia may impact patients' everyday life by interfering with their safe and independent functioning. Symptom awareness has been linked to executive dysfunctions caused by damage to frontal regions. Apathy is a frequent neuropsychiatric manifestation of Parkinson's disease (PD) and is considered a consequence of altered functioning of cortico-subcortical circuitries connecting the prefrontal cortex (PFC) with the basal ganglia. Thus, apathetic PD patients may be not be fully aware of their condition due to shared neuropathophysiological mechanisms. The present study aimed to explore the awareness of apathy in PD patients by comparing the self-reported evaluations with their caregivers' ratings. Moreover, we explored the clinical predictors of possible discrepancies and their consequences on patients' self-reported evaluation of quality of life (QoL). We found a fair agreement between patients' self-reports and caregivers' ratings on apathy scores, with patients reporting less severe apathetic symptoms, especially those related to executive and auto-activation processing, compared to their caregivers' reports. Executive functioning was found to mediate the relationship between disease stage and awareness of the apathetic state. Awareness of executive apathy impacted patients' self-reported QoL. Therefore, PD patients might be unaware of their apathetic symptoms, especially those with worse executive functioning, which plays a key role in metacognitive processes such as self-monitoring and error detection. Anosognosia for apathy in PD patients may affect their QoL perception and leads to misleading self-report evaluations that delay diagnosis and treatment.},
}
@article {pmid37363526,
year = {2023},
author = {Kara Tahhan, N and Abou Azan, A and Jomaa Al Ali, I and Abdul Aziz, J and Sara, S},
title = {Cutaneous metastases as a primary manifestation of invasive ductal carcinoma of the breast: a case report.},
journal = {Annals of medicine and surgery (2012)},
volume = {85},
number = {6},
pages = {3062-3065},
pmid = {37363526},
issn = {2049-0801},
abstract = {UNLABELLED: Cutaneous metastases as the first sign of invasive ductal carcinoma are not common. The ambiguous presentation of asymptomatic lesions may result in various diagnoses including dermatologic causes. Early diagnosis is essential in such cases.<br><br>CASE PRESENTATION: A 43-year-old woman with no risk factors for developing breast cancer at a young age was diagnosed with invasive ductal carcinoma of the left breast after dermatologic complaints of diffuse lesions on the left-back and right subclavian region. The patient remained asymptomatic except for the recent cutaneous presentation, which did not arouse much suspicion.<br><br>CONCLUSION: Cutaneous metastases of breast cancer remain uncommon, but at the same time represent a poor prognosis for the patient, and when they do occur, treatment options are limited. The delay in taking the proper diagnostic measures in such cases imposes a need to adopt a wider perspective when dealing with the possible occurrence of advanced disease. This also adds up to the importance of breast self-examination by women at a young age and full examination by physicians, especially when they encounter a misguiding presentation.},
}
@article {pmid37363420,
year = {2023},
author = {Singh, S and Singh, AL and Pal, KK and Reddy, KK and Gangadhara, K and Dey, R and Mahatma, MK and Verma, A and Kumar, N and Patel, CB and Thawait, LK and Ahmed, S and Navapara, R and Rani, K and Kona, P},
title = {Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.},
journal = {Physiology and molecular biology of plants : an international journal of functional plant biology},
volume = {29},
number = {5},
pages = {725-737},
pmid = {37363420},
issn = {0971-5894},
abstract = {UNLABELLED: Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe[2+]) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml[-1]), carotenoid accumulation (1.96-2.08 µg ml[-1]), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm[-1]) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.},
}
@article {pmid37363122,
year = {2023},
author = {Wani, K and Patel, K and Dabak, V},
title = {Hepatotoxicity After CDK 4/6 Inhibitor Initiation in the Treatment of Hormone-Positive Metastatic Breast Cancer.},
journal = {Cureus},
volume = {15},
number = {6},
pages = {e40871},
pmid = {37363122},
issn = {2168-8184},
abstract = {Cancer cells proliferate using various mechanisms. One mechanism of preventing tumor cell growth is blockade of the cyclin-dependent kinase (CDK) 4/6 axis. Multiple CDK 4/6 inhibitors - ribociclib, palbociclib, and abemaciclib - have significantly improved progression-free survival rates. However, they can cause hepatotoxicity. We present a case of a 67-year-old female who was diagnosed with stage 1C invasive ductal carcinoma. She was treated with letrozole and ribociclib due to recurrence as metastatic disease, but within 10 days, she developed transaminitis. She then started palbociclib but experienced elevated transaminases within two weeks, needing discontinuation of palbociclib. Subsequent positron-emission tomography/computed tomography imaging showed disease progression, and she was started on fulvestrant. We considered adding abemaciclib, but the patient declined and has had stable disease for more than a year on fulvestrant. CDK 4/6 inhibitors are used to treat metastatic breast cancer and are generally well tolerated. The most common side effect is neutropenia; however, our patient developed transaminitis. The novelty of our case is the development of hepatotoxicity even after the introduction of another CDK 4/6 inhibitor, indicating at least some degree of class effect. In summary, CDK 4/6 inhibitors have significantly improved outcomes in hormone-positive metastatic breast cancers. However, a small percentage suffer from hepatic injury enough to warrant discontinuation of the drug, and we must continue to assess the risk versus benefit profile when offering them to our patients.},
}
@article {pmid37324312,
year = {2023},
author = {Jain, AK},
title = {Locally Advanced Breast Cancer: Response Evaluation to Neoadjuvant Chemotherapy by Clinico-Histopathological Parameters and Molecular Imaging.},
journal = {Indian journal of surgical oncology},
volume = {14},
number = {2},
pages = {279-287},
pmid = {37324312},
issn = {0975-7651},
abstract = {In India, breast cancer (BC) is not only the commonest cancer but also the commonest cause of cancer mortality among females. Advanced BC constitutes >70% of BC cases at initial presentation in India, among which locally advanced breast cancer (LABC) requires a multi-disciplinary approach with a combination of systemic and locoregional therapies. This descriptive hospital-based study was conducted over 1½ years after seeking approval from the institutional ethics committee. Fifty-five patients satisfying all the criteria of the study were enrolled. The data, thus, collected was pooled into Excel spreadsheet and analyzed using appropriate statistical tools. Most of the patients were postmenopausal, multiparous with breast lump being the commonest symptom. Mean baseline characteristics were age - 48 years, SUV max - 9.2, and Ki-67 - 17.8%. cT4 and cN2 were the commonest pre-NACT tumor and lymph node stage. Invasive ductal carcinoma was the commonest tumor type with the most common tumor grade being grade 3. Hormone receptor positivity and HER2 overexpression were seen in 33 and 17 patients respectively. Post-NACT 32 patients underwent breast-conserving surgery. Pathological complete response (pCR), i.e., ypT0N0, was seen in 13 patients (23.6%). There was slight alteration in hormone receptor status, HER2 expression and Ki-67 in the post-NACT resected tumor. pCR, which is a surrogate marker for improved clinical outcome (DFS and OS) in LABC patients, occurred more commonly in patients with pre-NACT grade 3 tumors, high Ki-67, hormone receptor-negative, and HER2 overexpressing BC (overall, in triple negative BC) but was statistically significant only with Ki-67. Post-NACT, SUV max with a cut off ≤1.5, and ΔSUV max of >80% correlated closely with pCR.},
}
@article {pmid37301537,
year = {2023},
author = {Wu, K and Li, W and Liu, H and Niu, C and Shi, Q and Zhang, J and Gao, G and Sun, H and Liu, F and Fu, L},
title = {Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis.},
journal = {The American journal of pathology},
volume = {193},
number = {9},
pages = {1267-1283},
doi = {10.1016/j.ajpath.2023.05.010},
pmid = {37301537},
issn = {1525-2191},
mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Disease-Free Survival ; *Carcinoma, Papillary/pathology ; *Breast Neoplasms/metabolism ; Metabolome ; Methyltransferases/metabolism ; Prognosis ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; Repressor Proteins/metabolism ; },
abstract = {Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.},
}
@article {pmid37290673,
year = {2023},
author = {Nieborak, A and Lukauskas, S and Capellades, J and Heyn, P and Santos, GS and Motzler, K and Zeigerer, A and Bester, R and Protzer, U and Schelter, F and Wagner, M and Carell, T and Hruscha, A and Schmid, B and Yanes, O and Schneider, R},
title = {Depletion of pyruvate kinase (PK) activity causes glycolytic intermediate imbalances and reveals a PK-TXNIP regulatory axis.},
journal = {Molecular metabolism},
volume = {74},
number = {},
pages = {101748},
pmid = {37290673},
issn = {2212-8778},
mesh = {Animals ; *Pyruvate Kinase/genetics ; Reactive Oxygen Species ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; *Neoplasms/genetics/metabolism ; Thioredoxins/chemistry/metabolism ; },
abstract = {OBJECTIVE: Cancer cells convert more glucose into lactate than healthy cells, what contributes to their growth advantage. Pyruvate kinase (PK) is a key rate limiting enzyme in this process, what makes it a promising potential therapeutic target. However, currently it is still unclear what consequences the inhibition of PK has on cellular processes. Here, we systematically investigate the consequences of PK depletion for gene expression, histone modifications and metabolism.<br><br>METHODS: Epigenetic, transcriptional and metabolic targets were analysed in different cellular and animal models with stable knockdown or knockout of PK.<br><br>RESULTS: Depleting PK activity reduces the glycolytic flux and causes accumulation of glucose-6-phosphate (G6P). Such metabolic perturbation results in stimulation of the activity of a heterodimeric pair of transcription factors MondoA and MLX but not in a major reprogramming of the global H3K9ac and H3K4me3 histone modification landscape. The MondoA:MLX heterodimer upregulates expression of thioredoxin-interacting protein (TXNIP) - a tumour suppressor with multifaceted anticancer activity. This effect of TXNIP upregulation extends beyond immortalised cancer cell lines and is applicable to multiple cellular and animal models.<br><br>CONCLUSIONS: Our work shows that actions of often pro-tumorigenic PK and anti-tumorigenic TXNIP are tightly linked via a glycolytic intermediate. We suggest that PK depletion stimulates the activity of MondoA:MLX transcription factor heterodimers and subsequently, increases cellular TXNIP levels. TXNIP-mediated inhibition of thioredoxin (TXN) can reduce the ability of cells to scavenge reactive oxygen species (ROS) leading to the oxidative damage of cellular structures including DNA. These findings highlight an important regulatory axis affecting tumour suppression mechanisms and provide an attractive opportunity for combination cancer therapies targeting glycolytic activity and ROS-generating pathways.},
}
@article {pmid37283256,
year = {2023},
author = {Bukamal, Z and AlRayes, A},
title = {Prevalence of BRCA1 and BRCA2 Mutations Among High-risk Bahraini Patients with Breast Cancer.},
journal = {The Gulf journal of oncology},
volume = {1},
number = {42},
pages = {22-25},
pmid = {37283256},
issn = {2078-2101},
mesh = {Humans ; Female ; Male ; *Breast Neoplasms/epidemiology/genetics/diagnosis ; Bahrain/epidemiology ; Retrospective Studies ; Prevalence ; Mutation ; *Carcinoma, Ductal ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; },
abstract = {OBJECTIVE: The purpose is to study the prevalence of BRCA1 and BRCA2 mutations in high-risk Bahraini patients diagnosed with breast cancer, its relation to family history, and to determine the clinicopathologic features of breast cancer associated with these genetic mutations, over a period of 7 years.<br><br>BACKGROUND: Breast cancer is the most common type of cancer occurring in women and the second most common type generally. Approximately 12% of women worldwide will develop carcinoma of the breast sometime during their life. Additionally, 72% of women with an inherited BRCA1 mutation and 69% of those with a mutated BRCA2 will develop breast cancer by 80 years of age. The incidence of breast cancer in Bahraini women have increased over the last decade. Still, the data on BRCA1 &amp; BRCA2 mutations in relation to breast cancer patients is limited in the Arab region, not omitting Bahrain as a country with deficient BRCA prevalence data.<br><br>METHODS: This retrospective study was carried out in Salmaniya Medical Complex, Bahrain, to determine the prevalence of BRCA1 and BRCA2 mutations and to observe the breast cancer's histopathologic features that are associated with these mutations.<br><br>RESULTS: 271 patients underwent the BRCA gene testing between 2013 and 2019. Out of 271 patients, 35 were excluded. Out of the 236 breast cancer patients, 219 (93%) did not have the mutation. The BRCA gene was carried by a total of 17 (7%) patients; 13 (5%) BRCA1 and 4 (2%) BRCA2. Thirteen BRCA carrier patients had invasive ductal carcinoma (IDC) (76%), 2 had ductal carcinoma in situ (DCIS) (12%), while 2 patients' histopathology was not available. Molecular subtypes showed 4 triple negative basal sub-type (TNBC), 10 positive ER and PR hormonal status, 1 positive HER-2, while 2 patients' hormonal receptor status was not available. Two BRCA1 carriers had both breast and ovarian cancers. A total of 5 (2%) breast cancer male patients were among the tested population, out of which, 1 (0.4% of the total and 20% of the male patients) was a BRCA2 carrier. Out of the 236 patients, 76 (32%) were younger than 40 years of age at the time of diagnosis. Then again, out of the 17 BRCA carrier patients, 7 (41%) were younger than 40 years.<br><br>CONCLUSION: The prevalence of BRCA mutation in high risk Bahraini breast cancer patients is 7%. Among those patients, BRCA1 mutation is the most prevalent (5%) and invasive ductal carcinoma (IDC) is the most common histopathological subtype. However, there was not enough data to conclude the most prevalent molecular subtype of breast cancer in BRCA carriers due to deficiency of overseas pathology reports for patients operated outside Bahrain. When developing treatment plans for younger patients with breast cancer, inherited syndromes and precisely BRCA mutations need to be considered. Bahrain is implementing genetic testing for breast cancer patients &#x2264; 50 years of age since 2018, according to NCCN guidelines. We will continue to build our database to better characterize breast cancer subtypes and determine their hereditary pattern for identification of high risk families in Bahrain and for future development of more specific therapeutic approaches.<br><br>KEY WORDS: Breast cancer, BRCA1, BRCA2, BRCA mutation, Bahrain, Arab region.},
}
@article {pmid37251671,
year = {2023},
author = {Kender, Z and von Rauchhaupt, E and Schwarz, D and Tsilingiris, D and Schimpfle, L and Bartl, H and Longo, VD and Bendszus, M and Kopf, S and Herzig, S and Heiland, S and Szendroedi, J and Sulaj, A},
title = {Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1143799},
pmid = {37251671},
issn = {1664-2392},
mesh = {Humans ; Action Potentials ; *Diabetes Mellitus, Type 2/complications/pathology ; *Diabetic Neuropathies/diagnosis ; Fasting ; Pain ; },
abstract = {BACKGROUND AND AIM: Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D).<br><br>STUDY DESIGN AND METHODS: Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 &#xb1; 1.3% [61.4 &#xb1; 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention.<br><br>RESULTS: Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both.<br><br>CONCLUSIONS: Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients.<br><br>CLINICAL TRIAL REGISTRATION: https://drks.de/search/en/trial/DRKS00014287, identifier DRKS00014287.},
}
@article {pmid37246414,
year = {2023},
author = {Lee, J and Park, S and Jung, HA and Lee, SH and Seo, S and Kim, SB and Kim, JW and Lee, KW and Kang, EJ and Kim, JW and Choi, YJ and Shim, BY and An, HJ and Park, LC and Shin, SH and Kim, JJ and Oh, SY and Kim, MK and Ahn, MJ},
title = {A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.},
journal = {Cancer},
volume = {129},
number = {19},
pages = {2966-2974},
doi = {10.1002/cncr.34892},
pmid = {37246414},
issn = {1097-0142},
mesh = {Humans ; Female ; Docetaxel/therapeutic use ; Micelles ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Trastuzumab/therapeutic use ; Receptor, ErbB-2/genetics/metabolism ; *Carcinoma, Ductal ; Salivary Glands/metabolism ; *Breast Neoplasms/drug therapy ; },
abstract = {BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab.<br><br>METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of &#x2265;2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of &#x2265;2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75&#xa0;mg/m[2]) and trastuzumab-pkrb (8&#xa0;mg/kg in the first cycle and 6&#xa0;mg/kg in subsequent cycles) every 3&#xa0;weeks. Primary end point was objective response rate (ORR).<br><br>RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio &#x2265;2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively.<br><br>CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC.<br><br>PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9&#xa0;months, median duration of response of 6.7&#xa0;months, and median overall survival of 23.3&#xa0;months.},
}
@article {pmid37222952,
year = {2023},
author = {Abdollahi, E and Mozdarani, H and Alizadeh, BZ},
title = {Role of circ-FOXO3 and miR-23a in radiosensitivity of breast cancer.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {30},
number = {5},
pages = {714-726},
pmid = {37222952},
issn = {1880-4233},
support = {Grant Number: IG-39711//Tarbiat Modares University/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/radiotherapy ; Leukocytes, Mononuclear ; Apoptosis/genetics ; *Carcinoma ; *Drug-Related Side Effects and Adverse Reactions ; *MicroRNAs/genetics ; Cell Proliferation ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Forkhead Box Protein O3/genetics ; },
abstract = {Identifying the radiosensitivity of cells before radiotherapy (RT) in breast cancer (BC) patients allows appropriate switching between routinely used treatment regimens and reduces adverse side effects in exposed patients. In this study, blood was collected from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC and 20 healthy women. To predict cellular radiosensitivity, a standard G2-chromosomal assay was performed. From these 60 samples, 20 BC patients were found to be radiosensitive based on the G2 assay. Therefore, molecular studies were finally performed on two equal groups (20 samples each) of patients with and without cellular radiosensitivity. QPCR was performed to examine the expression levels of circ-FOXO3 and miR-23a in peripheral blood mononuclear cells (PBMCs) and RNA sensitivity and specificity were determined by plotting Receiver Operating Characteristic (ROC) curves. Binary logistic regression was performed to identify RNA involvement in BC and cellular radiosensitivity (CR) in BC patients. Meanwhile, qPCR was used to compare differential RNA expression in the radiosensitive MCF-7 and radioresistant MDA-MB-231 cell lines. An annexin -V FITC/PI binding assay was used to measure cell apoptosis 24 and 48 h after 2 Gy, 4 Gy, and 8 Gy gamma-irradiation. Results indicated that circ-FOXO3 was downregulated and miR-23a was upregulated in BC patients. RNA expression levels were directly associated with CR. Cell line results showed that circ-FOXO3 overexpression induced apoptosis in the MCF-7 cell line and miR-23a overexpression inhibited apoptosis in the MDA-MB-231 cell line. Evaluation of the ROC curves revealed that both RNAs had acceptable specificity and sensitivity in predicting CR in BC patients. Binary logistic regression showed that both RNAs were also successful in predicting breast cancer. Although only circ-FOXO3 has been shown to predict CR in BC patients, circ-FOXO3 may function as a tumor suppressor and miR-23a may function as oncomiR in BC. Circ-FOXO3 and miR-23a may be promising potential biomarkers for BC prediction. Furthermore, Circ-FOXO3 could be a potential biomarker for predicting CR in BC patients.},
}
@article {pmid37217416,
year = {2023},
author = {Rummel, KA and Gao, RW and Francis, LN and Petersen, IA and Mutter, RW and Corbin, KS},
title = {Secondary breast angiosarcoma following accelerated partial breast irradiation with intracavitary multicatheter applicator brachytherapy.},
journal = {Brachytherapy},
volume = {22},
number = {4},
pages = {487-490},
doi = {10.1016/j.brachy.2023.04.007},
pmid = {37217416},
issn = {1873-1449},
mesh = {Female ; Humans ; Aged ; *Hemangiosarcoma/etiology ; *Brachytherapy/methods ; *Breast Neoplasms/surgery ; Breast/pathology ; Mastectomy, Segmental ; },
abstract = {PURPOSE: Secondary angiosarcoma of the breast is a rare complication of breast radiotherapy and is associated with a poor prognosis. There are many reported cases of secondary angiosarcoma following whole breast irradiation (WBI), however development of secondary angiosarcoma following brachytherapy-based accelerated partial breast irradiation (APBI) is not as well characterized.<br><br>METHODS AND MATERIALS: We reviewed and reported a case of a patient who developed secondary angiosarcoma of the breast following intracavitary multicatheter applicator brachytherapy APBI.<br><br>RESULTS: A 69-year-old female was originally diagnosed with T1N0M0 invasive ductal carcinoma of the left breast and treated with lumpectomy followed by adjuvant intracavitary multicatheter applicator brachytherapy APBI. Seven years following her treatment, she developed secondary angiosarcoma. However, the diagnosis of secondary angiosarcoma was delayed due to nonspecific imaging findings and a negative biopsy.<br><br>CONCLUSIONS: Our case highlights the need for secondary angiosarcoma to be considered in the differential diagnosis when patients present with symptoms such as breast ecchymosis and skin thickening following WBI or APBI. Prompt diagnosis and referral to a high-volume sarcoma treatment center for multidisciplinary evaluation is vital.},
}
@article {pmid37202608,
year = {2023},
author = {Shawky, A and Sabit, H and Nazih, M and Baraka, K and El-Zawahry, M},
title = {CYP2C19 Polymorphism in Ischemic Heart Disease Patients Taking Clopidogrel After Percutaneous Coronary Intervention in Egypt.},
journal = {Journal of epidemiology and global health},
volume = {13},
number = {2},
pages = {374-383},
pmid = {37202608},
issn = {2210-6014},
mesh = {Humans ; *Cardiovascular Diseases ; Clopidogrel/adverse effects/metabolism/therapeutic use ; Cytochrome P-450 CYP2C19/genetics/metabolism ; Egypt/epidemiology ; *Myocardial Ischemia/genetics/therapy/chemically induced ; *Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/adverse effects/metabolism/therapeutic use ; Treatment Outcome ; },
abstract = {BACKGROUND: Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in the CYP2C19 gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study.<br><br>METHODS: The genetic variations in the CYP2C19 gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1&#xa0;year to monitor MACE, and the correlations between the allelic variations in CYP2C19 and MACE were recorded.<br><br>RESULTS: During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping of CYP2C19 in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotype CYP2C19*1/*1 and 52 patients (51%) were abnormal metabolizers, with genotypes CYP2C19*1/*2 (n&#x2009;=&#x2009;15), CYP2C19*1/*3 (n&#x2009;=&#x2009;1), CYP2C19*1/*17 (n&#x2009;=&#x2009;35), and CYP2C19*2/*17 (n&#x2009;=&#x2009;1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on the CYP2C19 allelic distribution.<br><br>CONCLUSION: This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs.},
}
@article {pmid37201361,
year = {2023},
author = {Mekni, K and Mejri, O and Ayadi, A and ElFekif, C},
title = {Unexpected association between breast cancer and molar pregnancy in a 52-year-old woman: A case report.},
journal = {International journal of surgery case reports},
volume = {107},
number = {},
pages = {108253},
pmid = {37201361},
issn = {2210-2612},
abstract = {INTRODUCTION: There was no prior discussion about the association between breast cancer and molar pregnancy, particularly at an advanced age. Through our case and a systematic review, we will discuss the relevance of ovarian castration in hormone-receptor-positive breast cancer.<br><br>CASE PRESENTATION: We reported the case of a 52-year-old woman, not yet menopausal, who was diagnosed with a right breast tumor classified as BI-RADS category 4. The anatomopathological analysis of mammary biopsy revealed an invasive ductal carcinoma of no special type (grade 2). Hormone receptors were positive. It was a HER2-negative Breast cancer. It was then decided to treat the patient with radical surgery followed by chemotherapy, radiotherapy, and hormonotherapy. The patient had a "Patey operation". The postoperative course was without significant complications. No medical or surgical castration was indicated in the expectation that chemotherapy would cause ovarian failure. Unlikely, during chemotherapy course our patient developed a molar pregnancy.<br><br>CLINICAL DISCUSSION: Our case illustrates the possibility of pregnancy in non-menopausal women with estrogen-receptor-positive breast cancer. The combination of tamoxifen or aromatase inhibitors with ovarian suppression as standard adjuvant therapy may be recommended in such cases.<br><br>CONCLUSIONS: Ovarian function suppression in non-menopausal women with hormone receptor-positive breast cancer seems to be necessary. So that, we can avoid unexpected manifestations like molar pregnancy.},
}
@article {pmid37201100,
year = {2023},
author = {Koçberber, Z and Willemsen, N and Bartelt, A},
title = {The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1176733},
pmid = {37201100},
issn = {1664-2392},
mesh = {Animals ; Mice ; *Adipocytes, Brown/metabolism ; *Proteasome Endopeptidase Complex/metabolism ; Adipose Tissue, Brown/metabolism ; Adipogenesis/genetics ; Temperature ; Nuclear Proteins/metabolism ; },
abstract = {INTRODUCTION: Brown adipocytes produce heat through non shivering thermogenesis (NST). To adapt to temperature cues, they possess a remarkably dynamic metabolism and undergo substantial cellular remodeling. The proteasome plays a central role in proteostasis and adaptive proteasome activity is required for sustained NST. Proteasome activators (PAs) are a class of proteasome regulators but the role of PAs in brown adipocytes is unknown. Here, we studied the roles of PA28α (encoded by Psme1) and PA200 (encoded by Psme4) in brown adipocyte differentiation and function.<br><br>METHODS: We measured gene expression in mouse brown adipose tissue. In cultured brown adipocytes, we silenced Psme1 and/or Psme4 expression through siRNA transfection. We then assessed impact on the ubiquitin proteasome system, brown adipocyte differentiation and function.<br><br>RESULTS: We found that Psme1 and Psme4 are expressed in brown adipocytes in vivo and in vitro. Through silencing of Psme1 and/or Psme4 expression in cultured brown adipocytes, we found that loss of PAs did not impair proteasome assembly or activity, and that PAs were not required for proteostasis in this model. Loss of Psme1 and/or Psme4 did not impair brown adipocyte development or activation, suggesting that PAs are neither required for brown adipogenesis nor NST.<br><br>DISCUSSION: In summary, we found no role for Psme1 and Psme4 in brown adipocyte proteostasis, differentiation, or function. These findings contribute to our basic understanding of proteasome biology and the roles of proteasome activators in brown adipocytes.},
}
@article {pmid37200388,
year = {2023},
author = {Amer, NN and Khairat, R and Hammad, AM and Kamel, MM},
title = {DDX43 mRNA expression and protein levels in relation to clinicopathological profile of breast cancer.},
journal = {PloS one},
volume = {18},
number = {5},
pages = {e0284455},
pmid = {37200388},
issn = {1932-6203},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Neoplasm Proteins/genetics ; RNA, Messenger/genetics ; Prognosis ; Disease Progression ; Biomarkers, Tumor/genetics/analysis ; DEAD-box RNA Helicases/genetics/metabolism ; },
abstract = {BACKGROUND: Breast cancer (BC) is the most often diagnosed cancer in women globally. Cancer cells appear to rely heavily on RNA helicases. DDX43 is one of DEAD- box RNA helicase family members. But, the relationship between clinicopathological, prognostic significance in different BC subtypes and DDX43 expression remains unclear. Therefore, the purpose of this study was to assess the clinicopathological significance of DDX43 protein and mRNA expression in different BC subtypes.<br><br>MATERIALS AND METHODS: A total of 80 females newly diagnosed with BC and 20 control females that were age-matched were recruited for this study. DDX43 protein levels were measured by ELISA technique. We used a real-time polymerase chain reaction quantification (real-time PCR) to measure the levels of DDX43 mRNA expression. Levels of DDX43 protein and mRNA expression within BC patients had been compared to those of control subjects and correlated with clinicopathological data.<br><br>RESULTS: The mean normalized serum levels of DDX43 protein were slightly higher in control than in both benign and malignant groups, but this result was non-significant. The mean normalized level of DDX43 mRNA expression was higher in the control than in both benign and malignant cases, although the results were not statistically significant and marginally significant, respectively. Moreover, the mean normalized level of DDX43 mRNA expression was significantly higher in benign than in malignant cases. In malignant cases, low DDX43 protein expression was linked to higher nuclear grade and invasive duct carcinoma (IDC), whereas high mRNA expression was linked to the aggressive types of breast cancer such as TNBC, higher tumor and nuclear grades.<br><br>CONCLUSION: This study explored the potential of using blood DDX43 mRNA expression or protein levels, or both in clinical settings as a marker of disease progression in human breast cancer. DDX43 mRNA expression proposes a less invasive method for discriminating benign from malignant BC.},
}
@article {pmid37195240,
year = {2023},
author = {Murata, S and Yamashita, H and Kido, S and Harada, D and Ohtsuru, S and Sato, N},
title = {DYNAMIC METABOLIC CHANGES OBSERVED IN AN LPS-INDUCED SYSTEMIC INFLAMMATION RAT MODEL USING CONTINUOUS LONG-TERM INDIRECT CALORIMETRY EXPERIMENTS.},
journal = {Shock (Augusta, Ga.)},
volume = {60},
number = {1},
pages = {130-136},
pmid = {37195240},
issn = {1540-0514},
mesh = {Humans ; *Lipopolysaccharides/toxicity ; Calorimetry, Indirect/methods ; *Critical Illness ; Energy Metabolism/physiology ; Critical Care ; },
abstract = {Background : Nutritional management is crucial for severely ill patients. Measuring metabolism is believed to be necessary for the acute sepsis phase to accurately estimate nutrition. Indirect calorimetry (IDC) is assumed to be useful for acute intensive care; however, there are few studies on long-term IDC measurement in patients with systemic inflammation. Methods : Rats were categorized into the LPS received or control groups; LPS rats were categorized into underfeeding (UF), adjusted feeding (AF), and overfeeding (OF) groups. Indirect calorimetry measurement was performed until 72 or 144 h. Body composition was measured at -24 and 72 or 144 h, and tissue weight was measured at 72 or 144 h. Results : Low energy consumption and loss of diurnal variation of resting energy expenditure were observed in the LPS group compared with the control group until 72 h, after which the LPS group recovered. The resting energy expenditure in the OF group was higher than that in the UF and AF groups. In the first phase, low energy consumption was observed in all groups. In the second and third phases, higher energy consumption occurred in the OF group than in the UF and AF groups. In the third phase, diurnal variation recovered in all groups. Muscle atrophy caused body weight loss, but fat tissue loss did not occur. Conclusions : We observed metabolic changes with IDC during the acute systemic inflammation phase owing to differences in calorie intake. This is the first report of long-term IDC measurement using the LPS-induced systemic inflammation rat model.},
}
@article {pmid37186041,
year = {2023},
author = {Wei, S and Bao, M and Zhu, Y and Zhang, W and Jiang, L},
title = {Identifying potential targets for lung cancer intervention by analyzing the crosstalk of cancer-associated fibroblasts and immune and metabolism microenvironment.},
journal = {Environmental toxicology},
volume = {38},
number = {8},
pages = {1951-1967},
doi = {10.1002/tox.23821},
pmid = {37186041},
issn = {1522-7278},
support = {82103309//Youth Found of National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Cancer-Associated Fibroblasts/metabolism/pathology ; *Lung Neoplasms/pathology ; Lung/pathology ; Signal Transduction ; Glycerophospholipids/metabolism ; Tumor Microenvironment/genetics ; },
abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to play a crucial role in the tumor microenvironment and progression.<br><br>METHODS: The data used in this study were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases, and all analyses were performed using R software.<br><br>RESULTS: We first quantified the CAFs infiltration through single sample gene set enrichment analysis in the TCGA and combined GEO cohort (GSE30219, GSE37745, and GSE50081). Our result showed that patients with high levels of CAF infiltration were associated with worse clinical features and poor prognosis. Immune microenvironment analysis indicated that high CAF infiltration might result in increased infiltration of immune cells, including aDC, B cells, CD8+ T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, neutrophils, NK CD56dim cells, NK cells, pDC, and T cells. Correlation analysis showed a significant positive correlation between CAFs and M2 macrophages, while a negative correlation was found between CAFs and glycerophospholipid metabolism. Kaplan-Meier survival curves indicated that glycerophospholipid metabolism was a protective factor against lung cancer. Biological enrichment analysis showed that pathways such as allograft rejection, epithelial-mesenchymal transition, KRAS signaling, TNF-&#x3b1; signaling, myogenesis, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling were upregulated in the patients with high CAF infiltration. Moreover, patients with high CAF infiltration had a lower proportion of immunotherapy responders. Genome analysis showed that low CAFs infiltration was associated with high genome instability. We identified FGF5 and CELF3 as key genes involved in the interaction between CAFs, M2 macrophages, and glycerophospholipid metabolism, and further analyzed FGF5. In vitro experiments showed that FGF5 promoted the proliferation, invasion and migration of lung cancer cells and was primarily localized in the nucleoli fibrillar center.<br><br>CONCLUSIONS: Our study provides novel insights into the roles of CAFs in lung cancer progression and the underlying crosstalk of tumor metabolism and immune microenvironment.},
}
@article {pmid37171457,
year = {2023},
author = {Traberg, WC and Uribe, J and Druet, V and Hama, A and Moysidou, CM and Huerta, M and McCoy, R and Hayward, D and Savva, A and Genovese, AMR and Pavagada, S and Lu, Z and Koklu, A and Pappa, AM and Fitzgerald, R and Inal, S and Daniel, S and Owens, RM},
title = {Organic Electronic Platform for Real-Time Phenotypic Screening of Extracellular-Vesicle-Driven Breast Cancer Metastasis.},
journal = {Advanced healthcare materials},
volume = {12},
number = {27},
pages = {e2301194},
pmid = {37171457},
issn = {2192-2659},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology ; Cell Line, Tumor ; Early Detection of Cancer ; *Triple Negative Breast Neoplasms/drug therapy/pathology ; *Extracellular Vesicles ; Epithelial-Mesenchymal Transition/genetics ; Cell Movement ; Melanoma, Cutaneous Malignant ; },
abstract = {Tumor-derived extracellular vesicles (TEVs) induce the epithelial-to-mesenchymal transition (EMT) in nonmalignant cells to promote invasion and cancer metastasis, representing a novel therapeutic target in a field severely lacking in efficacious antimetastasis treatments. However, scalable technologies that allow continuous, multiparametric monitoring for identifying metastasis inhibitors are absent. Here, the development of a functional phenotypic screening platform based on organic electrochemical transistors (OECTs) for real-time, noninvasive monitoring of TEV-induced EMT and screening of antimetastatic drugs is reported. TEVs derived from the triple-negative breast cancer cell line MDA-MB-231 induce EMT in nonmalignant breast epithelial cells (MCF10A) over a nine-day period, recapitulating a model of invasive ductal carcinoma metastasis. Immunoblot analysis and immunofluorescence imaging confirm the EMT status of TEV-treated cells, while dual optical and electrical readouts of cell phenotype are obtained using OECTs. Further, heparin, a competitive inhibitor of cell surface receptors, is identified as an effective blocker of TEV-induced EMT. Together, these results demonstrate the utility of the platform for TEV-targeted drug discovery, allowing for facile modeling of the transient drug response using electrical measurements, and provide proof of concept that inhibitors of TEV function have potential as antimetastatic drug candidates.},
}
@article {pmid37170638,
year = {2024},
author = {Antón Rodriguez, &#xc1; and Odriozola Herrán, A and Echavarría Rodríguez, VJ and Alonso Fernández, S},
title = {Secondary sclerosing cholangitis induced by systemic chemotherapy.},
journal = {Revista espanola de enfermedades digestivas},
volume = {116},
number = {3},
pages = {173-174},
doi = {10.17235/reed.2023.9653/2023},
pmid = {37170638},
issn = {1130-0108},
mesh = {Female ; Humans ; Middle Aged ; *Cholangitis, Sclerosing/chemically induced/complications ; Cholangiopancreatography, Endoscopic Retrograde ; Liver ; Paclitaxel/adverse effects ; Immunoglobulin G ; },
abstract = {There are multiple causes of secondary sclerosing cholangitis (SSC), including mechanical obstruction, ischemia, congenital abnormalities, cholangiopathy of the critically ill patient and rarely, chemotherapy (1,2). We present the case of a 52-year-old female with a history of left breast invasive ductal carcinoma treated with neoadjuvant chemotherapy (adriamycin, cyclophosphamide and paclitaxel), surgery and radiotherapy in March 2021. She was admitted in July 2022 due to painless jaundice and pruritus with marked serum cholestasis. Magnetic resonance cholangiopancreatography showed multiple strictures and dilatations involving the intra and extrahepatic bile ducts (Figure 1.A), without any extrinsic stenotic cause. Findings were confirmed by endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy (Figure 1.B). Biopsies were negative for malignancy and IgG4 disease. In addition, autoantibodies were negative and serum IgG4 levels were normal. Due to these findings and the history of recent chemotherapy, the patient was diagnosed with paclitaxel-induced sclerosing cholangitis, initiating treatment with ursodeoxycholic acid. Over the following two months, she suffered two episodes of Klebsiella Pneumoniae bacteraemia due to acute cholangitis. Dilatation and placement of plastic stents in both biliary trees were performed and prophylactic antibiotherapy was started. The patient had a poor evolution and was not candidate for liver transplantation on account of a recent neoplasia. She died six months later due to sepsis secondary to multiple hepatic abscesses.},
}
@article {pmid37143728,
year = {2023},
author = {Cipolletti, M and Leone, S and Bartoloni, S and Acconcia, F},
title = {A functional genetic screen for metabolic proteins unveils GART and the de novo purine biosynthetic pathway as novel targets for the treatment of luminal A ERα expressing primary and metastatic invasive ductal carcinoma.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1129162},
pmid = {37143728},
issn = {1664-2392},
mesh = {Female ; Humans ; Estrogen Receptor alpha/genetics/metabolism ; Biosynthetic Pathways ; Neoplasm Recurrence, Local ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast ; Purines ; *Carbon-Nitrogen Ligases/metabolism ; Phosphoribosylglycinamide Formyltransferase/metabolism ; },
abstract = {Targeting tumor cell metabolism is a new frontier in cancer management. Thus, metabolic pathway inhibitors could be used as anti-estrogen receptor α (ERα) breast cancer (BC) drugs. Here, the interplay among metabolic enzyme(s), the ERα levels and cell proliferation was studied. siRNA-based screen directed against different metabolic proteins in MCF10a, MCF-7 and MCF-7 cells genetically resistant to endocrine therapy (ET) drugs and metabolomic analyses in numerous BC cell lines unveil that the inhibition of GART, a key enzyme in the purine de novo biosynthetic pathway, induces ERα degradation and prevent BC cell proliferation. We report here that a reduced GART expression correlates with a longer relapse-free-survival (RFS) in women with ERα-positive BCs. ERα-expressing luminal A invasive ductal carcinomas (IDCs) are sensitive to GART inhibition and GART expression is increased in receptor-positive IDCs of high grade and stage and plays a role in the development of ET resistance. Accordingly, GART inhibition reduces ERα stability and cell proliferation in IDC luminal A cells where it deregulates 17β-estradiol (E2):ERα signaling to cell proliferation. Moreover, the GART inhibitor lometrexol (LMX) and drugs approved for clinical treatment of primary and metastatic BC (4OH-tamoxifen and the CDK4/CDK6 inhibitors) exert synergic antiproliferative effects in BC cells. In conclusion, GART inhibition by LMX or other inhibitors of the de novo purine biosynthetic pathway could be a novel effective strategy for the treatment of primary and metastatic BCs.},
}
@article {pmid37139855,
year = {2023},
author = {Tsilingiris, D and Schimpfle, L and von Rauchhaupt, E and Sulaj, A and Seebauer, L and Bartl, H and Herzig, S and Szendroedi, J and Kopf, S and Kender, Z},
title = {Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {108},
number = {10},
pages = {e979-e988},
pmid = {37139855},
issn = {1945-7197},
mesh = {Humans ; Male ; *Diabetes Mellitus, Type 2/complications ; *Metabolic Syndrome/complications/epidemiology ; *Peripheral Nervous System Diseases/epidemiology/etiology ; *Insulin Resistance ; Glycation End Products, Advanced ; },
abstract = {AIM: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development.<br><br>METHODS: A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence.<br><br>RESULTS: Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011).<br><br>CONCLUSION: We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.},
}
@article {pmid37121885,
year = {2023},
author = {Ikegami, M},
title = {Prognostic benefit of comprehensive genomic profiling in clinical practice remains uncertain.},
journal = {Cancer science},
volume = {114},
number = {7},
pages = {3053-3055},
pmid = {37121885},
issn = {1349-7006},
support = {#22K15571//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; *Pancreatic Neoplasms/pathology ; Prognosis ; *Adenocarcinoma/genetics ; Retrospective Studies ; Genomics ; *Carcinoma, Pancreatic Ductal/genetics/therapy ; },
abstract = {The overall survival of patients who received genomically matched therapy was not significantly longer than that of patients receiving treatment only other than genomically matched therapy in the breast invasive ductal carcinoma (A), colorectal adenocarcinoma (B), and pancreatic adenocarcinoma (C) cohorts.},
}
@article {pmid37101747,
year = {2023},
author = {Xiang, S and Wei, M and Zhao, L and Lin, A and Xiong, Z},
title = {Integrated Analyses of the Expression and Prognostic Value of EPHB6 in Cervical Cancer and Its Correlation with Immune Infiltrates.},
journal = {Journal of oncology},
volume = {2023},
number = {},
pages = {2258906},
pmid = {37101747},
issn = {1687-8450},
abstract = {Among women, cervical cancer (CC) ranks as the third most frequent form of carcinoma and the fourth greatest cancer-related cause of deaths. There is increasing evidence that points to the dysregulation of EPH receptor B6 (EPHB6) in various cancers. On the other hand, neither the expression nor the function of EPHB6 in CC has been researched. In the first part of this investigation, we analyzed the data from the TCGA and discovered that the level of EPHB6 was much lower in CC tissues than in normal cervical tissues. ROC assays revealed that high EPHB6 expression had an AUC value of 0.835 for CC. The survival study revealed that both the overall and disease-specific survivals in this condition were considerably lower among patients who had a low EPHB6 level compared to those who had a high EPHB6 level. It is important to note that the multivariate COX regression analysis indicated that the expression of EPHB6 was an independent predictive factor. In addition to this, the C-indexes and calibration plots of a nomogram derived from multivariate assays revealed an accurate prediction performance among patients with CC. Immune infiltration analysis indicated that the expression of EPHB6 was positively associated with the levels of Tcm, TReg, B cells, T cells, iDC, T helper cells, cytotoxic cells, and DC, while negatively associated with NK CD56bright cells and neutrophils. In summary, the downregulation of EPHB6 was strongly linked to a more aggressive clinical development of CC, suggesting its potential utility as a diagnostic and therapeutic target in CC.},
}
@article {pmid37095978,
year = {2023},
author = {Norooznezhad, AH and Yarani, R and Payandeh, M and Hoseinkhani, Z and Mahmoudi, H and Kiani, S and Mansouri, K},
title = {Treatment of persistent chemotherapy-induced hair loss (Alopecia) with human mesenchymal stromal cells exosome enriched extracellular vesicles: A case report.},
journal = {Heliyon},
volume = {9},
number = {4},
pages = {e15165},
pmid = {37095978},
issn = {2405-8440},
abstract = {INTRODUCTION: Cancer is among the leading causes of death worldwide and affects a considerable number of individuals. Chemotherapy is one the most common treatment for this condition and hair loss is among one of the most prevalent side effects. In this study, we report successful treatment of a patient suffering from persistent chemotherapy-induced alopecia (PCIA) with extracellular enriched vesicles (EVs) derived from human placental mesenchymal stromal cells (MSCs).<br><br>CASE PRESENTATION: The patient was a 36-year-old woman with a history of invasive ductal carcinoma, underwent six courses of chemotherapy with paclitaxel and adriamycin. Following this treatment and for almost 18 months, she, unfortunately, had no regrowth of hair except some light vellus hairs on the scalp. She then received MSC-derived EVs with scalp injection (subcutaneous) every 4 weeks for 3 continuous months at which point she presented complete regrowth of terminal hair on her scalp.<br><br>CONCLUSION: This report demonstrates that MSC-derived EVs could be a possible treatment for permanent chemotherapy-induced alopecia; however, further studies and trials are necessary.},
}
@article {pmid37094629,
year = {2023},
author = {Chovsepian, A and Prokopchuk, O and Petrova, G and Gjini, T and Kuzi, H and Heisz, S and Janssen, KP and Martignoni, ME and Friess, H and Hauner, H and Rohm, M},
title = {Diabetes increases mortality in patients with pancreatic and colorectal cancer by promoting cachexia and its associated inflammatory status.},
journal = {Molecular metabolism},
volume = {73},
number = {},
pages = {101729},
pmid = {37094629},
issn = {2212-8778},
mesh = {Humans ; Cachexia/metabolism ; Retrospective Studies ; C-Reactive Protein ; *Diabetes Mellitus, Type 2/complications ; *Pancreatic Neoplasms/complications/metabolism ; Body Weight ; Obesity/complications ; Biomarkers ; *Colorectal Neoplasms/complications ; },
abstract = {OBJECTIVES: Cancer is considered an emerging diabetes complication, with higher incidence and worse prognosis in patients with diabetes. Cancer is frequently associated with cachexia, a systemic metabolic disease causing wasting. It is currently unclear how diabetes affects the development and progression of cachexia.<br><br>METHODS: We investigated the interplay between diabetes and cancer cachexia retrospectively in a cohort of 345 patients with colorectal and pancreatic cancer. We recorded body weight, fat mass, muscle mass, clinical serum values, and survival of these patients. Patients were grouped either into diabetic/non-diabetic groups based on previous diagnosis, or into obese/non-obese groups based on body mass index (BMI &#x2265;30&#xa0;kg/m[2] was considered obese).<br><br>RESULTS: The pre-existence of type 2 diabetes, but not obesity, in patients with cancer led to increased cachexia incidence (80%, compared to 61% without diabetes, p&#xa0;&#x2264;&#xa0;0.05), higher weight loss (8.9% vs. 6.0%, p&#xa0;&#x2264;&#xa0;0.001), and reduced survival probability (median survival days: 689 vs. 538, Chi square&#xa0;=&#xa0;4.96, p&#xa0;&#x2264;&#xa0;0.05) irrespective of the initial body weight or tumor progression. Patients with diabetes and cancer showed higher serum levels of C-reactive protein (0.919&#xa0;&#x3bc;g/mL vs. 0.551&#xa0;&#x3bc;g/mL, p&#xa0;&#x2264;&#xa0;0.01) and interleukin 6 (5.98&#xa0;pg/mL vs. 3.75&#xa0;pg/mL, p&#xa0;&#x2264;&#xa0;0.05) as well as lower serum albumin levels (3.98&#xa0;g/dL vs. 4.18&#xa0;g/dL, p&#xa0;&#x2264;&#xa0;0.05) than patients with cancer without diabetes. In a sub-analysis of patients with pancreatic cancer, pre-existing diabetes worsened weight loss (9.95% vs. 6.93%, p&#xa0;&#x2264;&#xa0;0.01), and increased the duration of hospitalization (24.41 days vs. 15.85 days, p&#xa0;&#x2264;&#xa0;0.001). Further, diabetes aggravated clinical manifestations of cachexia, as changes in the aforementioned biomarkers were more pronounced in patients with diabetes and cachexia co-existence, compared to cachectic patients without diabetes (C-reactive protein: 2.300&#xa0;&#x3bc;g/mL vs. 0.571&#xa0;&#x3bc;g/mL, p&#xa0;&#x2264;&#xa0;0.0001; hemoglobin: 11.24&#xa0;g/dL vs. 12.52&#xa0;g/dL, p&#xa0;&#x2264;&#xa0;0.05).<br><br>CONCLUSIONS: We show for the first time that pre-existing diabetes aggravates cachexia development in patients with colorectal and pancreatic cancer. This is important when considering cachexia biomarkers and weight management in patients with co-existing diabetes and cancer.},
}
@article {pmid37085500,
year = {2023},
author = {Zhou, D and Li, M and Yasin, MH and Lu, Q and Fu, J and Jiang, K and Hong, R and Wang, S and Xu, F},
title = {The prognostic value and immune microenvironment association of AR in HER2+ nonmetastatic breast cancer.},
journal = {NPJ breast cancer},
volume = {9},
number = {1},
pages = {30},
pmid = {37085500},
issn = {2374-4677},
support = {320.6750.2021-10-97//Ministry of Health of China | Wu Jieping Medical Foundation/ ; 2019A1515011945//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; },
abstract = {This study aimed to investigate the prognostic value of AR in HER2+ nonmetastatic breast invasive ductal carcinoma (IDC) and its relationship with the immune microenvironment. HER2+ nonmetastatic breast IDC patients diagnosed by pathology who underwent surgery at Sun Yat-sen University Cancer Center from 2016 to 2017 were included. AR+ and AR- breast IDC samples were matched 1:1 in age, T stage, and N stage for immune infiltration analysis. A total of 554 patients with HER2+ nonmetastatic breast cancer were included in this retrospective study, regardless of HR status. The cut-off value for AR was set at 10%. ER+ (p < 0.001) and PR+ (p < 0.001) were associated with positive AR expression. Kaplan-Meier survival curve analysis suggested that AR was closely correlated with overall survival (OS) (p = 0.001) but not disease-free survival (DFS) (p = 0.051). After eliminating the potential impact caused by HR, AR also predicted longer OS (p = 0.014) and was an independent predictive factor for OS of HER2+HR- nonmetastatic breast IDC patients, as revealed by multivariate analysis (p = 0.036). For AR+ and AR- matched HER2+HR- patients, TILs (p = 0.043) and PD-L1 (p = 0.027) levels were significantly lower in AR+ patients. The strongest negative correlation was observed between AR and PD-L1 (Pearson's r = -0.299, p = 0.001). AR+ status was markedly related to better OS in HER2+HR- nonmetastatic breast cancer patients, while a negative correlation was observed between AR and PD-L1/TILs. We provide new insights into the prognostic value of AR and its association with the immune microenvironment to optimize treatment strategies in HER2+ nonmetastatic breast IDCs.},
}
@article {pmid37085014,
year = {2023},
author = {van Balkom, IDC and Burdeus-Olavarrieta, M and Cooke, J and de Cuba, AG and Turner, A and , and Vogels, A and Maruani, A},
title = {Consensus recommendations on mental health issues in Phelan-McDermid syndrome.},
journal = {European journal of medical genetics},
volume = {66},
number = {6},
pages = {104770},
doi = {10.1016/j.ejmg.2023.104770},
pmid = {37085014},
issn = {1878-0849},
mesh = {Humans ; *Mental Health ; Quality of Life ; *Chromosome Disorders/genetics/psychology ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics ; },
abstract = {Phelan-McDermid syndrome is a rare genetic condition caused by a deletion encompassing the 22q13.3 region or a pathogenic variant of the gene SHANK3. The clinical presentation is variable, but main characteristics include global developmental delay/intellectual disability (ID), marked speech impairment or delay, along with other features like hypotonia and somatic or psychiatric comorbidities. This publication delineates mental health, developmental and behavioural themes across the lifetime of individuals with PMS as informed by parents/caregivers, experts, and other key professionals involved in PMS care. We put forward several recommendations based on the available literature concerning mental health and behaviour in PMS. Additionally, this article aims to improve our awareness of the importance of considering developmental level of the individual with PMS when assessing mental health and behavioural issues. Understanding how the discrepancy between developmental level and chronological age may impact concerning behaviours offers insight into the meaning of those behaviours and informs care for individuals with PMS, enabling clinicians to address unmet (mental health) care needs and improve quality of life.},
}
@article {pmid37083566,
year = {2023},
author = {Bilici, A and Olmez, OF and Kaplan, MA and Oksuzoglu, B and Sezer, A and Karadurmus, N and Cubukcu, E and Sendur, MAN and Aksoy, S and Erdem, D and Basaran, G and Cakar, B and Shbair, ATM and Arslan, C and Sumbul, AT and Sezgin Goksu, S and Karadag, I and Cicin, I and Gumus, M and Selcukbiricik, F and Harputluoglu, H and Demirci, U},
title = {Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.},
journal = {Acta oncologica (Stockholm, Sweden)},
volume = {62},
number = {4},
pages = {381-390},
doi = {10.1080/0284186X.2023.2202330},
pmid = {37083566},
issn = {1651-226X},
mesh = {Humans ; Female ; Trastuzumab/therapeutic use ; *Breast Neoplasms/pathology ; Neoadjuvant Therapy/methods ; Docetaxel ; Retrospective Studies ; Receptor, ErbB-2 ; Neoplasm Recurrence, Local/drug therapy/genetics ; Paclitaxel ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting.<br><br>METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR.<br><br>RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p&#x2009;<&#x2009;0.001) and lower relapse (4.5 vs. 12.2%, p&#x2009;<&#x2009;0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p&#x2009;<&#x2009;0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p&#x2009;<&#x2009;0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p&#x2009;<&#x2009;0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p&#x2009;<&#x2009;0.001) and NCT-HP (41.5 vs. 32.1%, p&#x2009;<&#x2009;0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p&#x2009;<&#x2009;0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p&#x2009;<&#x2009;0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p&#x2009;<&#x2009;0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p&#x2009;<&#x2009;0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p&#x2009;=&#x2009;0.008) significantly predicted the pCR.<br><br>CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.},
}
@article {pmid37082801,
year = {2023},
author = {Hacking, SM and Yakirevich, E and Wang, Y},
title = {Defining triple-negative breast cancer with neuroendocrine differentiation (TNBC-NED).},
journal = {The journal of pathology. Clinical research},
volume = {9},
number = {4},
pages = {313-321},
pmid = {37082801},
issn = {2056-4538},
mesh = {Humans ; *Triple Negative Breast Neoplasms/genetics/pathology ; Biomarkers, Tumor/analysis ; Tumor Suppressor Protein p53/genetics ; Retinoblastoma Protein/genetics/metabolism ; Retrospective Studies ; *Neuroendocrine Tumors/pathology ; *Carcinoma, Neuroendocrine/pathology ; *Carcinoma, Ductal, Breast ; Cell Differentiation ; RNA, Messenger ; Repressor Proteins ; },
abstract = {Primary breast neuroendocrine (NE) neoplasms are uncommon, and definitions harbor controversy. We retrospectively collected 73 triple-negative breast cancers (TNBC) and evaluated NE biomarker expression along with p53 aberrant staining (which correlates with TP53 gene mutation) and Rb protein loss by immunohistochemistry. In the study cohort, we found 11 (15%) cases of TNBC with neuroendocrine differentiation (TNBC-NED) showing positivity for one or more NE markers (synaptophysin/chromogranin/insulinoma-associated protein 1 [INSM1]). We also identified one separate small cell neuroendocrine carcinoma. Histologic types for these 11 TNBC-NED cases were as follows: 8 invasive ductal carcinoma (IDC) not otherwise specified (NOS), 2 IDC with apocrine features, 1 IDC with solid papillary features. INSM1 had the highest positivity and was seen in all 11 carcinomas. Seven (64%) cases showed p53 aberrant staining, 6 (55%) had Rb protein loss, while 6 (55%) had p53/Rb co-aberrant staining/protein loss. TNBC-NED was associated with Rb protein loss (p < 0.001), as well as p53/Rb co-aberrant staining/protein loss (p < 0.001). In 61 cases negative for NE markers, 37 (61%) showed p53 aberrant staining, while 5 (8%) had Rb protein loss. We also analyzed genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) PanCancer Atlas of 171 basal/TNBC patients. Transcriptomic analysis revealed mRNA expression of RB1 to be correlated negatively with SYN1 mRNA expression (p = 0.0400) and INSM1 mRNA expression (p = 0.0106) in this cohort. We would like to highlight the importance of these findings. TNBC-NED is currently diagnosed as TNBC, and although it overlaps morphologically with TNBC without NED, the unique p53/Rb signature highlights a genetic overlap with NE carcinomas of the breast.},
}
@article {pmid37061239,
year = {2023},
author = {López-Janeiro, &#xc1; and Rodriguez, AM and Mendiola, M and Sabbagh, RN and Feliu, J and Villadóniga, A and Mendez, MDC},
title = {Pancreatic intraductal papillary mucinous neoplasm with sarcomatous transformation. A case report.},
journal = {Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia},
volume = {56},
number = {2},
pages = {124-128},
doi = {10.1016/j.patol.2021.05.004},
pmid = {37061239},
issn = {1988-561X},
mesh = {Female ; Humans ; Aged ; *Pancreatic Intraductal Neoplasms ; *Carcinoma, Pancreatic Ductal/pathology ; *Adenocarcinoma, Mucinous/genetics/pathology ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/pathology ; },
abstract = {Mixed pancreatic epithelial and mesenchymal tumors are rare, usually invasive, entities. Intraductal papillary mucinous neoplasm (IPMN) is a precursor of invasive ductal carcinoma and shares mutations with its invasive counterparts. We report the case of a 72-year-old female with a previously undescribed sarcomatous transformation of a residual IPMN with no evidence of an invasive component. The mesenchymal component showed no heterologous differentiation. Both the epithelial and the mesenchymal populations showed aberrant expression of p53 protein and the same point mutation in KRAS gene. After a 6 month follow up, there were no signs of local or distant relapse. The present case suggests that sarcomatous transformation is possible in non-invasive, intraductal pancreatic lesions.},
}
@article {pmid37055018,
year = {2023},
author = {De Angelis Rigotti, F and Wiedmann, L and Hubert, MO and Vacca, M and Hasan, SS and Moll, I and Carvajal, S and Jiménez, W and Starostecka, M and Billeter, AT and Müller-Stich, B and Wolff, G and Ekim-Üstünel, B and Herzig, S and Fandos-Ramo, C and Krätzner, R and Reich, M and Keitel-Anselmino, V and Heikenwälder, M and Mogler, C and Fischer, A and Rodriguez-Vita, J},
title = {Semaphorin 3C exacerbates liver fibrosis.},
journal = {Hepatology (Baltimore, Md.)},
volume = {78},
number = {4},
pages = {1092-1105},
doi = {10.1097/HEP.0000000000000407},
pmid = {37055018},
issn = {1527-3350},
mesh = {Animals ; Humans ; Mice ; *Hepatic Stellate Cells/metabolism ; Liver/pathology ; Liver Cirrhosis/pathology ; Phosphorylation ; *Semaphorins/genetics/metabolism ; Transforming Growth Factor beta/metabolism ; },
abstract = {BACKGROUND AND AIMS: Chronic liver disease is a growing epidemic, leading to fibrosis and cirrhosis. TGF-β is the pivotal profibrogenic cytokine that activates HSC, yet other molecules can modulate TGF-β signaling during liver fibrosis. Expression of the axon guidance molecules semaphorins (SEMAs), which signal through plexins and neuropilins (NRPs), have been associated with liver fibrosis in HBV-induced chronic hepatitis. This study aims at determining their function in the regulation of HSCs.<br><br>APPROACH AND RESULTS: We analyzed publicly available patient databases and liver biopsies. We used transgenic mice, in which genes are deleted only in activated HSCs to perform ex vivo analysis and animal models. SEMA3C is the most enriched member of the semaphorin family in liver samples from patients with cirrhosis. Higher expression of SEMA3C in patients with NASH, alcoholic hepatitis, or HBV-induced hepatitis discriminates those with a more profibrotic transcriptomic profile. SEMA3C expression is also elevated in different mouse models of liver fibrosis and in isolated HSCs on activation. In keeping with this, deletion of SEMA3C in activated HSCs reduces myofibroblast marker expression. Conversely, SEMA3C overexpression exacerbates TGF-&#x3b2;-mediated myofibroblast activation, as shown by increased SMAD2 phosphorylation and target gene expression. Among SEMA3C receptors, only NRP2 expression is maintained on activation of isolated HSCs. Interestingly, lack of NRP2 in those cells reduces myofibroblast marker expression. Finally, deletion of either SEMA3C or NRP2, specifically in activated HSCs, reduces liver fibrosis in mice.<br><br>CONCLUSION: SEMA3C is a novel marker for activated HSCs that plays a fundamental role in the acquisition of the myofibroblastic phenotype and liver fibrosis.},
}
@article {pmid37028455,
year = {2023},
author = {Lin, Y and Amkul, K and Laosatit, K and Liu, J and Yimram, T and Chen, J and Yuan, X and Chen, X and Somta, P},
title = {Fine mapping of QTL conferring resistance to calcareous soil in mungbean reveals VrYSL3 as candidate gene for the resistance.},
journal = {Plant science : an international journal of experimental plant biology},
volume = {332},
number = {},
pages = {111698},
doi = {10.1016/j.plantsci.2023.111698},
pmid = {37028455},
issn = {1873-2259},
mesh = {Quantitative Trait Loci/genetics ; *Vigna/genetics/metabolism ; Genome-Wide Association Study ; Soil ; Iron/metabolism ; *Iron Deficiencies ; },
abstract = {Iron is a crucial nutrient for biological functions in plants. High-pH and calcareous soil is a major stress causing iron deficiency chlorosis (IDC) symptoms and yield losses in crops. Use of calcareous soil-tolerance genetic resources is the most effective preventative method to combat the effects of high-pH and calcareous soils. A previous study using a mungbean recombinant inbred line (RIL) population of the cross Kamphaeg Saen 2 (KPS2; IDC susceptible) × NM-10-12 identified a major quantitative trait locus (QTL), qIDC3.1, which controls resistance and explains more than 40% of IDC variation. In this study, we fine-mapped qIDC3.1 and identified an underlying candidate gene. A genome wide association analysis (GWAS) using 162 mungbean accessions identified single nucleotide polymorphisms (SNPs) on chromosome 6; several SNPs were associated with soil plant analysis development (SPAD) values and IDC visual scores of mungbeans planted on calcareous soil, respectively. These SNPs corresponded to qIDC3.1. Using the same RIL population as in the previous study and an advanced backcross population developed from KPS2 and IDC-resistant inbred line RIL82, qIDC3.1 was further confirmed and fine-mapped to an interval of 217 kilobases harboring five predicted genes, including LOC106764181 (VrYSL3), which encodes a yellow stripe1-like-3 (YSL3) protein, YSL3 is involved in iron deficiency resistance. Gene expression analysis revealed that VrYSL3 was highly expressed in mungbean roots. In calcareous soil, expression of VrYSL3 was significantly up-regulated, and it was more obviously upregulated in the roots of RIL82, than in those of KPS2. Sequence comparison of VrYSL3 between the RIL82 and KPS2 revealed four SNPs that result in amino acid changes in the VrYSL3 protein and a 20-bp insertion/deletion in the promoter where a cis-regulatory element resides. Transgenic Arabidopsis thaliana plants overexpressing VrYSL3 showed enhanced iron and zinc contents in the leaves. Taken together, these results indicate that VrYSL3 is a strong candidate gene responsible for calcareous soil resistance in mungbean.},
}
@article {pmid37020090,
year = {2023},
author = {Kawaguchi, S and Kinowaki, K and Tamura, N and Masumoto, T and Nishikawa, A and Shibata, A and Tanaka, K and Kobayashi, Y and Ogura, T and Sato, J and Kawabata, H},
title = {High-accuracy prediction of axillary lymph node metastasis in invasive lobular carcinoma using focal cortical thickening on magnetic resonance imaging.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {30},
number = {4},
pages = {637-646},
pmid = {37020090},
issn = {1880-4233},
mesh = {Humans ; Female ; Middle Aged ; Aged ; *Breast Neoplasms/pathology ; Lymphatic Metastasis/diagnostic imaging/pathology ; *Carcinoma, Lobular/diagnostic imaging/surgery/pathology ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; Lymph Nodes/pathology ; Magnetic Resonance Imaging ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) grows diffusely in a single-cell fashion, sometimes presenting only subtle changes in preoperative imaging; therefore, axillary lymph node (ALN) metastases of ILC are difficult to detect using magnetic resonance imaging (MRI). Preoperative underestimation of nodal burden occurs more frequently in ILC than in invasive ductal carcinoma (IDC), however, the morphological assessment for metastatic ALNs of ILC have not fully been investigated. We hypothesized that the high false-negative rate in ILC is caused by the discrepancy in the MRI findings of ALN metastases between ILC and IDC and aimed to identify the MRI finding with a strong correlation with ALN metastasis of ILC.<br><br>METHOD: This retrospective analysis included 120 female patients (mean&#x2009;&#xb1;&#x2009;standard deviation age, 57.2&#x2009;&#xb1;&#x2009;11.2&#xa0;years) who underwent upfront surgery for ILC at a single center between April 2011 and June 2022. Of the 120 patients, 35 (29%) had ALN metastasis. Using logistic regression, we constructed prediction models based on MRI findings: primary tumor size, focal cortical thickening (FCT), cortical thickness, long-axis diameter (LAD), and loss of hilum (LOH).<br><br>RESULTS: The area under the curves were 0.917 (95% confidence interval [CI] 0.869-0.968), 0.827 (95% CI 0.758-0.896), 0.754 (95% CI 0.671-0.837), and 0.621 (95% CI 0.531-0.711) for the FCT, cortical thickness, LAD, and LOH models, respectively.<br><br>CONCLUSIONS: FCT may be the most relevant MRI finding for ALN metastasis of ILC, and although its prediction model may lead to less underestimation of the nodal burden, rigorous external validation is required.},
}
@article {pmid37017594,
year = {2023},
author = {Zheng, L and Wu, H and Wen, N and Zhang, Y and Wang, Z and Peng, X and Tan, Y and Qiu, L and Qu, F and Tan, W},
title = {Aptamer-Functionalized Nanovaccines: Targeting In Vivo DC Subsets for Enhanced Antitumor Immunity.},
journal = {ACS applied materials &amp; interfaces},
volume = {15},
number = {15},
pages = {18590-18597},
doi = {10.1021/acsami.2c20846},
pmid = {37017594},
issn = {1944-8252},
mesh = {Humans ; *Cancer Vaccines ; Immunotherapy/methods ; T-Lymphocytes ; Antigens, Neoplasm/genetics ; *Neoplasms/therapy ; Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Dendritic Cells ; },
abstract = {Cancer vaccines, which directly pulsed in vivo dendritic cells (DCs) with specific antigens and immunostimulatory adjuvants, showed great potential for cancer immunoprevention. However, most of them were limited by suboptimal outcomes, mainly owing to overlooking the complex biology of DC phenotypes. Herein, based on adjuvant-induced antigen assembly, we developed aptamer-functionalized nanovaccines for in vivo DC subset-targeted codelivery of tumor-related antigens and immunostimulatory adjuvants. We chose two aptamers, iDC and CD209, and tested their performance on DC targeting. Our results verified that these aptamer-functionalized nanovaccines could specifically recognize circulating classical DCs (cDCs), a subset of DCs capable of priming naïve T cells, noting that iDC outperformed CD209 in this regard. With excellent cDC-targeting capability, the iDC-functionalized nanovaccine induced potent antitumor immunity, leading to effective inhibition of tumor occurrence and metastasis, thus providing a promising platform for cancer immunoprevention.},
}
@article {pmid37013774,
year = {2023},
author = {Oh, J and Oh, JM and Cho, SY},
title = {METTL3-mediated downregulation of splicing factor SRSF11 is associated with carcinogenesis and poor survival of cancer patients.},
journal = {European review for medical and pharmacological sciences},
volume = {27},
number = {6},
pages = {2561-2570},
doi = {10.26355/eurrev_202303_31793},
pmid = {37013774},
issn = {2284-0729},
mesh = {Humans ; *Adenocarcinoma of Lung ; Carcinogenesis ; *Colonic Neoplasms ; Down-Regulation ; *Lung Neoplasms/genetics/pathology ; *Methyltransferases/genetics ; *Serine-Arginine Splicing Factors/genetics ; },
abstract = {OBJECTIVE: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms.<br><br>MATERIALS AND METHODS: We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression.<br><br>RESULTS: Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression.<br><br>CONCLUSIONS: These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.},
}
@article {pmid37008917,
year = {2023},
author = {Kender, Z and Jende, JME and Kurz, FT and Tsilingiris, D and Schimpfle, L and Sulaj, A and von Rauchhaupt, E and Bartl, H and Mooshage, C and Göpfert, J and Nawroth, P and Herzig, S and Szendroedi, J and Bendszus, M and Kopf, S},
title = {Sciatic nerve fractional anisotropy and neurofilament light chain protein are related to sensorimotor deficit of the upper and lower limbs in patients with type 2 diabetes.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1046690},
pmid = {37008917},
issn = {1664-2392},
mesh = {Humans ; *Diabetes Mellitus, Type 2/pathology ; Anisotropy ; Intermediate Filaments ; Sciatic Nerve/diagnostic imaging/pathology ; *Diabetic Neuropathies/complications ; Lower Extremity/diagnostic imaging ; Biomarkers ; },
abstract = {BACKGROUND: Diabetic sensorimotor polyneuropathy (DSPN) is one of the most prevalent and poorly understood diabetic microvascular complications. Recent studies have found that fractional anisotropy (FA), a marker for microstructural nerve integrity, is a sensitive parameter for the structural and functional nerve damage in DSPN. The aim of this study was to investigate the significance of proximal sciatic nerve's FA on different distal nerve fiber deficits of the upper and lower limbs and its correlation with the neuroaxonal biomarker, neurofilament light chain protein (NfL).<br><br>MATERIALS AND METHODS: Sixty-nine patients with type 2 diabetes (T2DM) and 30 healthy controls underwent detailed clinical and electrophysiological assessments, complete quantitative sensory testing (QST), and diffusion-weighted magnetic resonance neurography of the sciatic nerve. NfL was measured in the serum of healthy controls and patients with T2DM. Multivariate models were used to adjust for confounders of microvascular damage.<br><br>RESULTS: Patients with DSPN showed a 17% lower sciatic microstructural integrity compared to healthy controls (p<0.001). FA correlated with tibial and peroneal motor nerve conduction velocity (NCV) (r=0.6; p<0.001 and r=0.6; p<0.001) and sural sensory NCV (r=0.50; p<0.001). Participants with reduced sciatic nerve&#xb4;s FA showed a loss of function of mechanical and thermal sensation of upper (r=0.3; p<0.01 and r=0.3; p<0.01) and lower (r=0.5; p<0.001 and r=0.3; p=<0.01) limbs and reduced functional performance of upper limbs (Purdue Pegboard Test for dominant hand; r=0.4; p<0.001). Increased levels of NfL and urinary albumin-creatinine ratio (ACR) were associated with loss of sciatic nerve&#xb4;s FA (r=-0.5; p<0.001 and r= -0.3, p= 0.001). Of note, there was no correlation between sciatic FA and neuropathic symptoms or pain.<br><br>CONCLUSION: This is the first study showing that microstructural nerve integrity is associated with damage of different nerve fiber types and a neuroaxonal biomarker in DSPN. Furthermore, these findings show that proximal nerve damage is related to distal nerve function even before clinical symptoms occur. The microstructure of the proximal sciatic nerve and is also associated with functional nerve fiber deficits of the upper and lower limbs, suggesting that diabetic neuropathy involves structural changes of peripheral nerves of upper limbs too.},
}
@article {pmid36976351,
year = {2023},
author = {Aiello, EN and D'Iorio, A and Solca, F and Torre, S and Bonetti, R and Scheveger, F and Colombo, E and Maranzano, A and Maderna, L and Morelli, C and Doretti, A and Amboni, M and Vitale, C and Verde, F and Ferrucci, R and Barbieri, S and Zirone, E and Priori, A and Pravettoni, G and Santangelo, G and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B},
title = {Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {130},
number = {5},
pages = {687-696},
pmid = {36976351},
issn = {1435-1463},
mesh = {Humans ; *Parkinson Disease/complications/diagnosis/psychology ; Reproducibility of Results ; Cross-Sectional Studies ; Feasibility Studies ; Neuropsychological Tests ; *Cognitive Dysfunction/etiology/complications ; Language ; },
abstract = {BACKGROUND: This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease (PD) patients.<br><br>METHODS: N&#x2009;=&#x2009;109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N&#x2009;=&#x2009;96); (6) assessing its test-retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a &#x2248; 6-month interval, within a subsample of patients (N&#x2009;=&#x2009;33).<br><br>RESULTS: The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach.<br><br>DISCUSSION: The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.},
}
@article {pmid36973739,
year = {2023},
author = {Cheng, X and Jia, X and Wang, C and Zhou, S and Chen, J and Chen, L and Chen, J},
title = {Hyperglycemia induces PFKFB3 overexpression and promotes malignant phenotype of breast cancer through RAS/MAPK activation.},
journal = {World journal of surgical oncology},
volume = {21},
number = {1},
pages = {112},
pmid = {36973739},
issn = {1477-7819},
support = {2021Y29//Medical science and technology program in Ningbo/ ; },
mesh = {Female ; Humans ; Phosphofructokinase-2/genetics/metabolism ; Cell Proliferation ; Cell Line, Tumor ; *MicroRNAs/genetics ; *Hyperglycemia/complications/genetics ; Phenotype ; *Carcinoma, Ductal/genetics ; Cell Movement ; Gene Expression Regulation, Neoplastic ; },
abstract = {BACKGROUND: Breast cancer is the most common tumor in women worldwide. Diabetes mellitus is a global chronic metabolic disease with increasing incidence. Diabetes mellitus has been reported to positively regulate the development of many tumors. However, the specific mechanism of hyperglycemic environment regulating breast cancer remains unclear. PFKFB3 (6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3) is a key regulatory factor of the glycolysis process in diabetes mellitus, as well as a promoter of breast cancer. So, we want to explore the potential link between PFKFB3 and the poor prognosis of breast cancer patients with hyperglycemia in this study.<br><br>METHODS: Cell culture was utilized to construct different-glucose breast cancer cell lines. Immunohistochemistry was adopted to analyze the protein level of PFKFB3 in benign breast tissues, invasive ductal carcinoma with diabetes and invasive ductal carcinoma without diabetes. The Kaplan-Meier plotter database and GEO database (GSE61304) was adopted to analyze the survival of breast cancer patients with different PFKFB3 expression. Western blot was adopted to analyze the protein level of PFKFB3, epithelial-mesenchymal transition (EMT)-related protein and extracellular regulated protein kinases (ERK) in breast cancer cells. Gene Set Cancer Analysis (GSCA) was utilized to investigate the potential downstream signaling pathways of PFKFB3. TargetScan and OncomiR were utilized to explore the potential mechanism of PFKFB3 overexpression by hyperglycemia. Transfections (including siRNAs and miRNA transfection premiers) was utilized to restrain or mimic the expression of the corresponding RNA. Cell functional assays (including cell counting, MTT, colony formation, wound-healing, and cell migration assays) were utilized to explore the proliferation and migration of breast cancer cells.<br><br>RESULTS: In this study, we demonstrated that the expression of PFKFB3 in breast cancer complicated with hyperglycemia was higher than that in breast cancer with euglycemia through cell experiment in vitro and histological experiment. PFKFB3 overexpression decreased the survival period of breast cancer patients and was correlated with a number of clinicopathological parameters of breast cancer complicated with diabetes. PFKFB3 promoted the proliferation and migration of breast cancer in a hyperglycemic environment and might be regulated by miR-26. In addition, PFKFB3 stimulated epithelial-mesenchymal transition of breast cancer in a hyperglycemic environment. In terms of downstream mechanism exploration, we predicted and verified the cancer-promoting effect of PFKFB3 in breast cancer complicated with hyperglycemia through RAS/MAPK pathway.<br><br>CONCLUSIONS: In conclusion, PFKFB3 could be overexpressed by hyperglycemia and might be a potential therapeutic target for breast cancer complicated with diabetes.},
}
@article {pmid36973678,
year = {2023},
author = {Tong, S and Jiang, N and Wan, JH and Chen, CR and Wang, SH and Wu, CY and Guo, Q and Xiao, XY and Huang, H and Zhou, T},
title = {The effects of the prognostic biomarker SAAL1 on cancer growth and its association with the immune microenvironment in lung adenocarcinoma.},
journal = {BMC cancer},
volume = {23},
number = {1},
pages = {275},
pmid = {36973678},
issn = {1471-2407},
mesh = {Humans ; Cyclin D1 ; Prognosis ; *Lung Neoplasms/pathology ; *Adenocarcinoma of Lung/genetics ; Biomarkers, Tumor/genetics ; Tumor Microenvironment ; },
abstract = {BACKGROUND: Inhibition of Serum Amyloid A-like 1 (SAAL1) expression could inhibit cancer progression and improve the prognosis of cancer patients. At present, the correlation between SAAL1 and lung adenocarcinoma (LAC) remains unclear. Therefore, this study surveyed the worth and pathway of SAAL1 in LAC progression and immunity.<br><br>METHODS: Bioinformatics and immunohistochemistry were used to identify the SAAL1 expression in LAC. The roles of SAAL1 expression in the existence values of LAC patients were explored, and the nomograms were constructed. Clinical values of SAAL1 co-expressed genes were evaluated by COX regression, survival, and Receiver operating characteristic (ROC) analysis. EDU and western blotting methods were used to inquiry the functions and pathways of the SAAL1 in cell growths. The correlation between the SAAL1 level and immune microenvironment was visualized using correlation research.<br><br>RESULTS: SAAL1 level was elevated in LAC tissues, and was observed in cancer tissues of dead patients. SAAL1 overexpression had something to do with shorter overall survival, progression-free interval, and disease-specific survival in LAC. The area under the curve of SAAL1 was 0.902 in normal tissues and cancer tissues. Inhibition of SAAL1 expression could inhibit cancer cell proliferation, which may be related to the decreased expression of cyclin D1 and Bcl-2 proteins. In LAC, SAAL1 level had something to do with stromal, immune, and estimate scores, and correlated with macrophages, T cells, Th2 cells, CD8 T cells, NK CD56dim cells, DC, eosinophils, NK CD56bright cells, pDC, iDC, cytotoxic cells, Tgd, aDC cells, B cells, Tcm, and TFH levels. SAAL1 overexpression had something to do with existence values and the immunity in LAC.<br><br>CONCLUSIONS: Inhibition of SAAL1 expression could regulate cancer growth via cyclin D1 and Bcl-2. SAAL1 is a promising prognostic biomarker in LAC patients.},
}
@article {pmid36939123,
year = {2023},
author = {Mareti, E and Vavoulidis, E and Papanastasiou, A and Maretis, T and Tsampazis, N and Margioula-Siarkou, C and Chatzinikolaou, F and Giasari, S and Nasioutziki, M and Daniilidis, A and Zepiridis, L and Dinas, K},
title = {Evaluating the potential role of human papilloma virus infection in breast carcinogenesis via real-time polymerase chain reaction analyzes of breast fine needle aspiration samples from Greek patients.},
journal = {Diagnostic cytopathology},
volume = {51},
number = {7},
pages = {414-422},
doi = {10.1002/dc.25130},
pmid = {36939123},
issn = {1097-0339},
mesh = {Biopsy, Fine-Needle ; Human papillomavirus 18 ; *Papillomavirus Infections ; *Breast Neoplasms/pathology ; Female ; Carcinogenesis ; Human Papillomavirus Viruses ; Humans ; Greece/epidemiology ; Papillomaviridae/genetics ; Real-Time Polymerase Chain Reaction ; },
abstract = {BACKGROUND: Human papilloma virus (HPV), in addition to its known clinical contribution to cervical cancer is probably actively involved in the development of breast tumors in various populations worldwide. Predominant HPV types in breast cancer patients vary geographically. The present study further examines HPV incidence in Greece, based on molecular analysis of clinical cytological samples.<br><br>METHODS: Greek patient fine needle aspiration (FNA) biopsy samples were examined using RT-PCR and immunohistological staining. FNA biopsy samples were collected from 114 female patients, diagnosed between the years 2018 and 2021, 57 with C5 diagnosed breast cancer lesions and 57 diagnosed with benign diseases.<br><br>RESULTS: A total of three different HPV types were identified within the patient sample. HPV-39 was found only in the control group, in 1.8% of patients, while HPV-59 was present in both control and study groups in 1.8% and 3.5% respectively. HPV-16, on the other hand, was present only in the study group in 12.3% of cases. HPV type presence was statistically differentiated between histological groups. HPV-16 was exclusively in IDC, HPV-39 was present in one cyst diagnosed sample and HPV-59 was present in 3 samples that included fibroadenoma, IDC and LN diagnosis.<br><br>CONCLUSION: More international comparative studies are required to investigate population differences and HPV genotype distribution to offer definite answers to the effect that certain HPV types might have a role in breast cancer, as this study also supports, albeit in a cofactory role.},
}
@article {pmid36934657,
year = {2023},
author = {Varun, K and Zoltan, K and Alba, S and Manuel, B and Elisabeth, K and Dimitrios, T and Jan B, G and Maik, B and Khurrum, S and Berend, I and Stephen, H and Thomas, F and Julia, S and Peter, N and Stefan, K},
title = {Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetes.},
journal = {EBioMedicine},
volume = {90},
number = {},
pages = {104516},
pmid = {36934657},
issn = {2352-3964},
mesh = {Mice ; Animals ; *Diabetes Mellitus, Type 2/complications ; Follow-Up Studies ; Interleukin-6 ; *Prediabetic State ; Albuminuria/complications ; Cross-Sectional Studies ; Prospective Studies ; *Lung Diseases ; Fibrosis ; DNA Damage ; Cellular Senescence ; },
abstract = {BACKGROUND: This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes.<br><br>METHODS: Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and &#x264;H2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-&#x3b2;1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes. Urinary albumin-creatinine-ratio, lung function, and transient elastography of the liver were performed in a prospective follow-up study over 4 years.<br><br>FINDINGS: db/db mice showed an increased nuclear &#x264;H2AX signal in all tissues as compared to the background control. Markers for DNA damage, senescence, and SASP were increased in patients with diabetes. The presence of nephropathy, restrictive lung disease (RLD), and increased liver stiffness was in a cross-sectional design associated with increased markers for DNA damage, senescence, and SASP. The progression of nephropathy over 4 years was predicted by increased DNA damage, senescence, and SASP, while the progression of RLD was associated with increased DNA damage and IL-6 only. The progression of liver stiffness was not associated with any of these parameters. HbA1c was not predictive for progression.<br><br>INTERPRETATION: In db/db mice, the cascade of DNA damage is associated with diabetes-related complications. In patients with diabetes, the progression of complications in the kidney and lung is predicted by markers reflecting DNA damage, and senescence-triggered organ fibrosis.<br><br>FUNDING: This work was supported by the German Research Foundation (DFG) in the CRC 1118 and CRC 1158, by the GRK DIAMICOM, by the German Center for Diabetes Research (DZD e.V.), and by the Ministry of Science, Research and the Arts, Baden-W&#xfc;rttemberg (Kompetenznetzwerk Pr&#xe4;ventivmedizin).},
}
@article {pmid36933394,
year = {2023},
author = {Vormittag-Nocito, E and Acosta, AM and Agarwal, S and Narayan, KD and Kumar, R and Al Rasheed, MRH and Kajdacsy-Balla, A and Behm, FG and Mohapatra, G},
title = {In-Depth Comparison of Genetic Variants Demonstrates a Close Relationship Between Invasive and Intraductal Components of Prostate Cancer.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {36},
number = {6},
pages = {100130},
doi = {10.1016/j.modpat.2023.100130},
pmid = {36933394},
issn = {1530-0285},
mesh = {Male ; Humans ; *Prostatic Intraepithelial Neoplasia/genetics/pathology ; *Prostatic Neoplasms/pathology ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostatectomy ; },
abstract = {Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.},
}
@article {pmid36931261,
year = {2023},
author = {Cardona Barberán, A and Bonte, D and Boel, A and Thys, V and Paredis, R and Machtelinckx, F and De Sutter, P and De Croo, I and Leybaert, L and Stoop, D and Coucke, P and Vanden Meerschaut, F and Heindryckx, B},
title = {Assisted oocyte activation does not overcome recurrent embryo developmental problems.},
journal = {Human reproduction (Oxford, England)},
volume = {38},
number = {5},
pages = {872-885},
doi = {10.1093/humrep/dead051},
pmid = {36931261},
issn = {1460-2350},
mesh = {Pregnancy ; Child ; Humans ; Male ; Female ; Animals ; Mice ; *Sperm Injections, Intracytoplasmic/methods ; *Calcium ; Ionomycin ; Calcimycin ; Prospective Studies ; Semen ; Pregnancy Rate ; Oocytes ; Embryonic Development ; Retrospective Studies ; Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; },
abstract = {STUDY QUESTION: Can recurrent embryo developmental problems after ICSI be overcome by assisted oocyte activation (AOA)?<br><br>SUMMARY ANSWER: AOA did not improve blastocyst formation in our patient cohort with recurrent embryo developmental problems after ICSI.<br><br>WHAT IS KNOWN ALREADY: The use of AOA to artificially induce calcium (Ca2+) rises by using Ca2+ ionophores (mainly calcimycin and ionomycin) has been reported as very effective in overcoming fertilization failure after ICSI, especially in patients whose Ca2+ dynamics during fertilization are deficient. However, there is only scarce and contradictory literature on the use of AOA to overcome embryo developmental problems after ICSI, and it is not clear whether abnormal Ca2+ patterns during fertilization disturb human preimplantation embryo development. Moreover, poor embryo development after ICSI has also been linked to genetic defects in the subcortical maternal complex (SCMC) genes.<br><br>STUDY DESIGN, SIZE, DURATION: This prospective cohort single-center study compared ICSI-AOA cycles and previous ICSI cycles in couples with normal fertilization rates (&#x2265;60%) but impaired embryonic development (&#x2264;15% blastocyst formation) in at least two previous ICSI cycles. In total, 42 couples with embryo developmental problems were included in this study from January 2018 to January 2021.<br><br>Of the 42 couples included, 17 underwent an ICSI-AOA cycle consisting of CaCl2 injection and double ionomycin exposure. Fertilization, blastocyst development, pregnancy, and live birth rates after ICSI-AOA were compared to previous ICSI cycles. In addition, the calcium pattern induced by the male patient's sperm was investigated by mouse oocyte calcium analysis. Furthermore, all 42 couples underwent genetic screening. Female patients were screened for SCMC genes (TLE6, PADI6, NLRP2, NLRP5, NLRP7, and KHDC3L) and male patients were screened for the sperm-oocyte-activating factor PLCZ1.<br><br>We compared 17 AOA cycles to 44 previous ICSI cycles from the same patient cohort. After AOA, a total fertilization rate of 68.95% (131/190), a blastocyst development rate of 13.74% (18/131), a pregnancy rate of 29.41% (5/17), and a live birth rate of 23.53% (4/17) were achieved, which was not different from the previous ICSI cycles (76.25% (321/421, P-value&#x2009;=&#x2009;0.06); 9.35% (30/321, P-value&#x2009;=&#x2009;0.18), 25.00% (11/44, P-value&#x2009;=&#x2009;0.75), and 15.91% (7/44, P-value&#x2009;=&#x2009;0.48), respectively). Calcium analysis showed that patient's sperm induced calcium patterns similar to control sperm samples displaying normal embryo developmental potential. Genetic screening revealed 10 unique heterozygous variants (in NLRP2, NLRP5, NLRP7, TLE6, and PADI6) of uncertain significance (VUS) in 14 females. Variant NLRP5 c.623-12_623-11insTTC (p.?) was identified in two unrelated individuals and variant NLRP2 c.1572T>C (p.Asp524=) was identified in four females. Interestingly, we identified a previously reported homozygous mutation PLCZ1, c.1499C>T (p.Ser500Leu), in a male patient displaying impaired embryonic development, but not showing typical fertilization failure.<br><br>Our strict inclusion criteria, requiring at least two ICSI cycles with impaired embryo development, reduced cycle-to-cycle variability, while the requirement of a lower blastocyst development not influenced by a poor fertilization excluded couples who otherwise would be selective cases for AOA; however, these criteria limited the sample size of this study. Targeted genetic screening might be too restricted to identify a genetic cause underlying the phenotype of poor embryo development for all patients. Moreover, causality of the identified VUS should be further determined.<br><br>Strong evidence for AOA overcoming impaired embryonic development is still lacking in the literature. Thus far, only one article has reported a beneficial effect of AOA (using calcimycin) compared to previous ICSI cycles in this patient population, whilst two more recent sibling-oocyte control studies (one using calcimycin and the other ionomycin) and our research (using ionomycin) could not corroborate these findings. Although no major abnormalities have been found in children born after AOA, this technique should be reserved for couples with a clear Ca2+-release deficiency. Finally, genetic screening by whole-exome sequencing may reveal novel genes and variants linked to embryo developmental problems and allow the design of more personalized treatment options, such as wild-type complementary RNA or recombinant protein injection.<br><br>This study was supported by the Flemish Fund for Scientific Research (grant FWO.OPR.2015.0032.01 to B.H. and grant no. 1298722N to A.B.). A.C.B., D.B., A.B., V.T., R.P., F.M., I.D.C., L.L., D.S., P.D.S., P.C., and F.V.M. have nothing to disclose. B.H. reports a research grant from the Flemish Fund for Scientific Research and reports being a board member of the Belgian Society for Reproductive Medicine and the Belgian Ethical Committee on embryo research.<br><br>TRIAL REGISTRATION NUMBER: NCT03354013.},
}
@article {pmid36927911,
year = {2023},
author = {Mitsuyoshi, A and Yanagawa, T and Kikumori, K and Hori, A and Oshima, K and Shinke, G and Katsuyama, S and Ikeshima, R and Hiraki, M and Ohmura, Y and Sugimura, K and Masuzawa, T and Hata, T and Takeda, Y and Murata, K},
title = {[A Case of De Novo Stage Ⅳ Breast Cancer with Umbilical Metastasis and Peritoneal Dissemination].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {50},
number = {3},
pages = {366-368},
pmid = {36927911},
issn = {0385-0684},
mesh = {Female ; Humans ; Middle Aged ; Peritoneum ; *Breast Neoplasms/surgery/pathology ; Positron Emission Tomography Computed Tomography ; Umbilicus/surgery/pathology ; *Carcinoma, Ductal ; },
abstract = {The patient was a 48-year-old woman. At the time of consultation, a hard mass of 30 mm in size was palpated in area A of the right breast, and a firm mass of about 10 mm was seen in the umbilical region. Histological diagnosis of the breast mass was invasive ductal carcinoma. PET-CT scan showed accumulation in the right breast, as well as suspicion of umbilical metastasis and peritoneal dissemination, uterine mass, and left ovarian cancer. Since this is an atypical metastatic site for invasive ductal carcinoma of the breast, and the possibility of peritoneal dissemination due to gynecological cancer complications cannot be ruled out, resection of the umbilical mass and laparoscopy was performed. The review laparoscopy revealed no evidence of primary cancer in the uterine body or left ovary, and a white nodular lesion of suspected seeding in the peritoneum around the left ovary. The histology and immunostaining results of the umbilical mass and left peri-ovarian nodule both showed glandular luminal structures similar to those of the primary breast cancer, and the left peri-ovarian nodule was ER positive, GATA3 positive, and PAX8 negative, leading to the diagnosis of umbilical metastasis and peritoneal seeding derived from breast cancer. Umbilical metastasis is often referred to as Sister Mary Joseph's nodule in the case of visceral malignancies and is often associated with peritoneal dissemination and is often caused by invasive metastasis of peritoneal dissemination lesions on the dorsal side of the umbilical region. In this case, histological examination of the umbilical specimen showed no disseminated lesion on the peritoneal side, so it was not considered to be an invasive metastasis due to peritoneal dissemination.},
}
@article {pmid36897545,
year = {2023},
author = {Kikuchi, M and Gomi, N and Ueki, A and Osako, T and Terauchi, T},
title = {Effectiveness and tasks of breast MRI surveillance for high-risk women with cancer susceptibility genes other than BRCA1/2: a single institution study.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {30},
number = {4},
pages = {577-583},
pmid = {36897545},
issn = {1880-4233},
mesh = {*Breast Neoplasms/diagnostic imaging/genetics/pathology ; Magnetic Resonance Imaging ; Risk ; *Genetic Predisposition to Disease ; Japan ; Ataxia Telangiectasia Mutated Proteins/genetics ; Fanconi Anemia Complementation Group N Protein/genetics ; Antigens, CD/genetics ; Cadherins/genetics ; Tumor Suppressor Protein p53/genetics ; *Early Detection of Cancer/methods ; *Genes, Neoplasm ; Neoplasm Staging ; Humans ; Female ; Adult ; Middle Aged ; Aged ; },
abstract = {BACKGROUND: In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer.<br><br>METHODS: We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021. MRI exams were evaluated independently by two radiologists. Final histopathological diagnosis for malignant lesions were obtained from surgical specimen.<br><br>RESULTS: A total of 16 patients included TP53, CDH1, PALB2, ATM pathogenic variants and 3 variant of unknown significance. 2 patients with TP53 pathogenic variants were detected breast cancer by annual MRI surveillance. The rate of cancer detection was 12.5% (2/16). One patient was detected synchronous bilateral breast cancer and unilateral multiple breast cancers (3 lesions in 1 patient), so there were 4 malignant lesions in total. Surgical pathology of 4 lesions were 2 ductal carcinoma in situ, 1 invasive lobular carcinoma, and 1 invasive ductal carcinoma. MRI findings of 4 malignant lesions were detected as 2 non mass enhancement, 1 focus and 1 small mass. All of 2 patients with PALB2 pathogenic variants had previously developed breast cancer.<br><br>CONCLUSIONS: Germline TP53 and PALB2 were strongly associated with breast cancer, suggesting that MRI surveillance is essential for breast cancer-related hereditary predisposition.},
}
@article {pmid36893606,
year = {2023},
author = {Göransson, S and Chen, S and Olofsson, H and Larsson, O and Strömblad, S},
title = {An extracellular matrix stiffness-induced breast cancer cell transcriptome resembles the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC).},
journal = {Biochemical and biophysical research communications},
volume = {654},
number = {},
pages = {73-79},
doi = {10.1016/j.bbrc.2023.03.001},
pmid = {36893606},
issn = {1090-2104},
mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Transcriptome ; Extracellular Matrix/genetics/pathology ; *Breast Neoplasms/genetics/pathology ; *Carcinoma in Situ ; },
abstract = {Identifying mechanisms driving the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer remains a challenge in breast cancer research. Breast cancer progression is accompanied by remodelling and stiffening of the extracellular matrix, leading to increased proliferation, survival, and migration. Here, we studied stiffness-dependent phenotypes in MCF10CA1a (CA1a) breast cancer cells cultured on hydrogels with stiffness corresponding to normal breast and breast cancer. This revealed a stiffness-associated morphology consistent with acquisition of an invasive phenotype in breast cancer cells. Surprisingly, this strong phenotypic switch was accompanied by relatively modest transcriptome-wide alterations in mRNA levels, as independently quantified using both DNA-microarrays and bulk RNA sequencing. Strikingly, however, the stiffness-dependent alterations in mRNA levels overlapped with those contrasting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). This supports a role of matrix stiffness in driving the pre-invasive to invasive transition and suggests that mechanosignalling may be a target for prevention of invasive breast cancer.},
}
@article {pmid36890060,
year = {2023},
author = {Verspyck, E and Attal, N},
title = {Diagnosing nociplastic pain in cancer survivors: a major step forward.},
journal = {British journal of anaesthesia},
volume = {130},
number = {5},
pages = {515-518},
doi = {10.1016/j.bja.2023.02.006},
pmid = {36890060},
issn = {1471-6771},
mesh = {Humans ; *Cancer Survivors ; Pain ; *Fibromyalgia/complications/diagnosis/therapy ; Headache ; Pain Management ; *Neoplasms/complications ; },
abstract = {Nociplastic pain syndromes include particular fibromyalgia, irritable bowel syndrome, headache, complex regional pain syndrome, and idiopathic orofacial pain. Several mechanisms have been proposed to account for nociplastic pain including central sensitisation, alterations of pain modulatory controls, epigenetic changes, and peripheral mechanisms. Importantly, nociplastic pain might also be present in patients with cancer pain, particularly those with pain related to complications of cancer treatment. Increased awareness of nociplastic pain associated with cancer should have important implications for monitoring and managing such patients.},
}
@article {pmid36883155,
year = {2022},
author = {Ali Khadem, Z and Abdul Wadood Al-Shammaree, S},
title = {Prognostic Value of Intracellular Transcription of Factors HIF-1α and p53 and Their Relation to Estradiol and TNM Parameters of Breast Cancer Tissues in Women with Invasive Ductal Carcinoma in Thi-Qar Province, Iraq.},
journal = {Archives of Razi Institute},
volume = {77},
number = {4},
pages = {1341-1348},
pmid = {36883155},
issn = {2008-9872},
mesh = {Adolescent ; Adult ; Female ; Humans ; Young Adult ; *Breast Neoplasms/chemistry/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/chemistry/genetics/metabolism/pathology ; *Estradiol/analysis/genetics/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/analysis/genetics/metabolism ; Iraq/epidemiology ; Prognosis ; *Tumor Suppressor Protein p53/analysis/genetics/metabolism ; },
abstract = {Breast cancer is the most common malignancy affecting women's health, with an increasing incidence worldwide. This study aimed to measure the intracellular concentration of the hypoxia-inducible factor 1 α (HIF-1α), tumor suppression protein p53, and estradiol (E2) in tumor tissues of adult females with breast cancer and their relation to tumor grade, tumor size, and lymph node metastases (LNM). The study was conducted on 65 adult female participants with breast mass admitted to the operating theater in Al-Hussein Teaching Hospital and Al-Habboby Teaching Hospital in Nasiriyah, Iraq, from January to November 2021. Fresh breast tumor tissues were collated and homogenized for intracellular biochemical analysis using the enzyme-linked immunosorbent assay method. In total, 44 (58%) out of 65 patients, in the age range of 18-42 years and the mean±SD age of 32.55±6.40 years, had fibroadenomas, and other 21 (42%) cases, in the age range of 32-80 years and the mean±SD age of 56±14.4 years had invasive ductal carcinoma (IDC) breast cancer. Intracellular levels of HIF-1α, p53, and E2 were elevated significantly (P<0.001) in IDC cases compared to the benign group. The most malignant tumors of IDC cases were in grade III and sizes T2 and T3. The tissue concentrations of HIF-1α, P53, and E2 were significantly elevated in patients with tumor stage T3 compared to T2 and T1. A significant elevation was found in the levels of HIF-1α, p53, and E2 in the positive LNM subgroup compared to the negative LNM group. Based on the obtained results, the prognostic value of the intracellular HIF-1α is considered to be a useful prognostic factor in Iraqi women with ICD and the combination of a HIF-1α protein with the nonfunctional p53 and E2 tends to indicate the proliferation, invasiveness, and metastases of the breast tumors.},
}
@article {pmid36868097,
year = {2023},
author = {Aktan, &#xc7; and Küçükaslan, A&#x15e; and Türk, BA and Yildirim, I},
title = {Expression analysis of novel long non-coding RNAs for invasive ductal and invasive lobular breast carcinoma cases.},
journal = {Pathology, research and practice},
volume = {244},
number = {},
pages = {154391},
doi = {10.1016/j.prp.2023.154391},
pmid = {36868097},
issn = {1618-0631},
mesh = {Female ; Humans ; *RNA, Long Noncoding/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Treatment Outcome ; *Breast Neoplasms/pathology ; },
abstract = {AIM: Long non-coding RNAs (LncRNAs) serve as important regulatory molecules of gene expression and protein functionality at multiple biological levels, and their deregulation plays a key role in tumorigenesis including in breast cancer metastasis. Therefore, in this study, we aim to compare the expression of novel lncRNAs in the landscape of invasive ductal carcinoma (IDC) and invasive lobular (ILC) carcinoma of breast.<br><br>MAIN METHODS: We have designed an in-silico approach to find the lncRNAs that regulate the breast cancer. Then, we used the clinical samples to carry out the verification of our in silico finding. In the present study, the tissues of breast cancer were deparaffinized. RNA was extracted by the TRIzole method. After synthesizing cDNA from the extracted RNA, expression levels of lncRNAs were analyzed by qPCR using primers specifically designed and validated for the targeted lncRNAs. In this study, breast biopsy materials from 41 female patients with IDC and 10 female patients with ILC were examined histopathological and expression changes of candidate lncRNAs were investigated in line with the findings. The results were analyzed using IBM SPSS Statistics 25 version.<br><br>RESULTS: The mean age of the cases was 53.78&#xa0;&#xb1;&#xa0;14.96. The minimum age was 29, while the maximum age was 87. While 27 of the cases were pre-menopausal, 24 cases were post-menopausal. The number of hormone receptor-positive cases was found to be 40, 35, and 27 for ER, PR, and cerb2/neu, respectively. While the expressions of LINC00501, LINC00578, LINC01209, LINC02015, LINC02584, ABCC5-AS1, PEX5L-AS2, SHANK2-AS3 and SOX2-OT showed significant differences (p&#xa0;<&#xa0;0.05), the expressions of LINC01206, LINC01994, SHANK2-AS1, and TPRG1-AS2 showed no significant differences (p&#xa0;>&#xa0;0.05). In addition, it was determined that the regulation of all lncRNAs could be able to involve in the development of cancer such as the NOTCH1, NFKB, and estrogen receptor signalings.<br><br>CONCLUSION: As a result, it was thought that the discovery of novel lncRNAs might be an important player in the diagnosis, prognosis and therapeutic development of breast cancer.},
}
@article {pmid36797734,
year = {2023},
author = {Arias Ramos, D and Alzate, JA and Moreno Gómez, GA and Hoyos Pulgarín, JA and Olaya Gómez, JC and Cortés Bonilla, I and Vargas Mosquera, C},
title = {Empirical treatment and mortality in bacteremia due to extended spectrum β-lactamase producing Enterobacterales (ESβL-E), a retrospective cross-sectional study in a tertiary referral hospital from Colombia.},
journal = {Annals of clinical microbiology and antimicrobials},
volume = {22},
number = {1},
pages = {13},
pmid = {36797734},
issn = {1476-0711},
mesh = {Humans ; Retrospective Studies ; Cross-Sectional Studies ; *Escherichia coli Infections/drug therapy ; Tertiary Care Centers ; Colombia/epidemiology ; beta-Lactamases/genetics ; Anti-Bacterial Agents/therapeutic use ; Risk Factors ; *Bacteremia/drug therapy/microbiology ; },
abstract = {BACKGROUND: Infections caused by extended spectrum β-lactamase (ESβL) producing bacteria are common and problematic. When they cause bloodstream infections, they are associated with significant morbidity and mortality.<br><br>METHODS: A retrospective cross-sectional observational study was conducted in a single center in Pereira, Colombia. It included people hospitalized with bacteremia due to gram-negative bacilli with the extended-spectrum &#x3b2;-lactamase producing phenotype. A logistic regression analysis was constructed. Clinical characteristics and risk factors for death from sepsis were established.<br><br>RESULTS: The prevalence of bacteremia due to Enterobacterales with extended-spectrum &#x3b2;-lactamase producing phenotype was 17%. 110 patients were analyzed. Most patients were men (62%) with a median age of 58&#xa0;years, hospital mortality was 38%. Admission to intensive care was 45%. The following risk factors for mortality were established: shock requiring vasoactive support, Pitt score&#x2009;>&#x2009;3 points, and not having an infectious disease consultation (IDC).<br><br>CONCLUSIONS: bacteremia due to Enterobacterales with extended-spectrum &#x3b2;-lactamase producing phenotype have a high mortality. Early recognition of sepsis, identification of risk factors for antimicrobial resistance, and prompt initiation of appropriate empiric antibiotic treatment are important. An infectious disease consultation may help improve outcomes.},
}
@article {pmid36781838,
year = {2023},
author = {Sekido, N and Matsuoka, M and Takahashi, R and Sengoku, A and Nomi, M and Matsuyama, F and Murata, T and Kitta, T and Mitsui, T},
title = {Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.},
journal = {Spinal cord series and cases},
volume = {9},
number = {1},
pages = {3},
pmid = {36781838},
issn = {2058-6124},
mesh = {Humans ; *Urinary Catheters/adverse effects ; Cross-Sectional Studies ; Urinary Catheterization/adverse effects ; Japan/epidemiology ; *Urinary Tract Infections/epidemiology/etiology ; Spinal Cord ; },
abstract = {STUDY DESIGN: Cross-sectional study by members of patient advocacy groups.<br><br>OBJECTIVES: To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan.<br><br>SETTING: An internet survey.<br><br>METHODS: We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC).<br><br>RESULTS: Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p&#x2009;=&#x2009;0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p&#x2009;=&#x2009;0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC.<br><br>CONCLUSIONS: sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.},
}
@article {pmid36769184,
year = {2023},
author = {Górnicki, T and Lambrinow, J and Mrozowska, M and Romanowicz, H and Smolarz, B and Piotrowska, A and Gomułkiewicz, A and Podhorska-Okołów, M and Dzięgiel, P and Grzegrzółka, J},
title = {Expression of RBMS3 in Breast Cancer Progression.},
journal = {International journal of molecular sciences},
volume = {24},
number = {3},
pages = {},
pmid = {36769184},
issn = {1422-0067},
mesh = {Humans ; Female ; *Breast Neoplasms/metabolism ; Breast/metabolism ; *Carcinoma, Ductal, Breast/pathology ; MCF-7 Cells ; RNA, Messenger/genetics ; Cell Line, Tumor ; Trans-Activators/metabolism ; RNA-Binding Proteins/metabolism ; },
abstract = {The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues (p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens (p < 0.05) and ER(-) cancer specimens (p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells (p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines (p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.},
}
@article {pmid36765396,
year = {2023},
author = {Sui, Y and Li, S and Fu, XQ and Zhao, ZJ and Xing, S},
title = {Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.},
journal = {Journal of translational medicine},
volume = {21},
number = {1},
pages = {109},
pmid = {36765396},
issn = {1479-5876},
mesh = {Humans ; *Lupus Erythematosus, Systemic/genetics ; Janus Kinases/therapeutic use ; *Neoplasms ; Carcinogenesis ; Computational Biology ; RNA, Messenger/metabolism ; },
abstract = {BACKGROUND: Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up.<br><br>METHODS: Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses.<br><br>RESULTS: The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway.<br><br>CONCLUSION: The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the&#xa0;IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.},
}
@article {pmid36763857,
year = {2023},
author = {Langley, RG and Sofen, H and Dei-Cas, I and Reich, K and Sigurgeirsson, B and Warren, RB and Paul, C and Szepietowski, JC and Tsai, TF and Hampele, I and You, R and Charef, P and Papavassilis, C},
title = {Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.},
journal = {The British journal of dermatology},
volume = {188},
number = {2},
pages = {198-207},
doi = {10.1093/bjd/ljac040},
pmid = {36763857},
issn = {1365-2133},
mesh = {Humans ; Quality of Life ; *Nasopharyngitis/chemically induced ; Antibodies, Monoclonal, Humanized/adverse effects ; *Psoriasis/drug therapy ; *Respiratory Tract Infections ; Treatment Outcome ; Severity of Illness Index ; Double-Blind Method ; },
abstract = {BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis.<br><br>OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis.<br><br>METHODS: Responders with &#x2265; 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150&#x2005;mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300&#x2005;mg continuing on their dose, while those on secukinumab 150&#x2005;mg or placebo received secukinumab 150 or 300&#x2005;mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595.<br><br>RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300&#x2005;mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively.<br><br>CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.},
}
@article {pmid36730303,
year = {2023},
author = {Chang, H and Hu, T and Hu, J and Ding, T and Wang, Q and Cheng, J},
title = {Complete response in patient with liver metastasis of HER2-positive breast cancer following therapy with margetuximab: a case report.},
journal = {Anti-cancer drugs},
volume = {34},
number = {7},
pages = {883-887},
pmid = {36730303},
issn = {1473-5741},
mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/pathology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Trastuzumab ; Receptor, ErbB-2/metabolism ; *Liver Neoplasms/drug therapy/etiology ; },
abstract = {Metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer has a poor prognosis and few effective targeted therapies. However, several anti-HER2 agents are emerging in conjunction with chemotherapy, which may lead to increased rates of pathological complete response in patients with HER2-positive metastatic breast cancer. Among them, margetuximab demonstrated a significant improvement in progression-free survival compared with trastuzumab, when combined with chemotherapy in pretreated patients. Here we present a case of a 67-year-old female patient who was diagnosed with HER2-positive, histological grade III and invasive ductal carcinoma of the left breast in September 2018. She received postoperative adjuvant therapy with EC-TH plus radiotherapy, followed by therapy with HER2-targeted trastuzumab for 1 year (till December 2019). In May 2020, routine reexamination showed a supraclavicular lymph node and bone metastasis. Patient was then treated with pyrotinib, capecitabine and bisphosphonate for a period of 3 months. In December 2020, liver MRI revealed multiple liver metastases. The patient received eight cycles of second-line therapy (vinorelbine plus margetuximab) from January 2021. Since the ninth cycle, the patient was continued with only margetuximab. In March 2021, MRI showed a 70% decrease in the liver metastasis lesions. By June 2021, liver lesions were totally disappeared. During therapy, patient experienced only grade-1 anemia. This case demonstrates that margetuximab plus chemotherapy is safe and might bring clinical benefits for patients with HER2-positive breast cancer with liver metastasis. Further studies evaluating the efficacy and safety of margetuximab in Chinese HER2-positive breast cancer patients are needed.},
}
@article {pmid36708642,
year = {2023},
author = {Maggi, G and Vitale, C and Cerciello, F and Santangelo, G},
title = {Sleep and wakefulness disturbances in Parkinson's disease: A meta-analysis on prevalence and clinical aspects of REM sleep behavior disorder, excessive daytime sleepiness and insomnia.},
journal = {Sleep medicine reviews},
volume = {68},
number = {},
pages = {101759},
doi = {10.1016/j.smrv.2023.101759},
pmid = {36708642},
issn = {1532-2955},
mesh = {Humans ; *REM Sleep Behavior Disorder/etiology/complications ; *Parkinson Disease/complications/epidemiology/drug therapy ; Wakefulness ; *Sleep Initiation and Maintenance Disorders/epidemiology/complications ; Quality of Life ; Prevalence ; Sleep ; *Disorders of Excessive Somnolence/epidemiology/diagnosis ; *Sleep Wake Disorders ; },
abstract = {Sleep disorders (SDs) are common non-motor symptoms of Parkinson's disease (PD) with wide variability in their prevalence rates. The etiology of SDs in PD is multifactorial because the degenerative processes underlying the disease and their interaction with drugs and clinical features may promote REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS) and insomnia. Therefore, we designed a meta-analytic study to provide a reliable estimate of the prevalence and associated clinical and neuropsychiatric aspects of SDs in PD. A systematic literature search was performed up to February 2022. Pooled RBD prevalence was 46%, and its occurrence was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose (LEDD), worse motor and autonomic manifestations, poorer quality of life and autonomy, and more severe neuropsychiatric symptoms. The pooled prevalence of EDS was 35% and was associated with older age, longer disease duration, worse motor and autonomic symptoms, higher LEDD, reduced autonomy, and more severe neuropsychiatric symptoms. Insomnia was reported in 44% of PD patients and was related to longer disease duration, higher LEDD, and more severe depression. SDs are associated with a more severe PD clinical phenotype; further studies should explore the pathophysiological mechanisms underlying SDs and develop targeted therapeutic strategies.},
}
@article {pmid36678422,
year = {2023},
author = {Feredj, E and Audureau, E and Boueilh, A and Fihman, V and Fourati, S and Lelièvre, JD and Gallien, S and Grimbert, P and Matignon, M and Melica, G},
title = {Impact of a Dedicated Pretransplant Infectious Disease Consultation on Respiratory Tract Infections in Kidney Allograft Recipients: A Retrospective Study of 516 Recipients.},
journal = {Pathogens (Basel, Switzerland)},
volume = {12},
number = {1},
pages = {},
pmid = {36678422},
issn = {2076-0817},
abstract = {BACKGROUND: Respiratory tract infections (RTIs) are a leading cause of death after kidney transplant. Preventive strategies may be implemented during a dedicated infectious disease consultation (IDC) before transplantation. Impact of IDC on RTIs after transplant has not been determined.<br><br>METHODS: We conducted a monocentric retrospective cohort analysis including all kidney transplant recipients from January 2015 to December 2019. We evaluated the impact of IDC on RTIs and identified risk and protective factors associated with RTIs.<br><br>RESULTS: We included 516 kidney transplant recipients. Among these, 145 had an IDC before transplant. Ninety-five patients presented 123 RTIs, including 75 (61%) with pneumonia. Patient that benefited from IDC presented significantly less RTIs (p = 0.049). RTIs were an independent risk factor of mortality (HR = 3.64 (1.97-6.73)). Independent risk factors for RTIs included HIV (OR = 3.33 (1.43-7.74)) and HCV (OR = 3.76 (1.58-8.96)). IDC was identified as an independent protective factor (OR = 0.48 (0.26-0.88)). IDC prior to transplantation is associated with diminished RTIs and is an independent protective factor. RTIs after kidney transplant are an independent risk factor of death. Implementing systematic IDC may have an important impact on reducing RTIs and related morbidity and mortality.},
}
@article {pmid36671532,
year = {2023},
author = {Yang, Y and Luo, D and Gao, W and Wang, Q and Yao, W and Xue, D and Ma, B},
title = {Combination Analysis of Ferroptosis and Immune Status Predicts Patients Survival in Breast Invasive Ductal Carcinoma.},
journal = {Biomolecules},
volume = {13},
number = {1},
pages = {},
pmid = {36671532},
issn = {2218-273X},
support = {81602337//National Natural Science Foundation of China/ ; 81702564//National Natural Science Foundation of China/ ; 81570579//National Natural Science Foundation of China/ ; UNPYSCT-2017062//Education Department of Heilongjiang Province/ ; LH2021H050//Natural Science Foundation of Heilongjiang Province/ ; },
mesh = {Humans ; *Ferroptosis/genetics ; Algorithms ; Cell Death ; Iron ; *Carcinoma, Ductal ; },
abstract = {Ferroptosis is a new form of iron-dependent cell death and plays an important role during the occurrence and development of various tumors. Increasingly, evidence shows a convincing interaction between ferroptosis and tumor immunity, which affects cancer patients' prognoses. These two processes cooperatively regulate different developmental stages of tumors and could be considered important tumor therapeutic targets. However, reliable prognostic markers screened based on the combination of ferroptosis and tumor immune status have not been well characterized. Here, we chose the ssGSEA and ESTIMATE algorithms to evaluate the ferroptosis and immune status of a TCGA breast invasive ductal carcinoma (IDC) cohort, which revealed their correlation characteristics as well as patients' prognoses. The WGCNA algorithm was used to identify genes related to both ferroptosis and immunity. Univariate COX, LASSO regression, and multivariate Cox regression models were used to screen prognostic-related genes and construct prognostic risk models. Based on the ferroptosis and immune scores, the cohort was divided into three groups: a high-ferroptosis/low-immune group, a low-ferroptosis/high-immune group, and a mixed group. These three groups exhibited distinctive survival characteristics, as well as unique clinical phenotypes, immune characteristics, and activated signaling pathways. Among them, low-ferroptosis and high-immune statuses were favorable factors for the survival rates of patients. A total of 34 differentially expressed genes related to ferroptosis-immunity were identified among the three groups. After univariate, Lasso regression, and multivariate stepwise screening, two key prognostic genes (GNAI2, PSME1) were identified. Meanwhile, a risk prognosis model was constructed, which can predict the overall survival rate in the validation set. Lastly, we verified the importance of model genes in three independent GEO cohorts. In short, we constructed a prognostic model that assists in patient risk stratification based on ferroptosis-immune-related genes in IDC. This model helps assess patients' prognoses and guide individualized treatment, which also further eelucidatesthe molecular mechanisms of IDC.},
}
@article {pmid36653542,
year = {2023},
author = {Maggi, G and D'Iorio, A and Aiello, EN and Poletti, B and Ticozzi, N and Silani, V and Amboni, M and Vitale, C and Santangelo, G},
title = {Psychometrics and diagnostics of the Italian version of the Beck Depression Inventory-II (BDI-II) in Parkinson's disease.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {44},
number = {5},
pages = {1607-1612},
pmid = {36653542},
issn = {1590-3478},
mesh = {Humans ; Psychometrics ; *Depression/diagnosis/etiology ; *Parkinson Disease/complications/diagnosis/psychology ; Quality of Life ; Reproducibility of Results ; Psychiatric Status Rating Scales ; },
abstract = {INTRODUCTION: Depression is one of the most disabling neuropsychiatric manifestations of Parkinson's disease (PD) and requires proper screening and diagnosis because it affects the overall prognosis and quality of life of patients. This study aimed to assess the psychometric and diagnostic properties of the Beck Depression Inventory-II (BDI-II) in an Italian PD cohort.<br><br>MATERIALS AND METHODS: Fifty consecutive outpatients with PD underwent the Italian version of the BDI-II and other questionnaires to evaluate anxiety and apathetic symptoms. Patients' caregivers completed the depression/dysphoria domain of the Neuropsychiatric Inventory (NPI-D). We evaluated the internal consistency, convergent and divergent validity, and factorial structure of BDI-II. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios were computed using ROC analyses, and an optimal cutoff was defined using the Youden index.<br><br>RESULTS: The BDI-II proved to be internally consistent (Cronbach's &#x3b1; = 0.840) and substantially met the bi-factorial structure. Regarding construct validity, the BDI-II was substantially related to anxiety measures, but not to apathy. With the combination of the NPI-D and anxiety score used as the gold standard, the BDI-II overall showed good accuracy (AUC = 0.859) with adequate sensitivity (75%) and specificity (87%). The optimal cutoff point was defined at 14.50.<br><br>CONCLUSIONS: We provide evidence of the psychometric and diagnostic properties of the Italian version of the BDI-II as a screening tool for depression in patients with PD. The BDI-II was found to be reliable and valid for the measurement of depression in patients with PD; therefore, it is available for use in clinical research and practice.},
}
@article {pmid36641657,
year = {2022},
author = {Manginstar, C and Oley, MH and Oley, MC and Merung, M and Langi, FLFG and Kepel, BJ and Rusli, LV and Islam, AA and Faruk, M},
title = {Correlation analysis of HIF-1α and Ca15-3 in response to neoadjuvant chemotherapy in locally advanced breast cancer: A cohort study in Indonesia.},
journal = {Breast disease},
volume = {41},
number = {1},
pages = {481-487},
doi = {10.3233/BD-229004},
pmid = {36641657},
issn = {1558-1551},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Prognosis ; Biomarkers, Tumor/metabolism ; Cohort Studies ; Neoadjuvant Therapy ; Prospective Studies ; Hypoxia-Inducible Factor 1, alpha Subunit/therapeutic use ; Indonesia ; Hypoxia ; Tumor Microenvironment ; },
abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC.<br><br>METHODS: This observational study used the prospective cohort method included 11 patients with histopathologically&#xa0;confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1&#x3b1; and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks).<br><br>RESULTS: Among the 11 patients included in this study, HIF-1&#x3b1;, Ca15-3, and RECIST decreased significantly after NAC. The changes in RECIST correlated with Ca15-3: each unit decrease in RECIST score was associated with a 0.3-unit decrease in Ca15-3 levels (p =&#xa0;0.019).<br><br>CONCLUSIONS: There was a decrease in HIF-1&#x3b1;, followed by a decrease in Ca15-3 and RECIST in response to chemotherapy. There was a statistically significant correlation between Ca15-3 and response to chemotherapy. This study evidences the relationship between factors that shape the local tumor microenvironment.},
}
@article {pmid36641655,
year = {2022},
author = {Kridis, WB and Feki, A and Khmiri, S and Toumi, N and Chaabene, K and Daoud, J and Ayedi, I and Khanfir, A},
title = {Prognostic factors in inflammatory breast cancer: A single-center study.},
journal = {Breast disease},
volume = {41},
number = {1},
pages = {461-469},
doi = {10.3233/BD-220034},
pmid = {36641655},
issn = {1558-1551},
mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/diagnosis/genetics ; Hormones ; *Inflammatory Breast Neoplasms/diagnosis/genetics ; Neoplasm Recurrence, Local ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Adult ; Aged ; Aged, 80 and over ; },
abstract = {BACKGROUND: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes.<br><br>METHODS: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim of this study was to analyze the factors of poor prognosis of this entity.<br><br>RESULTS: During a period of 12 years (2008-2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26-87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++, triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse.<br><br>CONCLUSION: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis.},
}
@article {pmid36637351,
year = {2023},
author = {Zhi, R and Wu, K and Zhang, J and Liu, H and Niu, C and Li, S and Fu, L},
title = {PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast.},
journal = {Cancer science},
volume = {114},
number = {5},
pages = {1912-1928},
pmid = {36637351},
issn = {1349-7006},
support = {31870860//National Natural Science Foundation of China/ ; 81872164//National Natural Science Foundation of China/ ; 82173344//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Breast/pathology ; *Breast Neoplasms/pathology ; Histones ; *Carcinoma, Papillary/metabolism ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; },
abstract = {Invasive micropapillary carcinoma (IMPC) is a special histopathological subtype of breast cancer. Clinically, IMPC exhibits a higher incidence of lymphovascular invasion and lymph node metastasis compared with that of invasive ductal carcinoma (IDC), the most common type. However, the metabolic characteristics and related mechanisms underlying malignant IMPC biological behaviors are unknown. We performed large-scale targeted metabolomics analysis on resected tumors obtained from chemotherapy-naïve IMPC (n = 25) and IDC (n = 26) patients to investigate metabolic alterations, and we integrated mass spectrometry analysis, RNA sequencing, and ChIP-sequencing data to elucidate the potential molecular mechanisms. The metabolomics revealed distinct metabolic profiles between IMPC and IDC. For IMPC patients, the metabolomic profile was characterized by significantly high levels of arginine methylation marks, and protein arginine methyltransferase 3 (PRMT3) was identified as a critical regulator that catalyzed the formation of these arginine methylation marks. Notably, overexpression of PRMT3 was an independent risk factor for poor IMPC prognosis. Furthermore, we demonstrated that PRMT3 was a key regulator of breast cancer cell proliferation and metastasis both in vitro and in vivo, and treatment with a preclinical PRMT3 inhibitor decreased the xenograft tumorigenic capacity. Mechanistically, PRMT3 regulated the endoplasmic reticulum (ER) stress signaling pathway by facilitating histone H4 arginine 3 asymmetric dimethylation (H4R3me2a), which may endow breast cancer cells with great proliferative and metastatic capacity. Our findings highlight PRMT3 importance in regulating the malignant biological behavior of IMPC and suggest that small-molecule inhibitors of PRMT3 activity might be promising breast cancer treatments.},
}
@article {pmid36602069,
year = {2022},
author = {Serrano-Quintero, A and Sequeda-Juárez, A and Pérez-Hernández, CA and Sosa-Delgado, SM and Mendez-Tenorio, A and Ramón-Gallegos, E},
title = {Immunogenic analysis of epitope-based vaccine candidate induced by photodynamic therapy in MDA-MB-231 triple-negative breast cancer cells.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {40},
number = {},
pages = {103174},
doi = {10.1016/j.pdpdt.2022.103174},
pmid = {36602069},
issn = {1873-1597},
mesh = {Humans ; Female ; Photosensitizing Agents ; *Photochemotherapy/methods ; Calreticulin/metabolism/therapeutic use ; Epitopes/therapeutic use ; *Triple Negative Breast Neoplasms/drug therapy ; *Breast Neoplasms ; Chromatography, Liquid ; Tandem Mass Spectrometry ; *Vaccines/therapeutic use ; Cytokines/metabolism ; Cell Line, Tumor ; },
abstract = {BACKGROUND: Photodynamic therapy (PDT) is used to treat tumors through selective cytotoxic effects. PDT induces damage-associated molecular patterns (DAMPs) expression, which can cause an immunogenic death cell (IDC). In this study we identified potential immunogenic epitopes generated by PDT on triple-negative breast cancer cell line (MDA-MB-231).<br><br>METHODS: MDA-MB-231 cells were exposed to PDT using ALA (160&#xa0;&#xb5;g/mL)/630&#xa0;nm at 8&#xa0;J/cm[2]. Membrane proteins were extracted and separated by 2D PAGE. Proteins overexpressed were identified by LC-MS/MS and analyzed in silico through a peptide-HLA docking in order to identify the epitopes with more immunogenicity and antigenicity properties, as well as lower allergenicity and toxicity activity. The selected peptides were evaluated in response to macrophage activation and cytokine release by flow cytometry.<br><br>RESULTS: Differential proteins were overexpressed in the cells treated with PDT. A group of 16 peptides were identified from them, established in a rigorous selection by measuring antigenicity, immunogenicity, allergenicity, and toxicity in silico. The final selection was based on molecular dynamics, where 2 peptides showed the highest stability regarding to the RMSD value. These peptides were obtained from the proteins calreticulin and HSP90. The cytokine analysis evidenced macrophage activation by the releasing of TNF.<br><br>CONCLUSION: Two peptides were identified from calreticulin and HSP90; proteins induced by PDT in MDA-MB-231 cells. Both epitopes showed immunogenic potential as a peptide-based vaccine for triple-negative breast cancer.},
}
@article {pmid38384043,
year = {2023},
author = {Soman, PS and Hemalatha, A and Sreeramulu, PN},
title = {Expression of BRCA1 by immunohistochemistry and its association with ER, PR, Her2neu status in infiltrative ductal carcinoma of breast.},
journal = {Journal of cancer research and therapeutics},
volume = {19},
number = {Suppl 2},
pages = {S706-S711},
doi = {10.4103/jcrt.jcrt_639_22},
pmid = {38384043},
issn = {1998-4138},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Immunohistochemistry ; Receptor, ErbB-2/genetics/metabolism ; Mastectomy ; *Carcinoma, Ductal, Breast/genetics/therapy/metabolism ; Biomarkers, Tumor/genetics/metabolism ; BRCA1 Protein/genetics ; },
abstract = {BACKGROUND: Breast cancer is a heterogeneous disease, which differs in its clinical behaviors and responses to treatment and outcome. The prognosis of breast cancer depends on histopathological parameters and molecular subtypes. Among more than 300 genes, which are involved in the pathogenesis of breast cancer tumor suppressor gene such as BRCA1 is known to play a significant role in hereditary cancers. However, its role in sporadic cases of infiltrating ductal carcinoma is yet to be established.<br><br>AIMS AND OBJECTIVES: To evaluate the expression of BRCA1 in infiltrative ductal carcinoma and to analyze the association of BRCA1 with histopathological parameters and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (Her2) neu expression.<br><br>MATERIALS AND METHODS: This was a laboratory-based exploratory study in which 56 patients with infiltrative ductal carcinoma who underwent radical mastectomy from October 2019 to July 2021 were included. Patients with chemotherapy and radiotherapy, trucut biopsies, and incomplete patient details were excluded. Immunostaining for BRCA1 was performed. Individual clinicopathological parameters were compared with the BRCA1 mutation. Statistical analysis was done using SPSS 22. A P value of < 0.05 was considered statistically significant.<br><br>RESULTS: Among 56 cases of IDC, 18 cases (32.1%) showed BRCA1 mutation. BRCA1 mutation was associated with postmenopausal age, larger tumor size, lower tumor grade, and higher tumor staging. When we analyzed the biomarkers with BRCA1 mutation, it showed a negative association with ER, PR, and Her2 neu and a high Ki67 proliferation index. No family history of breast carcinoma was seen in 34/56 patients where history was available.<br><br>CONCLUSION: Our study showed BRCA1 mutation in 32.1% and associated with postmenopausal age group, larger tumor size, and higher staging and negative hormonal status of breast carcinoma.},
}
@article {pmid38375814,
year = {2023},
author = {Huang, T and Lu, C and Zhang, Y and Lin, BY and Zhang, ZJ and Zhu, D and Wang, L and Lu, Y},
title = {Effect of activating cancer-associated fibroblasts biomarker TNC on immune cell infiltration and prognosis in breast cancer.},
journal = {Annals of medicine},
volume = {55},
number = {2},
pages = {2250987},
pmid = {38375814},
issn = {1365-2060},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Biomarkers/metabolism ; Tumor Microenvironment ; },
abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) are the most important components of the tumor microenvironment (TME). CAFs are heterogeneous and involved in tumor tumorigenesis and drug resistance, contributing to TME remodeling and predicting clinical outcomes as prognostic factors. However, the effect of CAFs the TME and the prognosis of patients with breast cancer (BC) is not fully understood. This study investigated the correlation between CAFs-activating biomarkers immune cell infiltration and survival in patients with breast cancer.<br><br>METHODS: RNA sequencing data and survival information for patients with breast cancer were downloaded from The Cancer Genome Atlas (TCGA) using R software. We then analyzed the correlation between CAFs-expressing biomarkers and immune cells using the clusterProfiler package, and evaluated the prognostic role of appealing genes using the Survminer package. Immunohistochemical (IHC) staining was used to determine the expression levels of TNC in 160 breast cancer samples pathologically diagnosed as invasive ductal carcinoma that were not otherwise specified (IDC-NOS).<br><br>RESULTS: Data analysis showed that CAFs-expressing genes was higher than in normal tissues (p&#x2009;<&#x2009;0.05). Pathway enrichment revealed that the overexpression of CAFs-related genes was mainly enriched in the focal adhesion and phosphoinositol-3 kinase-serine/threonine kinase (PI3K-AKT) signaling pathways. Immune infiltration analysis suggested that high expression of CAFs-related genes was significantly positively correlated with the infiltration of naive B cells and resting dendritic cells and inversely correlated with macrophages cell infiltration. In addition, high TNC expression in tumor cells was associated with the most adverse clinicopathological features and reduced metastasis-free survival (MFS) (hazard ratio (HR) 0.574, 95% confidence interval (CI) 0.404-0.815, p&#x2009;=&#x2009;0.035).<br><br>CONCLUSIONS: This study found that CAFs may participate in immunosuppression and regulate tumor cell proliferation and invasion. High TNC expression is associated with several adverse clinicopathological features, and high TNC expression in tumor cells has been identified as an independent prognostic factor for IDC-NOS.},
}
@article {pmid36587134,
year = {2023},
author = {Levy-Jurgenson, A and Tekpli, X and Kristensen, VN and Yakhini, Z},
title = {Analysis of Spatial Molecular Data.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2614},
number = {},
pages = {349-356},
pmid = {36587134},
issn = {1940-6029},
mesh = {Humans ; *Neoplasms/diagnosis/genetics ; Phenotype ; Algorithms ; Microscopy/methods ; },
abstract = {Digital analysis of pathology whole-slide images has been recently gaining interest in the context of cancer diagnosis and treatment. In particular, deep learning methods have demonstrated significant potential in supporting pathology analysis, recently detecting molecular traits never before recognized in pathology H&amp;E whole-slide images (WSIs). Alongside these advancements in the digital analysis of WSIs, it is becoming increasingly evident that both spatial and overall tumor heterogeneity may be significant determinants of cancer prognosis and treatment outcome. In this chapter, we describe methods that aim to support these two elements. We describe both an end-to-end deep learning pipeline for producing limited spatial transcriptomics from WSIs with associated bulk gene expression data, as well as an algorithm for quantifying spatial tumor heterogeneity based on the results of this pipeline.},
}
@article {pmid36574856,
year = {2023},
author = {Ying, Z and van Eenige, R and Beerepoot, R and Boon, MR and Kloosterhuis, NJ and van de Sluis, B and Bartelt, A and Rensen, PCN and Kooijman, S},
title = {Mirabegron-induced brown fat activation does not exacerbate atherosclerosis in mice with a functional hepatic ApoE-LDLR pathway.},
journal = {Pharmacological research},
volume = {187},
number = {},
pages = {106634},
doi = {10.1016/j.phrs.2022.106634},
pmid = {36574856},
issn = {1096-1186},
mesh = {Animals ; Humans ; Mice ; *Adipose Tissue, Brown ; Adrenergic Agonists/metabolism/pharmacology ; Apolipoproteins E/genetics/metabolism ; *Atherosclerosis/drug therapy/metabolism ; Cholesterol/metabolism ; Fatty Acids/metabolism ; Lipoproteins, LDL/metabolism ; Liver/metabolism ; Triglycerides ; Receptors, LDL/metabolism ; },
abstract = {Activation of brown adipose tissue (BAT) with the β3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of metabolically active BAT is associated with cardiometabolic health in humans. In contrast, exposure to cold or treatment with the clinically used β3-adrenergic receptor agonist mirabegron to activate BAT exacerbates atherosclerosis in apolipoprotein E (ApoE)- and low-density lipoprotein receptor (LDLR)-deficient mice, both lacking a functional ApoE-LDLR pathway crucial for lipoprotein remnant clearance. We, therefore, investigated the effects of mirabegron treatment on dyslipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a humanized lipoprotein metabolism model with a functional ApoE-LDLR clearance pathway. Mirabegron activated BAT and induced white adipose tissue (WAT) browning, accompanied by selectively increased fat oxidation and attenuated fat mass gain. Mirabegron increased the uptake of fatty acids derived from triglyceride (TG)-rich lipoproteins by BAT and WAT, which was coupled to increased hepatic uptake of the generated cholesterol-enriched core remnants. Mirabegron also promoted hepatic very low-density lipoprotein (VLDL) production, likely due to an increased flux of fatty acids from WAT to the liver, and resulted in transient elevation in plasma TG levels followed by a substantial decrease in plasma TGs. These effects led to a trend toward lower plasma cholesterol levels and reduced atherosclerosis. We conclude that BAT activation by mirabegron leads to substantial metabolic benefits in APOE*3-Leiden.CETP mice, and mirabegron treatment is certainly not atherogenic. These data underscore the importance of the choice of experimental models when investigating the effect of BAT activation on lipoprotein metabolism and atherosclerosis.},
}
@article {pmid36572997,
year = {2023},
author = {Bendarkawi, Y and Cherif Chefchaouni, A and Lkhoyaali, S and Bechar, H and Boudina, Y and Abercha, Y and Belahcen, MJ and Rahali, Y},
title = {Tamoxifen induced hands deformities.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {29},
number = {5},
pages = {1246-1250},
doi = {10.1177/10781552221147507},
pmid = {36572997},
issn = {1477-092X},
mesh = {Humans ; Female ; Middle Aged ; *Tamoxifen/adverse effects ; Antineoplastic Agents, Hormonal/adverse effects ; *Breast Neoplasms/pathology ; Arthralgia/chemically induced ; },
abstract = {INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer. In this article, we report a case of a patient who developed hand deformities following long-term administration of tamoxifen.<br><br>CASE REPORT: A 57-year-old woman, followed for invasive ductal carcinoma of the left breast under tamoxifen for 7 years, presenting joint pain with deformities in her fingers.<br><br>MANAGEMENT &amp; OUTCOME: Following the appearance of the adverse effect, tamoxifen was stopped. A series of biologic and radiologic analysis were performed in order to explain the appearance of this event. A substitution treatment was discussed and a rheumatologist's opinion was requested.<br><br>DISCUSSION: Tamoxifen appears to be associated with the development of inflammatory osteoarthritis resembling rheumatoid arthritis. Possible mechanisms of such an effect are discussed.},
}
@article {pmid36563298,
year = {2023},
author = {Braun, A and Reddy, S and Cheng, L and Gattuso, P and Yan, L},
title = {Clinicopathologic Review of Metastatic Breast Cancer to the Gynecologic Tract.},
journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists},
volume = {42},
number = {4},
pages = {414-420},
doi = {10.1097/PGP.0000000000000920},
pmid = {36563298},
issn = {1538-7151},
mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; *Genital Neoplasms, Female/secondary ; *Krukenberg Tumor ; *Ovarian Neoplasms ; },
abstract = {Metastatic spread is the single most significant predictor of poor survival in breast cancer. Some of the most common metastatic sites are the bones, lungs, liver, brain, and peritoneal cavity. Clinically metastatic breast cancer to the gynecologic tract is usually asymptomatic and diagnosed as an incidental finding during a histologic examination of gynecologic specimens resected for other reasons. Cases of metastatic breast cancer to gynecologic organs diagnosed from August 1995 to January 2021 were retrieved from our institution's pathology databases, and their clinicopathologic features were reviewed. The most common site of metastasis was the ovary which was involved in about 79% (22 of 28 cases) of metastases to the gynecologic tract. Clinically, only 8 cases (36%) presented with ovarian mass detected in imaging studies and the rest of the cases were all incidental findings. Among ovarian metastasis, 59% of cases were invasive lobular carcinoma and 41% were invasive ductal carcinoma. In 5 cases, metastatic breast cancer was found in the endometrium, including 2 cases with endometrial metastasis only and 3 cases with multiple gynecologic organs involved. Metastatic breast cancer rarely involved the lower gynecologic tract, with only 7% vaginal metastasis and 4% found in the vulva. The absolute majority of metastatic breast cancer outside of the ovaries were lobular carcinoma (88%). Most of the metastatic breast carcinomas were positive for estrogen receptor on immunohistochemistry (27 of 28 cases, 96%). Her-2/neu immunostaining was positive in 4 cases only (14%). Metastatic breast cancer needs to be distinguished from gynecologic primary neoplasms and metastatic tumors from adjacent urinary and GI tracts. A careful review of the patient's history and adequate immunohistochemistry panel are helpful to render the diagnosis.},
}
@article {pmid36548300,
year = {2022},
author = {Shapiro-Kulnane, L and Selengut, M and Salz, HK},
title = {Safeguarding Drosophila female germ cell identity depends on an H3K9me3 mini domain guided by a ZAD zinc finger protein.},
journal = {PLoS genetics},
volume = {18},
number = {12},
pages = {e1010568},
pmid = {36548300},
issn = {1553-7404},
support = {R01 GM129478/GM/NIGMS NIH HHS/United States ; S10 OD016164/OD/NIH HHS/United States ; },
mesh = {Animals ; Male ; *Drosophila/metabolism ; Drosophila melanogaster/genetics/metabolism ; *Drosophila Proteins/genetics/metabolism ; Germ Cells/metabolism ; Homeodomain Proteins/metabolism ; Zinc Fingers/genetics ; Female ; },
abstract = {H3K9me3-based gene silencing is a conserved strategy for securing cell fate, but the mechanisms controlling lineage-specific installation of this epigenetic mark remain unclear. In Drosophila, H3K9 methylation plays an essential role in securing female germ cell fate by silencing lineage inappropriate phf7 transcription. Thus, phf7 regulation in the female germline provides a powerful system to dissect the molecular mechanism underlying H3K9me3 deposition onto protein coding genes. Here we used genetic studies to identify the essential cis-regulatory elements, finding that the sequences required for H3K9me3 deposition are conserved across Drosophila species. Transposable elements are also silenced by an H3K9me3-mediated mechanism. But our finding that phf7 regulation does not require the dedicated piRNA pathway components, piwi, aub, rhino, panx, and nxf2, indicates that the mechanisms of H3K9me3 recruitment are distinct. Lastly, we discovered that an uncharacterized member of the zinc finger associated domain (ZAD) containing C2H2 zinc finger protein family, IDENTITY CRISIS (IDC; CG4936), is necessary for H3K9me3 deposition onto phf7. Loss of idc in germ cells interferes with phf7 transcriptional regulation and H3K9me3 deposition, resulting in ectopic PHF7 protein expression. IDC's role is likely to be direct, as it localizes to a conserved domain within the phf7 gene. Collectively, our findings support a model in which IDC guides sequence-specific establishment of an H3K9me3 mini domain, thereby preventing accidental female-to-male programming.},
}
@article {pmid36527274,
year = {2022},
author = {Ansari, N and Nisar, MI and Khalid, F and Mehmood, U and Usmani, AA and Shaheen, F and Hotwani, A and Begum, K and Barkat, A and Yoshida, S and Manu, AA and Sazawal, S and Baqui, AH and Bahl, R and Jehan, F},
title = {Prevalence and risk factors of Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in peri-urban communities in Pakistan: A prospective cohort study.},
journal = {Journal of global health},
volume = {12},
number = {},
pages = {05055},
pmid = {36527274},
issn = {2047-2986},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Child ; Female ; Humans ; Child, Preschool ; *COVID-19/epidemiology ; Seroepidemiologic Studies ; Prevalence ; Pakistan/epidemiology ; Prospective Studies ; Antibodies, Viral ; Risk Factors ; },
abstract = {BACKGROUND: Population-based seroepidemiological surveys provide accurate estimates of disease burden. We compare the COVID-19 prevalence estimates from two serial serological surveys and the associated risk factors among women and children in a peri-urban area of Karachi, Pakistan.<br><br>METHODS: The AMANHI-COVID-19 study enrolled women and children between November 2020 and March 2021. Blood samples were collected from March to June 2021 (baseline) and September to December 2021 (follow-up) to test for anti-SARS-CoV-2 antibodies using ROCHE Elecsys&#xae;. Participants were visited or called weekly during the study for recording symptoms of COVID-19. We report the proportion of participants with anti-SARS-CoV-2 antibodies and symptoms in each survey and describe infection risk factors using step-wise binomial regression analysis.<br><br>RESULTS: The adjusted seroprevalence among women was 45.3% (95% confidence interval (CI)&#x2009;=&#x2009;42.6-47.9) and 82.3% (95% CI&#x2009;=&#x2009;79.9-84.4) at baseline and follow-up survey, respectively. Among children, it was 18.4% (95% CI&#x2009;=&#x2009;16.1-20.7) and 57.4% (95% CI&#x2009;=&#x2009;54.3-60.3) at baseline and follow-up, respectively. Of the women who were previously seronegative, 404 (74.4%) tested positive at the follow-up survey, as did 365 (50.4%) previously seronegative children. There was a high proportion of asymptomatic infection. At baseline, being poorest and lacking access to safe drinking water lowered the risk of infection for both women (risk ratio (RR)&#x2009;=&#x2009;0.8, 95% CI&#x2009;=&#x2009;0.7-0.9 and RR&#x2009;=&#x2009;1.2, 95% CI&#x2009;=&#x2009;1.1-1.4, respectively) and children (RR&#x2009;=&#x2009;0.7, 95% CI&#x2009;=&#x2009;0.5-1.0 and RR&#x2009;=&#x2009;1.4, 95% CI&#x2009;=&#x2009;1.0-1.8, respectively). At the follow-up survey, the risk of infection was lower for underweight women and children (RR&#x2009;=&#x2009;0.4, 95% CI&#x2009;=&#x2009;0.3-0.7 and RR&#x2009;=&#x2009;0.7, 95% CI&#x2009;=&#x2009;0.5-0.8, respectively) and for women in the 30-39 years age group and children who were 24-36 months of age (RR&#x2009;=&#x2009;0.6, 95% CI&#x2009;=&#x2009;0.4-0.9 and RR&#x2009;=&#x2009;0.7, 95% CI&#x2009;=&#x2009;0.5-0.9, respectively). In both surveys, paternal employment was an important predictor of seropositivity among children (RR&#x2009;=&#x2009;0.7, 95% CI&#x2009;=&#x2009;0.6-0.9 and RR&#x2009;=&#x2009;0.8, 95% CI&#x2009;=&#x2009;0.7-1.0, respectively).<br><br>CONCLUSION: There was a high rate of seroconversion among women and children. Infection was generally mild. Parental education plays an important role in protection of children from COVID-19.},
}
@article {pmid36519609,
year = {2023},
author = {Yuce, E and Karakullukcu, S and Bulbul, H and Alandag, C and Saygin, I and Kavgaci, H},
title = {The effect of the change in hemoglobin-albumin-lymphocyte-platelet scores occurring with neoadjuvant chemotherapy on clinical and pathological responses in breast cancer.},
journal = {Bratislavske lekarske listy},
volume = {124},
number = {1},
pages = {59-63},
doi = {10.4149/BLL_2023_009},
pmid = {36519609},
issn = {0006-9248},
mesh = {Female ; Humans ; Albumins/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; Hemoglobins ; Ki-67 Antigen ; Lymphocytes ; *Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Adult ; Middle Aged ; },
abstract = {INTRODUCTION: Breast-cancer is a common-cause of death in women.(1) We investigated the effects of before/after-NACT on hemoglobin-albumin-lymphocyte-platelet (HALP) scores and of changes therein on clinical/pathological-responses.<br><br>MATERIALS AND METHODS: One-hundred-twenty-seven breast-cancer-patients receiving-NACT between December 2009 - January 2019 were investigated retrospectively.<br><br>RESULTS: The mean - age was 50.3&#xb1;12.3 (min 27 - max 79), and 125 patients (98.4 %) were women. Fifty-four (42.5 %) were premenopausal and 71 (55.9 %) postmenopausal. Invasive-ductal-carcinoma was present in 111 patients (92.5 %). Eighty patients (70.2 %) were &#x2264; T2 and 34 (29.8 %) > T2. Lymph-node-status was positive in 99 patients (83.2 %) and negative in 20 (16.8 %). Ki-67 was &#x2264; 10 % in 22 (28.9 %), 11-20 % in 23 (30.3 %), and > 20 % in 31 (40.8 %). Complete clinical response was observed in 27 (21.3 %), partial-response in 76 (59.8 %), stable-disease in 21 (16.5 %), and progressive-disease in 3 patients (2.4 %). The objective-response-rate (ORR) was 103 (81.1 %). Pathological-complete-response (pCR) was observed in 24 patients (18.9 %). ORR was higher in Ki-67 > 20 % compared to &#x2264; 10 % and 10-20 % (90.3 % vs 59.0 % / 78.3 %, respectively, p: 0.027), but no difference occurred in pCR. Neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR), prognostic-nutritional-index (PNI), and HALP were measured before/after NACT. Associations with ORR and pCR were investigated via changes in these with NACT (excepting-PNI), but no-significant results emerged.<br><br>CONCLUSIONS: Higher ORR occurred post-NACT in patients with Ki-67 >20 %, while NLR, PLR, PNI, and HALP before/after-NACT and post-NACT-changes (excepting-PNI) had no-effect on ORR/pCR (Tab. 5, Ref. 21). Text in PDF www.elis.sk Keywords: breast cancer, objective response rate (ORR), pathological complete response (pCR), hemoglobin-albumin-lymphocyte-platelet (HALP) score.},
}
@article {pmid36510982,
year = {2022},
author = {Azmat, H and Faridi, J and Habib, HM and Bugti, UJ and Sheikh, AK and Riaz, SK},
title = {Correlation of B-cell lymphoma 2 immunoexpression in invasive carcinoma of breast, no special type with hormone receptor status, proliferation index, and molecular subtypes.},
journal = {Journal of cancer research and therapeutics},
volume = {18},
number = {Supplement},
pages = {S313-S319},
doi = {10.4103/jcrt.JCRT_735_20},
pmid = {36510982},
issn = {1998-4138},
mesh = {Humans ; Female ; Receptor, ErbB-2/genetics/metabolism ; Ki-67 Antigen/genetics/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; *Carcinoma/pathology ; *Breast Neoplasms/pathology ; Prognosis ; Hormones ; Cell Proliferation/genetics ; Proto-Oncogene Proteins c-bcl-2 ; Biomarkers, Tumor/metabolism ; },
abstract = {BACKGROUND: B-cell lymphoma 2 is involved in various cancers including breast carcinoma. Its expression in breast cancer has been associated with good prognostic factors such as hormone receptor expression, low Ki-67, low grade, and earlier stage. It is also considered to be an independent prognostic factor for luminal and triple-negative tumors.<br><br>OBJECTIVE: We aimed to determine the expression of B-cell lymphoma 2 (BCL2) in different molecular subtypes of invasive ductal carcinoma of breast and its association with prognostic indicators.<br><br>MATERIALS AND METHODS: Fifty samples of invasive carcinoma of breast, no special type (NST), were categorized into molecular subtypes according to immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 and then evaluated for BCL2 expression. The expression of BCL2 was correlated with ER, PR, HER2, and Ki-67 and compared between luminal and nonluminal subtypes.<br><br>RESULTS: The BCL2 expression was seen in 68% of the cases with a significant association with ER, PR, and luminal subtypes. No significant association of BCL2 expression was seen with grade, HER2 and Ki-67 status of the tumor, or age group of the patients. BCL2 expression is significantly associated with ER, PR, and luminal subtypes in breast cancer.<br><br>CONCLUSION: BCL2 is a marker of good prognosis in invasive carcinoma of breast, NST.},
}
@article {pmid36505983,
year = {2022},
author = {Gupta, NK and Gaur, S and Pal, DK},
title = {Role of videourodynamics in the identification of causes of lower urinary tract symptoms and low uroflow in young men.},
journal = {Urology annals},
volume = {14},
number = {4},
pages = {332-335},
pmid = {36505983},
issn = {0974-7796},
abstract = {INTRODUCTION: The etiology of lower urinary tract symptoms (LUTS) is multifactorial with causes attributed either to the dysfunction of the bladder or its outlet. Although the etiologies are well studied in aged men, very limited research trials are available in young men with LUTS. Most of the time young men presenting with chronic irritative or obstructive symptoms are labeled with chronic prostatitis or prostatodynia and are treated empirically. In this study using videourodynamics, we prospectively investigated the etiologies of LUTS and low uroflow in young men.<br><br>MATERIALS AND METHODS: Fifty male patients, 18-50 years of age attending the urology outpatient department at a tertiary care center from January 2021 to December 2021 with symptoms suggestive of chronic LUTS and low uroflow (maximum urinary flow rate [Qmax] <15 ml/s at a voided volume >150 ml) were included in the study and underwent multichannel videourodynamic study (VUDS). Clinical characteristics and urodynamic results in different diagnostic groups were tabulated and analyzed. The P &#x2264; 0.05 was considered statistically significant.<br><br>RESULTS: Out of 50 enrolled patients, primary bladder neck obstruction was seen in 21 patients (42%), dysfunctional voiding in 14 (28%), impaired detrusor contractility (IDC) in 9 (18%), and benign prostatic obstruction (BPO) was noted in 6 patients (12%). The mean age and size of the prostate of patients with BPO were greater than those in the remaining groups and patients with IDC had lower Qmax and Pdet at Qmax than those in the remaining patients.<br><br>CONCLUSION: Chronic LUTS in young men has a variety of underlying etiologies and VUDS in this population is helpful in attaining an accurate diagnosis and thus may guide toward efficient management.},
}
@article {pmid36501121,
year = {2022},
author = {Leikin-Frenkel, A and Schnaider Beeri, M and Cooper, I},
title = {How Alpha Linolenic Acid May Sustain Blood-Brain Barrier Integrity and Boost Brain Resilience against Alzheimer's Disease.},
journal = {Nutrients},
volume = {14},
number = {23},
pages = {},
pmid = {36501121},
issn = {2072-6643},
mesh = {Humans ; *Alzheimer Disease/drug therapy ; Blood-Brain Barrier/metabolism ; alpha-Linolenic Acid/metabolism ; Brain/metabolism ; Apolipoprotein E4/genetics/metabolism ; },
abstract = {Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing body of evidence is converging on brain lipids, and blood-brain barrier (BBB) dysfunction, as crucial players involved in AD development. The critical role of lipids metabolism in the brain and its vascular barrier, and its constant modifications particularly throughout AD development, warrants investigation of brain lipid metabolism as a high value therapeutic target. Yet, there is limited knowledge on the biochemical and structural roles of lipids in BBB functionality in AD. Within this framework, we hypothesize that the ApoE4 genotype, strongly linked to AD risk and progression, may be related to altered fatty acids composition in the BBB. Interestingly, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements, and this may be primarily relevant to ApoE4 carriers.},
}
@article {pmid36472800,
year = {2023},
author = {Chang, YS and Tu, SJ and Chen, HD and Hsu, MH and Chen, YC and Chao, DS and Chung, CC and Chou, YP and Chang, CM and Lee, YT and Yen, JC and Jeng, LB and Chang, JG},
title = {Integrated genomic analyses of hepatocellular carcinoma.},
journal = {Hepatology international},
volume = {17},
number = {1},
pages = {97-111},
pmid = {36472800},
issn = {1936-0541},
support = {DMR-111-135//China Medical University Hospital/ ; MOST-109-2320-B-039-052//Ministry of Science and Technology (TW)/ ; MOST-110-2321-B-039-002//Ministry of Science and Technology (TW)/ ; },
mesh = {Humans ; *Carcinoma, Hepatocellular/genetics/pathology ; *Liver Neoplasms/genetics/pathology ; Mutation ; Genomics ; Gene Expression Profiling ; Aldehyde Dehydrogenase, Mitochondrial/genetics ; },
abstract = {BACKGROUND: Genomic alterations play important roles in the development of cancer. We explored the impact of protein-coding genes and transcriptomic changes on clinical and molecular alterations in Taiwanese hepatocellular carcinoma (HCC) patients.<br><br>METHODS: We analyzed 147 whole-exome sequencing and 100 RNA sequencing datasets of HCC and compared them with The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma cohort and develop a panel of 81 apoptosis-related genes for molecular classification.<br><br>RESULTS: TERT (50%), TP53 (25%), CTNNB1 (14%), ARID1A (12%), and KMT2C (11%) were the most common genetic alterations of cancer-related genes. ALDH2 and KMT2C mutated at much higher frequencies in our cohort than in TCGA, whereas CTNNB1 was found only in 14% of our Taiwanese patients. A high germline mutation rate of ALDH2 in the APOBEC mutational signature and herb drug-related aristolochic acid-associated signature was also observed. Groups A and B of HCC were identified when we used apoptosis-related genes for molecular classification. The latter group, which had poorer survival outcomes, had significantly more aDC, CD4+&#x2009;Tem, macrophages M2, NKT, plasma cells, and Th1 cells, and less CD4+&#x2009;memory T cells, CD8+&#x2009;Tcm, cDC, iDC, and Th2 cells, as well as more inter-chromosome fusion genes. Metatranscriptomic analysis revealed 54 cases of HBV infection. Moreover, we found that the main target gene of HBV integration is ALB.<br><br>CONCLUSIONS: Unique genomic alterations were observed in our Taiwanese HCC patients. Molecular classification using apoptosis-related genes could lead to new therapeutic approaches for HCC.},
}
@article {pmid36472640,
year = {2023},
author = {Maalmi, H and Strom, A and Petrera, A and Hauck, SM and Strassburger, K and Kuss, O and Zaharia, OP and Bönhof, GJ and Rathmann, W and Trenkamp, S and Burkart, V and Szendroedi, J and Ziegler, D and Roden, M and Herder, C and , },
title = {Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy.},
journal = {Diabetologia},
volume = {66},
number = {3},
pages = {579-589},
pmid = {36472640},
issn = {1432-0428},
mesh = {Adult ; Humans ; Biomarkers ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2 ; *Diabetic Neuropathies/diagnosis ; Intermediate Filaments ; *Polyneuropathies/diagnosis/complications ; },
abstract = {AIMS/HYPOTHESIS: No established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.<br><br>METHODS: This cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.<br><br>RESULTS: DSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p&#x2264;0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.<br><br>CONCLUSIONS/INTERPRETATION: Our findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.},
}
@article {pmid36472055,
year = {2022},
author = {Ortiz-Rey, JA and Bellas-Pereira, A and San Miguel-Fraile, P and Morellón-Baquera, R and Domínguez-Arístegui, P and González-Carreró Fojón, J},
title = {Intraductal Carcinoma of the Prostate without High-Grade Invasive Adenocarcinoma: Report of Two Cases and Review of the Literature.},
journal = {Archivos espanoles de urologia},
volume = {75},
number = {9},
pages = {738-745},
doi = {10.56434/j.arch.esp.urol.20227509.108},
pmid = {36472055},
issn = {0004-0614},
mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Prostatic Intraepithelial Neoplasia/genetics/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery ; Prostatectomy ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; *Adenocarcinoma/surgery ; },
abstract = {OBJECTIVES: Intraductal carcinoma of the prostate (IDC-P) is usually associated with high grade, aggresive acinar adenocarcinomas. IDC-P is supposed to result from the spread of the adenocarcinoma along the prostatic ducts. IDC-P rarely occurs without invasive carcinoma or with a coexistent low grade adenocarcinoma.<br><br>MATERIAL AND METHODS: We report two patients, 66 and 75 year-old, who presented IDC-P and low-grade acinar adenocarcinoma foci in their radical prostatectomy surgical specimens.<br><br>RESULTS: Acinar adenocarcinomas were grade group 1, PTEN+, pT2. In the first case, the invasive adenocarcinoma was adjacent but nor intermingled with the IDC-P, and a discordance in the immunophenotype between them was outstanding (positivity for ERG in the acinar carcinoma being negative in the IDC-P). In the second case, the foci of adenocarcinoma were distant from the IDC-P. The first patient had not biochemical recurrence after a 34 month follow-up period.<br><br>CONCLUSIONS: This kind of cases supports the existence of an infrequent subtype of IDC-P that could be considered as an in situ neoplasia.},
}
@article {pmid36444584,
year = {2022},
author = {Shahi, V and Agarwal, P and Qayoom, S and Kumar, V and Tewari, S and Raghuvanshi, S and Singh, US and Goel, MM},
title = {Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F, EA- 2R) along with Epstein-Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {23},
number = {11},
pages = {3717-3723},
pmid = {36444584},
issn = {2476-762X},
mesh = {Humans ; Female ; *Breast Neoplasms ; Herpesvirus 4, Human/genetics ; *Epstein-Barr Virus Infections/complications ; Reproducibility of Results ; Epstein-Barr Virus Nuclear Antigens ; India/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating ; *Carcinoma, Ductal ; },
abstract = {INTRODUCTION: Worldwide, breast cancer (BC) is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world's population. Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India.<br><br>METHODOLOGY: In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)- EBV PCR and Epstein-Barr virus latent membrane protein 1 (LMP1) IHC.<br><br>RESULTS: Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection.<br><br>CONCLUSION: The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.},
}
@article {pmid36434575,
year = {2022},
author = {Gupta, RB and Dang, H and Albreiki, D and Dollin, ML and Weston, B and Gottlieb, CC},
title = {Acute annular outer retinopathy preceded by invasive ductal breast carcinoma: a case report.},
journal = {BMC ophthalmology},
volume = {22},
number = {1},
pages = {452},
pmid = {36434575},
issn = {1471-2415},
mesh = {Humans ; Female ; Fluorescein Angiography/methods ; *Retinal Diseases/complications/diagnosis ; Tomography, Optical Coherence/methods ; Vision Disorders ; Acute Disease ; Atrophy ; *Breast Neoplasms/complications/diagnosis ; },
abstract = {BACKGROUND: Acute annular outer retinopathy (AAOR) is an uncommon disease. To date, there are few documented cases in the literature. Our case report is the first to describe a case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma.<br><br>CASE PRESENTATION: The patient presented with photopsias and visual loss approximately 3&#xa0;weeks prior to a diagnosis of invasive ductal breast carcinoma. We have documented the outer annular white ring seen in the acute phase of this disease and correlate it anatomically with Spectral-domain optical coherence tomography (SD-OCT) imaging. We identified RPE atrophy with nodular hyperreflectivity and loss of ellipsoid layer within the white annular ring with corresponding visual field loss. Fundus autofluorescence correlated with structural alterations seen on SD-OCT and showed both presumed active hyperautofluorescent zones with patchy hypoautofluorescent zones of atrophy and a classic annular hyperautofluorescent border. This case provides additional information about the natural history of this rare entity and its prognosis and varied presentation.<br><br>CONCLUSIONS: The authors report a single case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma with the corresponding SD-OCT, fundus autofluorescence and visual field findings, during the acute phase of the disease. These findings provide new insight into the characteristic features, etiology and progression of this rare disease.},
}
@article {pmid36420590,
year = {2023},
author = {Roberts, AC and Lunt, LG and Coogan, AC and Madrigrano, A},
title = {The Role of Radiation Therapy in Locally Advanced Breast Cancer in a Patient With Li-Fraumeni Syndrome.},
journal = {The American surgeon},
volume = {89},
number = {11},
pages = {4958-4960},
doi = {10.1177/00031348221135780},
pmid = {36420590},
issn = {1555-9823},
mesh = {Female ; Humans ; Adult ; *Li-Fraumeni Syndrome/complications/surgery ; *Breast Neoplasms/radiotherapy/surgery/pathology ; *Neoplasms, Radiation-Induced/etiology/surgery ; Mastectomy/adverse effects ; },
abstract = {Li-Fraumeni syndrome (LFS) is associated with many different cancers, including early onset breast cancer. Due to an increased risk of radiation-induced malignancy, radiation therapy is often avoided in this patient population. This case study evaluates a 38-year-old female with a history of juvenile granulosa cell tumor of the ovary and malignant phyllodes tumor of right breast, who subsequently developed bilateral invasive ductal carcinoma and was treated with bilateral mastectomies. Studies show that in a high-risk patient, post-mastectomy radiation therapy (PMRT) should not be ruled out due to a history of LFS, as the benefit of PMRT may outweigh the risk of a radiation-induced malignancy.},
}
@article {pmid36414494,
year = {2023},
author = {Zhang, C and Liang, Z and Feng, Y and Xiong, Y and Manwa, C and Zhou, Q},
title = {Risk Factors for Lymphovascular Invasion in Invasive Ductal Carcinoma Based on Clinical and Preoperative Breast MRI Features: a Retrospective Study.},
journal = {Academic radiology},
volume = {30},
number = {8},
pages = {1620-1627},
doi = {10.1016/j.acra.2022.10.029},
pmid = {36414494},
issn = {1878-4046},
mesh = {Humans ; Retrospective Studies ; Lymphatic Metastasis ; *Magnetic Resonance Imaging ; Risk Factors ; *Carcinoma, Ductal ; },
abstract = {RATIONALE AND OBJECTIVES: Lymphovascular invasion (LVI) plays an important role in the prediction of metastasis and prognosis in breast cancer (BC) patients. The present study assessed correlations between preoperative breast MRI, clinical features, and LVI in patients with invasive ductal carcinoma (IDC) and identified risk factors based on these correlation factors.<br><br>MATERIALS AND METHODS: Patients confirmed with IDC between 01/2012 and 12/2021 were retrospectively reviewed at our hospital. A total of 5 clinical and 14 MRI features to characterize tumours were extracted. LVI evaluated in hematoxylin and eosin sections. T-test and chi-square tests were used to compare the differences in clinical and MRI features between the LVI positive and negative groups. The associations between individual features and LVI were analysed by univariable logistic regression analysis, and risk factors for LVI were identified by multivariable logistic regression analysis based on these correlation factors.<br><br>RESULTS: This study included 353 patients with IDC, including 130 with positive LVI. Age, CEA, CA-153, amount of fibroglandular tissue (FGT), background parenchymal enhancement, tumour size, shape, skin thickening, nipple retraction, adjacent vessel sign, and axillary lymph node (ALN) size in the LVI positive group were significantly different from the LVI negative group (all p<0.05). Multivariate logistic regression analysis revealed that age (odds ratio OR&#xa0;=&#xa0;1.030), CA-153 (OR&#xa0;=&#xa0;1.018), heterogeneous FGT (OR&#xa0;=&#xa0;2.484), shape (OR&#xa0;=&#xa0;2.157), and ALN size (OR&#xa0;=&#xa0;1.051) were risk factors for LVI (all p<0.05).<br><br>CONCLUSION: Preoperative breast MRI and clinical features correlated with LVI, age, CA-153, heterogeneous FGT, shape, and ALN size are risk factors for LVI in patients with IDC.},
}
@article {pmid36412439,
year = {2022},
author = {Abbas, Z and Nouroz, F and Ejaz, S},
title = {Exceptional behavior of breast cancer-associated type 1 gene in breast invasive carcinoma.},
journal = {Journal of cancer research and therapeutics},
volume = {18},
number = {6},
pages = {1743-1753},
doi = {10.4103/jcrt.JCRT_1310_20},
pmid = {36412439},
issn = {1998-4138},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Genes, BRCA1 ; BRCA1 Protein/genetics ; *Carcinoma/genetics ; *Antineoplastic Agents ; },
abstract = {BACKGROUND: Cellular expression level of Breast Cancer-Associated Type 1 (BRCA1) encoded protein is the sign of genome integrity, stability, and surveillance. BRCA1 after sensing DNA damage activates repairing system and if mutated leaves genomic lesions unrepaired and triggers transformation of normal breast cells into cancerous ones.<br><br>AIMS OF STUDY: We conducted in silico study to have a holistic view of BRCA1's correlation with multiple variables of breast invasive carcinoma.<br><br>MATERIALS AND METHODS: We used user-friendly online GeneCardsSuite pathway-level enrichment analysis, UALCAN portal differential expression analysis, cBioPortal cancer genome platform for mutatome map construction, and cancer cell lines encyclopedia genomics of drug sensitivity toolkit to understand correlation of BRCA1 expression with the effectiveness of anti-cancer drugs.<br><br>RESULTS: Contrary to general behavior of a tumor suppressor gene our study revealed BRCA1 overexpression under all circumstances. This novel finding needs to be explored further to understand functional impact of BRCA1 overexpression on the expression of many genes which are transcriptionally regulated by BRCA1 and promotion of tumriogenesis.<br><br>CONCLUSION: Our study highlights the potential role of BRCA1-regulated genes in oncogenesis and recommends use of BRCA1-linked genes as future therapeutic targets for effective disease management.},
}
@article {pmid36411355,
year = {2022},
author = {Kalyan, VSRK and Meena, S and Karthikeyan, S and Jawahar, D},
title = {Isolation, screening, characterization, and optimization of bacteria isolated from calcareous soils for siderophore production.},
journal = {Archives of microbiology},
volume = {204},
number = {12},
pages = {721},
pmid = {36411355},
issn = {1432-072X},
support = {E28ACC//Science and Engineering Research Board/ ; },
mesh = {*Siderophores ; *Soil ; India ; Bacteria/genetics ; Iron Chelating Agents ; },
abstract = {The most effective agricultural practice to prevent iron deficiency in calcareous soils is fertilizing with synthetic chelates. These compounds are non-biodegradable, and persistent in the environment; hence, there is a risk of leaching metals into the soil horizon. To tackle iron deficiency-induced chlorosis (IDC) in crops grown on calcareous soils, environmentally friendly solutions are needed rather than chemical application as it affects the soil health further. Hence, the present work focused on isolating and screening calcareous soil-specific bacteria capable of producing iron-chelating siderophores. Siderophore-producing bacteria (SPB) was isolated from the groundnut (Arachis hypogea L.) rhizosphere region, collected from Coimbatore district, Tamil Nadu, of which 17 bacterial isolates were positive for siderophore production assayed by chrome azurol sulphonate. The performance of SPB isolates was compared for siderophore kinetics, level of siderophore production, type of siderophore produced and iron-chelating capacity under 15 mM KHCO3. Four best performing isolates were screened, with average siderophores yield ranging ∼60-80% under pH 8, with sucrose as carbon source and NH2SO4 as nitrogen source at 37 °C. The four efficient SPB were molecularly identified as B. licheniformis, B. subtilis, B. licheniformis, and O. grignonense based on 16S rDNA sequencing. The simultaneous inhibition method showed T.viride has the highest antagonistic effect against S.rolfsii, and M.phaseolina with a reduction of mycelial growth by 69.3 and 65.1%, respectively, compared to control. Our results indicate that the optimized conditions enhanced siderophores chelation by suppressing the stem and root rot fungi, which could help in a cost-effective and environmentally friendly manner.},
}
@article {pmid36395590,
year = {2022},
author = {Lin, Z and He, Y and Qiu, C and Yu, Q and Huang, H and Yiwen Zhang, and Li, W and Qiu, T and Xiaoping Li, },
title = {A multi-omics signature to predict the prognosis of invasive ductal carcinoma of the breast.},
journal = {Computers in biology and medicine},
volume = {151},
number = {Pt A},
pages = {106291},
doi = {10.1016/j.compbiomed.2022.106291},
pmid = {36395590},
issn = {1879-0534},
mesh = {Humans ; *Breast ; Area Under Curve ; ROC Curve ; Risk Factors ; *Carcinoma, Ductal ; },
abstract = {BACKGROUND: Precisely evaluating the prognosis of invasive ductal carcinoma (IDC) of the breast is challenging as most prognostic signatures use single-omics data based on gene or clinical information.<br><br>METHODS: Whole-slide images (WSIs), transcriptome, and clinical data of breast IDC were collected from the Cancer Genome Atlas Database. The cancer-associated fibroblast (CAF) gene sets were downloaded from the Molecular Signatures Database. The WSI feature was extracted by artificial feature engineering. The CAF prognostic genes were determined by the Gene Set Enrichment Analysis, the Wilcoxon test, and univariate Cox regression. The IDC patients were divided into the training and test sets. The prognostic signatures based on WSIs, IDC-CAFs, bi-omics, and tri-omics were constructed using multivariate Cox regression. The samples were divided into low- and high-risk groups according to the median risk score. The Kaplan-Meier survival and receiver operating characteristic curves were applied to validate the prediction performance of the four signatures.<br><br>RESULTS: In total, 508 IDC patients with complete data were included. The area under the curve (AUC) of single-omics signature based on WSI characteristics and CAFs was 0.765 and 0.775, whereas the AUC of bi-omics was 0.823. The tri-omics signature based on WSIs, CAFs, and lymph node status demonstrated the best predictive value with an AUC of 0.897.<br><br>CONCLUSION: The multi-omics signature based on WSIs, CAFs, and clinical characteristics showed excellent prediction ability in breast IDC patients, whose risk factors can also provide a valuable diagnostic reference for the clinical course.},
}
@article {pmid36394689,
year = {2023},
author = {Mamtani, A and Grabenstetter, A and Sevilimedu, V and Morrow, M and Gemignani, ML},
title = {Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?.},
journal = {Breast cancer research and treatment},
volume = {197},
number = {2},
pages = {417-423},
pmid = {36394689},
issn = {1573-7217},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30CA008748//NIH/NCI Cancer Center Support Grant/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Lobular/pathology ; *Carcinoma, Ductal, Breast/pathology ; Neoadjuvant Therapy ; Breast/pathology ; },
abstract = {PURPOSE: Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown.<br><br>METHODS: Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated.<br><br>RESULTS: Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2&#x2009;+&#x2009;(25% versus 7%) and TN (21% versus 0%, all p&#x2009;<&#x2009;0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR.<br><br>CONCLUSION: NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.},
}
@article {pmid36376280,
year = {2022},
author = {Haythorne, E and Lloyd, M and Walsby-Tickle, J and Tarasov, AI and Sandbrink, J and Portillo, I and Exposito, RT and Sachse, G and Cyranka, M and Rohm, M and Rorsman, P and McCullagh, J and Ashcroft, FM},
title = {Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {6754},
pmid = {36376280},
issn = {2041-1723},
support = {/WT_/Wellcome Trust/United Kingdom ; MR/V011979/1/MRC_/Medical Research Council/United Kingdom ; BB/R017220/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/T002107/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Glucose/metabolism ; Glycolysis/physiology ; Insulin/metabolism ; *Hyperglycemia/metabolism ; Pyruvic Acid/metabolism ; *Islets of Langerhans/metabolism ; *Diabetes Mellitus/metabolism ; },
abstract = {Chronic hyperglycaemia causes a dramatic decrease in mitochondrial metabolism and insulin content in pancreatic β-cells. This underlies the progressive decline in β-cell function in diabetes. However, the molecular mechanisms by which hyperglycaemia produces these effects remain unresolved. Using isolated islets and INS-1 cells, we show here that one or more glycolytic metabolites downstream of phosphofructokinase and upstream of GAPDH mediates the effects of chronic hyperglycemia. This metabolite stimulates marked upregulation of mTORC1 and concomitant downregulation of AMPK. Increased mTORC1 activity causes inhibition of pyruvate dehydrogenase which reduces pyruvate entry into the tricarboxylic acid cycle and partially accounts for the hyperglycaemia-induced reduction in oxidative phosphorylation and insulin secretion. In addition, hyperglycaemia (or diabetes) dramatically inhibits GAPDH activity, thereby impairing glucose metabolism. Our data also reveal that restricting glucose metabolism during hyperglycaemia prevents these changes and thus may be of therapeutic benefit. In summary, we have identified a pathway by which chronic hyperglycaemia reduces β-cell function.},
}
@article {pmid36357366,
year = {2022},
author = {Willemsen, N and Kotschi, S and Bartelt, A},
title = {Fire up the pyre: inosine thermogenic signaling for obesity therapy.},
journal = {Signal transduction and targeted therapy},
volume = {7},
number = {1},
pages = {375},
pmid = {36357366},
issn = {2059-3635},
support = {PROTEOFIT/ERC_/European Research Council/International ; },
mesh = {Humans ; *Bacterial Proteins ; *Signal Transduction ; Inosine ; Obesity/genetics ; },
}
@article {pmid36353989,
year = {2023},
author = {Vos, DY and Wijers, M and Smit, M and Huijkman, N and Kloosterhuis, NJ and Wolters, JC and Tissink, JJ and Pronk, ACM and Kooijman, S and Rensen, PCN and Kuivenhoven, JA and van de Sluis, B},
title = {Cargo-Specific Role for Retriever Subunit VPS26C in Hepatocyte Lipoprotein Receptor Recycling to Control Postprandial Triglyceride-Rich Lipoproteins.},
journal = {Arteriosclerosis, thrombosis, and vascular biology},
volume = {43},
number = {1},
pages = {e29-e45},
doi = {10.1161/ATVBAHA.122.318169},
pmid = {36353989},
issn = {1524-4636},
mesh = {Animals ; Humans ; Mice ; Hepatocytes/metabolism ; Lipoproteins/metabolism ; *Low Density Lipoprotein Receptor-Related Protein-1/genetics ; Mice, Knockout ; *Proprotein Convertase 9/genetics/metabolism ; Receptors, LDL ; Triglycerides/metabolism ; },
abstract = {BACKGROUND: The copper metabolism MURR1 domains/coiled-coil domain containing 22/coiled-coil domain containing 93 (CCC) complex is required for the transport of low-density lipoprotein receptor (LDLR) and LRP1 (LDLR-related protein 1) from endosomes to the cell surface of hepatocytes. Impaired functioning of hepatocytic CCC causes hypercholesterolemia in mice, dogs, and humans. Retriever, a protein complex consisting of subunits VPS26C, VPS35L, and VPS29, is associated with CCC, but its role in endosomal lipoprotein receptor transport is unclear. We here investigated the contribution of retriever to hepatocytic lipoprotein receptor recycling and plasma lipids regulation.<br><br>METHODS: Using somatic CRISPR/Cas9 gene editing, we generated liver-specific VPS35L or VPS26C-deficient mice. We determined total and surface levels of LDLR and LRP1 and plasma lipids. In addition, we studied the protein levels and composition of CCC and retriever.<br><br>RESULTS: Hepatocyte VPS35L deficiency reduced VPS26C levels but had minimal impact on CCC composition. VPS35L deletion decreased hepatocytic surface expression of LDLR and LRP1, accompanied by a 21% increase in plasma cholesterol levels. Hepatic VPS26C ablation affected neither levels of VPS35L and CCC subunits, nor plasma lipid concentrations. However, VPS26C deficiency increased hepatic LDLR protein levels by 2-fold, probably compensating for reduced LRP1 functioning, as we showed in VPS26C-deficient hepatoma cells. Upon PCSK9 (proprotein convertase subtilisin/kexin type 9)-mediated LDLR elimination, VPS26C ablation delayed postprandial triglyceride clearance and increased plasma triglyceride levels by 26%.<br><br>CONCLUSIONS: Our study suggests that VPS35L is shared between retriever and CCC to facilitate LDLR and LRP1 transport from endosomes to the cell surface. Conversely, retriever subunit VPS26C selectively transports LRP1, but not LDLR, and thereby may control hepatic uptake of postprandial triglyceride-rich lipoprotein remnants.},
}
@article {pmid36350000,
year = {2022},
author = {Chen, W and Wang, G and Zhang, G},
title = {Insights into the transition of ductal carcinoma in situ to invasive ductal carcinoma: morphology, molecular portraits, and the tumor microenvironment.},
journal = {Cancer biology &amp; medicine},
volume = {19},
number = {10},
pages = {1487-1495},
pmid = {36350000},
issn = {2095-3941},
mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Tumor Microenvironment/genetics ; *Carcinoma, Ductal, Breast/pathology ; Biomarkers, Tumor ; *Breast Neoplasms/genetics ; },
}
@article {pmid36335424,
year = {2022},
author = {Mekheal, E and Kania, BE and Kumari, P and Kumar, V and Maroules, M},
title = {Gynecomastia and Malignancy: A Case of Male Invasive Ductal Breast Carcinoma Treated with Neoadjuvant Chemotherapy.},
journal = {The American journal of case reports},
volume = {23},
number = {},
pages = {e937370},
pmid = {36335424},
issn = {1941-5923},
mesh = {Humans ; Male ; Female ; Neoadjuvant Therapy ; *Breast Neoplasms/pathology ; Receptors, Progesterone/therapeutic use ; Receptor, ErbB-2 ; Receptors, Estrogen/therapeutic use ; Mastectomy ; *Breast Neoplasms, Male/surgery ; *Gynecomastia/etiology/drug therapy/surgery ; Estrogens/therapeutic use ; *Carcinoma, Ductal/drug therapy/surgery ; *Carcinoma, Ductal, Breast/therapy/drug therapy ; Chemotherapy, Adjuvant ; },
abstract = {BACKGROUND Male breast cancer represents a rare malignancy with identifiable risk factors, including genetics, radiation exposure, liver dysfunction, and concomitant diagnosis of Klinefelter syndrome. Gynecomastia can commonly present in these patients, and despite increased estrogen levels in adipose breast tissue, gynecomastia has not been proven to be a significant risk factor for carcinoma development. Male patients with new-onset breast masses are recommended to undergo diagnostic mammograms and breast ultrasound for further evaluation. Those diagnosed with breast cancer most commonly have invasive ductal carcinoma of the breast, and over half of these patients are found to have estrogen and progesterone receptor (ER/PR) positivity. CASE REPORT In this case report, we present a Black man with gynecomastia and an areolar lesion for a 6-month duration following a traumatic event. He was initially referred to the surgical team for further evaluation, and subsequent imaging and biopsy data revealed ER/PR-positive invasive ductal carcinoma. Multidisciplinary discussions were held, and the patient was arranged to begin neoadjuvant treatment with doxorubicin hydrochloride and cyclophosphamide, followed by treatment with paclitaxel (AC-T) chemotherapy, followed by bilateral mastectomy and adjuvant hormonal therapy. CONCLUSIONS The treatment of male breast cancer has remained relatively like that of female breast cancer, which may be due to the limited data in the treatment of male breast cancer. Thus far, studies involving neoadjuvant chemotherapy of female patients have demonstrated promising responses to expand surgical options for patients and possibly decrease the rates of recurrence. Additional studies are warranted to discern optimal therapy for the male patient population.},
}
@article {pmid36332363,
year = {2022},
author = {Davis, AA and Gerratana, L and Clifton, K and Medford, AJ and Velimirovic, M and Hensing, WL and Bucheit, L and Shah, AN and D'Amico, P and Reduzzi, C and Zhang, Q and Dai, CS and Denault, EN and Bagegni, NA and Opyrchal, M and Ademuyiwa, FO and Bose, R and Gradishar, WJ and Behdad, A and Ma, CX and Bardia, A and Cristofanilli, M},
title = {Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer.},
journal = {EBioMedicine},
volume = {86},
number = {},
pages = {104316},
pmid = {36332363},
issn = {2352-3964},
support = {UL1 TR001422/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Circulating Tumor DNA/genetics ; Retrospective Studies ; DNA Copy Number Variations ; Phosphatidylinositol 3-Kinases/genetics ; },
abstract = {BACKGROUND: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology.<br><br>METHODS: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360&#x2122;. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies.<br><br>FINDINGS: ILC was significantly associated with HR+&#xa0;HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P&#xa0;<&#xa0;0.05). In multivariable analysis, HR+&#xa0;HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q&#xa0;<&#xa0;0.05).<br><br>INTERPRETATION: Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment.<br><br>FUNDING: Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422.},
}
@article {pmid36309875,
year = {2022},
author = {Chen, K and Chen, X and Su, Y},
title = {Is conservative treatment a good choice for pediatric intervertebral disc calcification in children?.},
journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society},
volume = {31},
number = {12},
pages = {3324-3329},
pmid = {36309875},
issn = {1432-0932},
mesh = {Humans ; Male ; Female ; Child ; Child, Preschool ; Conservative Treatment ; *Intervertebral Disc Degeneration/diagnostic imaging/therapy/complications ; *Ossification of Posterior Longitudinal Ligament/complications ; Longitudinal Ligaments ; *Calcinosis/diagnostic imaging/therapy/complications ; Magnetic Resonance Imaging ; *Intervertebral Disc/diagnostic imaging/pathology ; *Intervertebral Disc Displacement/complications ; },
abstract = {PURPOSE: Paediatric intervertebral disc calcification (PIDC) is a rare disease, and its aetiology remains unknown. This study aimed to analyse the characteristics and clinical outcomes of patients with PIDC.<br><br>METHODS: After applying the exclusion and inclusion criteria, 159 children diagnosed with PIDC were analysed at our hospital between January 2010 and November 2020. Patients' demographic and clinical data were collected, such as sex, pain, duration time, physical examination, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and radiography, computed tomography, and magnetic resonance imaging findings. Patients were followed up for at least 6&#xa0;months, and radiography or symptoms were evaluated. Fisher's exact test or &#x3c7;[2]-test was used for statistical analyses.<br><br>RESULTS: One hundred and fifty-nine patients were ultimately followed up with for about 12.5&#x2009;&#xb1;&#x2009;5.8&#xa0;months. There were 103 male and 56 female, with an average age of 6.08&#x2009;&#xb1;&#x2009;2.62&#xa0;years (2&#xa0;months to 12&#xa0;years). A total of 109 patients had only one PIDC, 29 patients had two PIDCs, and 21 patients had multiple PIDCs. Thirty patients were found incidentally and were asymptomatic. A total of 106 patients had neck torticollis. Sixteen patients had IDC herniations, fifteen patients had posterior longitudinal ligament calcification, two patients had anterior longitudinal ligament calcification, and 17 patients had herniation of the vertebral canal. All patients underwent conservative treatment, and none underwent surgery. All patients' symptoms resolved after either collar fixation or neck traction.<br><br>CONCLUSION: PIDC can be treated conservatively, even when accompanied by herniation, longitudinal ligament calcification, or clinical neck symptoms.<br><br>LEVEL OF EVIDENCE: IV.},
}
@article {pmid36308374,
year = {2022},
author = {Gautam, P and Feroz, Z and Tiwari, S and Vijayraghavalu, S and Shukla, GC and Kumar, M},
title = {Investigating the Role of Glutathione S- Transferase Genes, Histopathological and Molecular Subtypes, Gene-Gene Interaction and Its Susceptibility to Breast Carcinoma in Ethnic North- Indian Population.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {23},
number = {10},
pages = {3481-3490},
pmid = {36308374},
issn = {2476-762X},
support = {R15 CA252997/CA/NCI NIH HHS/United States ; },
mesh = {Female ; Humans ; *Breast Neoplasms/epidemiology/genetics ; Case-Control Studies ; *Genetic Predisposition to Disease ; Genotype ; Glutathione ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Risk Factors ; },
abstract = {BACKGROUND: Breast Cancer (BC) is a genetically and clinically heterogeneous disease including complex interactions between gene-gene and gene-environment components. This study aimed, to explore whether the Glutathione S- transferase (GSTs) gene polymorphism has role in BC susceptibility. We further evaluated the frequency of four subtypes of BC based on molecular classification followed by microscopic histological analysis to study the grades of invasive ductal carcinoma (IDC).<br><br>MATERIALS AND METHOD: Polymorphism in GST genes in North-Indian BC patients was assessed by multiplex-PCR and PCR-RFLP methods. 105 BC patients and 145 healthy controls were enrolled for this study. Data was analyzed by calculating the odds ratio (OR) and 95% CI from logistic regression analyses.<br><br>RESULTS: Our findings revealed that GSTM1 null genotype (OR = 2.231; 95% CI = 1.332-3.737; p-value= 0.002) is significantly associated to BC risk in ethnic North- Indian population. However, the risk for BC susceptibility in North-Indians does not appear to be associated with GSTT1 null genotype. The GSTP1 (Val/Val) genotype (OR=1.545; CI=0.663-3.605; p-value= 0.314) was also found to be susceptible for BC risk. Combination of three high risk GST genotypes association exhibiting gene-gene interaction further confirmed the increased risk to BC in this region.<br><br>CONCLUSIONS: The results of present study indicated that polymorphism in GSTM1 and rs1695 of GSTP1 genes may influence BC development among North-Indian women. Thus, the screening of GSTM1 and GSTP1 gene should be recommended for the earlier investigation for BC as a precautionary measure.},
}
@article {pmid36303871,
year = {2022},
author = {Al-Saoudi, E and Christensen, MMB and Nawroth, P and Fleming, T and Hommel, EE and Jørgensen, ME and Fleischer, J and Hansen, CS},
title = {Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes.},
journal = {Frontiers in endocrinology},
volume = {13},
number = {},
pages = {891442},
pmid = {36303871},
issn = {1664-2392},
mesh = {Young Adult ; Humans ; *Diabetic Neuropathies/complications ; *Diabetes Mellitus, Type 1/complications ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2/complications ; Lipids ; },
abstract = {AIMS/HYPOTHESIS: Advanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).<br><br>METHODS: This cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) "glycolytic dysfunction", ii) "lipid peroxidation", iii) "oxidative stress", and iv) "glucotoxicity".<br><br>RESULTS: A higher z-score of "glycolytic dysfunction" was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), "lipid peroxidation" was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and "glucotoxicity" was associated with lower SDNN (-4.20% (95% CI -8.1416; -0.0896), p = 0.047). No significance remained after adjustment for multiple testing.<br><br>CONCLUSIONS/INTERPRETATIONS: In young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.},
}
@article {pmid36284635,
year = {2022},
author = {Zhang, H and Yuan, J and Xiang, Y and Liu, Y},
title = {Comprehensive Analysis of NPSR1-AS1 as a Novel Diagnostic and Prognostic Biomarker Involved in Immune Infiltrates in Lung Adenocarcinoma.},
journal = {Journal of oncology},
volume = {2022},
number = {},
pages = {2099327},
pmid = {36284635},
issn = {1687-8450},
abstract = {The incidence of lung adenocarcinoma (LUAD), the most common subtype of lung cancer, continues to make lung cancer the largest cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been shown to have a significant role in both the onset and progression of lung cancer. In this study, we aimed to investigate the clinical significance and underlying mechanism of lncRNA NPSR1-AS1 (NPSR1-AS1) in LUAD. First, we performed an analysis on TCGA and identified 229 differentially expressed lncRNAs (DELs) (including 216 upregulated lncRNAs and 13 downregulated lncRNAs). Then, we carried out a screening of the lncRNAs associated with survival, and a total of 382 survival-related lncRNAs were found. 15 survival-related DELs were identified. Among them, our attention focused on NPSR1-AS1. We found that the expression of NPSR1-AS1 was much higher in LUAD specimens compared to nontumor tissues. According to the results of the ROC assays, high NPSR1-AS1 expression had an AUC value of 0.904 for LUAD, with a 95% confidence interval ranging from 0.881 to 0.927. The expression of NPSR1-AS1 was shown to be significantly elevated in a wide variety of cancers, according to the findings of a pancancer investigation. Functional enrichment analysis confirmed that NPSR1-AS1 was involved in LUAD progression via regulating several tumor-related pathways. Patients with high levels of NPSR1-AS1 expression were shown to have a shorter disease-specific survival (DSS) or overall survival (OS) than those with low levels of NPSR1-AS1 expression, according to the findings of a clinical investigation. It was determined by multivariate analysis that NPSR1-AS1 expressions served as an independent prognostic factor for the overall survival of LUAD patients. The results of immune cell infiltration revealed that the expressions of NPSR1-AS1 were negatively associated with CD8 T cells, pDC, cytotoxic cells, mast cells, iDC, neutrophils, NK CD56dim cells, DC, Th17 cells, Tgd, and macrophages, while they were positively associated with NK CD56bright cells and B cells. Overall, our findings revealed that NPSR1-AS1 could serve as a potential biomarker to assess the clinical outcome and immune infiltration level in LUAD.},
}
@article {pmid36283996,
year = {2024},
author = {Sanderson, C and Verdellen, C and Debes, N and Tárnok, Z and van de Griendt, J and Zimmerman-Brenner, S and Murphy, T},
title = {Addressing co-occurring conditions in behavioural therapy for tic disorders: a review and guideline.},
journal = {European child &amp; adolescent psychiatry},
volume = {33},
number = {7},
pages = {2111-2127},
pmid = {36283996},
issn = {1435-165X},
mesh = {Humans ; *Tic Disorders/therapy ; *Behavior Therapy/methods ; *Comorbidity ; Child ; Attention Deficit Disorder with Hyperactivity/therapy/complications ; Autism Spectrum Disorder/therapy/complications ; Obsessive-Compulsive Disorder/therapy ; Practice Guidelines as Topic ; Adult ; Tourette Syndrome/therapy ; Adolescent ; },
abstract = {Co-occurring psychiatric conditions are very common in tic disorders and Tourette syndrome. These additional symptoms are often detrimental to quality of life and may impact upon the implementation and efficacy of evidence-based behavioural therapies (BT) for tics. Combining a review of the available literature, relevant theory, and expert clinical practice, we present a guideline for implementing behavioural and psychosocial interventions when common comorbidities are present. These include attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, disruptive behaviour, autism spectrum disorder (ASD) and depression. Practical recommendations are provided for assessment, formulation and management of specific and multiple comorbidities in BT for both children and adults. Despite comorbidities being common in tic disorders, few studies have comprehensively addressed how they may influence the efficacy or implementation of existing therapies or how such treatments may need to be modified or sequenced. We outline recommendations for future research, including randomised control trials of BT for those with specific or multiple comorbidities, as well as adequately powered sub-group analyses within larger scale trials or naturalistic study designs. Transdiagnostic models of psychiatric disorders and treatment, including modular cross-diagnostic therapies, which recognise the dimensionality of psychiatric disorders are also highlighted as an important focus in treatment development in tic disorders.},
}
@article {pmid36245246,
year = {2022},
author = {Blawski, R and Toska, E},
title = {A Unique FOXA1-Associated Chromatin State Dictates Therapeutic Resistance in Lobular Breast Cancer.},
journal = {Cancer research},
volume = {82},
number = {20},
pages = {3668-3670},
pmid = {36245246},
issn = {1538-7445},
support = {K22 CA245487/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; R21 CA252530/CA/NCI NIH HHS/United States ; },
mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Receptors, Estrogen/genetics/metabolism ; Retrospective Studies ; Tamoxifen/pharmacology/therapeutic use ; },
abstract = {Invasive lobular carcinomas (ILC) are the second most common histologic subtype of breast cancer, accounting for up to 15% of cases. ILC is estrogen receptor (ER) positive, yet its biology is distinct from invasive ductal carcinomas (IDC), and retrospective analyses have indicated a poorer outcome with endocrine therapy. In this issue of Cancer Research, Nardone and colleagues investigated the mechanisms of this differential therapy response in ILC, which cannot be solely explained by the genetic profile of these tumors. The authors conducted a thorough examination of the epigenome of ILC compared with IDC in clinical and preclinical models and revealed an alternative chromatin accessibility state in ILC driven by the pioneer factor FOXA1. FOXA1 regulates its own expression in a feed-forward mechanism by binding to an ILC-unique FOXA1 enhancer site. This results in a FOXA1-ER axis that promotes the transcription of genes associated with tumor progression and tamoxifen resistance. Targeting the FOXA1 enhancer region blocks this transcriptional program and inhibits ILC proliferation. These results shed light on a new epigenetic mechanism driving ILC tumor progression and treatment resistance, which may have profound therapeutic implications. See related article by Nardone et al., p. 3673.},
}
@article {pmid36243006,
year = {2022},
author = {Sekar, R and Motzler, K and Kwon, Y and Novikoff, A and Jülg, J and Najafi, B and Wang, S and Warnke, AL and Seitz, S and Hass, D and Gancheva, S and Kahl, S and Yang, B and Finan, B and Schwarz, K and Okun, JG and Roden, M and Blüher, M and Müller, TD and Krahmer, N and Behrends, C and Plettenburg, O and Miaczynska, M and Herzig, S and Zeigerer, A},
title = {Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes.},
journal = {Cell metabolism},
volume = {34},
number = {11},
pages = {1824-1842.e9},
doi = {10.1016/j.cmet.2022.09.022},
pmid = {36243006},
issn = {1932-7420},
mesh = {Animals ; Mice ; *Diabetes Mellitus, Type 2/metabolism ; Endosomes/metabolism ; Glucagon/metabolism ; Glucose/metabolism ; Lipids ; Liver/metabolism ; Mammals/metabolism ; Mice, Inbred C57BL ; *Receptors, Glucagon/metabolism ; Endosomal Sorting Complexes Required for Transport/metabolism ; },
abstract = {During mammalian energy homeostasis, the glucagon receptor (Gcgr) plays a key role in regulating both glucose and lipid metabolisms. However, the mechanisms by which these distinct signaling arms are differentially regulated remain poorly understood. Using a Cy5-glucagon agonist, we show that the endosomal protein Vps37a uncouples glucose production from lipid usage downstream of Gcgr signaling by altering intracellular receptor localization. Hepatocyte-specific knockdown of Vps37a causes an accumulation of Gcgr in endosomes, resulting in overactivation of the cAMP/PKA/p-Creb signaling pathway to gluconeogenesis without affecting β-oxidation. Shifting the receptor back to the plasma membrane rescues the differential signaling and highlights the importance of the spatiotemporal localization of Gcgr for its metabolic effects. Importantly, since Vps37a knockdown in animals fed with a high-fat diet leads to hyperglycemia, although its overexpression reduces blood glucose levels, these data reveal a contribution of endosomal signaling to metabolic diseases that could be exploited for treatments of type 2 diabetes.},
}
@article {pmid36238494,
year = {2022},
author = {Zhao, W and Wu, T and Zhan, J and Dong, Z},
title = {Identification of the Immune Status of Hypertrophic Cardiomyopathy by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.},
journal = {Computational and mathematical methods in medicine},
volume = {2022},
number = {},
pages = {7153491},
pmid = {36238494},
issn = {1748-6718},
mesh = {Animals ; Biomarkers ; *Cardiomyopathy, Hypertrophic/genetics/metabolism ; Gene Regulatory Networks ; Mice ; *MicroRNAs ; Sequence Analysis, RNA ; },
abstract = {OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy and immune infiltration is considered an indispensable factor involved in its pathogenesis. In this study, we attempted to combine bulk sequencing and single-cell sequencing to map the immune infiltration-related genes in hypertrophic cardiomyopathy.<br><br>METHODS: The GSE36961, GSE160997, and GSE122930 datasets were obtained from the Gene Expression Omnibus database. The compositional patterns of the 18 types of immune cell fraction and pathway enrichment score in control and HCM patients were estimated based on the GSE36961 cohort using xCell algorithm. The Weighted Gene Coexpression Network Analysis (WGCNA) was performed to identify genes associated with immune infiltration for hypertrophic cardiomyopathy. The area under the curve (AUC) value was obtained and used to evaluate the discriminatory ability of common immune-related DEGs. "NetworkAnalyst" platform was used to identify TF-gene and TF-miRNA interaction with identified common genes. Heat map was used to determine the association between common DEGs and various immune cells.<br><br>RESULTS: Immune infiltration analysis by the xCell algorithm showed a higher level of CD8+ naive T cells, CD8+ T cells, as well as a lower level of activated dendritic cells (aDC), dendritic cells (DC), immature dendritic cells (iDC), conventional dendritic cells (cDC), macrophages, M1 macrophages, monocytes, and NKT cell in HCM compared with the control group in GSE36961 dataset. aDC, macrophages, and M1 macrophages were the top three discriminators between HCM and control groups with the area under the curve (AUC) of 0.907, 0.867, and 0.941. WGCNA analysis showed that 1258 immune-related genes were included in four different modules. Of these modules, the turquoise module showed a pivotal correlation with HCM. 13 common immune-related DEGs were found by intersecting common DEGs in GSE36961 and GSE160997 datasets with genes from the genes in turquoise module. 5 hub immune-related genes (S100A9, TYROBP, FCER1G, CD14, and S100A8) were identified by protein interaction network. Through analysis of single-cell sequencing data, S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory macrophage cells in the heart immune microenvironment while Cd14 was expressed by infiltrated M1 proinflammatory macrophage cells and M2 macrophages in transverse aortic constriction (TAC) mice at 1 week. Higher M2 macrophage and M1 proinflammatory macrophage infiltration as well as lower Ccr2-M1 proinflammatory macrophage and dendritic cells were shown in TAC 1week mice compared with sham mice.<br><br>CONCLUSIONS: There was a difference in immune infiltration between HCM patients and normal groups. aDC, macrophages, and M1 macrophages were the top three discriminator immune cell subsets between HCM and control groups. S100A9, TYROBP, FCER1G, CD14, and S100A8 were identified as potential biomarkers to discriminate HCM from the control group. S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory cells in the heart immune microenvironment while Cd14 was expressed by M2 macrophages in transverse aortic constriction (TAC) mice at 1 week.},
}
@article {pmid36230503,
year = {2022},
author = {Chang, YS and Chou, YP and Chung, CC and Lee, YT and Yen, JC and Jeng, LB and Chang, JG},
title = {Molecular Classification of Hepatocellular Carcinoma Using Wnt-Hippo Signaling Pathway-Related Genes.},
journal = {Cancers},
volume = {14},
number = {19},
pages = {},
pmid = {36230503},
issn = {2072-6694},
support = {DMR-111-131//China Medical University Hospital/ ; MOST-109-2320-B-039-052 and MOST-110-2321-B-039-002//Ministry of Science and Technology of Taiwan/ ; },
abstract = {In Taiwan, a combination of hepatitis B and C infection, economic boom-related food and alcohol overconsumption, and Chinese medicine prescriptions has led to a high rate of hepatocellular carcinoma (HCC). However, the causative factors and underlying tumor biology for this unique HCC environment have not been identified. Wnt and Hippo signaling pathways play an important regulatory role in HCC development, and their functions are generally considered as positive and negative regulators of cell proliferation, respectively. In this study, we characterized the molecular features of HCC using a newly developed classification system based on the expression of the Wnt-Hippo signaling pathway-related genes. RNA sequencing (RNA-Seq) was performed on liver tumor tissues from 100 patients with liver cancer. RNA-Seq data for 272 previously characterized Wnt-Hippo signaling pathway-related genes were used for hierarchical clustering. We analyzed the data in terms of prognostic value, transcriptome features, immune infiltration, and clinical characteristics, and compared the resulting subclasses with previously published classifications. Four subclasses of HCC (HCCW1-4) were identified. Subclass HCCW1 displayed the highest PCDHB4 expression. Subclass HCCW2 displayed lower Edmondson-Steiner grades (I and II) and CTNNB1 mutation frequencies. Subclass HCCW3 was associated with a good prognosis, the highest PCDHGB7 expression, high CD8+ naïve T cells abundance, and relatively low TP53 mutation rates. Subclass HCCW4 was associated with a poor prognosis, the highest PCDHB2 and PCDHB6 expression, a relatively high abundance of Th1 cells, NKT and class-switched memory B cells, relatively low enrichment of cDC, iDC, and CD4+ memory T cells, and high Edmondson-Steiner grades (III and IV). We also identified Wnt-Hippo signaling pathway-related genes that may influence immune cell infiltration. We developed a panel of 272 Wnt-Hippo signaling pathway-related genes to classify HCC into four groups based on Taiwanese HCC and The Cancer Genome Atlas Liver Hepatocellular Carcinoma datasets. This novel molecular classification system may aid the treatment of HCC.},
}
@article {pmid36229464,
year = {2022},
author = {Wong, HY and Sheng, Q and Hesterberg, AB and Croessmann, S and Rios, BL and Giri, K and Jackson, J and Miranda, AX and Watkins, E and Schaffer, KR and Donahue, M and Winkler, E and Penson, DF and Smith, JA and Herrell, SD and Luckenbaugh, AN and Barocas, DA and Kim, YJ and Graves, D and Giannico, GA and Rathmell, JC and Park, BH and Gordetsky, JB and Hurley, PJ},
title = {Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {6036},
pmid = {36229464},
issn = {2041-1723},
support = {S10 OD023475/OD/NIH HHS/United States ; R01 CA194024/CA/NCI NIH HHS/United States ; R01 CA211695/CA/NCI NIH HHS/United States ; S10 OD016355/OD/NIH HHS/United States ; T32 CA009582/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; R01 CA214494/CA/NCI NIH HHS/United States ; R01 CA218526/CA/NCI NIH HHS/United States ; R01 CA217987/CA/NCI NIH HHS/United States ; },
mesh = {Apolipoproteins E ; *Carcinoma, Intraductal, Noninfiltrating/genetics ; Extracellular Matrix Proteins ; Humans ; Ligands ; Male ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; RNA ; Receptors, Antigen, T-Cell ; Single-Cell Analysis ; Tumor Microenvironment/genetics ; },
abstract = {Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1[+]ASPN[+]FAP[+]ENG[+]) along with fewer T cells, elevated T cell dysfunction, and increased C1QB[+]TREM2[+]APOE[+]-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.},
}
@article {pmid36223973,
year = {2022},
author = {Singh, N and Singh, R and Decker, B and Robins, D and Vidal, G},
title = {Metastatic triple negative breast cancer with NTRK gene fusion on tissue but not on ctDNA molecular profile.},
journal = {BMJ case reports},
volume = {15},
number = {10},
pages = {},
pmid = {36223973},
issn = {1757-790X},
mesh = {*Breast Neoplasms/genetics/pathology ; Carcinoma ; *Circulating Tumor DNA/genetics ; Female ; Gene Fusion ; Humans ; Oncogene Proteins, Fusion/genetics ; Protein Kinase Inhibitors ; *Triple Negative Breast Neoplasms/drug therapy/genetics ; },
abstract = {A woman presented to medical oncology with almost 4 years of untreated, slowly progressing, triple negative metastatic breast cancer to the lung. About 15 years prior, she was diagnosed with invasive ductal carcinoma of the right breast with ipsilateral chest wall recurrence 6 years later. Comprehensive molecular profiling of a metastatic lesion detected a hotspot ETV6-NTRK3 fusion, which was not present on circulating tumour DNA or molecular profile performed 4 years prior. A second look pathological examination demonstrated tumour characteristics consistent with secretory breast carcinoma. Identification of ETV6--NKRT3 fusion allowed for treatment with larotrectinib, a tyrosine kinase inhibitor specifically indicated for secretory breast carcinoma. After 3 months, she experienced a partial response.},
}
@article {pmid36208091,
year = {2023},
author = {Lu, X and Ying, Y and Zhang, W and Li, R and Zhang, J},
title = {High MutS homolog 2 expression predicts poor prognosis and is related to immune infiltration in endometrial carcinoma.},
journal = {Cell biology international},
volume = {47},
number = {1},
pages = {201-215},
doi = {10.1002/cbin.11925},
pmid = {36208091},
issn = {1095-8355},
support = {182102410095//Science and Technology Department of Henan Province/ ; 212102310466//Science and Technology Department of Henan Province/ ; 2019GGJS004//Education Department of Henan Province/ ; LHGJ20220473//Health Commission of Henan Province/ ; SBGJ202002119//Health Commission of Henan Province/ ; },
mesh = {Female ; Humans ; *Endometrial Neoplasms/diagnosis/pathology ; *MutS Homolog 2 Protein/genetics/metabolism ; Promoter Regions, Genetic ; *Biomarkers, Tumor/genetics/metabolism ; },
abstract = {Several studies have shown that MutS homolog 2 (MSH2) is highly expressed in many cancer tissues. Transcriptome expression data were collected from the Cancer Genome Atlas (TCGA) database. We analyzed the expression of MSH2 in normal and tumor tissues, the relationship between MSH2 expression and various prognostic factors, and the relationship between MSH2 expression and overall survival, disease specific survival, and progression free interval. We also examined MSH2 promoter methylation between endometrial cancer and normal endometrial tissues, and identified the prognostic value of MSH2 methylation in endometrial cancer. MSH2 was highly expressed in endometrial cancer tumor tissues compared with normal tissues. High MSH2 expression might be an independent prognostic factor for OS, DSS, and PFI. Further, high MSH2 expression was correlated with age and histological type, but not with BMI, clinical stage, tumor invasion, or other clinical features. MSH2 promoter methylation in endometrial cancer was significantly lower than in normal tissues. Additionally, MSH2 levels, OS, DSS, and PFI were associated with BMI, age, tumor invasion, and histological type. ssGSEA showed that MSH2 expression was positively correlated with the infiltration of Th2 cells, Tcm cells, T helper cells, and Tgd cells, whereas it was negatively correlated with NK CD56 bright cells, pDC cells, iDC cells, cytotoxic cells, and neutrophils. Increased MSH2 expression and reduced MSH2 methylation in endometrial cancer predicts poor prognosis. MSH2 may be used as a biomarker for the diagnosis and prognosis of endometrial cancer and as an immunotherapy target.},
}
@article {pmid36206823,
year = {2022},
author = {Maggi, G and Di Meglio, D and Vitale, C and Amboni, M and Obeso, I and Santangelo, G},
title = {The impact of executive dysfunctions on Theory of Mind abilities in Parkinson's disease.},
journal = {Neuropsychologia},
volume = {176},
number = {},
pages = {108389},
doi = {10.1016/j.neuropsychologia.2022.108389},
pmid = {36206823},
issn = {1873-3514},
mesh = {Humans ; *Theory of Mind/physiology ; *Parkinson Disease/complications/psychology ; Neuropsychological Tests ; Executive Function/physiology ; *Cognitive Dysfunction ; },
abstract = {Theory of Mind (ToM) is the ability to infer and reason about others' mental states, a process impaired by Parkinson's disease (PD). ToM performance in PD seems to be strongly related to executive functioning but the exact nature of this relationship is still unclear. We aim to investigate the direct impact of several executive dysfunctions on ToM deficits (Affective and Cognitive ToM) in PD patients. Sixty-eight PD patients underwent neuropsychological tests evaluating executive control such as inhibition, cognitive flexibility, processing speed or working memory and Cognitive and Affective ToM. We divided participants into two groups based on their performance on executive tests: PD patients with poor executive functioning (PD-EF-) and those with preserved executive functioning (PD-EF+). To explore the direct impact of executive subdomains on ToM abilities, two mediation models were executed in the whole sample. We found that PD patients with poor executive functioning reported poorer scores on Affective and Cognitive ToM tasks than PD patients with preserved executive functions, controlling for age and education. Moreover, parallel mediation models, conducted in the whole sample, indicated that performance on phonological fluency mediated the relationships between educational level and both Affective and Cognitive ToM, controlling the effect of other executive tests. These findings further support the idea that executive functions are crucial in ToM processes. Particularly, phonological fluency, whose execution requires both verbal abilities and cognitive flexibility, mediated ToM performance controlling the effect of other executive functions. The identification of neuropsychological processes underpinning ToM abilities might represent a plausible target for cognitive training to strengthen ToM abilities in PD.},
}
@article {pmid36189356,
year = {2022},
author = {Saeed, U and Piracha, ZZ and Uppal, SR and Waheed, Y and Uppal, R},
title = {SARS-CoV-2 induced hepatic injuries and liver complications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {12},
number = {},
pages = {726263},
pmid = {36189356},
issn = {2235-2988},
mesh = {Aged ; *COVID-19/complications ; *Carcinoma, Hepatocellular ; *Gastrointestinal Diseases ; Humans ; Liver/pathology ; *Liver Neoplasms/pathology ; Pandemics ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction.<br><br>DISCUSSION: Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver.<br><br>CONCLUSION: During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.},
}
@article {pmid36178915,
year = {2022},
author = {Mussa, FM and Massawe, HP and Bhalloo, H and Moledina, S and Assenga, E},
title = {Magnitude and associated factors of anti-retroviral therapy adherence among children attending HIV care and treatment clinics in Dar es Salaam, Tanzania.},
journal = {PloS one},
volume = {17},
number = {9},
pages = {e0275420},
pmid = {36178915},
issn = {1932-6203},
mesh = {Child ; Cross-Sectional Studies ; *HIV Infections/complications/drug therapy/epidemiology ; Humans ; Odds Ratio ; Surveys and Questionnaires ; Tanzania/epidemiology ; },
abstract = {INTRODUCTION: The HIV pandemic continues to contribute significantly towards childhood mortality and morbidity. The up-scaling of the Anti-retroviral therapy (ART) access has seen more children surviving and sanctions great effort be made on ensuring adherence. Adherence is a dynamic process that changes over time and is determined by variable factors. This necessitates the urgency to conduct studies to determine the potential factors affecting adherence in our setting and therefore achieve the 90-90-90 goal of sustainable viral suppression.<br><br>OBJECTIVES: To assess the magnitude and associated factors of ART adherence among children (1-14 years) attending HIV care and treatment clinics during the months of July to November 2018 in Dar es Salaam.<br><br>METHODS: A cross-sectional clinic-based study, conducted in three selected HIV care and treatment clinics in urban Dar es Salaam; Muhimbili National Hospital (MNH), Temeke Regional Referral Hospital (TRRH), Infectious Disease Centre- DarDar Paediatric Program (IDC-DPP) HIV clinics during the months of July to November 2018. HIV-infected children aged 1-14 years who had been on treatment for at least six months were consecutively enrolled until the sample size was achieved. A structured questionnaire was used for data collection. Four-day self-report, one-month self-recall report and missed clinic appointments were used to assess adherence. Frequencies and percentages were used to describe categorical data. The odds ratio was used to analyse the possible factors affecting ART adherence Logistic regression models were used to determine the factors associated with ART adherence. Analysis was conducted using SPSS version 20.0 and p-value <0.05 were considered statistically significant.<br><br>RESULTS: 333 participants were recruited. The overall good adherence (&#x2265;95%) was approximated to be 60% (CI-54.3-65.1) when subjected to all three measures. On multivariable logistic regression, factors associated with higher odds of poor adherence were found to be caregivers aged 17-25 years [AOR = 3.5, 95%CI-(1.5-8.4)], children having an inter-current illness [AOR = 10.8, 95%CI-(2.3-50.4)], disbelief in ART effectiveness [AOR = 5.495; 95%CI-(1.669-18.182)] and advanced clinical stage [AOR = 1.972; 95% CI-(1.119-3.484)]. The major reasons reported by caregivers for missing medications included forgetfulness (41%), high pill burden (21%), busy schedule (11%) and long waiting hours at the clinic (9%).<br><br>In the urban setting of Dar es Salaam, ART adherence among children was found to be relatively low when combined adherence measures were used. Factors associated with poor ART adherence found were younger aged caregivers, and child intercurrent illness, while factors conferring good adherence were belief in ART effectiveness and lower HIV clinical stage. More attention and support should be given to younger aged caregivers, children with concomitant illness and advanced HIV clinical stages. Educating caregivers on ART effectiveness may also aid in improving adherence.},
}
@article {pmid36175695,
year = {2022},
author = {Silva, FHS and Underwood, A and Almeida, CP and Ribeiro, TS and Souza-Fagundes, EM and Martins, AS and Eliezeck, M and Guatimosim, S and Andrade, LO and Rezende, L and Gomes, HW and Oliveira, CA and Rodrigues, RC and Borges, IT and Cassali, GD and Ferreira, E and Del Puerto, HL},
title = {Transcription factor SOX3 upregulated pro-apoptotic genes expression in human breast cancer.},
journal = {Medical oncology (Northwood, London, England)},
volume = {39},
number = {12},
pages = {212},
pmid = {36175695},
issn = {1559-131X},
support = {05/20160//PRPq UFMG/ ; },
mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Caspase 3 ; Female ; Fluorescein-5-isothiocyanate ; Humans ; RNA, Messenger ; SOXB1 Transcription Factors ; Tumor Suppressor Proteins ; Up-Regulation ; bcl-2-Associated X Protein ; },
abstract = {BACKGROUND: Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27). Breast cancer cell line MDA-MD-231 transfected with pEF1-SOX3 + and pEF1-Empty vector followed by cytotoxicity assay (MTT), Annexin-V FITC PI for apoptosis percentage assessment by flow cytometry, qPCR for apoptotic-related gene expression, immunofluorescence, and immunohistochemistry to SOX3 immunolocalization in culture cells, and paraffin-embedded invasive ductal carcinoma tissue samples.<br><br>RESULTS: Apoptotic rate was higher in cells transfected with pEF1-SOX3&#x2009;+&#x2009;(56%) than controls (10%). MDA-MB-231 transfected with pEF1-SOX3&#x2009;+&#x2009;presented upregulation of pro-apoptotic mRNA from CASP3, CASP8, CASP9, and BAX genes, contrasting with downregulation antiapoptotic mRNA from BCL2, compared to non-transfected cells and cells transfected with pEF1-empty vector (p&#x2009;<&#x2009;0.005). SOX3 protein nuclear expression was detected in 14% (4/27 cases) of ductal carcinoma cases, and pro-Caspase-3 expression was positive in 50% of the cases.<br><br>CONCLUSION: Data suggest that SOX3 transcription factor upregulates apoptosis in breast cancer cell line MDA-MB-231, and has a down nuclear expression in ductal carcinoma cases, and need to be investigated as a tumor suppressor protein, and its loss of expression and non-nuclear action turn the cells resistant to apoptosis. Further studies are necessary to understand how SOX3 protein regulates the promoter regions of genes involved in apoptosis.},
}
@article {pmid36172685,
year = {2022},
author = {Alinezhadi, M and Makvandi, M and Kaydani, GA and Jazayeri, SN and Charostad, J and Talaeizadeh, AT and Angali, KA},
title = {Detection of High-Risk Human Papillomavirus DNA in Invasive Ductal Carcinoma Specimens.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {23},
number = {9},
pages = {3201-3207},
pmid = {36172685},
issn = {2476-762X},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Alphapapillomavirus/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal ; Case-Control Studies ; DNA ; DNA, Viral/genetics ; Female ; *Fibroadenoma/genetics ; Formaldehyde ; Humans ; Middle Aged ; Papillomaviridae/genetics ; *Papillomavirus Infections ; Paraffin Embedding ; Young Adult ; },
abstract = {BACKGROUND: According to several studies, there is an association between human papillomavirus (HPV) and breast cancer. Therefore, detection and genotyping of HPV seem important. The present study aimed to investigate the presence of HPV DNA in breast tissues by analyzing the L1 gene.<br><br>MATERIALS AND METHODS: This case-control study was conducted on 63 formalin-fixed paraffin-embedded (FFPE) tissues of invasive ductal carcinoma (IDC) as the case group and 32 FFPE tissues of fibroadenoma as the control group. HPV DNA was detected using the polymerase chain reaction assay. Positive samples were then subjected to genotyping. All statistical analyses were performed in SPSS version 22.0.<br><br>RESULTS: The patients' age ranged from 15 to 92 years, with a mean age of 43.54&#xb1;16.36 years. HPV DNA was detected in 17/95 (17.89%) samples, including 9/32 (28.12%) fibroadenoma samples and 8/63 (12.69%) IDC samples. No significant difference was observed regarding the presence of HPV DNA between the IDC and fibroadenoma tissues (P=0.08). However, a significant difference was found in the detection of high-risk HPV (HR-HPV) between the case and control groups (P=0.03). In the case group, 87.5% of the detected viruses (7/8 samples) were HR-HPV, while in the control group, 22.22% of positive samples (2/9 samples) were HR-HPV (P=0.03). Based on the results, HR-HPV and low-risk HPV genotypes were detected in 53% (9/17) and 47% (8/17) of positive samples, respectively.<br><br>CONCLUSION: In this study, 12.69% of IDC samples were positive for HPV genomes, and HR-HPV was detected in 87.5% of these samples. The present results suggest the important role of HR-HPV in the development of breast cancer.},
}
@article {pmid36168441,
year = {2022},
author = {Wenger, D and Kurumety, S and Aydi, ZB},
title = {A case report: invasive ductal carcinoma in mosaic Li-Fraumeni syndrome.},
journal = {Journal of surgical case reports},
volume = {2022},
number = {9},
pages = {rjac408},
pmid = {36168441},
issn = {2042-8812},
abstract = {Li-Fraumeni syndrome (LFS) is a rare autosomal dominant condition caused by pathogenic variants in the TP53 tumor suppressor gene and characterized by a high lifetime risk of various cancers with a very early age of onset. We are presenting a 41-year-old woman with right invasive ductal cancer and no family history of cancers, diagnosed with mosaic LFS confirmed with blood and skin punch biopsy samples. She was treated with neoadjuvant chemotherapy, mastectomy and sentinel node biopsy with completion axillary dissection. Adjuvant radiation was not recommended due to increased risk of secondary cancers. She also elected to undergo risk reducing contralateral mastectomy. Further research is warranted to determine the appropriate clinical management and surveillance strategies in patients with mosaic LFS as whether individuals with mosaic LFS have differing cancer risks in comparison to classic germline LFS is unknown.},
}
@article {pmid36107313,
year = {2022},
author = {Walth-Hummel, AA and Herzig, S and Rohm, M},
title = {Nuclear Receptors in Energy Metabolism.},
journal = {Advances in experimental medicine and biology},
volume = {1390},
number = {},
pages = {61-82},
pmid = {36107313},
issn = {0065-2598},
mesh = {Adipose Tissue/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Energy Metabolism/physiology ; Humans ; *Metabolic Diseases/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; },
abstract = {Nuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical research and represents a treatment approach for metabolic syndrome. This chapter focuses on key nuclear receptors involved in regulating the metabolic function of liver, adipose tissue, skeletal muscle, and pancreatic β-cells. It also addresses the importance of nuclear co-factors for fine-tuning of nuclear receptor function. The mode of action, role in energy metabolism, and therapeutic potential of prominent nuclear receptors is outlined.},
}
@article {pmid36082773,
year = {2023},
author = {Ryder, JH and Van Schooneveld, TC and Lyden, E and El Ramahi, R and Stohs, EJ},
title = {The interplay of infectious diseases consultation and antimicrobial stewardship in candidemia outcomes: A retrospective cohort study from 2016 to 2019.},
journal = {Infection control and hospital epidemiology},
volume = {44},
number = {7},
pages = {1102-1107},
doi = {10.1017/ice.2022.209},
pmid = {36082773},
issn = {1559-6834},
mesh = {Adult ; Humans ; *Candidemia/drug therapy ; Retrospective Studies ; *Antimicrobial Stewardship ; *Communicable Diseases/drug therapy ; Candida ; Referral and Consultation ; Antifungal Agents/therapeutic use ; },
abstract = {OBJECTIVE: To evaluate the need for mandatory infectious diseases consultation (IDC) for candidemia in the setting of antimicrobial stewardship guidance.<br><br>DESIGN: Retrospective cohort study from January 2016 to December 2019.<br><br>SETTING: Academic quaternary-care referral center.<br><br>PATIENTS: All episodes of candidemia in adults (n = 92), excluding concurrent bacterial infection or death or hospice care within 48 hours.<br><br>METHODS: Primary outcome was all-cause 30-day mortality. Secondary outcomes included guideline-adherence and treatment choice. Guideline-adherence was assessed with the EQUAL Candida score.<br><br>RESULTS: Of 186 episodes of candidemia, 92 episodes in 88 patients were included. Central venous catheters (CVCs) were present in 66 episodes (71.7%) and were the most common infection source (N = 38, 41.3%). The most frequently isolated species was Candida glabrata (40 of 94, 42.6%). IDC was performed in 84 (91.3%) of 92 candidemia episodes. Mortality rates were 20.8% (16 of 77) in the IDC group versus 25% (2 of 8) in the no-IDC group (P = .67). Other comparisons were numerically different but not significant: repeat blood culture (98.8% vs 87.5%; P = .17), echocardiography (70.2% vs 50%; P = .26), CVC removal (91.7% vs 83.3%; P = .45), and initial echinocandin treatment (67.9% vs 50%; P = .44). IDC resulted in more ophthalmology examinations (67.9% vs 12.5%; P = .0035). All patients received antifungal therapy. Antimicrobial stewardship recommendations were performed in 19 episodes (20.7%). The median EQUAL Candida score with CVC was higher with IDC (16 vs 11; P = .001) but not in episodes without CVC (12 vs 11.5; P = .81).<br><br>CONCLUSIONS: In the setting of an active antimicrobial stewardship program and high consultation rates, mandatory IDC may not be warranted for candidemia.},
}
@article {pmid36074318,
year = {2022},
author = {Pellegata, NS and Berriel Diaz, M and Rohm, M and Herzig, S},
title = {Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases.},
journal = {Cancer metastasis reviews},
volume = {41},
number = {3},
pages = {517-547},
pmid = {36074318},
issn = {1573-7233},
mesh = {Adipose Tissue ; *Adrenergic Agents ; Extracellular Matrix ; Humans ; *Neoplasms/epidemiology ; Obesity/complications ; },
abstract = {Obesity is an established risk factor for several human cancers. Given the association between excess body weight and cancer, the increasing rates of obesity worldwide are worrisome. A variety of obesity-related factors has been implicated in cancer initiation, progression, and response to therapy. These factors include circulating nutritional factors, hormones, and cytokines, causing hyperinsulinemia, inflammation, and adipose tissue dysfunction. The impact of these conditions on cancer development and progression has been the focus of extensive literature. In this review, we concentrate on processes that can link obesity and cancer, and which provide a novel perspective: extracellular matrix remodeling, angiogenesis, and adrenergic signaling. We describe molecular mechanisms involved in these processes, which represent putative targets for intervention. Liver, pancreas, and breast cancers were chosen as exemplary disease models. In view of the expanding epidemic of obesity, a better understanding of the tumorigenic process in obese individuals might lead to more effective treatments and preventive measures.},
}
@article {pmid36065259,
year = {2022},
author = {Malakzai, HA and Haidary, AM and Gulzar, S and Haidari, M and Ibrahimkhil, AS and Saadaat, R and Hakimi, A and Sadat Hofiani, SM and Rahmani, S and Abdul-Ghafar, J},
title = {Prevalence, Distribution, and Histopathological Features of Malignant Tumors Reported at Tertiary Level in Afghanistan: A 3-Year Study.},
journal = {Cancer management and research},
volume = {14},
number = {},
pages = {2569-2582},
pmid = {36065259},
issn = {1179-1322},
support = {001/WHO_/World Health Organization/International ; },
abstract = {PURPOSE: Cancer is one of the leading causes of mortality and morbidity, and therefore, tremendous research work is continuously being done around the world with consideration of etiopathogenesis as well as identification of therapeutic targets. Decades of continuous war in Afghanistan has left the medical infrastructure of the country in a miserable situation. There is a serious deficiency in research work in the fields of pathology and oncology at the moment with minimal data available to elaborate about the demographic characteristics of various malignant disorders in the country, which would be indispensable to pave the way for further research and development.<br><br>PATIENTS AND METHODS: A descriptive cross-sectional study was conducted to describe the prevalence, distribution, and important histopathological features of malignant tumors reported at tertiary level in Afghanistan.<br><br>RESULTS: Out of 2328 consecutive cases of solid malignant tumors included in our study, 93.8% were primary and 6.2% were metastatic. Breast was the most common site of origin for primary malignancy (29.5%) in females; however, in males, esophagus was the leading site for primary malignant tumors (16.3%). Invasive ductal carcinoma was the most common histologic type of malignancy in females (87.9%). However, in both genders, squamous cell carcinoma of esophagus and skin, osteosarcoma of bone and soft tissue, and glioblastoma of central nervous system were the most common histologic types of malignancies diagnosed. Small intestine was a frequently involved site affected by extranodal non-Hodgkin lymphomas. Overall, the majority of the cancers were diagnosed in stage-II.<br><br>CONCLUSION: Findings in our study were somewhat similar to data presented elsewhere in the world, with some significant differences that could be related to the local factors. Our study revealed that most of the malignant tumors were diagnosed in later stages of the disease, attributable to scarcity of specialized oncology institutions and public awareness.},
}
@article {pmid36040027,
year = {2023},
author = {Thompson, LDR and Bishop, JA},
title = {Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification.},
journal = {Advances in anatomic pathology},
volume = {30},
number = {2},
pages = {112-129},
pmid = {36040027},
issn = {1533-4031},
mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Salivary Gland Neoplasms/pathology ; Transcription Factors ; Salivary Glands/pathology ; Biomarkers, Tumor/genetics ; },
abstract = {Salivary gland intraductal carcinoma (IDC) is a very uncommon group of neoplasms. Many names, variations in diagnostic criteria, and newly observed molecular findings (including NCOA4 :: RET , TRIM27 :: RET , HRAS point mutations, and PIK3CA pathway alterations) have generated further confusion in being able to recognize and categorize this group of tumors. Different histologic appearances and patterns of growth suggest there is more than one tumor category, with intercalated duct, apocrine, oncocytic, and hybrid features seen. Frankly destructive invasion further complicates the category, as the name "intraductal" would suggest an "in situ" neoplasm. Recent evidence on fusion-positive IDC demonstrates the same molecular underpinnings in both the ductal and the myoepithelial cells, which aids in further separating these tumors. This article summarizes the historical group of 183 neoplasms classified under the umbrella of IDC and highlights the unique histologic, immunohistochemistry, and molecular features that may further guide nomenclature standardization and harmonization.},
}
@article {pmid36012443,
year = {2022},
author = {Kmiecik, A and Ratajczak-Wielgomas, K and Grzegrzółka, J and Romanowicz, H and Smolarz, B and Dziegiel, P},
title = {Expression of NUCB2/NESF-1 in Breast Cancer Cells.},
journal = {International journal of molecular sciences},
volume = {23},
number = {16},
pages = {},
pmid = {36012443},
issn = {1422-0067},
support = {STM.A350.20.064//Wroc&#x142;aw Medical University/ ; },
mesh = {*Breast Neoplasms/genetics/metabolism ; *Carcinoma, Ductal, Breast/pathology ; Cytoplasm/metabolism ; Female ; Humans ; RNA, Messenger/genetics/metabolism ; },
abstract = {Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.},
}
@article {pmid36002899,
year = {2022},
author = {Molinaro, J and DeVries, P and Ha, J and Knight, JM},
title = {New-onset hallucinations with amiodarone: a case report.},
journal = {Annals of general psychiatry},
volume = {21},
number = {1},
pages = {34},
pmid = {36002899},
issn = {1744-859X},
abstract = {BACKGROUND: Amiodarone is a commonly used antiarrhythmic for the treatment of atrial fibrillation with a unique pharmacokinetic profile. While general side effects can be frequently associated with amiodarone, psychiatric adverse reactions to this medication are uncommon. The relationship between amiodarone and hallucinations independent of delirium has been rarely reported in the literature.<br><br>CASE PRESENTATION: We report the case of a 63-year-old female with a history of estrogen and progesterone receptor positive invasive ductal carcinoma with osseous metastases to the ribs and skull, major depressive disorder, and unspecified anxiety. She was diagnosed with invasive ductal carcinoma 12&#xa0;years prior and underwent a lumpectomy with axillary lymph node dissection and radiation, currently maintained on anastrozole and trastuzumab for the past 11&#xa0;years. Her symptoms of major depressive disorder and anxiety have remained in remission on a regimen of bupropion extended release, duloxetine, and trazodone without recent dose changes. This patient presented to the emergency department with dyspnea and was admitted to the general medical floor with new-onset atrial fibrillation. She was subsequently started on amiodarone for rhythm control. Shortly after its initiation, the patient developed new onset auditory and visual hallucinations with an unremarkable extensive medical evaluation. Auditory hallucinations consisted of music and unintelligible conversations, while visual hallucinations were of a family member crying on the floor and a man carrying a gun. The differential diagnoses included depression with psychotic features, delirium, and amiodarone-induced hallucinations. Given the lack of current depressive symptoms, absence of altered cognition, and the temporal relationship between the initiation of amiodarone and the onset of hallucinations, amiodarone was suspected to be probable etiology of her hallucinations. For this reason, amiodarone was replaced with dronedarone. Visual and auditory hallucinations ceased within less than 3&#xa0;days after the discontinuation of amiodarone.<br><br>CONCLUSIONS: Psychiatric adverse events from amiodarone are uncommon, and associated isolated hallucinations have only been rarely reported in the literature. While the risk of visual and auditory hallucinations appears to be low with amiodarone initiation, clinicians should be aware of this potential side effect.},
}
@article {pmid35982591,
year = {2022},
author = {Kovalenko, I and Roy, P and Soni, B and Sangha, L and Toom, S},
title = {Secretory Carcinoma of the Breast Mimicking Invasive Ductal Carcinoma: A Case Report.},
journal = {The American journal of case reports},
volume = {23},
number = {},
pages = {e936665},
pmid = {35982591},
issn = {1941-5923},
mesh = {*Breast Neoplasms/diagnosis/genetics/therapy ; *Carcinoma/pathology ; *Carcinoma, Ductal/genetics/surgery ; *Carcinoma, Ductal, Breast/diagnosis/therapy ; Female ; Humans ; In Situ Hybridization, Fluorescence/methods ; Mastectomy ; Translocation, Genetic ; },
abstract = {BACKGROUND Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation. CASE REPORT A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment. CONCLUSIONS Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.},
}
@article {pmid35976519,
year = {2023},
author = {Eum, SY and Schurhoff, N and Teglas, T and Wolff, G and Toborek, M},
title = {Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.},
journal = {Molecular and cellular biochemistry},
volume = {478},
number = {3},
pages = {581-595},
pmid = {35976519},
issn = {1573-4919},
support = {R01 MH128022/MH/NIMH NIH HHS/United States ; DA050528/DA/NIDA NIH HHS/United States ; DA047157/DA/NIDA NIH HHS/United States ; MH128022/MH/NIMH NIH HHS/United States ; R01 DA039576/DA/NIDA NIH HHS/United States ; R01 DA050528/DA/NIDA NIH HHS/United States ; R01 DA040537/DA/NIDA NIH HHS/United States ; DA044579/DA/NIDA NIH HHS/United States ; MH072567/MH/NIMH NIH HHS/United States ; R01 DA044579/DA/NIDA NIH HHS/United States ; DA039576/DA/NIDA NIH HHS/United States ; MH122235/MH/NIMH NIH HHS/United States ; R01 HL126559/HL/NHLBI NIH HHS/United States ; DA040537/DA/NIDA NIH HHS/United States ; R21 MH122235/MH/NIMH NIH HHS/United States ; R01 DA047157/DA/NIDA NIH HHS/United States ; HL126559/HL/NHLBI NIH HHS/United States ; R01 MH072567/MH/NIMH NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Catenins/genetics ; *Circadian Rhythm ; Gene Expression Regulation ; },
abstract = {We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.},
}
@article {pmid35963427,
year = {2022},
author = {Brecklinghaus, T and Albrecht, W and Duda, J and Kappenberg, F and Gründler, L and Edlund, K and Marchan, R and Ghallab, A and Cadenas, C and Rieck, A and Vartak, N and Tolosa, L and Castell, JV and Gardner, I and Halilbasic, E and Trauner, M and Ullrich, A and Zeigerer, A and Demirci Turgunbayer, &#xd6; and Damm, G and Seehofer, D and Rahnenführer, J and Hengstler, JG},
title = {In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay.},
journal = {Toxicology letters},
volume = {368},
number = {},
pages = {33-46},
doi = {10.1016/j.toxlet.2022.08.006},
pmid = {35963427},
issn = {1879-3169},
mesh = {*Chemical and Drug Induced Liver Injury/etiology ; *Drug-Related Side Effects and Adverse Reactions ; *Fatty Liver/chemically induced ; Hepatocytes ; Humans ; Oxazines/toxicity ; },
abstract = {The accumulation of lipid droplets in hepatocytes is a key feature of drug-induced liver injury (DILI) and can be induced by a subset of hepatotoxic compounds. In the present study, we optimized and evaluated an in vitro technique based on the fluorescent dye Nile Red, further named Nile Red assay to quantify lipid droplets induced by the exposure to chemicals. The Nile Red assay and a cytotoxicity test (CTB assay) were then performed on cells exposed concentration-dependently to 60 different compounds. Of these, 31 were known to induce hepatotoxicity in humans, and 13 were reported to also cause steatosis. In order to compare in vivo relevant blood concentrations, pharmacokinetic models were established for all compounds to simulate the maximal blood concentrations (Cmax) at therapeutic doses. The results showed that several hepatotoxic compounds induced an increase in lipid droplets at sub-cytotoxic concentrations. To compare how well (1) the cytotoxicity test alone, (2) the Nile Red assay alone, and (3) the combination of the cytotoxicity test and the Nile Red assay (based on the lower EC10 of both assays) allow the differentiation between hepatotoxic and non-hepatotoxic compounds, a previously established performance metric, the Toxicity Separation Index (TSI) was calculated. In addition, the Toxicity Estimation Index (TEI) was calculated to determine how well blood concentrations that cause an increased DILI risk can be estimated for hepatotoxic compounds. Our findings indicate that the combination of both assays improved the TSI and TEI compared to each assay alone. In conclusion, the study demonstrates that inclusion of the Nile Red assay into in vitro test batteries may improve the prediction of DILI compounds.},
}
@article {pmid35958350,
year = {2022},
author = {Fujita, K and Okamura, M and Imakita, T and Yamamoto, Y and Sawai, S and Moriyoshi, K and Mio, T},
title = {Natural course of pulmonary hyalinizing granuloma over a decade.},
journal = {Respiratory medicine case reports},
volume = {39},
number = {},
pages = {101715},
pmid = {35958350},
issn = {2213-0071},
abstract = {BACKGROUND: Pulmonary hyalinizing granuloma (PHG) is a very rare pulmonary disease characterized by multiple fibrosclerotic inflammatory lung nodules. The disease is supposedly caused by an unusual immune response.<br><br>CASE PRESENTATION: We present a case involving a 53-year-old female with a history of lumpectomy surgery due to invasive ductal carcinoma who was admitted for slowly progressive pulmonary nodules. The patient's elevated serum IgG4 level and the pathological findings obtained in surgical biopsy indicated IgG4-related lung disease. The nodules continued to enlarge despite administration of corticosteroid therapy, and we performed a second surgical biopsy to obtain a correct diagnosis. The pathological findings obtained in the second biopsy were different and consistent with the features of PHG.<br><br>CONCLUSIONS: In this report, the radiological follow-up data obtained after lumpectomy surgery demonstrate the very early stage of PHG and the following radiological changes over a decade, and the two surgical biopsies support us to realize the pathological change from previous diagnosed disease before PHG.},
}
@article {pmid35950920,
year = {2022},
author = {Nardone, A and Qiu, X and Spisak, S and Nagy, Z and Feiglin, A and Feit, A and Cohen Feit, G and Xie, Y and Font-Tello, A and Guarducci, C and Hermida-Prado, F and Syamala, S and Lim, K and Munoz Gomez, M and Pun, M and Cornwell, M and Liu, W and Ors, A and Mohammed, H and Cejas, P and Brock, JB and Freedman, ML and Winer, EP and Fu, X and Schiff, R and Long, HW and Metzger Filho, O and Jeselsohn, R},
title = {A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer.},
journal = {Cancer research},
volume = {82},
number = {20},
pages = {3673-3686},
pmid = {35950920},
issn = {1538-7445},
support = {K08 CA191058/CA/NCI NIH HHS/United States ; P01 CA250959/CA/NCI NIH HHS/United States ; R01 CA193910/CA/NCI NIH HHS/United States ; R01 CA237414/CA/NCI NIH HHS/United States ; },
mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Prognosis ; Receptors, Estrogen/metabolism ; Tamoxifen/pharmacology/therapeutic use ; },
abstract = {UNLABELLED: Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor-positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1-estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1-ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1-ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype.<br><br>SIGNIFICANCE: A unique FOXA1-ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease. See related commentary by Blawski and Toska, p. 3668.},
}
@article {pmid35945526,
year = {2022},
author = {Xu, A and Chu, X and Zhang, S and Zheng, J and Shi, D and Lv, S and Li, F and Weng, X},
title = {Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.},
journal = {BMC cancer},
volume = {22},
number = {1},
pages = {872},
pmid = {35945526},
issn = {1471-2407},
support = {2021KY1161 and 2022KY1316//Medical and Health Research Project of Zhejiang Province/ ; 2021ZA138//Zhejiang Province Chinese Medicine Science Research Fund Project/ ; },
mesh = {Bayes Theorem ; *Breast Neoplasms/diagnostic imaging/genetics ; *Carcinoma, Ductal ; China ; Female ; Humans ; Ki-67 Antigen ; Nomograms ; Retrospective Studies ; },
abstract = {BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status.<br><br>METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n&#x2009;=&#x2009;128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n&#x2009;=&#x2009;86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 (http://keyan.deepwise.com/), then radiomics feature extraction was implemented with PyRadiomics library. Recursive&#xa0;feature&#xa0;elimination&#xa0;(RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA).<br><br>RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical&#xa0;factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p&#x2009;=&#x2009;0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p&#x2009;=&#x2009;0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and&#xa0;the DCA verified the benefits of the nomogram.<br><br>CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.},
}
@article {pmid35943964,
year = {2022},
author = {Sorotos, M and Paolini, G and D'Orsi, G and Firmani, G and Timmermans, FW and Santanelli di Pompeo, F},
title = {Oncologic Outcome of 1000 Postmastectomy Breast Reconstructions with Fat Transfer: A Single-Center, Matched Case-Control Study.},
journal = {Plastic and reconstructive surgery},
volume = {150},
number = {},
pages = {4S-12S},
doi = {10.1097/PRS.0000000000009494},
pmid = {35943964},
issn = {1529-4242},
mesh = {Adipose Tissue/pathology ; *Breast Neoplasms/etiology ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; *Mammaplasty/adverse effects ; Mastectomy/adverse effects ; Neoplasm Recurrence, Local/epidemiology/etiology/prevention &amp; control ; Retrospective Studies ; },
abstract = {BACKGROUND: Autologous fat transfer has an important role in breast reconstructive surgery. Nevertheless, some concerns remain with regard to its oncologic safety. The authors present a single-center, case-matching study analyzing the impact of autologous fat transfer in the cumulative incidence of local recurrences.<br><br>METHODS: From a prospectively maintained database, the authors identified 902 patients who underwent 1025 breast reconstructions from 2005 to 2017. Data regarding demographics, tumor characteristics, surgery details, and follow-up were collected. Exclusion criteria were patients with distant metastases at diagnosis, recurrent tumor, or incomplete data regarding primary tumor; and patients who underwent prophylactic mastectomies and breast-conserving operations. Statistical analysis was conducted to evaluate the impact of the variables on the incidence of local recurrence. A value of p < 0.05 was considered statistically significant.<br><br>RESULTS: After 1: n case-matching, we selected 919 breasts, of which 425 patients (46.2 percent) received at least one autologous fat transfer session versus 494 control cases (53.8 percent). Local recurrences had an overall rate of 6.8 percent, and we found local recurrences in 14 autologous fat transfer cases (3.0 percent) and 54 controls (9.6 percent). Statistical analysis showed that autologous fat transfer did not increase the risk of local recurrences (hazard ratio, 0.337; CI, 0.173 to 0.658; p = 0.00007). Multivariate analysis identified invasive ductal carcinoma subtype and lymph node metastases to have an increased risk of local recurrences (hazard ratio >1). Conversely, positive hormonal receptor status was associated with a reduced risk of events (hazard ratio <1).<br><br>CONCLUSIONS: Autologous fat transfer was not associated with a higher probability of locoregional recurrence in patients undergoing breast reconstruction; therefore, it can be safely used for total breast reconstruction or aesthetic refinements.<br><br>Risk, II.},
}
@article {pmid35932126,
year = {2022},
author = {Yaltirik Bilgin, E and Unal, O and Ciledag, N},
title = {Vasogenic Edema Pattern in Brain Metastasis.},
journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP},
volume = {32},
number = {8},
pages = {1020-1025},
doi = {10.29271/jcpsp.2022.08.1020},
pmid = {35932126},
issn = {1681-7168},
mesh = {Brain/pathology ; *Brain Edema/diagnostic imaging/etiology ; *Brain Neoplasms/complications/diagnostic imaging/pathology ; Cross-Sectional Studies ; Edema/etiology ; Humans ; *Lung Neoplasms/complications ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; },
abstract = {OBJECTIVE: To determine the relationship of the presence and amount of vasogenic edema with origin, type, and grade of primary cancer.<br><br>STUDY DESIGN: Cross-sectional study.<br><br>PLACE AND DURATION OF STUDY: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiology Clinic, Ankara, Turkey, from July 2017 to October 2021.<br><br>METHODOLOGY: Brain MRI scans of 292 patients were retrospectively evaluated. Age, gender, origin, type, and grade of primary cancer were determined. Metastasis type, and presence of vasogenic edema accompanying metastatic lesion were questioned. In cases of vasogenic edema accompanying metastatic lesions, the largest diameter of the vasogenic edema mass complex was measured in T2 sequences. In the contrast-enhanced series, the largest diameter of the metastatic lesion was measured, and the edema-mass ratio (EMR) was calculated by proportioning the diameter of the edema mass complex to the diameter of the mass.<br><br>RESULTS: The frequency of vasogenic edema was found higher in patients with lung cancer compared to other primaries. The EMR was found statistically significantly higher in patients with primary lung cancer (p=0.001). This was particularly evident in the adenocarcinoma group. In the patient group with primary breast cancer, EMR was found significantly lower in patients with invasive ductal carcinoma. (IDC&#x2192;1.95&#xb1;0.66 vs. Other&#x2192;2.48&#xb1;0.52, Z=-2.301, p=0.021).<br><br>CONCLUSION: The amount and presence of vasogenic edema in patients with brain metastases may differ according to the origin and type of primary tumour.<br><br>KEY WORDS: Brain edema, Metastatic disease, Magnetic resonance imaging.},
}
@article {pmid35929120,
year = {2023},
author = {Kim, KN and Salerno, M and Shah, PD and Matro, J and LaRiviere, MJ},
title = {Severe acute radiation dermatitis after palbociclib therapy in the setting of palliative radiotherapy.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {29},
number = {3},
pages = {764-767},
doi = {10.1177/10781552221118841},
pmid = {35929120},
issn = {1477-092X},
mesh = {Humans ; Female ; Middle Aged ; Retrospective Studies ; Pyridines/adverse effects ; *Breast Neoplasms/drug therapy/radiotherapy/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Dermatitis/drug therapy/etiology ; Protein Kinase Inhibitors/therapeutic use ; },
abstract = {INTRODUCTION: Cyclin-dependent-kinase 4/6(CDK4/6) inhibitors are widely used as a first-line systemic treatment for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer. Although many patients with metastatic breast cancer require palliative radiotherapy (RT), there are limited data on the safety of combining a CDK4/6 inhibitor with palliative RT.<br><br>CASE REPORT: Presented is a case of acute high-grade radiation dermatitis with low-dose palliative RT following administration of palbociclib. A 49-year-old woman with newly diagnosed hormone receptor-positive invasive ductal carcinoma of the left breast presented with lytic bone lesions in the left femur and lumbar spine. The patient initiated treatment with goserelin, tamoxifen, and palbociclib. She underwent prophylactic surgical fixation of the left femur and received post-operative RT encompassing the entire surgical nail (30 Gy/10 fractions) and palliative RT to the lumbar spine for pain relief (20 Gy/5 fractions). During cycle 4, palbociclib was stopped 3 days prior to the start of RT to reduce the risk of toxicity risk. However, 16 days after starting RT, she developed painful erythematous papules and bullae with moist desquamation on the left groin and lumbar spine.<br><br>MANAGEMENT &amp; OUTCOME: Her symptoms were managed with topical Aquaphor-lidocaine, silver sulfadiazine, and aluminum acetate soaks. Dermatitis subsided to dry desquamation within 2 weeks. The patient denied late toxicity at 11 months follow-up.<br><br>DISCUSSION: Larger retrospective or prospective studies are needed to further elucidate the safety of combined CDK4/6 inhibitors and RT. In the meantime, special precautions are warranted in patients receiving combined therapy.},
}
@article {pmid35909232,
year = {2023},
author = {Yang, ZJ and Liu, YX and Huang, Y and Chen, ZJ and Zhang, HZ and Yu, Y and Wang, X and Cao, XC},
title = {The regrouping of Luminal B (HER2 negative), a better discriminator of outcome and recurrence score.},
journal = {Cancer medicine},
volume = {12},
number = {3},
pages = {2493-2504},
pmid = {35909232},
issn = {2045-7634},
mesh = {Humans ; Female ; Ki-67 Antigen/metabolism ; *Receptor, ErbB-2/metabolism ; Retrospective Studies ; *Breast Neoplasms/pathology ; Disease-Free Survival ; Receptors, Progesterone/metabolism ; Biomarkers, Tumor/metabolism ; Prognosis ; },
abstract = {BACKGROUND: Breast cancer (BC) remains the leading cause of cancer-related deaths worldwide. High recurrence risk Luminal BC receives adjuvant chemotherapy in addition to standard hormone therapy. Considering the heterogeneity of Luminal B BC, a more accurate classification model is urgently needed.<br><br>METHODS: In this study, we retrospectively reviewed the data of 1603 patients who were diagnosed with HER2-negative breast invasive ductal carcinoma. According to the expression level of PR and Ki-67 index, the Luminal B (HER2-negative) BCs were divided into three groups: ER+PR-Ki67low (ER-positive, PR-negative, and Ki-67 index <20%), ER+PR+Ki67high (ER-positive, PR-positive, and Ki-67 index &#x2265;20%), and ER+PR-Ki67high (ER-positive, PR-negative, and Ki-67 index &#x2265;20%). The cox proportional hazards regression model was used to evaluate the correlation between each variable and outcomes. Besides, discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve and log-rank &#x3c7;[2] value.<br><br>RESULTS: The analysis results showed that there was a significant correlation between subtypes using this newly defined classification and overall survival (p&#x2009;<&#x2009;0.001) and disease-free survival (DFS) (p&#x2009;<&#x2009;0.001). Interestingly, patients in the ER+PR-Ki67high subgroup have the worst survival outcome in Luminal B (HER2-negative) subtype, similar to Triple-negative patients. Besides, the ER+PR+Ki67high has worse 5-year DFS compared with Luminal A group. There was a significant relationship between the regrouping subtype and the recurrence score index (RI) (p&#x2009;<&#x2009;0.001). Moreover, the results showed that patients in ER+PR-Ki67high subtype were more likely to have high RI for distance recurrence (RI-DR) and local recurrence (RI-LRR). Our newly defined classification has a better discrimination ability to predict survival outcome and recurrence score of Luminal B (HER2-negative) BC patients, which may help in clinical decision-making for individual treatment.},
}
@article {pmid35907957,
year = {2022},
author = {Oehler, D and Spychala, A and Gödecke, A and Lang, A and Gerdes, N and Ruas, J and Kelm, M and Szendroedi, J and Westenfeld, R},
title = {Full-length transcriptomic analysis in murine and human heart reveals diversity of PGC-1α promoters and isoforms regulated distinctly in myocardial ischemia and obesity.},
journal = {BMC biology},
volume = {20},
number = {1},
pages = {169},
pmid = {35907957},
issn = {1741-7007},
mesh = {Alternative Splicing ; Animals ; Humans ; Mice ; *Myocardial Ischemia/genetics ; Obesity/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism ; Protein Isoforms/genetics ; RNA, Messenger/metabolism ; *Transcriptome ; },
abstract = {BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) acts as a transcriptional coactivator and regulates mitochondrial function. Various isoforms are generated by alternative splicing and differentially regulated promoters. In the heart, total PGC-1α deficiency knockout leads to dilatative cardiomyopathy, but knowledge on the complexity of cardiac isoform expression of PGC-1α remains sparse. Thus, this study aims to generate a reliable dataset on cardiac isoform expression pattern by long-read mRNA sequencing, followed by investigation of differential regulation of PGC-1α isoforms under metabolic and ischemic stress, using high-fat-high-sucrose-diet-induced obesity and a murine model of myocardial infarction.<br><br>RESULTS: Murine (C57Bl/6J) or human heart tissue (obtained during LVAD-surgery) was used for long-read mRNA sequencing, resulting in full-length transcriptomes including 58,000 mRNA isoforms with 99% sequence accuracy. Automatic bioinformatic analysis as well as manual similarity search against exonic sequences leads to identification of putative coding PGC-1&#x3b1; isoforms, validated by PCR and Sanger sequencing. Thereby, 12 novel transcripts generated by hitherto unknown splicing events were detected. In addition, we postulate a novel promoter with homologous and strongly conserved sequence in human heart. High-fat diet as well as ischemia/reperfusion (I/R) injury transiently reduced cardiac expression of PGC-1&#x3b1; isoforms, with the most pronounced effect in the infarcted area. Recovery of PGC-1&#x3b1;-isoform expression was even more decelerated when I/R was performed in diet-induced obese mice.<br><br>CONCLUSIONS: We deciphered for the first time a complete full-length transcriptome of the murine and human heart, identifying novel putative PGC-1&#x3b1; coding transcripts including a novel promoter. These transcripts are differentially regulated in I/R and obesity suggesting transcriptional regulation and alternative splicing that may modulate PGC-1&#x3b1; function in the injured and metabolically challenged heart.},
}
@article {pmid35906698,
year = {2022},
author = {Lee, S and Osmanbeyoglu, HU},
title = {Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.},
journal = {Breast cancer research : BCR},
volume = {24},
number = {1},
pages = {54},
pmid = {35906698},
issn = {1465-542X},
support = {R00 CA207871/CA/NCI NIH HHS/United States ; },
mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Chromatin/genetics ; Female ; Humans ; Transcription Factors/genetics ; },
abstract = {BACKGROUND: Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored.<br><br>METHODS: Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq)&#xa0;dataset.<br><br>RESULTS: We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC.<br><br>CONCLUSIONS: This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.},
}
@article {pmid35898837,
year = {2023},
author = {Suzuki, Y and Hoshi, K and Tominaga, K and Inaba, Y and Yoshinaga, T and Kojimahara, S and Maki, R and Nemoto, R and Tetsuka, Y and Kawata, Y and Yamamiya, A and Sugaya, T and Iso, Y and Takada-Owada, A and Ishida, K and Goda, K and Irisawa, A},
title = {A case of obstructive jaundice caused by metastasis of breast cancer to the intra/extrahepatic bile duct.},
journal = {DEN open},
volume = {3},
number = {1},
pages = {e144},
pmid = {35898837},
issn = {2692-4609},
abstract = {A 38-year-old woman was admitted to our hospital for a detailed examination of jaundice. Three years before, she had undergone a right total mastectomy and axillary lymph node dissection of her right breast because of cancer. Histopathological evaluation revealed invasive ductal carcinoma. Postoperatively, because multiple bone metastases were found, she underwent chemoradiotherapy. Endoscopic retrograde cholangiopancreatography was performed, which revealed widespread multiple stenoses with a smooth surface from the intrahepatic to the extrahepatic bile duct. A transpapillary biliary biopsy was performed. Histopathological examination revealed adenocarcinoma extending into the subepithelium of the bile duct. The obtained cancer cells were similar to those of the earlier invasive breast cancer. This rare case demonstrates bile duct metastasis of breast cancer with specific endoscopic retrograde cholangiopancreatography findings.},
}
@article {pmid35880762,
year = {2022},
author = {Billeter, AT and Scheurlen, KM and Israel, B and Straub, BK and Schirmacher, P and Kopf, S and Nawroth, PP and Müller-Stich, BP},
title = {Gastric Bypass Resolves Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Low-BMI Patients: A Prospective Cohort Study.},
journal = {Annals of surgery},
volume = {276},
number = {5},
pages = {814-821},
pmid = {35880762},
issn = {1528-1140},
mesh = {Adipokines ; Adolescent ; Adult ; Aged ; Blood Glucose/metabolism ; Body Mass Index ; C-Peptide ; *Diabetes Mellitus, Type 2/complications ; *Gastric Bypass ; *Gastrointestinal Hormones/metabolism ; Glucagon ; Glycated Hemoglobin/metabolism ; Humans ; Insulin ; *Liver Diseases/complications ; Middle Aged ; *Obesity, Morbid/complications/metabolism/surgery ; Prospective Studies ; Sirtuin 1 ; Young Adult ; },
abstract = {OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.<br><br>METHODS: Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35&#xa0;kg/m 2 , glucagon-stimulated C-peptide of >1.5&#xa0;ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value <0.05 was defined as significant.<br><br>RESULTS: MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45&#xb1;0.27% to 7.09&#xb1;0.26%, P =0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and &#x3b2;-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.<br><br>CONCLUSIONS: RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.},
}
@article {pmid35880695,
year = {2023},
author = {Zhang, J and Lin, H and Hou, L and Xiao, H and Gong, X and Guo, X and Cao, X and Liu, Z},
title = {Exploration of the breast ductal carcinoma in situ signature and its prognostic implications.},
journal = {Cancer medicine},
volume = {12},
number = {3},
pages = {3758-3772},
pmid = {35880695},
issn = {2045-7634},
mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Prognosis ; Prospective Studies ; *Breast Neoplasms/pathology ; Kaplan-Meier Estimate ; Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/pathology ; Protein Serine-Threonine Kinases ; NIMA-Related Kinases ; },
abstract = {Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%-50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time-dependent receiver operating characteristic (ROC), Kaplan-Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein-protein interaction). A unique six-gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision-making for individual care.},
}
@article {pmid35866222,
year = {2022},
author = {Khanam, R and Islam, S and Rahman, S and Ahmed, S and Islam, A and Hasan, T and Hasan, E and Chowdhury, NH and Roy, AD and Jaben, IA and Nehal, AA and Yoshida, S and Manu, AA and Raqib, R and McCollum, ED and Shahidullah, M and Jehan, F and Sazawal, S and Bahl, R and Baqui, AH},
title = {Sero-prevalence and risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in a rural district of Bangladesh: A cohort study.},
journal = {Journal of global health},
volume = {12},
number = {},
pages = {05030},
pmid = {35866222},
issn = {2047-2986},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Antibodies, Viral ; Bangladesh/epidemiology ; *COVID-19/epidemiology ; Child ; Cohort Studies ; Communicable Disease Control ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Seroepidemiologic Studies ; },
abstract = {BACKGROUND: Bangladesh reported its first COVID-19 case on March 8, 2020. Despite lockdowns and promoting behavioural interventions, as of December 31, 2021, Bangladesh reported 1.5 million confirmed cases and 27 904 COVID-19-related deaths. To understand the course of the pandemic and identify risk factors for SARs-Cov-2 infection, we conducted a cohort study from November 2020 to December 2021 in rural Bangladesh.<br><br>METHODS: After obtaining informed consent and collecting baseline data on COVID-19 knowledge, comorbidities, socioeconomic status, and lifestyle, we collected data on COVID-like illness and care-seeking weekly for 54 weeks for women (n&#x2009;=&#x2009;2683) and their children (n&#x2009;=&#x2009;2433). Between March and July 2021, we tested all participants for SARS-CoV-2 antibodies using ROCHE's Elecsys&#xae; test kit. We calculated seropositivity rates and 95% confidence intervals (95% CI) separately for women and children. In addition, we calculated unadjusted and adjusted relative risk (RR) and 95% CI of seropositivity for different age and risk groups using log-binomial regression models.<br><br>RESULTS: Overall, about one-third of women (35.8%, 95% CI&#x2009;=&#x2009;33.7-37.9) and one-fifth of children (21.3%, 95% CI&#x2009;=&#x2009;19.2-23.6) were seropositive for SARS-CoV-2 antibodies. The seroprevalence rate doubled for women and tripled for children between March 2021 and July 2021. Compared to women and children with the highest household wealth (HHW) tertile, both women and children from poorer households had a lower risk of infection (RR, 95% CI for lowest HHW tertile women (0.83 (0.71-0.97)) and children (0.75 (0.57-0.98)). Most infections were asymptomatic or mild. In addition, the risk of infection among women was higher if she reported chewing tobacco (RR&#x2009;=&#x2009;1.19,95% CI&#x2009;=&#x2009;1.03-1.38) and if her husband had an occupation requiring him to work indoors (RR&#x2009;=&#x2009;1.16, &#x2009;95% CI&#x2009;=&#x2009;1.02-1.32). The risk of infection was higher among children if paternal education was >5 years (RR&#x2009;=&#x2009;1.37, 95% CI&#x2009;=&#x2009;1.10-1.71) than in children with a paternal education of &#x2264;5 years.<br><br>CONCLUSIONS: We provided prospectively collected population-based data, which could contribute to designing feasible strategies against COVID-19 tailored to high-risk groups. The most feasible strategy may be promoting preventive care practices; however, collecting data on reported practices is inadequate. More in-depth understanding of the factors related to adoption and adherence to the practices is essential.},
}
@article {pmid35864546,
year = {2022},
author = {Zhu, S and Zhao, J and Nie, L and Yin, W and Zhang, Y and Zhao, F and Ni, Y and Zhang, X and Wang, Z and Dai, J and Liu, Z and Chen, J and Zeng, Y and Wang, Z and Sun, G and Liang, J and Zhao, X and Zhu, X and Tao, R and Yang, J and He, B and Chen, N and Shen, P and Zeng, H},
title = {Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P).},
journal = {BMC medicine},
volume = {20},
number = {1},
pages = {237},
pmid = {35864546},
issn = {1741-7015},
mesh = {*Adenocarcinoma/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Homologous Recombination/genetics ; Humans ; Male ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; },
abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.<br><br>METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.<br><br>RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score&#x2265;21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.<br><br>CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.},
}
@article {pmid35855704,
year = {2022},
author = {Bhatia, JK and Chaudhary, T and Boruah, D and Bharadwaj, R},
title = {Study of angiogenesis in invasive breast carcinoma by morphometry and immunohistochemistry.},
journal = {Medical journal, Armed Forces India},
volume = {78},
number = {3},
pages = {345-354},
pmid = {35855704},
issn = {0377-1237},
abstract = {BACKGROUND: Breast cancer is the leading cause of cancer-related deaths in Asia and is emerging as the commonest female malignancy. Angiogenesis or neovascularization is important for the growth and spread of malignant tumors, and quantitative assessment of angiogenesis may prove valuable in prognostication. This study was undertaken to quantify and explore angiogenesis with immunohistochemistry with CD 34, CD 105, and vascular endothelial growth factor (VEGF), as well as morphometric analysis and correlate with the grades of the invasive breast carcinoma.<br><br>METHODS: Angiogenesis was assessed by morphometry and immunohistochemistry. Seventy cases of invasive ductal carcinoma (IDC) and twenty-five benign cases as controls were included in the study. Morphometry was performed on the CD34 and CD105 (Endoglin) stained representative histologic sections with the use of a computerized digital photomicrograph system using image analyzing software. Morphometric analysis and evaluation of vascular parameters, i.e. microvessel density (MVD), microvessel caliber (VC), and total microvessel boundary density (TVBD), were calculated. Semiquantitative assessment of angiogenesis of VEGF-stained sections was done by scoring. Immunohistochemical staining was correlated with the histological grade of the tumors. MVD, mean VC, TVBD with their mean values, SD, and range were calculated using Statistical Package for The Social Sciences&#xa0;(Version 20). One-way analysis of variance (ANOVA) with Tukey HSD was performed to assess the difference of the parameters for the groups. Spearman rank correlation coefficients &#x3c1; were calculated.<br><br>RESULTS: The vascular parameters were significantly more in malignant lesions as compared to benign lesions and showed differences with increasing grade. Grades of breast carcinoma showed a mild positive correlation with VEGF (&#x3c1;&#xa0;=&#xa0;0.467), MVD-CD34 (&#x3c1;&#xa0;=&#xa0;0.422) and VC-CD34 (&#x3c1;&#xa0;=&#xa0;0.482); and moderate positive correlation with TVBD-CD34 (&#x3c1;&#xa0;=&#xa0;0.615), VC-CD105 (&#x3c1;&#xa0;=&#xa0;0.527), and TVBD-CD105 (&#x3c1;&#xa0;=&#xa0;0.354). When these parameters were compared with each other for all four groups, VEGF showed a mild positive correlation with MVD-CD34 (&#x3c1;&#xa0;=&#xa0;0.295), TVBD-CD34 (&#x3c1;&#xa0;=&#xa0;0.339), and TVBD-CD105 ((&#x3c1;&#xa0;=&#xa0;0.277). MVD-CD105 showed a mild positive correlation with MVD-CD34 TVBD-CD105 also showed a strong positive correlation with MVD-CD34. VC-CD105 showed a moderate positive correlation with VC-CD34. CD 105 stained fewer but larger caliber&#xa0;vessels.<br><br>CONCLUSIONS: In this study, vascular parameters showed significant differences in three grades of IDC with CD34. Differences were seen in vascular parameters stained with CD105 in three grades of IDC. Expression of VEGF also showed significant differences with positive correlations in the three grades of IDC. CD34 highlighted both old and newly formed microvessels. CD 105 stained fewer but larger caliber microvessels. VC-CD105 can be an extremely useful adjunct along with VEGF and CD34 to study angiogenesis of vessels in IDC.},
}
@article {pmid35855193,
year = {2022},
author = {Somashekhar, SP and Jaiswal, R and Kumar, R and Ashok, BC and Rakshit, S and Rauthan, A and Patil, P and Yashas, N and Karthik, HK and Prasad, A and Islam, H and Ashwin, KR},
title = {An Overview of the Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy in Operable Breast Cancer in a Tertiary Care Centre in South India.},
journal = {European journal of breast health},
volume = {18},
number = {3},
pages = {271-278},
pmid = {35855193},
issn = {2587-0831},
abstract = {OBJECTIVE: The incidence of female breast cancer in the world is 11.7% with a mortality rate of 6.9%. According to Globocon 2020, breast cancer is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer-related death amongst women worldwide. The purpose of this study was to analyze the impact of Body Mass Index (BMI) on pathological complete response (pCR) rates for operable breast cancer after neoadjuvant chemotherapy (NACT). The primary endpoint was to assess histopathological features of the surgical specimen in response to NACT and to investigate the relationship with pre-chemotherapy BMI taking into account the various molecular subtypes of breast cancer.<br><br>MATERIALS AND METHODS: Patients with biopsy-proven breast carcinoma who underwent surgery after NACT between January 2017 and May 2021 were included. All patients were initially divided into three groups depending on their pre-chemotherapy BMI. With BMI <22.9 as normal or underweight category, BMI of 23-27.4, was taken as overweight category and BMI &#x2265;27.5 as obese category.<br><br>RESULTS: The study included 184 patients. Normal weight patients had the highest rate of pCR (75%) and the lowest was seen in the obese category (33.75%). Furthermore, the subtype most likely to achieve pCR was HER2+/ER negative followed by triple negative BC with odds ratios of 3.46 and 2.21, respectively.<br><br>CONCLUSION: This retrospective study established that overweight and obese patients suffering from breast carcinoma had a lessened pCR rate following NACT in comparison with those who were under-/normal weight.},
}
@article {pmid35852797,
year = {2022},
author = {Tokura, M and Nakayama, J and Prieto-Vila, M and Shiino, S and Yoshida, M and Yamamoto, T and Watanabe, N and Takayama, S and Suzuki, Y and Okamoto, K and Ochiya, T and Kohno, T and Yatabe, Y and Suto, A and Yamamoto, Y},
title = {Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ.},
journal = {Cancer research},
volume = {82},
number = {18},
pages = {3236-3248},
doi = {10.1158/0008-5472.CAN-22-0090},
pmid = {35852797},
issn = {1538-7445},
mesh = {Biomarkers ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Female ; Gene Expression Profiling ; Humans ; },
abstract = {UNLABELLED: Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. The frequency of DCIS is increasing because of routine mammography; however, the biological features and intratumoral heterogeneity of DCIS remain obscure. To address this deficiency, we performed single-cell transcriptomic profiling of DCIS and invasive ductal carcinoma (IDC). DCIS was found to be composed of several transcriptionally distinct subpopulations of cancer cells with specific functions. Several transcripts, including long noncoding RNAs, were highly expressed in IDC compared with DCIS and might be related to the invasive phenotype. Closeness centrality analysis revealed extensive heterogeneity in DCIS, and the prediction model for cell-to-cell interactions implied that the interaction network among luminal cells and immune cells in DCIS was comparable with that in IDC. In addition, transcriptomic profiling of HER2+ luminal DCIS indicated HER2 genomic amplification at the DCIS stage. These data provide novel insight into the intratumoral heterogeneity and molecular features of DCIS, which exhibit properties similar to IDC.<br><br>SIGNIFICANCE: Investigation of the molecular features of ductal carcinoma in situ at single cell resolution provides new insights into breast cancer biology and identifies candidate therapeutic targets and diagnostic biomarkers.},
}
@article {pmid35842661,
year = {2022},
author = {Zhang, WT and Zhu, GL and Xu, WQ and Zhang, W and Wang, HZ and Wang, YB and Li, YX},
title = {Association of PD-1/PD-L1 expression and Epstein--Barr virus infection in patients with invasive breast cancer.},
journal = {Diagnostic pathology},
volume = {17},
number = {1},
pages = {61},
pmid = {35842661},
issn = {1746-1596},
support = {No.2008085QH408//Natural Science Foundation of Anhui Province/ ; No.81874063//National Natural Science Foundation of China/ ; },
mesh = {B7-H1 Antigen/metabolism ; Biomarkers, Tumor/analysis ; *Breast Neoplasms ; *Epstein-Barr Virus Infections/complications ; Female ; Herpesvirus 4, Human ; Humans ; Ligands ; Prognosis ; Programmed Cell Death 1 Receptor ; },
abstract = {PURPOSE: Causative factors of breast cancer include infections, such as Epstein-Barr virus (EBV) infection. The aim of this study was to analyze the clinicopathological features of EBV-positive (IBC) and determine if EBV affects programmed cell death receptor 1 (PD-1)/PD ligand 1 (PD-L1) expression in IBC, similar to other EBV-infected tumors with PD-L1/PD-1 expression.<br><br>METHODS: We collected 140 samples of IBC tissues and 25 samples of adjacent tissues. All patients were followed-up by telephone from the day of surgery to December 2020. Chromogenic in-situ hybridization was performed to evaluate EBV-encoded RNA (EBER). Immunohistochemistry was performed to evaluate PD-L1 and PD-1 expressions. The correlation between PD1/PDL1 expression and clinicopathological features was also analyzed.<br><br>RESULTS: EBER was detected in 57 of 140 (40.7%) IBC tissues and not detected in any adjacent tissue (P&#x2009;<&#x2009;0.05). Clinicopathologic features of patients were consistent with EBV-associated IBC. EBV infection was correlated with the mass size, menopausal status, axillary lymph node metastasis, vascular invasion, Ki-67 index, clinical stage, and estrogen receptor and progesterone receptor expressions (all P&#x2009;<&#x2009;0.05), but not with the histological type, invasive ductal carcinoma histological grade, or human epidermal growth factor receptor 2 (HER2) expression (all P&#x2009;>&#x2009;0.05). The positive rate of PD-1/PD-L1 expression was higher in the EBV-positive group than in the EBV-negative group (P&#x2009;<&#x2009;0.05). The Kaplan-Meier univariate survival analysis showed that EBV was associated with poor disease-free survival and overall survival in patients with IBC. PD-L1/PD-1 expression could predict a poor prognosis.<br><br>CONCLUSIONS: In this study, clinicopathologic characteristics of patients were consistent with EBV-infected IBC. Patients with EBV-positive breast cancer were more likely to have elevated PD-1/PDL-1 expression compared to those with EBV-negative breast cancer. This finding could serve as a basis to explore therapeutic targets, particularly immunotherapy, for patients with IBC.},
}
@article {pmid35834927,
year = {2022},
author = {Syamsu, SA and Setiady, R and Smaradania, N and Prihantono, and Irsandy, F and Faruk, M},
title = {Synchronous breast cancer and non-Hodgkin lymphoma: A case report.},
journal = {International journal of surgery case reports},
volume = {97},
number = {},
pages = {107398},
pmid = {35834927},
issn = {2210-2612},
abstract = {INTRODUCTION: Among women, breast cancer (BC) is the most prevalent type of cancer and the top cause of cancer deaths. Although non-Hodgkin lymphoma (NHL) is the most prevalent hematological cancer, it is rarely reported synchronous with BC. Moreover, which malignancy appears first can rarely be explained because they are usually detected incidentally while diagnosing and treating other malignancies. This paper reports a case of invasive ductal carcinoma (IDC) concomitant with NHL.<br><br>PRESENTATION OF CASE: A 35-year-old woman presented with simultaneous IDC in the left breast and NHL in a lymph node in the neck. The patient underwent a modified radical mastectomy for stage IIIA IDC and received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for stage I NHL.<br><br>CLINICAL DISCUSSION: Treating BC and NHL remains challenging due to their significantly different management, the lack of guidelines for treating BC and lymphoma simultaneously, and uncertainty about whether synchronous tumors should be treated separately as distinct clinical entities or as one disease with treatment covering both. Therefore, the best approach continues to be focusing on the most biologically aggressive malignancies.<br><br>CONCLUSION: The enlargement of lymph nodes not in the lymphatic drainage of the primary tumor should be suspected of indicating multiple primary malignancies until proven otherwise. For patients with luminal-B BC, NHL chemotherapy can involve receiving the R-CHOP regimen, including doxorubicin and cyclophosphamide, which can help to mitigate BC.},
}
@article {pmid35821630,
year = {2022},
author = {Ciudad, P and Escandón, JM and Manrique, OJ and Gutierrez-Arana, J and Mayer, HF},
title = {Lymphedema prevention and immediate breast reconstruction with simultaneous gastroepiploic vascularized lymph node transfer and deep inferior epigastric perforator flap: A case report.},
journal = {Microsurgery},
volume = {42},
number = {6},
pages = {617-621},
doi = {10.1002/micr.30939},
pmid = {35821630},
issn = {1098-2752},
mesh = {*Breast Neoplasms/complications/surgery ; Female ; Humans ; Lymph Nodes/blood supply ; *Lymphedema/etiology/prevention &amp; control/surgery ; *Mammaplasty/adverse effects/methods ; Mastectomy/adverse effects ; Middle Aged ; *Perforator Flap/blood supply ; },
abstract = {Breast cancer-related lymphedema following axillary lymph node dissection (ALND) has been documented in 6%-55% of patients, mostly occurring within the next 3 years after radiation or surgery. We present a case of a 53-year-old patient with hormone positive, stage IB, left breast invasive ductal carcinoma treated with immediate lymphatic and microvascular breast reconstruction (MBR) using vascularized lymph node transfer (VLNT) for lymphedema prevention. A deep inferior epigastric perforator (DIEP) flap (18.3 × 11.2-cm) and simultaneous prophylactic gastroepiploic-VLNT (7 × 3-cm), orthotopically inset in the axilla, were used for reconstruction following mastectomy and radical ALND. The procedure was uneventful. The patient did not display increased postoperative arm circumferences. ICG lymphography did not show any changes at 2- and 3-years after surgery. Preventive lymphatic reconstruction with GE-VLNT and immediate MBR using the DIEP flap offers a new possibility for the primary prevention of lymphedema and simultaneous immediate autologous breast reconstruction without the risk of iatrogenic lymphedema. Further studies will be directed to unveil the external validity of these findings and the risk reduction rate of this approach.},
}
@article {pmid35804316,
year = {2022},
author = {Chang, C and Zhu, J and Li, H and Yang, Q},
title = {Enhanced magnetic resonance imaging manifestations of paediatric intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: case report and literature review.},
journal = {BMC pediatrics},
volume = {22},
number = {1},
pages = {400},
pmid = {35804316},
issn = {1471-2431},
mesh = {*Calcinosis/diagnostic imaging ; Cervical Vertebrae/diagnostic imaging ; Child ; Female ; Humans ; *Intervertebral Disc/diagnostic imaging/pathology ; Longitudinal Ligaments/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; *Ossification of Posterior Longitudinal Ligament/complications/diagnostic imaging ; Osteogenesis ; },
abstract = {BACKGROUND: Since the first description of paediatric intervertebral disc calcification (IDC) by Báron in 1924, only approximately 400 cases have been reported in the literature. Paediatric IDC combined with ossification of the posterior longitudinal ligament (OPLL) is an even rarer condition, with only 8 cases described in detail to date. In this paper, we present a review of the disease characteristics described in the relevant English language literature and discuss the possible mechanisms of lesion enhancement in contrast-enhanced magnetic resonance imaging (MRI).<br><br>CASE PRESENTATION: In May 2020, a 6-year-old Han nationality girl presented with the chief complaint of neck pain that had lasted for a week. She did not report a history of trauma or a past illness. On admission, there was no personal and family history, congenital diseases, or non-specific infections such as tuberculosis, among others. Further physical examination revealed that the movement of her cervical spine was limited. Computed tomography (CT) and MRI revealed ossification of the intervertebral discs and posterior longitudinal ligament (PLL) at the C4/5 levels and an absence of obvious spinal cord compression. When contrast-enhanced MRI was performed, significant enhancement was observed in the intervertebral discs and PLL at the C4/5 level. We adopted a non-interventional approach and performed an imaging re-examination 8 months later. Both the plain and contrast-enhanced MRI scans indicated swelling in the C4/5 intervertebral discs and disappearance of the previously observed enhancement in the nucleus pulposus (NP) and PLL at the corresponding levels; CT examination revealed that the ossified lesions had been completely resorbed.<br><br>CONCLUSION: Obvious lesion enhancement in contrast-enhanced MRI is an extremely rare manifestation of paediatric IDC combined with OPLL. However, the exact mechanisms of this phenomenon remain unclear. We surmise that it may be caused by a series of biophysical changes related to vertebral endplate injury and repair, but further research will be required for in-depth investigation.},
}
@article {pmid35776197,
year = {2022},
author = {Rakshit, S and Sunny, JS and George, M and Hanna, LE and Leela, KV and Sarkar, K},
title = {T helper cell-mediated epitranscriptomic regulation via m6A RNA methylation bridges link between coronary artery disease and invasive ductal carcinoma.},
journal = {Journal of cancer research and clinical oncology},
volume = {148},
number = {12},
pages = {3421-3436},
pmid = {35776197},
issn = {1432-1335},
support = {ECR/2016/000965//Science and Engineering Research Board/ ; },
mesh = {Humans ; Female ; Methylation ; *Coronary Artery Disease/genetics ; Tumor Suppressor Protein p53 ; RNA/genetics ; T-Lymphocytes, Helper-Inducer ; Lactate Dehydrogenases ; *Carcinoma, Ductal ; },
abstract = {PURPOSE: Invasive ductal carcinoma (IDC) and coronary artery disease (CAD), remains the greatest cause of death annually in women, driven by complex signalling pathways and shared several predisposing risk factors together. Therefore, it is important to find out the common epigenetic modifications which are responsible for possible disease progression from CAD to IDC.<br><br>METHODS: CD4+T cell isolation by MACS, RT2 profiler PCR array, Gene ontology study, m6A RNA methylation, ChIP-qPCR, Q-PCR, CRISPR/Cas9-mediated knockout/overexpression, Lactate dehydrogenase release assay, RDIP-qPCR.<br><br>RESULTS: We have identified several epigenetic regulators (e.g., VEGFA, AIMP1, etc.) which are mainly involved in inflammatory pathways in both the diseased conditions. Epitranscriptomic alterations such as m6A RNA methylation found abnormal in CD4+T helper cells in both IDC as well as CAD. CRISPR-Cas9 mediated knockout/overexpression of specific gene (BRCA1) are promising therapeutic approaches in diseased conditions by regulating m6A RNA methylation and also tumor suppressor gene P53. It also affected the R-loop formation which is vulnerable to DNA damage and BRCA1 can also induce CTL mediated cytotoxicity in breast cancer cells.<br><br>CONCLUSIONS: Therefore, by understanding the modifications of epigenetic mechanisms, their alterations and interactions will aid in the development of newer therapeutic approaches to stop the possible spread from one disease to another.},
}
@article {pmid35749404,
year = {2022},
author = {Hardeman, AA and Han, YJ and Grushko, TA and Mueller, J and Gomez, MJ and Zheng, Y and Olopade, OI},
title = {Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer.},
journal = {PloS one},
volume = {17},
number = {6},
pages = {e0268693},
pmid = {35749404},
issn = {1932-6203},
support = {K12 CA139160/CA/NCI NIH HHS/United States ; UL1 RR024999/RR/NCRR NIH HHS/United States ; },
mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; DNA Copy Number Variations ; Female ; Humans ; Protein Serine-Threonine Kinases ; RNA, Messenger/genetics ; *Triple Negative Breast Neoplasms/genetics ; },
abstract = {Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of MELK aberrations in aggressive breast cancer, we assessed MELK gene amplification and expression in breast tumors. MELK mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. MELK copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in MELK expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma in situ (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of MELK to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.},
}
@article {pmid35749114,
year = {2022},
author = {Weis, S and Hagel, S and Palm, J and Scherag, A and Kolanos, S and Bahrs, C and Löffler, B and Schmitz, RPH and Rißner, F and Brunkhorst, FM and Pletz, MW and , },
title = {Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.},
journal = {JAMA network open},
volume = {5},
number = {6},
pages = {e2218515},
pmid = {35749114},
issn = {2574-3805},
mesh = {Adolescent ; Aged ; *Bacteremia/therapy ; *Communicable Diseases ; Female ; Hospitals ; Humans ; Male ; Referral and Consultation ; Retrospective Studies ; *Staphylococcal Infections/therapy ; Staphylococcus aureus ; Telephone ; Treatment Outcome ; },
abstract = {IMPORTANCE: Staphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals.<br><br>OBJECTIVES: To investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB.<br><br>This patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n&#x2009;=&#x2009;59); palliative care (n&#x2009;=&#x2009;41); recurrence of SAB (n&#x2009;=&#x2009;9); discharge from the hospital before enrollment (n&#x2009;=&#x2009;77); age younger than 18 years (n&#x2009;=&#x2009;5); duplicate report from a single patient (n&#x2009;=&#x2009;26); late report (n&#x2009;=&#x2009;17); blood culture reported during the washout phase (n&#x2009;=&#x2009;48); and no signed informed consent for other or unknown reasons (n&#x2009;=&#x2009;361).<br><br>INTERVENTIONS: During the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included.<br><br>MAIN OUTCOMES AND MEASURES: Thirty-day all-cause mortality.<br><br>RESULTS: A total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P&#x2009;=&#x2009;.81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P&#x2009;=&#x2009;.62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P&#x2009;=&#x2009;.89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P&#x2009;=&#x2009;.90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P&#x2009;=&#x2009;.01).<br><br>CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB.<br><br>TRIAL REGISTRATION: drks.de Identifier: DRKS00010135.},
}
@article {pmid35743985,
year = {2022},
author = {Ortega, MA and Fraile-Martinez, O and García-Montero, C and Borja-Vergel, S and Torres-Carranza, D and Pekarek, L and Arribas, CB and De León-Luis, JA and Sánchez-Rojo, C and Alvarez-Mon, MA and García-Honduvilla, N and Buján, J and Coca, S and Alvarez-Mon, M and Saez, MA and Guijarro, LG},
title = {Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {58},
number = {6},
pages = {},
pmid = {35743985},
issn = {1648-9144},
support = {MITICAD//Comunidad de Madrid/ ; },
mesh = {*Breast Neoplasms/drug therapy/genetics ; *Carcinoma, Ductal, Breast/diagnosis/drug therapy/genetics ; *Carcinoma, Lobular/pathology ; Cyclin D1/therapeutic use ; Cyclooxygenase 2 ; Female ; Humans ; Insulin Receptor Substrate Proteins/genetics ; },
abstract = {Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.},
}
@article {pmid35739035,
year = {2022},
author = {Clawson, A and Zahir, SF and Stewart, S and Torr, S and Hempenstall, N and Vernon, C and Subedi, S},
title = {Characteristics and outcomes of hospitalised inpatients with indwelling urinary catheter-a retrospective study from a large regional hospital in Queensland.},
journal = {Infection, disease &amp; health},
volume = {27},
number = {4},
pages = {219-226},
doi = {10.1016/j.idh.2022.05.004},
pmid = {35739035},
issn = {2468-0869},
mesh = {Adult ; Humans ; Urinary Catheters/adverse effects ; Catheters, Indwelling/adverse effects ; Retrospective Studies ; Urinary Catheterization/adverse effects ; *Catheter-Related Infections/epidemiology/etiology ; Inpatients ; Queensland/epidemiology ; *Urinary Tract Infections/epidemiology/etiology ; Hospitals ; },
abstract = {BACKGROUND: Indwelling urinary catheters (IDCs) are a common invasive device in hospitalised patients. Their use is associated with increased risks of developing catheter associated urinary tract infections (CAUTI), and blood stream infections (BSI).<br><br>AIMS: To examine the characteristics and outcomes of adult inpatients with an IDC inserted in hospital and identify risk factors for developing CAUTI and BSI.<br><br>METHODS: We performed a retrospective observational study of 430 patients with IDC admitted to medical and surgical units of a leading (tertiary) hospital between Nov 2019 till April 2020. Multiple logistic regression analysis was performed to determine independent risk factors for developing urinary tract infection and blood stream infection.<br><br>RESULTS: The prevalence of CAUTI in our study was 7.4%. Results of multiple logistic regression indicated that with each day of IDC in situ, the likelihood of UTI development increased by 9% (OR 1.09; 95% CI 1.00 to 1.18; p&#xa0;=&#xa0;0.03). Age, gender, and catheter reinsertion were not associated with UTI development.<br><br>CONCLUSIONS: Longer duration of IDC was associated with elevated risk of developing CAUTI. CAUTI rates were higher than some of those previously published. There was no statistical significance in frequency of CAUTI between medical and surgical patients. No statistically significant variables that contributed to the development of BSI were found. Interventions targeted at reducing catheter days should be used to improve CAUTI rates.},
}
@article {pmid35714104,
year = {2022},
author = {Icht, M and Bergerzon-Bitton, O and Ben-David, BM},
title = {Validation and cross-linguistic adaptation of the Frenchay Dysarthria Assessment (FDA-2) speech intelligibility tests: Hebrew version.},
journal = {International journal of language &amp; communication disorders},
volume = {57},
number = {5},
pages = {1023-1049},
pmid = {35714104},
issn = {1460-6984},
mesh = {Aged ; *Dysarthria/psychology ; Humans ; Linguistics ; Reproducibility of Results ; Speech Disorders/complications ; *Speech Intelligibility ; Speech Production Measurement/methods ; Young Adult ; },
abstract = {'Dysarthria' is a group of motor speech disorders resulting from a disturbance in neuromuscular control. Most individuals with dysarthria cope with communicative restrictions due to speech impairments and reduced intelligibility. Thus, language-sensitive measurements of intelligibility are important in dysarthria neurological assessment. The Frenchay Dysarthria Assessment, 2nd edition (FDA-2), is a validated tool for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. The current study conducted a careful culture- and linguistic-sensitive adaption of the two intelligibility subtests of the FDA-2 to Hebrew (words and sentences) and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (acquired dysarthria, n = 15; and developmental dysarthria, n = 19). Analysis indicated that the new subtests were found to be specific and sensitive, valid and reliable, as scores significantly differ between healthy older adults and adults with dysarthria, correlated with other subjective measures of intelligibility, and showed high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers, thus may be an important addition to the speech-language pathologist's toolbox, for clinical work as well as for research purposes. WHAT THIS PAPER ADDS: What is already known on the subject 'Dysarthria' is a group of disorders reflecting impairments in the strength, speed and precision of movements required for adequate control of the various speech subsystems. Reduced speech intelligibility is one of the main consequences of all dysarthria subtypes, irrespective of their underlying cause. Indeed, most individuals with dysarthria cope with communicative restrictions due to speech impairments. Thus, language-sensitive measurements of intelligibility are important in dysarthria assessment. The FDA-2's words and sentences subtests present standardized and validated tools for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. What this paper adds to existing knowledge The lack of assessment tools in Hebrew poses challenges to clinical evaluation as well as research purposes. The current study conducted a careful culture- and linguistic-sensitive adaption of the FDA-2 intelligibility subtests to Hebrew and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (adults with acquired dysarthria, n = 15; and young adults with developmental dysarthria, n = 19). What are the potential or actual clinical implications of this work? Analyses indicated that the new word and sentence subtests are specific, sensitive, valid and reliable. Namely, (1) they successfully differentiate between healthy individuals and individuals with dysarthria; (2) they correlate with other subjective measures of intelligibility; and (3) they show high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers. Thus, they may be an important addition to the speech-language pathologist's toolbox, for clinical and research purposes. The methods described here can be emulated for the adaptation of speech assessment tools to other languages.},
}
@article {pmid35711899,
year = {2022},
author = {Choi, JDW and Hughes, TMD and Marx, G and Boyages, J and Rutovitz, J and Hasovits, C and Parasyn, A and Edirimanne, S and Ngui, NK},
title = {The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.},
journal = {The breast journal},
volume = {2022},
number = {},
pages = {1199245},
pmid = {35711899},
issn = {1524-4741},
mesh = {Australia ; *Breast Neoplasms/drug therapy/genetics/pathology ; Female ; Gene Expression Profiling/methods ; Humans ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Receptors, Estrogen/genetics ; Retrospective Studies ; },
abstract = {INTRODUCTION: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score.<br><br>METHODS: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS&#x2009;<&#x2009;11) (n&#x2009;=&#x2009;10, 14%), intermediate risk (RS 11-25) (n&#x2009;=&#x2009;45, 63%), and high risk (RS&#x2009;>&#x2009;25) (n&#x2009;=&#x2009;16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20&#x2009;mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67%&#x2009;>&#x2009;14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%).<br><br>CONCLUSION: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.},
}
@article {pmid35697697,
year = {2022},
author = {Rebbeck, CA and Xian, J and Bornelöv, S and Geradts, J and Hobeika, A and Geiger, H and Alvarez, JF and Rozhkova, E and Nicholls, A and Robine, N and Lyerly, HK and Hannon, GJ},
title = {Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {3399},
pmid = {35697697},
issn = {2041-1723},
support = {A21143/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/metabolism ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Disease Progression ; Female ; Homeodomain Proteins/genetics/metabolism ; Humans ; Transcription Factors/genetics ; Transcriptome ; },
abstract = {Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.},
}
@article {pmid35695947,
year = {2023},
author = {Gur, N and Zimmerman-Brenner, S and Fattal-Valevski, A and Rotstein, M and Pilowsky Peleg, T},
title = {Group comprehensive behavioral intervention for tics contribution to broader cognitive and emotion regulation in children.},
journal = {European child &amp; adolescent psychiatry},
volume = {32},
number = {10},
pages = {1925-1933},
pmid = {35695947},
issn = {1435-165X},
mesh = {Adolescent ; Child ; Humans ; *Tics/therapy/complications ; *Emotional Regulation ; Severity of Illness Index ; *Tic Disorders/psychology ; *Tourette Syndrome/psychology ; Cognition ; },
abstract = {There is increasing evidence for the effectiveness of behavioral techniques in managing tics in youth with Tourette syndrome and tics disorders (TDs). One such intervention is Comprehensive Behavioral Intervention for Tics (CBIT), which focuses on reducing tic severity by training control and regulation. In view of the regulation deficits characteristic to TDs, in the current study, we aimed to explore the contribution of CBIT beyond tic control, to a wider expression of regulation abilities-cognitive inhibition and emotion regulation. A total of 55 participants with TDs, aged 8-15, who were randomly assigned to group-CBIT or group-Educational Intervention for Tics, were compared on cognitive inhibition tests and use of emotion-regulation strategies, pre- and post-intervention. Whereas on none of the scales a significant interaction effect was found reflecting superiority of CBIT over EIT, repeated measures ANOVA revealed a significant time effect, with post hoc analyses indicating that cognitive inhibition and cognitive reappraisal significantly increased following CBIT intervention only. Within the group-CBIT, the increase in cognitive reappraisal was associated with higher intellectual ability. These findings may lead to a broader understanding of CBIT contribution to more than tic control, but rather to better cognitive and emotional regulation abilities.},
}
@article {pmid35695563,
year = {2022},
author = {Agostinetto, E and Nader-Marta, G and Paesmans, M and Ameye, L and Veys, I and Buisseret, L and Neven, P and Taylor, D and Fontaine, C and Duhoux, FP and Canon, JL and Denys, H and Coussy, F and Chakiba, C and Ribeiro, JM and Piccart, M and Desmedt, C and Ignatiadis, M and Aftimos, P},
title = {ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast.},
journal = {Future oncology (London, England)},
volume = {18},
number = {22},
pages = {2383-2392},
doi = {10.2217/fon-2022-0358},
pmid = {35695563},
issn = {1744-8301},
mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; Cadherins ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/pathology ; Clinical Trials, Phase II as Topic ; Female ; Humans ; Neoadjuvant Therapy ; Protein-Tyrosine Kinases/therapeutic use ; Proto-Oncogene Proteins ; Receptor, ErbB-2/genetics/metabolism ; },
abstract = {Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.},
}
@article {pmid35687769,
year = {2022},
author = {Silva, DJ and Miranda, G and Mesquita, A},
title = {Clinical relevance of receptor conversion in metastatic breast cancer: Case report.},
journal = {Medicine},
volume = {101},
number = {23},
pages = {e29136},
pmid = {35687769},
issn = {1536-5964},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/therapy ; Disease Progression ; Female ; Humans ; Mastectomy ; Quality of Life ; Receptor, ErbB-2/genetics/metabolism ; },
abstract = {INTRODUCTION: Breast cancer comprises several different pathological entities defined by the presence or absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2). During the disease course, the increase in tumor heterogeneity contributes to the discordant expression of estrogen/progesterone receptors and HER2 status between primary and metastatic lesions. We describe a case that demonstrates the clinical relevance of molecular reassessment during metastatic breast cancer progression.<br><br>PATIENT CONCERNS: A 40-year-old Caucasian woman with germline breast cancer gene mutation was referred to a general surgery appointment after breast ultrasound revealed a suspicious nodular lesion in 2012.<br><br>DIAGNOSIS: Ultrasound-guided microbiopsy revealed an invasive ductal carcinoma of no special type, hormone receptor-positive, and HER2-negative.<br><br>INTERVENTIONS: The patient underwent modified radical left mastectomy, adjuvant radiotherapy, chemotherapy, and endocrine therapy. Four years after the diagnosis, HER2 positive lung progression was documented, and the patient received anti-HER2 targeted systemic therapy for 15 months. New disease progression with a triple-negative profile was found, and palliative systemic treatment was changed to carboplatin for 3 months until new progression. Based on the results of the OlympiAD trial, monotherapy with Olaparib 300&#x200a;mg twice daily for 28 days was initiated.<br><br>OUTCOMES: After seven cycles of treatment, patient showed progressive improvement in quality of life and maintained stable disease without significant adverse events.<br><br>CONCLUSION: The clinical relevance of hormone receptor and HER2 status discordance between primary tumors and metastatic lesions has been studied in recent years. This case report illustrates the clinical impact of molecular changes during disease progression and the adaptation of treatment options. This allows for an increase in both survival and quality of life in patients with metastatic breast cancer.},
}
@article {pmid35666367,
year = {2022},
author = {Zhang, Y and Luo, X and Chen, M and Yang, L and Lei, T and Pu, T and Wei, B and Bu, H and Zhang, Z},
title = {Biomarker profile of invasive lobular carcinoma: pleomorphic versus classic subtypes, clinicopathological characteristics and prognosis analyses.},
journal = {Breast cancer research and treatment},
volume = {194},
number = {2},
pages = {279-295},
pmid = {35666367},
issn = {1573-7217},
support = {2022YFS0376//Department of Science and Technology of Sichuan Province/ ; },
mesh = {*Breast Neoplasms ; *Carcinoma, Ductal, Breast/metabolism ; *Carcinoma, Lobular/pathology ; Female ; Humans ; Ki-67 Antigen/genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; },
abstract = {PURPOSE: To compare the clinicopathologic features and prognosis of pleomorphic invasive lobular carcinoma (P-ILC) and classic ILC (C-ILC) according to the biomarker profile.<br><br>METHODS: A total of 667 C-ILCs and 133 P-ILCs between 2011 and 2021 were included. Clinicopathologic features and stromal tumor-infiltrating lymphocytes (sTILs) status were evaluated. P-ILCs were divided into subtypes based on ER/PR and HER2 expression. The overall survival and disease-free survival (DFS) of patients were compared among matched P-ILCs, C-ILCs, and invasive ductal carcinomas (IDCs) with biomarker subtypes.<br><br>RESULTS: Compared to C-ILCs, P-ILCs had greater tumor sizes and stages, fewer ER-positive, more HER2-positive, triple negative (TN), and Ki-67&#x2009;>&#x2009;20% tumors (P&#x2009;<&#x2009;0.05). P-ILCs were subdivided into ER+&#x2009;(63.1%), HER2+&#x2009;(21.1%) and TN (15.8%). ER+&#x2009;P-ILCs were mainly&#xa0;showed trabecular and solid&#xa0;growth patterns. Apocrine and solid features&#xa0;were more strongly associated with HER2+&#x2009;P-ILCs and TN-P-ILCs, respectively.&#xa0;The prognosis of each biomarker group (ER+, HER2+ and TN) differed by subtype. The P-ILC biomarker subtypes had&#xa0;worse prognosis than the same subtypes in the IDC group, while there was&#xa0;no difference between the P-ILC and the C-ILC counterparts. Solid variants of P-ILC&#xa0;had the worst prognosis. Bone was the most common metastatic site in ER+&#x2009;P-ILCs and TN-P-ILCs. HER2+&#x2009;P-ILCs tended to metastasize to the brain and liver. DFS of HER2+&#x2009;P-ILCs and TN-P-ILCs were worse than that of ER+&#x2009;P-ILCs. Lacking lobular carcinoma in situ and sTILs&#x2009;&#x2264;&#x2009;10% were associated with worse survival of ER+&#x2009;P-ILCs and TN-P-ILCs, respectively. For HER2+&#x2009;P-ILCs, Ki-67&#x2009;>&#x2009;20% and sTILs&#x2009;&#x2264;&#x2009;10% were significant factors for lower DFS.<br><br>CONCLUSION: P-ILCs is an aggressive subtype of ILCs. Analyzing the prognostic factors of P-ILCs with heterogeneous morphological and biomarker characteristics is helpful for creating an individualized treatment.},
}
@article {pmid35665642,
year = {2022},
author = {Elangovan, A and Hooda, J and Savariau, L and Puthanmadhomnarayanan, S and Yates, ME and Chen, J and Brown, DD and McAuliffe, PF and Oesterreich, S and Atkinson, JM and Lee, AV},
title = {Loss of E-cadherin Induces IGF1R Activation and Reveals a Targetable Pathway in Invasive Lobular Breast Carcinoma.},
journal = {Molecular cancer research : MCR},
volume = {20},
number = {9},
pages = {1405-1419},
pmid = {35665642},
issn = {1557-3125},
support = {F30 CA250167/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA224909/CA/NCI NIH HHS/United States ; R01 CA252378/CA/NCI NIH HHS/United States ; },
mesh = {*Breast Neoplasms/pathology ; Cadherins/genetics/metabolism ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; Female ; Humans ; Receptor, IGF Type 1/genetics/metabolism ; Signal Transduction ; },
abstract = {UNLABELLED: No special-type breast cancer [NST; commonly known as invasive ductal carcinoma (IDC)] and invasive lobular carcinoma (ILC) are the two major histological subtypes of breast cancer with significant differences in clinicopathological and molecular characteristics. The defining pathognomonic feature of ILC is loss of cellular adhesion protein, E-cadherin (CDH1). We have previously shown that E-cadherin functions as a negative regulator of the IGF1R and propose that E-cadherin loss in ILC sensitizes cells to growth factor signaling that thus alters their sensitivity to growth factor-signaling inhibitors and their downstream activators. To investigate this potential therapeutic vulnerability, we generated CRISPR-mediated CDH1 knockout (CDH1 KO) IDC cell lines (MCF7, T47D, and ZR75.1) to uncover the mechanism by which loss of E-cadherin results in IGF pathway activation. CDH1 KO cells demonstrated enhanced invasion and migration that was further elevated in response to IGF1, serum and collagen I. CDH1 KO cells exhibited increased sensitivity to IGF resulting in elevated downstream signaling. Despite minimal differences in membranous IGF1R levels between wild-type (WT) and CDH1 KO cells, significantly higher ligand-receptor interaction was observed in the CDH1 KO cells, potentially conferring enhanced downstream signaling activation. Critically, increased sensitivity to IGF1R, PI3K, Akt, and MEK inhibitors was observed in CDH1 KO cells and ILC patient-derived organoids.<br><br>IMPLICATIONS: Overall, this suggests that these targets require further exploration in ILC treatment and that CDH1 loss may be exploited as a biomarker of response for patient stratification.},
}
@article {pmid35662504,
year = {2022},
author = {Lone, Z and Benidir, T and Rainey, M and Nair, M and Davicioni, E and Gibb, EA and Williamson, S and Gupta, S and Chaim Ornstein, M and Tendulkar, R and Weight, C and Nguyen, JK and Klein, EA and Mian, OY},
title = {Transcriptomic Features of Cribriform and Intraductal Carcinoma of the Prostate.},
journal = {European urology focus},
volume = {8},
number = {6},
pages = {1575-1582},
doi = {10.1016/j.euf.2022.05.005},
pmid = {35662504},
issn = {2405-4569},
support = {L30 CA220908/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; Prostate ; *Carcinoma, Intraductal, Noninfiltrating/genetics/surgery ; Genomics ; *Prostatic Neoplasms/genetics/surgery ; },
abstract = {BACKGROUND: Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes.<br><br>OBJECTIVE: The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined.<br><br>We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+).<br><br>Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (>0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status.<br><br>RESULTS AND LIMITATIONS: A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p&#xa0;<&#xa0;0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p&#xa0;<&#xa0;0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p&#xa0;<&#xa0;0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p&#xa0;=&#xa0;0.046). Other enriched pathways included E2F targets (NES: 1.69, p&#xa0;=&#xa0;0.031) and oxidative phosphorylation (NES: 1.68, =0 .033).<br><br>CONCLUSIONS: This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures.<br><br>PATIENT SUMMARY: Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.},
}
@article {pmid35661214,
year = {2022},
author = {Sulaj, A and Kopf, S and von Rauchhaupt, E and Kliemank, E and Brune, M and Kender, Z and Bartl, H and Cortizo, FG and Klepac, K and Han, Z and Kumar, V and Longo, V and Teleman, A and Okun, JG and Morgenstern, J and Fleming, T and Szendroedi, J and Herzig, S and Nawroth, PP},
title = {Six-Month Periodic Fasting in Patients With Type 2 Diabetes and Diabetic Nephropathy: A Proof-of-Concept Study.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {107},
number = {8},
pages = {2167-2181},
pmid = {35661214},
issn = {1945-7197},
support = {236360313-SFB 1118//German Research Foundation/ ; //Deutsches Zentrum f&#xfc;r Diabetesforschung/ ; 82DZD07C2G//Diabetes Research/ ; 236360313-SFB 1118//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Albuminuria/etiology ; Biomarkers ; Creatinine ; DNA/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy ; *Diabetic Nephropathies/etiology ; Fasting ; Humans ; *Insulin Resistance ; Lipids ; Receptors, Urokinase Plasminogen Activator ; },
abstract = {CONTEXT: Novel fasting interventions have gained scientific and public attention. Periodic fasting has emerged as a dietary modification promoting beneficial effects on metabolic syndrome.<br><br>OBJECTIVE: Assess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways.<br><br>DESIGN/PARTICIPANTS: Proof-of-concept study where individuals with type 2 diabetes (n = 40) and increased albumin-to-creatinine ratio (ACR) were randomly assigned to receive a monthly fasting-mimicking diet (FMD) or a Mediterranean diet for 6 months with 3-month follow-up.<br><br>MAIN OUTCOMES MEASURES: Change in ACR was assessed by analysis of covariance adjusted for age, sex, weight loss, and baseline value. Prespecified subgroup analysis for patients with micro- vs macroalbuminuria at baseline was performed. Change in homeostatic model assessment for insulin resistance (HOMA-IR), circulating markers of dicarbonyl detoxification (methylglyoxal-derived hydroimidazolone 1, glyoxalase-1, and hydroxyacetone), DNA-damage/repair (phosphorylated histone H2AX), lipid oxidation (acylcarnitines), and senescence (soluble urokinase plasminogen activator receptor) were assessed as exploratory endpoints.<br><br>RESULTS: FMD was well tolerated with 71% to 95% of the participants reporting no adverse effects. After 6 months, change in ACR was comparable between study groups [110.3 (99.2, 121.5) mg/g; P = 0.45]. FMD led to a reduction of ACR in patients with microalbuminuria levels at baseline [-30.3 (-35.7, -24.9) mg/g; P &#x2264; 0.05] but not in those with macroalbuminuria [434.0 (404.7, 463.4) mg/g; P = 0.23]. FMD reduced HOMA-IR [-3.8 (-5.6, -2.0); P &#x2264; 0.05] and soluble urokinase plasminogen activator receptor [-156.6 (-172.9, -140.4) pg/mL; P &#x2264; 0.05], while no change was observed in markers of dicarbonyl detoxification or DNA-damage/repair. Change in acylcarnitines was related to patient responsiveness to ACR improvement. At follow-up only HOMA-IR reduction [-1.9 (-3.7, -0.1), P &#x2264; 0.05]) was sustained.<br><br>CONCLUSIONS: Improvement of microalbuminuria and of markers of insulin resistance, lipid oxidation, and senescence suggest the potential beneficial effects of periodic fasting in type 2 diabetes.},
}
@article {pmid35647336,
year = {2022},
author = {Hamed, MM and Gouida, MS and Abd El-Aziz, SR and El-Sokkary, AMA},
title = {Evaluation PD-L1, CD8 and CD20 as early predictor and tracking markers for breast cancer (BC) in Egypt.},
journal = {Heliyon},
volume = {8},
number = {5},
pages = {e09474},
pmid = {35647336},
issn = {2405-8440},
abstract = {BACKGROUND: Breast cancer (BC) is considered as a common type of cancer threatening women throughout the world. Therefore, development of early predication biomarkers for BC got more concern especially for Egyptian females. This study was aimed to evaluate PD-L1, CD8, and CD20 as early prediction breast cancer biomarkers.<br><br>METHODS: Flow cytometry (FC), immunohistochemistry (IHC), Western Blot, and q-PCR were used to compare PD-L1, CD20, and CD8 levels in tissues and blood samples of Breast Cancer and controls.<br><br>RESULTS: Blood samples showed a significant increase in PD-L1, CD20, and CD8 compared to controls (p&#x2c2;0.005). A Significant correlation was shown between PD-L1, CD8, and CD20 in tissue and breast cancer subtypes. Whereas, invasive lobular carcinoma (ILC) was characterized by superior PD-L1 and CD20 levels compared to invasive ductal carcinoma (IDC). FC studies on Blood showed 83% and 45.7% PD-L1 expressions for IDC and ILC, respectively. CD20 in ILC and IDC were 78.2% and 62.5%, respectively. Nevertheless, CD8 was 74.2% for IDC and 67.7% for ILC. Whereas, FC studies for PD-L1, CD20, and CD8 in ILC in tissues gave 34.4%, 30.2% and 35.1%, respectively. In addition, IDC tissue samples showed 16%, 12.5, and 13.5% for PD-L1, CD20, and CD8. The moderate stage of adenocarcinoma caused expression of PD-L1 within inflammatory cells, while expression was within neoplastic glandular cells in late stage.<br><br>CONCLUSION: PD-L1, CD8, and CD20 are considered as early predictor and tracking markers for breast cancer.},
}
@article {pmid35636710,
year = {2022},
author = {Willemsen, N and Arigoni, I and Studencka-Turski, M and Krüger, E and Bartelt, A},
title = {Proteasome dysfunction disrupts adipogenesis and induces inflammation via ATF3.},
journal = {Molecular metabolism},
volume = {62},
number = {},
pages = {101518},
pmid = {35636710},
issn = {2212-8778},
mesh = {Adipocytes, Brown/metabolism ; *Adipogenesis/genetics ; Animals ; Inflammation/metabolism ; *Lipodystrophy/metabolism ; Mice ; Proteasome Endopeptidase Complex/metabolism ; },
abstract = {OBJECTIVE: Regulation of proteasomal activity is an essential component of cellular proteostasis and function. This is evident in patients with mutations in proteasome subunits and associated regulators, who suffer from proteasome-associated autoinflammatory syndromes (PRAAS). These patients display lipodystrophy and fevers, which may be partly related to adipocyte malfunction and abnormal thermogenesis in adipose tissue. However, the cell-intrinsic pathways that could underlie these symptoms are unclear. Here, we investigate the impact of two proteasome subunits implicated in PRAAS, Psmb4 and Psmb8, on differentiation, function and proteostasis of brown adipocytes.<br><br>METHODS: In immortalized mouse brown pre-adipocytes, levels of Psmb4, Psmb8, and downstream effectors genes were downregulated through reverse transfection with siRNA. Adipocytes were differentiated and analyzed with various assays of adipogenesis, lipogenesis, lipolysis, inflammation, and respiration.<br><br>RESULTS: Loss of Psmb4, but not Psmb8, disrupted proteostasis and adipogenesis. Proteasome function was reduced upon Psmb4 loss, but partly recovered by the activation of Nuclear factor, erythroid-2, like-1 (Nfe2l1). In addition, cells displayed higher levels of surrogate inflammation and stress markers, including Activating transcription factor-3 (Atf3). Simultaneous silencing of Psmb4 and Atf3 lowered inflammation and restored adipogenesis.<br><br>CONCLUSIONS: Our study shows that Psmb4 is required for adipocyte development and function in cultured adipocytes. These results imply that in humans with PSMB4 mutations, PRAAS-associated lipodystrophy is partly caused by disturbed adipogenesis. While we uncover a role for Nfe2l1 in the maintenance of proteostasis under these conditions, Atf3 is a key effector of inflammation and blocking adipogenesis. In conclusion, our work highlights how proteasome dysfunction is sensed and mitigated by the integrated stress response in adipocytes with potential relevance for PRAAS patients and beyond.},
}
@article {pmid35621626,
year = {2022},
author = {Cho, YA and Ko, SY and Suh, YJ and Kim, S and Park, JH and Park, HR and Seo, J and Choi, HG and Kang, HS and Lim, H and Park, HY and Kwon, MJ},
title = {PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy.},
journal = {Current oncology (Toronto, Ont.)},
volume = {29},
number = {5},
pages = {2895-2908},
pmid = {35621626},
issn = {1718-7729},
mesh = {*Asian People/genetics ; B7-H1 Antigen/metabolism ; *Breast Neoplasms/drug therapy/genetics/surgery ; Chemotherapy, Adjuvant ; *Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Microsatellite Instability ; Middle Aged ; Mutation ; Prognosis ; },
abstract = {Background: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy. Methods: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored. Results: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data. Conclusions: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.},
}
@article {pmid35606411,
year = {2022},
author = {Shah, RB and Palsgrove, DN and Desai, NB and Gagan, J and Mennie, A and Raj, G and Hannan, R},
title = {Enrichment of "Cribriform" morphologies (intraductal and cribriform adenocarcinoma) and genomic alterations in radiorecurrent prostate cancer.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {35},
number = {10},
pages = {1468-1474},
doi = {10.1038/s41379-022-01093-9},
pmid = {35606411},
issn = {1530-0285},
mesh = {*Adenocarcinoma/genetics/pathology/radiotherapy ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Genomics ; Humans ; Male ; Neoplasm Grading ; Neoplasm Recurrence, Local/genetics/pathology/radiotherapy ; Prostatectomy ; *Prostatic Neoplasms/genetics/pathology/radiotherapy ; },
abstract = {Locally relapsed prostate cancer (PCa) after radiation therapy (RT) is associated with substantial morbidity and mortality. Morphological and molecular consequences that may contribute to RT resistance and local recurrence remain poorly understood. Locally recurrent PCa tissue from 53 patients with clinically localized PCa who failed with primary RT and subsequently underwent salvage radical prostatectomy (RP) was analyzed for tumor focality, clinicopathological, molecular, and genomic characteristics. Targeted next-generation sequencing with full exon coverage of 1,425 cancer-related genes was performed on 10 representative radiorecurrent PCas exhibiting no RT effect with matched adjacent benign prostate tissue. At RP, 37 (70%) of PCas had no RT effect with the following characteristics: grade group (GG) ≥ 3 (70%), unifocal tumor (75%), extraprostatic disease (78%), lymph node metastasis (8%), and "cribriform" morphologies (84%) [cribriform PCa (78%) or intraductal carcinoma (IDC-P) (61%)] at a median percentage of approximately 80% of tumor volume. In the setting of multifocal tumors (25%) at RP, the cribriform morphologies were restricted to index tumors. Of 32 patients with available pre-RT biopsy information, 16 had GG1 PCa, none had cribriform morphologies at baseline but 81% demonstrated cribriform morphologies at RP. Notable alterations detected in the sequenced tumors included: defects in DNA damage response and repair (DDR) genes (70%) (TP53, BRCA2, PALB2, ATR, POLQ), PTEN loss (50%), loss of 8p (80%), and gain of MYC (70%). The median tumor mutational burden was 4.18 mutations/Mb with a range of 2.16 to 31.86. Our findings suggest that most radiorecurrent PCas are enriched in cribriform morphologies with potentially targetable genomic alterations. Understanding this phenotypic and genotypic diversity of radiorecurrent PCa is critically important to facilitate optimal patient management.},
}
@article {pmid35590107,
year = {2022},
author = {Bean, GR and Najjar, S and Shin, SJ and Hosfield, EM and Caswell-Jin, JL and Urisman, A and Jones, KD and Chen, YY and Krings, G},
title = {Genetic and immunohistochemical profiling of small cell and large cell neuroendocrine carcinomas of the breast.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {35},
number = {10},
pages = {1349-1361},
pmid = {35590107},
issn = {1530-0285},
mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Intraductal, Noninfiltrating ; *Carcinoma, Large Cell/genetics/pathology ; *Carcinoma, Neuroendocrine/pathology ; Carrier Proteins ; Cell Cycle Proteins ; Class I Phosphatidylinositol 3-Kinases/metabolism ; Female ; Humans ; *Neuroendocrine Tumors/pathology ; Proto-Oncogene Proteins/metabolism ; Tumor Suppressor Protein p53/genetics ; },
abstract = {Neuroendocrine carcinomas (NEC) of the breast are exceedingly rare tumors, which are classified in the WHO system as small cell (SCNEC) and large cell (LCNEC) carcinoma based on indistinguishable features from their lung counterparts. In contrast to lung and enteropancreatic NEC, the genomics of breast NEC have not been well-characterized. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of 13 breast NEC (7 SCNEC, 4 LCNEC, 2 NEC with ambiguous small versus large cell morphology [ANEC]). Co-alterations of TP53 and RB1 were identified in 86% (6/7) SCNEC, 100% (2/2) ANEC, and 50% (2/4) LCNEC. The one SCNEC without TP53/RB1 alteration had other p53 pathway aberrations (MDM2 and MDM4 amplification) and was immunohistochemically RB negative. PIK3CA/PTEN pathway alterations and ZNF703 amplifications were each identified in 46% (6/13) NEC. Two tumors (1 SCNEC, 1 LCNEC) were CDH1 mutated. By immunohistochemistry, 100% SCNEC (6/6) and ANEC (2/2) and 50% (2/4) LCNEC (83% NEC) showed RB loss, compared to 0% (0/8) grade 3 neuroendocrine tumors (NET) (p < 0.001) and 38% (36/95) grade 3 invasive ductal carcinomas of no special type (IDC-NST) (p = 0.004). NEC were also more often p53 aberrant (60% vs 0%, p = 0.013), ER negative (69% vs 0%, p = 0.005), and GATA3 negative (67% vs 0%, p = 0.013) than grade 3 NET. Two mixed NEC had IDC-NST components, and 69% (9/13) of tumors were associated with carcinoma in situ (6 neuroendocrine DCIS, 2 non-neuroendocrine DCIS, 1 non-neuroendocrine LCIS). NEC and IDC-NST components of mixed tumors were clonally related and immunophenotypically distinct, lacking ER and GATA3 expression in NEC relative to IDC-NST, with RB loss only in NEC of one ANEC. The findings provide insight into the pathogenesis of breast NEC, underscore their classification as a distinct tumor type, and highlight genetic similarities to extramammary NEC, including highly prevalent p53/RB pathway aberrations in SCNEC.},
}
@article {pmid35585552,
year = {2022},
author = {Oride, Y and Koi, Y and Sasada, T and Kajitani, K and Ohara, M and Kondo, T and Daimaru, Y and Kawamura, S},
title = {Endobronchial ultrasound-guided transbronchial needle aspiration facilitating diagnosis of sarcoidosis in a breast cancer patient with multiple lymphadenopathy: a case report.},
journal = {Journal of medical case reports},
volume = {16},
number = {1},
pages = {194},
pmid = {35585552},
issn = {1752-1947},
mesh = {Aged ; *Breast Neoplasms/complications/pathology ; Bronchoscopy/methods ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods ; Female ; Fluorodeoxyglucose F18 ; Humans ; *Lung Neoplasms/pathology ; Lymph Nodes/diagnostic imaging/pathology ; *Lymphadenopathy/diagnostic imaging/pathology ; Mastectomy ; Mediastinum/pathology ; Receptors, Interleukin-2 ; *Sarcoidosis/complications/diagnosis/pathology ; },
abstract = {BACKGROUND: Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology. Cell-mediated immunity disorder is often found in sarcoidosis patients, and an association between malignant tumors and sarcoidosis has been suggested. Sarcoidosis and malignant disease can occur simultaneously or sequentially, leading to misdiagnosis and mistreatment. Sarcoidosis is diagnosed clinically, radiologically, and histologically. We report herein a case of sarcoidosis diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration from the mediastinal lymph nodes of a breast cancer patient.<br><br>CASE PRESENTATION: The patient was a 70-year-old Asian woman who presented with right breast tumor. A 20-mm movable mass was identified in the inferolateral quadrant of the right breast, and mammography revealed a spiculated mass with calcification. Ultrasonography revealed a mass with internal hypoechogenicity, and biopsy revealed estrogen receptor-positive, human epidermal growth factor receptor 2-positive invasive ductal carcinoma. Positron emission tomography/computed tomography showed multiple lymphadenopathy including mediastinal lymph nodes, with fluorodeoxyglucose accumulation in those nodes suggesting breast cancer metastases. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymph node revealed noncaseous epithelioid granuloma. Due to a history of uveitis and elevated soluble interleukin 2 receptor, lymphadenopathy due to sarcoidosis and stage IIA breast cancer were diagnosed. Right partial mastectomy and axillary lymph node dissection were performed after preoperative chemotherapy. No exacerbation of sarcoidosis symptoms has been observed during treatment.<br><br>CONCLUSION: We report a case of breast cancer in which sarcoidosis could be diagnosed based on endobronchial ultrasound-guided transbronchial needle aspiration, a history of uveitis, and elevated soluble interleukin 2 receptor despite fluorodeoxyglucose positron emission tomography/computed tomography suggesting multiple lymph node metastases. This report emphasizes the importance of differential diagnosis of lymph node involvements in cancer patients.},
}
@article {pmid35578939,
year = {2022},
author = {Higashi, T and Ozawa, K and Takei, S and Takagi, S and Yokoyama, M and Mase, K and Moriya, T and Takeshita, A and Mizutani, M},
title = {[A Case of Postoperative Pulmonary Metastasis of Breast Cancer with Complete Response by Abemaciclib plus Fulvestrant Therapy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {49},
number = {5},
pages = {581-583},
pmid = {35578939},
issn = {0385-0684},
mesh = {Aged ; Aged, 80 and over ; Aminopyridines ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Benzimidazoles ; *Breast Neoplasms/drug therapy/pathology/surgery ; Female ; Fulvestrant/therapeutic use ; Humans ; *Lung Neoplasms/drug therapy/surgery ; Mastectomy ; Neoplasm Recurrence, Local/surgery ; },
abstract = {A 66-year-old woman underwent total mastectomy with level Ⅰ and Ⅱ axillary lymph node dissection for right breast cancer in July 2007. The pathology results indicated the presence of T2N0M0 invasive ductal carcinoma(tubule forming type), that was estrogen receptor-positive and human epidermal growth factor 2-negative. She received postoperative adjuvant therapy with oral anastrozole(ANA)for 5 years. Eleven years after surgery, at the age of 77 years, a chest X-ray examination during a routine health checkup identified a mass shadow in the right lung. Further investigation revealed bilateral multiple lung metastases due to breast cancer recurrence. Histological examination of a tissue obtained by computed tomography(CT)-guided lung biopsy confirmed that the histological type and subtype were identical to those found in the initial surgery. Hence, endocrine therapy with ANA plus CDK4/6 inhibitor was started in November 2018. However, the first CDK4/6 inhibitor, palbociclib, caused severe myelosuppression even when the dose was reduced by 2 levels. Therefore in January 2019, the patient was switched to abemaciclib, with the dose reduced by 1 level initially and then reduced by 2 levels from August 2019. In June 2019, new multiple lung metastases appeared, and the patient was switched from ANA to fulvestrant, after which complete response was achieved in 6 months. CT in June 2021 showed no recurrence, and the patient(now 80-year-old)continues to take abemaciclib plus fulvestrant therapy.},
}
@article {pmid35576836,
year = {2022},
author = {He, S and Jia, Q and Zhou, L and Wang, Z and Li, M},
title = {SIRT5 is involved in the proliferation and metastasis of breast cancer by promoting aerobic glycolysis.},
journal = {Pathology, research and practice},
volume = {235},
number = {},
pages = {153943},
doi = {10.1016/j.prp.2022.153943},
pmid = {35576836},
issn = {1618-0631},
mesh = {*Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Glucose/metabolism ; Glycolysis/genetics ; Humans ; *Sirtuins/metabolism/pharmacology ; },
abstract = {OBJECTIVE: Breast cancer (BC) is the most commonly diagnosed cancer among females and has a poor prognosis, breast invasive ductal carcinoma is the most common histological type. The occurrence and development of BC is closely related to aberrant glucose metabolism. In the hyperglycemic environment caused by abnormal glucose metabolism, hypoxia-inducible factor-1 alpha (HIF-1α) enables tumor cells to absorb large amounts of glucose and enhance glycolysis by inducing the expression of glucose transporter type1 (GLUT1) and glycolysis genes, thus promoting tumor cell proliferation and metastasis. Mitochondrial Sirtuin5 (SIRT5) plays a role in the rewiring of glucose metabolism during the progression of cancers. Thus, we aimed to elucidate whether SIRT5 promotes BC proliferation and metastasis by facilitating aerobic glycolysis in BC.<br><br>METHODS: The expression of SIRT5 in breast carcinoma tissue and cells was evaluated using immunohistochemical staining, western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis to confirm the biological role of SIRT5 in breast carcinoma. We established a stable cell line with SIRT5 knockdown using lentiviral transduction in T47D cells to reduce SIRT5 expression and then evaluated the effect of SIRT5 on cells cultured in the presence of high glucose (4500&#xa0;mg/L) and normal glucose (2000&#xa0;mg/L) concentrations. Cell proliferation was detected using the CCK-8 assay, the cell cycle and cell apoptosis were measured using flow cytometry and Annexin V staining, and cell migration was tested by performing Celigo scratch and Transwell assays. The expression of PKM2, HK2, mTOR and HIF-1&#x3b1;, which play roles in aerobic glycolysis, was investigated using western blot.<br><br>RESULTS: SIRT5 was overexpressed in BC tissues compared with paired normal tissues. Prognostic and OS analyses showed that the SIRT5 expression level was an individual prognostic factor for patients with BC. SIRT5 knockdown inhibited proliferation and metastasis and slightly increased apoptosis in T47D cells under high-glucose conditions. Furthermore, the downregulation of HK2 and HIF-1&#x3b1; caused by SIRT5 knockdown was a high glucose-dependent process, while the downregulation of PKM2 was mediated by a high glucose-independent process.<br><br>CONCLUSIONS: SIRT5 is an independent prognostic factor for BC and contributes to cell proliferation and metastasis in a high glucose-dependent manner to some degree, which might be mediated by promoting aerobic glycolysis.},
}
@article {pmid35567670,
year = {2022},
author = {Wilson, GM and Dinh, P and Pathmanathan, N and Graham, JD},
title = {Ductal Carcinoma in Situ: Molecular Changes Accompanying Disease Progression.},
journal = {Journal of mammary gland biology and neoplasia},
volume = {27},
number = {1},
pages = {101-131},
pmid = {35567670},
issn = {1573-7039},
mesh = {Biomarkers ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Disease Progression ; Female ; Humans ; Tumor Microenvironment/genetics ; },
abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC), whereby if left untreated, approximately 12% of patients develop invasive disease. The current standard of care is surgical removal of the lesion, to prevent potential progression, and radiotherapy to reduce risk of recurrence. There is substantial overtreatment of DCIS patients, considering not all DCIS lesions progress to invasive disease. Hence, there is a critical imperative to better predict which DCIS lesions are destined for poor outcome and which are not, allowing for tailored treatment. Active surveillance is currently being trialed as an alternative management practice, but this approach relies on accurately identifying cases that are at low risk of progression to invasive disease. Two DCIS-specific genomic profiling assays that attempt to distinguish low and high-risk patients have emerged, but imperfections in risk stratification coupled with a high price tag warrant the continued search for more robust and accessible prognostic biomarkers. This search has largely turned researchers toward the tumor microenvironment. Recent evidence suggests that a spectrum of cell types within the DCIS microenvironment are genetically and phenotypically altered compared to normal tissue and play critical roles in disease progression. Uncovering the molecular mechanisms contributing to DCIS progression has provided optimism for the search for well-validated prognostic biomarkers that can accurately predict the risk for a patient developing IDC. The discovery of such markers would modernize DCIS management and allow tailored treatment plans. This review will summarize the current literature regarding DCIS diagnosis, treatment, and pathology.},
}
@article {pmid35547416,
year = {2022},
author = {Smith, PD and Bhenderu, LS and Kommuri, S and Fleener, EE and Hoover, JM},
title = {Treatment of Leptomeningeal Carcinomatosis Following Treatment of Cerebellar Metastasis of HER2+ (Human Epidermal Growth Factor Receptor 2 Positive) Breast Cancer: Case Report and Review of Literature.},
journal = {Cureus},
volume = {14},
number = {4},
pages = {e24008},
pmid = {35547416},
issn = {2168-8184},
abstract = {Leptomeningeal carcinomatosis (LC) after metastasis of breast cancer is a rare occurrence with potentially devastating complications. Treatment options are limited, and there is a lack of literature on this topic. We report the case of a 38-year-old woman with estrogen/progesterone receptor negative (ER/PR-), human epidermal growth factor receptor 2 positive (HER2+) invasive ductal carcinoma of the left breast who underwent bilateral mastectomies with axillary lymph node dissection and chemotherapy treatment. The patient returned 11 months later with persistent headaches. Imaging and resection found cerebellar metastasis of the breast carcinoma. The brain metastasis was treated with further chemotherapy and stereotactic radiosurgery. Follow-up imaging showed the development of small lesions outside the radiation site. Metabolic studies were performed to determine if the new lesions were due to tumor recurrence or radiation necrosis, but the studies were inconclusive as to the etiology of these lesions. The patient later developed LC that was successfully treated with full resolution of the disease using intrathecal trastuzumab. There are currently no consensuses on treatment guidelines for treating LC. Here, we demonstrate successful treatment of LC from an ER/PR-, HER2+ breast carcinoma with intrathecal trastuzumab.},
}
@article {pmid35538300,
year = {2022},
author = {D'Iorio, A and Baiano, C and Maraucci, G and Vitale, C and Amboni, M and Santangelo, G},
title = {A longitudinal study on the effects of COVID-19 pandemic on non-motor symptoms in Parkinson's disease.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {43},
number = {8},
pages = {4605-4609},
pmid = {35538300},
issn = {1590-3478},
mesh = {Aged ; Anhedonia ; *COVID-19 ; Humans ; Longitudinal Studies ; Pandemics ; *Parkinson Disease/complications/diagnosis/epidemiology ; Quality of Life/psychology ; },
abstract = {INTRODUCTION: The COVID-19 pandemic led to psychological consequences on people's mental health, representing a condition of increased vulnerability for the weakest sections of population, including elderly patients with Parkinson's disease (PD). This longitudinal study aimed at exploring the impact of the most frequent non-motor symptoms and their contribute on health-related quality of life of PD patients after the COVID-19 outbreak, in comparison with the pre-pandemic status.<br><br>METHODS: Forty-two non-demented PD patients underwent a first assessment between December 2018 and January 2020 (T0). Then, between March and May 2021 (T1), they were contacted again and asked to complete the second assessment. Levels of global functioning, several non-motor symptoms (i.e. depression, apathy, anxiety, anhedonia) and health-related quality of life were investigated.<br><br>RESULTS: Results of the the paired Wilcoxon signed-rank test showed that at T1, PD patients scored lower on the emotional subscale of the DAS, Z&#x2009;=&#x2009;&#x2009;-&#x2009;2.49; p&#x2009;=&#x2009;0.013; Cohen dz&#x2009;=&#x2009;0.691. Higher scores of the TEPS total score, Z&#x2009;=&#x2009;&#x2009;-&#x2009;2.38; p&#x2009;=&#x2009;0.025; Cohen dz&#x2009;=&#x2009;0.621, and LEDD, Z&#x2009;=&#x2009;&#x2009;-&#x2009;2.63; p&#x2009;=&#x2009;0.008; Cohen dz&#x2009;=&#x2009;0.731, were also reported at T1.<br><br>CONCLUSION: The present study suggested that self-isolation at home might lead to a reduction of apathy and anhedonia in PD patients due to the increase in social support provided by families during COVID-19 restrictions. This evidence brings out the need of a consistent and persistent social support which might be represented by caregivers or/and social assistive robotics.},
}
@article {pmid35538223,
year = {2022},
author = {Simond, AM and Bui, T and Zuo, D and Sanguin-Gendreau, V and Rao, T and Phillips, WA and Cardiff, RD and Muller, WJ},
title = {Physiological expression of PI3K H1047R mutation reveals its anti-metastatic potential in ErbB2-driven breast cancer.},
journal = {Oncogene},
volume = {41},
number = {25},
pages = {3445-3451},
pmid = {35538223},
issn = {1476-5594},
support = {FDN-148373//CIHR/Canada ; },
mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Mutation ; Phosphatidylinositol 3-Kinase/genetics ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Receptor, ErbB-2/genetics ; },
abstract = {p110α is a catalytic subunit of phosphoinositide 3-kinase (PI3K), a major downstream effector of receptor tyrosine kinase ErbB2, that is amplified and overexpressed in 20-30% of breast cancers, 40% of which have an activating mutation in p110α. Despite the high frequency of PIK3CA gain-of-function mutations, their prognostic value is controversial. Here, we employ a knock-in transgenic strategy to restrict the expression of an activated form of ErbB2 and p110α kinase domain mutation (p110α[HR]) in the mammary epithelium. Physiological levels of transgene expression under the control of their endogenous promoters did not result in a major synergistic effect. However, tumors arising in ErbB2/p110α[HR] bi-genic strain metastasized to the lung with significantly reduced capacity compared to tumors expressing ErbB2 alone. The reduced metastasis was further associated with retention of the myoepithelial layer reminiscent of ductal carcinoma in situ (DCIS), a non-invasive stage of human breast cancer. Molecular and biochemical analyses revealed that these poorly metastatic tumors exhibited a significant decrease in phospho-myosin light chain 2 (MLC2) associated with cellular contractility and migration. Examination of human samples for MLC2 activity revealed a progressive increase in cellular contractility between non-invasive DCIS and invasive ductal carcinoma. Collectively, these data argue that p110α[HR] mutation attenuates metastatic behavior in the context of ErbB2-driven breast cancer.},
}
@article {pmid35522890,
year = {2022},
author = {Butcher, MR and White, MJ and Rooper, LM and Argani, P and Cimino-Mathews, A},
title = {MYB RNA In Situ Hybridization Is a Useful Diagnostic Tool to Distinguish Breast Adenoid Cystic Carcinoma From Other Triple-negative Breast Carcinomas.},
journal = {The American journal of surgical pathology},
volume = {46},
number = {7},
pages = {878-888},
doi = {10.1097/PAS.0000000000001913},
pmid = {35522890},
issn = {1532-0979},
mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Adenoid Cystic/diagnosis/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; In Situ Hybridization ; RNA ; *Salivary Gland Neoplasms/pathology ; *Triple Negative Breast Neoplasms/diagnosis/genetics/pathology ; },
abstract = {Breast adenoid cystic carcinoma (AdCC) has overlapping features with basal-like triple-negative breast carcinoma (TNBC), yet carries a more favorable prognosis, and accurate diagnosis is critical. Like salivary gland AdCC, breast AdCC demonstrates recurrent alterations in the MYB gene. Novel chromogenic RNA in situ hybridization (ISH) for MYB has emerged as sensitive and specific for salivary gland AdCC. Here, we evaluate MYB RNA ISH in invasive ductal carcinomas (IDCs) including basal-like TNBC, and in the histologic mimics ductal carcinoma in situ (DCIS) and collagenous spherulosis. MYB RNA ISH was also performed on previously constructed tissue microarrays containing 78 evaluable IDC, including 30 basal-like TNBC (EGFR+ and/or CK5/6+), 19 luminal A (ER+/HER-2-), 12 HER-2+ (ER-/HER-2+), 11 non-basal-like TNBC, and 6 luminal B (ER+/HER-2+). MYB RNA ISH overexpression was seen in 100% (n=18/18) of primary breast AdCC and 10% (n=8/78) of IDC (P<0.0001). MYB RNA ISH was overexpressed in 37% (n=7/19) of luminal A and 8% (n=1/12) of HER-2+ IDC, and in no cases of TNBC or luminal B IDC. The majority (67%, n=8/12) of DCIS and all (n=7) cases of collagenous spherulosis demonstrated overexpression of MYB RNA. MYB gene rearrangement was detected in 67% (n=4/6) evaluable AdCC. Although MYB RNA ISH overexpression cannot be used to distinguish between cribriform DCIS or collagenous spherulosis and AdCC, MYB RNA ISH is absent in basal-like TNBC and rare in ER+ or HER-2+ IDC. MYB RNA ISH could be a useful, sensitive, and rapid diagnostic adjunct in the workup of a triple-negative carcinoma in the breast.},
}
@article {pmid35478129,
year = {2022},
author = {Salih, MM and Higgo, AA and Khalifa, AS and Eed, EM},
title = {Incidence of Epstein-Barr Virus Among Women With Breast Cancer Using Monoclonal Antibodies for Latent Membrane Protein 1 (LMP1).},
journal = {In vivo (Athens, Greece)},
volume = {36},
number = {3},
pages = {1513-1518},
pmid = {35478129},
issn = {1791-7549},
mesh = {Adult ; Antibodies, Monoclonal ; *Antineoplastic Agents, Immunological ; *Breast Neoplasms/epidemiology/pathology ; *Carcinoma, Ductal/complications ; *Epstein-Barr Virus Infections/complications/epidemiology/pathology ; Female ; Herpesvirus 4, Human ; Humans ; Incidence ; Membrane Proteins ; Middle Aged ; Viral Proteins ; },
abstract = {BACKGROUND/AIM: Breast cancer is a common type of cancer in Sudan. Numerous studies propose viral oncogenesis as an etiological factor for breast cancer. The aim of the study was to analyze the presence of the Epstein-Barr virus (EBV) using monoclonal antibodies against latent membrane protein 1 (LAMP1) and determine the correlation between the presence of EBV and clinicopathological characteristics.<br><br>PATIENTS AND METHODS: This study used immunohistochemistry to analyze the presence of EBV in 202 samples from Sudanese women diagnosed with breast cancer. Clinicopathological data were collected from patient records from the Radiation and Isotopes Centre in Khartoum State, Republic of Sudan.<br><br>RESULTS: This study included 202 patients 168 (83.2%), 16 (7.9%), and 18 (8.9%), diagnosed with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. Axillary lymph node metastasis was present in 57 (28.2%) of cases, while 11 patients (5.4%) tested positive for EBV. The mean age of patients was 48.14&#xb1;14.4 years. EBV infection was more frequently detected in invasive ductal carcinoma cases, and EBV positivity was not associated with cancer type, grade, progesterone levels, and HER2 expression. On the other hand, a statistically significant association was found between EBV presence and lymph node involvement, estrogen receptor status, and age group.<br><br>CONCLUSION: EBV may not play a vital role in the pathogenesis of breast carcinoma in Sudanese women.},
}
@article {pmid35456414,
year = {2022},
author = {Zadrożna-Nowak, A and Romanowicz, H and Zadrożny, M and Bryś, M and Forma, E and Smolarz, B},
title = {Analysis of Long Non-Coding RNA (lncRNA) uc.38 and uc.63 Expression in Breast Carcinoma Patients.},
journal = {Genes},
volume = {13},
number = {4},
pages = {},
pmid = {35456414},
issn = {2073-4425},
mesh = {*Breast Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Staging ; *RNA, Long Noncoding/genetics/metabolism ; },
abstract = {Background. The role of the transcribed ultra-conserved regions (T-UCRs) has not yet been fully discovered, but the studies showed some indications that impaired expression of T-UCRS were present in malignant tumors, including breast cancer. Aim. The presented work assessed the expression of two transcribed-ultra conserved regions−uc.63 and uc.38−in breast cancer tissue samples. Material and methods. The research was carried out on a group of 100 patients with invasive ductal carcinoma and 100 patients (test group) with benign tumors in breast tissue (control group). Results. As a result of the statistical analysis, it was shown that the expression of uc.63 and uc.38 is statistically significant, and, accordingly, higher (p < 0.0001) and lower (p < 0.0001) in the test group than in the control group. Statistical dependency analysis of the expression of uc.63 and uc.38 and the selected clinical and pathological factors showed that the expression of uc.63 statistically drops with the patient’s age (p = 0.04), and is higher in the breast cancer tissue type M1 according to the TNM classification (p = 0.036) and in tissues with overexpressed HER2 (p = 0.035). Conclusion. The obtained results of the statistical analysis indicate a relationship between the expression of uc.63 and uc.38 and the occurrence of breast cancer.},
}
@article {pmid35405500,
year = {2022},
author = {Acevedo, DS and Fang, WB and Rao, V and Penmetcha, V and Leyva, H and Acosta, G and Cote, P and Brodine, R and Swerdlow, R and Tan, L and Lorenzi, PL and Cheng, N},
title = {Regulation of growth, invasion and metabolism of breast ductal carcinoma through CCL2/CCR2 signaling interactions with MET receptor tyrosine kinases.},
journal = {Neoplasia (New York, N.Y.)},
volume = {28},
number = {},
pages = {100791},
pmid = {35405500},
issn = {1476-5586},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R01 CA172764/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; *Breast Neoplasms/metabolism/pathology ; *Carcinoma, Ductal, Breast/metabolism/pathology ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Cell Line, Tumor ; *Chemokine CCL2/genetics/metabolism ; Disease Progression ; Female ; Humans ; Neoplasm Recurrence, Local/metabolism/pathology ; *Proto-Oncogene Proteins c-met/metabolism ; *Receptors, CCR2/metabolism ; },
abstract = {With over 60,000 cases diagnosed annually in the US, ductal carcinoma in situ (DCIS) is the most prevalent form of early-stage breast cancer. Because many DCIS cases never progress to invasive ductal carcinomas (IDC), overtreatment remains a significant problem. Up to 20% patients experience disease recurrence, indicating that standard treatments do not effectively treat DCIS for a subset of patients. By understanding the mechanisms of DCIS progression, we can develop new treatment strategies better tailored to patients. The chemokine CCL2 and its receptor CCR2 are known to regulate macrophage recruitment during inflammation and cancer progression. Recent studies indicate that increased CCL2/CCR2 signaling in breast epithelial cells enhance formation of IDC. Here, we characterized the molecular mechanisms important for CCL2/CCR2-mediated DCIS progression. Phospho-protein array profiling revealed that CCL2 stimulated phosphorylation of MET receptor tyrosine kinases in breast cancer cells. Co-immunoprecipitation and proximity ligation assays demonstrated that CCL2-induced MET activity depended on interactions with CCR2 and SRC. Extracellular flux analysis and biochemical assays revealed that CCL2/CCR2 signaling in breast cancer cells enhanced glycolytic enzyme expression and activity. CRISPR knockout and pharmacologic inhibition of MET revealed that CCL2/CCR2-induced breast cancer cell proliferation, survival, migration and glycolysis through MET-dependent mechanisms. In animals, MET inhibitors blocked CCR2-mediated DCIS progression and metabolism. CCR2 and MET were significantly co-expressed in patient DCIS and IDC tissues. In summary, MET receptor activity is an important mechanism for CCL2/CCR2-mediated progression and metabolism of early-stage breast cancer, with important clinical implications.},
}
@article {pmid35397740,
year = {2022},
author = {Ensenyat-Mendez, M and Rünger, D and Orozco, JIJ and Le, J and Baker, JL and Weidhaas, J and Marzese, DM and DiNome, ML},
title = {Epigenetic Signatures Predict Pathologic Nodal Stage in Breast Cancer Patients with Estrogen Receptor-Positive, Clinically Node-Positive Disease.},
journal = {Annals of surgical oncology},
volume = {29},
number = {8},
pages = {4716-4724},
pmid = {35397740},
issn = {1534-4681},
support = {CP17/00188//European Regional Development Fund/ ; PI19/01514)//European Regional Development Fund/ ; UL1TR000124UCLA//CTSI UCLA/ ; },
mesh = {Axilla/pathology ; *Breast Neoplasms/genetics/metabolism/surgery ; Epigenesis, Genetic ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Receptors, Estrogen/metabolism ; Sentinel Lymph Node Biopsy/methods ; },
abstract = {BACKGROUND: Breast cancer patients with clinically positive nodes who undergo upfront surgery are often recommended for axillary lymph node dissection (ALND), yet more than half are found to have limited nodal disease (≤ 3 positive nodes, pN1) at surgery. In this study, we examined the efficiency of molecular classifiers in stratifying patients with clinically positive nodes to pN1 versus > pN1 disease.<br><br>METHODS: We evaluated the clinical and epigenetic data of patients in The Cancer Genome Atlas with estrogen receptor-positive, human epidermal growth factor receptor 2-negative invasive ductal carcinoma who underwent ALND for node-positive disease. Patients were divided into control (pN1, &#x2264;&#x2009;3 positive nodes) and case (>&#x2009;pN1, >&#x2009;3 positive nodes) groups. Machine learning algorithms were trained on 50% of the cohort and validated on the remaining 50% to identify DNA methylation signatures that predict >&#x2009;pN1 disease. Clinical variables and epigenetic signatures were compared.<br><br>RESULTS: Controls (n&#xa0;=&#xa0;34) and case (n&#xa0;=&#xa0;24) cohorts showed similar mean age (56.4&#xa0;&#xb1;&#xa0;12.2 vs. 57.6&#xa0;&#xb1;&#xa0;16.7&#xa0;years; p&#xa0;=&#xa0;0.77), number of nodes removed (16.1&#xa0;&#xb1;&#xa0;7.3 vs. 17.5&#xa0;&#xb1;&#xa0;6.2; p&#xa0;=&#xa0;0.45), tumor grade (p&#xa0;=&#xa0;0.76), presence of lymphovascular invasion (p&#xa0;=&#xa0;0.18), extranodal extension (p&#xa0;=&#xa0;0.17), tumor laterality (p&#xa0;=&#xa0;0.89), and tumor location (p&#xa0;=&#xa0;0.42). The mean number of positive nodes was significantly different (1.76&#xa0;&#xb1;&#xa0;0.82, pN1; 8.83&#xa0;&#xb1;&#xa0;5.36, >&#x2009;pN1; p&#xa0;<&#xa0;0.001). Three epigenetic signatures (EpiSig14, EpiSig13, EpiSig10) based on DNA methylation patterns of the primary tumors demonstrated high accuracy in predicting >&#x2009;pN1 disease (area under the curve 0.98).<br><br>CONCLUSIONS: Epigenetic signatures have an excellent diagnostic accuracy for stratifying nodal disease in patients with clinically positive nodes. Validation of this tool is warranted and may provide an accurate and cost-effective method of identifying patients with predicted low nodal burden who could be spared the morbidity of ALND.},
}
@article {pmid35393463,
year = {2022},
author = {Foroozani, E and Akbari, A and Amanat, S and Rashidi, N and Bastam, D and Ataee, S and Sharifnia, G and Faraouei, M and Dianatinasab, M and Safdari, H},
title = {Adherence to a western dietary pattern and risk of invasive ductal and lobular breast carcinomas: a case-control study.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {5859},
pmid = {35393463},
issn = {2045-2322},
mesh = {*Breast Neoplasms/complications/etiology ; *Carcinoma, Ductal, Breast/complications/etiology ; *Carcinoma, Lobular/epidemiology/etiology/pathology ; Case-Control Studies ; Diet, Western ; Female ; Humans ; },
abstract = {Little is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case-control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients' medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants' dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.},
}
@article {pmid35389579,
year = {2022},
author = {Clarey, D and DiMaio, D and Trowbridge, R},
title = {Deep Sweet Syndrome Secondary to Pegfilgrastim.},
journal = {Journal of drugs in dermatology : JDD},
volume = {21},
number = {4},
pages = {422-424},
doi = {10.36849/JDD.4794},
pmid = {35389579},
issn = {1545-9616},
mesh = {Filgrastim/adverse effects ; Granulocyte Colony-Stimulating Factor/adverse effects ; Humans ; Polyethylene Glycols/adverse effects ; *Sweet Syndrome/chemically induced/diagnosis/drug therapy ; },
abstract = {Sweet syndrome, or acute febrile neutrophilic dermatosis, is a skin condition consisting of erythematous papules and plaques in association with fever, neutrophilia, and a neutrophilic infiltrate that typically involves the papillary dermis. Although development is most commonly idiopathic, medications are also frequently associated with the eruption, notably, the granulocyte colony-stimulating factor (G-CSF), filgrastim. Pegylated G-CSF, despite similar activity, is not commonly reported, with only four published cases. We present a case of drug-induced sweet syndrome with unique histologic features (deep inflammatory infiltrate) in association with the usage of pegfilgrastim in the treatment of invasive ductal carcinoma of the breast. J Drugs Dermatol. 2022;21(4):422-424. doi:10.36849/JDD.4794.},
}
@article {pmid35384456,
year = {2022},
author = {Bhaludin, BN and Tunariu, N and Koh, DM and Messiou, C and Okines, AF and McGrath, SE and Ring, AE and Parton, MM and Sharma, B and Gagliardi, T and Allen, SD and Pope, R and Johnston, SRD and Downey, K},
title = {A review on the added value of whole-body MRI in metastatic lobular breast cancer.},
journal = {European radiology},
volume = {32},
number = {9},
pages = {6514-6525},
pmid = {35384456},
issn = {1432-1084},
mesh = {*Bone Neoplasms/secondary ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Lobular/diagnostic imaging ; Female ; Fluorodeoxyglucose F18 ; Humans ; Magnetic Resonance Imaging/methods ; Positron Emission Tomography Computed Tomography/methods ; Positron-Emission Tomography/methods ; Whole Body Imaging/methods ; },
abstract = {Invasive lobular breast carcinomas (ILC) account for approximately 15% of breast cancer diagnoses. They can be difficult to diagnose both clinically and radiologically, due to their infiltrative growth pattern. The pattern of metastasis of ILC is unusual, with spread to the serosal surfaces (pleura and peritoneum), retroperitoneum and gastrointestinal (GI)/genitourinary (GU) tracts and a higher rate of leptomeningeal spread than IDC. Routine staging and response assessment with computed tomography (CT) can be undertaken quickly and measurements can be reproduced easily, but this is challenging with metastatic ILC as bone-only/bone-predominant patterns are frequently seen and assessment of the disease status is limited in these scenarios. Functional imaging such as whole-body MRI (WBMRI) allows the assessment of bone and soft tissue disease by providing functional information related to differences in cellular density between malignant and benign tissues. A number of recent studies have shown that WBMRI can detect additional sites of disease in metastatic breast cancer (MBC), resulting in a change in systemic anti-cancer therapy. Although WBMRI and fluorodeoxyglucose-positron-emission tomography-computed tomography (FDG-PET/CT) have a comparable performance in the assessment of MBC, WBMRI can be particularly valuable as a proportion of ILC are non-FDG-avid, resulting in the underestimation of the disease extent. In this review, we explore the added value of WBMRI in the evaluation of metastatic ILC and compare it with other imaging modalities such as CT and FDG-PET/CT. We also discuss the spectrum of WBMRI findings of the different metastatic sites of ILC with CT and FDG-PET/CT correlation. KEY POINTS: • ILC has an unusual pattern of spread compared to IDC, with metastases to the peritoneum, retroperitoneum and GI and GU tracts, but the bones and liver are the commonest sites. • WBMRI allows functional assessment of metastatic disease, particularly in bone-only and bone-predominant metastatic cancers such as ILC where evaluation with CT can be challenging and limited. • WBMRI can detect more sites of disease compared with CT, can reveal disease progression earlier and provides the opportunity to change ineffective systemic treatment sooner.},
}
@article {pmid35372457,
year = {2022},
author = {Niknam, K and Safaei, A and Ghaderi, A},
title = {Evaluation of the Prognostic Value of CD56 (140 kDa Isoform) Expression in Breast Cancer Tissues: an Eight-Year Retrospective Study.},
journal = {Iranian biomedical journal},
volume = {26},
number = {3},
pages = {175-182},
pmid = {35372457},
issn = {2008-823X},
mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/pathology ; *CD56 Antigen/genetics ; Female ; Humans ; Mastectomy ; Prognosis ; Protein Isoforms/genetics ; Retrospective Studies ; },
abstract = {BACKGROUND: Identification of specific antigens is highly beneficial for early detection, diagnosis, staging, and outcome prediction of cancer. This study aimed to evaluate the expression and prognostic value of CD56 (140 kDa isoform) in invasive ductal carcinoma (IDC).<br><br>METHODS: Sixty-five patients with IDC who underwent radical surgery or mastectomy as the primary treatment were included. Proper formalin-fixed and paraffin embedded tissue blocks of the patients were prepared and stained by IHC for CD56 (140 kDa isoform) molecule. Chi-square and fisher exact tests were used to compare the results against the clinicopathologic data of patients. Kaplan-Meier and log-rank test were employed to study the prognostic value of the target antigen.<br><br>RESULTS: The expression pattern of CD56 was granular and cytoplasmic. There were significant associations between the intensity of CD56 expression in invasive cells and carcinoma in situ (p = 0.005) and normal ducts (p = 0.010). Among all clinicipathologic parameters, there was only a significant association between the expression of estrogen receptor (ER) and CD56 (p = 0.023). Neither OS (overall survival; p = 0.356) nor DFS (disease-free survival; p = 0.976) had significant correlation with CD56 expression.<br><br>CONCLUSION: Our data indicated that the CD56 marker offers no prognostic value in terms of predicting the OS or DFS for up to eight years after primary surgery. Furthermore, the intensity of its expression is similar between normal, non-invasive, and invasive cells. Considering the generally better outcome of ER+ BC patients than their ER-counterparts, the CD56 marker may be indirectly associated with a more favorable prognosis among IDC patients.},
}
@article {pmid35364707,
year = {2023},
author = {Wu, Y and Sun, S and Huang, Y and Xiao, M and Zhao, X and Lu, X and Xia, B and Qiao, K and Zhang, S and Wu, Q and Xiong, J and Cheng, S and Song, Y},
title = {Correlation analysis between androgen receptor and the clinicopathological features and prognosis of mammary Paget's disease.},
journal = {Journal of cancer research and clinical oncology},
volume = {149},
number = {3},
pages = {1175-1184},
pmid = {35364707},
issn = {1432-1335},
support = {No.HLJ2019010//Ministry of Education Chunhui Project Cooperative Research Project/ ; No.LH2020H120//Heilongjiang Natural Science Foundation of China/ ; No.JJZD2020-04//Haiyan Research Fund of Harbin Medical University Cancer Hospital/ ; },
mesh = {Humans ; Female ; *Paget's Disease, Mammary/complications/metabolism/pathology ; Receptors, Androgen ; Prognosis ; Gene Expression ; *Breast Neoplasms/complications ; *Carcinoma, Ductal, Breast/pathology ; },
abstract = {PURPOSE: Little is known about the prognostic value of androgen receptor (AR) status in mammary Paget's disease (MPD). The purpose of this study was to explore AR status and the distribution of molecular subtypes in MPD as well as the relationship between AR expression and clinicopathological factors and to evaluate its prognostic value.<br><br>METHODS: We analyzed 170 MPD patients of varying subtypes. AR expression was verified by immunohistochemical staining, and the correlations between AR expression and clinicopathological characteristics and survival status were analyzed. We further investigated 91 MPD patients with invasive ductal carcinoma (MPD-IDC).<br><br>RESULTS: AR was expressed in 55.3% of overall MPD patients, and 78.2% had the human epidermal growth factor receptor 2 (HER2) overexpression subtype. AR positivity was significantly correlated with BMI (P&#x2009;=&#x2009;0.037) and pathological N stage (P&#x2009;=&#x2009;0.023). Multivariate analysis indicated that pathological T stage and pathological N stage were independent prognostic factors for overall survival (OS). The positive AR group was significantly associated with better OS (P&#x2009;=&#x2009;0.014). Among 91 MPD-IDC patients, AR was expressed in 56.0%, and 80.0% had the HER2 overexpression subtype. AR positivity was significantly correlated with pathological N stage (P&#x2009;=&#x2009;0.033). Multivariate analysis indicated that AR and pathological T stage were independent prognostic factors for OS. Furthermore, AR positivity was significantly related to better OS (P&#x2009;=&#x2009;0.005) in MPD-IDC patients as well as in patients with the HER2 overexpression subtype (P&#x2009;=&#x2009;0.029).<br><br>CONCLUSION: Our results confirmed that AR is a potential biomarker for evaluating the prognosis of patients.},
}
@article {pmid35348974,
year = {2022},
author = {Sivadas, A and Kok, VC and Ng, KL},
title = {Multi-omics analyses provide novel biological insights to distinguish lobular ductal types of invasive breast cancers.},
journal = {Breast cancer research and treatment},
volume = {193},
number = {2},
pages = {361-379},
pmid = {35348974},
issn = {1573-7217},
support = {MOST 109-2221-E-468-013//Ministry of Science and Technology, Taiwan/ ; MOST 108-2221-E-468-020//Ministry of Science and Technology, Taiwan/ ; 07-Asia-02//Asia University Taiwan/ ; 107-Asia-09//Asia University Taiwan/ ; IA/E/19/1/504945//The Wellcome Trust DBT India Alliance/ ; },
mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/pathology ; Female ; Humans ; *Immediate-Early Proteins ; Prognosis ; Receptors, G-Protein-Coupled ; Survival Analysis ; Tumor Suppressor Proteins ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) treatment is similar to invasive ductal carcinoma (IDC; now invasive carcinoma-no special type, IBC-NST), based on its intrinsic subtype. However, further investigation is required for an integrative understanding of differentially perturbed molecular patterns and pathways in these histotypes.<br><br>METHODS: A dataset of 780 IDC and 201 ILC samples from the TCGA-BRCA project for cross-platform multi-omics was analyzed. We leveraged a consensus approach integrating different bioinformatic algorithms to analyze mutations, CNAs, mRNA, miRNA abundance, methylation, and protein abundance to understand the complex crosstalks that distinguish ILC and IDC samples. A histotype-matched comparison was performed. We performed Cox survival analyses for prognosis based on our identified 53 histotype-specific and four discordant genes.<br><br>RESULTS: Approximately 90% of ILC cases were of the luminal subtype. Somatic mutations in CDH1 were higher in ILC than in IDC (FDR-adjusted p&#x2009;<&#x2009;0.01). Fifty-three significant oncogenic or tumor-suppressive DEGs were identified in a single histotype. PPAR signaling and lipolysis regulation in adipocytes were significantly enriched in ILC tumors. CDH1 protein had the highest differential abundance (AUC: 0.85). Moreover, BTG2, GSTA2, GPR37L1, and PGBD5 amplification was associated with poorer OS in ILC compared with no alteration. RIMS2, NACA4P, MYC, ZFPM2, and POU5F1B amplification showed a lower overall survival in patients with IDC. miR-195 showed an IDC-specific downregulation, causing overexpression of CCNE1. Integrative multi-omics supervised analysis identified 296 differentially expressed genes that successfully distinguished IDC and ILC histotypes.<br><br>CONCLUSIONS: Our findings identify novel molecular candidates that potentially drive and modify the disease differentially among these histotypes.},
}
@article {pmid35348061,
year = {2021},
author = {Khan, NA and Nguyen, ST and Teh, PG and Ranpura, VN and Bhatia, T},
title = {Duodenal Metastasis in Triple-Negative Invasive Ductal Breast Carcinoma With Negative Mammography: A Case Report and Review of the Literature.},
journal = {The Permanente journal},
volume = {25},
number = {},
pages = {},
pmid = {35348061},
issn = {1552-5775},
mesh = {*Breast Neoplasms/diagnostic imaging/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/secondary ; *Carcinoma, Lobular/pathology/secondary ; Female ; Humans ; Mammography ; Receptors, Estrogen ; },
abstract = {Breast cancer metastasis to the gastrointestinal tract is uncommon, and duodenal involvement is exceptionally rare. Those cases that do metastasize are reported to be lobular, with ductal carcinomas comprising only a small percentage of reported cases. Furthermore, these invasive carcinomas are typically estrogen receptor-, progesterone receptor-positive ± human epidermal growth factor receptor 2 malignancies. We present a unique case of a patient with duodenal metastasis as the first sign of metastatic breast cancer. The rarity of this case is highlighted by the fact that the patient had no known breast malignancy, and pathological findings revealed triple-negative invasive ductal carcinoma consistent with primary breast cancer. Diagnostic mammogram and ultrasound were negative for any lesions.},
}
@article {pmid35343265,
year = {2022},
author = {Zhao, CM and Li, LL and Xu, JW and Li, ZW and Shi, P and Jiang, R},
title = {LINC00092 Suppresses the Malignant Progression of Breast Invasive Ductal Carcinoma Through Modulating SFRP1 Expression by Sponging miR-1827.},
journal = {Cell transplantation},
volume = {31},
number = {},
pages = {9636897221086967},
pmid = {35343265},
issn = {1555-3892},
mesh = {*Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; },
abstract = {Breast invasive ductal carcinoma (IDC) is a most common kind of breast cancer (BC), yet to date the corresponding effective therapies are limited. Extensive evidence has indicated that lncRNAs are involved in multiple cancers, and the potential mechanism of lncRNAs, such as LINC00092, mentioned in IDC remains elusive. IDC clinical samples from TCGA database were used to analyze the expression levels of LINC00092, miR-1827 and SFRP1. Kaplan-Meier method was applied to plot the overall survival curves. KEGG and GO were employed to screen the pathway that LINC00092 participated in. Pearson's correlation analysis determined the relationship between LINC00092 and SFRP1. Bioinformatics analysis and dual-luciferase reporter assay examined the association among LINC00092, miR-1827, and SFRP1. Cell counting kit-8, colony formation and transwell assays were performed to detect cell viability, colony formation, and migration and invasion, respectively. Quantitative reverse-transcription polymerase chain reaction and western blot were utilized to investigate the expression at RNA and protein levels. LINC00092 expression was down-regulated in IDC tissues and cells, which was correlated with poor prognosis. Down-regulated LINC00092 facilitated cell proliferation, colony formation, and cell migration and invasion, while up-regulated LINC00092 inhibited cell malignant behaviors. LINC00092/SFRP1 physically bound to miR-1827 in IDC. SFRP1 expression was proportional to LINC00092 expression and inversely proportional to miR-1827 expression. The inhibitory effects of LINC00092 on cell aggressive behaviors were partially regulated by miR-1827/SFRP1. In summary, our results indicated that overexpression of LINC00092 inhibited the development of IDC through modulating miR-1827/SFRP1 axis, suggesting new therapeutic targets to treat IDC.},
}
@article {pmid35340411,
year = {2022},
author = {Du, W and Miao, Y and Zhang, G and Luo, G and Yang, P and Chen, F and Zhang, B and Yang, C and Li, G and Chang, J},
title = {The Regulatory Role of Neuropeptide Gene Glucagon in Colorectal Cancer: A Comprehensive Bioinformatic Analysis.},
journal = {Disease markers},
volume = {2022},
number = {},
pages = {4262600},
pmid = {35340411},
issn = {1875-8630},
mesh = {Biomarkers, Tumor/metabolism ; *Colonic Neoplasms/genetics ; Computational Biology ; Gene Expression Regulation, Neoplastic ; *Glucagon/genetics/metabolism ; Humans ; },
abstract = {BACKGROUND: Colorectal cancer is highly prevalent and causes high global mortality, and glucagon axis has been implicated in colon cancer. The present study is aimed at investigating the regulating mechanisms of glucagon involvement in colorectal cancer.<br><br>METHODS: Publicly available data from the TCGA database was utilized to explore the expression pattern and regulating role of glucagon (GCG) in colorectal cancer (COADREAD) including colon adenocarcinomas (COAD) and rectum adenocarcinomas (READ). Statistical analyses were performed using the R software packages and public web servers. The expression pattern and prognostic significance of GCG gene in pan-cancer and TCGA-COADREAD data were investigated by performing unpaired and paired sample analyses. The association of GCG expression with clinical characteristics was investigated using logistic regression analysis. Univariate cox regression analysis was performed to test the prognostic value of GCG expression for overall survival in COADREAD patients. GCG-significantly correlated genes were obtained. Biological functions and signaling pathways were identified by performing functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Additionally, the potential involvement of GCG in tumor immunity was researched by investigating the correlation between GCG expression and 24 tumor infiltrating immune cells.<br><br>RESULTS: GCG was found to be significantly downregulated in COADREAD tumor samples compared with healthy control samples. GCG gene was shown to be associated with the prognostic outcomes of COADREAD, whereby its upregulation predicted improved survival outcomes. Functional enrichment analysis showed that the top 100 positively and top 100 negatively GCG-correlated genes were mainly enriched in three signaling pathways including ribosome, nitrogen metabolism, and proximal tubule bicarbonate reclamation. The GSEA showed that GCG-significantly correlated genes were mainly enriched in cell cycle-related pathways (reactome cell cycle, reactome cell cycle mitotic, reactome cell cycle checkpoints, reactome M phase, Reactome G2 M DNA damage checkpoint, and Reactome G2 M checkpoints), neuropeptide ligand receptor interaction, RHO GTPases signaling, WNT signaling, RUNX1 signaling, NOTCH signaling, ESR signaling, HCMV infection, and oxidative stress-related signaling. GCG was positively correlated with Th17 cells, pDC, macrophages, TFH cells, iDC, Tem, B cells, dendritic cells, neutrophils, mast cells, and eosinophils and was negatively associated with NK cells.<br><br>CONCLUSIONS: GCG dysregulation with high prognostic value in COADREAD was noted. Several tumor progression-related pathways and tumor immune-modulatory cells were linked to GCG expression in COADREAD. Therefore, GCG may be regarded as a potential therapeutic target for treating colorectal cancer.},
}
@article {pmid35337805,
year = {2022},
author = {Rajabi, F and Mozdarani, H},
title = {Expression level of miR-155, miR-15a and miR-19a in peripheral blood of ductal carcinoma breast cancer patients: Possible bioindicators for cellular inherent radiosensitivity.},
journal = {Experimental and molecular pathology},
volume = {126},
number = {},
pages = {104758},
doi = {10.1016/j.yexmp.2022.104758},
pmid = {35337805},
issn = {1096-0945},
mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/genetics/radiotherapy ; Environmental Biomarkers ; Female ; Humans ; *MicroRNAs ; ROC Curve ; Radiation Tolerance/genetics ; },
abstract = {Examination of cellular radiosensitivity (RS) helps prevent the adverse side-effects of radiotherapy in radioresistant tumors. We aim to study whether miRNA-155 (miR-155), miR-19a and miR-15a can predict inherent RS according to cellular RS in breast cancer (BC) patients. This study was done on the blood samples of 40 invasive ductal carcinoma (IDC) BC patients and 15 healthy women. G2 assay was performed to evaluate cellular RS. To study the expression level of these miRNAs in blood, qRT-PCR was used. The sensitivity and specificity of the studied miRNAs were assessed by the receiver operating characteristic (ROC) curve. The yield of spontaneous (SY) and radiation-induced (RIY) chromatid breaks (CBs) was significantly different between control and patient groups (p < 0.0001). A cut-off value was specified to recognize the patients with cellular RS from those without. Expression of miR-15a was significantly downregulated (p < 0.0001) in BC patients. However, miR-19a showed upregulation in the blood of BC patients. It was also found the expression level of miR-155 and miR-19a were significantly associated with frequency of CBs (FCB) (p < 0.05). ROC curve analysis manifested that the miR-15a and miR-19a differentiate BC patients and healthy women with 0.91 and 0.68 yielding an area under the ROC curve, respectively. miR-155 and miR-19a discriminate between BC patients with and without cellular RS with area under the ROC curve 0.98 and 0.68. Our findings uncovered miR-155 and miR-19a could be applied as a bioindicator to predict cellular radiosensitivity of BC patients.},
}
@article {pmid35324454,
year = {2022},
author = {Wang, K and Schütze, I and Gulde, S and Bechmann, N and Richter, S and Helm, J and Lauseker, M and Maurer, J and Reul, A and Spoettl, G and Klink, B and William, D and Knösel, T and Friemel, J and Bihl, M and Weber, A and Fankhauser, M and Schober, L and Vetter, D and Broglie Däppen, M and Ziegler, CG and Ullrich, M and Pietzsch, J and Bornstein, SR and Lottspeich, C and Kroiss, M and Fassnacht, M and Wenter, VUJ and Ladurner, R and Hantel, C and Reincke, M and Eisenhofer, G and Grossman, AB and Pacak, K and Beuschlein, F and Auernhammer, CJ and Pellegata, NS and Nölting, S},
title = {Personalized drug testing in human pheochromocytoma/paraganglioma primary cultures.},
journal = {Endocrine-related cancer},
volume = {29},
number = {6},
pages = {285-306},
doi = {10.1530/ERC-21-0355},
pmid = {35324454},
issn = {1479-6821},
mesh = {*Adrenal Gland Neoplasms/drug therapy/genetics/metabolism ; Animals ; *Antineoplastic Agents/pharmacology/therapeutic use ; Everolimus/therapeutic use ; Humans ; Mice ; *Paraganglioma/drug therapy/genetics/pathology ; *Pheochromocytoma/drug therapy/genetics/metabolism ; Zoledronic Acid/therapeutic use ; },
abstract = {Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.},
}
@article {pmid35311108,
year = {2022},
author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY},
title = {Anesthesia With Propofol Sedation Reduces Locoregional Recurrence in Patients With Breast Cancer Receiving Total Mastectomy Compared With Non-Propofol Anesthesia.},
journal = {Frontiers in oncology},
volume = {12},
number = {},
pages = {708632},
pmid = {35311108},
issn = {2234-943X},
abstract = {PURPOSE: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.<br><br>PATIENTS AND METHODS: Patients with breast IDC receiving TM were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).<br><br>RESULTS: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.52 (0.28-0.96) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 1, and pN stage 2-3 were 1.16 (1.04-2.08), 1.28 (1.07-2.12), 3.71 (1.82-7.59), 4.67 (1.65-13.18), 1.09 (1.02-1.21), 1.17 (1.03-2.16), 1.10 (1.03-1.33), and 1.22 (1.06-2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64-0.94) compared with that for no adjuvant RT.<br><br>CONCLUSION: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.},
}
@article {pmid35272171,
year = {2022},
author = {Acikgoz, E and Duzagac, F and Guven, U and Yigitturk, G and Kose, T and Oktem, G},
title = {"Double hit" strategy: Removal of sialic acid from the dendritic cell surface and loading with CD44+/CD24-/low cell lysate inhibits tumor growth and metastasis by targeting breast cancer stem cells.},
journal = {International immunopharmacology},
volume = {107},
number = {},
pages = {108684},
doi = {10.1016/j.intimp.2022.108684},
pmid = {35272171},
issn = {1878-1705},
mesh = {Animals ; *Cancer Vaccines/therapeutic use ; Dendritic Cells ; Mice ; N-Acetylneuraminic Acid ; *Neoplasms ; Neoplastic Stem Cells ; },
abstract = {Cancer stem cells (CSCs), which represent the root cause of resistance to conventional treatments, recurrence, and metastasis, constitute the critical point of failure in cancer treatments. Targeting CSCs with dendritic cell (DC)-based vaccines have been an effective strategy, but sialic acids on the surface of DCs limit the interaction with loaded antigens. We hypothesized that removal of sialic acid moieties on immature DCs (iDCs) could significantly affect DC-CSC-antigen loading, thereby leading to DC maturation and improving immune recognition and activity. The lysate of CD44[+]/CD24[-/low] breast CSCs (BCSCs) was pulsed with sialidase-treated DCs to obtain mature dendritic cells (mDCs). The roles of cytoskeletal elements in antigen uptake and dendritic cell maturation were determined by immunofluorescence staining, flow cytometry, and cytokine measurement, respectively. To test the efficacy of the vaccine in vivo, CSCs tumor-bearing mice were immunized with iDC or mDC. Pulsing DCs with antigen increased the expression levels of actin, gelsolin, talin, WASp, and Arp2, especially in podosome-like regions. Compared with iDCs, mDCs expressed high levels of CD40, CD80, CD86 costimulatory molecules and increased IL-12 production. Vaccination with mDC: i) increased CD8+ and CD4 + T-cell numbers, ii) prevented tumor growth with anti-mitotic activity and apoptotic induction, iii) suppressed metastasis by decreasing Snail, Slug, and Twist expressions. This study reveals for the first time that sialic acid removal and loading with CSC antigens induces significant molecular, morphological, and functional changes in DCs and that this new DC identity may be considered for future combined immunotherapy strategies against breast tumors.},
}
@article {pmid35266635,
year = {2022},
author = {Karabid, NM and Wiedemann, T and Gulde, S and Mohr, H and Segaran, RC and Geppert, J and Rohm, M and Vitale, G and Gaudenzi, G and Dicitore, A and Ankerst, DP and Chen, Y and Braren, R and Kaissis, G and Schilling, F and Schillmaier, M and Eisenhofer, G and Herzig, S and Roncaroli, F and Honegger, JB and Pellegata, NS},
title = {Angpt2/Tie2 autostimulatory loop controls tumorigenesis.},
journal = {EMBO molecular medicine},
volume = {14},
number = {5},
pages = {e14364},
pmid = {35266635},
issn = {1757-4684},
mesh = {*Angiopoietin-2/metabolism ; Animals ; Carcinogenesis ; Endothelial Cells/metabolism ; Heterografts ; Humans ; Mice ; Neoplasm Recurrence, Local ; *Pituitary Neoplasms/genetics/metabolism/pathology ; Rats ; Receptor, TIE-2/genetics/metabolism ; Zebrafish ; },
abstract = {Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression.},
}
@article {pmid35262438,
year = {2022},
author = {Jones, VM and Pearce, JB and Khalil, M and Cain, O and Coldren, D and Martin, H and Howard-McNatt, M and Levine, E and Chiba, A},
title = {Upstage Rate of Complex Sclerosing Lesions/Radial Scars.},
journal = {The American surgeon},
volume = {88},
number = {5},
pages = {964-967},
doi = {10.1177/00031348211056282},
pmid = {35262438},
issn = {1555-9823},
mesh = {Biopsy, Large-Core Needle/methods ; Breast/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/pathology/surgery ; Cicatrix/pathology ; Female ; Humans ; Mammography ; Retrospective Studies ; },
abstract = {BACKGROUND: Radial scars (RS) and complex sclerosing lesions (CSL) are breast radiologic findings described as small, stellate lesions causing architectural distortion. This can mimic malignancy. Core needle biopsy (CNB) is often performed. Advances in breast imaging have led to increased detection of RS/CSL. The upstage rate of RS/CSL to in situ or invasive disease is 0-40%. We sought to determine the upstaging rate of RS/CSL to in situ, invasive disease, or high-risk lesion at our institution to create excision guidelines.<br><br>METHODS: The pathology database of a single center was searched for RS/CSL, from January 2013 to September 2020. We included CNB without malignancy or high-risk lesion (eg, atypical ductal hyperplasia). Patient demographics, indications for biopsy, imaging findings, biopsy procedure, and final pathology were collected.<br><br>RESULTS: Forty-four patients were included. 52.3% had CNB for architectural distortion on mammography, 18.2% for mass, 11.4% for calcifications, 2.3% for abnormal MRI, and 15.9% for multiple reasons (eg, calcifications and mass). Most had an ultrasound: 43.2% had no abnormality and 34.1% had a mass. All CNB were vacuum assisted, 65.9% with 9-gauge needle, and averaged 10.0 cores. 77.3% were stereotactic biopsies, 13.6% ultrasound, and 6.8% MRI. 59.1% had excision after CNB. 82.1% of patients did not upstage. One patient upstaged to invasive ductal carcinoma (3.6%) and two patients to high-risk lesion (7.1%).<br><br>DISCUSSION: There was low upstage rate of RS/CSL on excisional biopsy. Centers could consider close surveillance for RS/CSL on CNB. Longer follow-up in cases of deferred excision is needed to ensure oncologic safety.},
}
@article {pmid35260605,
year = {2022},
author = {McLamore, Q and Syropoulos, S and Leidner, B and Hirschberger, G and Young, K and Zein, RA and Baumert, A and Bilewicz, M and Bilgen, A and van Bezouw, MJ and Chatard, A and Chekroun, P and Chinchilla, J and Choi, HS and Euh, H and Gomez, A and Kardos, P and Khoo, YH and Li, M and Légal, JB and Loughnan, S and Mari, S and Tan-Mansukhani, R and Muldoon, O and Noor, M and Paladino, MP and Petrović, N and Selvanathan, HP and Uluğ, &#xd6;M and Wohl, MJ and Yeung, WLV and Burrows, B},
title = {Trust in scientific information mediates associations between conservatism and coronavirus responses in the U.S., but few other nations.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {3724},
pmid = {35260605},
issn = {2045-2322},
support = {2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; },
mesh = {Adult ; Aged ; Attitude ; COVID-19/*epidemiology/virology ; Canada ; Female ; Health Behavior ; Humans ; Indonesia ; Male ; Middle Aged ; *Politics ; Quarantine ; SARS-CoV-2/isolation &amp; purification ; Surveys and Questionnaires ; *Trust ; United States/epidemiology ; },
abstract = {U.S.-based research suggests conservatism is linked with less concern about contracting coronavirus and less preventative behaviors to avoid infection. Here, we investigate whether these tendencies are partly attributable to distrust in scientific information, and evaluate whether they generalize outside the U.S., using public data and recruited representative samples across three studies (Ntotal = 34,710). In Studies 1 and 2, we examine these relationships in the U.S., yielding converging evidence for a sequential indirect effect of conservatism on compliance through scientific (dis)trust and infection concern. In Study 3, we compare these relationships across 19 distinct countries. Although the relationships between trust in scientific information about the coronavirus, concern about coronavirus infection, and compliance are consistent cross-nationally, the relationships between conservatism and trust in scientific information are not. These relationships are strongest in North America. Consequently, the indirect effects observed in Studies 1-2 only replicate in North America (the U.S. and Canada) and in Indonesia. Study 3 also found parallel direct and indirect effects on support for lockdown restrictions. These associations suggest not only that relationships between conservatism and compliance are not universal, but localized to particular countries where conservatism is more strongly related to trust in scientific information about the coronavirus pandemic.},
}
@article {pmid35247977,
year = {2022},
author = {Foster, GJ and Sievert, MAC and Button-Simons, K and Vendrely, KM and Romero-Severson, J and Ferdig, MT},
title = {Cyclical regression covariates remove the major confounding effect of cyclical developmental gene expression with strain-specific drug response in the malaria parasite Plasmodium falciparum.},
journal = {BMC genomics},
volume = {23},
number = {1},
pages = {180},
pmid = {35247977},
issn = {1471-2164},
support = {P01 AI127338/AI/NIAID NIH HHS/United States ; P01 AI127338/NH/NIH HHS/United States ; },
mesh = {Animals ; *Antimalarials/pharmacology/therapeutic use ; Drug Resistance ; Genes, Developmental ; Humans ; *Malaria, Falciparum/parasitology ; *Parasites/genetics ; Plasmodium falciparum ; Protozoan Proteins/genetics ; },
abstract = {BACKGROUND: The cyclical nature of gene expression in the intraerythrocytic development cycle (IDC) of the malaria parasite, Plasmodium falciparum, confounds the accurate detection of specific transcriptional differences, e.g. as provoked by the development of drug resistance. In lab-based studies, P. falciparum cultures are synchronized to remove this confounding factor, but the rapid detection of emerging resistance to artemisinin therapies requires rapid analysis of transcriptomes extracted directly from clinical samples. Here we propose the use of cyclical regression covariates (CRC) to eliminate the major confounding effect of developmentally driven transcriptional changes in clinical samples. We show that elimination of this confounding factor reduces both Type I and Type II errors and demonstrate the effectiveness of this approach using a published dataset of 1043 transcriptomes extracted directly from patient blood samples with different patient clearance times after treatment with artemisinin.<br><br>RESULTS: We apply this method to two publicly available datasets and demonstrate its ability to reduce the confounding of differences in transcript levels due to misaligned intraerythrocytic development time. Adjusting the clinical 1043 transcriptomes dataset with CRC results in detection of fewer functional categories than previously reported from the same data set adjusted using other methods. We also detect mostly the same functional categories, but observe fewer genes within these categories. Finally, the CRC method identifies genes in a functional category that was absent from the results when the dataset was adjusted using other methods. Analysis of differential gene expression in the clinical data samples that vary broadly for developmental stage resulted in the detection of far fewer transcripts in fewer functional categories while, at the same time, identifying genes in two functional categories not present in the unadjusted data analysis. These differences are consistent with the expectation that CRC reduces both false positives and false negatives with the largest effect on datasets from samples with greater variance in developmental stage.<br><br>CONCLUSIONS: Cyclical regression covariates have immediate application to parasite transcriptome sequencing directly from clinical blood samples and to cost-constrained in vitro experiments.},
}
@article {pmid35245349,
year = {2022},
author = {Hophan, SL and Odnokoz, O and Liu, H and Luo, Y and Khan, S and Gradishar, W and Zhou, Z and Badve, S and Torres, MA and Wan, Y},
title = {Ductal Carcinoma In Situ of Breast: From Molecular Etiology to Therapeutic Management.},
journal = {Endocrinology},
volume = {163},
number = {4},
pages = {},
pmid = {35245349},
issn = {1945-7170},
support = {R01 CA202948/CA/NCI NIH HHS/United States ; R01 CA245699/CA/NCI NIH HHS/United States ; UG3 CA256967/CA/NCI NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; },
mesh = {Breast ; *Breast Neoplasms/genetics/therapy ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/therapy ; Female ; Humans ; },
abstract = {Ductal carcinoma in situ (DCIS) makes up a majority of noninvasive breast cancer cases. DCIS is a neoplastic proliferation of epithelial cells within the ductal structure of the breast. Currently, there is little known about the progression of DCIS to invasive ductal carcinoma (IDC), or the molecular etiology behind each DCIS lesion or grade. The DCIS lesions can be heterogeneous in morphology, genetics, cellular biology, and clinical behavior, posing challenges to our understanding of the molecular mechanisms by which approximately half of all DCIS lesions progress to an invasive status. New strategies that pinpoint molecular mechanisms are necessary to overcome this gap in understanding, which is a barrier to more targeted therapy. In this review, we will discuss the etiological factors associated with DCIS, as well as the complexity of each nuclear grade lesion. Moreover, we will discuss the possible molecular features that lead to progression of DCIS to IDC. We will highlight current therapeutic management and areas for improvement.},
}
@article {pmid35238350,
year = {2023},
author = {Egea, V and Megens, RTA and Santovito, D and Wantha, S and Brandl, R and Siess, W and Khani, S and Soehnlein, O and Bartelt, A and Weber, C and Ries, C},
title = {Properties and fate of human mesenchymal stem cells upon miRNA let-7f-promoted recruitment to atherosclerotic plaques.},
journal = {Cardiovascular research},
volume = {119},
number = {1},
pages = {155-166},
pmid = {35238350},
issn = {1755-3245},
mesh = {Mice ; Animals ; Humans ; *MicroRNAs/genetics ; *Plaque, Atherosclerotic ; *Atherosclerosis/genetics ; Cytokines ; Immunologic Factors ; *Mesenchymal Stem Cells ; },
abstract = {AIMS: Atherosclerosis is a chronic inflammatory disease of the arteries leading to the formation of atheromatous plaques. Human mesenchymal stem cells (hMSCs) are recruited from the circulation into plaques where in response to their environment they adopt a phenotype with immunomodulatory properties. However, the mechanisms underlying hMSC function in these processes are unclear. Recently, we described that miRNA let-7f controls hMSC invasion guided by inflammatory cytokines and chemokines. Here, we investigated the role of let-7f in hMSC tropism to human atheromas and the effects of the plaque microenvironment on cell fate and release of soluble factors.<br><br>METHODS AND RESULTS: Incubation of hMSCs with LL-37, an antimicrobial peptide abundantly found in plaques, increased biosynthesis of let-7f and N-formyl peptide receptor 2 (FPR2), enabling chemotactic invasion of the cells towards LL-37, as determined by qRT-PCR, flow cytometry, and cell invasion assay analysis. In an Apoe-/- mouse model of atherosclerosis, circulating hMSCs preferentially adhered to athero-prone endothelium. This property was facilitated by elevated levels of let-7f in the hMSCs, as assayed by ex vivo artery perfusion and two-photon laser scanning microscopy. Exposure of hMSCs to homogenized human atheromatous plaque material considerably induced the production of various cytokines, chemokines, matrix metalloproteinases, and tissue inhibitors of metalloproteinases, as studied by PCR array and western blot analysis. Moreover, exposure to human plaque extracts elicited differentiation of hMSCs into cells of the myogenic lineage, suggesting a potentially plaque-stabilizing effect.<br><br>CONCLUSIONS: Our findings indicate that let-7f promotes hMSC tropism towards atheromas through the LL-37/FPR2 axis and demonstrate that hMSCs upon contact with human plaque environment develop a potentially athero-protective signature impacting the pathophysiology of atherosclerosis.},
}
@article {pmid35231053,
year = {2022},
author = {Troughton, LD and O'Loughlin, DA and Zech, T and Hamill, KJ},
title = {Laminin N-terminus α31 is upregulated in invasive ductal breast cancer and changes the mode of tumour invasion.},
journal = {PloS one},
volume = {17},
number = {3},
pages = {e0264430},
pmid = {35231053},
issn = {1932-6203},
support = {MR/S008632/1/MRC_/Medical Research Council/United Kingdom ; BB/L020513/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P0257731/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal ; Cell Line, Tumor ; Cell Movement ; Female ; Humans ; Immunohistochemistry ; Laminin/genetics/metabolism ; Neoplasm Invasiveness ; },
abstract = {Laminin N-terminus α31 (LaNt α31) is an alternative splice isoform derived from the laminin α3 gene. The LaNt α31 protein is enriched around the terminal duct lobular units in normal breast tissue. In the skin and cornea the protein influences epithelial cell migration and tissue remodelling. However, LaNt α31 has never been investigated in a tumour environment. Here we analysed LaNt α31 in invasive ductal carcinoma and determined its contribution to breast carcinoma invasion. LaNt α31 expression and distribution were analysed by immunohistochemistry in human breast tissue biopsy sections and tissue microarrays covering 232 breast cancer samples. This analysis revealed LaNt α31 to be upregulated in 56% of invasive ductal carcinoma specimens compared with matched normal tissue, and further increased in nodal metastasis compared with the tumour mass in 45% of samples. 65.8% of triple negative cases displayed medium to high LaNt α31 expression. To study LaNt α31 function, an adenoviral system was used to induce expression in MCF-7 and MDA-MB-231 cells. 2D cell migration and invasion into collagen hydrogels were not significantly different between LaNt α31 overexpressing cells and control treated cells. However, LaNt α31 overexpression reduced the proliferation rate of MCF-7 and MDA-MB-231 cells. Moreover, LaNt α31 overexpressing MDA-MB-231 cells displayed a striking change in their mode of invasion into laminin-containing Matrigel; changing from multicellular streaming to individual cellular-invasion. In agreement with these results, 66.7% of the tumours with the highest LaNt α31 expression were non-cohesive. Together these findings indicate that breast cancer-associated changes in LaNt α31 expression could contribute to the processes involved in tumour invasion and may represent a new therapeutic target.},
}
@article {pmid35220223,
year = {2022},
author = {Dantas, FT and Felix-Silva, PH and Angotti-Carrara, HH and Dos-Reis, FJC and Junior, MT and DE-Souza, SLS and Palioto, DB},
title = {A New Method for Obtaining Tumor Interstitial Fluid Applied to Cytokine Analysis of Breast Carcinoma Samples.},
journal = {Anticancer research},
volume = {42},
number = {3},
pages = {1327-1332},
doi = {10.21873/anticanres.15600},
pmid = {35220223},
issn = {1791-7530},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Biopsy, Large-Core Needle ; Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Enzyme-Linked Immunosorbent Assay ; Extracellular Fluid/*immunology ; Female ; Humans ; Interleukin-1beta/*analysis ; Middle Aged ; Tumor Microenvironment ; },
abstract = {BACKGROUND/AIM: Tumor interstitial fluid (TIF), a component of the tumor microenvironment, is a valuable source of molecules and substances that help in diagnosis and prognosis of solid tumors. There is still no consensus on the optimal method for collecting TIF. Therefore, this study aimed to evaluate the effectiveness of a new method of collecting TIF in invasive ductal carcinoma (IDC) samples for cytokine interleukin 1β (IL1β) quantification.<br><br>MATERIALS AND METHODS: Forty women allowed the collection of TIF using absorbent paper strips during the performance of the core biopsy. The samples were stored at a temperature of -80&#xb0;C and then analyzed using an enzyme-linked immunoassay.<br><br>RESULTS: The mean values for IL1&#x3b2; and total protein were 11.39 mg/ml and 2.15 mg/ml, respectively.<br><br>CONCLUSION: it was possible to quantify the cytokine IL1&#x3b2; and the total protein concentration present in the tumor tissue through TIF collection with the use of absorbent paper filters, demonstrating the effectiveness of this new method in oncology.},
}
@article {pmid35207775,
year = {2022},
author = {Huang, CC and Chang, CL and Sun, M and Chiang, MF and Sum, SY and Zhang, J and Wu, SY},
title = {Adjuvant Radiotherapy Is Associated with an Increase in the Survival of Old (Aged over 80 Years) and Very Old (Aged over 90 Years) Women with Breast Cancer Receiving Breast-Conserving Surgery.},
journal = {Journal of personalized medicine},
volume = {12},
number = {2},
pages = {},
pmid = {35207775},
issn = {2075-4426},
abstract = {This study is the first to examine the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM) in old (aged ≥80 years) and very old (aged ≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving surgery. After propensity score matching, adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old and very old women with IDC compared with no use of adjuvant WBRT. Background: To date, no data on the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available for old (aged ≥80 years) and very old (≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving conservative surgery (BCS). Patients and Methods: We enrolled old (≥80 years old) and very old (≥90 years old) women with breast IDC who had received BCS followed by adjuvant WBRT or no adjuvant WBRT. We grouped them based on adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. To reduce the effects of potential confounders when comparing all-cause mortality between the groups, propensity score matching was performed. Results: Overall, 752 older women with IDC received BCS followed by adjuvant WBRT, and 752 with IDC received BCS with no adjuvant WBRT. In multivariable Cox regression analysis, the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) of all-cause death for adjuvant WBRT compared with no adjuvant WBRT in older women with IDC receiving BCS was 0.56 (0.44-0.70). The aHRs (95% CIs) of LRR and DM for adjuvant WBRT were 0.29 (0.19-0.45) and 0.45 (0.32-0.62), respectively, compared with no adjuvant WBRT. Conclusions: Adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old (aged ≥80 years) and very old (aged ≥90 years) women with IDC compared with no adjuvant WBRT.},
}
@article {pmid35200056,
year = {2022},
author = {Hannarici, Z and Yılmaz, A and Buyukbayram, ME and Turhan, A and Tekin, SB and Bilici, M},
title = {Lipegfilgrastim may cause hyperleukocytosis.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {28},
number = {8},
pages = {1902-1905},
doi = {10.1177/10781552221082645},
pmid = {35200056},
issn = {1477-092X},
mesh = {Humans ; Female ; Middle Aged ; Filgrastim/therapeutic use ; *Allopurinol ; *Uric Acid ; Polyethylene Glycols ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Pain/chemically induced ; },
abstract = {INTRODUCTION: Granulocyte colony-stimulating factors (G-CSF) are utilized both in the treatment and prophylaxis of chemotherapy-induced neutropenia. Lipegfilgrastim is a long-acting G-CSF. Albeit it provides ease of administration compared to short-acting GCSFs, some lipegfilgrastim-related adverse events may occur. Bone pain, widespread body pain, and feeling of fever are among common adverse effects, while rare but more serious adverse effects such as leukocytosis, spleen rupture, interstitial pneumonia, acute respiratory distress syndrome, capillary leak syndrome, hypokalemia, and glomerulonephritis may occur as well.<br><br>CASE REPORT: We reported a case of hyperleukocytosis that developed due to prophylactic administration of lipegfilgrastim following the first course of neoadjuvant pertuzumab (840-420&#x2005;mg), trastuzumab (8-6mg/kg), and docetaxel (75&#x2005;mg/m2) in a 45-year-old female patient with a diagnosis of breast invasive ductal carcinoma. The patient, who presented with weakness, loss of appetite, and oral intake disorder, had elevated white blood cell (WBC), lactate dehydrogenase (LDH), and uric acid levels in her test results. Peripheral smear (PS) had a left shift.<br><br>MANAGEMENT AND OUTCOME: Intravenous 0.9% NaCl and peroral allopurinol were started to be administered to the patient. On the ninth day of hospitalization, the patient's clinical manifestation improved, and her WBC, LDH, uric acid, and PS returned to normal. Besides, the progression to tumor lysis syndrome (TLS) was prevented by appropriate hydration and allopurinol treatment. In subsequent chemotherapies (CTs), lipegfilgrastim was discontinued and filgrastim was started. The patient whose hyperleukocytosis did not recur was operated on following neoadjuvant CT. The patient's routine follow-up continues without any problems.<br><br>DISCUSSION: Although lipegfilgrastim-induced hyperleukocytosis has not been reported in the literature, it should be borne in mind that hyperleukocytosis and related complications may occur, as in our case.},
}
@article {pmid35187122,
year = {2022},
author = {Neves, EGA and Koh, CC and Souza-Silva, TG and Passos, LSA and Silva, ACC and Velikkakam, T and Villani, F and Coelho, JS and Brodskyn, CI and Teixeira, A and Gollob, KJ and Nunes, MDCP and Dutra, WO},
title = {T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies.},
journal = {Frontiers in cardiovascular medicine},
volume = {9},
number = {},
pages = {787423},
pmid = {35187122},
issn = {2297-055X},
abstract = {Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4[+], CD8[+], and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8[+] T-cells were highly activated in CCC as compared to IDC, CD4[+] T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.},
}
@article {pmid35178446,
year = {2022},
author = {Li, X and Zhao, G and Mi, X and Xu, T and Li, X and Liu, B},
title = {Ajuba Overexpression Promotes Breast Cancer Chemoresistance and Glucose Uptake through TAZ-GLUT3/Survivin Pathway.},
journal = {BioMed research international},
volume = {2022},
number = {},
pages = {3321409},
pmid = {35178446},
issn = {2314-6141},
mesh = {*Breast Neoplasms/drug therapy/genetics ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Glucose ; Glucose Transporter Type 3/genetics ; Humans ; *LIM Domain Proteins/genetics ; Survivin/genetics ; TEA Domain Transcription Factors/genetics ; },
abstract = {The LIM protein Ajuba has been implicated in the development of human cancers. To date, its expression pattern and biological significance in breast cancers (BC) have not been fully investigated. In the current study, we examined Ajuba protein levels in 93 invasive ductal carcinoma specimens by immunohistochemistry. The Ajuba expression level was elevated in breast cancer tissue compared with normal tissue. Ajuba overexpression is correlated with advanced tumor-node-metastasis (TNM) stage, positive node status, and adverse patient outcomes. The Ajuba protein level was also higher in BC cell lines compared to normal breast epithelial cell line MCF-10A. Ectopically expressed Ajuba in MCF-7 cells stimulated in vitro and in vivo cell growth, invasion, cell cycle progression, and decreased paclitaxel-induced apoptosis. RNA-sequencing (RNA-seq) followed by gene set enrichment analysis (GSEA) analysis showed that Ajuba overexpression regulated the Hippo signaling pathway. Ajuba overexpression also increased glucose uptake and increased expression of TAZ, GLUT3, and Survivin. TAZ knockdown abolished the role of Ajuba on GLUT3 and Survivin induction. The ChIP assay showed that TEAD4, a major TAZ binding transcription factor, could bind to the GLUT3 and Survivin promoter regions. In conclusion, our data demonstrated that elevated Ajuba expression is correlated with poor BC prognosis and regulated malignant behavior through TAZ-GLUT3/Survivin signaling in BC cells.},
}
@article {pmid35159086,
year = {2022},
author = {Pantazopoulos, H and Diop, MK and Grosset, AA and Rouleau-Gagné, F and Al-Saleh, A and Boblea, T and Trudel, D},
title = {Intraductal Carcinoma of the Prostate as a Cause of Prostate Cancer Metastasis: A Molecular Portrait.},
journal = {Cancers},
volume = {14},
number = {3},
pages = {},
pmid = {35159086},
issn = {2072-6694},
abstract = {Intraductal carcinoma of the prostate (IDC-P) is one of the most aggressive types of prostate cancer (PCa). IDC-P is identified in approximately 20% of PCa patients and is associated with recurrence, metastasis, and PCa-specific death. The main feature of this histological variant is the colonization of benign glands by PCa cells. Although IDC-P is a well-recognized independent parameter for metastasis, mechanisms by which IDC-P cells can spread and colonize other tissues are not fully known. In this review, we discuss the molecular portraits of IDC-P determined by immunohistochemistry and genomic approaches and highlight the areas in which more research is needed.},
}
@article {pmid35159065,
year = {2022},
author = {Chen, YC and Chen, WM and Chiang, MF and Shia, BC and Wu, SY},
title = {Association between Pre-Existing Sleep Disorders and Survival Rates of Patients with Breast Cancer.},
journal = {Cancers},
volume = {14},
number = {3},
pages = {},
pmid = {35159065},
issn = {2072-6694},
abstract = {PURPOSE: To investigate the effects of pre-existing sleep disorders on the survival outcomes of women receiving standard treatments for breast invasive ductal carcinoma (IDC).<br><br>METHODS: We recruited patients from the Taiwan Cancer Registry Database who had received surgery for clinical stage I-III breast IDC. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching.<br><br>RESULTS: In the multivariate Cox regression analysis, the adjusted hazard ratio for all-cause mortality for Group 1 compared with Group 2 was 1.51 (95% confidence interval: 1.19, 1.91; p < 0.001).<br><br>CONCLUSION: Our study demonstrated that the sleep disorder group had poorer survival rates than the non-sleep disorder group in breast cancer. Therefore, patients should be screened and evaluated for pre-existing sleep disorders prior to breast surgery, with such disorders serving as a predictor of survival in patients with breast cancer. Future studies may investigate the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with breast cancer.},
}
@article {pmid35155685,
year = {2022},
author = {Zhang, L and Du, J and Song, Q and Zhang, C and Wu, X},
title = {A Novel In Situ Dendritic Cell Vaccine Triggered by Rose Bengal Enhances Adaptive Antitumour Immunity.},
journal = {Journal of immunology research},
volume = {2022},
number = {},
pages = {1178874},
pmid = {35155685},
issn = {2314-7156},
mesh = {Adaptive Immunity ; Animals ; Antigen Presentation ; Antigens, Neoplasm/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cancer Vaccines/*immunology ; Cell Differentiation ; Dendritic Cells/*immunology/transplantation ; Humans ; Immunization ; Immunotherapy/*methods ; Lung Neoplasms/*immunology/secondary ; Lymphocytes, Tumor-Infiltrating/*immunology ; Melanoma/*immunology/pathology ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Rose Bengal/metabolism ; },
abstract = {Dendritic cell- (DC-) based vaccination has emerged as a promising antitumour immunotherapy. However, overcoming immune tolerance and immunosuppression in the tumour microenvironment (TME) is still a great challenge. Recent studies have shown that Rose Bengal (RB) can effectively induce immunogenic cell death (ICD) in cancer cells, presenting whole tumour antigens for DC processing and presentation. However, the synergistic antitumour effect of combining intralesional RB with immature DCs (RB-iDCs) remains unclear. In the present study, we investigated whether RB-iDCs have superior antitumour effects compared with either single agent and evaluated the immunological mechanism of RB-iDCs in a murine lung cancer model. The results showed that intralesional RB-iDCs suppressed subcutaneous tumour growth and lung metastasis, which resulted in 100% mouse survival and significantly increased TNF-α production by CD8[+] T cells. These effects were closely related to the induction of the expression of distinct ICD hallmarks by RB in both bulk cancer cells and cancer stem cells (CSCs), especially calreticulin (CRT), thus enhancing immune effector cell (i.e., CD4[+], CD8[+], and memory T cells) infiltration and attenuating the accumulation of immunosuppressive cells (i.e., Tregs, macrophages, and myeloid-derived suppressor cells (MDSCs)) in the TME. This study reveals that the RB-iDC vaccine can synergistically destroy the primary tumour, inhibit distant metastasis, and prevent tumour relapse in a lung cancer mouse model, which provides important preclinical data for the development of a novel combinatorial immunotherapy.},
}
@article {pmid35151355,
year = {2022},
author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY},
title = {Adjuvant postmastectomy radiotherapy might be associated with better survival in women with heart failure receiving total mastectomy.},
journal = {Radiation oncology (London, England)},
volume = {17},
number = {1},
pages = {33},
pmid = {35151355},
issn = {1748-717X},
mesh = {Adult ; Aged ; Female ; Heart Failure/*complications ; Humans ; *Mastectomy, Simple ; Middle Aged ; Radiotherapy, Adjuvant ; Survival Rate ; Unilateral Breast Neoplasms/*complications/*mortality/*radiotherapy/surgery ; Young Adult ; },
abstract = {BACKGROUND: To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).<br><br>PATIENTS AND METHODS: We enrolled 646 women with left-breast IDC at clinical stages I-IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).<br><br>RESULTS: In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37-0.74) was a significant independent prognostic factor for all-cause death (P&#x2009;=&#x2009;0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79-0.96; P&#x2009;=&#x2009;0.0356) and 0.89 (0.54-1.50; P&#x2009;=&#x2009;0.6854), respectively, compared with the nonadjuvant PMRT group.<br><br>CONCLUSION: Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.},
}
@article {pmid35137951,
year = {2022},
author = {Weiser, R and Polychronopoulou, E and Hatch, SS and Haque, W and Ghani, HA and He, J and Kuo, YF and Gradishar, WJ and Klimberg, VS},
title = {Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21-gene recurrence score: A National Cancer Database analysis.},
journal = {Cancer},
volume = {128},
number = {9},
pages = {1738-1747},
doi = {10.1002/cncr.34127},
pmid = {35137951},
issn = {1097-0142},
mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/drug therapy/genetics ; *Carcinoma, Lobular/drug therapy/genetics/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Prognosis ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients.<br><br>METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy.<br><br>RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2&#xa0;&#xb1;&#xa0;9.1 and 57.2&#xa0;&#xb1;&#xa0;9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P&#xa0;<&#xa0;.0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease.<br><br>CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease.<br><br>LAY SUMMARY: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.},
}
@article {pmid35130270,
year = {2022},
author = {Khanam, R and Applegate, J and Nisar, I and Dutta, A and Rahman, S and Nizar, A and Ali, SM and Chowdhury, NH and Begum, F and Dhingra, U and Tofail, F and Mehmood, U and Deb, S and Ahmed, S and Muhammad, S and Das, S and Ahmed, S and Mittal, H and Minckas, N and Yoshida, S and Bahl, R and Jehan, F and Sazawal, S and Baqui, AH},
title = {Burden and risk factors for antenatal depression and its effect on preterm birth in South Asia: A population-based cohort study.},
journal = {PloS one},
volume = {17},
number = {2},
pages = {e0263091},
pmid = {35130270},
issn = {1932-6203},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Adult ; Asia/epidemiology ; Bangladesh/epidemiology ; Cohort Studies ; Depression/complications/*epidemiology ; Female ; Humans ; Infant, Newborn ; Pakistan/epidemiology ; Pregnancy ; Pregnancy Complications/epidemiology/psychology ; Pregnancy Outcome/*epidemiology/psychology ; Premature Birth/*epidemiology ; Prenatal Care/statistics &amp; numerical data ; Risk Factors ; Young Adult ; },
abstract = {INTRODUCTION: Women experience high rates of depression, particularly during pregnancy and the postpartum periods. Using population-based data from Bangladesh and Pakistan, we estimated the burden of antenatal depression, its risk factors, and its effect on preterm birth.<br><br>METHODS: The study uses the following data: maternal depression measured between 24 and 28 weeks of gestation using the 9-question Patient Health Questionnaire (PHQ-9); data on pregnancy including an ultrasound before 19 weeks of gestation; data on pregnancy outcomes; and data on woman's age, education, parity, weight, height, history of previous illness, prior miscarriage, stillbirth, husband's education, and household socioeconomic data collected during early pregnancy. Using PHQ-9 cutoff score of &#x2265;12, women were categorized into none to mild depression or moderate to moderately severe depression. Using ultrasound data, preterm birth was defined as babies born <37 weeks of gestation. To identify risk ratios (RR) for antenatal depression, unadjusted and adjusted RR and 95% confidence intervals (CI) were calculated using log- binomial model. Log-binomial models were also used for determining the effect of antenatal depression on preterm birth adjusting for potential confounders. Data were analyzed using Stata version 16 (StataCorp LP).<br><br>RESULTS: About 6% of the women reported moderate to moderately severe depressive symptoms during the antenatal period. A parity of &#x2265;2 and the highest household wealth status were associated with an increased risk of depression. The overall incidence of preterm birth was 13.4%. Maternal antenatal depression was significantly associated with the risk of preterm birth (ARR, 95% CI: 1.34, 1.02-1.74).<br><br>CONCLUSION: The increased risk of preterm birth in women with antenatal depression in conjunction with other significant risk factors suggests that depression likely occurs within a constellation of other risk factors. Thus, to effectively address the burden of preterm birth, programs require developing and providing integrated care addressing multiple risk factors.},
}
@article {pmid35114136,
year = {2022},
author = {Bechmann, N and Barthel, A and Schedl, A and Herzig, S and Varga, Z and Gebhard, C and Mayr, M and Hantel, C and Beuschlein, F and Wolfrum, C and Perakakis, N and Poston, L and Andoniadou, CL and Siow, R and Gainetdinov, RR and Dotan, A and Shoenfeld, Y and Mingrone, G and Bornstein, SR},
title = {Sexual dimorphism in COVID-19: potential clinical and public health implications.},
journal = {The lancet. Diabetes &amp; endocrinology},
volume = {10},
number = {3},
pages = {221-230},
pmid = {35114136},
issn = {2213-8595},
support = {CH/16/3/32406/BHF_/British Heart Foundation/United Kingdom ; RG/16/14/32397/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {*COVID-19/complications/epidemiology/physiopathology ; Female ; *Health Status Disparities ; Humans ; Hypothalamo-Hypophyseal System ; Male ; Pituitary-Adrenal System ; Public Health ; *Sex Characteristics ; Post-Acute COVID-19 Syndrome ; },
abstract = {Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.},
}
@article {pmid35077053,
year = {2022},
author = {Yariv, O and Benouaich-Amiel, A and Kab, T and Yust-Katz, S and Yerushalmi, R and Goldvaser, H},
title = {[RAPIDLY PROGRESSING PARAPARESIS AND LOSS OF SENSATION BELOW T10 DURING NEOADJUVANT CHEMOTHERAPY FOR BREAST CANCER].},
journal = {Harefuah},
volume = {161},
number = {1},
pages = {14-16},
pmid = {35077053},
issn = {0017-7768},
mesh = {Adult ; *Breast Neoplasms/diagnosis/drug therapy ; Female ; *Guillain-Barre Syndrome ; Humans ; Neoadjuvant Therapy ; Paraparesis ; Sensation ; },
abstract = {A 35 years old woman was diagnosed with clinical stage 2, grade 3, hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative invasive ductal carcinoma, with ki-67 of 60%. She was treated with neoadjuvant chemotherapy with dose dense adriamycin and cyclophosphamide followed by paclitaxel. Six days following the third cycle of paclitaxel the patient presented with rapidly progressive weakness, proximal paresthesia and decreased sensation in both legs. Physical examination revealed hypoesthesia below level, proximal and distal weakness in both lower limbs and absence of reflexes. MRI of the spine demonstrated diffuse leptomeningeal enhancement from T11 to S1 including the cauda equina roots. The rapidly progressive neurological symptoms and the MRI findings were initially interpreted as leptomeningeal spread. High dose dexamethasone was promptly initiated and the patient was urgently planned for radiotherapy and received the first fraction of 3 Gy to level T11-S1. Further workup included lumbar puncture which showed elevated protein level (350 mg/dL), negative cytology for malignancy and EMG which demonstrated demyelinating injury compatible with Guillain-Barre syndrome (GBS). A diagnosis of GBS was made and treatment with intravenous immunoglobulins (IVIG) was initiated, followed by a gradual clinical improvement. Two months after the initial diagnosis, she had a near complete resolution of her neurological deficits. This case illustrates both the tendency to ascribe new symptoms and clinical findings in cancer patients to progressive disease, and the importance of keeping a wide differential diagnosis for non-cancer etiologies when treating our patients.},
}
@article {pmid35074971,
year = {2022},
author = {Kumari, S and Mishra, S and Husain, N and Verma, T and Tiwari, V and Kaif, M and Agarwal, A and Rastogi, M and Shukla, S and Sonkar, AA},
title = {Comparison of circulating DNA in malignant neoplasia from diverse locations: Investigating a diagnostic role.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {65},
number = {1},
pages = {93-99},
doi = {10.4103/IJPM.IJPM_474_20},
pmid = {35074971},
issn = {0974-5130},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/genetics ; Brain Neoplasms/blood/diagnosis/genetics ; Carcinoma, Squamous Cell/blood/diagnosis/genetics ; Cell-Free Nucleic Acids/*blood ; Female ; Gallbladder Neoplasms/blood/diagnosis/genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms/blood/classification/*diagnosis/*genetics ; Young Adult ; },
abstract = {CONTEXT: Circulating free DNA (cfDNA) analysis has emerged as novel noninvasive diagnostic biomarker in several solid tumors. Raised levels have been reported in several malignancies and may correlate with clinicopathological and treatment response. The current study was designed to assess the diagnostics of cfDNA in different tumor types of malignancies correlating with tumor (T), nodes (N), and metastases (M) stage.<br><br>DESIGN: Serum samples were collected from treatment na&#xef;ve cases with histologically diagnosed tumors including 23 brain tumors, 48 breasts, 50 gallbladder carcinoma (GBC), 13 lungs, 68 oral squamous cell carcinoma (OSCC), and 25 normal controls. CfDNA was quantified with real-time polymerase chain reaction (PCR), Invasive ductal carcinoma (IDC) using beta-globin gene amplification. Cut off values for diagnostics were calculated using receiver operating curve analysis.<br><br>RESULTS: Contrary to other cfDNA studies where it was postulated that cfDNA would not cross the blood-brain barrier and reach the systemic circulation, we found detectable cfDNA in glioma with median (Q1-Q3) of 349.22 ng/ml (19.87-1276.58). Median cfDNA concentration in breast, gallbladder, lung, oral and normal controls was 328.72 (128.38-624.44), 778.50 (589.88-1864.35), 348.73 (194.67-483.61), 386.27 (47.88-959.67), and 74.12 (49.66-120.00), respectively. Grades I and II glioma had significantly lower levels compared to Grades III and IV (P = 0.0001). Significant difference in median cfDNA values in IDC and GBC was observed with increasing tumor grades, stage, T stage, nodal stage and metastasis and with stage of OSCC cases.<br><br>CONCLUSION: CfDNA levels showed good diagnostic discrimination in glioma, GBC, breast, lung carcinoma, and OSCC. Significant increase in titers was evident with increase in cancer stage from I to IV in breast, GBC and OSCC.},
}
@article {pmid35071526,
year = {2022},
author = {Wang, L and Jiang, Q and He, MY and Shen, P},
title = {HER2 changes to positive after neoadjuvant chemotherapy in breast cancer: A case report and literature review.},
journal = {World journal of clinical cases},
volume = {10},
number = {1},
pages = {260-267},
pmid = {35071526},
issn = {2307-8960},
abstract = {BACKGROUND: As the most common cancer in women, breast cancer is the leading cause of death. Most patients are initially diagnosed as stage I-III. Among those without distant metastases, 64% are local tumors and 27% are regional tumors. Patients in stage IIA-IIIC and those who meet the breast-conserving criterion with the exception of tumor size can consider neoadjuvant chemotherapy (NACT). It is worth noting that the status of tumor cell biomarkers is not consistently static. Endocrine-related estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) encoded by erythroblastic leukemia viral oncogene homolog 2 gene can all alter from positive to negative or vice versa, especially in luminal B subtype after NACT. In addition, determination of HER2 status currently mainly relies on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), but FISH is commonly used when the result of IHC is uncertain. HER2 is regarded as negative when the IHC result is 0/1+ without the addition of FISH. To the best of our knowledge, this is the first report of a case harboring HER2 status transformation and IHC1+ with positive amplification by FISH after NACT.<br><br>CASE SUMMARY: A 49-year-old woman discovered a mass in her right breast and underwent diagnostic workup. Biopsies of the right breast lesion and axillary lymph nodes were obtained. The results pointed to invasive ductal carcinoma with the IHC result for ER (80%), PR (60%), Ki-67 (20%) and ambiguous expression of HER2 (IHC 2+) with negative amplification by FISH (HER2/CEP17 ratio of 1.13). She underwent surgery after NACT. The pathological findings of the surgically resected sample supported invasive ductal carcinoma with the tumor measuring 1.1 cm &#xd7; 0.8 cm &#xd7; 0.5 cm and had spread to one of fifteen dissected lymph nodes. Retesting of the specimen showed that the tumor was positive for ER (2+, 85%) and PR (2+, 10%) but negative for HER2 by IHC (1+). Also Ki-67 had dropped to 2%. The patient was regularly monitored every 3 mo without evidence of recurrence.<br><br>CONCLUSION: Biomarker status should be reassessed after NACT especially in luminal subtypes.},
}
@article {pmid35064153,
year = {2022},
author = {Tewari, SG and Kwan, B and Elahi, R and Rajaram, K and Reifman, J and Prigge, ST and Vaidya, AB and Wallqvist, A},
title = {Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {1167},
pmid = {35064153},
issn = {2045-2322},
support = {T32 AI138953/AI/NIAID NIH HHS/United States ; R01 AI154499/AI/NIAID NIH HHS/United States ; R01 AI132508/AI/NIAID NIH HHS/United States ; T32 AI007417/AI/NIAID NIH HHS/United States ; R01 AI125534/AI/NIAID NIH HHS/United States ; R01 AI098413/AI/NIAID NIH HHS/United States ; },
mesh = {Antimalarials/*pharmacology/therapeutic use ; Carbohydrate Metabolism/drug effects/genetics ; Dose-Response Relationship, Drug ; Drug Resistance ; Erythrocytes/parasitology ; Gene Expression Profiling ; Humans ; Inositol/biosynthesis ; Malaria, Falciparum/*drug therapy/parasitology ; Metabolomics ; Oxidative Stress ; Plasmodium falciparum/*drug effects/genetics/metabolism ; Pyrazoles/*pharmacology/therapeutic use ; RNA, Protozoan/biosynthesis ; },
abstract = {Due to the recurring loss of antimalarial drugs to resistance, there is a need for novel targets, drugs, and combination therapies to ensure the availability of current and future countermeasures. Pyrazoleamides belong to a novel class of antimalarial drugs that disrupt sodium ion homeostasis, although the exact consequences of this disruption in Plasmodium falciparum remain under investigation. In vitro experiments demonstrated that parasites carrying mutations in the metabolic enzyme PfATP4 develop resistance to pyrazoleamide compounds. However, the underlying mechanisms that allow mutant parasites to evade pyrazoleamide treatment are unclear. Here, we first performed experiments to identify the sublethal dose of a pyrazoleamide compound (PA21A092) that caused a significant reduction in growth over one intraerythrocytic developmental cycle (IDC). At this drug concentration, we collected transcriptomic and metabolomic data at multiple time points during the IDC to quantify gene- and metabolite-level alterations in the treated parasites. To probe the effects of pyrazoleamide treatment on parasite metabolism, we coupled the time-resolved omics data with a metabolic network model of P. falciparum. We found that the drug-treated parasites adjusted carbohydrate metabolism to enhance synthesis of myoinositol-a precursor for phosphatidylinositol biosynthesis. This metabolic adaptation caused a decrease in metabolite flux through the pentose phosphate pathway, causing a decreased rate of RNA synthesis and an increase in oxidative stress. Our model analyses suggest that downstream consequences of enhanced myoinositol synthesis may underlie adjustments that could lead to resistance emergence in P. falciparum exposed to a sublethal dose of a pyrazoleamide drug.},
}
@article {pmid35046349,
year = {2021},
author = {Adachi, K and Kubota, H and Suzuki, S and Hirano, T and Ishibashi, N and Sakurai, K},
title = {[Hereditary Breast and Ovarian Cancer(HBOC)in a Young Adult-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {48},
number = {13},
pages = {1843-1845},
pmid = {35046349},
issn = {0385-0684},
mesh = {Adult ; Axilla ; *Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Lymph Nodes ; Mastectomy ; *Ovarian Neoplasms/genetics/surgery ; },
abstract = {We report a case of hereditary breast and ovarian cancer(HBOC)in a young adult. A 31-year-old woman consulted at our hospital for a lump on her left breast. Ultrasonography revealed an irregular-shaped mass. A core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. There were multiple enlarged lymph nodes in the axilla and internal mammary areas but no evidence of metastasis. She underwent mastectomy and axially dissection. The pathological findings from the surgically resected specimens showed scirrhous carcinoma positive for ER and PgR and negative for HER2/neu protein expression. The tumor size was 16 mm, and 3 axillary lymph node metastases were seen. We identified the pathological stage as T1cN3bM0, stage ⅢC. She received chemotherapy, radiotherapy, and endocrine therapy after surgery. At present, 1 year after surgery, the patient is alive without recurrence. With a low age of onset and a family history of ovarian cancer, she was diagnosed with HBOC as a result of breast cancer susceptibility gene(BRCA)genetic testing. In addition to the recommended surveillance, prophylactic surgery will be performed in the future.},
}
@article {pmid35029184,
year = {2022},
author = {Hussain, M and Abbott, M and Zargham, R and Pabani, A and Khan, OF},
title = {Evolution of an invasive ductal carcinoma to a small cell carcinoma of the breast: A case report.},
journal = {Medicine},
volume = {101},
number = {2},
pages = {e28433},
pmid = {35029184},
issn = {1536-5964},
mesh = {*Breast Neoplasms/diagnosis/therapy ; *Carcinoma, Ductal, Breast/diagnosis/therapy ; *Carcinoma, Small Cell/diagnosis/therapy ; Female ; Humans ; *Lymphadenopathy ; Middle Aged ; Retrospective Studies ; },
abstract = {RATIONALE: Small cell carcinoma (SCC) is a rare subtype of breast cancer and presents a complex diagnostic and treatment challenge, due to paucity of data. To the best of our knowledge, most cases of breast SCC reported in the literature describe a de novo breast primary. Our case is unique as it describes the evolution of an invasive ductal carcinoma after treatment into a SCC of the breast.<br><br>We report a case of a 53-year-old female, lifelong non-smoker, who initially presented with breast mass noted on self examination. Breast and axillary lymph node biopsy demonstrated a hormone receptor positive invasive ductal carcinoma with a metastatic T3 lesion.<br><br>INTERVENTION: She was treated with first-line palbociclib/letrozole with initial clinical response, and at progression was switched to capecitabine with no response. Repeat biopsy of the axillary lesion showed evolution of the tumor into a triple negative breast cancer. She was then treated with third-line paclitaxel and radiation therapy with good initial response. She eventually had further disease progression and presented with a new mediastinal lymphadenopathy causing SVC syndrome. Biopsy of this showed a small cell variant of breast neuroendocrine carcinoma. Due to the evolution of histology in this case, a retrospective review of her initial breast specimen as well as the second biopsy from the axilla was conducted which confirmed that the mediastinal lymphadenopathy was metastatic from the original breast tumor.<br><br>OUTCOMES AND LESSONS: We speculate that the initial treatment allowed a minority of treatment-resistant neuroendocrine cells to grow and become the dominant face of the tumor. Our patient had an excellent response to carboplatin/etoposide and consolidative locoregional radiotherapy but presented with an early intracranial recurrence. This is a similar pattern of metastases as seen in lung SCC and highlights a potential role for prophylactic cranial irradiation in breast SCC. Further studies are needed to better understand the biology and treatment of breast SCC which continues to present a challenge for clinicians.},
}
@article {pmid35011590,
year = {2021},
author = {Greulich, F and Bielefeld, KA and Scheundel, R and Mechtidou, A and Strickland, B and Uhlenhaut, NH},
title = {Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages.},
journal = {Cells},
volume = {11},
number = {1},
pages = {},
pmid = {35011590},
issn = {2073-4409},
support = {GR 5179/1-1//Deutsche Forschungsgemeinschaft/ ; UH 275/1-1//Deutsche Forschungsgemeinschaft/ ; ERC-2014-StG 638573/ERC_/European Research Council/International ; TRR205, The Adrenal//Deutsche Forschungsgemeinschaft/ ; CRC1064 Chromatin Dynamics//Deutsche Forschungsgemeinschaf/ ; },
mesh = {Acetylation/drug effects ; Animals ; Binding Sites ; *Enhancer Elements, Genetic ; Gene Expression Profiling ; *Gene Expression Regulation/drug effects ; Glucocorticoids/*pharmacology ; Histones/metabolism ; Lysine/metabolism ; Macrophages/drug effects/*metabolism ; Male ; Mice, Inbred C57BL ; Nuclear Proteins/metabolism ; Organ Specificity/drug effects ; RNA/*genetics/metabolism ; Receptors, Glucocorticoid/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects ; Mice ; },
abstract = {Glucocorticoids are potent anti-inflammatory drugs; however, their molecular mode of action remains complex and elusive. They bind to the glucocorticoid receptor (GR), a nuclear receptor that controls gene expression in almost all tissues in a cell type-specific manner. While GR's transcriptional targets mediate beneficial reactions in immune cells, they also harbor the potential of adverse metabolic effects in other cell types such as hepatocytes. Here, we have profiled nascent transcription upon glucocorticoid stimulation in LPS-activated primary murine macrophages using 4sU-seq. We compared our results to publicly available nascent transcriptomics data from murine liver and bioinformatically identified non-coding RNAs transcribed from intergenic GR binding sites in a tissue-specific fashion. These tissue-specific enhancer RNAs (eRNAs) correlate with target gene expression, reflecting cell type-specific glucocorticoid responses. We further associate GR-mediated eRNA expression with changes in H3K27 acetylation and BRD4 recruitment in inflammatory macrophages upon glucocorticoid treatment. In summary, we propose a common mechanism by which GR-bound enhancers regulate target gene expression by changes in histone acetylation, BRD4 recruitment and eRNA expression. We argue that local eRNAs are potential therapeutic targets downstream of GR signaling which may modulate glucocorticoid response in a cell type-specific way.},
}
@article {pmid34999280,
year = {2022},
author = {Kotschi, S and Jung, A and Willemsen, N and Ofoghi, A and Proneth, B and Conrad, M and Bartelt, A},
title = {NFE2L1-mediated proteasome function protects from ferroptosis.},
journal = {Molecular metabolism},
volume = {57},
number = {},
pages = {101436},
pmid = {34999280},
issn = {2212-8778},
mesh = {Animals ; *Ferroptosis ; Homeostasis ; Humans ; Mice ; Mitochondria/metabolism ; *NF-E2-Related Factor 1/genetics/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Proteasome Endopeptidase Complex/metabolism ; },
abstract = {OBJECTIVE: Ferroptosis continues to emerge as a novel modality of cell death with important therapeutic implications for a variety of diseases, most notably cancer and degenerative diseases. While susceptibility, initiation, and execution of ferroptosis have been linked to reprogramming of cellular lipid metabolism, imbalances in iron-redox homeostasis, and aberrant mitochondrial respiration, the detailed mechanisms of ferroptosis are still insufficiently well understood.<br><br>METHODS AND RESULTS: Here we show that diminished proteasome function is a new mechanistic feature of ferroptosis. The transcription factor nuclear factor erythroid-2, like-1 (NFE2L1) protects from ferroptosis by sustaining proteasomal activity. In cellular systems, loss of NFE2L1 reduced cellular viability after the induction of both chemically and genetically induced ferroptosis, which was linked to the regulation of proteasomal activity under these conditions. Importantly, this was reproduced in a Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) patient-derived cell line carrying mutated glutathione peroxidase-4 (GPX4), a critical regulator of ferroptosis. Also, reduced proteasomal activity was associated with ferroptosis in Gpx4-deficient mice. In a mouse model for genetic Nfe2l1 deficiency, we observed brown adipose tissue (BAT) involution, hyperubiquitination of ferroptosis regulators, including the GPX4 pathway, and other hallmarks of ferroptosis.<br><br>CONCLUSION: Our data highlight the relevance of the NFE2L1-proteasome pathway in ferroptosis. Manipulation of NFE2L1 activity might enhance ferroptosis-inducing cancer therapies as well as protect from aberrant ferroptosis in neurodegeneration, general metabolism, and beyond.},
}
@article {pmid34987224,
year = {2022},
author = {Rasmussen, M and Reddy, M and Nolan, R and Camunas-Soler, J and Khodursky, A and Scheller, NM and Cantonwine, DE and Engelbrechtsen, L and Mi, JD and Dutta, A and Brundage, T and Siddiqui, F and Thao, M and Gee, EPS and La, J and Baruch-Gravett, C and Santillan, MK and Deb, S and Ame, SM and Ali, SM and Adkins, M and DePristo, MA and Lee, M and Namsaraev, E and Gybel-Brask, DJ and Skibsted, L and Litch, JA and Santillan, DA and Sazawal, S and Tribe, RM and Roberts, JM and Jain, M and Høgdall, E and Holzman, C and Quake, SR and Elovitz, MA and McElrath, TF},
title = {RNA profiles reveal signatures of future health and disease in pregnancy.},
journal = {Nature},
volume = {601},
number = {7893},
pages = {422-427},
pmid = {34987224},
issn = {1476-4687},
support = {P50 HD103556/HD/NICHD NIH HHS/United States ; R01 HD089940/HD/NICHD NIH HHS/United States ; },
mesh = {*Cell-Free Nucleic Acids/blood ; Female ; Humans ; *Pre-Eclampsia/diagnosis/genetics ; Predictive Value of Tests ; Pregnancy ; *RNA/blood ; Retrospective Studies ; Sensitivity and Specificity ; },
abstract = {Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden[1]. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method[2]. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.},
}
@article {pmid34975349,
year = {2021},
author = {Rafiq, MT and Hamid, MSA and Hafiz, E},
title = {Short-Term Effects of Strengthening Exercises of the Lower Limb Rehabilitation Protocol on Pain, Stiffness, Physical Function, and Body Mass Index among Knee Osteoarthritis Participants Who Were Overweight or Obese: A Clinical Trial.},
journal = {TheScientificWorldJournal},
volume = {2021},
number = {},
pages = {6672274},
pmid = {34975349},
issn = {1537-744X},
mesh = {*Body Mass Index ; *Exercise Therapy ; Female ; Humans ; Lower Extremity/*physiopathology ; Male ; Middle Aged ; Obesity/*complications ; Osteoarthritis, Knee/complications/physiopathology/*rehabilitation ; Overweight/*complications ; Pain/*complications ; Range of Motion, Articular ; Single-Blind Method ; },
abstract = {BACKGROUND: Osteoarthritis (OA) of the knee is defined as a progressive disease of the synovial joints and is characterized by wear and tear of the cartilage and underlying bone. This study aimed to determine the short-term effects of the lower limb rehabilitation protocol (LLRP) on pain, stiffness, physical function, and body mass index (BMI) among knee OA participants who were overweight or obese. Methodology. A single-blinded randomized controlled trial of one-month duration was conducted at Rehmatul-Lil-Alameen Postgraduate Institute, Lahore, Pakistan. Fifty overweight or obese participants with knee OA were randomly divided into two groups by a computer-generated number. Participants in the rehabilitation protocol group (RPG) were provided with leaflets explaining the strengthening exercises of the LLRP and instruction of daily care (IDC), while the participants in the control group (CG) were provided with leaflets explaining the IDC only for a duration of four weeks. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical function. The secondary outcome measures were BMI, exercise adherence, and patients' satisfaction assessed by using the numeric rating scale ranging from 0 to 10. The paired-sample t-test was used to analyze the differences within groups from baseline to posttest evaluations. The analysis of variance 2 × 2 factor was used to analyze the differences in BMI, knee pain, stiffness, and physical function between the groups.<br><br>RESULTS: Participants in the RPG and CG reported a statistically significant reduction in knee pain and stiffness (p &#x2264; 0.05) within the group. The reduction in the scores of knee pain was higher in participants in the RPG than that in participants in the CG (p=0.001). Additionally, participants in the RPG reported greater satisfaction (p=0.001) and higher self-reported exercise adherence (p=0.010) and coordinator-reported exercise adherence (p=0.046) than the participants in the CG.<br><br>CONCLUSION: Short-term effects of the LLRP appear to reduce knee pain and stiffness only, but not physical function and BMI.},
}
@article {pmid34972731,
year = {2022},
author = {Salih, MM and Higgo, AA and Eed, EM},
title = {Prognostic Significance of p16 Protein Expression in Breast Cancer.},
journal = {In vivo (Athens, Greece)},
volume = {36},
number = {1},
pages = {336-340},
pmid = {34972731},
issn = {1791-7549},
mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Female ; Humans ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Progesterone/genetics ; },
abstract = {BACKGROUND/AIM: Breast cancer is the most common cancer in Sudan. The p16 protein plays a vital role in the regulation of the cell cycle.<br><br>PATIENTS AND METHODS: This study analysed the protein expression of p16 in 202 paraffin blocks from Sudanese women with breast cancer using immunohistochemistry.<br><br>RESULTS: This study included 168 (83.2%), 16 (7.9%), and 18 (8.9%) patients with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. There were 95 cases (47.0%) with grade III, 70 cases (34.6%) with grade II, and 23 cases (11.4%) with grade I breast cancer. The hormone receptor status was available for 119 of the cases, and 31 (15.3%), 25 (12.4%), and 63 (31.2%) cases were positive for oestrogen, progesterone, and HER2 receptors, respectively.<br><br>CONCLUSION: p16 protein expression was associated with high histologic grade, lymph node metastasis, and poor prognosis. p16 protein expression may potentially be used as a prognostic marker.},
}
@article {pmid34969739,
year = {2022},
author = {Takada, K and Kashiwagi, S and Asano, Y and Goto, W and Morisaki, T and Shibutani, M and Tanaka, H and Hirakawa, K and Ohira, M},
title = {The Effect of Smoking on Progression from Ductal Carcinoma In Situ to Invasive Ductal Breast Carcinoma: A Retrospective Study.},
journal = {Anticancer research},
volume = {42},
number = {1},
pages = {311-320},
doi = {10.21873/anticanres.15487},
pmid = {34969739},
issn = {1791-7530},
mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/chemically induced/*diagnosis/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology/pathology ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis/*diagnosis/diagnostic imaging/pathology ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy/methods ; Smoking/*adverse effects ; },
abstract = {BACKGROUND/AIM: If ductal carcinoma in situ (DCIS) is diagnosed by needle biopsy, invasion is often found by removing the entire tumor and performing pathological examination. Smoking is a risk factor for carcinogenesis in breast cancer. We examined the correlation between the risk of invasion found by postoperative pathology and smoking history in patients diagnosed with DCIS by preoperative biopsy.<br><br>PATIENTS AND METHODS: We examined 128 patients who were diagnosed with DCIS by preoperative biopsy. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy.<br><br>RESULTS: Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. Number of pack-years was not an independent factor (p=0.349, OR=0.329), but current-smoker status (p=0.006, OR=not calculable) was an independent factor with VAB (p=0.018, OR=0.327).<br><br>CONCLUSION: Tobacco components may have an influence on the progression from DCIS to invasive ductal carcinoma.},
}
@article {pmid34949235,
year = {2021},
author = {Mavhungu, R and Bhuiyan, M and Ooko, F},
title = {Profile of patients seen at Pietersburg and Mankweng breast cancer clinics in Limpopo.},
journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde},
volume = {111},
number = {11b},
pages = {1129-1131},
doi = {10.7196/SAMJ.2021.v111i11b.16108},
pmid = {34949235},
issn = {2078-5135},
mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/pathology ; Breast Neoplasms, Male/epidemiology/pathology ; Female ; Humans ; Incidence ; Male ; Mammography ; Middle Aged ; Neoplasm Staging ; Prevalence ; Retrospective Studies ; South Africa/epidemiology ; },
abstract = {BACKGROUND: Breast cancer is the most common cancer diagnosed among women worldwide. It is the most prevalent cancer and leading cause of death among South African (SA) women. The increasing incidence of breast cancer is a major health concern. Until now, the distribution of breast cancer demography, stage at first presentation, and histological characterisation have not been studied in Limpopo Province, SA.<br><br>OBJECTIVES: To record the demographic profile of breast cancer patients, to report the stage at the time of presentation and to characterise the pattern of malignant disease in Limpopo, SA.<br><br>METHODS: We conducted a retrospective descriptive review of the records of patients managed at Pietersburg Hospital oncology and Mankweng Hospital breast cancer clinics during the period 1 March 2015 - 28 February 2017. Stata was used to analyse data.<br><br>RESULTS: A total of 248 patients with a mean age of 55 years were included for analysis, 7 males (3%) and 241 females (97%). Capricorn and Vhembe districts constituted 32% and 27% respectively. The majority (69%) of patients were diagnosed with disease stage III or IV. The&#xa0;most common histological type was invasive ductal cell carcinoma (IDC) (87%).<br><br>CONCLUSIONS: More than one-third of patients were younger than 50 years. The majority (69%) had an advanced breast cancer (stage III or&#xa0;IV). We recommend provision of mammography services in regional hospitals.},
}
@article {pmid34945830,
year = {2021},
author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY},
title = {Adjuvant Whole Breast Radiotherapy Improve Survival in Women with Heart Failure with Reduced Ejection Fraction Receiving Breast-Conserving Surgery.},
journal = {Journal of personalized medicine},
volume = {11},
number = {12},
pages = {},
pmid = {34945830},
issn = {2075-4426},
abstract = {BACKGROUND: to date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).<br><br>PATIENTS AND METHODS: we included 294 women with left-breast IDC at clinical stages IA-IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).<br><br>RESULTS: in the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44-0.94) was a significant independent prognostic factor for all-cause death (p = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24-0.71; p = 0.0017) and 0.37 (0.22-0.63; p = 0.0004), respectively, compared with the non-adjuvant WBRT group.<br><br>CONCLUSION: Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with non-adjuvant WBRT.},
}
@article {pmid34928689,
year = {2022},
author = {Shoshani, A and Kor, A},
title = {The mental health effects of the COVID-19 pandemic on children and adolescents: Risk and protective factors.},
journal = {Psychological trauma : theory, research, practice and policy},
volume = {14},
number = {8},
pages = {1365-1373},
doi = {10.1037/tra0001188},
pmid = {34928689},
issn = {1942-969X},
mesh = {Child ; Female ; Adolescent ; Humans ; Male ; *Pandemics/prevention &amp; control ; *COVID-19 ; Mental Health ; Protective Factors ; Communicable Disease Control ; },
abstract = {OBJECTIVE: The restrictions to contain the coronavirus disease 2019 (COVID-19) pandemic have led to considerable social isolation, posing significant threats to mental health worldwide. The preventive lockdowns may be especially difficult for children and adolescents, who rely extensively on their daily routines and peer connections for stability and optimal development. However, there is a dearth of longitudinal research examining the mental health and daily life impact of the pandemic among children and adolescents. This study addresses this gap by examining the influence of the COVID-19 pandemic on children and adolescents' mental health and well-being, and potential risk and protective moderators of mental health change.<br><br>METHOD: In the present study, 1,537 Israeli children and adolescents (Mage = 13.97; 52% girls) completed a battery of questionnaires in September 2019; before the COVID-19 outbreak and immediately after an 8-week lockdown period when schools reopened in May 2020.<br><br>RESULTS: A repeated measures multivariant analysis of variance (MANOVA) revealed significantly greater anxiety, depression, and panic symptoms, increases in video game, Internet and TV screen time use, and decreases in positive emotions, life satisfaction, social media use, and peer support during the pandemic. Participants with higher baseline mental health symptoms showed greater symptoms after the lockdown period. Perceived social support and consistent daily routines were found to act as significant protective factors against symptomatology.<br><br>CONCLUSIONS: The results highlight the significant mental health consequences of the pandemic on children and adolescents, and substantiate the significant parents' and peers' roles in children's and adolescents' coping during this global pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).},
}
@article {pmid34899603,
year = {2021},
author = {Kopf, S and Kumar, V and Kender, Z and Han, Z and Fleming, T and Herzig, S and Nawroth, PP},
title = {Diabetic Pneumopathy-A New Diabetes-Associated Complication: Mechanisms, Consequences and Treatment Considerations.},
journal = {Frontiers in endocrinology},
volume = {12},
number = {},
pages = {765201},
pmid = {34899603},
issn = {1664-2392},
mesh = {Animals ; DNA Damage/genetics ; Diabetes Complications/blood/*complications/genetics ; Diabetes Mellitus, Type 1/blood/*complications/genetics ; Diabetes Mellitus, Type 2/blood/*complications/genetics ; Humans ; Pulmonary Fibrosis/blood/*etiology/genetics ; },
abstract = {Patients with diabetes are over-represented among the total cases reported with "idiopathic" pulmonary fibrosis (IPF). This raises the question, whether this is an association only or whether diabetes itself can cause pulmonary fibrosis. Recent studies in mouse models of type 1 and type 2 diabetes demonstrated that diabetes causes pulmonary fibrosis. Both types of diabetes trigger a cascade, starting with increased DNA damage, an impaired DNA repair, and leading to persistent DNA damage signaling. This response, in turn, induces senescence, a senescence-associated-secretory phenotype (SASP), marked by the release of pro-inflammatory cytokines and growth factors, finally resulting in fibrosis. Restoring DNA repair drives fibrosis into remission, thus proving causality. These data can be translated clinically to patients with type 2 diabetes, characterized by long-term diabetes and albuminuria. Hence there are several arguments, to substitute the term "idiopathic" pulmonary fibrosis (IPF) in patients with diabetes (and exclusion of other causes of lung diseases) by the term "diabetes-induced pulmonary fibrosis" (DiPF). However, future studies are required to establish this term and to study whether patients with diabetes respond to the established therapies similar to non-diabetic patients.},
}
@article {pmid34884926,
year = {2021},
author = {Kang, M and Lee, H and Byeon, SJ and Kwon, GY and Jeon, SS},
title = {Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate.},
journal = {International journal of molecular sciences},
volume = {22},
number = {23},
pages = {},
pmid = {34884926},
issn = {1422-0067},
support = {NRF-2020R1A2C2007662//National Research Foundation of Korea/ ; NRF-2020R1C1C1005054//National Research Foundation of Korea/ ; },
mesh = {Animals ; DNA Repair/genetics ; Genomic Instability ; Humans ; Male ; *Mutation ; Precision Medicine ; Prostatic Neoplasms/*genetics/*pathology/therapy ; Xenograft Model Antitumor Assays ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2-ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate-ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.},
}
@article {pmid34884498,
year = {2021},
author = {Betz, IR and Qaiyumi, SJ and Goeritzer, M and Thiele, A and Brix, S and Beyhoff, N and Grune, J and Klopfleisch, R and Greulich, F and Uhlenhaut, NH and Kintscher, U and Foryst-Ludwig, A},
title = {Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation.},
journal = {International journal of molecular sciences},
volume = {22},
number = {23},
pages = {},
pmid = {34884498},
issn = {1422-0067},
mesh = {Animals ; Cardiomegaly/chemically induced/*drug therapy/metabolism/pathology ; Cardiotonic Agents/*pharmacology ; Catecholamines/*toxicity ; Fatty Acids, Monounsaturated/*pharmacology ; Gene Expression Regulation/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac/drug effects/metabolism/pathology ; PPAR alpha/genetics/*metabolism ; PPAR delta/genetics/*metabolism ; },
abstract = {Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 (Angptl4) and Pyruvate Dehydrogenase Kinase 4 (Pdk4). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage.},
}
@article {pmid34881777,
year = {2022},
author = {Sidhanth, C and Bindhya, S and Shabna, A and Krishnapriya, S and Manasa, P and Nagare, RP and Joshua, T and Sneha, S and Murhekar, K and Ganesan, TS},
title = {LASP-1 interacts with ErbB2 in ovarian cancer cells.},
journal = {The Biochemical journal},
volume = {479},
number = {1},
pages = {23-38},
doi = {10.1042/BCJ20210173},
pmid = {34881777},
issn = {1470-8728},
mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adult ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Ovarian Epithelial/*metabolism/pathology ; Cell Line, Tumor ; Cohort Studies ; Cytoskeletal Proteins/genetics/*metabolism ; Female ; HEK293 Cells ; Humans ; LIM Domain Proteins/genetics/*metabolism ; Lapatinib/pharmacology ; Middle Aged ; Ovarian Neoplasms/*metabolism/pathology ; Phosphorylation/drug effects/genetics ; Plasmids ; Protein Kinase Inhibitors/pharmacology ; Quinazolines/pharmacology ; Receptor, ErbB-2/genetics/*metabolism ; Signal Transduction/drug effects/*genetics ; Transfection ; },
abstract = {LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76 Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40 kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n = 101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (P < 0.001). Analysis of the expression of an independent dataset of ovarian and breast tumours from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (P < 0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer.},
}
@article {pmid34851990,
year = {2021},
author = {D'Amora, P and Silva, IDCG and Budib, MA and Ayache, R and Silva, RMS and Silva, FC and Appel, RM and Júnior, SS and Pontes, HBD and Alvarenga, AC and Arima, EC and Martins, WG and Silva, NLF and Diaz, RS and Salzgeber, MB and Palma, AM and Evans, SS and Nagourney, RA},
title = {Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection.},
journal = {PloS one},
volume = {16},
number = {12},
pages = {e0259909},
pmid = {34851990},
issn = {1932-6203},
support = {UL1 TR001414/TR/NCATS NIH HHS/United States ; },
mesh = {Adult ; Aged ; Area Under Curve ; COVID-19/mortality/*pathology/virology ; Carnitine/metabolism ; Citrulline/metabolism ; Female ; Glutamic Acid/metabolism ; Humans ; Kynurenine/metabolism ; Male ; *Metabolome ; Metabolomics/*methods ; Middle Aged ; Ornithine/metabolism ; ROC Curve ; Risk Factors ; SARS-CoV-2/isolation &amp; purification ; Severity of Illness Index ; Tryptophan/metabolism ; },
abstract = {This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.},
}
@article {pmid34841287,
year = {2021},
author = {Erener, S and Ellis, CE and Ramzy, A and Glavas, MM and O'Dwyer, S and Pereira, S and Wang, T and Pang, J and Bruin, JE and Riedel, MJ and Baker, RK and Webber, TD and Lesina, M and Blüher, M and Algül, H and Kopp, JL and Herzig, S and Kieffer, TJ},
title = {Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice.},
journal = {Cell reports. Medicine},
volume = {2},
number = {11},
pages = {100434},
pmid = {34841287},
issn = {2666-3791},
support = {//CIHR/Canada ; },
mesh = {Animals ; Apoptosis ; Base Sequence ; Cell Line, Tumor ; Cell Movement ; Diet, High-Fat ; *Disease Progression ; *Gene Deletion ; Humans ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism/*pathology ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/*genetics/metabolism ; Organ Specificity ; Pancreatic Neoplasms/*genetics/*pathology ; Rats ; Mice ; },
abstract = {miRNAs have crucial functions in many biological processes and are candidate biomarkers of disease. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. Deletion of miR-216a in mice leads to a reduction in islet size, β-cell mass, and insulin levels. Single-cell RNA sequencing reveals a subpopulation of β-cells with upregulated acinar cell markers under a high-fat diet. miR-216a is induced by TGF-β signaling, and inhibition of miR-216a increases apoptosis and decreases cell proliferation in pancreatic cells. Deletion of miR-216a in the pancreatic cancer-prone mouse line Kras[G12D];Ptf1a[CreER] reduces the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels are elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA and also suggests miR-216a as a potential biomarker for diagnosis of pancreatic diseases.},
}
@article {pmid34829743,
year = {2021},
author = {Liu, PF and Shu, CW and Yang, HC and Lee, CH and Liou, HH and Ger, LP and Tzeng, YT and Wang, WC},
title = {Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer.},
journal = {Biomedicines},
volume = {9},
number = {11},
pages = {},
pmid = {34829743},
issn = {2227-9059},
support = {MOST 108-2320-B-037-038, MOST 109-2320-B-037-015-MY3//The Ministry of Science and Technology/ ; KMU-Q109008; KMU-Q110002//Kaohsiung Medical University Research Foundation/ ; NSYSUKMU 109-I007; NSYSUKMU-110-I006//The National Sun Yat-sen University-KMU Joint Research Project/ ; KMU-TC108A04//Kaohsiung Medical University Research Center Grant/ ; VGHKS106-015; VGHKS107-014//Kaohsiung Veterans General Hospital/ ; },
abstract = {Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients.},
}
@article {pmid34816360,
year = {2022},
author = {Mizukoshi, K and Fujii, M and Yamauchi, Y and Fukuda, A and Seno, H},
title = {A rare case of malignant biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma.},
journal = {Clinical journal of gastroenterology},
volume = {15},
number = {1},
pages = {199-204},
pmid = {34816360},
issn = {1865-7265},
mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal/surgery ; Constriction, Pathologic/etiology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Retroperitoneal Neoplasms/surgery ; },
abstract = {A 50-year-old woman was referred to our hospital for elevated hepatobiliary enzymes. She had a medical history of mastectomy for left breast invasive ductal carcinoma about 10 years ago, and no apparent recurrence had been observed. Contrast-enhanced computed tomography (CT) revealed soft-tissue shadows surrounding the portal vein, celiac artery, and other vessels. The lesions involved the hilar bile duct, and the upstream bile ducts were dilated. Endoscopic retrograde cholangiography showed an obstruction in the hilar bile duct, and biopsies were taken at the site of biliary stenosis. H&amp;E staining showed that cells with strong nuclear atypia and prominent chromatin staining infiltrated in the stroma. Immunohistochemical analysis revealed that the cells were positive for CK7, GATA3 and weakly positive for CK20. Based on these results, we made the diagnosis of biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma. Biliary inside stents were placed across the biliary stricture, and she received chemotherapy plus endocrine therapy for breast cancer. So far, the partial response has been maintained for 1 year since the diagnosis of retroperitoneal metastasis. Although retroperitoneal metastasis from breast cancer, especially breast invasive ductal carcinoma, is extremely rare, it could be a differential diagnosis for biliary stenosis.},
}
@article {pmid34812516,
year = {2022},
author = {Verbrugge, SAJ and Alhusen, JA and Kempin, S and Pillon, NJ and Rozman, J and Wackerhage, H and Kleinert, M},
title = {Genes controlling skeletal muscle glucose uptake and their regulation by endurance and resistance exercise.},
journal = {Journal of cellular biochemistry},
volume = {123},
number = {2},
pages = {202-214},
doi = {10.1002/jcb.30179},
pmid = {34812516},
issn = {1097-4644},
mesh = {Animals ; *Blood Glucose/genetics/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Humans ; Insulin Resistance/*genetics ; Muscle, Skeletal/*metabolism ; Physical Endurance/*genetics ; *Resistance Training ; },
abstract = {Exercise improves the insulin sensitivity of glucose uptake in skeletal muscle. Due to that, exercise has become a cornerstone treatment for type 2 diabetes mellitus (T2DM). The mechanisms by which exercise improves skeletal muscle insulin sensitivity are, however, incompletely understood. We conducted a systematic review to identify all genes whose gain or loss of function alters skeletal muscle glucose uptake. We subsequently cross-referenced these genes with recently generated data sets on exercise-induced gene expression and signaling. Our search revealed 176 muscle glucose-uptake genes, meaning that their genetic manipulation altered glucose uptake in skeletal muscle. Notably, exercise regulates the expression or phosphorylation of more than 50% of the glucose-uptake genes or their protein products. This included many genes that previously have not been associated with exercise-induced insulin sensitivity. Interestingly, endurance and resistance exercise triggered some common but mostly unique changes in expression and phosphorylation of glucose-uptake genes or their protein products. Collectively, our work provides a resource of potentially new molecular effectors that play a role in the incompletely understood regulation of muscle insulin sensitivity by exercise.},
}
@article {pmid34812466,
year = {2021},
author = {Feresin, RG and Johnson, SA and Elam, ML and Pourafshar, S and Navaei, N and Akhavan, NS and Tenenbaum, G and Figueroa, A and Arjmandi, BH},
title = {Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.},
journal = {Food &amp; function},
volume = {12},
number = {24},
pages = {12526-12534},
doi = {10.1039/d1fo01555a},
pmid = {34812466},
issn = {2042-650X},
mesh = {Aged ; Biomarkers/blood ; Bone Density/*drug effects ; Bone Resorption/blood/drug therapy ; Female ; *Fragaria ; Humans ; Hypertension/blood/complications/*drug therapy ; Middle Aged ; Osteoporosis, Postmenopausal/blood/complications/*prevention &amp; control ; Plant Extracts/blood/*pharmacology ; Polyphenols/blood/*pharmacology ; Postmenopause ; },
abstract = {Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m[-2]; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.},
}
@article {pmid34801929,
year = {2022},
author = {Mampel, A and Sottile, ML and Denita-Juárez, SP and Vargas, AL and Vargas-Roig, LM},
title = {Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer.},
journal = {Cancer genetics},
volume = {260-261},
number = {},
pages = {14-17},
doi = {10.1016/j.cancergen.2021.11.003},
pmid = {34801929},
issn = {2210-7762},
mesh = {Adult ; Aged ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Heterozygote ; Humans ; Neoplasms, Second Primary/*genetics ; Pedigree ; *Point Mutation ; Sequence Analysis, DNA ; *Sequence Deletion ; },
abstract = {Double heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. The proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants NM_007300.4(BRCA1):c.4201C>T (p.Gln1401Ter), and NM_000059.3(BRCA2):c.5146_5149del (p.Tyr1716fs). . The patient's son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. There are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.},
}
@article {pmid34781971,
year = {2021},
author = {Kostoglou, A and Vlastos, D and Bakalis, A and Ghosh, D},
title = {Breast cancer-associated opsoclonus-myoclonus syndrome: a case report.},
journal = {World journal of surgical oncology},
volume = {19},
number = {1},
pages = {328},
pmid = {34781971},
issn = {1477-7819},
mesh = {Adult ; *Breast Neoplasms/complications ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Opsoclonus-Myoclonus Syndrome/etiology ; Positron Emission Tomography Computed Tomography ; Prognosis ; },
abstract = {BACKGROUND: Paraneoplastic neurological syndromes constitute rare neurological complications of malignant disease, manifesting in <1% of patients with cancer. Opsoclonus-myoclonus syndrome (OMS) presents with chaotic ocular saccades (opsoclonus), spontaneous muscular jerking (myoclonus) that may be accompanied by ataxia, strabismus, aphasia, or mutism. Its paraneoplastic variant in the adult is most commonly associated with small-cell lung cancer, followed by breast cancer. Importantly, neurological symptoms usually precede the diagnosis of breast cancer and tend to recure after its treatment.<br><br>CASE PRESENTATION: A 43-year-old premenopausal Caucasian woman with a medical history of hypertension was admitted following an episode of focal seizure. This progressed to generalised tonic-clonic seizures and she was subsequently loaded with phenytoin, valproate, and levetiracetam. Initial workup included whole body CT scan, viral and autoimmune serology. The CT scan revealed an enhancing right axillary lymph node, which in combination with Anti-Ri antibody positivity raised the spectre of paraneoplastic OMS. MRI of the head revealed subtle nonspecific white matter signal change within the centrum semiovale without any mass lesions, while MRI of the spine was unremarkable. An uncomplicated right mastectomy and axillary lymph node clearance was performed: histopathology revealed a 9-mm, grade 2, oestrogen receptor-positive, progesterone receptor-negative (ER8, PR0), Her2-negative invasive ductal carcinoma, and 4/6 positive lymph nodes (T1b N2 M0). Two months later, she was readmitted with vertigo, diplopia, facial weakness, and ataxia, setting the diagnosis anti-Ri syndrome recurrence. MDT recommended mammogram and ultrasound of the left breast, which were normal. Subsequently, four months after initial discharge, she suffered another neurological recurrence; due to concomitant abdominal pain, PET-CT was performed demonstrating a hypermetabolic right ovarian focus. Bilateral salpingo-oophorectomy was performed as per gynaecology MDT and final histology showed normal tubes and ovaries. She has remained on remission since then, with a negative annual mammogram follow-up.<br><br>CONCLUSIONS: In conclusion, we report a case of OMS associated with breast cancer anti-Ri onconeural antibody. Its manifestations preceded the diagnosis of malignancy and it persisted after cancer treatment, underlining the importance for high clinical suspicion in cases of classical paraneoplastic neurological syndromes as well as the need for long-term clinical follow-up.},
}
@article {pmid34781210,
year = {2021},
author = {Jeong, JS and Cho, KJ and Kim, D and Lee, YS and Song, JS},
title = {Genomic alteration in rare subtype of sarcomatoid salivary duct carcinoma.},
journal = {Pathology, research and practice},
volume = {228},
number = {},
pages = {153678},
doi = {10.1016/j.prp.2021.153678},
pmid = {34781210},
issn = {1618-0631},
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma, Ductal/genetics/*pathology ; Humans ; Male ; Middle Aged ; Salivary Ducts/pathology ; Salivary Gland Neoplasms/genetics/*pathology ; },
abstract = {AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary gland neoplasm with a poor prognosis. Morphologically, it has many variants including sarcomatoid SDC. We evaluated the morphological features, immunohistochemistry profile, and genomic alteration of the rare variant, sarcomatoid SDC.<br><br>METHODS AND RESULTS: We evaluated the clinicopathological and molecular pathology for rare variant of sarcomatoid SDC. Among 102 SDC patients, three had sarcomatoid SDC. Review of clinicopathological features and immunohistochemistry and targeted exome sequencing was performed according to carcinomatous and sarcomatoid areas, respectively. The tumors were present in two submandibular glands and one parotid gland. In one case, a SDC arose in carcinoma ex pleomorphic adenoma. All consisted of a conventional invasive ductal carcinoma area and sarcomatoid features including spindle cells and multinucleated giant cells. AR and epithelial membrane antigen (EMA) were positive in both carcinoma and sarcomatoid areas. Cytokeratin AE1/AE3 were negative in all sarcomatoid areas. Targeted exome sequencing revealed multiple heterogeneous alterations including PIK3CA and TP53. Genomic alterations were nearly identical between typical carcinoma and sarcomatoid areas.<br><br>CONCLUSIONS: Clinicopathological features of sarcomatoid SDCs were not different from typical SDC, and genomic alteration according to subtypes was also similar to that of the conventional type. Androgen receptor (AR) expression is helpful in the diagnosis of SDC. The findings indicate that EMA and AR are useful in diagnosing sarcomatoid SDC when the tumor is composed of predominantly sarcomatoid components.},
}
@article {pmid34778983,
year = {2022},
author = {O'Donnell, AJ and Greischar, MA and Reece, SE},
title = {Mistimed malaria parasites re-synchronize with host feeding-fasting rhythms by shortening the duration of intra-erythrocytic development.},
journal = {Parasite immunology},
volume = {44},
number = {3},
pages = {e12898},
pmid = {34778983},
issn = {1365-3024},
support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Animals ; Circadian Rhythm/physiology ; Fasting ; *Malaria/parasitology/prevention &amp; control ; *Parasites ; *Plasmodium chabaudi/physiology ; },
abstract = {AIMS: Malaria parasites exhibit daily rhythms in the intra-erythrocytic development cycle (IDC) that underpins asexual replication in the blood. The IDC schedule is aligned with the timing of host feeding-fasting rhythms. When the IDC schedule is perturbed to become mismatched to host rhythms, it readily reschedules but it is not known how.<br><br>METHODS: We intensively follow four groups of infections that have different temporal alignments between host rhythms and the IDC schedule for 10&#xa0;days, before and after the peak in asexual densities. We compare how the duration, synchrony and timing of the IDC differs between parasites in control infections and those forced to reschedule by 12&#xa0;hours and ask whether the density of parasites affects the rescheduling process.<br><br>RESULTS AND CONCLUSIONS: Our experiments reveal parasites shorten the IDC duration by 2-3&#xa0;hours to become realigned to host feeding-fasting rhythms with 5-6&#xa0;days, in a density-independent manner. Furthermore, parasites are able to reschedule without significant fitness costs for them or their hosts. Understanding the extent of, and limits on, plasticity in the IDC schedule may reveal targets for novel interventions, such as drugs to disrupt IDC regulation and preventing IDC dormancy conferring tolerance to existing drugs.},
}
@article {pmid34769077,
year = {2021},
author = {Kohlhase, DR and McCabe, CE and Singh, AK and O'Rourke, JA and Graham, MA},
title = {Comparing Early Transcriptomic Responses of 18 Soybean (Glycine max) Genotypes to Iron Stress.},
journal = {International journal of molecular sciences},
volume = {22},
number = {21},
pages = {},
pmid = {34769077},
issn = {1422-0067},
support = {3625-21220-006-00D//USDA-ARS/ ; IOW04714//USDA/ ; FAR0024859//North Central Soybean Research Program/ ; },
mesh = {*Gene Expression Regulation, Plant ; Genome-Wide Association Study ; Iron/*metabolism ; Quantitative Trait Loci ; Glycine max/*genetics/metabolism ; Stress, Physiological ; Transcriptome ; },
abstract = {Iron deficiency chlorosis (IDC) is an abiotic stress that negatively affects soybean (Glycine max [L.] Merr.) production. Much of our knowledge of IDC stress responses is derived from model plant species. Gene expression, quantitative trait loci (QTL) mapping, and genome-wide association studies (GWAS) performed in soybean suggest that stress response differences exist between model and crop species. Our current understanding of the molecular response to IDC in soybeans is largely derived from gene expression studies using near-isogenic lines differing in iron efficiency. To improve iron efficiency in soybeans and other crops, we need to expand gene expression studies to include the diversity present in germplasm collections. Therefore, we collected 216 purified RNA samples (18 genotypes, two tissue types [leaves and roots], two iron treatments [sufficient and deficient], three replicates) and used RNA sequencing to examine the expression differences of 18 diverse soybean genotypes in response to iron deficiency. We found a rapid response to iron deficiency across genotypes, most responding within 60 min of stress. There was little evidence of an overlap of specific differentially expressed genes, and comparisons of gene ontology terms and transcription factor families suggest the utilization of different pathways in the stress response. These initial findings suggest an untapped genetic potential within the soybean germplasm collection that could be used for the continued improvement of iron efficiency in soybean.},
}
@article {pmid34765304,
year = {2021},
author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY},
title = {Long-term oncologic outcomes of breast conserving surgery with propofol-based total intravenous anesthesia or volatile inhalational general anesthesia without propofol: a propensity score-matched, population-based cohort study.},
journal = {American journal of cancer research},
volume = {11},
number = {10},
pages = {4966-4980},
pmid = {34765304},
issn = {2156-6976},
abstract = {To estimate oncologic outcomes (overall survival [OS], locoregional recurrence [LRR], and distant metastasis [DM]) in patients with breast intraductal carcinoma (IDC) receiving breast conserving surgery (BCS) under propofol-based total intravenous anesthesia (TIVA) or volatile inhalational (INHA) general anesthesia (GA) without propofol. Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized by anesthesia techniques into propofol-based TIVA-GA and non-propofol-based INHA-GA groups, respectively. Cox regression analysis was performed to calculate hazard ratios and 95% confidence intervals (CIs). In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% CI) of all-cause mortality for TIVA-GA with propofol compared with INHA-GA without propofol was 0.94 (0.83-1.31). The aHR (95% CI) of LRR for TIVA-GA with propofol group compared with INHA-GA without propofol was 0.77 (0.58-0.87). The aHR (95% CI) of DM for TIVA-GA with propofol compared with INHA-GA without propofol was 0.91 (0.82-1.24). Propofol-based TIVA-GA might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with non-propofol-based INHA-GA.},
}
@article {pmid34763167,
year = {2021},
author = {Mallapasi, MN and Kusumanegara, J and Kabo, P and Usman, U and Mulyono, MT and Faruk, M},
title = {Cardiac metastasis of triple-negative breast cancer mimicking myxoma: A case report.},
journal = {International journal of surgery case reports},
volume = {88},
number = {},
pages = {106552},
pmid = {34763167},
issn = {2210-2612},
abstract = {INTRODUCTION: Metastatic heart tumors are rare, occurring in 1.5-20% of cancer patient autopsies. Lymphoma, melanoma, leukemia, and carcinomas of the lung, esophagus, and breast are the most prevalent causes of these metastases, although they can originate from any malignant tumor. Here we report a case of triple-negative breast cancer with cardiac metastasis mimicking myxoma.<br><br>PRESENTATION OF CASE: A 39-year-old woman presented at the emergency department with shortness of breath. Vital signs were hypotension and tachypnea. There were coarse crackles at the bases of both lungs. Electrocardiography results showed a normal sinus rhythm. Chest X-ray revealed cardiomegaly with signs of pulmonary edema. Echocardiography revealed a large left atrial (LA) mass protruding to the mitral valve and attached to the interatrial septum during diastole. The patient was diagnosed with cardiogenic shock, acute kidney injury, elevated liver enzymes, and an LA mass. Surgical excision through median sternotomy was planned. Intraoperatively, an LA mass was found. The histopathology evaluation showed an LA mass with invasive ductal carcinoma of metastatic breast tumors. Immunohistochemistry (IHC) confirmed the diagnosis of triple-negative breast cancer that had metastasized to the heart. Postoperative echocardiography confirmed complete excision of the tumor.<br><br>DISCUSSION: Breast cancer that has metastasized to the heart is uncommon. This patient was referred to the surgical oncology section for the treatment of triple-negative breast cancer with cardiac metastasis.<br><br>CONCLUSION: A heart mass should be suspected of having metastasized if the patient has a history of malignancy, even if it occurred several years earlier.},
}
@article {pmid34753585,
year = {2021},
author = {Othong, J and Boonmak, J and Cheansirisomboon, A and Puangmali, T and Phanchai, W and Youngme, S},
title = {pH modulated luminescent switching and discriminative detection of amino acid based on metal-organic framework.},
journal = {Analytica chimica acta},
volume = {1187},
number = {},
pages = {339157},
doi = {10.1016/j.aca.2021.339157},
pmid = {34753585},
issn = {1873-4324},
mesh = {Amino Acids ; Humans ; Hydrogen-Ion Concentration ; Luminescence ; *Metal-Organic Frameworks ; Reproducibility of Results ; },
abstract = {The detection of glutamic (Glu) or aspartic (Asp) acids is vital for human nutrition and diagnosis of disease. Herein, the dht ligand containing hydroxy group (-OH) is used to design and synthesize a 2D luminescent [Cd2(idc)(dht)(H2O)4] (1); H2idc = 4,5-imidazoledicarboxylic acid and H2dht = 2,5-dihydroxyterephthalic acid for sensing amino acids. The compound 1 can discriminatively detect Asp and Glu among other amino acids through blue-shifted emission (yellow → green). The dual sensing mechanism may be attributed to the intermolecular excited-state proton transfer between MOF and water to produce keto form along with the subsequent switching of keto form to enol form by protonation causing the increased band gap energy. This material can serve several benefits in terms of high selectivity, fast response (30s), good reproducibility and low LOD value of 11.34 μM which is less than the harmful concentration of Glu for human health (>400 μM). In addition, 1 shows the broad range detection of Glu covering in safe and unsafe levels. For on-site detection of Glu, MOF-based paper is devised and can be applied through color-scanning application in smartphone. Besides, this sensor can serve to detect Glu in real samples with good recovery.},
}
@article {pmid34725819,
year = {2022},
author = {Chen, X and Zhang, C and Guo, D and Wang, Y and Hu, J and Hu, J and Wang, S and Liu, X},
title = {Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.},
journal = {European journal of clinical investigation},
volume = {52},
number = {4},
pages = {e13704},
doi = {10.1111/eci.13704},
pmid = {34725819},
issn = {1365-2362},
support = {2017YFC0108602//The National Key Research and Development Program of China/ ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*mortality/pathology/*secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Nomograms ; Prognosis ; Risk Factors ; Survival Rate ; },
abstract = {OBJECTIVE: To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis.<br><br>METHOD: We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry.<br><br>RESULT: Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: &#x3c7;[2] &#xa0;=&#xa0;18784, p&#xa0;<&#xa0;0.001; &#x3c7;[2] &#xa0;=&#xa0;47.1, p&#xa0;<&#xa0;0.001; &#x3c7;[2] &#xa0;=&#xa0;20, p&#xa0;<&#xa0;0.001).<br><br>CONCLUSION: The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.},
}
@article {pmid34717732,
year = {2021},
author = {Ropri, AS and DeVaux, RS and Eng, J and Chittur, SV and Herschkowitz, JI},
title = {Cis-acting super-enhancer lncRNAs as biomarkers to early-stage breast cancer.},
journal = {Breast cancer research : BCR},
volume = {23},
number = {1},
pages = {101},
pmid = {34717732},
issn = {1465-542X},
mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Line ; Disease Progression ; Enhancer Elements, Genetic/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Proteins/genetics ; MicroRNAs/genetics ; RNA, Long Noncoding/*genetics ; Receptors, Estrogen/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; },
abstract = {BACKGROUND: Increased breast cancer screening over the past four decades has led to a substantial rise in the diagnosis of ductal carcinoma in situ (DCIS). Although DCIS lesions precede invasive ductal carcinoma (IDC), they do not always transform into cancer. The current standard-of-care for DCIS is an aggressive course of therapy to prevent invasive and metastatic disease resulting in over-diagnosis and over-treatment. Thus, there is a critical need to identify functional determinants of progression of DCIS to IDC to allow discrimination between indolent and aggressive disease. Recent studies show that super-enhancers, in addition to promoting other gene transcription, are themselves transcribed producing super-enhancer associated long noncoding RNAs (SE-lncRNAs). These SE-lncRNAs can interact with their associated enhancer regions in cis and influence activities and expression of neighboring genes. Furthermore, they represent a novel, untapped group of therapeutic targets.<br><br>METHODS: With an integrative analysis of enhancer loci with global expression of SE-lncRNAs in the MCF10A progression series, we have identified differentially expressed SE-lncRNAs which can identify mechanisms for DCIS to IDC progression. Furthermore, cross-referencing these SE-lncRNAs with patient samples in the The Cancer Genome Atlas (TCGA) database, we have unveiled 27 clinically relevant SE-lncRNAs that potentially interact with their enhancer to regulate nearby gene expression. To complement SE-lncRNA expression studies, we conducted an unbiased global analysis of super-enhancers that are acquired or lost in progression.<br><br>RESULTS: Here we designate SE-lncRNAs RP11-379F4.4 and RP11-465B22.8 as potential markers of progression of DCIS to IDC through regulation of the expression of their neighboring genes (RARRES1 and miR-200b, respectively). Moreover, we classified 403 super-enhancer regions in MCF10A normal cells, 627 in AT1, 1053 in DCIS, and 320 in CA1 cells. Comparison analysis of acquired/lost super-enhancer regions with super-enhancer regions classified in 47 ER positive patients, 10 triple negative breast cancer (TNBC) patients, and 11 TNBC cell lines reveal critically acquired pathways including STAT signaling and NF-kB signaling. In contrast, protein folding, and local estrogen production are identified as major pathways lost in progression.<br><br>CONCLUSION: Collectively, these analyses identify differentially expressed SE-lncRNAs and acquired/lost super-enhancers in progression of breast cancer important for promoting DCIS lesions to IDC.},
}
@article {pmid34716548,
year = {2021},
author = {Cattaneo, C and Rieg, S and Schwarzer, G and Müller, MC and Blümel, B and Kern, WV},
title = {Enterococcus faecalis bloodstream infection: does infectious disease specialist consultation make a difference?.},
journal = {Infection},
volume = {49},
number = {6},
pages = {1289-1297},
pmid = {34716548},
issn = {1439-0973},
mesh = {Adult ; Aged ; *Bacteremia/epidemiology ; *Communicable Diseases ; Enterococcus faecalis ; *Gram-Positive Bacterial Infections/epidemiology ; Humans ; Referral and Consultation ; Retrospective Studies ; Risk Factors ; *Sepsis ; },
abstract = {PURPOSE: To evaluate the relationship between mortality or relapse of bloodstream infection (BSI) due to Enterococcus faecalis and infectious diseases specialist consultation (IDC) and other factors potentially associated with outcomes.<br><br>METHODS: In a tertiary-care center, consecutive adult patients with E. faecalis BSI between January 1, 2016 and January 31, 2019, were prospectively followed. The management of E. faecalis BSI was evaluated in terms of adherence to evidence-based quality-of-care indicators (QCIs). IDC and other factors potentially associated with 90-day-mortality or relapse of E. faecalis BSI were analyzed by multivariate logistic regression.<br><br>RESULTS: A total of 151 patients with a median age of 68&#xa0;years were studied. IDC was performed in 38% of patients with E. faecalis BSI. 30 cases of endocarditis (20%) were diagnosed. All-cause in-hospital mortality was 23%, 90-day mortality was 37%, and 90-day relapsing E. faecalis BSI was 8%. IDC was significantly associated with better adherence to 5 QCIs. Factors significantly associated with 90-day mortality or relapsing EfB in multivariate analysis were severe sepsis or septic shock at onset (HR 4.32, CI 2.36e7.88) and deep-seated focus of infection (superficial focus HR 0.33, CI 0.14e0.76).<br><br>CONCLUSION: Enterococcus faecalis bacteremia is associated with a high mortality. IDC contributed to improved diagnostic and therapeutic management.},
}
@article {pmid34708717,
year = {2021},
author = {Wang, YY and Liu, C and Chen, X and Ji, J and Zhu, SL and Sun, Q and Zhang, K and Zhu, J and Zhao, S and Wang, YW and Ma, R and Wang, JL},
title = {Heat shock protein 90α in nipple discharge as a potential tumor marker for breast cancer.},
journal = {The Chinese journal of physiology},
volume = {64},
number = {5},
pages = {251-256},
doi = {10.4103/cjp.cjp_72_21},
pmid = {34708717},
issn = {0304-4920},
mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnosis ; Female ; HSP90 Heat-Shock Proteins/*genetics ; Humans ; *Nipple Discharge ; },
abstract = {Heat shock protein 90α (HSP90α) has been confirmed to be upregulated in the blood in various types of tumors and may therefore serve as a potential tumor marker. However, whether HSP90α exists in nipple discharge remains unknown, and its expression and diagnostic value in nipple discharge remain unclear. In this study, the expression of HSP90α, carcinoembryonic antigen (CEA), and cancer antigen 153 in nipple discharge and blood from 128 patients was measured. Receiver operating characteristic curve was used to assess the diagnostic value of HSP90α. Further, its relationship with clinicopathological parameters of patients with breast cancer was analyzed. The results showed that the expression of HSP90α in nipple discharge was significantly higher in patients with breast cancer than in those with benign disease, and its diagnostic value was better than that of CEA. Combination of HSP90α and CEA showed better diagnostic efficacy than HSP90α or CEA alone. Moreover, the expression of HSP90α displayed a stepwise increase from benign lesions, followed by carcinoma in situ to invasive ductal carcinoma. HSP90α was positively correlated with Ki67 expression. However, there was no significant difference in the expression of HSP90α in blood between patients with breast cancer and benign disease. Further, the expression of HSP90α was higher in nipple discharge than in blood. In summary, HSP90α was upregulated in the nipple discharge of patients with breast cancer, and it may be related to the occurrence and progression of breast cancer. HSP90α in nipple discharge may serve as a potential diagnostic marker for breast cancer.},
}
@article {pmid34707969,
year = {2021},
author = {Blum, K and Bowirrat, A and Gondre Lewis, MC and Simpatico, TA and Ceccanti, M and Steinberg, B and Modestino, EJ and Thanos, PK and Baron, D and McLaughlin, T and Brewer, R and Badgaiyan, RD and Ponce, JV and Lott, L and Gold, MS},
title = {Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) During Adolescent Brain Development.},
journal = {Current psychopharmacology},
volume = {10},
number = {},
pages = {},
pmid = {34707969},
issn = {2211-5560},
support = {R01 DA035923/DA/NIDA NIH HHS/United States ; R01 NS073884/NS/NINDS NIH HHS/United States ; R01 AA021262/AA/NIAAA NIH HHS/United States ; R41 MD012318/MD/NIMHD NIH HHS/United States ; R01 HD070888/HD/NICHD NIH HHS/United States ; I01 CX000479/CX/CSRD VA/United States ; R21 MH073624/MH/NIMH NIH HHS/United States ; R01 DA035949/DA/NIDA NIH HHS/United States ; },
abstract = {BACKGROUND: The risk for all addictive drug and non-drug behaviors, especially, in the unmyelinated Prefrontal Cortex (PFC) of adolescents, is important and complex. Many animal and human studies show the epigenetic impact on the developing brain in adolescents, compared to adults. Some reveal an underlying hyperdopaminergia that seems to set our youth up for risky behaviors by inducing high quanta pre-synaptic dopamine release at reward site neurons. In addition, altered reward gene expression in adolescents caused epigenetically by social defeat, like bullying, can continue into adulthood. In contrast, there is also evidence that epigenetic events can elicit adolescent hypodopaminergia. This complexity suggests that neuroscience cannot make a definitive claim that all adolescents carry a hyperdopaminergia trait.<br><br>OBJECTIVE: The primary issue involves the question of whether there exists a mixed hypo or hyper-dopaminergia in this population.<br><br>METHOD: Genetic Addiction Risk Score (GARS&#xae;) testing was carried out of 24 Caucasians of ages 12-19, derived from families with RDS.<br><br>RESULTS: We have found that adolescents from this cohort, derived from RDS parents, displayed a high risk for any addictive behavior (a hypodopaminergia), especially, drug-seeking (95%) and alcohol-seeking (64%).<br><br>CONCLUSION: The adolescents in our study, although more work is required, show a hypodopaminergic trait, derived from a family with Reward Deficiency Syndrome (RDS). Certainly, in future studies, we will analyze GARS in non-RDS Caucasians between the ages of 12-19. The suggestion is first to identify risk alleles with the GARS test and, then, use well-researched precision, pro-dopamine neutraceutical regulation. This "two-hit" approach might prevent tragic fatalities among adolescents, in the face of the American opioid/psychostimulant epidemic.},
}
@article {pmid34702045,
year = {2021},
author = {Ilbeigi, S and Naeimzadeh, Y and Davoodabadi Farahani, M and Rafi Monjezi, M and Dastsooz, H and Daraei, A and Farahani, F and Dastgheib, A and Mansoori, Y and Tabei, SMB},
title = {Clinical values of two estrogen receptor signaling targeted lncRNAs in invasive ductal breast carcinoma.},
journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti},
volume = {34},
number = {5},
pages = {382-391},
doi = {10.48095/ccko2021382},
pmid = {34702045},
issn = {1802-5307},
mesh = {Adult ; Aged ; Breast/metabolism ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cell Line, Tumor ; Computational Biology ; Female ; Humans ; Middle Aged ; *RNA, Long Noncoding ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Signal Transduction ; },
abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of quickly emerging new data regarding the molecular heterogeneity of invasive cancers, far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in the heterogeneity feature of BC.<br><br>METHODS: In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues. And finally, bio-informatic evaluation has been done.<br><br>RESULTS: The results of quantitative polymerase chain reaction showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P = 0.0085 and P = 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P = 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with the age at menarche < 14 years compared to patients with the age at menarche 14 (P = 0.041). It was observed in another result that lncRNA RP11-48B3.4 is significantly upregulated in tumors with a lower histological grade compared to tumor samples with higher grades (P = 0.047). And finally, using bio-informatic evaluation, we found a predicted interaction between RP11-48B3.4 and mRNA zinc finger and BTB domain containing 10 (ZBTB10).<br><br>CONCLUSION: Altogether, our findings suggest that these lncRNAs with potential oncogenic roles are involved in the pathogenesis of IDC with clinical significance and they may therefore serve as novel markers for the dia-gnosis and treatment of IDC.},
}
@article {pmid34698916,
year = {2022},
author = {Deshpande, SS and Malik, SC and Conforti, P and Lin, JD and Chu, YH and Nath, S and Greulich, F and Dumbach, MA and Uhlenhaut, NH and Schachtrup, C},
title = {P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke.},
journal = {Cell and tissue research},
volume = {387},
number = {3},
pages = {415-431},
pmid = {34698916},
issn = {1432-0878},
support = {1442/8-1//Deutsche Forschungsgemeinschaft/ ; 1442/9-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Animals ; Lateral Ventricles/metabolism ; Mice ; *Neural Stem Cells ; Neurogenesis ; Receptor, Nerve Growth Factor/metabolism ; *Stroke ; },
abstract = {Stroke is the leading cause of adult disability. Endogenous neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to the brain repair process. However, molecular mechanisms underlying CNS disease-induced SVZ NSPC-redirected migration to the lesion area are poorly understood. Here, we show that genetic depletion of the p75 neurotrophin receptor (p75[NTR-/-]) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75[NTR-/-] NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75[NTR] abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75[NTR-/-] NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75[NTR-/-] NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75[NTR] abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury.},
}
@article {pmid34695137,
year = {2021},
author = {Opoku, F and Bedu-Addo, K and Titiloye, NA and Atta Manu, E and Ameh-Mensah, C and Duduyemi, BM},
title = {Expression profile of tumour suppressor protein p53 and its regulator MDM2 in a cohort of breast cancer patients in a Tertiary Hospital in Ghana.},
journal = {PloS one},
volume = {16},
number = {10},
pages = {e0258543},
pmid = {34695137},
issn = {1932-6203},
mesh = {Humans ; *Proto-Oncogene Proteins c-mdm2/metabolism/genetics ; *Tumor Suppressor Protein p53/metabolism/genetics ; Female ; Middle Aged ; Adult ; *Breast Neoplasms/pathology/metabolism/genetics ; Aged ; Aged, 80 and over ; Retrospective Studies ; *Tertiary Care Centers ; Ghana/epidemiology ; Young Adult ; Adolescent ; Cross-Sectional Studies ; Immunohistochemistry ; Biomarkers, Tumor/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; Receptor, ErbB-2/metabolism/genetics ; },
abstract = {BACKGROUND: Inactivation or mutation of the tumour suppressor gene p53 or its regulator mouse double minute 2 (MDM2) is the commonest event in breast cancer. These altered genes usually express abnormally high levels of their proteins in many carcinomas. The phenotypic expression of p53 and MDM2 in breast cancer cases in our setting is not known. This study investigated the expression of the tumour suppressor protein p53 and its regulator MDM2, using immunohistochemistry in a Ghana breast cancer cohort.<br><br>METHOD: A 9-year retrospective cross-sectional study on archived tissue blocks-formalin fixed paraffin embedded tissue (FFPE) was carried out. Demographic data were abstracted. Based on complete clinical data and availability of FFPE archived blocks 203 cases were selected for tissue micro array (TMA) construction. The TMA sections were subjected to immunohistochemistry (IHC) (ER, PR, HER2, p53, and MDM2). Expression of p53 and MDM2 were related to grade and molecular subtypes.<br><br>RESULTS: The age ranged from 17 to 92 years (mean = 49.34 &#xb1; 13.74). Most of the cases were high grade; grade II (34.9%) and grade III (55.7%). Fifty-four percent of the cases were triple negative. Invasive ductal carcinoma no special type was the commonest histotype (87.1%). Thirty-six percent (36%) of the cases expressed p53. Significant associations were found between p53 overexpression and histological grade (p = 0.034), triple negative (p = 0.0333) and luminal B (p<0.01) tumors. Most cases (93.1%) were negative for MDM2 expression. Significant association was found between MDM2 and HER2 over-expression as well as Ki-67. There was no significant positive correlation between MDM2 and p53 co-expression (p>0.05).<br><br>CONCLUSION: The elevated level of p53 expression in the aggressive breast cancer phenotypes (high histological grade and triple negative) in our cohort suggest that P53 elevation may be a poor prognostic marker in our setting. High expression of MDM2 in our cohort with high Ki67; also in cases with Her2/neu overexpression known with predictable poor prognosis in the absence of target therapy suggest MDM2 may be associated with aggressive biological behaviour in our breast cancer cases. The non-significant association of p53 and MDM2 expression in the same cases as also documented by previous studies suggest independent genetic pathway in tumourigenesis.},
}
@article {pmid34689837,
year = {2021},
author = {Rafiq, MT and Abdul Hamid, MS and Hafiz, E},
title = {The effect of rehabilitation protocol using mobile health in overweight and obese patients with knee osteoarthritis: a clinical trial.},
journal = {Advances in rheumatology (London, England)},
volume = {61},
number = {1},
pages = {63},
pmid = {34689837},
issn = {2523-3106},
mesh = {Clinical Protocols ; Humans ; Middle Aged ; *Obesity/complications ; *Osteoarthritis, Knee/rehabilitation ; *Overweight/complications ; *Telemedicine ; Treatment Outcome ; },
abstract = {OBJECTIVE: The objective of this randomized controlled trial (RCT) was to investigate the effectiveness of the lower limb rehabilitation protocol (LLRP) combined with mobile health (mHealth) applications on knee pain, mobility, functional activity and activities of daily living (ADL) among knee osteoarthritis (OA) patients who were overweight and obese.<br><br>METHODS: This study was a single-blind, RCT conducted at Teaching Bay of Rehmatul-Lil-Alameen Post Graduate Institute of Cardiology between February and November 2020. 114 knee OA patients who were overweight and obese were randomly divided by a computer-generated number into the rehabilitation group with mHealth (RGw-mHealth) to receive LLRP&#x2009;+ instructions of daily care (IDC) combined with mHealth intervention, rehabilitation group without mHealth (RGwo-mHealth) to receive LLRP&#x2009;+&#x2009;IDC intervention and control group (CG) to receive IDC intervention. All three groups were also provided leaflets explaining about their intervention. The primary outcome measure was knee pain measured by the Western Ontario and McMaster Universities Osteoarthritis Index score. The secondary outcome measures were mobility measured by the Timed up and go (TUG) test, functional activity measured by the patient-specific functional scale (PSFS), and ADL measured by the Katz Index of independence in ADL scores.<br><br>RESULTS: Among the 114 patients who were randomized (mean age, 53&#xa0;years), 96 (84%) completed the trial. After 3-months of intervention, patients in all three groups had statistically significant knee pain reduction (RGw-mHealth: 2.54; RGwo-mHealth: 1.47; and CG: 0.37) within groups (P&#x2009;<&#x2009;0.05). Furthermore, patients in the RGw-mHealth and RGwo-mHealth had statistically significant improvement in mobility, functional activity, and ADL within groups (P&#x2009;<&#x2009;0.05), but no improvement was noted in the CG (p&#x2009;>&#x2009;0.05). As indicated in the overall analysis of covariance, there were statistically significant differences in the mean knee pain, mobility, functional activity, and ADL changes between groups after 3-months (p&#x2009;<&#x2009;0.001). The pairwise between-group comparisons (Bonferroni post hoc analysis) of the knee pain, mobility, functional activity, and ADL scores at 3-months revealed that patients in the RGw-mHealth had significantly higher mean change in the knee pain, TUG test, functional activity, and ADL scores compared to patients in the RGwo-mHealth or CG.<br><br>CONCLUSION: Reduction in knee pain, improvement in mobility, functional activity, and ADL were more among patients in the RGw-mHealth compared with the RGwo-mHealth or CG. Trial registration National Medical Research Registry: NMRR-20-1094-52911. Date of registration: 05-05-2020. URL: https://www.nmrr.gov.my .},
}
@article {pmid34673584,
year = {2021},
author = {Senel, F},
title = {The hormone receptor status in breast cancer and the relationship of subtypes with clinicopathological features.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {64},
number = {4},
pages = {671-676},
doi = {10.4103/IJPM.IJPM_606_20},
pmid = {34673584},
issn = {0974-5130},
mesh = {Adult ; Age Factors ; Biomarkers, Tumor/*genetics/*metabolism ; Breast Neoplasms/*genetics/*metabolism/*physiopathology ; Female ; Genetic Variation ; Genotype ; Humans ; Middle Aged ; Pathology, Clinical/methods ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Retrospective Studies ; },
abstract = {AIM: We aimed to determine the hormone receptor status in breast cancers and to investigate the relationship between single hormone receptor-positive, double hormone receptor-positive, double hormone receptor negativity, and human epidermal growth factor receptor 2 (HER2) status and some clinicopathological features.<br><br>MATERIALS AND METHODS: The study includes 85 patients who were diagnosed in our center between 2018 and 2019 and having surgical specimens were included in the study. Data of the cases, such as estrogen receptor (ER), progesterone receptor (PR), HER2 status, silver in situ hybridization (SISH) evaluation results, age distribution, histopathological findings were recorded.<br><br>RESULTS AND CONCLUSIONS: We investigated the relationship between age, grade, tumor size, lymph node metastases and ER, PR, and HER2. However, there was not a significant association between ER, PR, and HER2 and age, tumor size, lymph node metastases (P > 0.05). On the other hand, we found a significant association between grades and ER (P = 0.02) and PR (P = 0.004), but not between grades and HER2 (P > 0.05). High-grade tumors were tumors with the lowest ER, PR positivity rate. Considering the four subtypes, cases aged above 45 years were at most double hormone receptor-positive (75%) and ER-positive/PR-negative (56%), respectively (P < 0.001). High-grade tumors were mostly double hormone receptor-negative and at least double hormone receptor positive. The ER-positive/PR-negative subtype was between these two groups (P < 0.001). The increased tumor size (T3) and increased metastatic lymph node number (N2 and N3) were observed at least in the ER-positive/PR-negative subtype. The majority of cases are in the older age group and invasive ductal carcinoma (IDC) is the most common tumor type. Older cases are most frequently double hormone receptor-positive and ER-positive/PR-negative, respectively. The ER, PR positivity rate is low in high-grade tumors. ER-positive/PR-negative tumors are of a higher grade than double hormone receptor-positive tumors, but they are of a lower grade than double hormone receptor-negative tumors. The increased tumor size and increased lymph node metastasis number are at most in the double hormone negative subtype and at least in the ER-positive/PR-negative subtype. The ER-negative/PR-positive subtype is observed very rarely, which raises the question of whether ER-negative/PR-positive tumors really exist. Further studies are needed to investigate this subtype and its properties.},
}
@article {pmid34672684,
year = {2021},
author = {Yadav, S and Hu, C and Nathanson, KL and Weitzel, JN and Goldgar, DE and Kraft, P and Gnanaolivu, RD and Na, J and Huang, H and Boddicker, NJ and Larson, N and Gao, C and Yao, S and Weinberg, C and Vachon, CM and Trentham-Dietz, A and Taylor, JA and Sandler, DR and Patel, A and Palmer, JR and Olson, JE and Neuhausen, S and Martinez, E and Lindstrom, S and Lacey, JV and Kurian, AW and John, EM and Haiman, C and Bernstein, L and Auer, PW and Anton-Culver, H and Ambrosone, CB and Karam, R and Chao, E and Yussuf, A and Pesaran, T and Dolinsky, JS and Hart, SN and LaDuca, H and Polley, EC and Domchek, SM and Couch, FJ},
title = {Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {39},
number = {35},
pages = {3918-3926},
pmid = {34672684},
issn = {1527-7755},
support = {R01 CA097396/CA/NCI NIH HHS/United States ; Z01 ES049033/ImNIH/Intramural NIH HHS/United States ; K07 CA092044/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R35 CA253187/CA/NCI NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; R01 CA049449/CA/NCI NIH HHS/United States ; R01 CA192393/CA/NCI NIH HHS/United States ; U01 CA164973/CA/NCI NIH HHS/United States ; R01 CA185623/CA/NCI NIH HHS/United States ; R01 CA100598/CA/NCI NIH HHS/United States ; U01 CA199277/CA/NCI NIH HHS/United States ; R01 CA225662/CA/NCI NIH HHS/United States ; UM1 CA164917/CA/NCI NIH HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; HHSN268201600002C/HL/NHLBI NIH HHS/United States ; Z01 ES044005/ImNIH/Intramural NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; U01 CA164974/CA/NCI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; R01 CA098663/CA/NCI NIH HHS/United States ; HHSN268201600018C/HL/NHLBI NIH HHS/United States ; R01 CA204819/CA/NCI NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; P01 CA151135/CA/NCI NIH HHS/United States ; R01 CA067264/CA/NCI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; R01 CA058860/CA/NCI NIH HHS/United States ; R01 CA047147/CA/NCI NIH HHS/United States ; U01 CA082004/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; HHSN268201600003C/HL/NHLBI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; HHSN268201600004C/HL/NHLBI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; R01 CA077398/CA/NCI NIH HHS/United States ; U01 CA164920/CA/NCI NIH HHS/United States ; HHSN268201600001C/HL/NHLBI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; *Genetic Predisposition to Disease ; Genetic Testing/*methods ; *Germ-Line Mutation ; Humans ; Middle Aged ; Prognosis ; Young Adult ; },
abstract = {PURPOSE: To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast.<br><br>MATERIALS AND METHODS: The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC).<br><br>RESULTS: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC.<br><br>CONCLUSION: The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.},
}
@article {pmid34668757,
year = {2021},
author = {Saelens, JW and Petersen, JEV and Freedman, E and Moseley, RC and Konaté, D and Diakité, SAS and Traoré, K and Vance, N and Fairhurst, RM and Diakité, M and Haase, SB and Taylor, SM},
title = {Impact of Sickle Cell Trait Hemoglobin on the Intraerythrocytic Transcriptional Program of Plasmodium falciparum.},
journal = {mSphere},
volume = {6},
number = {5},
pages = {e0075521},
pmid = {34668757},
issn = {2379-5042},
support = {R21 AI125988/AI/NIAID NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; },
mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Hemoglobin A/*genetics ; Hemoglobin, Sickle/*genetics ; Hemoglobins/metabolism ; Humans ; Malaria, Falciparum/blood/*genetics/parasitology ; Male ; Plasmodium falciparum/physiology ; Sickle Cell Trait/blood/*genetics/parasitology ; Transcriptional Activation ; },
abstract = {Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by which HbAS confers these protective phenotypes remain incompletely understood. As a forward genetic screen for aberrant parasite transcriptional responses associated with parasite neutralization in HbAS red blood cells (RBCs), we performed comparative transcriptomic analyses of Plasmodium falciparum in normal (HbAA) and HbAS erythrocytes during both in vitro cultivation of reference parasite strains and naturally occurring P. falciparum infections in Malian children with HbAA or HbAS. During in vitro cultivation, parasites matured normally in HbAS RBCs, and the temporal expression was largely unperturbed of the highly ordered transcriptional program that underlies the parasite's maturation throughout the intraerythrocytic development cycle (IDC). However, differential expression analysis identified hundreds of transcripts aberrantly expressed in HbAS, largely occurring late in the IDC. Surprisingly, transcripts encoding members of the Maurer's clefts were overexpressed in HbAS despite impaired parasite protein export in these RBCs, while parasites in HbAS RBCs underexpressed transcripts associated with the endoplasmic reticulum and those encoding serine repeat antigen proteases that promote parasite egress. Analyses of P. falciparum transcriptomes from 32 children with uncomplicated malaria identified stage-specific differential expression: among infections composed of ring-stage parasites, only cyclophilin 19B was underexpressed in children with HbAS, while trophozoite-stage infections identified a range of differentially expressed transcripts, including downregulation in HbAS of several transcripts associated with severe malaria in collateral studies. Collectively, our comparative transcriptomic screen in vitro and in vivo indicates that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Because HbAS consistently protects from severe P. falciparum, modulation of these responses may offer avenues by which to neutralize P. falciparum parasites. IMPORTANCE Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening malaria, yet the molecular mechanisms that underlie HbAS protection from severe malaria remain incompletely understood. Here, we used transcriptome sequencing (RNA-seq) to measure the impact of HbAS on the blood-stage transcriptome of Plasmodium falciparum in in vitro time series experiments and in vivo samples from natural infections. Our in vitro time series data reveal that, during its blood stage, P. falciparum's gene expression in HbAS is impacted primarily through alterations in the abundance of gene products as opposed to variations in the timing of gene expression. Collectively, our in vitro and in vivo data indicate that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Due to the persistent association of HbAS and protection from severe disease, these processes that are modified in HbAS may offer strategies to neutralize P. falciparum.},
}
@article {pmid34659834,
year = {2021},
author = {Ntirenganya, F and Twagirumukiza, JD and Bucyibaruta, G and Rugwizangoga, B and Rulisa, S},
title = {Premenopausal Breast Cancer Risk Factors and Associations with Molecular Subtypes: A Case-Control Study.},
journal = {International journal of breast cancer},
volume = {2021},
number = {},
pages = {5560559},
pmid = {34659834},
issn = {2090-3170},
abstract = {BACKGROUND: Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women's cancer-related deaths and morbidity worldwide. In Rwanda, BC incidence is increasing with an unacceptably high mortality rate in premenopausal women.<br><br>OBJECTIVES: The purpose was to identify modifiable BC risk factors and assess associations between common breast cancer risks factors and molecular subtypes in premenopausal women in Rwanda.<br><br>METHODS: This was a case-control study. Premenopausal women with histological confirmation of BC and frequency-matched for age controls were recruited. A preestablished questionnaire was administered to both cases and controls for sociodemographics, BC probable risk factors, and clinical and pathological characteristics. BC was classified into luminal A, luminal B, HER2-type, basal-like (triple negative), and unclassified molecular subtypes by immunohistochemistry (IHC). Odds ratio (OR) and 95% confidence interval (CI) were estimated using multivariate logistic regression analysis.<br><br>RESULTS: 340 participants were recruited into the study (170 cases vs. 170 controls). The median age was 39 years. The majority of cases presented at advanced stages of the disease (51.2% in stages III and IV) and had invasive ductal carcinoma (98.2%). 60.6% had subtypes of poor prognosis (HER2 enriched 14.7%, triple negative 12.9%, and unclassified 32.9%). Alcohol intake (AOR = 3.73, 95%CI&#x2009;2.19 - 6.32, p < 0.001), obesity/overweight in adolescence or early adulthood (AOR = 10.86, 95%CI&#x2009;4.82 - 24.4, p < 0.001), history of primary infertility (AOR = 33.8, 95%CI&#x2009;3.5 - 321.5, p = 0.002), nulliparity (AOR = 3.75, 95%CI&#x2009;1.61 - 8.75, p = 0.002), and a history of benign breast disease (AOR = 6.06, 95%CI&#x2009;1.19 - 30.73, p = 0.03) were associated with the occurrence of premenopausal breast cancer. There was no significant difference between risk factor stratification per molecular subtype.<br><br>CONCLUSION: Several reproductive, environmental, and lifestyle risk factors have been identified to be associated with premenopausal BC. Among them, alcohol intake and obesity/overweight during adolescence/early adulthood can be modified. Interventions targeting alcohol consumption and obesity/overweight in adolescents and young adults may decrease the incidence of premenopausal breast cancer.},
}
@article {pmid34657058,
year = {2021},
author = {Takagi, H and Fukai, H and Misawa, S and Kurogochi, A and Kirii, Y},
title = {[A Case of Bone Marrow Carcinomatosis Associated with Breast Cancer with Anemia and Thrombocytopenia Successfully Treated with Aromatase Inhibitor Therapy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {48},
number = {10},
pages = {1255-1257},
pmid = {34657058},
issn = {0385-0684},
mesh = {*Anemia/drug therapy/etiology ; Aromatase Inhibitors ; Bone Marrow ; *Breast Neoplasms/complications/drug therapy/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Peritoneal Neoplasms ; *Thrombocytopenia/drug therapy/etiology ; },
abstract = {The patient was a 61-year-old woman who presented to the hospital with the chief complaints of anemia and thrombocytopenia. There was a mass in her left breast, and a needle biopsy with pathology revealed invasive ductal carcinoma, which was HR-positive and HER2-negative. A PET scan revealed multiple bone metastases, which were confirmed on bone marrow biopsy, leading to the diagnosis of bone marrow carcinomatosis. As the patient was in good general condition, an aromatase inhibitor(AI)therapy was selected. Rapid improvements in her hemoglobin level and platelet count were observed. At 19 months after the start of treatment, we were able to perform a left mastectomy with left axillary lymph node dissection. The histological evaluation of her response to treatment was Grade 2a, and severe lymph node metastasis was observed. The patient continued to receive the AI postoperatively. Thirty-two months after the start of treatment, there was no evidence of cancer on clinical imaging. Although it is rare for bone marrow carcinomatosis to occur, as in the present case, it is also notable that the patient had been in long-term remission with consistent AI therapy.},
}
@article {pmid34645713,
year = {2021},
author = {Teodorescu, K and Plonsky, O and Ayal, S and Barkan, R},
title = {Frequency of enforcement is more important than the severity of punishment in reducing violation behaviors.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {118},
number = {42},
pages = {},
pmid = {34645713},
issn = {1091-6490},
mesh = {COVID-19/*prevention &amp; control/virology ; Decision Making ; Humans ; Probability ; *Punishment ; SARS-CoV-2/isolation &amp; purification ; },
abstract = {External enforcement policies aimed to reduce violations differ on two key components: the probability of inspection and the severity of the punishment. Different lines of research offer different insights regarding the relative importance of each component. In four studies, students and Prolific crowdsourcing participants (Ntotal = 816) repeatedly faced temptations to commit violations under two enforcement policies. Controlling for expected value, we found that a policy combining a high probability of inspection with a low severity of fines (HILS) was more effective than an economically equivalent policy that combined a low probability of inspection with a high severity of fines (LIHS). The advantage of prioritizing inspection frequency over punishment severity (HILS over LIHS) was greater for participants who, in the absence of enforcement, started out with a higher violation rate. Consistent with studies of decisions from experience, frequent enforcement with small fines was more effective than rare severe fines even when we announced the severity of the fine in advance to boost deterrence. In addition, in line with the phenomenon of underweighting of rare events, the effect was stronger when the probability of inspection was rarer (as in most real-life inspection probabilities) and was eliminated under moderate inspection probabilities. We thus recommend that policymakers looking to effectively reduce recurring violations among noncriminal populations should consider increasing inspection rates rather than punishment severity.},
}
@article {pmid34634714,
year = {2021},
author = {Kufel, WD and Mastro, KA and Steele, JM and Wang, D and Riddell, SW and Paolino, KM and Thomas, SJ},
title = {Impact of a pharmacist-facilitated, evidence-based bundle initiative on Staphylococcus aureus bacteremia management.},
journal = {Diagnostic microbiology and infectious disease},
volume = {101},
number = {4},
pages = {115535},
doi = {10.1016/j.diagmicrobio.2021.115535},
pmid = {34634714},
issn = {1879-0070},
mesh = {Adult ; Anti-Bacterial Agents/*therapeutic use ; Antimicrobial Stewardship ; Bacteremia/*drug therapy/microbiology ; Female ; Humans ; Male ; Middle Aged ; *Patient Care Bundles ; Patient Compliance ; *Pharmacists ; Referral and Consultation ; Staphylococcal Infections/*drug therapy/microbiology ; Staphylococcus aureus/drug effects/isolation &amp; purification ; Treatment Outcome ; },
abstract = {OBJECTIVE: To evaluate a pharmacist-facilitated evidence-based bundle (EBB) initiative with infectious disease consultation (IDC) for Staphylococcus aureus bacteremia (SAB).<br><br>METHODS: This was a before-and-after quasi-experimental study of adult patients with SAB before and after the pharmacist-facilitated EBB initiative, which included IDC, timely definitive antibiotics, source control, echocardiography, and repeat blood cultures.<br><br>RESULTS: Ninety and 111 patients were included in pre- and post-intervention cohorts, respectively. We observed significant increases in adherence to all 5 (4.4% vs 68.5%, P < 0.001) and 4 (10.0% vs 76.6%, P < 0.001) EBB elements. Time to definitive antibiotics (48 vs 16 hours, P < 0.001), time to IDC (43.5 vs 32 hours, P < 0.001), SAB duration (95 vs 66 hours, P&#xa0;=&#xa0;0.009), persistent SAB (18.9% vs 9.0%, P&#xa0;=&#xa0;0.041), and length of stay (14 vs 13 days, P&#xa0;=&#xa0;0.027) also improved. No statistically significant differences for SAB-related readmission or all-cause mortality were observed.<br><br>CONCLUSIONS: Our pharmacist-facilitated SAB initiative was associated with improved EBB adherence and clinical outcomes.},
}
@article {pmid34624832,
year = {2021},
author = {Mohammed, AA},
title = {The clinical behavior of different molecular subtypes of breast cancer.},
journal = {Cancer treatment and research communications},
volume = {29},
number = {},
pages = {100469},
doi = {10.1016/j.ctarc.2021.100469},
pmid = {34624832},
issn = {2468-2942},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; },
abstract = {BACKGROUND: Breast cancer is a heterogeneous group of tumors classified, according to different gene expressions that encodes for the hormone receptor status, into 4 main categories which are: luminal types A and B, triple negative/basal-like, and Her-2 molecular subtypes.<br><br>PATIENTS AND METHODS: This retrospective study included 311 breast cancer females. Patients were classified according to the expression of hormone receptors into: Luminal-A, luminal-B, HER-2 enriched and basal-like types. All groups were then studied for differences in clinical course of the disease.<br><br>RESULTS: Luminal-B type was the commonest molecular type (43.73%). Invasive ductal carcinoma was the commonest histological type (89.1%). Stages IIB and IIIA were the commonest clinical stages (24.4% &amp; 22.2%) respectively. Most patients had no recurrence (85.5%), the commonest recurrence was local and axillary ones (7.1%). Low grade tumors were less frequent than intermediate and high grades (3.5%, 51.1%, and 45.3%). We found a significant correlation between molecular subtypes and survival status, tumor grade, and histopathological types (P values 0.029, 0.001, and 0.006) respectively, while it was not significant with age, BMI, recurrence &amp; metastatic disease, overall survival, and TNM stage (P values 0.648, 0.398, 0.5, 0.063 and 0.319).<br><br>CONCLUSION: Luminal types A and B are the commonest molecular subtypes of breast cancer. Luminal type A is associated with improved survival, and basal like has the highest breast cancer fatality rates. Invasive ductal carcinomas of specific types mostly found in patients with luminal types A and B, while other rare forms like Paget's disease was diagnosed HER-2 enriched types.},
}
@article {pmid34610495,
year = {2021},
author = {Rousseau, S and Katz, D and Shlomi-Polachek, I and Frenkel, TI},
title = {Prospective risk from prenatal anxiety to post traumatic stress following childbirth: The mediating effects of acute stress assessed during the postnatal hospital stay and preliminary evidence for moderating effects of doula care.},
journal = {Midwifery},
volume = {103},
number = {},
pages = {103143},
doi = {10.1016/j.midw.2021.103143},
pmid = {34610495},
issn = {1532-3099},
mesh = {Anxiety/etiology ; *Doulas ; Female ; Humans ; Length of Stay ; Parturition ; Postpartum Period ; Pregnancy ; Prospective Studies ; *Stress Disorders, Post-Traumatic/etiology ; },
abstract = {OBJECTIVE: Growing literature has identified childbirth as a potentially traumatic event, following which mothers may develop symptoms of Post-Traumatic-Stress-Following-Childbirth. The current study is the first to prospectively examine a pathway of risk from mothers' prenatal trait-anxiety, to Acute-Stress-Immediately-Following-Childbirth, and later symptoms of Post-Traumatic-Stress-Following-Childbirth, in a low-risk community sample. Auxiliary analyses explored whether doula care during childbirth moderated risk.<br><br>METHOD: 149 pregnant women were randomly selected. Prenatal trait-anxiety was assessed toward the end of pregnancy, Acute-Stress-Immediately-Following-Childbirth at two-days post-partum, and symptoms of Post-Traumatic-Stress-Following-Childbirth at one-month post-partum.<br><br>RESULTS: Results indicated a significant indirect pathway from prenatal trait-anxiety to Post-Traumatic-Stress-Following-Childbirth, through Acute-Stress-Immediately-Following-Childbirth. Two groups were generated ad hoc for auxiliary analyses: participants who opted to receive doula care during childbirth (n=21; 14%) versus participants who received care as usual (n=128; 86%). Analyses provided preliminary support for doula care as a potential moderator of risk.<br><br>CONCLUSIONS: Results point toward prenatal trait-anxiety and Acute-Stress-Immediately-Following-Childbirth as significant risk factors for Post-Traumatic-Stress-Following-Childbirth. Findings inform preventive screening implicating the prenatal period as well as the postnatal hospital stay as important time windows for preventive screening. Finally, preliminary support for moderating effects of doula care suggest that preventive interventions administered during the perinatal period may effectively reduce anxiety-related risk for Post-Traumatic-Stress-Following-Childbirth.},
}
@article {pmid34597458,
year = {2021},
author = {Viswanathan, K and Sadow, PM and Maleki, Z and Nishino, M and Baloch, ZW and Abbott, TE and Rao, R and Faquin, WC},
title = {Cytomorphologic features of intraductal salivary gland carcinoma: A multi-institutional study of 13 FNA cases with histologic, molecular, and clinical correlations.},
journal = {Cancer cytopathology},
volume = {129},
number = {12},
pages = {928-946},
pmid = {34597458},
issn = {1934-6638},
support = {P01 CA240239/CA/NCI NIH HHS/United States ; 1PO1CA240239-01//National Cancer Institute of the National Institutes of Health/ ; },
mesh = {Biopsy, Fine-Needle/methods ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Gene Fusion ; Humans ; *Salivary Gland Neoplasms/pathology ; Salivary Glands/pathology ; },
abstract = {BACKGROUND: Intraductal carcinoma of the salivary gland (IDC) is a rare cancer with potential actionable targets, including RET fusions. Histologic and molecular features of IDC were recently reported, but cytomorphologic data are limited. In the largest multi-institutional fine-needle aspiration (FNA) series, the authors describe the cytomorphologic features of 13 IDC cases with available clinical, radiologic, histopathologic, and molecular data.<br><br>METHODS: The cases included 13 FNAs for 9 low-grade (LG) IDCs and 4 high-grade (HG) IDCs with corresponding histopathology and available molecular, imaging, and clinical data. Smears and liquid-based preparations available for 12 FNAs were semiquantitatively scored for key cytomorphologic findings and correlated with the corresponding resection.<br><br>RESULTS: LG IDC FNAs showed a cellular, biphasic population of large, atypical ductal cells with mildly pleomorphic nuclei in a clean background and a minor population of small, uniform myoepithelial cells. In contrast, all HG IDC FNAs showed predominantly ductal cells with marked nuclear pleomorphism, coarse chromatin, and necrosis. With the Milan system, most LG and HG IDC FNAs were classified as either salivary gland neoplasms of uncertain malignant potential (54%) or malignant (31%). Immunohistochemistry showed ductal epithelial reactivity with mammaglobin, androgen receptor, and S100, whereas myoepithelial cells were positive for p63 and/or calponin. Among cases with next-generation sequencing, 4 LG IDCs showed NCOA4-RET gene fusions, whereas an HG IDC showed HRAS and PIK3CA mutations.<br><br>CONCLUSIONS: The cytomorphology of IDC overlaps with other benign and malignant salivary gland neoplasms. Immunohistochemistry limits the differential diagnosis, but definitive classification requires molecular analysis. A diagnosis of IDC has potential implications for patient management.},
}
@article {pmid34592934,
year = {2021},
author = {Mathew, D and Gupta, S and Ashman, N},
title = {A case report of breast cancer and membranous nephropathy with positive anti phospholipase A2 receptor antibodies.},
journal = {BMC nephrology},
volume = {22},
number = {1},
pages = {324},
pmid = {34592934},
issn = {1471-2369},
mesh = {Adult ; Autoantibodies/*blood ; Breast Neoplasms/*complications ; Estrogen Receptor beta/analysis ; Female ; Glomerulonephritis, Membranous/*complications/immunology ; Humans ; Kidney/pathology ; Receptors, Phospholipase A2/*immunology ; },
abstract = {BACKGROUND: Testing for antibodies against podocyte phospholipase A2 receptor-1 (PLA2R) allows clinicians to accurately identify primary membranous nephropathy (MN). Secondary MN is associated with a spectrum of pathology including solid organ malignancy. PLA2R positivity in these patients occurs, although no case of PLA2R-positive MN has been definitively linked to cancer.<br><br>CASE PRESENTATION: We describe a case of biopsy-proven PLA2R-positive MN, in whom invasive ductal carcinoma of the breast was discovered. The patient underwent surgery and adjuvant chemotherapy (including cyclophosphamide) and went into a sustained complete remission of her nephrotic syndrome.<br><br>DISCUSSION AND CONCLUSIONS: Case series have reported PLA2R positivity in patients with solid organ malignancy associated MN. Our case is unusual as it is a breast malignancy, and the patients nephrotic syndrome and anti-PLA2Rab titres improved with treatment of the cancer. Here we report, to the best of our knowledge, the first case of oestrogen receptor-2 positive breast cancer associated with PLA2R positive MN in a young lady that was treated successfully by treating the malignancy.},
}
@article {pmid34587404,
year = {2021},
author = {Yang, L and Xiong, Y and Sun, Z and Lin, X and Ni, H},
title = {Neferine Inhibits 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumorigenesis by Suppression of Cell Proliferation and Induction of Apoptosis via Modulation of the PI3K/AKT/NF-κB Signaling Pathway.},
journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer},
volume = {40},
number = {3},
pages = {51-61},
doi = {10.1615/JEnvironPatholToxicolOncol.2021038118},
pmid = {34587404},
issn = {2162-6537},
mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Animals ; Antineoplastic Agents, Phytogenic/*pharmacology ; Apoptosis/*drug effects/physiology ; Benzylisoquinolines/*pharmacology ; Body Weight/drug effects ; Carcinogens/toxicity ; Cell Proliferation/drug effects/physiology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Lipid Peroxidation/drug effects ; Mammary Neoplasms, Experimental/chemically induced/*drug therapy/metabolism/pathology ; NF-kappa B/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Signal Transduction/drug effects ; },
abstract = {AIM: To investigate the anticancer mechanism of neferine on DMBA-prompted mammary tumorigenesis in animals.<br><br>METHODS: Mammary cancer was prompted by the subcutaneous injection of 25 mg DMBA mixed in 1 ml of the vehicle (sunflower oil [0.5 ml] and saline [0.5 ml]). We analyzed the biochemical and molecular expression of cell-proliferation and apoptotic markers in normal and DMBA-induced rats.<br><br>RESULTS: We detected low body weight, elevated quantities of lipid peroxidation, and low antioxidant enzyme activities in mammary tissues of DMBA-induced animals. We also found an invasive ductal carcinoma in DMBA-induced animals by histopathological assessment. Furthermore, western blotting findings displayed an augmented expression of PI3K, AKT, NF-&#x3ba;B, PCNA, cyclin D1, Ki-67, and Bcl-2, while reducing expression of p53, Bax, caspase-3, and caspase-9 in DMBA-induced cancer-bearing animals. RT-PCR results found upregulation of cyclin D1, PCNA, and Ki-67, and reduced expression of p53 in DMBA-prompted animals. The oral administration of neferine effectually inhibited mammary tumors via improved antioxidants and prevented lipid peroxidation activities when compared with tumor-bearing rats. Furthermore, neferine also modulated PI3K/AKT/NF-&#x3ba;B signaling through inhibiting cell proliferation and induced apoptosis in tumor-bearing rats.<br><br>CONCLUSION: In our findings, we concluded that neferine has an anti-proliferative and enhancing apoptotic property against DMBA-induced mammary cancer.},
}
@article {pmid34561670,
year = {2021},
author = {Kumar, V and Nawroth, PP},
title = {Is the association between diabetes mellitus and pulmonary fibrosis real?.},
journal = {Nature reviews. Endocrinology},
volume = {17},
number = {12},
pages = {703-704},
pmid = {34561670},
issn = {1759-5037},
mesh = {*Diabetes Mellitus/epidemiology ; Humans ; *Pulmonary Fibrosis/epidemiology ; Risk Factors ; },
}
@article {pmid34560418,
year = {2021},
author = {Wan, D and Zhang, Y and Yu, Q and Li, F and Zhuo, J},
title = {14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression.},
journal = {Pathology, research and practice},
volume = {227},
number = {},
pages = {153619},
doi = {10.1016/j.prp.2021.153619},
pmid = {34560418},
issn = {1618-0631},
mesh = {14-3-3 Proteins/genetics/*metabolism ; Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Nuclear Proteins/analysis ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*analysis ; Tumor Suppressor Protein p53/analysis ; Up-Regulation ; Young Adult ; Zinc Finger Protein Gli2/analysis ; },
abstract = {BACKGROUND: HER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14-3-3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too.<br><br>METHODS: Immunohistochemistry experiment was performed to detect expression status of 14-3-3&#x3b6;, HER2, TGF-&#x3b2;, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC.<br><br>RESULTS: The positive expression rates of 14-3-3&#x3b6;/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14-3-3&#x3b6; was significantly increased in ADH, DCIS and IDC groups. 14-3-3&#x3b6; was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14-3-3&#x3b6; overexpression was significantly different between DCIS group and IDC with DCIS group (P&#xa0;=&#xa0;0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14-3-3&#x3b6; was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14-3-3&#x3b6; and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14-3-3&#x3b6; and HER2 was positively correlated with occurrence of lymph node metastasis (P&#xa0;=&#xa0;0.048). TGF-&#x3b2; was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-&#x3b2; expression was significantly increased in the IDC group with lymph node metastasis (P&#xa0;=&#xa0;0.015). In IDC cases with 14-3-3&#x3b6; and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P&#xa0;=&#xa0;0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P&#xa0;=&#xa0;0.038). The co-overexpression of 14-3-3&#x3b6; and HER2 was positively correlated with ER negative expression (P&#xa0;<&#xa0;0.001) and PR negative expression (P&#xa0;=&#xa0;0.038), respectively.<br><br>CONCLUSION: 14-3-3&#x3b6; synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14-3-3&#x3b6; and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14-3-3&#x3b6; and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis.},
}
@article {pmid34557972,
year = {2021},
author = {Han, J and Harrison, L and Patzelt, L and Wu, M and Junker, D and Herzig, S and Berriel Diaz, M and Karampinos, DC},
title = {Imaging modalities for diagnosis and monitoring of cancer cachexia.},
journal = {EJNMMI research},
volume = {11},
number = {1},
pages = {94},
pmid = {34557972},
issn = {2191-219X},
support = {SFB824/A9//deutsche forschungsgemeinschaft/ ; },
abstract = {Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities-that is, computed tomography, magnetic resonance imaging, ([18]F) fluoro-2-deoxy-D-glucose ([18]FDG) PET and dual-energy X-ray absorptiometry-shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed.},
}
@article {pmid34556291,
year = {2021},
author = {Mangiardi-Veltin, M and Chamming's, F and Jaffre, A and Rousvoal, A and Tunon de Lara, C and Brouste, V and Hoppe, S and Sénéchal, C},
title = {[Prophylactic mastectomy and occult cancer: a ten-year experience at a cancer center].},
journal = {Bulletin du cancer},
volume = {108},
number = {11},
pages = {999-1009},
doi = {10.1016/j.bulcan.2021.05.007},
pmid = {34556291},
issn = {1769-6917},
mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*epidemiology/genetics ; Cancer Care Facilities ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Middle Aged ; Mutation ; Neoplasms, Unknown Primary/diagnostic imaging/*epidemiology/genetics ; Postoperative Complications/*epidemiology ; Prevalence ; Prophylactic Mastectomy/*adverse effects/methods ; Reoperation ; Retrospective Studies ; Time Factors ; },
abstract = {INTRODUCTION: Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers.<br><br>METHODS: All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts.<br><br>RESULTS: 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%).<br><br>DISCUSSION: Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.},
}
@article {pmid34555180,
year = {2022},
author = {Giroud, M and Jodeleit, H and Prentice, KJ and Bartelt, A},
title = {Adipocyte function and the development of cardiometabolic disease.},
journal = {The Journal of physiology},
volume = {600},
number = {5},
pages = {1189-1208},
doi = {10.1113/JP281979},
pmid = {34555180},
issn = {1469-7793},
mesh = {Adipocytes, Brown/metabolism ; Adipose Tissue, Brown/physiology ; Adipose Tissue, White/metabolism ; Animals ; *Cardiovascular Diseases/etiology/metabolism ; Diet, High-Fat/adverse effects ; Energy Metabolism ; Mice ; Obesity/metabolism ; Thermogenesis/physiology ; },
abstract = {Obesity is a medical disorder caused by multiple mechanisms of dysregulated energy balance. A major consequence of obesity is an increased risk to develop diabetes, diabetic complications and cardiovascular disease. While a better understanding of the molecular mechanisms linking obesity, insulin resistance and cardiovascular disease is needed, translational research of the human pathology is hampered by the available cellular and rodent model systems. Major barriers are the species-specific differences in energy balance, vascular biology and adipose tissue physiology, especially related to white and brown adipocytes, and adipose tissue browning. In rodents, non-shivering thermogenesis is responsible for a large part of energy expenditure, but humans possess much less thermogenic fat, which means temperature is an important variable in translational research. Mouse models with predisposition to dyslipidaemia housed at thermoneutrality and fed a high-fat diet more closely reflect human physiology. Also, adipocytes play a key role in the endocrine regulation of cardiovascular function. Adipocytes secrete a variety of hormones, lipid mediators and other metabolites that directly influence the local microenvironment as well as distant tissues. This is specifically apparent in perivascular depots, where adipocytes modulate vascular function and inflammation. Altogether, these mechanisms highlight the critical role of adipocytes in the development of cardiometabolic disease.},
}
@article {pmid34547924,
year = {2022},
author = {Moghalu, O and Stoffel, JT and Elliott, SP and Welk, B and Zhang, C and Presson, A and Myers, J},
title = {Time-Related Changes in Patient Reported Bladder Symptoms and Satisfaction after Spinal Cord Injury.},
journal = {The Journal of urology},
volume = {207},
number = {2},
pages = {392-399},
pmid = {34547924},
issn = {1527-3792},
support = {UL1 RR025764/RR/NCRR NIH HHS/United States ; UL1 TR000105/TR/NCATS NIH HHS/United States ; UL1 TR001067/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Catheters, Indwelling/*adverse effects/statistics &amp; numerical data ; Cross-Sectional Studies ; Female ; Humans ; Intermittent Urethral Catheterization/*adverse effects/psychology/statistics &amp; numerical data ; Male ; Patient Reported Outcome Measures ; Patient Satisfaction/*statistics &amp; numerical data ; Prospective Studies ; Quality of Life ; Registries ; Self Report/statistics &amp; numerical data ; Spinal Cord Injuries/*complications/therapy ; Time Factors ; Urinary Bladder/physiopathology ; Urinary Bladder, Neurogenic/etiology/psychology/*therapy ; Young Adult ; },
abstract = {PURPOSE: Increased time after spinal cord injury (SCI) is associated with a migration to bladder managements with higher morbidity such as indwelling catheter (IDC). Still, it is unclear how this affects bladder-related quality of life (QoL). We hypothesized that time from injury (TFI) would be associated with changes in bladder management, symptoms and satisfaction.<br><br>MATERIALS AND METHODS: Cross-sectional analysis of time-related changes in patient-reported bladder management, symptoms and satisfaction using the Neurogenic Bladder Research Group SCI Registry. Outcomes included Neurogenic Bladder Symptom Score (NBSS) and bladder-related satisfaction (NBSS-satisfaction). Multivariable regression was performed to assess associations between TFI and outcomes, adjusting for participant characteristics, injury specifics, and psychosocial aspects of health-related QoL. Participants with TFI <1 year were excluded and TFI was categorized 1-5 (reference), 6-10, 11-15, 16-20 and >20 years.<br><br>RESULTS: Of 1,420 participants mean age at injury was 29.7 years (SD 13.4) and mean TFI was 15.2 years (SD 11.6). Participants grouped by TFI included 298 (21%) 1-5, 340 (24%) 6-10, 198 (14%) 11-15, 149 (10%) 16-20 and 435 (31%) >20 years. As TFI increased, clean intermittent catheterization (CIC) declined (55% 1-5 vs 45% >20 years, p <0.001) and IDC increased (16% 1-5 vs 21% >20 years, p <0.001). On multivariable analysis, increased TFI was associated with fewer bladder symptoms at >20 years from injury (-3.21 [CI -1.29, -5.14, p <0.001]) and better satisfaction (6-10 years -0.20 [CI -0.41, 0.01, p=0.070], 11-15 years -0.36 [CI -0.60, -0.11, p=0.002], 16-20 years -0.59 [CI -0.86, -0.32, p <0.001], >20 years -0.85 [CI -1.07, -0.63, <0.001]).<br><br>CONCLUSIONS: After SCI, CIC decreases and IDC increases over time; however, increasing TFI is associated with reduced urinary symptoms and improved bladder-related satisfaction.},
}
@article {pmid34538726,
year = {2022},
author = {Ramotar, M and Chua, MLK and Truong, H and Hosni, A and Pintilie, M and Davicioni, E and Fleshner, NE and Dicker, AP and Bristow, RG and He, HH and van der Kwast, T and Den, RB and Berlin, A},
title = {Subpathologies and genomic classifier for treatment individualization of post-prostatectomy radiotherapy.},
journal = {Urologic oncology},
volume = {40},
number = {1},
pages = {5.e1-5.e13},
doi = {10.1016/j.urolonc.2021.08.013},
pmid = {34538726},
issn = {1873-2496},
mesh = {Adult ; Aged ; Cohort Studies ; Combined Modality Therapy ; Genome ; Humans ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; *Prostatectomy ; Prostatic Neoplasms/*classification/genetics/*radiotherapy/surgery ; },
abstract = {PURPOSE/OBJECTIVE: Risk-stratification for post-prostatectomy radiotherapy (PORT) using conventional clinicopathologic indexes leads to substantial over- and under-treatment. Better patient selection could spare unnecessary toxicities and improve outcomes. We investigated the prognostic utility of unfavorable subpathologies intraductal carcinoma and cribriform architecture (IDC/CA), and a 22-gene Decipher genomic classifier (GC) in prostate cancer (PCa) patients receiving PORT.<br><br>MATERIAL/METHODS: A cohort of 302 men who received PORT at 2 academic institutions was pooled. PORT was predominately delivered as salvage (62% of cases); 20% received HT+PORT. Specimens were centrally reviewed for IDC/CA presence. In 104 cases, GC scores were determined. Endpoints were biochemical relapse-free (bRFR) and metastasis-free (mFR) rates.<br><br>RESULTS: After a median follow-up of 6.49-years, 135 (45%) and 40 (13%) men experienced biochemical relapse and metastasis, respectively. IDC/CA were identified in 160 (53%) of cases. Men harboring IDC/CA experienced inferior bRFR (HR 2.6, 95%CI 1.8-3.2, P<0.001) and mFR (HR 3.1, 95%CI 1.5-6.4, P&#x202f;=&#x202f;0.0014). Patients with GC scores, 22 (21%) were stratified low-, 30 (29%) intermediate-, and 52 (50%) high-risk. GC low-risk was associated with superior bRFR (HR 0.25, 95%CI 0.1-0.5, P<0.001) and mFR (HR 0.15, 95%CI 0.03-0.8, P&#x202f;=&#x202f;0.025). On multivariable analyses, IDC/CA and GC independently predicted for bRFR, corresponding to improved discrimination (C-index&#x202f;=&#x202f;0.737 (95%CI 0.662-0.813)).<br><br>CONCLUSIONS: IDC/CA subpathologies and GC predict for biochemical relapse and metastasis beyond conventional clinicopathologic indexes in the PORT setting. Patients harboring IDC/CA are at higher risk of relapse after maximal local therapies, thus warranting consideration for treatment intensification strategies. Conversely, for men with absence of IDC/CA and low GC scores, de-intensification strategies could be explored.},
}
@article {pmid34535389,
year = {2022},
author = {Lin, X and He, Y and Fu, S and Lin, S and Xue, E and Lin, L},
title = {The Ultrasonographic Characteristics of Focal Fibrocystic Change of the Breast and Analysis of Misdiagnosis.},
journal = {Clinical breast cancer},
volume = {22},
number = {3},
pages = {252-260},
doi = {10.1016/j.clbc.2021.08.004},
pmid = {34535389},
issn = {1938-0666},
mesh = {*Breast Neoplasms/diagnostic imaging/surgery ; *Calcinosis ; Capsules ; Diagnostic Errors/prevention &amp; control ; Female ; Humans ; Retrospective Studies ; Ultrasonography, Mammary ; },
abstract = {INTRODUCTION: To investigate ultrasonographic features and analyze causes of misdiagnosis of focal fibrocystic change (FC) of the breast.<br><br>MATERIALS AND METHODS: The ultrasonographic features of 95 women (104 lesions) with postoperatively pathologically confirmed focal FC (Group 1) were retrospectively analyzed and compared with those of 105 women (107 lesions) with ductal carcinoma in situ (DCIS) (Group 2), and 164 women (177 lesions) with invasive ductal carcinoma (IDC) (Group 3).<br><br>RESULTS: There were significant differences in 12 features among groups. The sizes and distributions of cystic changes among the groups were significantly different. In group 1, the incidence of cystic changes was 75%(78/104), and the main manifestation was scattered cystic changes (88.5%, 69/78) and microcapsules (81.8%, 63/78). Among focal FC lesions, 36.5% were preoperative BI-RADS classifications 4b-5 (30.8% 4b and 4c). Lesions misdiagnosed as malignant showed solid or cystic solid mixed echoes, and 70.2% of group 1 were irregularly shaped, and 63.5% had unclear edges. In group 1, 5 cases had "hyperechoic halo," 11.5% (12/104) appeared echo attenuation behind the mass, and 21 cases appeared punctate hyperechoic.<br><br>CONCLUSION: FC frequently exhibits low heterogeneity, scattered microcapsules with posterior enhancement, "pit-like" or "grid-like" changes, posterior enhancement, rare hyperechoic halo, calcification, and lack of blood supply. Certain focal FC are irregularly shaped with unclear edges, with malignant signs such as crab feet and burr, hyperechoic halo, and calcification, which ultrasound BI-RADS classification may easily misdiagnose as malignant. Local magnification function should be considered, and the internal structure should be carefully observed to prevent misdiagnosis.},
}
@article {pmid34528573,
year = {2021},
author = {Trontzas, IP and Syrigos, NK and Kotteas, EA},
title = {A case of trastuzumab-induced dermatomyositis.},
journal = {Journal of cancer research and therapeutics},
volume = {17},
number = {4},
pages = {1112-1114},
doi = {10.4103/jcrt.JCRT_209_19},
pmid = {34528573},
issn = {1998-4138},
mesh = {Antineoplastic Agents, Immunological/*adverse effects ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/pathology ; Dermatomyositis/chemically induced/*pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*metabolism ; Trastuzumab/*adverse effects ; },
abstract = {Human epidermal growth factor receptor 2 (HER-2) is a checkpoint, controlling cell proliferation and differentiation. Trastuzumab, a humanized monoclonal antibody directed against HER-2, is nowadays standard treatment for breast cancer patients whose tumors express HER-2. It is generally well tolerated, with a small number of patients developing mild adverse reactions. Dermatomyositis is a rare adverse event of trastuzumab therapy not well described in the literature. We herein present a case of a patient treated for hormone-sensitive invasive ductal carcinoma, who presented with symptoms of proximal muscle weakness, arthralgias, skin rash, and generalized fatigue. The symptoms started after the sixth cycle of trastuzumab and progressively deteriorated. The patient's medical and family history was unremarkable. Disease progression as a possible cause of dermatomyositis had been ruled out, and laboratory evaluation revealed moderate elevation of serum muscle proteins and acute-phase reactants. Trastuzumab treatment was discontinued, and 3 months later, the patient was free of symptoms without any further intervention.},
}
@article {pmid34527961,
year = {2021},
author = {Loft, A and Herzig, S and Schmidt, SF},
title = {Purification of GFP-tagged nuclei from frozen livers of INTACT mice for RNA- and ATAC-sequencing.},
journal = {STAR protocols},
volume = {2},
number = {3},
pages = {100805},
pmid = {34527961},
issn = {2666-1667},
mesh = {Animals ; Cell Nucleus/*chemistry/metabolism ; *Chromatin Immunoprecipitation Sequencing ; Cytological Techniques/*methods ; Female ; Green Fluorescent Proteins/*chemistry/genetics/metabolism ; Liver/chemistry/*cytology ; Male ; Mice ; *RNA-Seq ; },
abstract = {Isolation of nuclei tagged in specific cell types (INTACT) allows for stress-free and high-throughput analyses of cellular subpopulations. Here, we present an improved protocol for isolation of pure and high-quality GFP-labeled nuclei from frozen livers of INTACT mice, as well as protocols for downstream sequencing analyses. The adaptation to frozen tissue provides a pause point that allows sampling at multiple time points and/or phenotypic characterization of livers prior to nuclei isolation and downstream analyses. For complete details on the use of this protocol, please refer to Loft et al. (2021).},
}
@article {pmid34466203,
year = {2021},
author = {Zingue, S and Atenguena, EO and Zingue, LL and Tueche, AB and Njamen, D and Nkoum, AB and Ndom, P},
title = {Epidemiological and clinical profile, and survival of patients followed for breast cancer between 2010 and 2015 at the Yaounde General Hospital, Cameroon.},
journal = {The Pan African medical journal},
volume = {39},
number = {},
pages = {182},
pmid = {34466203},
issn = {1937-8688},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Cameroon/epidemiology ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology/pathology ; Early Detection of Cancer/methods ; Female ; Hospitals, General ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Retrospective Studies ; Risk Factors ; Survival Rate ; Young Adult ; },
abstract = {INTRODUCTION: approximately 6000 Cameroonian women died of cancer in 2018, and the breast is the most affected with 2625 new cases. The aim of this study was to establish a pattern of malignant breast tumours in Yaoundé (Cameroon).<br><br>METHODS: this study was a descriptive and analytical retrospective study of breast cancer between January 2010 and December 2015 in Yaound&#xe9; General Hospital (YGH) after the Institutional ethics committee approval. The variables studied were the socio-demographic characteristics, risk factors for breast cancer, types of tumours and type of treatments. The 5-year survival was analyzed by the Kaplan-Meier method. The adjusted hazard ratios and their 95% confidence intervals were calculated to assess the association between studied variables and patient survival through the cox regression using SPSS 23 software. The difference was considered significant at p < 0.05.<br><br>RESULTS: among the 344 files collected in this study, breast cancer patients were predominantly female (96.64%, n = 288) aged 45.39 &#xb1; 13.35 years, with invasive ductal carcinoma (68.03%, n = 270), located in the left breast (52%, n= 147). The average tumour size was ~6.5 &#xb1; 0.3 cm and diagnosed in grade II of Scarf Bloom Richardson (SBR) in 60% (n= 150) of cases. The 5-year survival was 43.3%. Factors associated with this poor survival were the religion (aHR 5.05, 95% CI: 1.57 - 16.25; p = 0.007 for animist and aHR 4.2, 95% CI: 1.53 - 11.46; p = 0.005 for protestant), location of the tumour (aHR 6.24, 95% CI: 1.58 - 24.60; p = 0.012), tumor height (aHR 0.21, 95% CI: 0.04 - 1.11; p = 0.011) and the time spent before medical treatment (aHR 5.12, 95% CI: 0.39 - 8.38; p = 0.011).<br><br>CONCLUSION: the young age, large tumour size and high histological grade in our studied population suggest a weak awareness of women about breast cancer. Action should be taken in early screening to improve the management of breast cancer in Cameroon.},
}
@article {pmid34461516,
year = {2022},
author = {Meng, J and Yang, Q and Wan, W and Zhu, Q and Zeng, X},
title = {Physicochemical properties and adaptability of amine-producing Enterobacteriaceae isolated from traditional Chinese fermented fish (Suan yu).},
journal = {Food chemistry},
volume = {369},
number = {},
pages = {130885},
doi = {10.1016/j.foodchem.2021.130885},
pmid = {34461516},
issn = {1873-7072},
mesh = {Animals ; *Biogenic Amines ; China ; Enterobacter ; *Enterobacteriaceae/genetics ; Fermentation ; },
abstract = {The formation of biogenic amines (BAs) is an important potential danger in traditional fermented fish (Suan yu), and Enterobacteriaceae play an important role in the formation of BAs. The amine production abilities of 97 strains of Enterobacteriaceae screened from traditional fermented Suan yu were analyzed by reversed-phased high-performance liquid chromatography (HPLC). The genotypic diversity of amino acid decarboxylase on 23 strains of high-yield BAs was verified by PCR. Enterobacteriaceae with the highest production of amines was determined by analysis of the effects of physicochemical factors (pH, NaCl, temperature, and aerobic/anaerobic) on BA production and principal component analysis (PCA). The adaptability of the strains was examined using surimi simulation fermentation system, and the correlations among the indicators were analyzed using Cytoscape. Results showed that 97 strains of Enterobacteriaceae had strong amine-producing ability. Furthermore, 23 strains producing high yields of putrescine, cadaverine, and histamine were identified. All of the strains carried Idc, odc, speA, speB, and adiA, and five strains carried hdc. pH mainly affected the BA production of amine-producing bacteria. Three strains (Enterobacter asburiae 26C3, Klebsiella pneumoniae 47C2, and Morganella morganii 45C3) had the best amine-producing ability and used as the inoculated group. In this group, the values of BA (228.70-290.05 mg/kg) and the total volatile base nitrogen (TVB-N, 173.87-221.87 mg/100 g) exceeded the limit. Moreover, myofibrillar protein degradation was significant as indicated by the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis and decreased FAA content. Cytoscape software and principal component analysis (PCA) indicated that Enterobacteriaceae and pH were related to BA formation in Suan yu. These results provide a theoretical basis for controlling the BA of fermented fish products.},
}
@article {pmid34452576,
year = {2021},
author = {Ameli, F and Ghafourina Nassab, F and Masir, N and Kahtib, F},
title = {Tumor-Derived Matrix Metalloproteinase-13 (MMP-13) Expression in Benign and Malignant Breast Lesions.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {22},
number = {8},
pages = {2603-2609},
pmid = {34452576},
issn = {2476-762X},
mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/enzymology/*pathology ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Matrix Metalloproteinase 13/*metabolism ; Middle Aged ; Neoplasms/enzymology/*pathology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {INTRODUCTION: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC).<br><br>MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.<br><br>RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.<br><br>CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.},
}
@article {pmid34449311,
year = {2021},
author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY},
title = {Paravertebral block in regional anesthesia with propofol sedation reduces locoregional recurrence in patients with breast cancer receiving breast conservative surgery compared with volatile inhalational without propofol in general anesthesia.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {142},
number = {},
pages = {111991},
doi = {10.1016/j.biopha.2021.111991},
pmid = {34449311},
issn = {1950-6007},
mesh = {Adult ; Aged ; Anesthesia, Conduction/*methods ; Anesthesia, General/*methods ; Anesthetics, Inhalation/administration &amp; dosage ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Cohort Studies ; Databases, Factual ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Staging ; Nerve Block/methods ; Propofol/administration &amp; dosage ; Radiotherapy, Adjuvant/methods ; Sevoflurane/administration &amp; dosage ; Young Adult ; },
abstract = {PURPOSE: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving breast conservative surgery (BCS) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.<br><br>PATIENTS AND METHODS: Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).<br><br>RESULTS: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.67 (0.46-0.99) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 2-3, and Her-2 positivity were 1.87 (1.03-3.42), 2.31 (1.20-4.44), 1.67 (1.09-2.56), 2.43 (1.18-4.97), 1.17 (1.03-1.19), 1.28 (1.13-2.24), 1.20 (1.05-2.22), and 1.59 (1.01-2.51), respectively, compared with those for differentiation grade I, clinical stage I, pT1, pN0, and HER-2 negativity. The aHR of LRR for adjuvant radiotherapy was 0.60 (0.38-0.97) compared with that for no adjuvant radiotherapy.<br><br>CONCLUSION: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with INHA-GA without propofol.},
}
@article {pmid34448091,
year = {2021},
author = {Jimbo, H and Horimoto, Y and Okazaki, M and Ishizuka, Y and Kido, H and Saito, M},
title = {Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report.},
journal = {Surgical case reports},
volume = {7},
number = {1},
pages = {197},
pmid = {34448091},
issn = {2198-7793},
abstract = {BACKGROUND: Pegfilgrastim is a modified version of granulocyte-colony stimulating factor (G-CSF), with a polyethylene glycol (PEG) that prolongs its half-life in peripheral blood. It is prophylactically administered during chemotherapy to prevent severe febrile neutropenia. G-CSF-related aortitis is a rare side effect but reports of this disease have been increasing in recent years, probably due to PEGylation. Herein, we report a case who developed pegfilgrastim-induced aortitis, localized to the right subclavian artery, during adjuvant chemotherapy. Her condition recovered without the use of steroids.<br><br>CASE PRESENTATION: A 58-year-old woman was diagnosed with invasive ductal carcinoma of the left breast. She had a medical history of contralateral breast cancer and pyelonephritis. Following curative surgery for her left breast cancer, she received adjuvant chemotherapy. Two days after the first course of dose-dense paclitaxel, pegfilgrastim was used as planned. Eight days after the administration of pegfilgrastim, she developed a high fever of 38&#xa0;&#xb0;C and visited the emergency outpatient clinic 3&#xa0;days after. Blood tests revealed an increased inflammatory response, and contrast-enhanced computed tomography (CT) revealed a wall thickening of the subclavian artery, suggesting aortitis caused by pegfilgrastim. She was hospitalized on day 15 when CRP increased to 21.5&#xa0;mg/dL and the high fever continued. Blood and urine culture tests were negative throughout. Pegfilgrastim-induced aortitis was suspected and she was observed without the use of steroids. Seven days later, her fever abated. A contrast-enhanced CT scan on day 26 showed the subclavian artery wall thickening had disappeared. The patient continues to be afebrile and is currently on weekly paclitaxel without use of G-CSF.<br><br>CONCLUSIONS: The onset of this disease is known to usually occur within 2&#xa0;weeks after the first pegfilgrastim administration. Aortitis localized to the subclavian artery is relatively rare with the most frequent site being the aortic arch. Clinicians should be aware of the timing and location of onset of this disease.},
}
@article {pmid34437555,
year = {2021},
author = {Shulman, D and Shnitzer-Akuka, M and Reifen-Tagar, M},
title = {The cost of attributing moral blame: Defensiveness and resistance to change when raising awareness to animal suffering in factory farming.},
journal = {PloS one},
volume = {16},
number = {8},
pages = {e0254375},
pmid = {34437555},
issn = {1932-6203},
mesh = {Diet, Vegan/ethics ; Farms/*ethics ; Female ; Food Industry/*ethics ; Humans ; Male ; Meat ; *Morals ; *Motivation ; },
abstract = {Social change campaigns often entail raising awareness of harm caused by people's behavior. For example, campaigns to reduce meat eating frequently highlight the suffering endured by animals. Such messages may simultaneously attribute moral blame to individuals for causing the harm described. Given people's motivation to protect their moral self-image, we expected that information about the suffering of animals in the meat industry presented with a blaming (versus absolving) frame would generate greater defensiveness and correspondingly resistance to change in support of veg*nism (veganism/vegetarianism). We ran three studies to test this expectation. In two studies, we found that raising awareness of animal suffering using a blaming frame increased defensiveness, leading to lower veg*n-supporting attitudes and behavioral intentions. In one study, our hypothesis was not supported, however, a mini-meta analysis across the three studies suggests the overall pattern is robust. This work expands our understanding of the role of moral self-image preservation in defensiveness and resistance to change, and has applied relevance for the development of effective communication strategies in social and moral campaigns.},
}
@article {pmid34427055,
year = {2021},
author = {Morigny, P and Kaltenecker, D and Zuber, J and Machado, J and Mehr, L and Tsokanos, FF and Kuzi, H and Hermann, CD and Voelkl, M and Monogarov, G and Springfeld, C and Laurent, V and Engelmann, B and Friess, H and Zörnig, I and Krüger, A and Krijgsveld, J and Prokopchuk, O and Fisker Schmidt, S and Rohm, M and Herzig, S and Berriel Diaz, M},
title = {Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {12},
number = {5},
pages = {1333-1351},
pmid = {34427055},
issn = {2190-6009},
support = {J 4224/FWF_/Austrian Science Fund FWF/Austria ; J4224-B34/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {1-Alkyl-2-acetylglycerophosphocholine Esterase ; Animals ; Benzaldehydes ; Biomarkers ; *Cachexia/drug therapy/etiology ; Humans ; Mice ; Oximes ; *Pancreatic Neoplasms ; Prospective Studies ; },
abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour-derived and host-derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities.<br><br>METHODS: Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia-inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well-established mouse models of CCx and in different cohorts of weight-stable and weight-losing cancer patients with different tumour entities. Genetic PLA2G7 knock-down in tumours and pharmacological treatment using the well-studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour-bearing mice.<br><br>RESULTS: High expression and secretion of PLA2G7 were hallmarks of cachexia-inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock-down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx.<br><br>CONCLUSIONS: Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre-cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.},
}
@article {pmid34423517,
year = {2021},
author = {Yun, NK and Slostad, JA and Naqib, A and Frankenberger, C and Perez, CB and Ghai, R and Usha, L},
title = {Histologic Discordance Between Primary Tumor and Nodal Metastasis in Breast Cancer: Solving a Clinical Conundrum in the Era of Genomics.},
journal = {The oncologist},
volume = {26},
number = {12},
pages = {1000-1005},
pmid = {34423517},
issn = {1549-490X},
mesh = {*Breast Neoplasms/genetics ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Precision Medicine ; Sequence Analysis, DNA ; },
abstract = {Next-generation sequencing (NGS) technologies have become increasingly used for managing breast cancer. In addition to the conventional use of NGS for predicting recurrence risk and identifying potential actionable mutations, NGS can also serve as a powerful tool to understand clonal origin and evolution of tumor pairs and play a unique role in clarifying complex clinical presentations. We report an unusual case of early-stage breast cancer in which the primary tumor and draining axillary node were histologically discordant. The primary tumor was invasive lobular carcinoma, whereas the nodal metastasis was invasive ductal carcinoma. This discordance led us to question whether the tumors had the same origin. NGS performed on both specimens identified no overlapping variants, leading us to conclude that the patient had two separate primary breast cancers, with the nodal tumor representing metastasis from an occult breast cancer. DNA sequencing of the primary tumor and the nodal metastasis allowed us to predict the patient's recurrence risk, and we initiated adjuvant chemotherapy and hormonal therapy based on these results. This case illustrates the utility of NGS for successfully managing a rare and challenging case. KEY POINTS: A degree of molecular concordance is expected for tumors originating from a common stem or progenitor cell. Histological discordance and absence of any genomic overlap should raise suspicion for two separate primary tumors. Paired DNA sequencing of the primary tumor and nodal metastasis can inform clinical decisions when primary breast tumor and axillary metastasis are histologically discordant. Molecular/Precision Oncology Tumor Board is the best setting to facilitate such decisions in these challenging cases. Paired DNA sequencing under these rare circumstances may suggest an occult breast tumor.},
}
@article {pmid34417460,
year = {2021},
author = {Gonzalez-Rellan, MJ and Fondevila, MF and Fernandez, U and Rodríguez, A and Varela-Rey, M and Veyrat-Durebex, C and Seoane, S and Bernardo, G and Lopitz-Otsoa, F and Fernández-Ramos, D and Bilbao, J and Iglesias, C and Novoa, E and Ameneiro, C and Senra, A and Beiroa, D and Cuñarro, J and Dp Chantada-Vazquez, M and Garcia-Vence, M and Bravo, SB and Da Silva Lima, N and Porteiro, B and Carneiro, C and Vidal, A and Tovar, S and Müller, TD and Ferno, J and Guallar, D and Fidalgo, M and Sabio, G and Herzig, S and Yang, WH and Cho, JW and Martinez-Chantar, ML and Perez-Fernandez, R and López, M and Dieguez, C and Mato, JM and Millet, O and Coppari, R and Woodhoo, A and Fruhbeck, G and Nogueiras, R},
title = {O-GlcNAcylated p53 in the liver modulates hepatic glucose production.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {5068},
pmid = {34417460},
issn = {2041-1723},
mesh = {Acetylglucosamine/*metabolism ; Animals ; Base Sequence ; Caloric Restriction ; Cell Line ; Colforsin/pharmacology ; Diabetes Mellitus, Type 2/complications/metabolism ; Epinephrine/metabolism ; Glucagon/metabolism ; Glucocorticoids/metabolism ; Gluconeogenesis/drug effects ; Glucose/*metabolism ; Glycosylation ; Hepatocytes/drug effects/metabolism ; Humans ; Hydrocortisone/metabolism ; Hyperglycemia/complications/metabolism ; Insulin Resistance ; Intracellular Signaling Peptides and Proteins/metabolism ; Liver/drug effects/*metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications/metabolism ; Phosphoenolpyruvate Carboxykinase (GTP)/metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding/drug effects ; Protein Stability/drug effects ; Pyruvic Acid/metabolism ; RNA, Messenger/genetics/metabolism ; Transcription, Genetic/drug effects ; Tumor Suppressor Protein p53/genetics/*metabolism ; Mice ; },
abstract = {p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.},
}
@article {pmid34413744,
year = {2021},
author = {Moghimi, M and Khodadadi, K},
title = {Dermatomyositis following Biosimilar Trastuzumab in a Breast Cancer Patient: A Case Report.},
journal = {Case reports in oncology},
volume = {14},
number = {2},
pages = {1134-1138},
pmid = {34413744},
issn = {1662-6575},
abstract = {Trastuzumab, as a recombinant IgG1 kappa, is a humanized monoclonal antibody against human epidermal growth factor receptor 2. Accordingly, it is widely used in breast cancers at early and advanced stages. Dermatomyositis is a rare adverse event of trastuzumab therapy, which is not well documented yet. In this study, a patient was treated for invasive ductal carcinoma with some symptoms of rash and generalized fatigue. These symptoms started after the fifth cycle of trastuzumab, which were gradually deteriorating. This patient's medical and family histories were unremarkable. The progression of the disease was ruled out as a possible cause of dermatomyositis, and the laboratory evaluation revealed a moderate increase in serum muscle protein (CPK). So, trastuzumab treatment was discontinued, and by passing 1 month from the start of prednisolone and hydroxychloroquine, the patient had no symptoms.},
}
@article {pmid34409828,
year = {2021},
author = {Shabanov, GA and Rybchenko, AA and Lugovaya, EA and Vdovenko, SI},
title = {[Biological age estimation based on the spectral analysis of the human brain bioelectric activity.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {34},
number = {3},
pages = {466-471},
pmid = {34409828},
issn = {1561-9125},
mesh = {*Aging ; *Brain ; Cell Differentiation ; Humans ; Risk Factors ; },
abstract = {For the first time, the research work offers a method of estimating human biological age based on the spectral analysis of the brain bioelectric activity. IDC decentralization index, which could consider summary degree of reduction of the background neurotrophic influences of the brain activating system on the peripheral tissues and organs, was developed. The close to linear dependence of the IDC index on the age of healthy people aged 10-90 as well as on the oncological patients' cancer G1-G4 cells differentiation was obtained. The cell disorders and mutations in relation with the age from 10 to 90 could be seen in growth of the IDC index from 100 to 900 units. The greater amount of the cell mutations in the oncological patients with the G1-G4 differentiation resulted in the IDC index growth up to the 3 000 units and more. All the obtained data allowed estimating the real biological age after a 10-minute registration of the human brain bioelectric activity. The accuracy increased with the averaging several surveys taken from one particular person. The technology will be highly efficient for scientific researches in the field of gerontology, monitoring of healthy people, revealing of risk groups, and for controlling of the cancer patients' medical treatment.},
}
@article {pmid34401774,
year = {2021},
author = {Madhavan, BK and Han, Z and Sickmann, A and Pepperkok, R and Nawroth, PP and Kumar, V},
title = {A laser-mediated photo-manipulative toolbox for generation and real-time monitoring of DNA lesions.},
journal = {STAR protocols},
volume = {2},
number = {3},
pages = {100700},
pmid = {34401774},
issn = {2666-1667},
mesh = {Biomechanical Phenomena/*physiology ; DNA/genetics ; DNA Breaks, Double-Stranded ; DNA Breaks, Single-Stranded ; DNA Damage/genetics ; DNA Repair/genetics/*physiology ; Kinetics ; Lasers ; Microscopy, Confocal/*methods ; },
abstract = {With the advancement of laser-based microscopy tools, it is now possible to explore mechano-kinetic processes occurring inside the cell. Here, we describe the advanced protocol for studying the DNA repair kinetics in real time using the laser to induce the DNA damage. This protocol can be used for inducing, testing, and studying the repair mechanisms associated with DNA double-strand breaks, interstrand cross-link repair, and single-strand break repair. For complete details on the use and execution of this protocol, please refer to Kumar et al. (2017, 2020).},
}
@article {pmid34396426,
year = {2021},
author = {Kobayashi, H and Nakai, T and Nakanishi, Y and Esumi, M and Masuda, S},
title = {Phylogenetic analysis of combined lobular and ductal carcinoma of the breast.},
journal = {Molecular medicine reports},
volume = {24},
number = {4},
pages = {},
pmid = {34396426},
issn = {1791-3004},
mesh = {Adult ; Breast ; Breast Neoplasms/*classification/genetics/pathology ; Carcinoma, Ductal, Breast/*classification/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Carcinoma, Lobular/*classification/genetics/pathology ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Mutation ; *Phylogeny ; Polymorphism, Single Nucleotide ; },
abstract = {Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal‑lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D‑loop, digital PCR targeting of chromosomes 1q and 16q, as well as next‑generation sequencing. DNA was extracted from formalin‑fixed paraffin‑embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, flat epithelial atypia, non‑neoplastic mammary gland and extramammary organs, using laser‑assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele‑specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma in situ. Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.},
}
@article {pmid34392891,
year = {2021},
author = {Roberts, WC and Jeong, M},
title = {Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy.},
journal = {The American journal of cardiology},
volume = {157},
number = {},
pages = {101-106},
doi = {10.1016/j.amjcard.2021.07.023},
pmid = {34392891},
issn = {1879-1913},
mesh = {Adult ; Aged ; Cardiomyopathies/complications/epidemiology ; Cardiomyopathy, Dilated/*complications/epidemiology ; Female ; Follow-Up Studies ; *Forecasting ; Heart Failure/epidemiology/etiology/surgery ; Heart Transplantation ; Humans ; Incidence ; Middle Aged ; Peripartum Period ; Pregnancy ; *Pregnancy Complications, Cardiovascular ; Retrospective Studies ; Texas/epidemiology ; Young Adult ; },
abstract = {Among women with idiopathic dilated cardiomyopathy (IDC), the percent who develop heart failure (HF) in the peripartum period (during pregnancy or within 6 months of parturition) compared with those women who develop HF outside the peripartum period is unclear. We studied 72 women with IDC who underwent orthotopic heart transplantation for severe HF, the onset of which was in the peripartum period in 8 (11%) and outside the period in 64 (89%). Comparison of many clinical and morphologic variables between these 2 groups showed significant differences only in the ages of onset of HF, age when orthotopic heart transplantation was performed, and the frequency of the presence of diabetes mellitus. Examination of the hearts in the 2 groups disclosed no significant differences. Thus, separation of the peripartum IDC cases from the nonperipartum IDC cases by either clinical or cardiac morphologic variables is difficult.},
}
@article {pmid34379693,
year = {2021},
author = {He, X and Anthony, DC and Catoni, Z and Cao, W},
title = {Pulmonary tumor embolism: A retrospective study over a 30-year period.},
journal = {PloS one},
volume = {16},
number = {8},
pages = {e0255917},
pmid = {34379693},
issn = {1932-6203},
mesh = {Adult ; Aged ; Aged, 80 and over ; Autopsy ; Breast Neoplasms/complications/diagnosis/pathology ; Carcinoma, Ductal/complications/diagnosis/pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/complications/diagnosis/*pathology ; Pulmonary Embolism/complications/*diagnosis ; Retrospective Studies ; Urinary Bladder Neoplasms/complications/diagnosis/pathology ; },
abstract = {BACKGROUND: Pulmonary tumor embolism (PTE) is difficult to detect before death, and it is unclear whether the discrepancy between antemortem clinical and postmortem diagnosis improves with the advance of the diagnostic technologies. In this study we determined the incidence of PTE and analyzed the discrepancy between antemortem clinical and postmortem diagnosis.<br><br>METHODS: We performed a retrospective autopsy study on patients with the history of malignant solid tumors from 1990 to 2020 and reviewed all the slides of the patients with PTE. We also analyzed the discrepancies between antemortem clinical and postmortem diagnosis in 1999, 2009 and 2019 by using the Goldman criteria. Goldman category major 1 refers to cases in which an autopsy diagnosis was the direct cause of death and was not recognized clinically, but if it had been recognized, it may have changed treatment or prolonged survival.<br><br>RESULTS: We found 20 (3%) cases with PTE out of the 658 autopsy cases with solid malignancies. Out of these 20 cases, urothelial carcinoma (30%, 6/20) and invasive ductal carcinoma of the breast (4/20, 20%) were the most common primary malignancies. Seven patients with shortness of breath died within 3-17 days (average 8.4&#xb1;2.2 days) after onset of the symptoms. Pulmonary embolism was clinically suspected in seven out of twenty (35%, 7/20) patients before death, but only two patients (10, 2/20) were diagnosed by imaging studies before death. The rate of Goldman category major 1 was 13.2% (10/76) in 1999, 7.3% (4/55) in 2009 and 6.9% (8/116) in 2019. Although the rate of Goldman category major 1 appeared decreasing, the difference was not statistically significant. The autopsy rate was significantly higher in 2019 (8.4%, 116/1386) than in 2009 (4.4%, 55/1240).<br><br>CONCLUSIONS: The incidence of PTE is uncommon. Despite the advances of the radiological techniques, radiological imaging studies did not detect the majority of PTEs. The discrepancy between the antemortem clinical and the postmortem diagnosis has not improved significantly over the past 30 years, emphasizing the value of autopsy.},
}
@article {pmid34359556,
year = {2021},
author = {Zhang, JQ and Cheng, TM and Lin, WC and Chiu, KC and Wu, SY},
title = {Impact of Smoking-Related Chronic Obstruction Pulmonary Disease on Mortality of Invasive Ductal Carcinoma Patients Receiving Standard Treatments: Propensity Score-Matched, Nationwide, Population-Based Cohort Study.},
journal = {Cancers},
volume = {13},
number = {15},
pages = {},
pmid = {34359556},
issn = {2072-6694},
abstract = {PURPOSE: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments.<br><br>METHODS: we recruited women with clinical stage I-III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group).<br><br>RESULTS: PSM yielded 2319 patients with stage I-III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83-1.22). The aHRs (95% CIs) of all-cause mortality for &#x2265;1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18-2.36) compared with no COPDAE.<br><br>CONCLUSION: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I-III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.},
}
@article {pmid34349234,
year = {2021},
author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL},
title = {Validity of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.},
journal = {Spinal cord},
volume = {59},
number = {9},
pages = {948-958},
pmid = {34349234},
issn = {1476-5624},
support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; 90IF0121/ACL/ACL HHS/United States ; 90IF0121/ACL/ACL HHS/United States ; },
mesh = {Catheters, Indwelling ; Humans ; Psychometrics ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; },
abstract = {STUDY DESIGN: Descriptive Psychometrics Study OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), or "neurogenic bladder" is a common and disruptive condition for individuals with spinal cord injury (SCI) and disease (including multiple sclerosis, MS). Our team has developed patient-centered instruments of urinary symptoms specific to patients with NLUTD, across bladder management methods. Validity evidence is needed to support the use of two new instruments, Urinary Symptom Questionnaires for people with Neurogenic Bladder (USQNB) for those who manage their bladder with indwelling catheters (IDC), or who void (V).<br><br>SETTING: Online surveys completed by individuals in the United States with NLUTD due to either SCI or MS who manage their bladder with indwelling catheters (SCI, n&#x2009;=&#x2009;306; MS, n&#x2009;=&#x2009;8), or by voiding (SCI, n&#x2009;=&#x2009;103; MS, n&#x2009;=&#x2009;383). A total of n&#x2009;=&#x2009;381 USQNB-IDC respondents (five control groups), and 351 USQNB-V respondents (four control groups), contributed to our convergent and divergent validity evidence.<br><br>METHODS: Data were collected online to estimate key aspects of psychometric validity (content, reflection of the construct to be measured; face, recognizability of the contents as representing the construct to be measured; structural, the extent to which the instrument captures recognizable dimensions of the construct to be measured). Divergent and convergent validity evidence was derived from multiple control groups, while evidence of criterion validity was derived from attribution of each item to their experience "with a UTI".<br><br>RESULTS: Evidence of face, content, criterion, convergent, and divergent validity was compiled for each instrument.<br><br>CONCLUSIONS: The instruments demonstrate adequate, multi-dimensional, validity evidence to recommend their use for decision-making by patients, clinicians, and researchers.},
}
@article {pmid34345005,
year = {2021},
author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL},
title = {Reliability of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.},
journal = {Spinal cord},
volume = {59},
number = {9},
pages = {939-947},
pmid = {34345005},
issn = {1476-5624},
support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; },
mesh = {Bayes Theorem ; Catheters, Indwelling ; Humans ; Reproducibility of Results ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; United States ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; },
abstract = {STUDY DESIGN: This is a descriptive psychometrics study.<br><br>OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), also called Neurogenic Bladder (NB), is a common and disruptive condition in a variety of neurologic diagnoses. Our team developed patient-centered instruments, Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB), specific to people with NLUTD who manage their bladders with intermittent catheterization (IC), indwelling catheters (IDC), or who void (V). This article reports evidence of reliability of the IDC and V instruments.<br><br>SETTING: Online surveys completed by individuals in the United States with NLUTD due to spinal cord injury (SCI), or multiple sclerosis (MS) who manage their bladder with IDC (SCI, n&#x2009;=&#x2009;306), or by voiding (SCI, n&#x2009;=&#x2009;103; MS, n&#x2009;=&#x2009;383).<br><br>METHODS: Reliability estimates were based on endorsement of the items on the USQNB-IDC and USQNB-V. Reliability evidence was representativeness of these symptoms for a national sample (by determining if endorsement&#x2009;>&#x2009;10%); internal consistency estimates (by Cronbach's alpha and item correlation coefficient, ICC); and interrelatedness of the items (by inferred Bayesian network, BN). We also tested whether a one-factor conceptualization of "urinary symptoms in NLUTD" was supportable for either instrument.<br><br>RESULTS: All items were endorsed by >20% of our samples. Urine quality symptoms tended to be the most commonly endorsed on both instruments. Cronbach's alpha and ICC estimates were high (>0.74), but not suggestive of redundancy. BNs showed interpretable associations among the items, and did not discover uninterpretable or unexpected associations. Neither instrument fit a one-factor model, as expected.<br><br>CONCLUSIONS: The USQNB-IDC and USQNB-V instruments show sufficient, multidimensional reliability for implementation and further study.},
}
@article {pmid34340541,
year = {2021},
author = {Pickford, AK and Michel-Todó, L and Dupuy, F and Mayor, A and Alonso, PL and Lavazec, C and Cortés, A},
title = {Expression Patterns of Plasmodium falciparum Clonally Variant Genes at the Onset of a Blood Infection in Malaria-Naive Humans.},
journal = {mBio},
volume = {12},
number = {4},
pages = {e0163621},
pmid = {34340541},
issn = {2150-7511},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Antigens, Protozoan/immunology ; *Gene Expression Profiling ; *Genetic Variation ; Host-Parasite Interactions/*genetics/immunology ; Humans ; Malaria, Falciparum/immunology/*parasitology ; Plasmodium falciparum/*genetics/immunology ; Protozoan Proteins/*genetics/immunology ; Transcriptome ; },
abstract = {Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum to fluctuating conditions of the human host. However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail for only a few specific gene families. Here, we provide a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in malaria-naive human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occurred in CVGs. In particular, we observed a major increase in the transcript levels of most genes of the pfmc-2tm and gbp families and of specific genes of other families, such as phist, hyp10, rif, or stevor, in addition to previously reported changes in var and clag3 gene expression. Increased transcript levels of individual pfmc-2tm, rif, and stevor genes involved activation in small subsets of parasites. Large transcriptional differences correlated with changes in the distribution of heterochromatin, confirming their epigenetic nature. Furthermore, the similar expression of several CVGs between parasites collected at different time points along the blood infection suggests that the epigenetic memory for multiple CVG families is lost during transmission stages, resulting in a reset of their transcriptional state. Finally, the CVG expression patterns observed in a volunteer likely infected by a single sporozoite suggest that new epigenetic patterns are established during liver stages. IMPORTANCE The ability of malaria parasites to adapt to changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in alterations in the antigenic and functional properties of the parasites. However, how these genes are expressed under the natural conditions of the human circulation and how their expression is affected by passage through transmission stages are not well understood. Here, we provide a comprehensive characterization of the expression patterns of these genes at the onset of human blood infections, which reveals major differences with in vitro-cultured parasites. We also show that, during transmission stages, the previous expression patterns for many CVG families are lost, and new patterns are established.},
}
@article {pmid34336518,
year = {2021},
author = {McCray, E and Naron, R and White, S and Messersmith, S and Stewart, C},
title = {Metastatic Breast Cancer Masked as Constipation.},
journal = {Cureus},
volume = {13},
number = {6},
pages = {e16031},
pmid = {34336518},
issn = {2168-8184},
abstract = {Even though screening mammography has been attributed to decreased mortality in recent decades, breast cancer is one of the leading causes of death among women in the United States. Disruption of screening protocols and variation in the presentation may alter the course of detection and management. We report a case of hormone receptor-positive breast cancer that presented as vague gastrointestinal symptoms in a patient with a delayed workup for a self-discovered breast lump during the coronavirus disease global pandemic. A 48-year-old woman with a history of gastroesophageal reflux and hypertension presented to the emergency department with primary complaints of constipation and abdominal distention with associated flatus and nausea. Vitals were within normal limits, and physical examination was notable for abdominal distention and diffuse tenderness to palpation. Labs demonstrated hypercalcemia and an unremarkable complete blood count. A chest X-ray showed a right hilar mass, and a CT chest revealed multiple lytic bone lesions diffusely scattered throughout the entire skeleton; no hilar mass was noted on the CT chest. A CT scan of the abdomen and pelvis incidentally revealed a right breast mass. A bone marrow biopsy identified invasive ductal carcinoma. Mammography and biopsy of the breast mass identified estrogen receptor/progesterone receptor-positive invasive ductal carcinoma, consistent with the bone marrow biopsy, confirming the diagnosis of metastatic breast cancer. Unpredicted disruptions in screening processes may result in delayed cancer diagnoses. This case illustrates the importance of routine self-breast examinations, screening mammography, and maintaining a broad differential diagnosis.},
}
@article {pmid34330920,
year = {2021},
author = {Thomson-Luque, R and Votborg-Novél, L and Ndovie, W and Andrade, CM and Niangaly, M and Attipa, C and Lima, NF and Coulibaly, D and Doumtabe, D and Guindo, B and Tangara, B and Maiga, F and Kone, AK and Traore, K and Kayentao, K and Ongoiba, A and Doumbo, S and Thera, MA and Traoré, B and Seydel, K and Osório, NS and Portugal, S},
title = {Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {4711},
pmid = {34330920},
issn = {2041-1723},
support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI099628/AI/NIAID NIH HHS/United States ; },
mesh = {Blood Circulation Time ; Erythrocytes/parasitology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Bacterial ; Gene Ontology ; Genes, Bacterial/genetics ; Humans ; Malaria, Falciparum/*blood/parasitology/physiopathology ; Parasitemia/*blood/parasitology/physiopathology ; Plasmodium falciparum/*genetics/physiology ; },
abstract = {Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum's tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.},
}
@article {pmid34321100,
year = {2021},
author = {Meyer, D and Kames, J and Bar, H and Komar, AA and Alexaki, A and Ibla, J and Hunt, RC and Santana-Quintero, LV and Golikov, A and DiCuccio, M and Kimchi-Sarfaty, C},
title = {Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.},
journal = {Genome medicine},
volume = {13},
number = {1},
pages = {122},
pmid = {34321100},
issn = {1756-994X},
support = {R01 HL151392/HL/NHLBI NIH HHS/United States ; },
mesh = {Biomarkers, Tumor ; *Codon ; *Codon Usage ; Computational Biology/*methods ; *Databases, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genome-Wide Association Study ; Genomics/methods ; Humans ; Kaplan-Meier Estimate ; Neoplasms/*diagnosis/*genetics/mortality ; Prognosis ; Transcriptome ; },
abstract = {BACKGROUND: Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest.<br><br>METHODS: We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues.<br><br>RESULTS: We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research.<br><br>CONCLUSIONS: Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.},
}
@article {pmid34320711,
year = {2021},
author = {Fan, T and Wang, CQ and Li, XT and Yang, H and Zhou, J and Song, YJ},
title = {MiR-22-3p Suppresses Cell Migration and Invasion by Targeting PLAGL2 in Breast Cancer.},
journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP},
volume = {31},
number = {8},
pages = {937-940},
doi = {10.29271/jcpsp.2021.08.937},
pmid = {34320711},
issn = {1681-7168},
mesh = {*Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; China ; DNA-Binding Proteins/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *MicroRNAs/genetics ; RNA-Binding Proteins/genetics ; Transcription Factors/genetics ; },
abstract = {OBJECTIVE: To investigate the expression of miR-22-3p in breast cancer and the mechanism of targeting PLAGL2 to inhibit the invasion and migration in human breast cancer.<br><br>STUDY DESIGN: An experimental study.<br><br>PLACE AND DURATION OF STUDY: Department of Oncology and Department of General Surgery, The People's Hospital of China Three Gorges University, China, from March 2019 to December 2020.<br><br>METHODOLOGY: The miR-22-3p expression level in 41 paired human primary breast invasive ductal carcinoma tissues and para-cancer tissues was obtained by real-time fluorescence quantitative reverse transcriptase PCR (qRT-PCR). The effect of miR-22-3p on the proliferation of breast cancer cells was detected by growth curve method. Online software TargetScan was used to predict the target genes of miR-22-3p. The prediction results were verified by luciferase reporter gene assay and qRT&#x2043;PCR.<br><br>RESULTS: MiR-22-3p expression was significantly decreased in the breast cancer tissues than in para&#x2043;carcinoma normal breast tissues (p<0.05). Over-expression of miR-22-3p can inhibit the proliferation of MCF-7 cells significantly. Pleomorphic adenoma gene-like protein 2(PLAGL2)&#xa0;is the predicted target gene of miR-22-3p. MiR-22-3p binds to its predicted target gene PLAGL2-3'UTR. The expression of miR-22-3p was negatively correlated with PLAGL2 in MCF-7 cells.<br><br>CONCLUSION: MiR-22-3p could suppress the proliferation of breast cancer by targeting PLAGL2. This suggests that miR-22-3p may be a strategy of choice for targeted therapy of breast cancer. Key Words: Breast cancer, MiR-22-3p, PLAGL2, Cell proliferation.},
}
@article {pmid34316107,
year = {2021},
author = {Ramani, SK and Rastogi, A and Nair, N and Shet, TM and Thakur, MH},
title = {Hyperechoic Lesions on Breast Ultrasound: All Things Bright and Beautiful?.},
journal = {The Indian journal of radiology &amp; imaging},
volume = {31},
number = {1},
pages = {18-23},
pmid = {34316107},
issn = {0971-3026},
abstract = {Ultrasound (US) lexicon of the Breast Imaging Reporting and Data System (BI-RADS) defines an echogenic breast mass as a lesion that is hyperechoic in comparison with subcutaneous adipose tissue. However, at sonography, only 0.6 to 5.6% of breast masses are echogenic and the majority of these lesions are benign. approximately, 0.5% of malignant breast lesions appear hyperechoic. The various benign pathologic entities that appear echogenic on US are lipoma, hematoma, seroma, fat necrosis, abscess, pseudoangiomatous stromal hyperplasia, galactocele, etc. The malignant diagnoses that may present as hyperechoic lesions on breast US are invasive ductal carcinoma, invasive lobular carcinoma, metastasis, lymphoma, and angiosarcoma. Echogenic breast masses need to be correlated with mammographic findings and clinical history. Lesions with worrisome features such as a spiculated margin, interval enlargement, interval vascularity, or association with suspicious microcalcifications on mammography require biopsy. In this article, we would like to present a pictorial review of patients who presented to our department with echogenic breast masses and were subsequently found to have various malignant as well as benign etiologies on histopathology.},
}
@article {pmid34315379,
year = {2021},
author = {Rafiq, MT and Hamid, MSA and Hafiz, E and Chaudhary, FA and Khan, MI},
title = {Feasibility and Acceptability of Instructions of Daily Care in Overweight and Obese Knee Osteoarthritis Participants.},
journal = {Current rheumatology reviews},
volume = {17},
number = {4},
pages = {421-427},
doi = {10.2174/1573397117666210727095552},
pmid = {34315379},
issn = {1875-6360},
mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Feasibility Studies ; Humans ; *Obesity/complications ; *Osteoarthritis, Knee/drug therapy/therapy ; *Overweight/complications ; Pain ; *Self Care/methods ; Treatment Outcome ; },
abstract = {INTRODUCTION: Knee Osteoarthritis (OA) is a weight-bearing joint disease and is more common in overweight and obese persons. The objective of the study was to assess the feasibility and acceptability of Instructions of Daily Care (IDC) on pain, mobility, and Body Mass Index (BMI) among knee OA participants who are overweight or obese.<br><br>MATERIALS AND METHODS: The study was an open-label randomized controlled trial of six weeks. Forty overweight and obese participants with knee OA were randomly divided into two groups by a computer-generated number. The participants in the Instruction Group (IG) were provided with leaflets explaining IDC for the duration of six weeks. Both groups were instructed to take low doses of the non-steroid anti-inflammatory drug (NSAIDs) on alternate days. The outcome measures were pain, mobility and BMI. The feasibility and acceptability of knee pain and mobility were assessed using a questionnaire designed by experts in rehabilitation.<br><br>RESULTS: Participants in the IG reported more statistically significant pain relief as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index score (p=0.001) and improvement in mobility (p=0.000) assessed by the Timed Up and Go test score after six weeks compared to the Control Group (CG). Both groups did not demonstrate any significant change in BMI (p-value > 0.05). The results of descriptive statistics showed a significantly higher satisfaction score for participants who received a combination of IDC and NSAIDs, indicating an acceptable intervention.<br><br>CONCLUSION: The IDC is effective and acceptable in terms of improving pain and mobility and should be recommended as the usual care of treatment.},
}
@article {pmid34297787,
year = {2021},
author = {Ahmed, F and Adnan, M and Malik, A and Tariq, S and Kamal, F and Ijaz, B},
title = {Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females.},
journal = {PloS one},
volume = {16},
number = {7},
pages = {e0255243},
pmid = {34297787},
issn = {1932-6203},
mesh = {Adult ; Breast Neoplasms/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/*genetics ; Female ; Humans ; MicroRNAs/genetics/*metabolism ; Middle Aged ; Pakistan ; Smad2 Protein/genetics/metabolism ; Smad4 Protein/genetics/metabolism ; Transforming Growth Factor beta/genetics/*metabolism ; },
abstract = {Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient's data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to this in silico analysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of the TGF-β1 signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients' biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulate SMAD4 and SMAD2 expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.},
}
@article {pmid34293926,
year = {2021},
author = {Chen, X and Li, X and Wang, J and Zhao, L and Peng, X and Zhang, C and Liu, K and Huang, G and Lai, Y},
title = {Breast invasive ductal carcinoma diagnosis with a three-miRNA panel in serum.},
journal = {Biomarkers in medicine},
volume = {15},
number = {12},
pages = {951-963},
doi = {10.2217/bmm-2020-0785},
pmid = {34293926},
issn = {1752-0371},
mesh = {Biomarkers, Tumor/blood/*genetics ; Breast Neoplasms/blood/diagnosis/*genetics ; Carcinoma, Ductal, Breast/blood/diagnosis/*genetics ; Cohort Studies ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity ; },
abstract = {Aim: Breast cancer, especially invasive ductal carcinoma (IDC), is the cause of a great clinical burden. miRNA could be considered as a noninvasive biomarkers for IDC diagnosis. Materials &amp; methods: Two hundred and sixty participants (135 IDC patients and 125 healthy controls) were enrolled in a three-cohort study. The expression of 28 miRNAs in serum were detected with quantitative reverse transcription-PCR. Bioinformatic analysis was used for predicting the target genes of three selected miRNAs. Results: The expression level of seven miRNAs (miR-9-5p, miR-34b-3p, miR-1-3p, miR-146a-5p, miR-20a-5p, miR-34a-5p, miR-125b-5p) was discrepant at the validation cohort. Through statistical test, a three-miRNA panel (miR-9-5p, miR-34b-3p, miR-146a-5p) was significant for IDC diagnosis (AUC = 0.880, sensitivity = 86.25%, specificity = 81.25%). Conclusion: The three-miRNA panel in serum could be used as a noninvasive biomarker in the diagnosis of IDC.},
}
@article {pmid34293708,
year = {2021},
author = {Okcu, O and Öztürk, &#xc7; and Şen, B and Arpa, M and Bedir, R},
title = {Tumor Budding is a reliable predictor for death and metastasis in invasive ductal breast cancer and correlates with other prognostic clinicopathological parameters.},
journal = {Annals of diagnostic pathology},
volume = {54},
number = {},
pages = {151792},
doi = {10.1016/j.anndiagpath.2021.151792},
pmid = {34293708},
issn = {1532-8198},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/diagnosis/*mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/diagnosis/*pathology ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Prognosis ; Receptors, Progesterone/metabolism ; },
abstract = {BACKGROUND AND OBJECTIVE: Breast cancers are the most common type of cancer and the most common cause of mortality in women worldwide. Different prognostic factors are the subject of research to differentiate the prognosis even between cases at a similar stage and identify risky patients earlier and create individual treatment approaches. Tumor budding (TB) has been identified as a poor prognostic factor in many types of cancer, especially colorectal carcinomas. In our study, we aimed to determine the prognostic significance of the TB by evaluating the TB in line with clinicopathological parameters in breast invasive ductal carcinoma cases.<br><br>MATERIALS AND METHODS: 311 breast carcinoma cases operated in our hospital between January 2010 and April 2020 were included in the study. In hematoxylin-eosin (H&amp;E) sections of the cases, TB was evaluated in a single high-power field (HPF). ROC analysis was performed with overall survival data, and low, and high TB cutoffs were obtained. The relationship of the high TB with clinicopathological parameters was evaluated, and survival analysis was performed.<br><br>RESULTS: We determined that high TB in breast invasive ductal carcinoma cases was associated with low survival time, metastasis, axillary lymph node metastasis, angiolymphatic invasion, advanced stage (pT3), high Ki-67 proliferation index, progesterone receptor (PR) loss, and advanced age. Tumor budding was identified as an independent risk factor in overall and disease-free survival analysis.<br><br>CONCLUSION: Tumor budding is a prognostic parameter that can be easily evaluated in all centers since it does not cause additional cost to routine pathological examinations. We think it may be helpful to establish a standard methodology in evaluating tumor bud in breast carcinomas and including it in regular pathology reporting.},
}
@article {pmid34279157,
year = {2021},
author = {Ren, X and Ju, Y and Wang, C and Wei, R and Sun, H and Zhang, Q},
title = {MARCKS on Tumor-Associated Macrophages is Correlated with Immune Infiltrates and Poor Prognosis in Hepatocellular Carcinoma.},
journal = {Cancer investigation},
volume = {39},
number = {9},
pages = {756-768},
doi = {10.1080/07357907.2021.1950757},
pmid = {34279157},
issn = {1532-4192},
mesh = {Biomarkers, Tumor/*genetics/metabolism ; Carcinoma, Hepatocellular/*genetics/metabolism/pathology ; Cell Line, Tumor ; Exosomes/genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/*genetics/metabolism/pathology ; MicroRNAs/genetics ; Myristoylated Alanine-Rich C Kinase Substrate/*genetics/metabolism ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; THP-1 Cells ; Tumor-Associated Macrophages/*metabolism ; },
abstract = {BACKGROUND: Hepatocellular carcinoma is the fourth most common cause of cancer-related death. However, the cross-talk between tumor immune microenvironment and hepatocellular carcinoma (HCC) remains unclear.<br><br>MATERIAL AND METHODS: We analyzed the expression of miR-143-3p in exosomes from different HCC cell lines. Differentially expressed genes (DEGs) in Tumor-associated macrophages (TAMs) co-cultured with HCC cell lines were overlapped with miR-143-3p target genes. We used the Oncomine, Kaplan-Meier plotter, and The Cancer Genome Atlas (TCGA) databases to assess Myristoylated alanine-rich C-kinase substrate (MARCKS) expression in various types of cancers. The relationship between patient clinicopathological characteristics and MARCKS expression level was identified using the Kaplan-Meier plotter database. Last, we analyzed how MARCKS expression correlated with immune infiltration makers using the TCGA database, Tumor IMmune Estimation Resource (TIMER), and Gene Expression Profiling Interactive Analysis (GEPIA).<br><br>RESULTS: Exosomal miR-143-3p was elevated after IL-6 treatment in the HCC cell line. MARCKS, a target gene of miR-143-3p, was up-regulated in Tumor-associated macrophages co-cultured with high-metastatic-potential HCC cell line. MARCKS expression was identified as significantly correlated with outcome in multiple types of cancer, especially in HCC. High MARCKS expression level was associated with poorer overall survival (OS), Progress-free survival (PFS), and also with patient gender, race, hepatitis virus background, stage, grade, AJCC_T, and vascular invasion. MARCKS was positively associated with levels of T follicular helper cells (TFH) (R&#x2009;=&#x2009;.48, p&#x2009;<&#x2009;.001), T helper type 2 (Th2) cells (R&#x2009;=&#x2009;.47, p&#x2009;<&#x2009;.001), macrophages (R&#x2009;=&#x2009;.41, p&#x2009;&#x2264;&#x2009;.001), T helper cells (R&#x2009;=&#x2009;.40, p&#x2009;<&#x2009;.001), T helper type 1 (Th1) cells (R&#x2009;=&#x2009;.38, p&#x2009;<&#x2009;.001), T cells (R&#x2009;=&#x2009;.34, p&#x2009;<&#x2009;.001), NK CD56bright cells (R&#x2009;=&#x2009;.34, p&#x2009;<&#x2009;.001) and immature DC (iDC) (R&#x2009;=&#x2009;.33, p&#x2009;<&#x2009;.001), and negatively associated with levels of T helper 17 (Th17) cells. Also, MARCKS may influence the M2 polarization and immune escape.<br><br>CONCLUSION: The present study suggests that MARCKS on TAMs is associated with poor prognosis and immune cell infiltration in HCC.},
}
@article {pmid34278746,
year = {2021},
author = {Qi, H and Schmöhl, F and Li, X and Qian, X and Tabler, CT and Bennewitz, K and Sticht, C and Morgenstern, J and Fleming, T and Volk, N and Hausser, I and Heidenreich, E and Hell, R and Nawroth, PP and Kroll, J},
title = {Reduced Acrolein Detoxification in akr1a1a Zebrafish Mutants Causes Impaired Insulin Receptor Signaling and Microvascular Alterations.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {8},
number = {18},
pages = {e2101281},
pmid = {34278746},
issn = {2198-3844},
support = {CRC1118//Deutsche Forschungsgemeinschaft/ ; IRTG1874/2 DIAMICOM//Deutsche Forschungsgemeinschaft/ ; CSC 201806230275//China Scholarship Council/ ; 81800390//National Natural Science Foundation of China/ ; },
mesh = {Acrolein/*metabolism ; Animals ; Diabetes Mellitus, Experimental/*metabolism ; Disease Models, Animal ; Glucose/*metabolism ; Homeostasis ; Larva/metabolism ; Liver/*metabolism ; Metabolomics/methods ; Receptor, Insulin/*metabolism ; Signal Transduction ; Transcriptome ; Zebrafish/metabolism ; },
abstract = {Increased acrolein (ACR), a toxic metabolite derived from energy consumption, is associated with diabetes and its complications. However, the molecular mechanisms are mostly unknown, and a suitable animal model with internal increased ACR does not exist for in vivo studying so far. Several enzyme systems are responsible for acrolein detoxification, such as Aldehyde Dehydrogenase (ALDH), Aldo-Keto Reductase (AKR), and Glutathione S-Transferase (GST). To evaluate the function of ACR in glucose homeostasis and diabetes, akr1a1a[-/-] zebrafish mutants are generated using CRISPR/Cas9 technology. Accumulated endogenous acrolein is confirmed in akr1a1a[-/-] larvae and livers of adults. Moreover, a series of experiments are performed regarding organic alterations, the glucose homeostasis, transcriptome, and metabolomics in Tg(fli1:EGFP) zebrafish. Akr1a1a[-/-] larvae display impaired glucose homeostasis and angiogenic retina hyaloid vasculature, which are caused by reduced acrolein detoxification ability and increased internal ACR concentration. The effects of acrolein on hyaloid vasculature can be reversed by acrolein-scavenger l-carnosine treatment. In adult akr1a1a[-/-] mutants, impaired glucose tolerance accompanied by angiogenic retina vessels and glomerular basement membrane thickening, consistent with an early pathological appearance in diabetic retinopathy and nephropathy, are observed. Thus, the data strongly suggest impaired ACR detoxification and elevated ACR concentration as biomarkers and inducers for diabetes and diabetic complications.},
}
@article {pmid34272624,
year = {2021},
author = {Considine, B and Adeniran, A and Hurwitz, ME},
title = {Current Understanding and Management of Intraductal Carcinoma of the Prostate.},
journal = {Current oncology reports},
volume = {23},
number = {9},
pages = {110},
pmid = {34272624},
issn = {1534-6269},
mesh = {Carcinoma, Ductal/*genetics/pathology/therapy ; DNA Mismatch Repair/*genetics ; Genetic Predisposition to Disease/*genetics ; Humans ; Male ; *Microsatellite Instability ; *Mutation ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/pathology/therapy ; Signal Transduction/genetics ; },
abstract = {PURPOSE OF REVIEW: This review will discuss current understanding and management approaches of Intraductal carcinoma of the prostate (IDC-P). IDC-P is a histological finding characterized by neoplastic cells that expand but do not invade prostate ducts.<br><br>RECENT FINDINGS: The presence of IDC-P on a prostate biopsy is almost always associated with an invasive disease component and is independently associated with worse clinical outcomes in both early and late disease. These tumors are enriched for mutations in homologous DNA recombination repair (HRR) leading to high genomic instability. Multiparametric MRI with targeted biopsy may aid in diagnosis. Given the poor clinical outcomes associated with this histologic entity, its presence in biopsies should warrant consideration of aggressive management.},
}
@article {pmid34249415,
year = {2021},
author = {Lin, Q and Chen, X and Meng, F and Ogawa, K and Li, M and Song, R and Zhang, S and Zhang, Z and Kong, X and Xu, Q and He, F and Liu, D and Bai, X and Sun, B and Hung, MC and Liu, L and Wands, JR and Dong, X},
title = {Multi-organ metastasis as destination for breast cancer cells guided by biomechanical architecture.},
journal = {American journal of cancer research},
volume = {11},
number = {6},
pages = {2537-2567},
pmid = {34249415},
issn = {2156-6976},
support = {P30 GM110759/GM/NIGMS NIH HHS/United States ; R01 CA123544/CA/NCI NIH HHS/United States ; },
abstract = {A majority of breast cancer patients die of widespread aggressive multidrug-resistant tumors. Aspartate β-hydroxylase (ASPH) is an α-ketoglutarate-dependent dioxygenase and oncofetal antigen involved in embryogenesis. To illustrate if ASPH could be targeted for metastatic breast cancer, embedded and on-top three-dimensional (3-D) cultures, 3-D invasion, mammosphere formation, immunofluorescence, immunohistochemistry, Western blot, co-IP and microarray were conducted. In vitro metastasis was developed to imitate how cancer cells invade basement membrane at the primary site, transendothelially migrate, consequently colonize and outgrow at distant sites. Orthotopic and experimental pulmonary metastatic (tail vein injection) murine models were established using stable breast cancer cell lines. Cox proportional hazards regression models and Kaplan-Meier plots were applied to assess clinical outcome of breast cancer patients. In adult non-cancerous breast tissue, ASPH is undetectable. Pathologically, ASPH expression re-emerged at ductal carcinoma in situ (DCIS), and enhanced with disease progression, from early-stage invasive ductal carcinoma (IDC) to late-stage carcinoma. ASPH at moderate to high levels contribute to aggressive molecular subtypes, early relapse or more frequent progression and metastases, whereas substantially shortened overall survival and disease-free survival of breast cancer patients. Through direct physical interactions with A disintegrin and metalloproteinase domain-containing protein (ADAM)-12/ADAM-15, ASPH could activate SRC cascade, thus upregulating downstream components attributed to multifaceted metastasis. ASPH-SRC axis initiated pro-invasive invadopodium formation causing breakdown/disorganization of extracellular matrix (ECM), simultaneously potentiated epithelial-mesenchymal transition (EMT), induced cancer stem cell markers (CD44 and EpCAM), enhanced mammosphere formation and intensified 3-dimentional invasion. Oncogenic SRC upregulated matrix metallopeptidases (MMPs) were assembled by invadopodia, acting as executive effectors for multi-step metastasis. ASPH-SRC signal guided multi-organ metastases (to lungs, liver, bone, spleen, lymph nodes, mesentery or colon) in immunocompromised mice. Malignant phenotypes induced by ASPH-SRC axis were reversed by the third-generation small molecule inhibitor (SMI) specifically against β-hydroxylase activity of ASPH in pre-clinical models of metastatic breast cancer. Collectively, ASPH could activate ADAMs-SRC-MMPs cascades to promote breast cancer tumor progression and metastasis. ASPH could direct invadopodium construction as a biomechanical sensor and pro-metastatic outlet. ASPH-mediated cancer progression could be specifically/efficiently subverted by SMIs of β-hydroxylase activity. Therefore, ASPH emerges as a therapeutic target for breast cancer.},
}
@article {pmid34243714,
year = {2021},
author = {Chiong, F and Wasef, MS and Liew, KC and Cowan, R and Tsai, D and Lee, YP and Croft, L and Harris, O and Gwini, SM and Athan, E},
title = {The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bacteraemia in adults: a retrospective cohort study.},
journal = {BMC infectious diseases},
volume = {21},
number = {1},
pages = {671},
pmid = {34243714},
issn = {1471-2334},
mesh = {Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/mortality/surgery ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio ; Prospective Studies ; Pseudomonas Infections/*drug therapy/mortality/surgery ; *Pseudomonas aeruginosa ; *Referral and Consultation ; Retrospective Studies ; Treatment Outcome ; },
abstract = {BACKGROUND: Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB.<br><br>METHODS: This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality.<br><br>RESULTS: A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p&#x2009;<&#x2009;0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p&#x2009;<&#x2009;0.01), undergo removal of infected catheter (27.5% vs 13.5%; p&#x2009;=&#x2009;0.049) and undergo surgical intervention (20.9% vs 5.4%, p&#x2009;=&#x2009;0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR]&#x2009;=&#x2009;10.63, p&#x2009;<&#x2009;0.001) and adjusted analysis (adjusted OR&#x2009;=&#x2009;7.84; 95% confidence interval, 2.95-20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups.<br><br>CONCLUSION: Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.},
}
@article {pmid34242220,
year = {2021},
author = {Xu, Z and Kurek, A and Cannon, SB and Beavis, WD},
title = {Predictions from algorithmic modeling result in better decisions than from data modeling for soybean iron deficiency chlorosis.},
journal = {PloS one},
volume = {16},
number = {7},
pages = {e0240948},
pmid = {34242220},
issn = {1932-6203},
mesh = {*Glycine max/genetics ; *Algorithms ; Bayes Theorem ; Genotype ; Iron Deficiencies ; Plant Necrosis and Chlorosis/genetics ; },
abstract = {In soybean variety development and genetic improvement projects, iron deficiency chlorosis (IDC) is visually assessed as an ordinal response variable. Linear Mixed Models for Genomic Prediction (GP) have been developed, compared, and used to select continuous plant traits such as yield, height, and maturity, but can be inappropriate for ordinal traits. Generalized Linear Mixed Models have been developed for GP of ordinal response variables. However, neither approach addresses the most important questions for cultivar development and genetic improvement: How frequently are the 'wrong' genotypes retained, and how often are the 'correct' genotypes discarded? The research objective reported herein was to compare outcomes from four data modeling and six algorithmic modeling GP methods applied to IDC using decision metrics appropriate for variety development and genetic improvement projects. Appropriate metrics for decision making consist of specificity, sensitivity, precision, decision accuracy, and area under the receiver operating characteristic curve. Data modeling methods for GP included ridge regression, logistic regression, penalized logistic regression, and Bayesian generalized linear regression. Algorithmic modeling methods include Random Forest, Gradient Boosting Machine, Support Vector Machine, K-Nearest Neighbors, Naïve Bayes, and Artificial Neural Network. We found that a Support Vector Machine model provided the most specific decisions of correctly discarding IDC susceptible genotypes, while a Random Forest model resulted in the best decisions of retaining IDC tolerant genotypes, as well as the best outcomes when considering all decision metrics. Overall, the predictions from algorithmic modeling result in better decisions than from data modeling methods applied to soybean IDC.},
}
@article {pmid34238275,
year = {2021},
author = {Samson, J and Derlipanska, M and Zaheed, O and Dean, K},
title = {Molecular and cellular characterization of two patient-derived ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.},
journal = {BMC cancer},
volume = {21},
number = {1},
pages = {790},
pmid = {34238275},
issn = {1471-2407},
mesh = {Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; },
abstract = {BACKGROUND: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.<br><br>METHODS: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile.<br><br>RESULTS: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in pathways involving receptor tyrosine kinases and DNA replication/cell cycle programs and in gene sets responsible for extracellular matrix organisation and ion transport.<br><br>CONCLUSIONS: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.},
}
@article {pmid34230895,
year = {2021},
author = {Muthumani, K and Xu, Z and Jeong, M and Maslow, JN and Kalyanaraman, VS and Srinivasan, A},
title = {Preexisting vs. de novo antibodies against SARS-CoV-2 in individuals without or with virus infection: impact on antibody therapy, vaccine research and serological testing.},
journal = {Translational medicine communications},
volume = {6},
number = {1},
pages = {13},
pmid = {34230895},
issn = {2396-832X},
abstract = {The causative agent of the ongoing pandemic in the world is SARS-CoV-2. The research on SARS-CoV-2 has progressed with lightning speed on various fronts, including clinical research and treatment, virology, epidemiology, drug development, and vaccine research. Recent studies reported that sera from healthy individuals, who were confirmed negative for SARS-CoV-2 by RT-PCR method, tested positive for antibodies against spike and nucleocapsid proteins of SARS-CoV-2. Further, such antibodies also exhibited neutralizing activity against the virus. These observations have prompted us to prepare a commentary on this topic. While the preexisting antibodies are likely to protect against SARS-CoV-2 infection, they may also complicate serological testing results. Another unknown is the influence of preexisting antibodies on immune responses in individuals receiving vaccines against SARS-CoV-2. The commentary identifies the potential limitations with the serological tests based on spike and nucleocapsid proteins as these tests may overestimate the seroprevalence due to cross-reactive antibodies. The inclusion of tests specific to SARS-CoV-2 (such as RBD of spike protein) could overcome these limitations.},
}
@article {pmid34225099,
year = {2021},
author = {Pariyar, M and Johns, A and Thorne, RF and Scott, RJ and Avery-Kiejda, KA},
title = {Copy number variation in triple negative breast cancer samples associated with lymph node metastasis.},
journal = {Neoplasia (New York, N.Y.)},
volume = {23},
number = {8},
pages = {743-753},
pmid = {34225099},
issn = {1476-5586},
mesh = {*Biomarkers, Tumor ; Chromosome Mapping ; Computational Biology/methods ; *DNA Copy Number Variations ; DNA Methylation ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Ontology ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Molecular Sequence Annotation ; Neoplasm Staging ; Prognosis ; Triple Negative Breast Neoplasms/*etiology/mortality/*pathology ; },
abstract = {Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs. CNV-associated genes were analyzed using GO-enrichment and Pathway analysis. The prognostic role for genes showing CNV-based changes in messenger RNA expression was determined using the Kaplan-Meier plotter database. For the IDCs, there were a number of variations that were common in both the study and independent cohorts in the amplified regions of 1q, 8q, 19 (p and q), 2p, 5p and the deleted regions in 8p followed by 5q, and 19p. The most frequently amplified regions in the LNmets of the study cohort were 4q28.3, 2p, 3q24, 1q21.2, 10p, 12p11.1, 8q, 20p11.22-20p11.21, 21q22.13, 6p22.1 and the most frequently deleted regions were in 1p36.23, 4q21.1 and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with LNmets. The LNmet-associated genes were highly enriched for "regulation of complement activation," "regulation of protein activation cascade," "regulation of humoral immune response," "oxytocin signalling pathway," and "TRAIL binding" pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse-free survival. This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.},
}
@article {pmid34219706,
year = {2022},
author = {Avau, F and Chintinne, M and Baudry, S and Buxant, F},
title = {Literature review and case report of bilateral intracystic papillary carcinoma associated with an invasive ductal carcinoma in a male breast.},
journal = {Breast disease},
volume = {41},
number = {1},
pages = {5-13},
doi = {10.3233/BD-210001},
pmid = {34219706},
issn = {1558-1551},
mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms, Male/*complications/drug therapy/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/complications/drug therapy/*secondary ; Carcinoma, Papillary/classification/*diagnostic imaging/drug therapy ; Humans ; Male ; Mammography ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; },
abstract = {Intracystic papillary carcinoma (IPC) is a rare tumor with good prognosis that occurs in only 5% to 7.5% of male breast cancer. We report a case of a 46-year-old man who presented a brown nipple discharge a few months ago. He had a bilateral IPC and an invasive ductal carcinoma on the right breast. A double mastectomy was then performed with a bilateral sentinel lymph node biopsy, and he received chemotherapy, radiotherapy, and hormonotherapy. Two years after the diagnosis, the patient recovered and was free of recurrence. Considering the scarcity of this tumor type, we conducted a systematic literature review on the PubMed of all the cases of IPC in men. The clinical presentation, imaging, and treatment of the 43 case reports from the 41 articles selected were described. Furthermore, no clear guidelines for IPC management are available. Conservative surgery should also be preferred, and a sentinel lymph node biopsy should be performed systematically. Moreover, radiotherapy should be proposed in the case of conservative surgery, and hormone therapy could be proposed in the case of invasive IPC or IPC associated with a ductal carcinoma in situ.},
}
@article {pmid34204158,
year = {2021},
author = {Itani, MM and Nassar, FJ and Tfayli, AH and Talhouk, RS and Chamandi, GK and Itani, ARS and Makoukji, J and Boustany, RN and Hou, L and Zgheib, NK and Nasr, RR},
title = {A Signature of Four Circulating microRNAs as Potential Biomarkers for Diagnosing Early-Stage Breast Cancer.},
journal = {International journal of molecular sciences},
volume = {22},
number = {11},
pages = {},
pmid = {34204158},
issn = {1422-0067},
support = {R. NASR Grant//Lebanese National Council for Scientific Research (CNRS-L)/ ; R NASR proposal//Medical Practice Plan, AUB/ ; R Nasr proposal//Northwestern University Kiphart award/ ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood/*genetics ; Breast Neoplasms/*blood/*diagnosis/genetics/pathology ; Circulating MicroRNA/*blood/*genetics ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Statistics, Nonparametric ; Young Adult ; },
abstract = {Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy.},
}
@article {pmid34198053,
year = {2021},
author = {Sela, Y and Bar-Or, RL and Kor, A and Lev-Ran, S},
title = {The Internet addiction test: Psychometric properties, socio-demographic risk factors and addictive co-morbidities in a large adult sample.},
journal = {Addictive behaviors},
volume = {122},
number = {},
pages = {107023},
doi = {10.1016/j.addbeh.2021.107023},
pmid = {34198053},
issn = {1873-6327},
mesh = {Adult ; *Behavior, Addictive/epidemiology ; Cross-Sectional Studies ; Humans ; Internet ; *Internet Addiction Disorder ; Prevalence ; Psychometrics ; Reproducibility of Results ; Risk Factors ; Surveys and Questionnaires ; },
abstract = {The Internet Addiction Test (IAT) (Young, 1998) is one of the most utilized diagnostic instruments to evaluate internet addiction. Despite the wide use of IAT in research and clinical settings, there is lack of an empirical validation of this scale among a largescale adult population. The present study aimed to: (1) investigate the psychometric properties of a Hebrew version of the IAT among large-scale Israeli adult sample. (2) Assess the socio-demographic characteristics of individuals who suffer from IA. (3) Assess the co-morbidity of IA in relation to substance and behavioral addictions. A cross sectional study was conducted, by constructing a representative sample (N = 4035) of the Jewish adult (18-70 y/o, M = 40.5, SD = 14.5) population in Israel. Participants responded an online survey, that measured IAT, socio-demographic characteristics, substance and behavioral addictions. Results showed that two-factor model (Emotional and Cognitive Preoccupation with the Internet and Loss of Control and Interference with Daily Life) has good psychometric properties and fits the data well. Young age, not being married (Risk Ratio [RR] = 1.98, 95% CI [1.51-2.63]), and having a low socio-economic status (RR = 1.41, 95% CI [1.05-1.90]) were found to be associated with IA. Drug (RR = 4.50, 95% CI [2.89-7.01]) and alcohol (RR = 3.54, 95% CI [1.50-5.42]) use disorders were associated with IA. High co-morbidity between behavioral addictions and IA was also found (RR = 15.24, 95% CI [11.17-20.78]). Overall, results show that the Hebrew version of the IAT is a valid and reliable instrument, and provide a comprehensive picture of IA prevalence and profile in adult Israeli sample.},
}
@article {pmid34188137,
year = {2021},
author = {Mayopoulos, GA and Ein-Dor, T and Li, KG and Chan, SJ and Dekel, S},
title = {COVID-19 positivity associated with traumatic stress response to childbirth and no visitors and infant separation in the hospital.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {13535},
pmid = {34188137},
issn = {2045-2322},
support = {R21 HD100817/HD/NICHD NIH HHS/United States ; R21HD100817//National Institute of Child Health and Human Development/ ; },
mesh = {Adult ; Anxiety/diagnosis ; Birth Weight ; COVID-19/diagnosis/*psychology/virology ; Female ; Hospitals ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Pain/pathology ; Parturition/*psychology ; Patient Admission/statistics &amp; numerical data ; Pregnancy ; Pregnant People/*psychology ; SARS-CoV-2/isolation &amp; purification ; Stress Disorders, Post-Traumatic/*diagnosis ; Stress, Psychological ; Surveys and Questionnaires ; },
abstract = {As the novel coronavirus (COVID-19) has spread globally, a significant portion of pregnant and delivering women were infected with COVID-19. While emerging studies examined birth outcomes in COVID-19 positive women, knowledge of the psychological experience of childbirth and maternal wellness remains lacking. This matched-control survey-based study included a sample of women recruited during the first wave of the pandemic in the US who gave birth in the previous six months. Women reporting confirmed/suspected COVID-19 (n = 68) during pregnancy or childbirth were matched on background factors with women reporting COVID-19 negativity (n = 2,276). We found nearly 50% of COVID positive women endorsed acute traumatic stress symptoms at a clinical level in response to childbirth. This group was more than twice as likely to endorse acute stress and to have no visitors during maternity hospitalization than COVID negative women; they were also less likely to room-in with newborns. The COVID positive group reported higher levels of pain in delivery, lower newborn weights, and more infant admission to neonatal intensive care units. Our findings suggest COVID-19 affected populations are at increased risk for traumatic childbirth and associated risk for psychiatric morbidity. Attention to delivering women's wellbeing is warranted during the pandemic.},
}
@article {pmid34185954,
year = {2022},
author = {Zhao, J and Sun, G and Zhu, S and Dai, J and Chen, J and Zhang, M and Ni, Y and Zhang, H and Shen, P and Zhao, X and Zhang, B and Pan, X and Nie, L and Yin, X and Liang, J and Zhang, X and Wang, Z and Zhu, X and Liao, B and Liu, Z and Armstrong, CM and Gao, AC and Huang, H and Chen, N and Zeng, H},
title = {Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate.},
journal = {BJU international},
volume = {129},
number = {3},
pages = {345-355},
doi = {10.1111/bju.15530},
pmid = {34185954},
issn = {1464-410X},
mesh = {*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Circulating Tumor DNA/genetics ; Humans ; Male ; Phenotype ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; },
abstract = {OBJECTIVES: To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC-P).<br><br>PATIENTS AND METHODS: We performed targeted sequencing of plasma cell-free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC-P and 84 without IDC-P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients' survival outcomes was also explored.<br><br>RESULTS: We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC-P harboured genomic alterations in DNA repair pathways, respectively (P&#x2009;=&#x2009;0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC-P carriers compared to IDC-P non-carriers (11.8% [19/161] vs 2.4% [two of 84], P&#x2009;=&#x2009;0.024). Germline BReast CAncer type 2 susceptibility protein (BRCA2) and somatic cyclin-dependent kinase 12 (CDK12) defects were specifically identified in IDC-P carriers relative to PAC (BRCA2: 8.7% [14/161] vs 0% and CDK12: 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC-P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 (NCOR2) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P&#x2009;=&#x2009;0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC-P proportion of &#x2265;10% vs those with an IDC-P proportion of <10% (6.4% [five of 78] vs 18.1% [15/83], P&#x2009;=&#x2009;0.045). For IDC-P carriers, tumour protein p53 (TP53) mutation was associated with shorter castration-resistant-free survival (median 10.9 vs 28.9&#x2009;months, P&#x2009;=&#x2009;0.026), and BRCA2 alteration was related to rapid prostate-specific antigen progression for those receiving abiraterone treatment (median 9.1 vs 11.9&#x2009;months, P&#x2009;=&#x2009;0.036).<br><br>CONCLUSION: Our findings provide genomic evidence explaining the aggressive phenotype of tumours with IDC-P, highlighting the potential therapeutic strategies for this patient population.},
}
@article {pmid34185678,
year = {2021},
author = {Fedorov, A and Longabaugh, WJR and Pot, D and Clunie, DA and Pieper, S and Aerts, HJWL and Homeyer, A and Lewis, R and Akbarzadeh, A and Bontempi, D and Clifford, W and Herrmann, MD and Höfener, H and Octaviano, I and Osborne, C and Paquette, S and Petts, J and Punzo, D and Reyes, M and Schacherer, DP and Tian, M and White, G and Ziegler, E and Shmulevich, I and Pihl, T and Wagner, U and Farahani, K and Kikinis, R},
title = {NCI Imaging Data Commons.},
journal = {Cancer research},
volume = {81},
number = {16},
pages = {4188-4193},
pmid = {34185678},
issn = {1538-7445},
support = {P41 EB015898/EB/NIBIB NIH HHS/United States ; HHSN261201500003C/CA/NCI NIH HHS/United States ; HHSN261201000031C/CA/NCI NIH HHS/United States ; HHSN261201500001C/CA/NCI NIH HHS/United States ; HHSN261201500001G/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; P41 EB028741/EB/NIBIB NIH HHS/United States ; HHSN261201500001W/CA/NCI NIH HHS/United States ; },
mesh = {Biomedical Research/trends ; Cloud Computing ; Computational Biology/methods ; Computer Graphics ; Computer Security ; Data Interpretation, Statistical ; Databases, Factual ; Diagnostic Imaging/*methods/standards ; Humans ; Image Processing, Computer-Assisted ; *National Cancer Institute (U.S.) ; Neoplasms/*diagnostic imaging/*genetics ; Pilot Projects ; Programming Languages ; Radiology/methods/standards ; Reproducibility of Results ; Software ; United States ; User-Computer Interface ; },
abstract = {The National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) aims to establish a national cloud-based data science infrastructure. Imaging Data Commons (IDC) is a new component of CRDC supported by the Cancer Moonshot. The goal of IDC is to enable a broad spectrum of cancer researchers, with and without imaging expertise, to easily access and explore the value of deidentified imaging data and to support integrated analyses with nonimaging data. We achieve this goal by colocating versatile imaging collections with cloud-based computing resources and data exploration, visualization, and analysis tools. The IDC pilot was released in October 2020 and is being continuously populated with radiology and histopathology collections. IDC provides access to curated imaging collections, accompanied by documentation, a user forum, and a growing number of analysis use cases that aim to demonstrate the value of a data commons framework applied to cancer imaging research. SIGNIFICANCE: This study introduces NCI Imaging Data Commons, a new repository of the NCI Cancer Research Data Commons, which will support cancer imaging research on the cloud.},
}
@article {pmid34181649,
year = {2021},
author = {Aftab, F and Ahmed, I and Ahmed, S and Ali, SM and Amenga-Etego, S and Ariff, S and Bahl, R and Baqui, AH and Begum, N and Bhutta, ZA and Biemba, G and Cousens, S and Das, V and Deb, S and Dhingra, U and Dutta, A and Edmond, K and Esamai, F and Ghosh, AK and Gisore, P and Grogan, C and Hamer, DH and Herlihy, J and Hurt, L and Ilyas, M and Jehan, F and Juma, MH and Kalonji, M and Khanam, R and Kirkwood, BR and Kumar, A and Kumar, A and Kumar, V and Manu, A and Marete, I and Mehmood, U and Minckas, N and Mishra, S and Mitra, DK and Moin, MI and Muhammad, K and Newton, S and Ngaima, S and Nguwo, A and Nisar, MI and Otomba, J and Quaiyum, MA and Sarrassat, S and Sazawal, S and Semrau, KE and Shannon, C and Singh, VP and Soofi, S and Soremekun, S and Suleiman, AM and Sunday, V and Dilip, TR and Tshefu, A and Wasan, Y and Yeboah-Antwi, K and Yoshida, S and Zaidi, AK and , },
title = {Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.},
journal = {PLoS medicine},
volume = {18},
number = {6},
pages = {e1003644},
pmid = {34181649},
issn = {1549-1676},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; Young Adult ; Africa South of the Sahara/epidemiology ; Asia/epidemiology ; *Infant Mortality ; *Maternal Mortality ; *Pregnancy Complications/diagnosis/mortality ; Pregnancy Outcome ; Prospective Studies ; Risk Assessment ; Risk Factors ; *Stillbirth/epidemiology ; },
abstract = {BACKGROUND: Maternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa.<br><br>METHODS AND FINDINGS: This is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes.<br><br>CONCLUSIONS: Our findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths.<br><br>TRIAL REGISTRATION: The study is not a clinical trial.},
}
@article {pmid34180038,
year = {2021},
author = {Uomori, T and Horimoto, Y and Takanashi, M and Shikanai, A and Nakai, K and Arakawa, A and Saito, M},
title = {Cerebral hemorrhage due to amyloid angiopathy that was difficult to differentiate from breast cancer metastasis: a case report.},
journal = {Surgical case reports},
volume = {7},
number = {1},
pages = {150},
pmid = {34180038},
issn = {2198-7793},
abstract = {BACKGROUND: Breast cancer patients are known to develop brain metastasis at a relatively high frequency. However, imaging findings of brain metastases vary, and it is sometimes very difficult to distinguish these from other tumorous lesions and non-neoplastic lesions, such as cerebral hemorrhage. Meanwhile, there are various causes of cerebral hemorrhage; a major one is cerebral amyloid angiopathy (CAA). With the advancement of imaging technology, CAA-related cerebral hemorrhage can be more precisely diagnosed with magnetic resonance imaging (MRI), but definitive diagnosis of CAA can only be made based on pathological assessment. Herein, we report a case of consciousness disorder appearing during adjuvant therapy for breast cancer. We initially considered that the patient's cerebral hemorrhage was due to a metastatic tumor, but based on excisional biopsy, she was diagnosed with CAA.<br><br>CASE PRESENTATION: A 73-year-old Japanese woman underwent curative surgery for left breast cancer. Her disease was hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-positive invasive ductal carcinoma (pStage IIB). While receiving adjuvant treatment, she developed disorientation, and emergent imaging revealed multiple cerebral hemorrhages. There was no apparent enhancement in the cerebral parenchyma on MRI, and differential diagnosis included hemorrhage due to a metastatic tumor, intravascular large B-cell lymphoma, CAA and thrombotic intracranial bleeding. After hospitalization, the bleeding lesion enlarged, resulting in cerebral hernia, and she needed emergency drainage surgery. The tissue surrounding the hemorrhage was pathologically assessed, and she was diagnosed with CAA. Although we initially suspected the lesion to be a metastatic tumor from breast cancer, there were no tumorous cells.<br><br>CONCLUSION: Atypical MRI findings made diagnosis difficult in this case, but it should be considered for differential diagnosis when multiple cerebral hemorrhages in elderly patients are observed, especially in cases with symptoms such as transient multifocal neurological deficits and dementia.},
}
@article {pmid34166430,
year = {2021},
author = {Nkadimeng, MV and Makombe, G and Mapiye, O and Mapiye, C and Oluwatayo, I and Dzama, K and Mojapelo, C and Mollel, N and Ngambi, J and Mautjana, MH},
title = {A gross margin analysis for Nguni cattle farmers in Limpopo Province, South Africa.},
journal = {PloS one},
volume = {16},
number = {6},
pages = {e0253657},
pmid = {34166430},
issn = {1932-6203},
mesh = {Animal Husbandry/*economics ; Animals ; Cattle ; *Farmers ; Farms/*economics ; Humans ; South Africa ; },
abstract = {Factors such as increases in population, urbanization, growth in per capita income and changes in consumer taste and preferences are causing gradual increases in livestock product consumption and demand. South Africa is addressing this predicted increase in livestock products demand by commercializing smallholder livestock producers. The Limpopo Industrial Development Corporation (IDC) Nguni Cattle Development Project is an example of such effort. The economic performance of these efforts needs to be evaluated. We use gross margin analysis to evaluate the performance of the Limpopo IDC Nguni Cattle Development Project. Additionally, we use regression analysis to identify factors influencing gross margins. Our results indicate that although smallholders show potential to commercialize, they lack commercial farming experience and require that a strong extension support system be used as one of the strategies to improve profitability. We also noted that individual farmers were more profitable than group farmers. Multiple regression analysis shows that three variables could be used to stimulate gross margin among the Limpopo IDC Nguni Cattle Development Project farmers. These are herd size, distance to market and farm size. Since farm size is a given, policy should focus on assisting farmers to build their herds and to have better access to markets.},
}
@article {pmid34142156,
year = {2021},
author = {Nakamura, T and Okabe, K and Hirayama, S and Chirifu, M and Ikemizu, S and Morioka, H and Nakabeppu, Y and Yamagata, Y},
title = {Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer.},
journal = {Nucleic acids research},
volume = {49},
number = {12},
pages = {7154-7163},
pmid = {34142156},
issn = {1362-4962},
mesh = {Adenine ; Adenomatous Polyposis Coli/genetics ; Amino Acid Motifs ; Animals ; DNA/chemistry ; DNA Glycosylases/*chemistry/genetics ; DNA Repair ; DNA Replication ; Guanine/analogs &amp; derivatives ; Humans ; Mice ; Models, Molecular ; Mutation ; Proliferating Cell Nuclear Antigen/chemistry ; Zinc ; },
abstract = {Mammalian MutY homologue (MUTYH) is an adenine DNA glycosylase that excises adenine inserted opposite 8-oxoguanine (8-oxoG). The inherited variations in human MUTYH gene are known to cause MUTYH-associated polyposis (MAP), which is associated with colorectal cancer. MUTYH is involved in base excision repair (BER) with proliferating cell nuclear antigen (PCNA) in DNA replication, which is unique and critical for effective mutation-avoidance. It is also reported that MUTYH has a Zn-binding motif in a unique interdomain connector (IDC) region, which interacts with Rad9-Rad1-Hus1 complex (9-1-1) in DNA damage response, and with apurinic/apyrimidinic endonuclease 1 (APE1) in BER. However, the structural basis for the BER pathway by MUTYH and its interacting proteins is unclear. Here, we determined the crystal structures of complexes between mouse MUTYH and DNA, and between the C-terminal domain of mouse MUTYH and human PCNA. The structures elucidated the repair mechanism for the A:8-oxoG mispair including DNA replication-coupled repair process involving MUTYH and PCNA. The Zn-binding motif was revealed to comprise one histidine and three cysteine residues. The IDC, including the Zn-binding motif, is exposed on the MUTYH surface, suggesting its interaction modes with 9-1-1 and APE1, respectively. The structure of MUTYH explains how MAP mutations perturb MUTYH function.},
}
@article {pmid34133406,
year = {2021},
author = {Akhavan, AA and Wirtz, EC and Ollila, DW and Bhatt, N},
title = {An Unusual Case of BIA-ALCL Associated with Prolonged/Complicated Biocell-Textured Expander, followed by Smooth Round Breast Implant Exposure, and Concurrent Use of Adalimumab.},
journal = {Plastic and reconstructive surgery},
volume = {148},
number = {2},
pages = {299-303},
doi = {10.1097/PRS.0000000000008155},
pmid = {34133406},
issn = {1529-4242},
mesh = {Adalimumab/*adverse effects ; Breast Implantation/*adverse effects/instrumentation ; Breast Implants/*adverse effects ; Breast Neoplasms/diagnosis/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/pathology/therapy ; Chemotherapy, Adjuvant/adverse effects/methods ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/*diagnosis/etiology/surgery ; Mastectomy/adverse effects ; Middle Aged ; Surface Properties ; Tissue Expansion Devices/*adverse effects ; },
abstract = {Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a malignancy associated with textured breast implants. BIA-ALCL is typically restricted to the periprosthetic capsule, presenting as a unilateral recurrent seroma years after placement of a textured breast implant. Current estimates suggest an incidence of one in 3300 for patients with Allergan Biocell textured implants. As of February 6, 2019, U.S. Medical Device Reporting associated with BIA-ALCL showed 457 unique cases of BIA-ALCL, with 24 "unverified and potentially inaccurate" cases associated with a nontextured implant. As of February of 2019, there were 688 reported cases to date worldwide. To date, there are no published case reports of BIA-ALCL associated exclusively with smooth implants or with smooth implants after textured expanders, and there has been no reported smooth-only case in any registry, database, or journal worldwide. The authors present a case of BIA-ALCL associated with smooth round implants and textured tissue expanders. A 56-year-old woman was treated for left stage IIA invasive ductal carcinoma with bilateral mastectomies and immediate reconstruction with bilateral subpectoral textured tissue expanders. She underwent exchange to Mentor smooth-round implants, and completed adjuvant chemotherapy. Magnetic resonance imaging and examination 4.5 years after implant placement showed no abnormal findings. The patient had left breast trauma 5 years following implant placement while taking adalimumab, and developed an open wound requiring explantation. A recurrent seroma developed, and tested positive for BIA-ALCL on cytology. Surgical pathologic examination after total capsulectomy demonstrated stage IA BIA-ALCL. To the authors' knowledge, this is the first case report of BIA-ALCL in a patient with textured expanders followed by prolonged exposure to smooth round implants.},
}
@article {pmid34119440,
year = {2021},
author = {Gnangnon, B and Duraisingh, MT and Buckee, CO},
title = {Deconstructing the parasite multiplication rate of Plasmodium falciparum.},
journal = {Trends in parasitology},
volume = {37},
number = {10},
pages = {922-932},
doi = {10.1016/j.pt.2021.05.001},
pmid = {34119440},
issn = {1471-5007},
mesh = {Animals ; Erythrocytes/parasitology ; Host-Parasite Interactions ; Humans ; Malaria, Falciparum/parasitology ; *Plasmodium falciparum/growth &amp; development ; *Protozoan Proteins/metabolism ; },
abstract = {Epidemiological indicators describing population-level malaria transmission dynamics are widely used to guide policy recommendations. However, the determinants of malaria outcomes within individuals are still poorly understood. This conceptual gap partly reflects the fact that there are few indicators that robustly predict the trajectory of individual infections or clinical outcomes. The parasite multiplication rate (PMR) is a widely used indicator for the Plasmodium intraerythrocytic development cycle (IDC), for example, but its relationship to clinical outcomes is complex. Here, we review its calculation and use in P. falciparum malaria research, as well as the parasite and host factors that impact it. We also provide examples of metrics that can help to link within-host dynamics to malaria clinical outcomes when used alongside the PMR.},
}
@article {pmid34117742,
year = {2021},
author = {Fortunato, A and Mallo, D and Rupp, SM and King, LM and Hardman, T and Lo, JY and Hall, A and Marks, JR and Hwang, ES and Maley, CC},
title = {A new method to accurately identify single nucleotide variants using small FFPE breast samples.},
journal = {Briefings in bioinformatics},
volume = {22},
number = {6},
pages = {},
pmid = {34117742},
issn = {1477-4054},
support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; },
mesh = {*Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Computational Biology/*methods ; DNA, Neoplasm ; Female ; Genetic Heterogeneity ; Genetic Testing/methods/standards ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; *Polymorphism, Single Nucleotide ; Workflow ; },
abstract = {Most tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however it is difficult to accurately sequence DNA from FFPE samples. We developed and validated a new bioinformatic pipeline to use existing variant-calling strategies to robustly identify somatic single nucleotide variants (SNVs) from whole exome sequencing using small amounts of DNA extracted from archival FFPE samples of breast cancers. We optimized this strategy using 28 pairs of technical replicates. After optimization, the mean similarity between replicates increased 5-fold, reaching 88% (range 0-100%), with a mean of 21.4 SNVs (range 1-68) per sample, representing a markedly superior performance to existing tools. We found that the SNV-identification accuracy declined when there was less than 40 ng of DNA available and that insertion-deletion variant calls are less reliable than single base substitutions. As the first application of the new algorithm, we compared samples of ductal carcinoma in situ of the breast to their adjacent invasive ductal carcinoma samples. We observed an increased number of mutations (paired-samples sign test, P < 0.05), and a higher genetic divergence in the invasive samples (paired-samples sign test, P < 0.01). Our method provides a significant improvement in detecting SNVs in FFPE samples over previous approaches.},
}
@article {pmid34103599,
year = {2021},
author = {Bin Kanner, Y and Ganoth, A and Tsfadia, Y},
title = {Extracellular mutation induces an allosteric effect across the membrane and hampers the activity of MRP1 (ABCC1).},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {12024},
pmid = {34103599},
issn = {2045-2322},
mesh = {Allosteric Regulation ; Amino Acid Substitution ; Humans ; Multidrug Resistance-Associated Proteins/*chemistry/*genetics ; *Mutation, Missense ; Protein Domains ; Protein Structure, Secondary ; },
abstract = {Dynamic conformational changes play a major role in the function of proteins, including the ATP-Binding Cassette (ABC) transporters. Multidrug Resistance Protein 1 (MRP1) is an ABC exporter that protects cells from toxic molecules. Overexpression of MRP1 has been shown to confer Multidrug Resistance (MDR), a phenomenon in which cancer cells are capable to defend themselves against a broad variety of drugs. In this study, we used varied computational techniques to explore the unique F583A mutation that is known to essentially lock the transporter in a low-affinity solute binding state. We demonstrate how macro-scale conformational changes affect MRP1's stability and dynamics, and how these changes correspond to micro-scale structural perturbations in helices 10-11 and the nucleotide-binding domains (NBDs) of the protein in regions known to be crucial for its ATPase activity. We demonstrate how a single substitution of an outward-facing aromatic amino acid causes a long-range allosteric effect that propagates across the membrane, ranging from the extracellular ECL5 loop to the cytoplasmic NBD2 over a distance of nearly 75 Å, leaving the protein in a non-functional state, and provide the putative allosteric pathway. The identified allosteric structural pathway is not only in agreement with experimental data but enhances our mechanical understanding of MRP1, thereby facilitating the rational design of chemosensitizers toward the success of chemotherapy treatments.},
}
@article {pmid34101373,
year = {2021},
author = {Icht, M and Zukerman, G and Ben-Itzchak, E and Ben-David, BM},
title = {Keep it simple: Identification of basic versus complex emotions in spoken language in individuals with autism spectrum disorder without intellectual disability: A meta-analysis study.},
journal = {Autism research : official journal of the International Society for Autism Research},
volume = {14},
number = {9},
pages = {1948-1964},
doi = {10.1002/aur.2551},
pmid = {34101373},
issn = {1939-3806},
mesh = {*Autism Spectrum Disorder/complications ; Emotions ; Humans ; *Intellectual Disability/complications ; Language ; },
abstract = {Daily functioning involves identifying emotions in spoken language, a fundamental aspect of social interactions. To date, there is inconsistent evidence in the literature on whether individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) experience difficulties in identification of spoken emotions. We conducted a meta-analysis (literature search following the PRISMA guidelines), with 26 data sets (taken from 23 peer-reviewed journal articles) comparing individuals with ASD-without-ID (N = 614) and typically-developed (TD) controls (N = 640), from nine countries and in seven languages (published until February 2020). In our analyses there was no sufficient evidence to suggest that individuals with HF-ASD differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, individuals with ASD-without-ID were found to perform significantly worse than controls in identification of complex prosodic emotions (e.g., envy and boredom). The level of the semantic content of the stimuli presented (e.g., sentences vs. strings of digits) was not found to have an impact on the results. In conclusion, the difference in findings between simple and complex emotions calls for a new-look on emotion processing in ASD-without-ID. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions and target improved performance with complex emotions. LAY SUMMARY: Individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) do not differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, they were found to perform significantly worse than controls in the identification of complex prosodic emotions (e.g., envy, boredom). This was found in a meta-analysis of 26 data sets with 1254 participants from nine countries and in seven languages. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions.},
}
@article {pmid34098822,
year = {2021},
author = {Maitre, T and Ok, V and Calin, R and Lassel, L and Canestri, A and Denis, M and Hamidi, M and Tavolaro, S and Verdet, C and Parrot, A and Cadranel, J and Pialoux, G},
title = {Pyogenic lung abscess in an infectious disease unit: a 20-year retrospective study.},
journal = {Therapeutic advances in respiratory disease},
volume = {15},
number = {},
pages = {17534666211003012},
pmid = {34098822},
issn = {1753-4666},
mesh = {Hospital Units ; Humans ; *Liver Abscess, Pyogenic/epidemiology/therapy ; Retrospective Studies ; Risk Factors ; },
abstract = {BACKGROUND: Pyogenic lung abscesses are rare and poorly described infections. This study aimed to describe their prognostic factors.<br><br>METHODS: We retrospectively included all patients hospitalized between 1 January 1998 and 1 June 2018, with an International Classification of Diseases, version 10 (IDC-10) diagnosis of pyogenic lung abscess, from the Diamm based medical records (Micro6, Nancy, France). Parasitic, fungal, or mycobacterial lung abscesses were excluded.<br><br>RESULTS: A total of 64 patients were included. Abscesses were associated with immunosuppression in 28 patients, including HIV infection and immunosuppressive therapy for eight and 12 patients, respectively. Bacterial identification was obtained for 36 patients. Nine patients (14%) developed lung abscesses after hematogenous dissemination. They differed from bronchogenic abscesses by their younger age (p&#x2009;=&#x2009;0.03), the absence of smoking or emphysema (p&#x2009;=&#x2009;0.05), Staphylococcus aureus (p&#x2009;=&#x2009;0.001) or Streptococcus spp. (p&#x2009;=&#x2009;0.05) isolation, and the smaller size of their abscess (p&#x2009;=&#x2009;0.02). Overall, evolution was marked by radiological sequelae (46.9%), relapse (12.5%), and death (4.8%). Radiological sequelae occurred more frequently during the course of bronchogenic abscesses (p&#x2009;=&#x2009;0.02), particularly when they spontaneously discharged (p&#x2009;=&#x2009;0.04). Relapses were more frequent in patients with emphysema (p&#x2009;=&#x2009;0.04) and when Haemophilus influenzae was isolated (p&#x2009;=&#x2009;0.04). In multivariate analysis, poor outcomes, including death, sequelae, and relapse occurred more frequently in patients who had bronchogenic abscess (p&#x2009;=&#x2009;0.02), and in those who received antibiotics during less than 6&#x2009;weeks (p&#x2009;=&#x2009;0.05).<br><br>CONCLUSION: A duration of antibiotic treatment of less than 6&#x2009;weeks and bronchogenic presentation were globally associated with poor outcome of pyogenic lung abscesses. These data should be considered when proposing guidelines for the care of pyogenic lung abscesses.The reviews of this paper are available via the supplemental material section.},
}
@article {pmid34096509,
year = {2021},
author = {Badak, B and Aykanat, NEB and Kacar, S and Sahinturk, V and Arik, D and Canaz, F},
title = {Effects of astaxanthin on metastasis suppressors in ductal carcinoma. A preliminary study.},
journal = {Annali italiani di chirurgia},
volume = {92},
number = {},
pages = {565-574},
pmid = {34096509},
issn = {2239-253X},
mesh = {*Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; Neoplasm Metastasis ; Xanthophylls/pharmacology ; },
abstract = {BACKGROUND: Breast cancer (BC) is a major public health problem diagnosed in more than 2 million women worldwide in 2018, causing more than 600,000 deaths. 90% of deaths due to breast cancer are caused by metastasis. Metastasis is a complex process that is divided into several steps, including separation of tumor cells from the primary tumor, invasion, cell migration, intravasation, vasculature survival, extravasation, and colonization of the secondary site. Astaxanthin (AXT) is a marine-based ketocarotenoid that has many different potential functions such as anti-oxidant, anti-inflammatory and oxidative stress-reducing properties to potentially reduce the incidence of cancer or inhibit the expansion of tumor cells. This study aims to investigate the effects of astaxanthin as a new metastasis inhibitor on T47D human invasive ductal carcinoma breast cancer cell.<br><br>MATERIAL AND METHODS: To investigate the effects of the astaxanthin as a new metastasis inhibitor on T47D cell, expression levels of anti-maspin, anti-Kai1, anti-BRMS1, and anti-MKK4 were examined by western blot. Also, we evaluated differences of these suppressors expression levels in tissue sections of 10 patients diagnosed with in situ and invasive ductal carcinoma by immunohistochemistry method.<br><br>RESULT: 250 &#x3bc;M astaxanthin increased the activation of all metastasis suppressing proteins. Also, these metastasis suppressors showed higher expression in invasive ductal carcinoma tissues than in situ ductal carcinoma patients.<br><br>CONCLUSION: We think that astaxanthin is a promising therapeutic agent for invasive ductal carcinoma patients. The effects of astaxanthin on metastasis in breast cancer should be investigated further based on these results.<br><br>KEY WORDS: Breast, cancer, metastasis.},
}
@article {pmid34083791,
year = {2021},
author = {Zhao, E and Stone, MR and Ren, X and Guenthoer, J and Smythe, KS and Pulliam, T and Williams, SR and Uytingco, CR and Taylor, SEB and Nghiem, P and Bielas, JH and Gottardo, R},
title = {Spatial transcriptomics at subspot resolution with BayesSpace.},
journal = {Nature biotechnology},
volume = {39},
number = {11},
pages = {1375-1384},
pmid = {34083791},
issn = {1546-1696},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; P01 CA225517/CA/NCI NIH HHS/United States ; F30 CA254168/CA/NCI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; },
mesh = {Bayes Theorem ; Cluster Analysis ; Gene Expression Profiling/methods ; Sequence Analysis, RNA/methods ; *Single-Cell Analysis/methods ; *Transcriptome/genetics ; },
abstract = {Recent spatial gene expression technologies enable comprehensive measurement of transcriptomic profiles while retaining spatial context. However, existing analysis methods do not address the limited resolution of the technology or use the spatial information efficiently. Here, we introduce BayesSpace, a fully Bayesian statistical method that uses the information from spatial neighborhoods for resolution enhancement of spatial transcriptomic data and for clustering analysis. We benchmark BayesSpace against current methods for spatial and non-spatial clustering and show that it improves identification of distinct intra-tissue transcriptional profiles from samples of the brain, melanoma, invasive ductal carcinoma and ovarian adenocarcinoma. Using immunohistochemistry and an in silico dataset constructed from scRNA-seq data, we show that BayesSpace resolves tissue structure that is not detectable at the original resolution and identifies transcriptional heterogeneity inaccessible to histological analysis. Our results illustrate BayesSpace's utility in facilitating the discovery of biological insights from spatial transcriptomic datasets.},
}
@article {pmid34062284,
year = {2021},
author = {Salles, DC and Vidotto, T and Faisal, FA and Tosoian, JJ and Guedes, LB and Muranyi, A and Bai, I and Singh, S and Yan, D and Shanmugam, K and Lotan, TL},
title = {Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies.},
journal = {The Journal of molecular diagnostics : JMD},
volume = {23},
number = {8},
pages = {1030-1041},
pmid = {34062284},
issn = {1943-7811},
support = {P30 CA006973/CA/NCI NIH HHS/United States ; P50 CA058236/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; *Biomarkers, Tumor ; Humans ; Immunohistochemistry/methods ; Kaplan-Meier Estimate ; Male ; Middle Aged ; *Molecular Diagnostic Techniques/methods/standards ; Neoplasm Grading ; Neoplasm Staging ; PTEN Phosphohydrolase/genetics/*metabolism ; Prognosis ; Prostate/metabolism/*pathology ; Prostatic Neoplasms/*diagnosis/genetics/*metabolism/mortality ; Protein Binding ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; Reproducibility of Results ; },
abstract = {This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non-organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74-24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.},
}
@article {pmid34058243,
year = {2021},
author = {Hesterberg, AB and Gordetsky, JB and Hurley, PJ},
title = {Cribriform Prostate Cancer: Clinical Pathologic and Molecular Considerations.},
journal = {Urology},
volume = {155},
number = {},
pages = {47-54},
pmid = {34058243},
issn = {1527-9995},
support = {R01 CA211695/CA/NCI NIH HHS/United States ; R01 CA218526/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; Molecular Diagnostic Techniques ; Neoplasm Grading ; Prostatic Neoplasms/*diagnosis/*genetics/pathology ; },
abstract = {Intraductal cribriform (IDC) and invasive cribriform morphologies are associated with worse prostate cancer outcomes. Limited retrospective studies have associated IDC and cribriform morphology with germline mutations in DNA repair genes, particularly BRCA2. These findings, which prompted the National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer and Genetic/Familial High- Risk Assessment to consider germline testing for individuals with IDC/cribriform histology, have been questioned in a recent prospective study. A deepened understanding of the molecular mechanisms driving disease aggressiveness in cribriform morphology is critical to provide more clarity in clinical decision making. This review summarizes the current understanding of IDC and cribriform prostate cancer, with an emphasis on clinical outcomes and molecular alterations.},
}
@article {pmid34048471,
year = {2021},
author = {Brock, EJ and Jackson, RM and Boerner, JL and Li, Q and Tennis, MA and Sloane, BF and Mattingly, RR},
title = {Sprouty4 negatively regulates ERK/MAPK signaling and the transition from in situ to invasive breast ductal carcinoma.},
journal = {PloS one},
volume = {16},
number = {5},
pages = {e0252314},
pmid = {34048471},
issn = {1932-6203},
support = {F31 CA213807/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R25 GM058905/GM/NIGMS NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism ; Cell Line, Tumor ; Cells, Cultured ; Female ; Humans ; Immunoblotting ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mitogen-Activated Protein Kinase 1/genetics/*metabolism ; Mitogen-Activated Protein Kinase 3/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; },
abstract = {Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Patients often receive surgery and radiotherapy, but this early intervention has not produced substantial decreases in late-stage disease. Sprouty proteins are important regulators of ERK/MAPK signaling and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry, we found reduced Sprouty4 expression in IDC patient samples compared to DCIS, and that ERK/MAPK phosphorylation had an inverse relationship to Sprouty4 expression. These observations were reproduced using a 3D culture model of disease progression. Knockdown of Sprouty4 in MCF10.DCIS cells increased ERK/MAPK phosphorylation as well as their invasive capability, while overexpression of Sprouty4 in MCF10.CA1d IDC cells reduced ERK/MAPK phosphorylation, invasion, and the aggressive phenotype exhibited by these cells. Immunofluorescence experiments revealed reorganization of the actin cytoskeleton and relocation of E-cadherin back to the cell surface, consistent with the restoration of adherens junctions. To determine whether these effects were due to changes in ERK/MAPK signaling, MEK1/2 was pharmacologically inhibited in IDC cells. Nanomolar concentrations of MEK162/binimetinib restored an epithelial-like phenotype and reduced pericellular proteolysis, similar to Sprouty4 overexpression. From these data we conclude that Sprouty4 acts to control ERK/MAPK signaling in DCIS, thus limiting the progression of these premalignant breast lesions.},
}
@article {pmid34044580,
year = {2021},
author = {Markus, HS and Egle, M and Croall, ID and Sari, H and Khan, U and Hassan, A and Harkness, K and MacKinnon, A and O'Brien, JT and Morris, RG and Barrick, TR and Blamire, AM and Tozer, DJ and Ford, GA and , },
title = {PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease.},
journal = {Stroke},
volume = {52},
number = {8},
pages = {2484-2493},
doi = {10.1161/STROKEAHA.120.032054},
pmid = {34044580},
issn = {1524-4628},
mesh = {Aged ; Antihypertensive Agents/*therapeutic use ; Blood Pressure ; Cerebral Small Vessel Diseases/complications/*diagnostic imaging/physiopathology ; *Cognition ; Diffusion Tensor Imaging ; Disease Progression ; Female ; Humans ; Hypertension/complications/*drug therapy/physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; *Patient Care Planning ; Stroke, Lacunar/complications/*diagnostic imaging/physiopathology ; White Matter/*diagnostic imaging ; },
abstract = {[Figure: see text].},
}
@article {pmid34031394,
year = {2021},
author = {Amit, I and Iancu, O and Levy-Jurgenson, A and Kurgan, G and McNeill, MS and Rettig, GR and Allen, D and Breier, D and Ben Haim, N and Wang, Y and Anavy, L and Hendel, A and Yakhini, Z},
title = {CRISPECTOR provides accurate estimation of genome editing translocation and off-target activity from comparative NGS data.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {3042},
pmid = {34031394},
issn = {2041-1723},
mesh = {Algorithms ; *CRISPR-Cas Systems ; Computational Biology/*methods ; DNA-Binding Proteins/genetics ; Gene Editing/*methods ; HEK293 Cells ; Homeodomain Proteins/genetics ; Humans ; Nuclear Proteins/genetics ; Software ; Transcription Factors/genetics ; },
abstract = {Controlling off-target editing activity is one of the central challenges in making CRISPR technology accurate and applicable in medical practice. Current algorithms for analyzing off-target activity do not provide statistical quantification, are not sufficiently sensitive in separating signal from noise in experiments with low editing rates, and do not address the detection of translocations. Here we present CRISPECTOR, a software tool that supports the detection and quantification of on- and off-target genome-editing activity from NGS data using paired treatment/control CRISPR experiments. In particular, CRISPECTOR facilitates the statistical analysis of NGS data from multiplex-PCR comparative experiments to detect and quantify adverse translocation events. We validate the observed results and show independent evidence of the occurrence of translocations in human cell lines, after genome editing. Our methodology is based on a statistical model comparison approach leading to better false-negative rates in sites with weak yet significant off-target activity.},
}
@article {pmid34022480,
year = {2021},
author = {Hoshina, H and Takei, H and Nakamura, M and Nishimoto, F and Hanamura, S},
title = {Carcinomatous cirrhosis as radiographically occult liver metastases of breast cancer: A systematic literature review.},
journal = {Cancer treatment and research communications},
volume = {28},
number = {},
pages = {100388},
doi = {10.1016/j.ctarc.2021.100388},
pmid = {34022480},
issn = {2468-2942},
mesh = {Ascites/*diagnosis/etiology ; Breast Neoplasms/*pathology ; Female ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Liver Neoplasms/complications/*diagnosis/secondary ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; },
abstract = {In the present study, we aimed to clarify features of carcinomatous cirrhosis from breast cancer presenting as refractory transudate ascites and acute liver failure. In our systematic literature review, we identified 26 studies and 31 cases including our case of this rare condition. Our patient was a 49-year-old woman with a history of ascites and liver failure for the past 4 years and currently being treated for invasive ductal breast cancer. On radiography, she had occult liver metastases that were confirmed using laparoscopic liver biopsy. In the 31 cases, data on the reported year, age, type of primary breast cancer, time from breast cancer diagnosis, presence of ascites and/or varices, liver biopsy, diagnostic modalities, outcomes, and survival were documented and analyzed. All cases were reported during 1984-2020, with a mean patient age of 52.9 years. Eighteen patients (58.1%) were diagnosed with ductal breast cancer. Twenty-two patients (70.9%) had ascites. All patients had gradual progression to liver dysfunction. The following tests were performed: computed tomography (77.4%); ultrasound (58.0%); liver biopsy (100%); postmortem biopsy (35.5%), transjugular liver biopsy (32.3%), and laparoscopic liver biopsy (3.2%). Outcomes were reported for 29 patients, of whom 24 (82.3%) died after 1 day to 16 months. Invasive ductal carcinoma was the most common histological type; however, invasive lobular carcinoma was more frequent (32.3%) than its reported incidence in the breast. Carcinomatous cirrhosis has poor prognosis at relatively rash and is difficult to diagnose with usual modalities. It may be associated with E-cadherin loss or CD44 pronouncement.},
}
@article {pmid34016966,
year = {2021},
author = {Georgiadi, A and Lopez-Salazar, V and Merahbi, RE and Karikari, RA and Ma, X and Mourão, A and Klepac, K and Bühler, L and Alfaro, AJ and Kaczmarek, I and Linford, A and Bosma, M and Shilkova, O and Ritvos, O and Nakamura, N and Hirose, S and Lassi, M and Teperino, R and Machado, J and Scheideler, M and Dietrich, A and Geerlof, A and Feuchtinger, A and Blutke, A and Fischer, K and Müller, TD and Kessler, K and Schöneberg, T and Thor, D and Hornemann, S and Kruse, M and Nawroth, P and Pivovarova-Ramich, O and Pfeiffer, AFH and Sattler, M and Blüher, M and Herzig, S},
title = {Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {2999},
pmid = {34016966},
issn = {2041-1723},
mesh = {3T3-L1 Cells ; Adipocytes/metabolism ; Adipose Tissue, White/cytology/*metabolism ; Adolescent ; Adult ; Aged ; Animals ; CHO Cells ; Cohort Studies ; Cricetulus ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood/metabolism/prevention &amp; control ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Female ; Gene Knockdown Techniques ; Glucose/metabolism ; HEK293 Cells ; Hep G2 Cells ; Humans ; Insulin/metabolism ; Insulin Resistance ; Islets of Langerhans/metabolism ; Liver/metabolism ; Male ; Membrane Proteins/administration &amp; dosage/blood/genetics/*metabolism ; Mice ; Mice, Knockout ; Middle Aged ; NIH 3T3 Cells ; Prediabetic State/blood/drug therapy/etiology/*metabolism ; Primary Cell Culture ; Proteins/analysis/*metabolism ; Receptors, G-Protein-Coupled/blood/genetics/*metabolism ; Recombinant Fusion Proteins/administration &amp; dosage/genetics/isolation &amp; purification ; Young Adult ; },
abstract = {The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.},
}
@article {pmid34016957,
year = {2021},
author = {Egea, V and Kessenbrock, K and Lawson, D and Bartelt, A and Weber, C and Ries, C},
title = {Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release.},
journal = {Cell death &amp; disease},
volume = {12},
number = {6},
pages = {516},
pmid = {34016957},
issn = {2041-4889},
mesh = {Animals ; Cell Communication/physiology ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; Chemokine CXCL12/*metabolism ; Disease Models, Animal ; Female ; Humans ; Mammary Neoplasms, Experimental/genetics/*metabolism/pathology ; Mesenchymal Stem Cells/*metabolism/pathology ; Mice ; Mice, Inbred BALB C ; MicroRNAs/biosynthesis/*genetics ; Transfection ; Tumor Hypoxia/*physiology ; },
abstract = {Bone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.},
}
@article {pmid34015750,
year = {2021},
author = {de Araújo, RA and Cordero da Luz, FA and da Costa Marinho, E and Mendes, TR and Nascimento, CP and Ribeiro Delfino, PF and Antonioli, RM and Ruas, AC and Alves, AR and Araújo, BJ and de Paula Machado, JP and Guedes Pereira, TO and França do Espírito Santo, M and Barbosa Silva, MJ},
title = {Operable breast cancer: How not to worsen the prognosis, especially in triple negative and stage II tumors.},
journal = {Surgical oncology},
volume = {38},
number = {},
pages = {101596},
doi = {10.1016/j.suronc.2021.101596},
pmid = {34015750},
issn = {1879-3320},
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; *Margins of Excision ; Mastectomy/*mortality ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*surgery ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/pathology/*surgery ; },
abstract = {INTRODUCTION: Oncological surgery must follow some fundamental principles to be truly curative, one of which is the resection of the tumor with surgical margins free of neoplasia. In breast cancer, surgery with positive margins should be expanded immediately. There are probably different intensities, between the stages and molecular subtypes of operable breast cancer, of worsening prognosis due to the surgical margin compromised by the neoplasia in women not submitted to the necessary enlargement of the positive surgical margin. MATERIALS AND.<br><br>METHODS: Seven hundred and forty-seven women with invasive ductal carcinoma of the breast, analyzing anatomical-pathological information, types of surgery, molecular subtypes, and the presence or absence of the surgical margin compromised by neoplasia.<br><br>RESULTS: Sixty-one (8.2%) patients had positive surgical margin, causing 2.85 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis. In subgroup analysis, among stages I, II and III, stage II was the most negatively impacted, with those patients presenting 2.42 times more risk of distant metastasis and 4.94 times more risk of locoregional relapses compared to negative surgical margin by multivariate analysis. Among the molecular subtypes, Triple Negative tumors with a positive surgical margin had 3.56 times more risk of death, 4.98 times more risk of distant metastasis and 5.55 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis.<br><br>CONCLUSIONS: The positive surgical margin, especially in Stage II and Triple-Negative breast cancer patients negatively impact the patient's evolution, increasing risk of distant metastasis and death.},
}
@article {pmid34014371,
year = {2021},
author = {Giroud, M and Tsokanos, FF and Caratti, G and Kotschi, S and Khani, S and Jouffe, C and Vogl, ES and Irmler, M and Glantschnig, C and Gil-Lozano, M and Hass, D and Khan, AA and Garcia, MR and Mattijssen, F and Maida, A and Tews, D and Fischer-Posovszky, P and Feuchtinger, A and Virtanen, KA and Beckers, J and Wabitsch, M and Uhlenhaut, H and Blüher, M and Tuckermann, J and Scheideler, M and Bartelt, A and Herzig, S},
title = {HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling.},
journal = {Diabetologia},
volume = {64},
number = {8},
pages = {1850-1865},
pmid = {34014371},
issn = {1432-0428},
mesh = {Adipocytes/*metabolism ; Adipogenesis/physiology ; Adipose Tissue, Brown/metabolism ; Adult ; Aged ; Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cross-Sectional Studies ; Female ; Gene Expression Regulation/*physiology ; Gene Silencing ; Glucocorticoids/*pharmacology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Obesity/*genetics ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Transcription Factors/*genetics ; Young Adult ; },
abstract = {AIMS/HYPOTHESIS: Adipocytes are critical cornerstones of energy metabolism. While obesity-induced adipocyte dysfunction is associated with insulin resistance and systemic metabolic disturbances, adipogenesis, the formation of new adipocytes and healthy adipose tissue expansion are associated with metabolic benefits. Understanding the molecular mechanisms governing adipogenesis is of great clinical potential to efficiently restore metabolic health in obesity. Here we investigate the role of heart and neural crest derivatives-expressed 2 (HAND2) in adipogenesis.<br><br>METHODS: Human white adipose tissue (WAT) was collected from two cross-sectional studies of 318 and 96 individuals. In vitro, for mechanistic experiments we used primary adipocytes from humans and mice as well as human multipotent adipose-derived stem (hMADS) cells. Gene silencing was performed using siRNA or genetic inactivation in primary adipocytes from loxP and or tamoxifen-inducible Cre-ERT2 mouse models with Cre-encoding mRNA or tamoxifen, respectively. Adipogenesis and adipocyte metabolism were measured by Oil Red O staining, quantitative PCR (qPCR), microarray, glucose uptake assay, western blot and lipolysis assay. A combinatorial RNA sequencing (RNAseq) and ChIP qPCR approach was used to identify target genes regulated by HAND2. In vivo, we created a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter (Hand2[AdipoqCre]) and performed a large panel of metabolic tests.<br><br>RESULTS: We found that HAND2 is an obesity-linked white adipocyte transcription factor regulated by glucocorticoids that was necessary but insufficient for adipocyte differentiation in vitro. In a large cohort of humans, WAT HAND2 expression was correlated to BMI. The HAND2 gene was enriched in white adipocytes compared with brown, induced early in differentiation and responded to dexamethasone (DEX), a typical glucocorticoid receptor (GR, encoded by NR3C1) agonist. Silencing of NR3C1 in hMADS cells or deletion of GR in a transgenic conditional mouse model results in diminished HAND2 expression, establishing that adipocyte HAND2 is regulated by glucocorticoids via GR in vitro and in vivo. Furthermore, we identified gene clusters indirectly regulated by the GR-HAND2 pathway. Interestingly, silencing of HAND2 impaired adipocyte differentiation in hMADS and primary mouse adipocytes. However, a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter did not mirror these effects on adipose tissue differentiation, indicating that HAND2 was required at stages prior to Adipoq expression.<br><br>CONCLUSIONS/INTERPRETATION: In summary, our study identifies HAND2 as a novel obesity-linked adipocyte transcription factor, highlighting new mechanisms of GR-dependent adipogenesis in humans and mice.<br><br>DATA AVAILABILITY: Array data have been submitted to the GEO database at NCBI (GSE148699).},
}
@article {pmid34011405,
year = {2021},
author = {Dinca, SC and Greiner, D and Weidenfeld, K and Bond, L and Barkan, D and Jorcyk, CL},
title = {Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment.},
journal = {Breast cancer research : BCR},
volume = {23},
number = {1},
pages = {56},
pmid = {34011405},
issn = {1465-542X},
support = {R25 GM123927/GM/NIGMS NIH HHS/United States ; 1C06RR020533/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; U54 GM104944/GM/NIGMS NIH HHS/United States ; 0619737//National Science Foundation/ ; 0923535//National Science Foundation/ ; AR298//Smylie Family Cancer Fund (US)/ ; 2017237//United States - Israel Binational Science Foundation/ ; },
mesh = {Amino Acid Oxidoreductases/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Collagen Type I/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Matrix/*metabolism ; Female ; Glycosylation ; Humans ; Inflammation ; Neoplasm Metastasis ; Oncostatin M/genetics/*metabolism/pharmacology ; Oncostatin M Receptor beta Subunit/genetics/metabolism ; Prognosis ; Signal Transduction ; Tumor Microenvironment ; Up-Regulation/genetics ; },
abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is a serious problem for patients as it metastasizes, decreasing 5-year patient survival from > 95 to ~ 27%. The breast tumor microenvironment (TME) is often saturated with proinflammatory cytokines, such as oncostatin M (OSM), which promote epithelial-to-mesenchymal transitions (EMT) in IDC and increased metastasis. The extracellular matrix (ECM) also plays an important role in promoting invasive and metastatic potential of IDC. Specifically, the reorganization and alignment of collagen fibers in stromal ECM leads to directed tumor cell motility, which promotes metastasis. Lysyl oxidase like-2 (LOXL2) catalyzes ECM remodeling by crosslinking of collagen I in the ECM. We propose a novel mechanism whereby OSM induces LOXL2 expression, mediating stromal ECM remodeling of the breast TME.<br><br>METHODS: Bioinformatics was utilized to determine survival and gene correlation in patients. IDC cell lines were treated with OSM (also IL-6, LIF, and IL-1&#x3b2;) and analyzed for LOXL2 expression by qRT-PCR and immunolabelling techniques. Collagen I contraction assays, 3D invasion assays, and confocal microscopy were performed with and without LOXL2 inhibition to determine the impact of OSM-induced LOXL2 on the ECM.<br><br>RESULTS: Our studies demonstrate that IDC patients with high LOXL2 and OSM co-expression had worse rates of metastasis-free survival than those with high levels of either, individually, and LOXL2 expression is positively correlated to OSM/OSM receptor (OSMR) expression in IDC patients. Furthermore, human IDC cells treated with OSM resulted in a significant increase in LOXL2 mRNA, which led to upregulated protein expression of secreted, glycosylated, and enzymatically active LOXL2. The expression of LOXL2 in IDC cells did not affect OSM-promoted EMT, and LOXL2 was localized to the cytoplasm and/or secreted. OSM-induced LOXL2 promoted an increase in ECM collagen I fiber crosslinking, which led to significant fiber alignment between cells and increased IDC cell invasion.<br><br>CONCLUSIONS: Aligned collagen fibers in the ECM provide pathways for tumor cells to migrate more easily through the stroma to nearby vasculature and tissue. These results provide a new paradigm through which proinflammatory cytokine OSM promotes tumor progression. Understanding the nuances in IDC metastasis will lead to better potential therapeutics to combat against the possibility.},
}
@article {pmid34009452,
year = {2021},
author = {Kusafuka, K and Ito, I and Hirata, K and Miyamoto, K and Shimizu, T and Satomi, H and Inagaki, H and Suzuki, M},
title = {A rare case of high-grade intraductal carcinoma of the upper lip: immunohistochemical and genetic analyses.},
journal = {Medical molecular morphology},
volume = {54},
number = {3},
pages = {281-288},
pmid = {34009452},
issn = {1860-1499},
mesh = {Asian People ; Biomarkers, Tumor/analysis ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism/surgery ; ErbB Receptors/analysis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Japan ; Keratin-19/analysis/genetics ; Keratin-5/analysis/genetics ; Keratin-6/analysis/genetics ; Lip/surgery ; Lip Neoplasms/*diagnosis/metabolism/surgery ; Middle Aged ; Receptors, Androgen/analysis/genetics ; SOXE Transcription Factors/analysis/genetics ; },
abstract = {Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.},
}
@article {pmid34002584,
year = {2021},
author = {Lei, S and Zheng, R and Zhang, S and Chen, R and Wang, S and Sun, K and Zeng, H and Wei, W and He, J},
title = {Breast cancer incidence and mortality in women in China: temporal trends and projections to 2030.},
journal = {Cancer biology &amp; medicine},
volume = {18},
number = {3},
pages = {900-909},
pmid = {34002584},
issn = {2095-3941},
support = {2018-I2M-3-003//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 2018YFC1315305//National Key Research and Development Program of China/ ; },
abstract = {OBJECTIVE: Breast cancer was the most common cancer and the fifth cause of cancer deaths among women in China in 2015. The evaluation of the long-term incidence and mortality trends and the prediction of the future burden of breast cancer could provide valuable information for developing prevention and control strategies.<br><br>METHODS: The burden of breast cancer in China in 2015 was estimated by using qualified data from 368 cancer registries from the National Central Cancer Registry. Incident cases and deaths in 22 cancer registries were used to assess the time trends from 2000 to 2015. A Bayesian age-period-cohort model was used to project the burden of breast cancer to 2030.<br><br>RESULTS: Approximately 303,600 new cases of breast cancer (205,100 from urban areas and 98,500 from rural areas) and 70,400 breast cancer deaths (45,100 from urban areas and 24,500 from rural areas) occurred in China in 2015. Urban regions of China had the highest incidence and mortality rates. The most common histological subtype of breast cancer was invasive ductal carcinoma, followed by invasive lobular carcinoma. The age-standardized incidence and mortality rates increased by 3.3% and 1.0% per year during 2000-2015, and were projected to increase by more than 11% until 2030. Changes in risk and demographic factors between 2015 and 2030 in cases are predicted to increase by approximately 13.3% and 22.9%, whereas deaths are predicted to increase by 13.1% and 40.9%, respectively.<br><br>CONCLUSIONS: The incidence and mortality of breast cancer continue to increase in China. There are no signs that this trend will stop by 2030, particularly in rural areas. Effective breast cancer prevention strategies are therefore urgently needed in China.},
}
@article {pmid34001921,
year = {2021},
author = {Hosio, M and Urpilainen, E and Hautakoski, A and Marttila, M and Arffman, M and Sund, R and Ahtikoski, A and Puistola, U and Läärä, E and Karihtala, P and Jukkola, A},
title = {Association of antidiabetic medication and statins with survival from ductal and lobular breast carcinoma in women with type 2 diabetes.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {10445},
pmid = {34001921},
issn = {2045-2322},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/complications/*mortality/therapy ; Carcinoma, Ductal, Breast/complications/*mortality/therapy ; Carcinoma, Lobular/complications/*mortality/therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Female ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Hypoglycemic Agents/*therapeutic use ; Middle Aged ; Prognosis ; Registries/statistics &amp; numerical data ; Survival Analysis ; },
abstract = {We investigated the survival of female patients with pre-existing type 2 diabetes (T2D) diagnosed with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of breast, in relation to the use of metformin, other antidiabetic medication (ADM) and statins. The study cohort consisted of 3,165 women (2,604 with IDC and 561 with ILC). The cumulative mortality from breast cancer (BC) and from other causes was calculated using the Aalen-Johansen estimator. The cause-specific mortality rates were analysed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of different medications. No evidence of an association of metformin use with BC mortality was observed in either IDC (HR 0.92, 95% confidence interval [CI] 0.64-1.31) or ILC (HR 0.68, 95% CI 0.32-1.46) patients, when compared to other oral ADMs. The mortality from other causes was found to be lower amongst the IDC patients using metformin (HR 0.64, 95% CI 0.45-0.89), but amongst ILC patients the evidence was inconclusive (HR 1.22, 95% CI 0.64-2.32). Statin use was consistently associated with reduced mortality from BC in IDC patients (HR 0.77, 95% CI 0.62-0.96) and ILC patients (HR 0.59, 95% CI 0.37-0.96), and also mortality from other causes in IDC patients (HR 0.81, 95% CI 0.67-0.96) and in ILC patients (HR 0.66, 95% CI 0.43-1.01). We found no sufficient evidence for the possible effects of metformin and statins on the prognosis of BC being different in the two histological subtypes.},
}
@article {pmid33983449,
year = {2022},
author = {March, DS and Lai, KB and Neal, T and Graham-Brown, MPM and Highton, PJ and Churchward, DR and Young, HML and Dungey, M and Stensel, DJ and Smith, AC and Bishop, NC and Szeto, CC and Burton, JO},
title = {Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.},
journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association},
volume = {37},
number = {2},
pages = {366-374},
doi = {10.1093/ndt/gfab178},
pmid = {33983449},
issn = {1460-2385},
mesh = {*Endotoxins ; Exercise ; Humans ; Inflammation/etiology ; Physical Fitness ; *Renal Dialysis/adverse effects ; },
abstract = {BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes.<br><br>METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n&#x2009;=&#x2009;46) or usual care only (control group; n&#x2009;=&#x2009;46). Outcome measures were obtained at baseline and then again at 6 months.<br><br>RESULTS: There was no significant (P&#x2009;=&#x2009;0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34&#x2009;&#xb1;&#x2009;0.08 EU/mL; control group: 0.37&#x2009;&#xb1;&#x2009;0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio.<br><br>CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.},
}
@article {pmid33966256,
year = {2021},
author = {Tsokanos, FF and Muley, C and Khani, S and Hass, D and Fleming, T and Wolff, G and Bartelt, A and Nawroth, P and Herzig, S},
title = {Methylglyoxal Drives a Distinct, Nonclassical Macrophage Activation Status.},
journal = {Thrombosis and haemostasis},
volume = {121},
number = {11},
pages = {1464-1475},
doi = {10.1055/s-0041-1726346},
pmid = {33966256},
issn = {2567-689X},
support = {Deutsche Forschungsgemeinschaft//SFB1118/ ; },
mesh = {Animals ; Cells, Cultured ; Gene Expression Profiling ; Glycolysis/*drug effects ; Macrophage Activation/*drug effects ; Macrophages/*drug effects/immunology/metabolism ; Mice ; Phenotype ; Phosphorylation ; Pyruvaldehyde/*toxicity ; Signal Transduction ; Transcriptome ; p38 Mitogen-Activated Protein Kinases/metabolism ; },
abstract = {Metabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated. However, a direct link between reactive metabolites and macrophage activation has not been demonstrated yet. Here, we show that acute MG treatment activated components of the p38 MAPK pathway and enhanced glycolysis in primary murine macrophages. MG induced a distinct gene expression profile sharing similarities with classically activated proinflammatory macrophages as well as metabolically activated macrophages usually found in obese patients. Transcriptomic analysis revealed a set of 15 surface markers specifically upregulated in MG-treated macrophages, thereby establishing a new set of targets for diagnostic or therapeutic purposes under high MG conditions, including diabetes. Overall, our study defines a new polarization state of macrophages that may specifically link aberrant macrophage activation to reactive metabolites in diabetes.},
}
@article {pmid33960872,
year = {2021},
author = {Alvarez, DR and Ospina, A and Barwell, T and Zheng, B and Dey, A and Li, C and Basu, S and Shi, X and Kadri, S and Chakrabarti, K},
title = {The RNA structurome in the asexual blood stages of malaria pathogen plasmodium falciparum.},
journal = {RNA biology},
volume = {18},
number = {12},
pages = {2480-2497},
pmid = {33960872},
issn = {1555-8584},
mesh = {Erythrocytes/*metabolism ; *Gene Expression Regulation ; Humans ; *Life Cycle Stages ; Malaria, Falciparum/*parasitology ; *Nucleic Acid Conformation ; Plasmodium falciparum/*genetics/growth &amp; development/pathogenicity ; Protozoan Proteins/genetics/metabolism ; RNA, Protozoan/*chemistry ; Transcriptome ; },
abstract = {Plasmodium falciparum is a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and non-coding transcripts from the asexual developmental cycle in P. falciparum in human red blood cells. Our comprehensive analysis that combined high-throughput nuclease mapping of RNA structures by duplex RNA-seq, SHAPE-directed RNA structure validation, immunoaffinity purification and characterization of antisense RNAs collectively measured differentially base-paired RNA regions throughout the parasite's asexual RBC cycle. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, approximately 71% of the genes with secondary structures are found to be protein coding mRNAs. The mapping pattern of these base-paired RNAs corresponded to all regions of mRNAs, including the 5' UTR, CDS and 3' UTR as well as the start and stop codons. Histone family genes which are known to form secondary structures in their mRNAs and transcripts from genes which are important for transcriptional and post-transcriptional control, such as the unique plant-like transcription factor family, ApiAP2, DNA-/RNA-binding protein, Alba3 and proteins important for RBC invasion and malaria cytoadherence also showed strong accumulation of duplex RNA reads in various asexual stages in P. falciparum. Intriguingly, our study determined stage-specific, dynamic relationships between mRNA structural contents and translation efficiency in P. falciparum asexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs. Abbreviations: CDS: Coding Sequence; DNA: Deoxyribonucleic Acid; dsRNA: double-stranded RNA; IDC: Intra-erythrocytic Developmental Cycle (IDC); m6A: N6-methyladenosine; mRNA: Messenger RNA; ncRNA: Non-coding RNA; RBC: Red Blood cells; RBP: RNA-Binding Protein; REC: Relative Expression Counts; RNA-seq: RNA-sequencing; RNA: Ribonucleic Acid; RNP: Ribonucleoprotein; RPKM: Reads Per Kilobase of transcript Per Million; rRNA: Ribosomal RNA 16. RUFs: RNAs of Unknown Function; SHAPE: Selective 2'-hydroxyl acylation analysed by primer extension; snoRNA: Small Nucleolar RNA; snRNA: Small Nuclear RNA; SRP-RNA: Signal Recognition Particle RNA; ssRNA: (Single-stranded RNA); TE: Translation Efficiency; tRNA: transfer RNA; UTR: Untranslated Region.},
}
@article {pmid33947745,
year = {2021},
author = {Sottnik, JL and Bordeaux, EK and Mehrotra, S and Ferrara, SE and Goodspeed, AE and Costello, JC and Sikora, MJ},
title = {Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Coregulator in Invasive Lobular Carcinoma of the Breast.},
journal = {Molecular cancer research : MCR},
volume = {19},
number = {8},
pages = {1270-1282},
pmid = {33947745},
issn = {1557-3125},
support = {P30 CA046934/CA/NCI NIH HHS/United States ; R00 CA193734/CA/NCI NIH HHS/United States ; T32 GM007635/GM/NIGMS NIH HHS/United States ; },
mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Breast/pathology ; Breast Neoplasms/drug therapy/*genetics/pathology ; Carcinoma, Lobular/drug therapy/*genetics/pathology ; Cell Cycle Proteins/*genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Female ; Humans ; MCF-7 Cells ; Promoter Regions, Genetic/drug effects/genetics ; Receptors, Estrogen/*genetics ; Signal Transduction/genetics ; Tamoxifen/therapeutic use ; Transcriptome/drug effects/genetics ; },
abstract = {Invasive lobular carcinoma (ILC) is the most common special histologic subtype of breast cancer, and nearly all ILC tumors express estrogen receptor alpha (ER). However, clinical and laboratory data suggest ILC are strongly estrogen-driven but not equally antiestrogen-sensitive. We hypothesized ILC-specific ER coregulators mediate ER functions and antiestrogen resistance in ILC, and profiled ER-associated proteins by mass spectrometry. Three ER[+] ILC cell lines (MDA MB 134VI, SUM44PE, and BCK4) were compared with ER[+] invasive ductal carcinoma (IDC) line data, and we examined whether siRNA of identified proteins suppressed ER-driven proliferation in ILC cells. This identified mediator of DNA damage checkpoint 1 (MDC1), a tumor suppressor in DNA damage response (DDR), as a novel ER coregulator in ILC. We confirmed ER:MDC1 interaction was specific to ILC versus IDC cells, and found MDC1 knockdown suppressed ILC cell proliferation and tamoxifen resistance. Using RNA-sequencing, we found in ILC cells MDC1 knockdown broadly dysregulates the ER transcriptome, with ER:MDC1 target genes enriched for promoter hormone response elements. Importantly, our data are inconsistent with MDC1 tumor suppressor functions in DDR, but suggest a novel oncogenic role for MDC1 as an ER coregulator. Supporting this, in breast tumor tissue microarrays, MDC1 protein was frequently low or absent in IDC, but MDC1 loss was rare in ER[+] ILC. ER:MDC1 interaction and MDC1 coregulator functions may underlie ER function in ILC and serve as targets to overcome antiestrogen resistance in ILC. IMPLICATIONS: MDC1 has novel ER coregulator activity in ILC, which may underlie ILC-specific ER functions, estrogen response, and antiestrogen resistance.},
}
@article {pmid33945869,
year = {2021},
author = {Sethy, C and Goutam, K and Das, B and Dash, SR and Kundu, CN},
title = {Nectin-4 promotes lymphangiogenesis and lymphatic metastasis in breast cancer by regulating CXCR4-LYVE-1 axis.},
journal = {Vascular pharmacology},
volume = {140},
number = {},
pages = {106865},
doi = {10.1016/j.vph.2021.106865},
pmid = {33945869},
issn = {1879-3649},
mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; *Cell Adhesion Molecules/metabolism ; Female ; Humans ; Lymphangiogenesis/physiology ; Lymphatic Metastasis/pathology ; *Lymphatic Vessels/metabolism ; *Nectins/metabolism ; *Receptors, CXCR4/metabolism ; *Vesicular Transport Proteins/metabolism ; },
abstract = {Tumor-induced lymphangiogenesis promotes tumor progression by generating new lymphatic vessels that helps in tumor dissemination to regional lymph nodes and distant sites. Recently, the role of Nectin-4 in cancer metastasis and angiogenesis has been studied, but its role in lymphangiogenesis is unknown. Here, we systematically delineated the role of Nectin-4 in lymphangiogenesis and its regulation in invasive duct carcinoma (IDC). Nectin-4 expression positively correlated with occurrence risk factors associated with breast cancer (alcohol, smoke, lifestyle habit, etc), CXCR4 expression, and LYVE-1-lymphatic vessel density (LVD). LVD was significantly higher in axillary lymph node (ALN) than primary tumor. Depleting Nectin-4, VEGF-C or both attenuated the important lymphangiogenic marker LYVE-1 expression, tube formation, and migration of ALN derived primary cells. Nectin-4 stimulated the expressions of CXCR4 and CXCL12 under hypoxic conditions in ALN derived primary cells. Further, Nectin-4 augmented expressions of lymphatic metastatic markers (e.g. eNOS, TGF-β, CD-105) and MMPs. Induced expressions of Nectin-4 along with other representative metastatic markers were noted in lymph and blood circulating tumor cells (LCTCs and BCTCs) of local and distant metastatic samples. Thus, Nectin-4 displayed a predominant role in promoting tumor-induced lymphangiogenesis and lymphatic metastasis by modulating CXCR4/CXCL12-LYVE-1- axis.},
}
@article {pmid33930678,
year = {2021},
author = {Solomon, Z and Ginzburg, K and Ohry, A and Mikulincer, M},
title = {Overwhelmed by the news: A longitudinal study of prior trauma, posttraumatic stress disorder trajectories, and news watching during the COVID-19 pandemic.},
journal = {Social science &amp; medicine (1982)},
volume = {278},
number = {},
pages = {113956},
pmid = {33930678},
issn = {1873-5347},
mesh = {*COVID-19 ; Humans ; Israel/epidemiology ; Longitudinal Studies ; Pandemics ; *Prisoners of War ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic/epidemiology/etiology ; *Veterans ; },
abstract = {RATIONALE: It has been recognized that exposure to mass trauma tends to increase the time spent watching television (TV) news. Yet, research on the effects of this tendency on individuals' well-being yielded inconclusive findings.<br><br>OBJECTIVE: The aim of this longitudinal study is to examine the effects of prior trauma and posttraumatic stress disorder (PTSD) on changes in the amount of TV news watching and its effect on subsequent PTSD. More specifically, we examined the interrelations of prior exposure to war captivity, long-term PTSD trajectories, and amount of change TV news watching with PTSD severity during the COVID-19 pandemic, among aging Israeli combat veterans.<br><br>METHODS: One-hundred-and-twenty Israeli ex-prisoners of war (ex-POWs) from 1973 Yom Kippur War and 65 matched controls (combat veterans from the same war) were followed up at five points of time: 1991 (T1), 2003 (T2), 2008 (T3), 2015 (T4), and in April-May 2020 (T5), during the outbreak of the COVID-19 pandemic.<br><br>RESULTS: Ex-POWs had higher odds of COVID-19 related increase in TV news watching, which, in turn, contributed to PTSD severity at T5. In addition, delayed PTSD trajectory was associated with COVID-19 related increase in TV news watching, which, in turn, contributed to more severe PTSD at T5.<br><br>CONCLUSIONS: These findings highlight the negative implications of TV news watching during a mass trauma for traumatized individuals. More specifically, they demonstrate its potential pathogenic role in exacerbating prior PTSD among trauma survivors.},
}
@article {pmid33927073,
year = {2021},
author = {Huang, X and Cai, S and Wu, P and Huang, S and Yao, M},
title = {Clinical and X-ray characteristics for expressions of different receptors in patients with breast cancer.},
journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences},
volume = {46},
number = {3},
pages = {263-271},
pmid = {33927073},
issn = {1672-7347},
mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnostic imaging/genetics ; Female ; Humans ; Receptor, ErbB-2/genetics ; Receptors, Estrogen ; Receptors, Progesterone ; X-Rays ; },
abstract = {OBJECTIVES: Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer.<br><br>METHODS: A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed.<br><br>RESULTS: Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all P<0.001). The age in the human epidermal growth factor 2 (HER2) overexpression type group was older, the proportions of menopause, the calcification score, and the calcification score with 9-12 were higher, the sizes of the tumor were greater in the HER2 overexpression type group than those in the other 3 molecular subtype groups (age P<0.05, the rest P<0.01). The proportions of regular shape, edge indistinct, and high-grade invasive ductal carcinoma in the triple-negative type group were higher than those in the other 3 molecular subtype groups (all P<0.001). The proportions of non-menopausal patients and spiculate tumors in the estrogen receptor (ER) positive and/or progesterone receptor (PR) positive groups were higher than those in both ER and PR negative group (P<0.001 and P=0.001, respectively). The proportions of calcification fraction and high-grade invasive ductal carcinoma were higher, tumor sizes were greater in the HER2 positive group, Ki-67&#x2265;20% group than those in the HER2 negative group, Ki-67<20% group, respectively (P<0.001 or P<0.05, respectively).<br><br>CONCLUSIONS: Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.},
}
@article {pmid33921735,
year = {2021},
author = {Oprean, CM and Badau, LM and Segarceanu, NA and Ciocoiu, AD and Rivis, IA and Vornicu, VN and Hoinoiu, T and Grujic, D and Bredicean, C and Dema, A},
title = {Unilateral Orbital Metastasis as the Unique Symptom in the Onset of Breast Cancer in a Postmenopausal Woman: Case Report and Review of the Literature.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {11},
number = {4},
pages = {},
pmid = {33921735},
issn = {2075-4418},
abstract = {The orbit represents an unusual metastases site for patients diagnosed with cancer, however, breast cancer is the main cause of metastases at this level. These orbital metastases were discovered in patients with a history of breast cancer as unique or synchronous lesions. We present a rare case of a unique retroocular metastasis as the first initial symptom of a tubulo-lobular mammary carcinoma in a postmenopausal woman. A 57-year-old patient complains of diplopia, diminishing visual acuity, orbital tenderness, slight exophthalmia and ptosis of the left eyelid, with insidious onset. Clinical examination and subsequent investigations revealed a left breast cancer cT2 cN1 pM1 stage IV. Breast conserving surgery was performed on the left breast. Pathological examination with immunohistochemistry staining established the complete diagnostic: pT2pN3aM1 Stage IV breast cancer, luminal B subtype. After two years from the initial breast cancer diagnosis, the patient was diagnosed by the psychiatrist with a depressive disorder and was treated accordingly. Orbital metastases are usually discovered in known breast cancer patients and they are found in the context of a multi-system end-stage disease. Most reports cite that up to 25% of the total orbital metastases cases are discovered before the diagnosis of the primary tumor, as our case did. MRI is the gold standard for evaluating orbital tumors. The ILC histological subtype metastasizes in the orbitals more frequently than invasive ductal carcinoma. The prognosis of patients with orbital metastases is poor. The median survival after diagnosis of orbital metastases from a breast cancer primary is ranging from 22 to 31 months. Overall survival of our patient was 56 months, longer than the median survival reported in literature. Orbital metastases must be taken into account when patients accuse ophthalmologic symptoms even in the absence of a personal history of cancer. Objective examination of every patient that incriminates these types of symptoms is essential, and breast palpation must be made in every clinical setting. Orbital biopsy is necessary for the confirmation of the diagnosis and for an adequate treatment. Although recommendations for management of orbital metastases are controversial, it appears that multidisciplinary treatment of both metastases and primary cancer improves overall survival.},
}
@article {pmid33915261,
year = {2021},
author = {López-Salazar, V and Tapia, MS and Tobón-Cornejo, S and Díaz, D and Alemán-Escondrillas, G and Granados-Portillo, O and Noriega, L and Tovar, AR and Torres, N},
title = {Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil.},
journal = {The Journal of nutritional biochemistry},
volume = {94},
number = {},
pages = {108751},
doi = {10.1016/j.jnutbio.2021.108751},
pmid = {33915261},
issn = {1873-4847},
mesh = {Animals ; Bacteria/classification/genetics ; Cells, Cultured ; Coconut Oil/*pharmacology ; Computational Biology ; DNA, Bacterial/genetics ; Feces/chemistry ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Regulation/drug effects ; Genotype ; Glucose Intolerance ; Hepatocytes/drug effects ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B/genetics/metabolism ; Non-alcoholic Fatty Liver Disease/*prevention &amp; control ; Olive Oil/*pharmacology ; Oxygen Consumption/drug effects ; PPAR alpha/genetics/*metabolism ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S ; Random Allocation ; Soybean Oil/*pharmacology ; Toll-Like Receptor 4/genetics/metabolism ; },
abstract = {Diets rich in mono or polyunsaturated fats have been associated with a healthy phenotype, but there is controversial evidence about coconut oil (CO), which is rich in saturated medium-chain fatty acids. Therefore, the purpose of the present work was to study whether different types of oils rich in polyunsaturated (soybean oil, SO), monounsaturated (olive oil, OO), or saturated fatty acids (coconut oil, CO) can regulate the gut microbiota, insulin sensitivity, inflammation, mitochondrial function in wild type and PPARα KO mice. The group that received SO showed the highest microbial diversity, increase in Akkermansia muciniphila, high insulin sensitivity and low grade inflammation, The OO group showed similar insulin sensitivity and insulin signaling than SO, increase in Bifidobacterium, increase in fatty acid oxidation and low grade inflammation. The CO consumption led to the lowest bacterial diversity, a 9-fold increase in the LPS concentration leading to metabolic endotoxemia, hepatic steatosis, increased lipogenesis, highest LDL-cholesterol concentration and the lowest respiratory capacity and fatty acid oxidation in the mitochondria. The absence of PPARα decreased alpha diversity and increased LPS concentration particularly in the CO group, and increased insulin sensitivity in the groups fed SO or OO. These results indicate that consuming mono or polyunsaturated fatty acids produced health benefits at the recommended intake but a high concentration of oils (three times the recommended oil intake in rodents) significantly decreased the microbial alpha-diversity independent of the type of oil.},
}
@article {pmid33907159,
year = {2021},
author = {He, Q and Xue, S and Wa, Q and He, M and Feng, S and Chen, Z and Chen, W and Luo, X},
title = {Mining immune-related genes with prognostic value in the tumor microenvironment of breast invasive ductal carcinoma.},
journal = {Medicine},
volume = {100},
number = {17},
pages = {e25715},
pmid = {33907159},
issn = {1536-5964},
support = {No. 81572769, No. 81372238//National Natural Science Foundation of China/ ; 2016ZDXM006//Natural Science Foundation of Chongqing (CN)/ ; No. 20PJ198//Scientific Research Foundation of Health Commission of Sichuan Provinc/ ; },
mesh = {Biomarkers, Tumor/*genetics ; *Breast Neoplasms/genetics/immunology/pathology ; *Carcinoma, Ductal/genetics/immunology/pathology ; Databases, Genetic ; Female ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Neoplastic ; Gene Ontology ; Humans ; Kaplan-Meier Estimate ; Molecular Targeted Therapy/methods ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; *Tumor Microenvironment/genetics/immunology ; },
abstract = {The tumor microenvironment (TME) plays an important role in the development of breast cancer. Due to limitations in experimental conditions, the molecular mechanism of TME in breast cancer has not yet been elucidated. With the development of bioinformatics, the study of TME has become convenient and reliable.Gene expression and clinical feature data were downloaded from The Cancer Genome Atlas database and the Molecular Taxonomy of Breast Cancer International Consortium database. Immune scores and stromal scores were calculated using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data algorithm. The interaction of genes was examined with protein-protein interaction and co-expression analysis. The function of genes was analyzed by gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis. The clinical significance of genes was assessed with Kaplan-Meier analysis and univariate/multivariate Cox regression analysis.Our results showed that the immune scores and stromal scores of breast invasive ductal carcinoma (IDC) were significantly lower than those of invasive lobular carcinoma. The immune scores were significantly related to overall survival of breast IDC patients and both the immune and stromal scores were significantly related to clinical features of these patients. According to the level of immune/stromal scores, 179 common differentially expressed genes and 5 hub genes with prognostic value were identified. In addition, the clinical significance of the hub genes was validated with data from the molecular taxonomy of breast cancer international consortium database, and gene set enrichment analysis analysis showed that these hub genes were mainly enriched in signaling pathways of the immune system and breast cancer.We identified five immune-related hub genes with prognostic value in the TME of breast IDC, which may partly determine the prognosis of breast cancer and provide some direction for development of targeted treatments in the future.},
}
@article {pmid33888263,
year = {2021},
author = {Schaub, JR and Tang, SC},
title = {Delayed Gemcitabine-Induced Posterior Reversible Encephalopathy Syndrome.},
journal = {The American journal of the medical sciences},
volume = {361},
number = {6},
pages = {795-798},
doi = {10.1016/j.amjms.2020.10.030},
pmid = {33888263},
issn = {1538-2990},
mesh = {Antimetabolites, Antineoplastic/*adverse effects ; Deoxycytidine/adverse effects/*analogs &amp; derivatives ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Posterior Leukoencephalopathy Syndrome/*chemically induced/*diagnostic imaging ; Time Factors ; Gemcitabine ; },
abstract = {INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical-radiographic syndrome that has been expanding rapidly in the world of clinical medical oncology and hematology. In this article, we provide a unique patient case of delayed gemcitabine-induced PRES.<br><br>BRIEF CASE REPORT: A 60-year-old African American female with significant past medical history of ER+/PR+/HER2- invasive ductal carcinoma of the left breast is seen in the medical oncology clinic with vague, mild complaints of lightheadedness. She had progressed on multiple lines of chemotherapy and was ultimately switched to gemcitabine. One month after her third dose of gemcitabine, she developed acute vision loss and soon developed generalized tonic-clonic seizure. Extensive workup was unrevealing other than PRES and she slowly improved with supportive care and withdrawal of the medication.<br><br>DISCUSSION: Multiple case reports have described PRES in the context of combination chemotherapy with gemcitabine and a platinum agent in the treatment of gastrointestinal malignancies. With growing evidence, this case is consistent with the hypothesis that gemcitabine as monotherapy has a direct association with PRES. This case highlights a unique aspect in that PRES can occur at a delayed time interval, much further than the expected hours to days after the previous treatment.},
}
@article {pmid33863935,
year = {2021},
author = {Nobili, S and Mannini, A and Parenti, A and Raggi, C and Lapucci, A and Chiorino, G and Paccosi, S and Di Gennaro, P and Vezzosi, V and Romagnoli, P and Susini, T and Coronnello, M},
title = {Establishment and characterization of a new spontaneously immortalized ER[-]/PR[-]/HER2[+] human breast cancer cell line, DHSF-BR16.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {8340},
pmid = {33863935},
issn = {2045-2322},
mesh = {Aged ; Breast Neoplasms/drug therapy/*genetics/*pathology/surgery ; CD24 Antigen/genetics/metabolism ; Carcinoma, Ductal/drug therapy/*genetics/*pathology/surgery ; Cell Line, Tumor ; Cell Movement ; Chemotherapy, Adjuvant ; Epithelial Cell Adhesion Molecule/genetics/metabolism ; Female ; Humans ; Hyaluronan Receptors/genetics/metabolism ; Intracellular Membranes/metabolism ; Keratin-7/genetics/metabolism ; Keratin-8/genetics/metabolism ; Neoadjuvant Therapy ; *Receptor, ErbB-2 ; *Receptors, Estrogen ; *Receptors, Progesterone ; Spheroids, Cellular/pathology ; },
abstract = {Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women's health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER[-]/PR[-]/HER2[+], and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44[+]/CD24[-/low]), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within - 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.},
}
@article {pmid33863525,
year = {2021},
author = {D'Iorio, A and Esposito, M and Maggi, G and Amboni, M and Vitale, C and Santangelo, G},
title = {Neuropsychological correlates of prospective memory: A comparison between tremor-dominant Parkinson's disease and cervical dystonia.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {87},
number = {},
pages = {156-161},
doi = {10.1016/j.jocn.2021.03.006},
pmid = {33863525},
issn = {1532-2653},
mesh = {Aged ; Cognitive Dysfunction/diagnosis/etiology/*psychology ; Executive Function/physiology ; Female ; Humans ; Male ; Memory Disorders/diagnosis/etiology/psychology ; *Memory, Episodic ; Middle Aged ; *Neuropsychological Tests ; Parkinson Disease/complications/diagnosis/*psychology ; Retrospective Studies ; Torticollis/complications/diagnosis/*psychology ; Tremor/complications/diagnosis/*psychology ; },
abstract = {Cervical Dystonia (CD) and Parkinson's disease, particularly tremor-dominant motor phenotype (TD-PD), showed a selective deficit of time-based prospective memory (TBPM). The two movement disorders are mainly characterized by dysfunctions of basal-ganglia and prefrontal cortex but it is reported that cerebellum also plays a key role in their pathogenesis. These cerebral structures are specifically involved in TBPM rather than in event-based PM (EBPM), but until now no study directly compared these two components of PM between CD and TD-PD patients. Therefore, the present study aimed at investigating if differences in PM functioning between CD and TD-PD patients might exist and if the type of movement disorder moderated the relationship between deficit of PM and deficit of executive functions and retrospective memory. Thirty TD-PD, 27CD patients and 29 healthy subjects (HCs), matched for demographic features, underwent neuropsychological tests for PM, executive functions, retrospective memory and self-rated questionnaires. The three groups did not differ on neuropsychological variables except for TBPM where TD-PD and CD patients performed worse than HCs; moreover, TD-PD performed worse than CD patients. Moderation analysis indicated that the type of movement disorder moderated the relationship between executive dysfunction and TBPM, but not EBPM. In conclusion, selective deficit of TBPM characterizes both CD and TD-PD but it is associated with executive dysfunction only in TD-PD. It might be possible to speculate that the involvement of the cerebellum, responsible for internal timing processes, could explain the impairment of TBPM in both movement disorders. This issue deserves to be explored in future neuroimaging studies.},
}
@article {pmid33850160,
year = {2021},
author = {Fayad, R and Rojas, MV and Partisani, M and Finetti, P and Dib, S and Abelanet, S and Virolle, V and Farina, A and Cabaud, O and Lopez, M and Birnbaum, D and Bertucci, F and Franco, M and Luton, F},
title = {EFA6B regulates a stop signal for collective invasion in breast cancer.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {2198},
pmid = {33850160},
issn = {2041-1723},
mesh = {Animals ; Breast Neoplasms/*genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Gene Knockout Techniques ; Guanine Nucleotide Exchange Factors/*genetics/*metabolism ; Humans ; Mice ; Mice, Nude ; Transcriptome ; cdc42 GTP-Binding Protein ; },
abstract = {Cancer is initiated by somatic mutations in oncogenes or tumor suppressor genes. However, additional alterations provide selective advantages to the tumor cells to resist treatment and develop metastases. Their identification is of paramount importance. Reduced expression of EFA6B (Exchange Factor for ARF6, B) is associated with breast cancer of poor prognosis. Here, we report that loss of EFA6B triggers a transcriptional reprogramming of the cell-to-ECM interaction machinery and unleashes CDC42-dependent collective invasion in collagen. In xenograft experiments, MCF10 DCIS.com cells, a DCIS-to-IDC transition model, invades faster when knocked-out for EFA6B. In addition, invasive and metastatic tumors isolated from patients have lower expression of EFA6B and display gene ontology signatures identical to those of EFA6B knock-out cells. Thus, we reveal an EFA6B-regulated molecular mechanism that controls the invasive potential of mammary cells; this finding opens up avenues for the treatment of invasive breast cancer.},
}
@article {pmid33835493,
year = {2021},
author = {Nash, Y and Ganoth, A and Borenstein-Auerbach, N and Levy-Barazany, H and Goldsmith, G and Kopelevich, A and Pozyuchenko, K and Sakhneny, L and Lazdon, E and Blanga-Kanfi, S and Alhadeff, R and Benromano, T and Landsman, L and Tsfadia, Y and Frenkel, D},
title = {From virus to diabetes therapy: Characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {35},
number = {5},
pages = {e21374},
doi = {10.1096/fj.201901945R},
pmid = {33835493},
issn = {1530-6860},
mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology ; Diabetes Mellitus, Experimental/etiology/pathology/*therapy ; Diabetes Mellitus, Type 1/etiology/pathology/*therapy ; Diabetes Mellitus, Type 2/etiology/pathology/*therapy ; Enzyme Inhibitors/administration &amp; dosage ; Female ; Herpesvirus 3, Human/physiology ; Insulin/*metabolism ; Insulysin/*antagonists &amp; inhibitors/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Peptide Fragments/*administration &amp; dosage ; Viral Envelope Proteins/*metabolism ; },
abstract = {Inhibition of insulin-degrading enzyme (IDE) is a possible target for treating diabetes. However, it has not yet evolved into a medical intervention, mainly because most developed inhibitors target the zinc in IDE's catalytic site, potentially causing toxicity to other essential metalloproteases. Since IDE is a cellular receptor for the varicella-zoster virus (VZV), we constructed a VZV-based inhibitor. We computationally characterized its interaction site with IDE showing that the peptide specifically binds inside IDE's central cavity, however, not in close proximity to the zinc ion. We confirmed the peptide's effective inhibition on IDE activity in vitro and showed its efficacy in ameliorating insulin-related defects in types 1 and 2 diabetes mouse models. In addition, we suggest that inhibition of IDE may ameliorate the pro-inflammatory profile of CD4[+] T-cells toward insulin. Together, we propose a potential role of a designed VZV-derived peptide to serve as a selectively-targeted and as an efficient diabetes therapy.},
}
@article {pmid33828234,
year = {2022},
author = {Hu, A and Hong, F and Li, D and Xie, Q and Chen, K and Zhu, L and He, H},
title = {KDM3B-ETF1 fusion gene downregulates LMO2 via the WNT/β-catenin signaling pathway, promoting metastasis of invasive ductal carcinoma.},
journal = {Cancer gene therapy},
volume = {29},
number = {2},
pages = {215-224},
pmid = {33828234},
issn = {1476-5500},
mesh = {Adaptor Proteins, Signal Transducing/genetics/metabolism ; Animals ; *Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics/metabolism ; LIM Domain Proteins ; Mice ; Mice, Nude ; Neoplasm Invasiveness/genetics ; Proto-Oncogene Proteins/genetics/metabolism ; Wnt Signaling Pathway ; beta Catenin/genetics/metabolism ; },
abstract = {Breast cancer is the most common malignancy for women, with invasive ductal carcinoma being the largest subtype of breast cancers, accounting for 75-80% of cases. However, the underlying mechanism of invasive ductal carcinoma remains unclear. In this study, we investigate the possible effects KDM3B-ETF1 fusion gene has on breast cancer cell metastasis, invasion and its downstream signaling mediators as revealed from RNA sequence data analysis. As predicted, KDM3B-ETF1 expression was increased in breast cancer tissues and cells. Overexpression of KDM3B-ETF1 in cancer cell lines promoted the growth and invasion of breast cancer cells, while KDM3B-ETF1 knockdown showed the opposite effects on malignant cell growth and invasion both in vivo and in vitro as evidenced by cell counting kit-8, Transwell assay and tumor xenograft in nude mice. On the contrary, LIM Domain Only 2 (LMO2) expression was significantly reduced in breast cancer tissues and cells. According to chromatin immunoprecipitation and Western blot analysis, KDM3B-ETF1 targets LMO2 and reduced the expression of LMO2, leading to an increase in WNT/β-catenin signaling pathway and thus promoting invasion. In conclusion, fusion gene KDM3B-ETF1 inhibits LMO2, activates the Wnt/β-catenin signaling pathway that leads to increased breast cancer cell invasion and metastasis, providing a novel insight into developing therapeutic strategies. These results provide novel insights into the molecular mechanism of invasive ductal carcinomas, which may lead to potential therapeutic targets.},
}
@article {pmid33827325,
year = {2021},
author = {Weaver, KD and Isom, J and Esnakula, A and Daily, K and Asirvatham, JR},
title = {Acinic Cell Carcinoma of the Breast: Report of a Case With Immunohistochemical and Next-Generation Sequencing Studies.},
journal = {International journal of surgical pathology},
volume = {29},
number = {8},
pages = {882-886},
doi = {10.1177/10668969211008508},
pmid = {33827325},
issn = {1940-2465},
mesh = {Adult ; Anoctamin-1/analysis/metabolism ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Breast/*pathology/surgery ; Carcinoma, Acinar Cell/*diagnosis/genetics/pathology ; DNA Mutational Analysis ; Female ; GATA3 Transcription Factor/analysis/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Mastectomy ; Neoplasm Proteins/analysis/metabolism ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/genetics/pathology ; Proto-Oncogene Proteins c-ret/genetics ; Sentinel Lymph Node Biopsy ; Triple Negative Breast Neoplasms/*diagnosis/genetics/pathology ; Tumor Suppressor Protein p53/genetics ; },
abstract = {Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.},
}
@article {pmid33824828,
year = {2021},
author = {Khanam, R and Fanous, IS and Fadhel, EN and Hyder, T and Brufsky, A},
title = {Voltage-Gated Calcium Channel Antibody-Induced Oropharyngeal Dysphagia Presenting as a Paraneoplastic Neurological Complication in Breast Cancer.},
journal = {Cureus},
volume = {13},
number = {3},
pages = {e13677},
pmid = {33824828},
issn = {2168-8184},
abstract = {Paraneoplastic neurologic syndromes (PNS) are a group of disorders characterized by an autoimmune response against the nervous system due to cross-reactivity between malignant and normal neural tissue. The most commonly associated malignancies include small cell lung cancer, ovarian cancer, breast cancer, and lymphoma. Multiple PNS have been reported including paraneoplastic cerebellar degeneration, retinopathy, sensorimotor peripheral neuropathy, encephalopathy, opsoclonus-myoclonus syndrome, and stiff-person syndrome. We report a case of a 67-year-old woman with breast cancer who presented with a history of progressive oropharyngeal dysphagia as a paraneoplastic neurologic complication. She was diagnosed with invasive ductal carcinoma, nuclear grade 3 with moderate peritumoral lymphoid infiltrate. Hormone receptors were weakly positive for estrogen receptor (ER) (H score 15), weakly positive for progesterone receptor (PR) (H score 30), and negative for human epidermal growth factor receptor 2 (HER-2/NEU). The patient underwent a localized segmental mastectomy but declined any further adjuvant treatment. Three years after being diagnosed with invasive ductal carcinoma of the breast, she developed progressive oropharyngeal dysphagia that warranted percutaneous endoscopic gastrostomy (PEG) tube placement. Testing for onconeural antibodies was positive for voltage-gated calcium channel antibody. An extensive workup was negative for any alternative etiology that would explain her neurological symptoms. The patient declined further treatment and eventually succumbed to her illness.},
}
@article {pmid33824344,
year = {2021},
author = {Kricheli-Katz, T and Regev, T},
title = {The effect of language on performance: do gendered languages fail women in maths?.},
journal = {NPJ science of learning},
volume = {6},
number = {1},
pages = {9},
pmid = {33824344},
issn = {2056-7936},
abstract = {Research suggests that gendered languages are associated with gender inequality. However, as languages are embedded in cultures, evidence for causal effects are harder to provide. We contribute to this ongoing debate by exploring the relationship between gendered languages and the gender gap in mathematics achievements. We provide evidence for causality by exploiting the prominent (but not exclusive) practice in gendered languages of using masculine generics to address women. In an experiment on a large representative sample of the Hebrew-speaking adult population in Israel, we show that addressing women in the feminine, compared to addressing them in the masculine, reduces the gender gap in mathematics achievements by a third. These effects are stronger among participants who acquired the Hebrew language early in childhood rather than later in life, suggesting that it is the extent of language proficiency that generates one's sensitivity to being addressed in the masculine or in the feminine. Moreover, when women are addressed in the masculine, their efforts (in terms of time spent on the maths test) decrease and they report feeling that "science is for men" more than when addressed in the feminine. We supplement the analysis with two experiments that explore the roles of general and task-specific stereotypes in generating these effects.},
}
@article {pmid33818021,
year = {2021},
author = {Alyami, H and Yoo, TK and Cheun, JH and Lee, HB and Jung, SM and Ryu, JM and Bae, SJ and Jeong, J and Yoon, CI and Ahn, J and Paik, PS and Cho, MK and Park, WC},
title = {Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations.},
journal = {Journal of breast cancer},
volume = {24},
number = {2},
pages = {175-182},
pmid = {33818021},
issn = {1738-6756},
abstract = {PURPOSE: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations.<br><br>METHODS: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea.<br><br>RESULTS: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8-222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer.<br><br>CONCLUSION: As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.},
}
@article {pmid33795819,
year = {2021},
author = {Nagasawa, S and Kuze, Y and Maeda, I and Kojima, Y and Motoyoshi, A and Onishi, T and Iwatani, T and Yokoe, T and Koike, J and Chosokabe, M and Kubota, M and Seino, H and Suzuki, A and Seki, M and Tsuchihara, K and Inoue, E and Tsugawa, K and Ohta, T and Suzuki, Y},
title = {Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast.},
journal = {Communications biology},
volume = {4},
number = {1},
pages = {438},
pmid = {33795819},
issn = {2399-3642},
mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Female ; GATA3 Transcription Factor/genetics/metabolism ; *Gene Amplification ; Gene Expression Profiling ; Humans ; Middle Aged ; *Mutation ; Receptor, ErbB-2/genetics/metabolism ; Young Adult ; },
abstract = {In a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.},
}
@article {pmid33785437,
year = {2021},
author = {Garcia, AM and Bishop, EL and Li, D and Jeffery, LE and Garten, A and Thakker, A and Certo, M and Mauro, C and Tennant, DA and Dimeloe, S and Evelo, CT and Coort, SL and Hewison, M},
title = {Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis.},
journal = {The Journal of steroid biochemistry and molecular biology},
volume = {211},
number = {},
pages = {105891},
pmid = {33785437},
issn = {1879-1220},
support = {MR/P021220/1/MRC_/Medical Research Council/United Kingdom ; MR/T016736/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; },
mesh = {*Adipogenesis ; *Cell Differentiation ; Cells, Cultured ; Dendritic Cells/drug effects/immunology/*metabolism ; Fatty Acids/*biosynthesis ; Glycolysis ; Humans ; *Immune Tolerance ; Vitamin D/*analogs &amp; derivatives/pharmacology ; },
abstract = {The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is a potent regulator of immune function, promoting anti-inflammatory, tolerogenic T cell responses by modulating antigen presentation by dendritic cells (DC). Transcriptomic analyses indicate that DC responses to 1,25D involve changes in glycolysis, oxidative phosphorylation, electron transport and the TCA cycle. To determine the functional impact of 1,25D-mediated metabolic remodelling, human monocyte-derived DC were differentiated to immature (+vehicle, iDC), mature (+LPS, mDC), and immature tolerogenic DC (+1,25D, itolDC) and characterised for metabolic function. In contrast to mDC which showed no change in respiration, itolDC showed increased basal and ATP-linked respiration relative to iDC. Tracer metabolite analyses using [13]C -labeled glucose showed increased lactate and TCA cycle metabolites. Analysis of lipophilic metabolites of [13]C-glucose revealed significant incorporation of label in palmitate and palmitoleate, indicating that 1,25D promotes metabolic fatty acid synthesis in itolDC. Inhibition of fatty acid synthesis in itolDC altered itolDC morphology and suppressed expression of CD14 and IL-10 by these cells. These data indicate that the ability of 1,25D to induce tolerogenic DC involves metabolic remodelling leading to synthesis of fatty acids.},
}
@article {pmid33776732,
year = {2021},
author = {Sugimoto, H and Oda, G and Yokoyama, M and Hayashi, K and Yoshino, M and Ogawa, A and Hosoya, T and Nakagawa, T and Uetake, H},
title = {Hydronephrosis Caused by Metastatic Breast Cancer.},
journal = {Case reports in oncology},
volume = {14},
number = {1},
pages = {378-385},
pmid = {33776732},
issn = {1662-6575},
abstract = {Breast cancer metastasizes mainly to organs such as bone, lung, and liver, whereas metastases to the peritoneum and urinary tract are rare. Metastasis to the peritoneum or urinary tract may result in renal dysfunction, infection, and painful hydronephrosis. In our hospital, 1,409 breast cancer surgeries were performed between January 2004 and December 2015, and 7 cases of hydronephrosis associated with recurrence were observed. The median age of patients was 69 years (57-79 years). The median time from surgery to diagnosis of hydronephrosis was 47 months (20-70 months). Histology was invasive ductal carcinoma (IDC) in 6 cases and invasive lobular carcinoma (ILC) in 1 case. There were 6 bilateral cases and 1 unilateral case of hydronephrosis. The causes were retroperitoneal metastasis in 5 cases and lymph node metastasis in 2 cases. The hydronephrosis was untreated in 2 cases, and treated with a ureteral stent in 2 cases, nephrostomy in 1 case, and nephrostomy due to ureteral stent failure in 2 cases. The median survival from the onset of hydronephrosis was 12 months (3-57 months). Although the probability of hydronephrosis in breast cancer recurrence was not high, care must be taken to avoid renal dysfunction, infection, or pain, which may require treatment.},
}
@article {pmid33759307,
year = {2021},
author = {Zhang, J and Zhou, B and Sun, J and Chen, H and Yang, Z},
title = {Betulin ameliorates 7,12-dimethylbenz(a)anthracene-induced rat mammary cancer by modulating MAPK and AhR/Nrf-2 signaling pathway.},
journal = {Journal of biochemical and molecular toxicology},
volume = {35},
number = {7},
pages = {e22779},
doi = {10.1002/jbt.22779},
pmid = {33759307},
issn = {1099-0461},
mesh = {9,10-Dimethyl-1,2-benzanthracene/*toxicity ; Animals ; Female ; MAP Kinase Signaling System/*drug effects ; Mammary Neoplasms, Animal/chemically induced/drug therapy/*metabolism/pathology ; NF-E2-Related Factor 2/*metabolism ; Neoplasm Proteins/*metabolism ; Rats ; Receptors, Aryl Hydrocarbon/*metabolism ; Triterpenes/*pharmacology ; },
abstract = {The aim of the present study is to explore the preventive efficacy of betulin (BE) in 7,12-dimethylbenz(a)anthracene (DMBA)-administered mammary cancer by modulating Ahr/Nrf2 signaling in experimental models. The mammary cancer was stimulated by the addition of DMBA (25 mg/kg/b.Wt) mixed in 1 ml of vehicle solution (sunflower oil and saline 1:1) through subcutaneous injection. The DMBA-exposed mammary tumor models showed low bodyweight, elevated quantities of lipid peroxidation molecules (TBARS and LOOH), and low enzymatic (GPx, SOD, and CAT), and nonenzymatic (GSH, vitamin C, and vitamin E) antioxidant activities in plasma and mammary tissues. Moreover, histopathological studies confirmed that invasive ductal carcinoma was observed in DMBA-induced mammary tissue of the experimental model. Dietary oral supplementation of BE prevents the loss of bodyweight, overproduces lipid peroxidation, and restores the antioxidant activities in DMBA-exposed experimental animals. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial antioxidant protein that involves preventing numerous cancers. Therefore, Nrf2-associated signaling concern is a significant target for preventing mammary cancer. This study observed an increased expression of MAPKs, Keap1, ARNT, AhR, and CYP1A1, whereas decreased expression of HO-1 and Nrf2 in DMBA-induced cancer-bearing experimental animals. The oral supplementation of BE effectively modulates the expression of MAPKs, AhR/Nrf2-associated protein expressions in DMBA-exposed experimental animals. This current study concluded that BE is a strong antioxidant, which triggers the MAPKs-mediated oxidative stress and inhibits proliferative markers by restoring the activity of Nrf2 signaling.},
}
@article {pmid33753865,
year = {2021},
author = {Bergeron, A and MacGrogan, G and Bertaut, A and Ladoire, S and Arveux, P and Desmoulins, I and Bonnefoi, H and Loustalot, C and Auriol, S and Beltjens, F and Degrolard-Courcet, E and Charon-Barra, C and Richard, C and Boidot, R and Arnould, L},
title = {Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {34},
number = {7},
pages = {1282-1296},
pmid = {33753865},
issn = {1530-0285},
mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Lobular/genetics/metabolism/*pathology ; DNA Mutational Analysis ; Female ; Humans ; Middle Aged ; Mutation ; Phosphatidylinositol 3-Kinases/genetics ; Receptor, ErbB-2/genetics ; Receptors, Androgen/genetics/*metabolism ; Receptors, Estrogen/*genetics ; Triple Negative Breast Neoplasms/*genetics/metabolism/*pathology ; ERRalpha Estrogen-Related Receptor ; },
abstract = {Primary triple-negative invasive lobular breast carcinomas (TN-ILCs), which do not express hormone receptors and HER2 at diagnosis, are rare and poorly known. In this study, we analyzed the largest TN-ILC series ever reported in the literature, in comparison to phenotypically similar breast tumor subtypes: triple-negative invasive ductal carcinoma (TN-IDC) and hormone receptor-positive invasive lobular carcinoma (HR + ILC). All primary TN-ILCs registered in our database between 2000 and 2018 (n = 38) were compared to tumors from control groups, matched by stage and Elston/Ellis grade, with regard to clinical, pathologic, and immunohistochemical characteristics. A comparative molecular analysis (whole-exome and RNA sequencing using next-generation technology) was also performed. We found that TN-ILC patients were older than those with HR + ILC (P = 0.002) or TN-IDC (P < 0.001). Morphologically, TN-ILCs had aggressive phenotypes, with more pleomorphism (P = 0.003) and higher nuclear grades than HR + ILCs (P = 0.009). Immunohistochemistry showed that TN-ILCs less frequently expressed basal markers (CK5/6, EGFR and SOX10) than TN-IDCs (P < 0.001), while androgen receptor (AR) positivity was more prevalent (P < 0.001). Survival curves analysis did not show differences between TN-ILC and TN-IDC patients, while overall and distant metastasis-free survival were significantly worse compared to those with HR + ILCs (P = 0.047 and P = 0.039, respectively). At a molecular level, we found that TN-ILCs had particular transcriptomic profiles, characterized by increased AR signaling, and associated with frequent alterations in the PI3K network and ERBB2. Interestingly, whole-exome analysis also identified three specific recurrent ESRRA hotspot mutations in these tumors, which have never been described in breast cancer to date and which were absent in the other two tumor subtypes. Our findings highlight that TN-ILC is a unique aggressive breast cancer associated with elderly age, which belong to the luminal androgen receptor subtype as determined by immunohistochemistry and transcriptomic profiling. Moreover, it harbors specific molecular alterations (PI3K, ERBB2 and ESRRA) which may pave the way for new targeted therapeutic strategies.},
}
@article {pmid33735776,
year = {2021},
author = {Levin, Y and Lev Bar-Or, R and Forer, R and Vaserman, M and Kor, A and Lev-Ran, S},
title = {The association between type of trauma, level of exposure and addiction.},
journal = {Addictive behaviors},
volume = {118},
number = {},
pages = {106889},
doi = {10.1016/j.addbeh.2021.106889},
pmid = {33735776},
issn = {1873-6327},
mesh = {*Alcoholism ; *Behavior, Addictive/epidemiology ; Checklist ; Humans ; Risk Factors ; *Substance-Related Disorders/epidemiology ; },
abstract = {Exposure to trauma is considered a risk factor for the development of addictive disorders. Currently, there is a knowledge gap concerning specific links between types and levels of exposure to traumatic events and addiction.In this study we explored the associations between interpersonal trauma and risk of addictive behaviors, stratified by type of trauma (physical, weapon, sexual assault, and combat) and level of exposure (direct/indirect), focusing on a wide range of substances and behaviors. Data from an online representative sample of 4025 respondents were collected, including the Life Events Checklist (LEC-5), substance use disorders and behavioral addictions metrics, and sociodemographic data. Substantial differences were found between specific types of trauma and risk of addiction. Among those exposed to sexual assault, the risk of alcohol use disorder was found to 15.4%, 95%CI[14.4-16.4%], compared to 12.1%,95%CI[11.3-12.8] among those exposed to combat-related trauma. Both direct and indirect exposure to trauma were found to be significantly related with risk of addiction. While direct exposure was most highly associated with addictions across several types of trauma, in the case of combat-related trauma, indirect exposure was more highly associated with alcohol and pornography addiction (14.5%,95%CI[13.2-15.8%] and 10.0%, 95%CI[6.3-15.0%], respectively) compared to direct exposure (10.7%,95%CI[9.9-11.6%] and 7.4%, 95%CI[4.7-11.6%], respectively). Our findings emphasize the strong association between all types of trauma and the risk of several specific substance and behavioral addictions. Specifically, the role of indirect exposure to trauma is highlighted.},
}
@article {pmid33730716,
year = {2021},
author = {Bar-Or, RL and Kor, A and Jaljuli, I and Lev-Ran, S},
title = {The Epidemiology of Substance Use Disorders among the Adult Jewish Population in Israel.},
journal = {European addiction research},
volume = {27},
number = {5},
pages = {362-370},
doi = {10.1159/000513776},
pmid = {33730716},
issn = {1421-9891},
mesh = {Adult ; *Alcoholism ; Humans ; Israel/epidemiology ; Jews/statistics &amp; numerical data ; Prevalence ; *Substance-Related Disorders/epidemiology ; Young Adult ; },
abstract = {INTRODUCTION: Substance use disorders (SUDs) are a leading cause of morbidity and mortality worldwide, having a profound and global impact on health, well-being, safety, and productivity. Although traditionally the prevalence of SUDs in Israel has been estimated to be lower than those in high-income countries, estimates and characteristics of individuals with SUDs in the past decade are lacking. In this work, we explored the prevalence of SUDs among the adult Jewish population in Israel, per different classes of substances across sex, age group, and other sociodemographic factors.<br><br>METHODS: Data from an online representative sample of 4,025 respondents were collected, including the alcohol, smoking, and substance involvement screening test (ASSIST) metric and sociodemographic data.<br><br>RESULTS: We found that the most common SUDs were alcohol (10.5% [9.5-11.4]), cannabis (9.0% [8.2-9.9]), and sedative (3.6% [3.0-4.2]) use disorders. Alcohol-cannabis (3.2% [2.7-3.7]) and alcohol-sedative (1.04% [0.7-1.35]) were the most prevalent co-occurring SUDs. Among those with cannabis use disorder, the prevalence of alcohol use disorder was found to be 35.3% [30.4-40.2]. The estimated risk for alcohol use disorder was found to be inversely proportional to age, cannabis use disorder increased, peaked, and decreased with age, and that of sedative use disorder increased with age, particularly among women. While older individuals (in the 51-60 years of age group) were at lower risk (OR = 0.5 [0.3, 0.8]) compared to those <20 years of age for alcohol use disorder, they were at increased risk for sedative use disorder (OR = 3.1 [1.2, 9.7]).<br><br>CONCLUSIONS: These findings represent substantially higher rates of SUDs in Israel than those previously reported and should affect resources allocated to addiction prevention and treatment. Further research on the role of gender, age, culture, and ethnicity in the propensity to develop SUDs is necessary for the development of more focused preventive and intervention measures. Focusing on non-Jewish populations in Israel and broadening the scope to include behavioral addictions should be addressed in future studies.},
}
@article {pmid33725931,
year = {2021},
author = {Oh, BH and Woo, CG and Lee, YJ and Park, YS},
title = {Brain metastasis with subtype conversion in a patient with male breast cancer: A case report.},
journal = {Medicine},
volume = {100},
number = {11},
pages = {e24373},
pmid = {33725931},
issn = {1536-5964},
support = {NRF-2019R1A2C1085809//Chungbuk National University Korea National University Development Project (2020)/ ; },
mesh = {Brain Neoplasms/metabolism/*secondary ; Breast Neoplasms, Male/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Humans ; Male ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {RATIONALE: Brain metastasis of male breast cancer is extremely rare, and the pathological changes between the primary tumor and the metastatic brain tumor have not been reported. Herein, we report for the first time a case of male breast cancer with metastasis to the parietal lobe with subtype conversion after metastasis.<br><br>PATIENT CONCERNS: we describe a 45-year-old male patient admitted for an incidentally found brain tumor after a motorcycle accident. The patient had been treated for breast cancer 5 years previously. The primary tumor was an invasive ductal carcinoma classified as pT1N1M0 with hormone receptor positivity (estrogen receptor ++, progesterone receptor +++, human epidermal growth factor receptor-type2 (HER2) +) and was treated with surgery, adjuvant chemotherapy, radiation therapy and endocrine therapy (tamoxifen).<br><br>DIAGNOSES: Magnetic resonance imaging revealed a well enhanced focal solid tumor in the right parietal lobe (5.0&#x200a;&#xd7;&#x200a;4.2&#x200a;cm in size), Immunohistochemical staining revealed cerebral metastases of breast cancer with HER2 subtype conversion (estrogen receptor +++, progesterone receptor +++, HER2 -).<br><br>INTERVENTIONS: The patient was successfully treated with surgery and whole brain irradiation (3 Gy&#x200a;&#xd7;&#x200a;10 fractions).<br><br>OUTCOMES: There was no additional complication after the surgery and the patient transferred to oncology department for chemotherapy. 2 years later, he had gamma knife radiosurgery due to the recurred brain lesion and after that he discontinued the treatment and opted for hospice care.<br><br>LESSONS: Male breast cancer with metastasis to the brain is an extremely rare condition. Although a few similar cases have been reported, subtype conversion in similar cases has not been reported. Therefore, we report this case of a male patient with brain metastasis of invasive ductal carcinoma with HER2 status conversion after metastasis.},
}
@article {pmid33710293,
year = {2021},
author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY},
title = {Neoadjuvant Chemotherapy or Endocrine Therapy for Invasive Ductal Carcinoma of the Breast With High Hormone Receptor Positivity and Human Epidermal Growth Factor Receptor 2 Negativity.},
journal = {JAMA network open},
volume = {4},
number = {3},
pages = {e211785},
pmid = {33710293},
issn = {2574-3805},
mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/*drug therapy/*mortality/pathology ; Carcinoma, Ductal/chemistry/*drug therapy/*mortality/pathology ; Cause of Death ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Receptor, ErbB-2/analysis ; Young Adult ; },
abstract = {IMPORTANCE: Although neoadjuvant endocrine therapy (NET) is an alternative to chemotherapy for strongly hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer, evidence is currently lacking regarding the probable survival outcomes of NET in comparison with those of neoadjuvant chemotherapy (NACT) for this cancer.<br><br>OBJECTIVE: To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT.<br><br>This cohort study included patients with a diagnosis of invasive ductal carcinoma (IDC) with strong HR positivity and ERBB2 negativity, treated between January 1, 2009, and December 31, 2016, with follow-up from the index date (ie, date of IDC diagnosis) to December 31, 2018. The data came from the Taiwan Cancer Registry Database. Data were analyzed from January to November 2020.<br><br>EXPOSURES: NET vs NACT for IDC with strong HR positivity and ERBB2 negativity.<br><br>MAIN OUTCOMES AND MEASURES: The primary end point was all-cause mortality. Propensity score matching was performed, and Cox proportional hazard models were used to analyze all-cause mortality among patients undergoing different neoadjuvant treatments.<br><br>RESULTS: A total of 640 patients (297 [46.4%] aged 20-49 years) undergoing NET (145 patients [22.7%]) or NACT (495 patients [77.3%]) were eligible for further analysis. In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) for all-cause mortality among the NET cohort compared with the NACT cohort was 2.67 (95% CI, 1.95-3.51; P&#x2009;<&#x2009;.001). The aHRs for age were 1.13 (95% CI, 1.03-2.24), 1.25 (95% CI, 1.13-2.45), and 1.37 (95% CI, 1.17-3.49) for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P&#x2009;=&#x2009;.002); the aHR for all-cause mortality among premenopausal women was 1.35 (95% CI, 1.13-1.56) compared with postmenopausal women (P&#x2009;<&#x2009;.001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P&#x2009;<&#x2009;.001). The aHRs of all-cause mortality for clinical tumor stage 2, 3, and 4 compared with 1 were 1.84 (95% CI, 1.07-3.40), 1.97 (95% CI, 1.03-3.77), and 2.49 (95% CI, 1.29-4.81), respectively (P&#x2009;=&#x2009;.009). The aHRs for all-cause mortality by clinical nodal (cN) stages were 1.49 (95% CI, 1.13-1.99) and 1.84 (95% CI, 1.31-2.61) for cN stage 1 and cN stages 2 or 3, respectively, compared with cN stage 0 (P&#x2009;=&#x2009;.005); those for differentiation were 1.77 (95% CI, 1.24-2.54) and 2.31 (95% CI, 1.61-3.34) for differentiation grade 2 and differentiation grade 3, respectively, compared with differentiation grade 1 (P&#x2009;<&#x2009;.001).<br><br>CONCLUSIONS AND RELEVANCE: The findings of this study suggest that for patients with strongly HR-positive and ERBB2-negative IDC, NACT may be considered the first choice for neoadjuvant treatment.},
}
@article {pmid33704190,
year = {2020},
author = {Bondy, S and Tajzler, C and Hotte, SJ and Kapoor, A and Zbuk, K and Lalani, AA},
title = {Genomic and Clinical Correlates of Adrenocortical Carcinoma in an Adult Patient with Li-Fraumeni Syndrome: A Case Report.},
journal = {Current oncology (Toronto, Ont.)},
volume = {28},
number = {1},
pages = {226-232},
pmid = {33704190},
issn = {1718-7729},
mesh = {*Adrenal Cortex Neoplasms/genetics ; *Adrenocortical Carcinoma/diagnosis/genetics ; Adult ; *Breast Neoplasms ; Female ; Genomics ; Humans ; *Li-Fraumeni Syndrome/genetics ; Mastectomy ; Neoplasm Recurrence, Local ; },
abstract = {Li-Fraumeni Syndrome (LFS) is defined by germline mutations of the p53 tumour suppressor gene. Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that is commonly associated with LFS. Most LFS-linked ACC cases occur in children, and limited research has been dedicated to the clinical outcomes and genomics of adult cases with LFS-linked ACC. We report on a 34-year-old female who was diagnosed with three separate malignancies: stage III invasive ductal carcinoma of the right breast, metastatic ACC from the right adrenal gland, and grade 2 pleomorphic sarcoma of the left hand. Her invasive breast ductal carcinoma was treated with neoadjuvant chemotherapy, and she received a bilateral mastectomy after her LFS was confirmed with genetic blood testing. Adrenal ACC was initially treated with a right nephrectomy and adrenalectomy, followed by adjuvant mitotane and two lines of chemotherapy after disease recurrence. Her hand sarcoma was treated by second ray amputation. Further, we conducted deep next-generation sequencing of each of her unique tumour tissue samples using FoundationONE CDx. A whole-genome shot capture followed by in vitro sequencing performed by the Illumina[®] HiSeq platform revealed a germline P191fs*18 TP53 mutation across all three tissue samples. This case provides insight into the genomics and clinical characteristics of LFS-linked adult-onset ACC and demonstrated that p53 mutations were preserved throughout each malignancy, without apparent treatment pressures on genomic profiling. This case reinforces the critical importance of adopting best practices for LFS, which include the implementation of highly vigilant screening and management of care in a multidisciplinary setting.},
}
@article {pmid33692758,
year = {2021},
author = {Togashi, K and Nishitsuka, K and Hayashi, S and Namba, H and Goto, S and Takeda, Y and Suzuki, S and Kato, T and Yamada, Y and Konno, E and Yoshioka, T and Yamakawa, M and Sonoda, Y and Suzuki, T and Yamashita, H},
title = {Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.},
journal = {Frontiers in endocrinology},
volume = {12},
number = {},
pages = {625663},
pmid = {33692758},
issn = {1664-2392},
mesh = {Breast Neoplasms/complications/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/complications/diagnostic imaging/*secondary ; Exophthalmos/diagnostic imaging/*etiology ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Orbital Neoplasms/complications/diagnostic imaging/*secondary ; },
abstract = {BACKGROUND: Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function.<br><br>CASE PRESENTATION: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation.<br><br>CONCLUSION: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.},
}
@article {pmid33676449,
year = {2021},
author = {Ji, L and Cheng, L and Zhu, X and Gao, Y and Fan, L and Wang, Z},
title = {Risk and prognostic factors of breast cancer with liver metastases.},
journal = {BMC cancer},
volume = {21},
number = {1},
pages = {238},
pmid = {33676449},
issn = {1471-2407},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/secondary/therapy ; Chemoradiotherapy, Adjuvant/methods ; Datasets as Topic ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Liver/diagnostic imaging/pathology ; Liver Neoplasms/*epidemiology/secondary/therapy ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/methods ; Prognosis ; Receptor, ErbB-2/analysis/antagonists &amp; inhibitors/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/mortality/*pathology/therapy ; Young Adult ; },
abstract = {BACKGROUND: Liver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM).<br><br>METHODS: Data on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients.<br><br>RESULTS: Young age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0&#x2009;months in the SEER database and 27.3&#x2009;months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0&#x2009;months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6&#x2009;months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR)&#x2009;=&#x2009;2.62; 95% confidence interval (CI)&#x2009;=&#x2009;1.88-3.66; P&#x2009;<&#x2009;0.001) and HR-/HER2+ (HR&#x2009;=&#x2009;3.43; 95% CI&#x2009;=&#x2009;2.28-5.15; P&#x2009;<&#x2009;0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR&#x2009;=&#x2009;0.74; 95% CI&#x2009;=&#x2009;0.58-0.95; P&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Breast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.},
}
@article {pmid33667646,
year = {2021},
author = {He, B and Chen, J and Song, W and Bai, Y},
title = {miR-646/TET1 mediated demethylation of IRX1 promoter upregulates HIST2H2BE and promotes the progression of invasive ductal carcinoma.},
journal = {Genomics},
volume = {113},
number = {3},
pages = {1469-1481},
doi = {10.1016/j.ygeno.2020.12.044},
pmid = {33667646},
issn = {1089-8646},
mesh = {*Carcinoma, Ductal ; Cell Line, Tumor ; DNA Methylation ; Demethylation ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/metabolism ; Humans ; *MicroRNAs/genetics/metabolism ; Mixed Function Oxygenases/genetics/metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism ; },
abstract = {BACKGROUND: This study aimed to explore role of miR-646 in breast IDC.<br><br>METHODS: miR-646, TET1, IRX1, and HIST2H2BE expression was detected by RT-qPCR and/or Western blot analysis. The methylation status of IRX1 promoter region was evaluated by methylation specific PCR. ChIP assay was used to determine the enrichment of TET1 at IRX1 promoter region. Loss- and gain-of functions were performed to determine the roles of miR-646, TET1, IRX1, and HIST2H2BE in cell proliferation, migration, invasion, and apoptosis. The tumor growth, volume, weight, and apoptosis status were measured.<br><br>RESULTS: miR-646 was upregulated while TET1 was downregulated in IDC tissues. miR-646 targeted TET1. Downregulated TET1 impairs demethylation of IRX1 promoter region resulting in reduced expression of IRX1, which subsequently leads to upregulation of HIST2H2BE in IDC. Consequently, elevated HIST2H2BE promotes progression of IDC.<br><br>CONCLUSION: Our study has demonstrated that miR-646 facilitates the tumorigenesis of IDC via regulating TET1/IRX1/HIST2H2BE axis.},
}
@article {pmid33667422,
year = {2021},
author = {Schwartz, CJ and Boroujeni, AM and Khodadadi-Jamayran, A and Heguy, A and Snuderl, M and Jour, G and Cotzia, P and Darvishian, F},
title = {Molecular analysis of encapsulated papillary carcinoma of the breast with and without invasion.},
journal = {Human pathology},
volume = {111},
number = {},
pages = {67-74},
doi = {10.1016/j.humpath.2021.02.005},
pmid = {33667422},
issn = {1532-8392},
support = {P30 CA016087/CA/NCI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Papillary/*genetics/*pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Middle Aged ; Mutation ; Retrospective Studies ; },
abstract = {Encapsulated papillary carcinomas (EPCs) of the breast are a unique variant of papillary carcinoma confined to a cystic space with absent or attenuated myoepithelial cell layer. Although staged as an in situ lesion, it can be associated with invasive ductal carcinoma (IDC). We sought to compare the genomic characteristics of pure EPC and EPC with associated invasive carcinoma (EPCi) at the genomic level. All cases of EPCi harbored recurrent hotspot mutations in PIK3CA. PIK3CA, KMT2A, and CREBBP deleterious somatic events were found across both tumor groups, irrespective of invasion status. At the whole transcriptomic level, EPCi cases displayed remarkably similar mRNA profiles when compared to EPC. When EPCi cases were compared with their corresponding IDC, despite significant overlap, we identified differential gene expression in 39 genes with enrichment of multiple pathways including extracellular matrix regulation, cell adhesion, and collagen fibril organization. Despite morphologic, genotypic, and transcriptomic overlap between pure EPC and EPCi, the latter tumors are likely advanced lesions with PIK3CA activating mutations and enrichment of stromal-related genes implicated in the switch to IDC.},
}
@article {pmid33665961,
year = {2021},
author = {Hartleben, G and Schorpp, K and Kwon, Y and Betz, B and Tsokanos, FF and Dantes, Z and Schäfer, A and Rothenaigner, I and Monroy Kuhn, JM and Morigny, P and Mehr, L and Lin, S and Seitz, S and Tokarz, J and Artati, A and Adamsky, J and Plettenburg, O and Lutter, D and Irmler, M and Beckers, J and Reichert, M and Hadian, K and Zeigerer, A and Herzig, S and Berriel Diaz, M},
title = {Combination therapies induce cancer cell death through the integrated stress response and disturbed pyrimidine metabolism.},
journal = {EMBO molecular medicine},
volume = {13},
number = {4},
pages = {e12461},
pmid = {33665961},
issn = {1757-4684},
mesh = {*Antineoplastic Agents ; Cell Death ; Humans ; *Neoplasms ; Niclosamide ; Pyrimidines ; },
abstract = {By accentuating drug efficacy and impeding resistance mechanisms, combinatorial, multi-agent therapies have emerged as key approaches in the treatment of complex diseases, most notably cancer. Using high-throughput drug screens, we uncovered distinct metabolic vulnerabilities and thereby identified drug combinations synergistically causing a starvation-like lethal catabolic response in tumor cells from different cancer entities. Domperidone, a dopamine receptor antagonist, as well as several tricyclic antidepressants (TCAs), including imipramine, induced cancer cell death in combination with the mitochondrial uncoupler niclosamide ethanolamine (NEN) through activation of the integrated stress response pathway and the catabolic CLEAR network. Using transcriptome and metabolome analyses, we characterized a combinatorial response, mainly driven by the transcription factors CHOP and TFE3, which resulted in cell death through enhanced pyrimidine catabolism as well as reduced pyrimidine synthesis. Remarkably, the drug combinations sensitized human organoid cultures to the standard-of-care chemotherapy paclitaxel. Thus, our combinatorial approach could be clinically implemented into established treatment regimen, which would be further facilitated by the advantages of drug repurposing.},
}
@article {pmid33663447,
year = {2021},
author = {Mills, MN and Walker, C and Thawani, C and Naz, A and Figura, NB and Kushchayev, S and Etame, A and Yu, HM and Robinson, TJ and Liu, J and Vogelbaum, MA and Forsyth, PA and Czerniecki, BJ and Soliman, HH and Han, HS and Ahmed, KA},
title = {Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases.},
journal = {BMC cancer},
volume = {21},
number = {1},
pages = {223},
pmid = {33663447},
issn = {1471-2407},
mesh = {Ado-Trastuzumab Emtansine/adverse effects/*therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Brain/pathology ; Brain Neoplasms/*secondary ; Breast Neoplasms/chemistry/mortality/pathology/*therapy ; Combined Modality Therapy ; Female ; Humans ; Middle Aged ; Necrosis ; *Radiosurgery/adverse effects ; Radiotherapy Dosage ; Receptor, ErbB-2/*analysis ; },
abstract = {BACKGROUND: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation.<br><br>METHODS: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6&#x2009;months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging.<br><br>RESULTS: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21&#x2009;Gy (14-24&#x2009;Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25&#x2009;Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2&#x2009;months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis.<br><br>CONCLUSIONS: We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.},
}
@article {pmid33662042,
year = {2021},
author = {Mohamed, RI and Bargal, SA and Mekawy, AS and El-Shiekh, I and Tuncbag, N and Ahmed, AS and Badr, E and Elserafy, M},
title = {The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine.},
journal = {PloS one},
volume = {16},
number = {3},
pages = {e0247837},
pmid = {33662042},
issn = {1932-6203},
mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; *DNA Repair ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; Precision Medicine ; Transcriptome ; Up-Regulation ; },
abstract = {In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients' response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients' samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients' samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients' samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.},
}
@article {pmid33645934,
year = {2021},
author = {Da Costa, I and Belnou, P and Soulier, A and Lapidus, N and Tsai, ES and Bourcier, E and Moisi, L and Sautet, A and Bonnet, F and Lescot, T and Verdonk, F},
title = {Impact of delayed patient flow on surgical outcomes after hip fracture: An observational study.},
journal = {European journal of anaesthesiology},
volume = {38 Suppl 1},
number = {},
pages = {S67-S68},
doi = {10.1097/EJA.0000000000001271},
pmid = {33645934},
issn = {1365-2346},
mesh = {Aged ; Aged, 80 and over ; Female ; France/epidemiology ; Hemorrhage/*epidemiology/etiology ; Hip Fractures/complications/*surgery ; Humans ; Male ; Middle Aged ; Outcome Assessment, Health Care ; Postoperative Complications/epidemiology ; Recovery of Function/*physiology ; Time Factors ; Time-to-Treatment/*statistics &amp; numerical data ; Treatment Outcome ; },
}
@article {pmid33641217,
year = {2021},
author = {Pramod, N and Nigam, A and Basree, M and Mawalkar, R and Mehra, S and Shinde, N and Tozbikian, G and Williams, N and Majumder, S and Ramaswamy, B},
title = {Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer.},
journal = {The oncologist},
volume = {26},
number = {6},
pages = {e943-e953},
pmid = {33641217},
issn = {1549-490X},
mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal, Breast ; *Carcinoma, Lobular/genetics/therapy ; Female ; Humans ; Mastectomy, Segmental ; },
abstract = {Invasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER)-positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. Lobular cancer presents significant challenges in detection and clinical management given its multifocality and multicentricity at presentation. Despite the unique features of ILC, it is often lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC. Despite both being treated as ER-positive breast cancer, querying the Cancer Genome Atlas database shows distinctive molecular aberrations in ILC compared with IDC, such as E-cadherin loss (66% vs. 3%), FOXA1 mutations (7% vs. 2%), and GATA3 mutations (5% vs. 20%). Moreover, compared with patients with IDC, patients with ILC are less likely to undergo breast-conserving surgery, with lower rates of complete response following therapy as these tumors are less chemosensitive. Taken together, this suggests that ILC is biologically distinct, which may influence tumorigenesis and therapeutic strategies. Long-term survival and clinical outcomes in patients with ILC are worse than in stage- and grade-matched patients with IDC; therefore, nuanced criteria are needed to better define treatment goals and protocols tailored to ILC's unique biology. This comprehensive review highlights the histologic and clinicopathologic features that distinguish ILC from IDC, with an in-depth discussion of ILC's molecular alterations and biomarkers, clinical trials and treatment strategies, and future targets for therapy. IMPLICATIONS FOR PRACTICE: The majority of invasive lobular breast cancers (ILCs) are hormone receptor (HR)-positive and low grade. Clinically, ILC is treated similar to HR-positive invasive ductal cancer (IDC). However, ILC differs distinctly from IDC in its clinicopathologic characteristics and molecular alterations. ILC also differs in response to systemic therapy, with studies showing ILC as less sensitive to chemotherapy. Patients with ILC have worse clinical outcomes with late recurrences. Despite these differences, clinical trials treat HR-positive breast cancers as a single disease, and there is an unmet need for studies addressing the unique challenges faced by patients diagnosed with ILC.},
}
@article {pmid33628571,
year = {2021},
author = {Sarawagi, A and Maxwell, J},
title = {Chyle Leak after Right Axillary Lymph Node Dissection in a Patient with Breast Cancer.},
journal = {Case reports in surgery},
volume = {2021},
number = {},
pages = {8812315},
pmid = {33628571},
issn = {2090-6900},
abstract = {BACKGROUND: A female patient was diagnosed with a right-sided chyle leak following right skin sparing mastectomy, axillary lymph node dissection, and immediate tissue expander placement in the setting of invasive ductal carcinoma status post neoadjuvant chemotherapy. Summary. Our patient underwent a level I and II right axillary lymph node dissection followed by an axillary drain placement. On the first postoperative day, a change from serosanguinous to milky fluid in this drain was noted. The patient was diagnosed with a chyle leak based on the milky appearance and elevated triglyceride levels in the fluid. While chyle leaks are rare after an axillary dissection and even rarer to present on the right side, it is a complication of which breast surgeons should be aware. The cause of this complication is thought to be due to injury of the main thoracic duct, its branches, the subclavian duct, or its tributaries. Management is usually conservative; however, awareness of this potential complication even on the right side is of the utmost importance.<br><br>CONCLUSION: Chyle leaks are an uncommon complication of axillary node dissections and even rarer for them to present on the right side. It can be diagnosed by monitoring the drainage for changes in appearance and volume and by conducting supporting laboratory tests. Conservative management is generally suggested.},
}
@article {pmid33626496,
year = {2021},
author = {Lozano, R and Salles, DC and Sandhu, S and Aragón, IM and Thorne, H and López-Campos, F and Rubio-Briones, J and Gutierrez-Pecharroman, AM and Maldonado, L and di Domenico, T and Sanz, A and Prieto, JD and García, I and Pacheco, MI and Garcés, T and Llacer, C and Romero-Laorden, N and Zambrana, F and López-Casas, PP and Lorente, D and Mateo, J and Pritchard, CC and Antonarakis, ES and Olmos, D and Lotan, TL and Castro, E},
title = {Association between BRCA2 alterations and intraductal and cribriform histologies in prostate cancer.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {147},
number = {},
pages = {74-83},
doi = {10.1016/j.ejca.2021.01.027},
pmid = {33626496},
issn = {1879-0852},
support = {R01 CA185297/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; BRCA2 Protein/*genetics ; Biomarkers, Tumor/*genetics ; Case-Control Studies ; DNA Mutational Analysis ; Gene Deletion ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; *Mutation ; Neoplasm Grading ; PTEN Phosphohydrolase/genetics ; Phenotype ; Prostatic Neoplasms/*genetics/pathology ; Risk Assessment ; Risk Factors ; Spain ; },
abstract = {BACKGROUND: Intraductal (IDC) and cribriform (CRIB) histologies in prostate cancer have been associated with germline BRCA2 (gBRCA2) mutations in small retrospective series, leading to the recommendation of genetic testing for patients with IDC in the primary tumour.<br><br>PATIENTS AND METHODS: To examine the association of gBRCA2 mutations and other tumour molecular features with IDC and/or cribriform (CRIB) histologies, we conducted a case-control study in which primary prostate tumours from 58 gBRCA2 carriers were matched (1:2) by Gleason Grade Group and specimen type to 116 non-carriers. Presence/absence of IDC and CRIB morphologies was established by two expert uropathologists blinded to gBRCA2 status. Fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect BRCA2 alterations, PTEN deletions and TMPRSS2-ERG fusions. Chi-squared tests were used to compare the frequency of IDC and CRIB in gBRCA2 carriers and controls&#xa0;and to assess associations with other variables. Logistic regression models were constructed to identify independent factors associated with both histology patterns.<br><br>RESULTS: No significant differences between gBRCA2 carriers and non-carriers were observed in the prevalence of IDC (36% gBRCA2 versus 50% non-carriers, p&#xa0;=&#xa0;0.085) or CRIB (53% gBRCA2 versus 43% non-carriers p&#xa0;=&#xa0;0.197) patterns. However, IDC histology was independently associated with bi-allelic BRCA2 alterations (OR 4.3, 95%CI 1.1-16.2) and PTEN homozygous loss (OR 5.2, 95%CI 2.1-13.1). CRIB morphology was also independently associated with bi-allelic BRCA2 alterations (OR 5.6, 95%CI 1.7-19.3).<br><br>CONCLUSIONS: While we found no association between gBRCA2 mutations and IDC or CRIB histologies, bi-allelic BRCA2 loss in primary prostate tumours was significantly associated with both variant morphologies, independently of other clinical-pathologic factors.},
}
@article {pmid33625616,
year = {2021},
author = {Chandrika, M and Chua, PJ and Muniasamy, U and Huang, RYJ and Thike, AA and Ng, CT and Tan, PH and Yip, GW and Bay, BH},
title = {Prognostic significance of phosphoglycerate dehydrogenase in breast cancer.},
journal = {Breast cancer research and treatment},
volume = {186},
number = {3},
pages = {655-665},
pmid = {33625616},
issn = {1573-7217},
support = {NMRC/CIRG/1370/2013//National Medical Research Council/ ; },
mesh = {*Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; *Phosphoglycerate Dehydrogenase/genetics ; Prognosis ; Serine ; },
abstract = {PURPOSE: Breast cancer is the most common type of cancer affecting women worldwide. Phosphoglycerate dehydrogenase (PHGDH) is an oxidoreductase in the serine biosynthesis pathway. Although it has been reported to affect growth of various tumors, its role in breast cancer is largely unknown. This study aimed to analyze the expression of PHGDH in breast cancer tissue samples and to determine if PHGDH regulates breast cancer cell proliferation.<br><br>METHODS: Tissue microarrays consisting of 305 cases of breast invasive ductal carcinoma were used for immunohistochemical evaluation of PHGDH expression. The role of PHGDH in breast cancer was investigated in vitro by knocking down its expression and determining the effect on cell proliferation and cell cycling, and in ovo by using a chorioallantoic membrane (CAM) assay.<br><br>RESULTS: Immunohistochemical examination showed that PHGDH is mainly localized in the cytoplasm of breast cancer cells and significantly associated with higher cancer grade, larger tumor size, increased PCNA expression, and lymph node positivity. Analysis of the GOBO dataset of 737 patients demonstrated that increased PHGDH expression was associated with poorer overall survival. Knockdown of PHGDH expression in breast cancer cells in vitro resulted in a decrease in cell proliferation, reduction in cells entering the S phase of the cell cycle, and downregulation of various cell cycle regulatory genes. The volume of breast tumor in an in ovo CAM assay was found to be smaller when PHGDH was silenced.<br><br>CONCLUSION: The findings suggest that PHGDH has a regulatory role in breast cancer cell proliferation and may be a potential prognostic marker and therapeutic target in breast cancer.},
}
@article {pmid33621744,
year = {2021},
author = {Gupta, V and Agarwal, P and Deshpande, P},
title = {Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer.},
journal = {Annals of diagnostic pathology},
volume = {52},
number = {},
pages = {151722},
doi = {10.1016/j.anndiagpath.2021.151722},
pmid = {33621744},
issn = {1532-8198},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/pathology ; Carcinoma, Lobular/diagnosis/epidemiology/pathology ; Cross-Sectional Studies ; DNA Methylation ; Disease Progression ; Epigenesis, Genetic/*genetics ; Female ; Humans ; India/epidemiology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging/methods ; Phyllodes Tumor/diagnosis/epidemiology/pathology ; Prognosis ; Promoter Regions, Genetic/*genetics ; Tumor Suppressor Proteins/*genetics ; },
abstract = {BACKGROUND: Breast cancer is the most common malignancy in women caused by genetic and epigenetic changes. Promoter DNA methylation in tumor suppressor gene plays a major role in breast cancer. The study determined the association of promoter DNA methylation of RASSF1A gene with clinicopathological features in tumor and non-tumor tissue.<br><br>MATERIALS AND METHODS: A cross sectional study was conducted in the Department of Pathology, Government Institute of Medical Sciences, Greater Noida and Molecular Pathology Laboratory, Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences. Two sections, one from tumor and the other from non-tumor tissue, were obtained and processed for DNA extraction and bisulphite conversion. Methylation specific PCR was done and results of RASSF1A promoter methylation were statistically correlated with clinicopathological features.<br><br>RESULTS: Of the 27 breast cancer tissue, 22 showed invasive ductal carcinoma, one showed invasive lobular carcinoma, another showed ductal carcinoma in situ and three cases showed malignant phyllodes tumor of breast. DNA promoter methylation was found in all the cases. 93% of tumor tissue samples and 67% of the non-tumor tissue samples were found to be aberrantly methylated. Tumor size and histological grade were found to be significantly (p-val <0.05) associated with the RASSF1A gene promoter methylation.<br><br>CONCLUSION: A significant association of higher tumor size and tumor histological grade with promoter methylation of RASSF1A gene exists suggestive of its being an important determinant of prognostic staging. This critical event in tumorigenesis may be of clinical utility in assessing breast cancer progression.<br><br>MICRO ABSTRACT: The study focuses on the RASSF1A gene promoter methylation and its impact on the clinicopathological features in Indian breast cancer patients highlighting the differences from other genetically different population. We found that RASFF1A gene methylation has significant impact on tumor size and tumor grade. The work carries high significance because it addresses the DNA methylation of tumor suppressor gene in relevance of breast cancer. It may also be the first such report on Indian patients with breast cancer.},
}
@article {pmid33611829,
year = {2021},
author = {Huang, D and Zhou, B and Luo, ZZ and Yu, SC and Tang, B},
title = {Cigarette smoke extract promotes DNA methyltransferase 3a expression in dendritic cells, inducing Th-17/Treg imbalance via the c-Jun/allograft inflammatory factor 1 axis.},
journal = {The Kaohsiung journal of medical sciences},
volume = {37},
number = {7},
pages = {594-603},
pmid = {33611829},
issn = {2410-8650},
support = {//The Science and Technology Plan of Jiangxi Province Health Committee, Grant/Award Number: 20204366/ ; //The Science and Technology Plan of Jiangxi Provincial Health and Family Planning Committee, Grant/Award Number: 20181001/ ; 20204366//The Science and Technology Plan of Jiangxi Province Health Committee/ ; 20181001//The Science and Technology Plan of Jiangxi Provincial Health and Family Planning Committee/ ; },
mesh = {Allografts ; Animals ; Anthracenes/pharmacology ; CD4-Positive T-Lymphocytes/cytology ; Calcium-Binding Proteins/*metabolism ; Cell Differentiation ; Cells, Cultured ; DNA Methyltransferase 3A/*metabolism ; Dendritic Cells/metabolism ; Disease Models, Animal ; Enzyme Inhibitors/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Microfilament Proteins/*metabolism ; Proto-Oncogene Proteins c-jun/*metabolism ; Pulmonary Disease, Chronic Obstructive/genetics ; Signal Transduction ; *Smoke ; Smoking/*adverse effects ; T-Lymphocytes, Regulatory/*metabolism ; Tetrazolium Salts/pharmacology ; Th17 Cells/metabolism ; Thiazoles/pharmacology ; },
abstract = {Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder. Although numerous studies on COPD have been conducted, therapeutic strategies for COPD are limited, and its pathological mechanism is still unclear. The present study aimed to explore the role of DNA methyltransferase 3a (DNMT3a) in dendritic cells (DCs) and the possible role of the Th-17/Treg cell balance in COPD. Immature DCs (iDCs) were induced and cocultured with CD4[+] T cells. An in vitro COPD model was established by treatment with cigarette smoke extract (CSE). DNMT3a or allograft inflammatory factor 1 (AIF1) and c-Jun N-terminal kinase (JNK) were inhibited and overexpressed, respectively, by transfection with sh-DNMT3a or sh-AIF1 and JNK overexpression plasmids. The 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure cell viability. The Th17/Treg cell ratio was determined by flow cytometry. The expression levels of DNMT3a, c-Jun and AIF1 were measured using RT-qPCR or western blotting. Chromatin immunoprecipitation (CHIP) was used to confirm the interaction between c-Jun and the AIF1 promoter region. CSE stimulation promoted the expression of DNMT3a, and AIF1, and the ratio of p-c-Jun/c-Jun in iDCs. Besides, the iDC-mediated differentiation of Th17 cells was in a dose-dependent manner. However, knockdown of DNMT3a or AIF1 reversed the above effects caused by CSE. Inhibition of c-Jun signaling by treatment with the JNK inhibitor SP600125 also suppressed the iDC-mediated differentiation of Th17 cells, which was promoted by CSE. CHIP analysis showed that c-Jun could bind to the promoter region of AIF1. DNMT3a could regulate the iDC-mediated Th17/Treg balance by regulating the c-Jun/AIF1 axis.},
}
@article {pmid33608011,
year = {2021},
author = {O'Donnell, AJ and Reece, SE},
title = {Ecology of asynchronous asexual replication: the intraerythrocytic development cycle of Plasmodium berghei is resistant to host rhythms.},
journal = {Malaria journal},
volume = {20},
number = {1},
pages = {105},
pmid = {33608011},
issn = {1475-2875},
support = {UF110155//The Royal Society/ ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; NF140517//The Royal Society/ ; RGP0046/2013//Human Frontier Science Program/ ; },
mesh = {Animals ; Anopheles/parasitology/*physiology ; *Circadian Rhythm ; Erythrocytes/parasitology ; Female ; Mosquito Vectors/parasitology/*physiology ; Plasmodium berghei/growth &amp; development/*physiology ; *Reproduction, Asexual ; },
abstract = {BACKGROUND: Daily periodicity in the diverse activities of parasites occurs across a broad taxonomic range. The rhythms exhibited by parasites are thought to be adaptations that allow parasites to cope with, or exploit, the consequences of host activities that follow daily rhythms. Malaria parasites (Plasmodium) are well-known for their synchronized cycles of replication within host red blood cells. Whilst most species of Plasmodium appear sensitive to the timing of the daily rhythms of hosts, and even vectors, some species present no detectable rhythms in blood-stage replication. Why the intraerythrocytic development cycle (IDC) of, for example Plasmodium chabaudi, is governed by host rhythms, yet seems completely independent of host rhythms in Plasmodium berghei, another rodent malaria species, is mysterious.<br><br>METHODS: This study reports a series of five experiments probing the relationships between the asynchronous IDC schedule of P. berghei and the rhythms of hosts and vectors by manipulating host time-of-day, photoperiod and feeding rhythms.<br><br>RESULTS: The results reveal that: (i) a lack coordination between host and parasite rhythms does not impose appreciable fitness costs on P. berghei; (ii) the IDC schedule of P. berghei is impervious to host rhythms, including altered photoperiod and host-feeding-related rhythms; (iii) there is weak evidence for daily rhythms in the density and activities of transmission stages; but (iv), these rhythms have little consequence for successful transmission to mosquitoes.<br><br>CONCLUSIONS: Overall, host rhythms do not affect the performance of P. berghei and its asynchronous IDC is resistant to the scheduling forces that underpin synchronous replication in closely related parasites. This suggests that natural variation in the IDC schedule across species represents different parasite strategies that maximize fitness. Thus, subtle differences in the ecological interactions between parasites and their hosts/vectors may select for the evolution of very different IDC schedules.},
}
@article {pmid33605547,
year = {2021},
author = {Xu, F and Gao, Y and Diao, X and Li, J and Jiang, H and Zhao, H},
title = {Diagnostic value of sialyl-Tn immunocytochemistry in breast cancer presenting with pathological nipple discharge.},
journal = {Cancer medicine},
volume = {10},
number = {5},
pages = {1783-1790},
pmid = {33605547},
issn = {2045-7634},
mesh = {Adult ; Antigens, Tumor-Associated, Carbohydrate/*analysis ; Biomarkers, Tumor/analysis ; Biopsy ; Breast/immunology/pathology ; Breast Neoplasms/complications/*immunology/pathology ; Carcinoma, Ductal, Breast/complications/*immunology/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*immunology/pathology ; Confidence Intervals ; Female ; Humans ; Hyperplasia/immunology/pathology ; Immunohistochemistry ; Logistic Models ; Nipple Discharge/*immunology ; Odds Ratio ; Papilloma, Intraductal/complications/*immunology/pathology ; Receptor, ErbB-2/analysis ; Risk Factors ; Sensitivity and Specificity ; },
abstract = {BACKGROUND: Mucin-associated sialyl-Tn (sTn) antigen is overexpressed and related with adverse outcome in breast cancer (BC). The role of sTn in BC has not been well defined in pathological nipple discharge (PND) cytology. The authors examined sTn immunocytochemistry (ICC) in PND to determine whether it could be a biomarker of malignancy or aggressive disease.<br><br>METHODS: PND was subjected to immunocytochemical staining for sTn antigen expression and thinprep cytology test (TCT) for enhancing the sensitivity and specificity. The examination data was compared with histological findings of subsequent biopsy specimens. Logistic regression analysis was used to determine which factors were most associated with malignant breast lesions.<br><br>RESULTS: PND specimens were collected including 120 cases of intraductal papilloma, 24 cases of hyperplasia, 45 cases of ductal carcinoma in situ (DCIS), and 48 cases of invasive ductal carcinoma (IDC). STn ICC differentiated BC from benign intraductal lesions with a low sensitivity of 41.9% and a high specificity of 95.8%, but increased in combination with TCT to 64.5% and 100%, respectively. A high degree of concordance was observed between the results of sTn expression in cell smears and histological specimens. Moreover, the sTn expression was strongly associated with HER2-positive IDC (p&#xa0;=&#xa0;0.039). Multivariate logistic analysis showed that positive sTn expression (OR: 14.241, 95%CI: 2.574, 78.794, p&#xa0;=&#xa0;0.010) and accompanying mass (OR: 3.307, 95%CI: 1.073, 10.188, p&#xa0;=&#xa0;0.037) were statistically significant independent risk factors for malignant PND.<br><br>CONCLUSIONS: Mucin-associated sTn expression in PND cytology appears to be a reliable diagnostic marker for BC patients with the chief complaint of malignant nipple discharge and indicates a more aggressive behavior in IDC.},
}
@article {pmid33593316,
year = {2021},
author = {Liu, J and Zheng, X and Han, Z and Lin, S and Han, H and Xu, C},
title = {Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis.},
journal = {BMC cancer},
volume = {21},
number = {1},
pages = {168},
pmid = {33593316},
issn = {1471-2407},
mesh = {Adenocarcinoma/*mortality/pathology/therapy ; Aged ; Breast Neoplasms/*mortality/pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Risk Factors ; SEER Program/*statistics &amp; numerical data ; Survival Rate ; },
abstract = {BACKGROUND: The prognositc factors in patient with invasive cribriform carcinoma (ICC) of breast is still remain controversal. The study aims to establish a nomogram to predict the survival outcomes in patients with ICC based on the Surveillance, Epidemiology and End Results (SEER) database.<br><br>METHODS: We retrieved SEER database for clinical data about patients including ICC and infiltrating ductal carcinoma (IDC) from 2004 to 2015. Kaplan-Meier survival was used to compare the difference survival outcomes between ICC and IDC. ICC patients were randomly allocated to training cohort and validation cohort. A nomogram was built to predict individual patient's 3-year and 5-year survival status for ICC. The established TMN model and the newly established nomogram was further evaluated by the concordance index (C-index) and the decision curve analysis (DCA).<br><br>RESULTS: Comparing the baseline clinical data between IDC and ICC, a significant of smaller tumor mass, less infiltrated lymph nodes, lower metastases rate, better tumor differentiation degree, higher proportion of estrogen receptor (ER) and progesterone receptor (PR) positive and lower rate of chemotherapy and radiotherapy was found in ICC. Age at diagnosis, marriage status, tumor location, T stage, M stage, ER status, surgery were independent significant prognostic factors for the overall survival (OS). A significantly higher C-index was found in nomogram compared with established TNM model in validation cohort.<br><br>CONCLUSIONS: The prognosis of ICC patients is better than that of IDC patients. The nomogram is recommended for future patient with ICC to survival analysis.},
}
@article {pmid33582923,
year = {2021},
author = {Hu, XQ and Peng, L and Wintermark, M and Lipson, JA and Zhang, YR and Gao, Y},
title = {Shear Wave Elastography of Invasive Ductal Carcinoma: Correlations between Shear Wave Velocity and Histological Prognostic Factors.},
journal = {Current medical science},
volume = {41},
number = {1},
pages = {173-179},
pmid = {33582923},
issn = {2523-899X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/classification/*diagnostic imaging/pathology ; Carcinoma, Ductal/classification/*diagnostic imaging/pathology ; Elasticity Imaging Techniques/*methods/standards ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/genetics ; Sensitivity and Specificity ; },
abstract = {The correlations between shear wave velocity (SWV) calculated from virtual touch tissue imaging quantification (VTIQ) technique and histological prognostic factors of invasive ductal carcinoma was investigated. A total of 76 breast tumors histologically confirmed as invasive ductal carcinomas were included in this study. SWV values were measured by VTIQ for each lesion preoperatively or prior to breast biopsy. The maximum values were recorded for statistical analysis. Medical records were reviewed to determine tumor size, histological grade, lymph node status and immunohistochemical results. Tumor subtypes were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative. The correlations between SWV and histological prognostic factors were analyzed. It was found that tumor size showed positive association with SWV (r=0.465, P<0.001). Larger tumors had significantly higher SWV than smaller ones (P=0.001). Histological grade 1 tumors had significantly lower SWV values than those with higher histological grade (P=0.015). The Ki67 expression, tumor subtypes and lymph node status showed no statistically significant correlations with SWV, although triple negative tumors and lymph node-positive tumors showed higher SWV values. It was concluded that tumor size was significantly associated with SWV. Higher histological grade was associated with increased SWV. There was no statistically significant correlations between SWV and other histological prognostic factors.},
}
@article {pmid33581714,
year = {2021},
author = {Saeed, U and Uppal, SR and Piracha, ZZ and Rasheed, A and Aftab, Z and Zaheer, H and Uppal, R},
title = {Evaluation of SARS-CoV-2 antigen-based rapid diagnostic kits in Pakistan: formulation of COVID-19 national testing strategy.},
journal = {Virology journal},
volume = {18},
number = {1},
pages = {34},
pmid = {33581714},
issn = {1743-422X},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Viral/immunology/*isolation &amp; purification ; COVID-19/*diagnosis/epidemiology/immunology/virology ; COVID-19 Serological Testing/*methods ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pakistan/epidemiology ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; SARS-CoV-2/genetics/immunology/*isolation &amp; purification ; Young Adult ; },
abstract = {Rapid diagnosis of SARS-CoV-2 during pandemic enables timely treatment and prevention of COVID-19. Evaluating the accuracy and reliability of rapid diagnostic testing kits is crucial for surveillance and diagnosis of SARS-CoV-2 infections in general population, injection drug users, multi-transfused populations, healthcare workers, prisoners, barbers and other high risk populations. The aim of this study was to evaluate performance and effectiveness of nasopharyngeal swab (NSP) and saliva based rapid antigen detection testing kits in comparison with USFDA approved triple target gold standard real-time polymerase chain reaction. A cross-sectional study was conducted on 33,000 COVID-19 suspected patients. From RT-PCR positive patients, nasopharyngeal swab (NSP) and saliva samples were obtained for evaluation of rapid COVID-19 testing kits (RDT). 100/33,000 (0.3%) of specimens were RT-PCR positive for SARS-CoV-2. Among RT-PCR positive, 62% were males, 34% were females, and 4% were children. The NSP-RDT (Lepu Medical China) analysis revealed 53% reactivity among males, 58% reactivity among females, and 25% reactivity among children. However saliva based RDT (Lepu Medical China) analysis showed 21% reactivity among males and 23% among females, and no reactivity in children. False negative results were significantly more pronounced in saliva based RDT as compared to NSP-RDT. The sensitivity of these NSP-RDT and saliva based RDT were 52% and 21% respectively. The RDTs evaluated in this study showed limited sensitivities in comparison to gold standard RT-PCR, indicating that there is a dire need in Pakistan for development of suitable testing to improve accurate COVID-19 diagnosis in line with national demands.},
}
@article {pmid33567280,
year = {2021},
author = {Greulich, F and Wierer, M and Mechtidou, A and Gonzalez-Garcia, O and Uhlenhaut, NH},
title = {The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers.},
journal = {Cell reports},
volume = {34},
number = {6},
pages = {108742},
pmid = {33567280},
issn = {2211-1247},
mesh = {Animals ; Enhancer Elements, Genetic/*immunology ; Inflammation/genetics/immunology ; Macrophages/*immunology ; Mice ; *Multiprotein Complexes/genetics/immunology ; *RNA-Seq ; *Receptors, Glucocorticoid/genetics/immunology ; Transcription, Genetic/*immunology ; },
abstract = {Glucocorticoids (GCs) are effective anti-inflammatory drugs; yet, their mechanisms of action are poorly understood. GCs bind to the glucocorticoid receptor (GR), a ligand-gated transcription factor controlling gene expression in numerous cell types. Here, we characterize GR's protein interactome and find the SETD1A (SET domain containing 1A)/COMPASS (complex of proteins associated with Set1) histone H3 lysine 4 (H3K4) methyltransferase complex highly enriched in activated mouse macrophages. We show that SETD1A/COMPASS is recruited by GR to specific cis-regulatory elements, coinciding with H3K4 methylation dynamics at subsets of sites, upon treatment with lipopolysaccharide (LPS) and GCs. By chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-seq, we identify subsets of GR target loci that display SETD1A occupancy, H3K4 mono-, di-, or tri-methylation patterns, and transcriptional changes. However, our data on methylation status and COMPASS recruitment suggest that SETD1A has additional transcriptional functions. Setd1a loss-of-function studies reveal that SETD1A/COMPASS is required for GR-controlled transcription of subsets of macrophage target genes. We demonstrate that the SETD1A/COMPASS complex cooperates with GR to mediate anti-inflammatory effects.},
}
@article {pmid33561470,
year = {2021},
author = {Kabay, S and Kabay, SC},
title = {The Sustained Therapeutic Effects of Percutaneous Posterior Tibial Nerve Stimulation in the Treatment of Neurogenic Lower Urinary Tract Symptoms in Patients with Parkinson's Disease: 24-months Clinical and Urodynamic Results.},
journal = {Urology},
volume = {153},
number = {},
pages = {49-55},
doi = {10.1016/j.urology.2021.01.044},
pmid = {33561470},
issn = {1527-9995},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Lower Urinary Tract Symptoms/etiology/*therapy ; Male ; Middle Aged ; Parkinson Disease/complications ; Prospective Studies ; *Tibial Nerve ; Time Factors ; *Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Urinary Bladder, Neurogenic/etiology/*therapy ; Urodynamics ; },
abstract = {OBJECTIVE: To determine the sustained therapeutic effect of percutaneous posterior tibial nerve stimulation (PTNS) treatment in Parkinson's disease patients with detrusor activity during 24 months.<br><br>METHODS: After 12 weeks therapy, PTNS was applied at 14-day intervals for 3 months, 21-day intervals for 3 months and 28-day intervals through 24 months. The patients completed a 3-day voiding diary and ICIQ-SF, OAB-V8, OAB-q SF questionnaires at 3[rd], 6[th], 9[th],12[th] and 24[th] month.<br><br>RESULTS: A total of 76 patients were enrolled in the study. Of these 44 (57.9%) were men and 32 (42.1%) women. The differences of compared parameters at baseline and at the end of 24 months were as follows; daytime frequency decreased by 4.6 voids daily, urge incontinence decreased by 4.2 episodes daily, urgency episodes decreased by 6.2 episodes daily, nocturia decreased by 2.4 voids (P <.001) and voided volume improved by a mean of 71.4 cc (P <.05). When compared with baseline significant improvements were seen in the volume at the first involuntary detrusor contraction (1st IDCV), maximum cystometric capacity (MCC), maximal detrusor pressure at first involuntary detrusor contraction (1st IDC Pdetmax), maximal detrusor pressure at MCC (MCC Pdetmax), detrusor pressure at maximal flow (PdetQmax) and post-void residual volume (PVR) after PTNS treatment at 3, 12, 24 months (P <.001 for each) except maximal flow rate (Qmax) value (P &#x2c3;.05).<br><br>CONCLUSIONS: These results have demonstrated the significant improvements both on voiding and urodynamic parameters under PTNS treatment with a tapering protocol for during 24-months in Parkinson's disease with detrusor activity.},
}
@article {pmid33554951,
year = {2020},
author = {Şahin, S and Cakir, A and Gonul, II and Seckin, S and Uluoglu, O},
title = {Clinicopathological significance of insulin-like growth factor-1 receptor expression in breast cancer.},
journal = {Annali italiani di chirurgia},
volume = {91},
number = {},
pages = {583-591},
pmid = {33554951},
issn = {2239-253X},
mesh = {Biomarkers, Tumor ; *Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/genetics ; Prognosis ; Receptor, IGF Type 1/*genetics ; },
abstract = {OBJECTIVE: Insulin-like growth factor 1 receptor (IGF1R) is a receptor protein tyrosine kinase that is claimed to be related with tumor development and progression of breast cancer with some conflicting results in the literature. The aims of the study are to investigate expression of IGF1R, and correlate with clinicopathological parameters to clarify the significance of IGF1R on breast cancer.<br><br>MATERIAL AND METHODS: IGF1R and Ki67 were applied immunohistochemically to the tissue microarray sections of 370 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings [ER, PR, HER2, CK5/6, and CK14] statistically.<br><br>RESULTS: IGF1R overexpression showed direct correlation with Ki67 index (P=0.028), HER2 positivity (P=0.001), mitotic count (P=0.004), tumor grade (P=0.015), and geographic necrosis (P=0.023); and negative correlation with ER positivity (P=0.003). There was statistically significant difference between IGF1R expression and the molecular subtypes (P<0.001), mostly HER2+ phenotype. IGF1R expression was found to be higher in invasive ductal carcinoma (IDC) than invasive lobular carcinoma (ILC) (P=0.036). Both IGF1R and Ki67 expression were negatively correlated with disease-free survival (DFS) (P=0.020, P=0.023, respectively) and overall survival (OS) [P<0.001, each] rates. The inverse association between IGF1R overexpression and OS rate was also supported by multivariate analyses (P=0.025).<br><br>CONCLUSIONS: Overexpression of IGF1R was found to be directly correlated with shorter DFS and OS as well as some clinicopathological features associated with adverse prognosis such as higher Ki67 index, mitotic count, tumor grade, presence of geographic necrosis, HER2 positivity, ER negativity, HER2+ molecular subtype, histological tumor type of IDC rather than ILC. Thus, IGF1R might be considered as an useful target for comprehensive future anti-tumor therapy investigations. Additionally, using IGF1R as well as Ki67 as a part of routine pathology practice might be fruitful in breast cancer therapy and prediction of prognosis.<br><br>KEY WORDS: Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.},
}
@article {pmid33536239,
year = {2021},
author = {Bühler, L and Maida, A and Vogl, ES and Georgiadi, A and Takacs, A and Kluth, O and Schürmann, A and Feuchtinger, A and von Toerne, C and Tsokanos, FF and Klepac, K and Wolff, G and Sakurai, M and Ekim Üstünel, B and Nawroth, P and Herzig, S},
title = {Lipocalin 13 enhances insulin secretion but is dispensable for systemic metabolic control.},
journal = {Life science alliance},
volume = {4},
number = {4},
pages = {},
pmid = {33536239},
issn = {2575-1077},
mesh = {Animals ; Biomarkers ; *Energy Metabolism ; Fluorescent Antibody Technique ; Gene Expression ; Gene Knockdown Techniques ; Glucose/metabolism ; *Insulin Secretion ; Islets of Langerhans/cytology/metabolism ; Lipid Metabolism ; Lipocalins/blood/*genetics/*metabolism ; Liver/metabolism ; Male ; Mice ; Obesity/etiology/metabolism ; },
abstract = {Members of the lipocalin protein family serve as biomarkers for kidney disease and acute phase inflammatory reactions, and are under preclinical development for the diagnosis and therapy of allergies. However, none of the lipocalin family members has made the step into clinical development, mostly due to their complex biological activity and the lack of in-depth mechanistic knowledge. Here, we show that the hepatokine lipocalin 13 (LCN13) triggers glucose-dependent insulin secretion and cell proliferation of primary mouse islets. However, inhibition of endogenous LCN13 expression in lean mice did not alter glucose and lipid homeostasis. Enhanced hepatic secretion of LCN13 in either diet-induced or genetic obesity led to no discernible impact on systemic glucose and lipid metabolism, neither in preventive nor therapeutic setting. Of note, loss or forced LCN13 hepatic secretion did not trigger any compensatory regulation of related lipocalin family members. Together, these data are in stark contrast to the suggested gluco-regulatory and therapeutic role of LCN13 in obesity, and imply complex regulatory steps in LCN13 biology at the organismic level mitigating its principal insulinotropic effects.},
}
@article {pmid33534078,
year = {2021},
author = {Oses, G and Cases, C and Valduvieco, I and Farrús, B and Alonso, I and Caparrós, X and Mases, J and Muñoz-Guglielmetti, D and Biete, A and Castro, C and Escudero, E and Molina, M and Herreros, A and Saez, J and Mollà, M},
title = {Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.},
journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico},
volume = {23},
number = {8},
pages = {1593-1600},
pmid = {33534078},
issn = {1699-3055},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*radiation effects ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/secondary/surgery ; Electrons/*therapeutic use ; Female ; Fibrosis/pathology ; Humans ; Intraoperative Period ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/prevention &amp; control ; Postoperative Complications ; Prospective Studies ; Radiation Injuries/pathology ; Radiotherapy Dosage ; Treatment Outcome ; },
abstract = {PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost.<br><br>MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12&#xa0;Gy boost was prescribed to 42 patients and 4 patients received a 20&#xa0;Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0.<br><br>RESULTS: The median age was 64.5&#xa0;years (40-90). The median follow-up was 62&#xa0;months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16&#xa0;mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema.<br><br>CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.},
}
@article {pmid33530236,
year = {2021},
author = {Liu, N and Li, S and Jia, J and Qiao, Y and Li, Y},
title = {Advanced breast cancer with cachexia: A case report.},
journal = {Medicine},
volume = {100},
number = {4},
pages = {e24397},
pmid = {33530236},
issn = {1536-5964},
mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*complications/therapy ; Cachexia/etiology/*therapy ; Fatal Outcome ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; },
abstract = {RATIONALE: Cachexia is a clinically relevant syndrome in cancer that is associated with reduced tolerance to anticancer therapy, reduced quality of life, and reduced survival rates. Cachexia is most prevalent in pancreatic, gastric, colorectal, lung, and head and neck cancers. It is rarely documented in breast cancer patients.<br><br>PATIENT CONCERNS: In our case report of a breast cancer patient with bone metastasis who was monitored throughout the course of her treatment, we document the development of cachexia using image analyses in relation to her metastatic burden. In the 2-year period, from April 10, 2015, to February 09, 2017, she lost 16% of her baseline weight. During this time, she was repeatedly hospitalized for chest tightness, edema of both lower limbs, numbness and pain in the left lower extremity and backache.<br><br>DIAGNOSES: Our patient was a 46-year-old premenopausal woman when she was firstly diagnosed. Several years after surgery for invasive ductal carcinoma of the left breast, she had multiple systemic bone metastases (the thoracic spine, the ribs, etc), lung metastasis, bilateral axillary lymph node metastasis, and metastasis of the right neck lymph node in IV area.<br><br>INTERVENTIONS: The patient completed 6 cycles of postoperative adjuvant chemotherapy and long-term endocrine therapy after a radical mastectomy for breast cancer. During the fourth progression, 6 cycles of rescue chemotherapy were performed. Local lumbosacral radiotherapy, and lumbar surgery were carried out to relieve symptoms after several progressions.<br><br>OUTCOMES: She became extremely thin, weighing only 50&#x200a;kg at admission on July 23, 2018. This eventually led to multiple organ failure and death.<br><br>LESSONS: We noted a strong negative correlation between the abdominal muscle area and the metastatic tumor area at the second lumbar vertebral (L2) level. The monitoring of abdominal muscle wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and the extent of metastatic disease. This is especially true with breast cancer, where metastasis to bone is frequent. Our data from a computational tomography radiological quantification, may provide clinicians with early indications of the extent of cachexia in metastatic breast cancer patients.},
}
@article {pmid33513952,
year = {2021},
author = {O'Rourke, JA and Graham, MA},
title = {Gene Expression Responses to Sequential Nutrient Deficiency Stresses in Soybean.},
journal = {International journal of molecular sciences},
volume = {22},
number = {3},
pages = {},
pmid = {33513952},
issn = {1422-0067},
support = {Project 5030-21220-006-00D//United States Department of Agriculture, Agricultural Research Service/ ; },
mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant/genetics ; Iron/metabolism ; Nutrients/*metabolism ; Phosphates/metabolism ; Plant Roots/genetics/growth &amp; development ; Glycine max/*genetics/growth &amp; development/metabolism ; Stress, Physiological/*genetics ; Transcriptome/*genetics ; },
abstract = {Throughout the growing season, crops experience a multitude of short periods of various abiotic stresses. These stress events have long-term impacts on plant performance and yield. It is imperative to improve our understanding of the genes and biological processes underlying plant stress tolerance to mitigate end of season yield loss. The majority of studies examining transcriptional changes induced by stress focus on single stress events. Few studies have been performed in model or crop species to examine transcriptional responses of plants exposed to repeated or sequential stress exposure, which better reflect field conditions. In this study, we examine the transcriptional profile of soybean plants exposed to iron deficiency stress followed by phosphate deficiency stress (-Fe-Pi). Comparing this response to previous studies, we identified a core suite of genes conserved across all repeated stress exposures (-Fe-Pi, -Fe-Fe, -Pi-Pi). Additionally, we determined transcriptional response to sequential stress exposure (-Fe-Pi) involves genes usually associated with reproduction, not stress responses. These findings highlight the plasticity of the plant transcriptome and the complexity of unraveling stress response pathways.},
}
@article {pmid33495219,
year = {2021},
author = {Tewari, SG and Rajaram, K and Swift, RP and Reifman, J and Prigge, ST and Wallqvist, A},
title = {Metabolic Survival Adaptations of Plasmodium falciparum Exposed to Sublethal Doses of Fosmidomycin.},
journal = {Antimicrobial agents and chemotherapy},
volume = {65},
number = {4},
pages = {},
pmid = {33495219},
issn = {1098-6596},
support = {R01 AI065853/AI/NIAID NIH HHS/United States ; R01 AI125534/AI/NIAID NIH HHS/United States ; T32 AI007417/AI/NIAID NIH HHS/United States ; },
mesh = {*Antimalarials/therapeutic use ; *Apicoplasts ; *Fosfomycin/analogs &amp; derivatives/pharmacology/therapeutic use ; Humans ; *Malaria, Falciparum/drug therapy ; Plasmodium falciparum/genetics ; },
abstract = {The malaria parasite Plasmodium falciparum contains the apicoplast organelle that synthesizes isoprenoids, which are metabolites necessary for posttranslational modification of Plasmodium proteins. We used fosmidomycin, an antibiotic that inhibits isoprenoid biosynthesis, to identify mechanisms that underlie the development of the parasite's adaptation to the drug at sublethal concentrations. We first determined a concentration of fosmidomycin that reduced parasite growth by ∼50% over one intraerythrocytic developmental cycle (IDC). At this dose, we maintained synchronous parasite cultures for one full IDC and collected metabolomic and transcriptomic data at multiple time points to capture global and stage-specific alterations. We integrated the data with a genome-scale metabolic model of P. falciparum to characterize the metabolic adaptations of the parasite in response to fosmidomycin treatment. Our simulations showed that, in treated parasites, the synthesis of purine-based nucleotides increased, whereas the synthesis of phosphatidylcholine during the trophozoite and schizont stages decreased. Specifically, the increased polyamine synthesis led to increased nucleotide synthesis, while the reduced methyl-group cycling led to reduced phospholipid synthesis and methyltransferase activities. These results indicate that fosmidomycin-treated parasites compensate for the loss of prenylation modifications by directly altering processes that affect nucleotide synthesis and ribosomal biogenesis to control the rate of RNA translation during the IDC. This also suggests that combination therapies with antibiotics that target the compensatory response of the parasite, such as nucleotide synthesis or ribosomal biogenesis, may be more effective than treating the parasite with fosmidomycin alone.},
}
@article {pmid33484951,
year = {2021},
author = {Lemmer, IL and Willemsen, N and Hilal, N and Bartelt, A},
title = {A guide to understanding endoplasmic reticulum stress in metabolic disorders.},
journal = {Molecular metabolism},
volume = {47},
number = {},
pages = {101169},
pmid = {33484951},
issn = {2212-8778},
mesh = {Adipocytes/metabolism ; Animals ; Autophagy ; Diabetes Mellitus, Type 2/metabolism ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress/*physiology ; Humans ; Inflammation/metabolism ; Insulin Resistance ; Lipid Metabolism ; Metabolic Diseases/*metabolism ; Obesity/metabolism ; Proteins/metabolism ; Ubiquitin ; Unfolded Protein Response ; },
abstract = {BACKGROUND: The global rise of metabolic disorders, such as obesity, type 2 diabetes, and cardiovascular disease, demands a thorough molecular understanding of the cellular mechanisms that govern health or disease. The endoplasmic reticulum (ER) is a key organelle for cellular function and metabolic adaptation and, therefore disturbed ER function, known as "ER stress," is a key feature of metabolic disorders.<br><br>SCOPE OF REVIEW: As ER stress remains a poorly defined phenomenon, this review provides a general guide to understanding the nature, etiology, and consequences of ER stress in metabolic disorders. We define ER stress by its type of stressor, which is driven by proteotoxicity, lipotoxicity, and/or glucotoxicity. We discuss the implications of ER stress in metabolic disorders by reviewing evidence implicating ER phenotypes and organelle communication, protein quality control, calcium homeostasis, lipid and carbohydrate metabolism, and inflammation as key mechanisms in the development of ER stress and metabolic dysfunction.<br><br>MAJOR CONCLUSIONS: In mammalian biology, ER is a phenotypically and functionally diverse platform for nutrient sensing, which is critical for cell type-specific metabolic control by hepatocytes, adipocytes, muscle cells, and neurons. In these cells, ER stress is a distinct, transient state of functional imbalance, which is usually resolved by the activation of adaptive programs such as the unfolded protein response (UPR), ER-associated protein degradation (ERAD), or autophagy. However, challenges to proteostasis also impact lipid and glucose metabolism and vice versa. In the ER, sensing and adaptive measures are integrated and failure of the ER to adapt leads to aberrant metabolism, organelle dysfunction, insulin resistance, and inflammation. In conclusion, the ER is intricately linked to a wide spectrum of cellular functions and is a critical component in maintaining and restoring metabolic health.},
}
@article {pmid33478862,
year = {2021},
author = {Zhang, H and Ge, XY and Qiao, HQ},
title = {Analysis of prognostic risk factors in 3427 patients with invasive ductal carcinoma of breast: Results based on the SEER database.},
journal = {Asian journal of surgery},
volume = {44},
number = {3},
pages = {577-579},
doi = {10.1016/j.asjsur.2020.12.014},
pmid = {33478862},
issn = {0219-3108},
mesh = {Breast/pathology ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Neoplasm Staging ; Prognosis ; Risk Factors ; },
}
@article {pmid33468810,
year = {2020},
author = {Ishihara, S and Kashiwagi, S and Asano, Y and Kawano, Y and Kouhashi, R and Yabumoto, A and Tauchi, Y and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M},
title = {[A Case of Dermatitis Caused by Metronidazole Gel That Needed to Be Differentiated from Breast Cancer Skin Metastasis].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {47},
number = {13},
pages = {2089-2091},
pmid = {33468810},
issn = {0385-0684},
mesh = {Aged ; Axilla ; *Breast Neoplasms/drug therapy ; *Dermatitis/drug therapy/etiology ; Female ; Humans ; Metronidazole ; Trastuzumab/adverse effects ; },
abstract = {Seventy years old woman noticed a mass in her right breast before 3 years. Since she had ulcer bleeding, she visited our hospital. In physical findings, a hemorrhagic about 8 cm mass with an ulcer was found in the upper right breast. Breast ultrasonography revealed a large tumor of approximately 8 cm in the right A area, and needle biopsy revealed invasive ductal carcinoma(ER positive, PgR positive, HER2 positive, Ki-67 low expression). Right axillary lymph node metastasis was confirmed, but no clear distant metastasis was observed. Pretreatment diagnosis was right breast cancer, cT4bN1M0, Stage ⅢB, Luminal HER. Chemotherapy was started with pertuzumab, trastuzumab, and docetaxel, and the tumor was reduced after 6 cycles. Due to side effects, the drug was changed to a molecular targeted drug only and the treatment was continued. However, redness was observed in the entire right breast, and breast cancer skin metastasis was suspected. Since the dermatitis caused by metronidazole gel was also distinguished, the redness was improved when the application was stopped. When confirmed by a patch test, a reaction to metronidazole gel was observed, leading to the diagnosis of dermatitis caused by metronidazole gel.},
}
@article {pmid33462507,
year = {2021},
author = {Gao, R and Bai, S and Henderson, YC and Lin, Y and Schalck, A and Yan, Y and Kumar, T and Hu, M and Sei, E and Davis, A and Wang, F and Shaitelman, SF and Wang, JR and Chen, K and Moulder, S and Lai, SY and Navin, NE},
title = {Delineating copy number and clonal substructure in human tumors from single-cell transcriptomes.},
journal = {Nature biotechnology},
volume = {39},
number = {5},
pages = {599-608},
pmid = {33462507},
issn = {1546-1696},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA240526/CA/NCI NIH HHS/United States ; T32 CA217789/CA/NCI NIH HHS/United States ; R01 CA236864/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Pancreatic Ductal/*genetics/pathology ; *Clonal Evolution ; DNA Copy Number Variations/*genetics ; Gene Expression Regulation, Neoplastic ; Genomics/trends ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation/genetics ; Single-Cell Analysis ; Transcriptome/*genetics ; Tumor Microenvironment/genetics ; },
abstract = {Single-cell transcriptomic analysis is widely used to study human tumors. However, it remains challenging to distinguish normal cell types in the tumor microenvironment from malignant cells and to resolve clonal substructure within the tumor. To address these challenges, we developed an integrative Bayesian segmentation approach called copy number karyotyping of aneuploid tumors (CopyKAT) to estimate genomic copy number profiles at an average genomic resolution of 5 Mb from read depth in high-throughput single-cell RNA sequencing (scRNA-seq) data. We applied CopyKAT to analyze 46,501 single cells from 21 tumors, including triple-negative breast cancer, pancreatic ductal adenocarcinoma, anaplastic thyroid cancer, invasive ductal carcinoma and glioblastoma, to accurately (98%) distinguish cancer cells from normal cell types. In three breast tumors, CopyKAT resolved clonal subpopulations that differed in the expression of cancer genes, such as KRAS, and signatures, including epithelial-to-mesenchymal transition, DNA repair, apoptosis and hypoxia. These data show that CopyKAT can aid in the analysis of scRNA-seq data in a variety of solid human tumors.},
}
@article {pmid33462216,
year = {2021},
author = {Deshpande, D and Agarwal, N and Fleming, T and Gaveriaux-Ruff, C and Klose, CSN and Tappe-Theodor, A and Kuner, R and Nawroth, P},
title = {Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {426},
pmid = {33462216},
issn = {2041-1723},
mesh = {Aged ; Aged, 80 and over ; Animals ; Diabetes Mellitus, Experimental/chemically induced/*complications ; Diabetic Neuropathies/etiology/*pathology ; Female ; Ganglia, Spinal/cytology/pathology ; Humans ; Lysosomes ; Male ; Mice ; Mice, Knockout ; Nociception/*physiology ; Pro-Opiomelanocortin/*deficiency/genetics ; Proteolysis ; Receptors, Opioid, mu/genetics/metabolism ; Sensory Receptor Cells/*pathology ; Streptozocin/toxicity ; },
abstract = {Painful neuropathy is a frequent complication in diabetes. Proopiomelanocortin (POMC) is an endogenous opioid precursor peptide, which plays a protective role against pain. Here, we report dysfunctional POMC-mediated antinociception in sensory neurons in diabetes. In streptozotocin-induced diabetic mice the Pomc promoter is repressed due to increased binding of NF-kB p50 subunit, leading to a loss in basal POMC level in peripheral nerves. Decreased POMC levels are also observed in peripheral nervous system tissue from diabetic patients. The antinociceptive pathway mediated by POMC is further impaired due to lysosomal degradation of μ-opioid receptor (MOR). Importantly, the neuropathic phenotype of the diabetic mice is rescued upon viral overexpression of POMC and MOR in the sensory ganglia. This study identifies an antinociceptive mechanism in the sensory ganglia that paves a way for a potential therapy for diabetic neuropathic pain.},
}
@article {pmid33445940,
year = {2020},
author = {Bartovská, Z and Andrle, F and Beran, O and Zlámal, M and Řezáč, D and Murinova, I and Holub, M},
title = {Data from the first wave of Covid-19 from the Central Military Hospital, Prague, Czech Republic.},
journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne},
volume = {69},
number = {4},
pages = {164-171},
pmid = {33445940},
issn = {1210-7913},
mesh = {COVID-19/diagnosis/*epidemiology/therapy ; Czech Republic/epidemiology ; Female ; Hospitals, Military ; Humans ; Male ; Middle Aged ; Retrospective Studies ; United States ; },
abstract = {AIMS: To process data from the first wave of Covid-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) collected in the Infectious Diseases Clinic (IDC) of the First Faculty of Medicine and Central Military Hospital, Prague. To analyse some clinical, diagnostic and therapeutic aspects of Covid-19 in the context of the Czech Republic and to compare them with the data from the most recent literature.<br><br>PATIENTS AND METHODS: This retrospective study analysed data on patients admitted to the IDC between 12 March 2020 and 5 May 2020. The study cohort included 53 patients with Covid-19, 25 females and 28 males, with an average age of 57 years. The parameters analysed were clinical symptoms, average length of hospital stay, complications, and death. Additional data concerned the age, weight, smoking habits, history of comorbidities, and selected laboratory results.&#xa0; These data were compared between groups of patients differing in severity of the course of Covid-19. Finally, imaging findings, serology results, and therapy outcomes were studied. Statistical analysis was performed using the SigmaStat software.<br><br>RESULTS: Eleven (20.8%) patients had a mild course of the disease, 16 (30.2%) patients had a moderate course, 22 (41.5%) patients had a severe course, and four (7.5%) patients had a critical course. The study patients presented with the following clinical symptoms: fever in 88.5% of cases, cough in 84.6% of cases, difficulty breathing in 77.4% of cases, diarrhoea in 23.1% of cases, chest pain in 17.3% of cases, and anosmia in 11.5% of cases. The average length of hospital stay was eight days. The most common complication was a bacterial superinfection, reported in 17 (32.1%) study patients. The overall case fatality rate for Covid-19 in our study was 5.7%. The average age of the study cohort was 57 years, and patients with a severe course of the disease were of older average age than those with a less severe course of the disease (p < 0.05). The predominant comorbidities were hypertension and diabetes mellitus. The analysis of the baseline laboratory data showed significant differences between the groups of patients differing in severity of the course of Covid-19 in CRP, procalcitonin, and d-dimers but not in lymphocyte count. High resolution computed tomography (HRCT) scan of the lungs was performed in 22 patients, and 21 of them had typical findings for Covid-19. The average MuLBSTA score for Covid-19 pneumonia severity in our study cohort was 11.5 points and was not associated with the severity of the course of the disease. Serology tests were performed in 43 study patients, with 29 (67.4%) of them turning out positive in the first test and other five (11.6%) testing positive when retested. Hydroxychloroquine (HCQ) was given experimentally as monotherapy or in combination with azithromycin (AZI) to 24 (45.3%) patients. Two patients on HCQ therapy also received inosinum pranobexum (isoprinosine) for severe lymphopenia, one patient received convalescent plasma, six patients were given AZI alone, and one patient was treated with inosinum pranobexum alone. Altogether 37.7% of study patients were prescribed other antibiotics for confirmed or suspected bacterial superinfection. Standard clinical and pharmaceutical care was provided to patients with particular focus on the safety of off-label drug use. HCQ was with drawn in three patients due to a prolonged corrected QT interval (QTc).<br><br>CONCLUSIONS: In the first wave of the SARS-CoV-2 epidemic, our study patients showed comorbidities and risk factors which are consistent with the international literature, but the course of the disease was mostly moderate to severe, with a low proportion of critically ill patients and fatal outcomes. As soon as new information became available, new diagnostic and therapeutic options were introduced into routine practice. Based on our experience, we are well prepared for a possible second wave of SARS-CoV-2 in terms of the diagnostics, but the therapeutic options still remain very limited.},
}
@article {pmid33443130,
year = {2021},
author = {Trinh, A and Gil Del Alcazar, CR and Shukla, SA and Chin, K and Chang, YH and Thibault, G and Eng, J and Jovanović, B and Aldaz, CM and Park, SY and Jeong, J and Wu, C and Gray, J and Polyak, K},
title = {Genomic Alterations during the In Situ to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System.},
journal = {Molecular cancer research : MCR},
volume = {19},
number = {4},
pages = {623-635},
pmid = {33443130},
issn = {1557-3125},
support = {R35 CA197623/CA/NCI NIH HHS/United States ; U01 CA195469/CA/NCI NIH HHS/United States ; U54 CA209988/CA/NCI NIH HHS/United States ; U54 CA193461/CA/NCI NIH HHS/United States ; U24 CA224331/CA/NCI NIH HHS/United States ; R50 CA211482/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*genetics/*immunology ; Carcinoma, Ductal, Breast/*genetics/*immunology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*immunology ; Female ; Genomics ; Humans ; Immune System ; },
abstract = {The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and recurrent IDC. We demonstrate through combined copy-number and mutational analysis that recurrent IDC can be genetically related to its pure DCIS despite long latency periods and therapeutic interventions. Immune "hot" and "cold" tumors can arise as early as DCIS and are subtype-specific. Topologic analysis showed a similar degree of pan-leukocyte-tumor mixing in both DCIS and IDC but differ when assessing specific immune subpopulations such as CD4 T cells and CD68 macrophages. Tumor-specific copy-number aberrations in MHC-I presentation machinery and losses in 3p, 4q, and 5p are associated with differences in immune signaling in estrogen receptor (ER)-negative IDC. Common oncogenic hotspot mutations in genes including TP53 and PIK3CA are predicted to be neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition, and are associated with differences in immune signaling. We highlight both tumor and immune-specific changes in the transition of pure DCIS to IDC, including genetic changes in tumor cells that may have a role in modulating immune function and assist in immune escape, driving the transition to IDC. IMPLICATIONS: We demonstrate that the in situ to IDC evolutionary bottleneck is shaped by both tumor and immune cells.},
}
@article {pmid33437736,
year = {2020},
author = {Abdolahi, M and Salehi, M and Shokatian, I and Reiazi, R},
title = {Artificial intelligence in automatic classification of invasive ductal carcinoma breast cancer in digital pathology images.},
journal = {Medical journal of the Islamic Republic of Iran},
volume = {34},
number = {},
pages = {140},
pmid = {33437736},
issn = {1016-1430},
abstract = {Background: Breast cancer is one of the most causes of death in women. Early diagnosis and detection of Invasive Ductal Carcinoma (IDC) is an important key for the treatment of IDC. Computer-aided approaches have great potential to improve diagnosis accuracy. In this paper, we proposed a deep learning-based method for the automatic classification of IDC in whole slide images (WSI) of breast cancer. Furthermore, different types of deep neural networks training such as training from scratch and transfer learning to classify IDC were evaluated. Methods: In total, 277524 image patches with 50×50-pixel size form original images were used for model training. In the first method, we train a simple convolutional neural network (named it baseline model) on these images. In the second approach, we used the pre-trained VGG-16 CNN model via feature extraction and fine-tuning for the classification of breast pathology images. Results: Our baseline model achieved a better result for the automatic classification of IDC in terms of F-measure and accuracy (83%, 85%) in comparison with original paper on this data set and achieved a comparable result with a new study that introduced accepted-rejected pooling layer. Also, transfer learning via feature extraction yielded better results (81%, 81%) in comparison with handcrafted features. Furthermore, transfer learning via feature extraction yielded better classification results in comparison with the baseline model. Conclusion: The experimental results demonstrate that using deep learning approaches yielded better results in comparison with handcrafted features. Also, using transfer learning in histopathology image analysis yielded significant results in comparison with training from scratch in much less time.},
}
@article {pmid33433431,
year = {2021},
author = {Xia, Y and Liu, X and Li, W and Zhu, Y},
title = {Potential role of significant GATA3 mutation in male breast cancer responding to endocrine therapy: A case report.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {64},
number = {1},
pages = {161-164},
doi = {10.4103/IJPM.IJPM_160_19},
pmid = {33433431},
issn = {0974-5130},
mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast/pathology ; Breast Neoplasms, Male/diagnostic imaging/*drug therapy/*genetics/secondary ; Endocrine System/drug effects ; GATA3 Transcription Factor/*genetics ; Humans ; Male ; Middle Aged ; *Mutation ; Positron Emission Tomography Computed Tomography ; },
abstract = {A 60-year-old Chinese male with a hard mass, pressure pain, and ulcerous skin under his left axilla was first diagnosed with apocrine carcinoma, most likely metastasis from breast cancer. PET/CT scan detected multiple bone metastasis and enlarged lymph nodes at left axilla, mediastinal area 7, and left pulmonary hilus. Lumpectomy was performed to remove the mass followed by chemotherapy and radiotherapy against focal bone metastasis, left axillary lesion, and left subcutaneous chest wall. PET/CT examination showed progressive disease after the completion of the treatments. Two nontender hard nodules were noticed on the patient's left upper arm and multiple immobile nodules were palpated under his left axillary skin. Immunohistochemistry (HER2++, ER+, PR+, AR-) of the biopsy tissue combined with histopathology indicated invasive ductal carcinoma with neuroendocrine differentiation. Metastatic Luminal B subtype breast cancer was preferred. Anti-estrogen endocrine therapy was then performed and PET/CT scan showed partial remission after one month's fulvestrant administration. Two significant somatic mutations, AR R616H and GATA3 S408Afs*99, were detected in the biopsy tissue by next-generation sequencing. GATA3 is associated with estrogen receptor signaling and was identified as a driver gene of female breast cancer. However, the function of GATA3 in male breast cancer remains controversial. Report of this case hopefully will contribute to exploring the role of GATA3 mutation in molecular mechanisms and endocrine therapy of male breast cancer.},
}
@article {pmid33433407,
year = {2021},
author = {Farrag, MS and Anter, AH and Farrag, NS and Ibrahiem, AT},
title = {"Switch of E-Cadherin to N-Cadherin expression in different molecular subtypes of breast invasive duct carcinomas and its correlation with clinicopathological features".},
journal = {Indian journal of pathology &amp; microbiology},
volume = {64},
number = {1},
pages = {38-46},
doi = {10.4103/IJPM.IJPM_924_19},
pmid = {33433407},
issn = {0974-5130},
mesh = {Antigens, CD/*genetics ; Biomarkers, Tumor ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/classification/*genetics/*pathology/secondary ; Cross-Sectional Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paraffin Embedding ; Prognosis ; Young Adult ; },
abstract = {BACKGROUND: In breast cancer, metastasis and recurrence is the main culprit in treatment failure. This study aimed to explore the role of E-cadherin/N-cadherin Switch in progression, spread and metastasis in breast invasive duct carcinoma.<br><br>MATERIALS AND METHODS: A cross-sectional study on 118 formalinfixed paraffinembedded mastectomy specimens of invasive breast duct carcinoma. Primary antibodies for E-cadherin (monoclonal, clone HECD-1; Zymed Laboratories; dilution 1:600) and N-cadherin (monoclonal, clone 3B9; Zymed Laboratories, Inc., Montrouge, France; dilution 1:200) were applied for all cases. The study revealed that E-cadherin high expression was significantly associated with advanced TNM clinical stage (P = 0.021), and nodal metastasis (P < 0.001). High expression of N-cadherin was significantly positively correlated with tumor sizes (P < 0.00), advanced clinical stage (P < 0.00), and nodal metastasis (P < 0.008). Mean OS was 39.99 months in cases with negative expression versus 41.8 months in cases with positive expression. Mean DFS in cases with positive E. cadh expression was 41.89 months was higher than mean DFS in cases with negative E. cadh expression which was 40.52 months, but it showed no statistical significance (P = 0.57).<br><br>CONCLUSIONS/SIGNIFICANCE: This study demonstrated that loss of E-cadherin and gain of N-cadherin promotes invasion, migration, and metastasis in invasive ductal carcinoma cells. Importantly, these findings may exploit new cancer therapies using N-cadherin antagonists.},
}
@article {pmid33429799,
year = {2021},
author = {Karatas, M and Zengel, B and Durusoy, R and Tasli, F and Adibelli, Z and Simsek, C and Uslu, A},
title = {Clinicopathologic features of single bone metastasis in breast cancer.},
journal = {Medicine},
volume = {100},
number = {1},
pages = {e24164},
pmid = {33429799},
issn = {1536-5964},
mesh = {Adult ; Aged ; Bone Neoplasms/*classification/pathology ; Bone and Bones/*pathology/physiopathology ; Breast Neoplasms/*complications ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis/*physiopathology ; },
abstract = {The most common site for metastasis in patients with breast cancer is the bone. In this case series, we investigated patients whose surgical and medical treatment for primary breast cancer was conducted at our center and first disease recurrence was limited to only 1 bone.We analyzed 910 breast cancer patients, 863 had no metastasis and 47 cases had a single bone metastasis ≥ 6 months after their first diagnosis. Demographic, epidemiological, histopathological and intrinsic tumor subtype differences between the non-metastatic group and the group with solitary bone metastases and their statistical significance were examined. Among established breast cancer risk factors, we studied twenty-nine variables.Three variables (Type of tumor surgery, TNM Stage III tumors and mixed type (invasive ductalcarsinoma + invasive lobular carcinoma) histology) were significant in multivariate logistic regression analysis. Accordingly, the risk of developing single bone metastasis was approximately 15 times higher in patients who underwent mastectomy and 4.8 and 2.8 times higher in those with TNM Stage III tumors and with mixed type (invasive ductal carcinoma + invasive lobular carcinoma) histology, respectively.In conclusion, the risk of developing single bone metastasis is likely in non-metastatic patients with Stage III tumors and possibly in mixed type tumors. Knowing this risk, especially in patients with mixed type tumors, may be instrumental in taking measures with different adjuvant therapies in future studies. Among these, treatment modalities such as prolonged hormone therapy and addition of bisphosphonates to the adjuvant treatments of stage III and mixed breast cancer patients may be considered.},
}
@article {pmid33428505,
year = {2021},
author = {Nevagi, RJ and Good, MF and Stanisic, DI},
title = {Plasmodium infection and drug cure for malaria vaccine development.},
journal = {Expert review of vaccines},
volume = {20},
number = {2},
pages = {163-183},
doi = {10.1080/14760584.2021.1874923},
pmid = {33428505},
issn = {1744-8395},
mesh = {Animals ; Antigens, Protozoan/immunology ; Antimalarials/administration &amp; dosage ; Humans ; Malaria/immunology/parasitology/*prevention &amp; control ; Malaria Vaccines/*administration &amp; dosage/immunology ; Plasmodium/*immunology/parasitology ; },
abstract = {Introduction: Despite decades of research into the development of a vaccine to combat the malaria parasite, a highly efficacious malaria vaccine is not yet available. Different whole parasite-based vaccine approaches, including deliberate Plasmodium infection and drug cure (IDC), have been evaluated in pre-clinical and early phase clinical trials. The advantage of whole parasite vaccines is that they induce immune responses against multiple parasite antigens, thus lowering the impact of antigenic diversity. Deliberate Plasmodium IDC, as a vaccine approach, involves administering infectious, live parasites in combination with an anti-malarial drug, which controls the infection and enables induction of protective immune responses.},
}
@article {pmid33421821,
year = {2021},
author = {Hoshina, H and Takei, H and Sakatani, T and Naito, Z},
title = {CDX2-positive breast cancer presented with axillary lymph node metastases: A case report.},
journal = {Cancer treatment and research communications},
volume = {26},
number = {},
pages = {100300},
doi = {10.1016/j.ctarc.2020.100300},
pmid = {33421821},
issn = {2468-2942},
mesh = {Axilla ; Biopsy, Large-Core Needle ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*diagnosis/pathology/therapy ; CDX2 Transcription Factor/analysis/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Ultrasonography ; },
abstract = {BACKGROUND: The caudal type homeobox 2 transcription factor (CDX2) is a specific and sensitive marker for intestinal carcinoma, but usually not expressed in breast cancer. In CDX2-positive metastatic cancer of occult primary, the origin is highly suspicious of an enteric carcinoma.<br><br>CASE PRESENTATION: A 50-year-old woman complained of enlarged lymph nodes (LNs) in the right axilla. Mammography and ultrasonography scans showed no abnormal findings in her breasts. Core needle biopsy (CNB) revealed metastatic adenocarcinoma. Immunohistochemical staining was positive for CDX2 intensely. The primary tumor was suspicious of intestinal adenocarcinoma. A dynamic contrast-enhanced magnetic resonance imaging scan revealed an accentuated lesion which was detected using a second-look ultrasound, and diagnosed invasive ductal carcinoma by CNB. A partial mastectomy of the right breast with level I and II axillary LN dissection was performed. A few cells of primary cancer were expressed CDX2 and estrogen receptor. The final pathological diagnosis was T1bN3aM0 stage IIIC. The fluorescent double staining showed that CDX2 simultaneously expressed on the Ki67 positive cells of metastatic tumors. The adjuvant treatment included chemotherapy and radiation, followed by tamoxifen administration. The patient survived without any recurrences over the following 36 months.<br><br>CONCLUSIONS: We report a rare case of CDX2-positive metastatic breast cancer in the axillary LNs. As some literatures reported vitamin D pathways induced cancer cell apoptosis and inhibition, these metastatic cells of our case might play the effort of autoregulation of inhibiting progression.},
}
@article {pmid33416185,
year = {2021},
author = {Lu, N and Zhang, M and Lu, L and Liu, YZ and Zhang, HH and Liu, XD},
title = {miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.},
journal = {Oncology reports},
volume = {45},
number = {2},
pages = {706-716},
pmid = {33416185},
issn = {1791-2431},
mesh = {Animals ; Breast/pathology/surgery ; Breast Neoplasms/*genetics/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics/mortality/secondary/surgery ; Cell Line, Tumor ; DNA-Binding Proteins/*genetics ; Disease Progression ; Disease-Free Survival ; Epithelial-Mesenchymal Transition/genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mastectomy ; Mice ; MicroRNAs/genetics/*metabolism ; Neoplasm Recurrence, Local/*epidemiology/genetics ; RNA-Binding Proteins/*genetics ; Xenograft Model Antitumor Assays ; },
abstract = {MicroRNA (miRNA/mir)‑490‑3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR‑490‑3p has been shown to function as a tumor suppressor and promoter in a context‑dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR‑490‑3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor‑adjacent normal tissue specimens (n=20). Its expression was also higher in the more metastatic breast cancer cell line, MDA‑MB‑231, compared to the non‑metastatic breast cancer cell line, MCF7, and the moderately metastatic breast cancer cell line, MDA‑MB‑468. The expression of miR‑490‑3p was induced following transforming growth factor (TGF)‑β‑induced epithelial‑to‑mesenchymal transition (EMT) in MCF10A cells. Gain‑and loss‑of‑function assays revealed that the expression of miR‑490‑3p regulated the proliferation, colony formation, EMT, migration and invasion in vitro, but not the apoptosis of MDA‑MB‑468 and MDA‑MB‑231 cells. The knockdown of miR‑490‑3p expression in MDA‑MB‑231 cells inhibited experimental metastasis in a tumor xenograft assay. As in lung cancer, miR‑490‑3p was found to target and downregulate the expression of the tumor suppressor RNA binding protein poly r(C) binding protein 1 (PCBP1). PCBP1 protein and miR‑490‑3p expression inversely correlated in patients with ductal carcinoma in situ (DCIS; n=10; no nodal involvement) and IDC (n=10; different stages of metastatic progression) with a significantly higher miR‑490‑3p expression in patients with IDC compared to those with DCIS. The expression of miR‑490‑3p was negatively associated with both overall and disease‑free survival in the patients with breast cancer included in the present study. On the whole, the results confirm a pro‑metastatic role of miR‑490‑3p in IDC, establishing it as a biomarker for disease progression in these patients.},
}
@article {pmid33415472,
year = {2022},
author = {Zimmerman-Brenner, S and Pilowsky-Peleg, T and Rachamim, L and Ben-Zvi, A and Gur, N and Murphy, T and Fattal-Valevski, A and Rotstein, M},
title = {Group behavioral interventions for tics and comorbid symptoms in children with chronic tic disorders.},
journal = {European child &amp; adolescent psychiatry},
volume = {31},
number = {4},
pages = {637-648},
pmid = {33415472},
issn = {1435-165X},
mesh = {Behavior Therapy ; Child ; Comorbidity ; Humans ; Severity of Illness Index ; *Tic Disorders/complications/therapy ; *Tics/therapy ; *Tourette Syndrome/complications/therapy ; },
abstract = {Exposure and Response Prevention (ERP), Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT) are effective in reducing tic severity. ERP and HRT have recently gained primary support in a group setting, while CBIT has not been examined similarly. We compared the efficacy of group-CBIT to group-Educational Intervention for Tics (group-EIT) for tics and comorbid symptoms. Children with Tourette Syndrome (TS) or Chronic Tic Disorder (CTD) were randomized to group-CBIT or group-EIT. Tics and comorbid symptoms were assessed in forty-six children pre- and postintervention, and 3-month later. Yale Global Tic Severity Scale (YGTSS) Motor tic severity decreased following both interventions, and was maintained at follow-up for group-CBIT only. The Parent Tic Questionnaire (PTQ) showed significant decrease in total and motor tic severity following group-CBIT only, a gain maintained three months later. YGTSS impairment score decreased following both interventions and was maintained at follow-up. YGTSS vocal tic severity score increased following both interventions, and then decreased significantly at follow up. Co-morbid symptoms including anxiety, behavioral problems, and aggressive behavior decreased following both interventions. Children with behavioral problems benefitted less while children with higher intellectual ability benefit more from intervention. Both group interventions showed efficacy in reducing tic impairment and comorbid symptoms. Group-CBIT was superior to group-EIT in reducing motor tic severity at 3-month follow-up, showing an advantage for tic-focused treatment. Based on the PTQ, group-CBIT was superior to group-EIT in reducing motor, vocal, and total tic scores, a gain maintained three months later. Clinical trial registry information-Group Intervention for Children with Chronic Tics Syndrome: CBIT vs Psychoeducational Intervention URL: http://clinicaltrials.gov , Identifier: NCT02407951, http://www.controlled-trials.com).},
}
@article {pmid33413755,
year = {2020},
author = {Zeng, XQ and Jiang, SS and Peng, YY and Liu, MF and Ye, CS and Dong, JY},
title = {Trastuzumab-Induced Severe Thrombocytopenia:A Case Report and Literature Review.},
journal = {Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih},
volume = {35},
number = {4},
pages = {377-382},
doi = {10.24920/003799},
pmid = {33413755},
issn = {1001-9294},
mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Female ; Humans ; Platelet Count ; Thrombocytopenia/blood/*chemically induced/drug therapy ; Trastuzumab/*adverse effects ; },
abstract = {We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×10[9]/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.},
}
@article {pmid33402291,
year = {2021},
author = {Mnejja, M and Kallel, S and Thabet, W and Regaieg, M and Kallel, R and Boudawara, T and Daoud, J and Hammami, B and Charfeddine, I},
title = {[Ductal carcinomas of the parotid gland].},
journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique},
volume = {25},
number = {2},
pages = {155-160},
doi = {10.1016/j.canrad.2020.06.034},
pmid = {33402291},
issn = {1769-6658},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Ductal/diagnostic imaging/pathology/secondary/*surgery ; Carcinoma, Ductal, Breast/pathology/secondary ; Facial Nerve/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neck Dissection/statistics &amp; numerical data ; Neoplasm Invasiveness ; Parotid Gland/diagnostic imaging/surgery ; Parotid Neoplasms/diagnostic imaging/pathology/secondary/*surgery ; Prognosis ; Retrospective Studies ; Skin Neoplasms/pathology ; },
abstract = {PURPOSE: To describe the clinical, therapeutic and prognostic features of ductal carcinomas of the parotid gland.<br><br>MATERIAL AND METHODS: Five patients with ductal carcinoma of the parotid gland (primary and secondary carcinoma) treated, between 2007 and 2019, in our ENT department, were reviewed.<br><br>RESULTS: Four men and one woman were included. The mean age was 61,4 years. One patient had a history of an invasive ductal carcinoma of the breast. Four patients consulted for swelling in the parotid region. One patient referred to our department for dysfunction of facial nerve. Skin invasion was found in one case. Four patients underwent total parotidectomy with sacrifice of the facial nerve (three cases). One patient underwent extended parotidectomy involving the skin. An ipsilateral selective neck dissection was performed in four cases. One patient had a parotid gland biopsy. Ductal carcinoma was primary in four cases and metastatic from breast origin in one case. Four patients were treated with postoperative radiotherapy. Remission was obtained in three cases. One patient had a local and meningeal recurrence. The patient with metastatic carcinoma had pulmonary, bone, hepatic and brain progression.<br><br>CONCLUSION: Ductal carcinoma is a rare and aggressive tumor of the parotid gland. It can be primary or secondary. The treatment is based on surgery and radiotherapy. The prognosis is poor.},
}
@article {pmid33391657,
year = {2020},
author = {De Pauw, V and Navez, J and Holbrechts, S and Lemaitre, J},
title = {Acute appendicitis as an unusual cause of invasive ductal breast carcinoma metastasis.},
journal = {Journal of surgical case reports},
volume = {2020},
number = {12},
pages = {rjaa535},
pmid = {33391657},
issn = {2042-8812},
abstract = {Acute appendicitis is one of the most common causes of abdominal pain at the emergency room. In rare cases, it can be caused by malignancy, even metastatic lesions from extra-abdominal neoplasia. Herein, we report a case of a 64-year-old female with a history of invasive ductal carcinoma of the breast treated by chemotherapy, surgery, radiotherapy and hormonotherapy, relapsing several years later as a bone and a pleura metastasis successfully cured by locoregional therapy and hormonal treatment. She presented with acute abdominal pain without signs of peritonitis. Abdominal computed tomodensitometry showed sign of appendicitis. Therefore, laparoscopic exploration and appendicectomy was performed. During surgery, multiple peritoneal nodules were found and harvested. Pathology showed metastatic nodules of invasive ductal breast carcinoma, including in the appendicular wall, concluding to peritoneal carcinomatosis. The postoperative course was uneventful, but the patient died 1 year later after refusing anticancer treatment.},
}
@article {pmid33371069,
year = {2020},
author = {Yue, L and Wentao, L and Xin, Z and Jingjing, H and Xiaoyan, Z and Na, F and Tonghui, M and Dalin, L},
title = {Human epidermal growth factor receptor 2-positive metastatic breast cancer with novel epidermal growth factor receptor -ZNF880 fusion and epidermal growth factor receptor E114K mutations effectively treated with pyrotinib: A case report.},
journal = {Medicine},
volume = {99},
number = {51},
pages = {e23406},
pmid = {33371069},
issn = {1536-5964},
mesh = {Acrylamides/administration &amp; dosage/*therapeutic use ; Adult ; Aminoquinolines/administration &amp; dosage/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; ErbB Receptors/*genetics/*metabolism ; Female ; Humans ; Mastectomy ; Neoplasm Metastasis ; Neoplasm Staging ; Receptor, ErbB-2/antagonists &amp; inhibitors/metabolism ; },
abstract = {INTRODUCTION: In about 15% to 20% of breast cancer cases, human epidermal growth factor receptor 2 (HER2) over-expression or gene-amplification is associated with poor prognosis. Thanks to the development of target therapies, HER2 positive patients can be managed using HER2-targeting drugs. There are several kinds ofHER2 inhibitors, such as trastuzumab, lapatinib, and pyrotinib. Pyrotinib which exert different functions, of note, the latest generation of the drug, is an irreversible small-molecule tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) (HER1) and/or HER2 and/or HER4. Both lapatinib and pyrotinib potentially target EGFR and/or HER2, but in some instances, induces different responses of patients with EGFR and/or HER2 mutations. This is attributed to the different mutations in EGFR and HER2 genes, which may form distinct types of HER2 dimers, with different binding capacities to drugs.<br><br>PATIENT CONCERNS: Five years ago, a patient underwent a radical mastectomy in an external hospital. Results of the resection histopathology revealed an invasive ductal carcinoma, pT3N0M0, stage IIB, HER2 positive. The lady patient received 6 cycles of adjuvant chemotherapy and was subjected to adjuvant trastuzumab therapy for 1 year. After a regular 1-year follow-up and in March 2018, she complained of chest pain and visited our hospital. We diagnosed her with metastatic breast cancer, positive for HER2.<br><br>DIAGNOSIS: positron emission tomography/computed tomography showed multiple metastases in the lung and sternum, while the breast lesions did not progress, the curative effect of which we evaluated as a progressive disease. Then, lapatinib integrated with chemotherapy was administered to the patient. After 5 cycles of the treatment, the patient experienced lower back pain. Through CT examination, it was revealed that she had multiple metastases in the lung and sternum, in addition to new metastases in the lumbar spine and right lobe of the liver. Moreover, magnetic resonance imaging revealed multiple metastases in the brain, and the disease further progressed. The results of circulating tumor DNA assays showed that other than HER2 amplification, novel EGFR-ZNF880 fusion and EGFR E114K mutations developed.<br><br>INTERVENTIONS: The patient was administered with a combination of pyrotinib with chemotherapy.<br><br>OUTCOMES: After 2 months of pyrotinib treatment, the metastases of the lung, sternum, lumbar spine, and right lobe of the liver disappeared. Also, the size of the brain metastases reduced while bone metastases were relieved. The curative effect was evaluated as a partial response. Following the results of circulating tumor DNA assays, HER2 amplification, EGFR-ZNF880 fusion, and EGFR E114K mutations disappeared. However, since a small lesion was present in the brain, the patient was subjected to radiotherapy in the head. Notably, after 9 months treatment with pyrotinib, enhanced CT indicated that tumors in the breast, liver, both lungs, brain, and bone were under control. The patient continually received oral pyrotinib, however, a new brain lesion appeared 6 months later. Overall, we managed to regulate the efficacy of pyrotinib for up to 15 months.<br><br>CONCLUSION: This case report demonstrates that EGFR-ZNF880 fusion and EGFR E114K mutations may contribute or lead to the formation of a special HER2 dimer, which is rapidly resistant to lapatinib but sensitive to pyrotinib. Of note, this is the first report that such a new fusion has been found.},
}
@article {pmid33370550,
year = {2021},
author = {Wang, M and Zeng, W and Zhang, Z and Zhang, W and Su, H and Zhang, Z and Jiang, L and Liu, Y and Shi, Q},
title = {The Improvement of Immune Effect of Recombinant Human Beta-Defensin 2 on Hepatitis B Vaccine in Mice.},
journal = {Viral immunology},
volume = {34},
number = {2},
pages = {96-111},
doi = {10.1089/vim.2020.0052},
pmid = {33370550},
issn = {1557-8976},
mesh = {Animals ; *Hepatitis B/prevention &amp; control ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens/genetics ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Immunity ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/immunology/therapeutic use ; *beta-Defensins/immunology/therapeutic use ; },
abstract = {Immunization with hepatitis B vaccine is an effective measure for prevention and control of hepatitis B Virus (HBV) infection. Although lots of efforts to improve the effect of hepatitis B vaccine have been made, the function of human beta defensin 2 (hBD2) on hepatitis B vaccine keeps unclear. In this article, we report that hBD2 not only promoted the activation and maturation of immature dendritic cells (iDCs) by increasing MHC II and CD86 expression, but it also significantly upregulated the mRNA level of IL-6 and IL-12B in mouse bone marrow-derived dendritic cells. The serum concentrations of IFN-γ in mice stimulated with 300 ng hBD2 increased from 25.21 to 42.04 pg/mL, with a time extension from 4 to 12 h post-injection. During the process of three times immunization (1, 14, 28 days) with 3 μg hepatitis B vaccine combined with or without 300 ng hBD2 with a 2 week interval in BALB/c mice, the antibody against HBsAg (HBsAb) concentration in serum at every time point of observation in the combined group was statistically higher than the hepatitis B vaccine group. The serum concentration of IgG2a subclass HBsAb on the 14th day post last injection in the combined group was significantly higher than the hepatitis B vaccine group. Further, the splenic cells from the mice treated with both hBD2 and hepatitis B vaccine possessed a greater ability to produce a surface antigen of hepatitis B virus (HBsAg) specific IFN-γ than those treated with hepatitis B vaccine alone. The percentages of CD3[+]/CD4[+] T cells and CD3[+]/CD8[+] T lymphocytes in spleens from the mice treated with 300 ng hBD2 were statistically higher than the phosphate buffered saline group. These data suggest that hBD2 improves iDC maturation and the immune efficiency of hepatitis B vaccine in BALB/c mice.},
}
@article {pmid33356097,
year = {2021},
author = {Zhong, S and Wong, HC and Low, HY and Zhao, R},
title = {Phototriggerable Transient Electronics via Fullerene-Mediated Degradation of Polymer:Fullerene Encapsulation Layer.},
journal = {ACS applied materials &amp; interfaces},
volume = {13},
number = {1},
pages = {904-911},
doi = {10.1021/acsami.0c18795},
pmid = {33356097},
issn = {1944-8252},
abstract = {Transient electronics is an emerging class of electronics that has attracted a lot of attention because of its potential as an environmental-friendly alternative to the existing end-of-life product disposal or treatments. However, the controlled degradation of transient electronics under environmentally benign conditions remains a challenge. In this work, the tunable degradation of transient electronics including passive resistor devices and active memory devices was realized by photodegradable thin polymer films comprising fullerene derivatives, [6,6]-phenyl-C61-butyric acid methyl esters (PCBM). The photodegradation of polymer:PCBM under an aqueous environment is triggered by ultraviolet (UV) light. Experimental results demonstrate that the addition of PCBM in commodity polymers, including but not limited to polystyrene, results in a catalytic effect on polymer photodegradation when triggered by UV light. The degradation mechanism of transient electronics is ascribed to the photodegradation of polymer:PCBM encapsulation layers caused by the synergistic effect between UV and water exposure. The polymer:PCBM encapsulation system presented herein offers a simple way to achieve the realization of light-triggered device degradation for bioapplication and expands the material options for tailorable degradation of transient electronics.},
}
@article {pmid33348399,
year = {2020},
author = {Reis, APAM and Teixeira, CMS and Medeiros, ARL and Chaves, KZC and Albuquerque, CR and Melo, MR},
title = {Sociodemographic and Clinical-pathological Study of Molecular Subtitles of Breast Carcinoma in a Reference Unit of Maranhão.},
journal = {Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia},
volume = {42},
number = {12},
pages = {820-828},
pmid = {33348399},
issn = {1806-9339},
mesh = {Brazil/epidemiology ; Breast Neoplasms/*epidemiology/etiology/pathology ; Cross-Sectional Studies ; Demography ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Medical Records ; Middle Aged ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Social Class ; },
abstract = {OBJECTIVE: To evaluate the distribution of the main sociodemographic and clinical-pathological characteristics in women with breast cancer according to the molecular profile by immunohistochemistry.<br><br>METHODS: &#x2003;A cross-sectional, retrospective, analytical and quantitative study was performed, with an analysis of 137 medical records from January 2015 to December 2018 of women attending the High Complexity in Oncology Unit of the city of Imperatriz, state of Maranh&#xe3;o, Brazil. The immunohistochemical profile of tumors based on the estrogen and progesterone receptor, Human Epidermal growth factor Receptor-type 2 (HER2) overexpression and Ki67 cell proliferation index was defined, from which six molecular subtypes were determined: luminal A, luminal B-HER2 negative, luminal B-HER2 positive, triple negative, overexpression of HER2 and inconclusive.<br><br>RESULTS: &#x2003;A total of 52.6% of the patients were postmenopausal, mean age 52.1 years old, brown (56.2%), had a schooling level&#x2009;<&#x2009;9 years (40%), staging&#x2009;>&#x2009;IIB (52.6%) and 23.4% had metastasis. Invasive ductal carcinoma accounted for 84.7%, tumor size was 2 to 5&#x2009;cm (48.9%), with lymph node involvement (56.2%), axillary lymphadenectomy in 67.2%, and mastectomy in 73.7% of the patients. The most frequent molecular subtype was the luminal B-HER2 negative (36.5%), and the luminal A subtype showed characteristics of better prognosis when compared with the others.<br><br>CONCLUSION: &#x2003;It was concluded that in the association of molecular subtypes with sociodemographic and clinical-pathological characteristics, there were no statistically significant results obtained, except for complementary therapy, referring to hormone therapy, and there was a high index of metastasis at diagnosis, which was a worrying factor and indicative of failures in the screening and early diagnosis of this population.},
}
@article {pmid33342987,
year = {2020},
author = {Shinseki, K and Takahashi, M and Kushima, A and Nakamoto, T and Wakata, M and Nakajima, T and Toda, T and Ito, K and Fujibayashi, M},
title = {[One Case of Accessory Breast Cancer Complicated by Contralateral Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {47},
number = {12},
pages = {1703-1705},
pmid = {33342987},
issn = {0385-0684},
mesh = {Axilla ; *Breast Diseases ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/complications/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; },
abstract = {We experienced a case of right sided accessory breast cancer complicated by contralateral breast cancer. A 50-year-old woman came to us for an examination because a tumor in her left breast was pointed out at breast cancer screening. A breast MRI confirmed a tumor in her left breast and a tumor continuing from the skin to the subcutis of the right axilla. A skin biopsy for the tumor in the right axilla and a core needle biopsy(CNB)for the tumor in the left breast were performed. The pathological result of the CNB for the left breast indicated an invasive ductal carcinoma of the tubular formative scirrhous type. Although the tumor of the right axilla was poorly differentiated adenocarcinoma demonstrating cord-like arrays, it was examined by skin biopsy and therefore no deep part of the tissue was included. We conducted immunostaining, in consideration of the possibility of metastasis from the left sided breast cancer. ER, PgR, mammaglobin, GATA 3 were positive, strongly suggesting that the tumor in the right axilla was also derived from a mammary gland. We also performed a wide local excision of the right axilla plus axillary dissection(level Ⅰ)in addition to conducting a left mastectomy plus sentinel lymph node biopsy, in consideration of the possibility of primary right sided accessory breast cancer. The pathological result following surgery confirmed a difference in the histologic features between both sides, residual normal accessory mammary glands around the tumor on the right side, and the presence of rich DCIS and a lobular replacement image, leading to a definitive diagnosis of primary invasive ductal carcinoma of the accessory breast on the right side.},
}
@article {pmid33336932,
year = {2021},
author = {Liang, RB and Yu, K and Wu, JL and Liu, JX and Lin, Q and Li, B and Zhang, YQ and Ge, QM and Li, QY and Shu, HY and Shao, Y},
title = {Risk factors and their diagnostic values for ocular metastases in invasive ductal carcinoma.},
journal = {Cancer medicine},
volume = {10},
number = {3},
pages = {824-832},
pmid = {33336932},
issn = {2045-7634},
mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/epidemiology/metabolism/*pathology/surgery ; Case-Control Studies ; Eye Neoplasms/epidemiology/metabolism/*secondary/surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; },
abstract = {Invasive ductal carcinoma (IDC) is a major type of breast cancer. Ocular metastasis (OM) in IDC is rarely seen, but patients with OM often have a poor prognosis. Furthermore, OM is difficult to detect in the early stages by common imaging examinations. In the present study, we tried to figure out the risk factors of OM in IDC and evaluate their diagnostic values for early detection. There were 1192 IDC patients who were divided into two groups according to ocular metastasis involved in this study. Clinical parameters of those patients were used to detect differences. The binary logistic regression test was then used to determine the risk factors of OM in IDC. Furthermore, ROC curves of both single and combined risk factors were established to examine their diagnostic values. The incidence of axillary lymph node metastases was significantly higher in the OM group (p = 0.002). Higher carbohydrate antigen 153 (CA153), lower apolipoprotein A1 (ApoA1), and hemoglobin (Hb) were risk factors for OM in IDC (p < 0.001, p < 0.001, p = 0.038, respectively). In the single risk factor ROC analysis, cutoff values of CA153, ApoA1, and Hb were 43.3 u/mL (CI: 0.966-0.984, p < 0.001), 1.11 g/L (CI: 0.923-0.951, p < 0.001), and 112 g/L (CI: 0.815-0.857, p < 0.001), respectively. Among the ROC curves of combined risk factors, CA153+ApoA1+Hb had the best accuracy, with the sensitivity and specificity of 89.47% and 99.32%, respectively (CI: 0.964-0.983, p < 0.001). CA153, ApoA1, and Hb are risk factors for OM in IDC. In clinical practice, the three parameters could be used as predictive factors for the early detection of OM.},
}
@article {pmid33335279,
year = {2021},
author = {Zeng, Y and Gao, W and Chen, X and Shen, K},
title = {Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component.},
journal = {British journal of cancer},
volume = {124},
number = {5},
pages = {975-981},
pmid = {33335279},
issn = {1532-1827},
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; },
abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.<br><br>METHODS: Consecutive ER-positive, HER2-negative, N0-1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.<br><br>RESULTS: A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P&#x2009;=&#x2009;0.038). IDC/DCIS patients more often had a low-risk RS (P&#x2009;=&#x2009;0.018) or intermediate-risk RS (P&#x2009;=&#x2009;0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.<br><br>CONCLUSIONS: IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.},
}
@article {pmid33331427,
year = {2020},
author = {Bertoldi, AS and Guetter, CR and Coltro, GA and Vosgerau, LM and Brighenti, LMV and Fauat, NI and Kubrusly, FB and Marques, CAM and Kubrusly, LF},
title = {CARVEDILOL AS PRIMARY PROPHYLAXIS FOR GASTRIC VARICEAL BLEEDING IN PORTAL HYPERTENSION MODEL IN RATS.},
journal = {Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery},
volume = {33},
number = {3},
pages = {e1525},
pmid = {33331427},
issn = {2317-6326},
mesh = {Adrenergic beta-Antagonists/*administration &amp; dosage ; Animals ; Antihypertensive Agents/*administration &amp; dosage ; Carvedilol/*administration &amp; dosage ; Esophageal and Gastric Varices/complications/prevention &amp; control ; Gastrointestinal Hemorrhage/etiology/*prevention &amp; control ; Hypertension, Portal/*complications ; Rats ; Rats, Wistar ; },
abstract = {BACKGROUND: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy.<br><br>AIM: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model.<br><br>METHOD: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days.<br><br>RESULTS: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups.<br><br>CONCLUSION: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.},
}
@article {pmid33329538,
year = {2020},
author = {Niespolo, C and Johnston, JM and Deshmukh, SR and Satam, S and Shologu, Z and Villacanas, O and Sudbery, IM and Wilson, HL and Kiss-Toth, E},
title = {Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells.},
journal = {Frontiers in immunology},
volume = {11},
number = {},
pages = {574046},
pmid = {33329538},
issn = {1664-3224},
support = {PG/16/44/32146/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {3' Untranslated Regions ; Animals ; Binding Sites ; Cell Line, Tumor ; Cytokines/*metabolism ; Gene Expression Regulation ; Humans ; Inflammation ; Interleukin-8/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism/*physiology ; Macrophages/*metabolism ; Male ; Mice ; Mice, Transgenic ; MicroRNAs/genetics/*metabolism ; Phenotype ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Protein Serine-Threonine Kinases/*antagonists &amp; inhibitors/genetics/metabolism/physiology ; RNA, Messenger/genetics/metabolism ; },
abstract = {The pseudokinase TRIB1 controls cell function in a range of contexts, by regulating MAP kinase activation and mediating protein degradation via the COP1 ubiquitin ligase. TRIB1 regulates polarization of macrophages and dysregulated Trib1 expression in murine models has been shown to alter atherosclerosis burden and adipose homeostasis. Recently, TRIB1 has also been implicated in the pathogenesis of prostate cancer, where it is often overexpressed, even in the absence of genetic amplification. Well described TRIB1 effectors include MAP kinases and C/EBP transcription factors, both in immune cells and in carcinogenesis. However, the mechanisms that regulate TRIB1 itself remain elusive. Here, we show that the long and conserved 3'untranslated region (3'UTR) of TRIB1 is targeted by miRNAs in macrophage and prostate cancer models. By using a systematic in silico analysis, we identified multiple "high confidence" miRNAs potentially binding to the 3'UTR of TRIB1 and report that miR-101-3p and miR-132-3p are direct regulators of TRIB1 expression and function. Binding of miR-101-3p and miR-132-3p to the 3'UTR of TRIB1 mRNA leads to an increased transcription and secretion of interleukin-8. Our data demonstrate that modulation of TRIB1 by miRNAs alters the inflammatory profile of both human macrophages and prostate cancer cells.},
}
@article {pmid33328559,
year = {2020},
author = {Wu, SG and Yang, SP and Zhang, WW and Wang, J and Lian, CL and Chen, YX and He, ZY},
title = {The longitudinal risk of mortality between invasive ductal carcinoma and metaplastic breast carcinoma.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {22070},
pmid = {33328559},
issn = {2045-2322},
mesh = {Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Neoplasm Invasiveness ; Risk Factors ; Survival Rate ; },
abstract = {The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.},
}
@article {pmid33316685,
year = {2021},
author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY},
title = {Pathologic response rates for breast cancer stages as a predictor of outcomes in patients receiving neoadjuvant chemotherapy followed by breast-conserving surgery.},
journal = {Surgical oncology},
volume = {36},
number = {},
pages = {91-98},
doi = {10.1016/j.suronc.2020.11.015},
pmid = {33316685},
issn = {1879-3320},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*pathology/therapy ; Chemotherapy, Adjuvant/*methods ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoadjuvant Therapy/*methods ; Prognosis ; Young Adult ; },
abstract = {PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.<br><br>PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients' PRRs; other independent predictors were controlled for or stratified in the analysis.<br><br>RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13-0.56), 0.36 (0.15-0.85), and 0.15 (0.08-0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35-0.89), 0.91 (0.62-0.96), and 0.63 (0.43-0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06-2.24), 1.08 (1.03-1.82), and 1.19 (1.07-2.01) for all-cause mortality, LRR, and DM, respectively.<br><br>CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.},
}
@article {pmid33302909,
year = {2020},
author = {Desa, DE and Strawderman, RL and Wu, W and Hill, RL and Smid, M and Martens, JWM and Turner, BM and Brown, EB},
title = {Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction.},
journal = {BMC cancer},
volume = {20},
number = {1},
pages = {1217},
pmid = {33302909},
issn = {1471-2407},
support = {R21 CA208921/CA/NCI NIH HHS/United States ; W81XWH-15-1-0040//U.S. Department of Defense/ ; W81XWH-17-1-0011//U.S. Department of Defense/ ; R21CA208921//Foundation for the National Institutes of Health/ ; },
mesh = {Breast Neoplasms/chemistry/*ultrastructure ; Carcinoma, Ductal, Breast/chemistry/secondary/*ultrastructure ; *Estrogens ; Female ; Fibrillar Collagens/*ultrastructure ; Humans ; Image Processing, Computer-Assisted ; *Neoplasm Metastasis ; Neoplasm Proteins/*ultrastructure ; Neoplasms, Hormone-Dependent/chemistry/*ultrastructure ; Prognosis ; Risk ; *Second Harmonic Generation Microscopy ; Single-Blind Method ; Stromal Cells/chemistry/ultrastructure ; Tumor Microenvironment ; },
abstract = {BACKGROUND: Metastases are the leading cause of breast cancer-related deaths. The tumor microenvironment impacts cancer progression and metastatic ability. Fibrillar collagen, a major extracellular matrix component, can be studied using the light scattering phenomenon known as second-harmonic generation (SHG). The ratio of forward- to backward-scattered SHG photons (F/B) is sensitive to collagen fiber internal structure and has been shown to be an independent prognostic indicator of metastasis-free survival time (MFS). Here we assess the effects of heterogeneity in the tumor matrix on the possible use of F/B as a prognostic tool.<br><br>METHODS: SHG imaging was performed on sectioned primary tumor excisions from 95 untreated, estrogen receptor-positive, lymph node negative invasive ductal carcinoma patients. We identified two distinct regions whose collagen displayed different average F/B values, indicative of spatial heterogeneity: the cellular tumor bulk and surrounding tumor-stroma interface. To evaluate the impact of heterogeneity on F/B's prognostic ability, we performed SHG imaging in the tumor bulk and tumor-stroma interface, calculated a 21-gene recurrence score (surrogate for OncotypeDX&#xae;, or S-ODX) for each patient and evaluated their combined prognostic ability.<br><br>RESULTS: We found that F/B measured in tumor-stroma interface, but not tumor bulk, is prognostic of MFS using three methods to select pixels for analysis: an intensity threshold selected by a blinded observer, a histogram-based thresholding method, and an adaptive thresholding method. Using both regression trees and Random Survival Forests for MFS outcome, we obtained data-driven prediction rules that show F/B from tumor-stroma interface, but not tumor bulk, and S-ODX both contribute to predicting MFS in this patient cohort. We also separated patients into low-intermediate (S-ODX <&#x2009;26) and high risk (S-ODX &#x2265;26) groups. In the low-intermediate risk group, comprised of patients not typically recommended for adjuvant chemotherapy, we find that F/B from the tumor-stroma interface is prognostic of MFS and can identify a patient cohort with poor outcomes.<br><br>CONCLUSIONS: These data demonstrate that intratumoral heterogeneity in F/B values can play an important role in its possible use as a prognostic marker, and that F/B from tumor-stroma interface of primary tumor excisions may provide useful information to stratify patients by metastatic risk.},
}
@article {pmid33278619,
year = {2021},
author = {Hadano, Y and Kakuma, T and Matsumoto, T and Ishibashi, K and Isoda, M and Yasunaga, H},
title = {Reduction of 30-day death rates from Staphylococcus aureus bacteremia by mandatory infectious diseases consultation: Comparative study interventions with and without an infectious disease specialist.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {103},
number = {},
pages = {308-315},
doi = {10.1016/j.ijid.2020.11.199},
pmid = {33278619},
issn = {1878-3511},
mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/microbiology/mortality ; Case Management ; Female ; Hospitals ; Humans ; Japan ; Male ; Middle Aged ; *Quality of Health Care ; Referral and Consultation ; Retrospective Studies ; Specialization ; Staphylococcal Infections/*drug therapy/microbiology ; Staphylococcus aureus/*drug effects ; Treatment Outcome ; },
abstract = {OBJECTIVES: Most Japanese hospitals need to keep to higher Staphylococcus aureus bacteremia (SAB) quality-of-care indicators (QCIs) and create strategies that can maximize the effect of these QCIs with only a small number of infectious disease specialists. This study aimed to evaluate the clinical outcomes of patients with SAB before and after the enhancement of the mandatory infectious disease consultations (IDCs).<br><br>METHODS: This retrospective study was conducted at a tertiary care hospital in Japan. The primary outcome was the 30-day mortality between each period. A generalized structural equation model was employed to examine the effect of the mandatory IDC enhancement on 30-day mortality among patients with SAB.<br><br>RESULTS: A total of 114 patients with SAB were analyzed. The 30-day all-cause mortality differed significantly between the two periods (17.3% vs. 4.8%, P = 0.02). Age, three-QCI point &#x2265; 1, and Pitt bacteremia score &#x2265; 3 were the significant risk factors for 30-day mortality. The intervention was also significantly associated with improved adherence to QCIs.<br><br>CONCLUSION: Mandatory IDCs for SAB improved 30-day mortality and adherence to QCIs after the intervention. In Japan, improving the quality of management in patients with SAB should be an important target.},
}
@article {pmid33263939,
year = {2021},
author = {D'Alfonso, TM and Pareja, F and Da Cruz Paula, A and Vahdatinia, M and Gazzo, A and Ferrando, L and da Silva, EM and Cheng, E and Sclafani, L and Chandarlapaty, S and Zhang, H and Hoda, SA and Wen, HY and Brogi, E and Weigelt, B and Reis-Filho, JS},
title = {Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma.},
journal = {The journal of pathology. Clinical research},
volume = {7},
number = {2},
pages = {113-120},
pmid = {33263939},
issn = {2056-4538},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; K12 CA184746/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Breast Neoplasms/complications/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; *DNA Copy Number Variations ; DNA Mutational Analysis ; Female ; Humans ; Mutation ; Papilloma/complications/diagnosis/*genetics/pathology ; Exome Sequencing ; },
abstract = {Juvenile papillomatosis (JP) of the breast is a rare benign mass-forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole-exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC-NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC-NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC-NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)-positive breast cancers. We observed JP to harbor a dominant aging-related mutational signature, whereas coexisting DCIS and IDC-NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop.},
}
@article {pmid33251496,
year = {2020},
author = {Li, X and Schmöhl, F and Qi, H and Bennewitz, K and Tabler, CT and Poschet, G and Hell, R and Volk, N and Poth, T and Hausser, I and Morgenstern, J and Fleming, T and Nawroth, PP and Kroll, J},
title = {Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish.},
journal = {iScience},
volume = {23},
number = {12},
pages = {101763},
pmid = {33251496},
issn = {2589-0042},
abstract = {Regulation of glucose homeostasis is a fundamental process to maintain blood glucose at a physiological level, and its dysregulation is associated with the development of several metabolic diseases. Here, we report on a zebrafish mutant for Aldo-keto-reductase 1a1b (akr1a1b) as a regulator of gluconeogenesis. Adult akr1a1b [-/-] mutant zebrafish developed fasting hypoglycemia, which was caused by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression as rate-limiting enzyme of gluconeogenesis. Subsequently, glucogenic amino acid glutamate as substrate for gluconeogenesis accumulated in the kidneys, but not in livers, and induced structural and functional pronephros alterations in 48-hpf akr1a1b [-/-] embryos. Akr1a1b [-/-] mutants displayed increased nitrosative stress as indicated by increased nitrotyrosine, and increased protein-S-nitrosylation. Inhibition of nitrosative stress using the NO synthase inhibitor L-NAME prevented kidney damage and normalized PEPCK expression in akr1a1b [-/-] mutants. Thus, the data have identified Akr1a1b as a regulator of gluconeogenesis in zebrafish and thereby controlling glucose homeostasis.},
}
@article {pmid33247280,
year = {2020},
author = {Puzis, R and Farbiash, D and Brodt, O and Elovici, Y and Greenbaum, D},
title = {Increased cyber-biosecurity for DNA synthesis.},
journal = {Nature biotechnology},
volume = {38},
number = {12},
pages = {1379-1381},
pmid = {33247280},
issn = {1546-1696},
mesh = {*Computer Security ; DNA/*biosynthesis ; Genetic Engineering ; Plasmids/genetics ; },
}
@article {pmid33243732,
year = {2020},
author = {Xu, X and Wang, J and Yan, C and Men, Y and Jiang, H and Fang, H and Xu, X and Yang, J},
title = {[Association of JMJD3, MMP-2 and VEGF expressions with clinicopathological features of invasive ductal breast carcinoma].},
journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University},
volume = {40},
number = {11},
pages = {1593-1600},
pmid = {33243732},
issn = {1673-4254},
mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A ; },
abstract = {OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells.<br><br>METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR.<br><br>RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue (P < 0.05). The positivity rates of JMJD3, MMP-2 and VEGF in breast cancer tissues were significantly correlated with tumor diameter, differentiation, TNM stage, lymph node metastasis, and molecular subtypes (P < 0.05). KaplanMeier analysis showed that JMJD3 expression level was positively while MMP-2 and VEGF were inversely correlated with the disease-free survival time of the patients (P < 0.05). Cox regression analysis identified JMJD3, MMP-2, VEGF and tumor differentiation as independent prognostic factors of breast cancer. Spearman correlation analysis suggested a negative correlation of JMJD3 with MMP2 (r=-0.569, P < 0.05) and VEGF (r=-0.533, P < 0.05) and a positive correlation between MMP2 and VEGF (r=0.923, P < 0.05). In MDA-MB-231 cells, overexpression of JMJD3 inhibited the proliferation of MDA-MB-231 cells and the expression of MMP-2 and VEGF.<br><br>CONCLUSIONS: The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.},
}
@article {pmid33239449,
year = {2021},
author = {Chen, J and Fleming, T and Katz, S and Dewenter, M and Hofmann, K and Saadatmand, A and Kronlage, M and Werner, MP and Pokrandt, B and Schreiter, F and Lin, J and Katz, D and Morgenstern, J and Elwakiel, A and Sinn, P and Gröne, HJ and Hammes, HP and Nawroth, PP and Isermann, B and Sticht, C and Brügger, B and Katus, HA and Hagenmueller, M and Backs, J},
title = {CaM Kinase II-δ Is Required for Diabetic Hyperglycemia and Retinopathy but Not Nephropathy.},
journal = {Diabetes},
volume = {70},
number = {2},
pages = {616-626},
doi = {10.2337/db19-0659},
pmid = {33239449},
issn = {1939-327X},
mesh = {Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism ; Diabetes Mellitus, Type 2/genetics/*metabolism ; Diabetic Nephropathies/genetics/*metabolism ; Diabetic Retinopathy/genetics/*metabolism ; Gene Expression ; Hyperglycemia/genetics/*metabolism ; Mice ; Mice, Knockout ; Receptors, Leptin/genetics/metabolism ; },
abstract = {Type 2 diabetes has become a pandemic and leads to late diabetic complications of organs, including kidney and eye. Lowering hyperglycemia is the typical therapeutic goal in clinical medicine. However, hyperglycemia may only be a symptom of diabetes but not the sole cause of late diabetic complications; instead, other diabetes-related alterations could be causative. Here, we studied the role of CaM kinase II-δ (CaMKIIδ), which is known to be activated through diabetic metabolism. CaMKIIδ is expressed ubiquitously and might therefore affect several different organ systems. We crossed diabetic leptin receptor-mutant mice to mice lacking CaMKIIδ globally. Remarkably, CaMKIIδ-deficient diabetic mice did not develop hyperglycemia. As potential underlying mechanisms, we provide evidence for improved insulin sensing with increased glucose transport into skeletal muscle and also reduced hepatic glucose production. Despite normoglycemia, CaMKIIδ-deficient diabetic mice developed the full picture of diabetic nephropathy, but diabetic retinopathy was prevented. We also unmasked a retina-specific gene expression signature that might contribute to CaMKII-dependent retinal diabetic complications. These data challenge the clinical concept of normalizing hyperglycemia in diabetes as a causative treatment strategy for late diabetic complications and call for a more detailed analysis of intracellular metabolic signals in different diabetic organs.},
}
@article {pmid33238981,
year = {2020},
author = {Huang, Z and Hu, C and Liu, K and Yuan, L and Li, Y and Zhao, C and Hu, C},
title = {Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infiltrating duct carcinoma of the breast: a population-based study.},
journal = {BMC cancer},
volume = {20},
number = {1},
pages = {1145},
pmid = {33238981},
issn = {1471-2407},
mesh = {Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*secondary/therapy ; Brain Neoplasms/*secondary/therapy ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*secondary/therapy ; Male ; Middle Aged ; *Nomograms ; Prognosis ; Retrospective Studies ; Risk Factors ; SEER Program ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer is the most common malignancy in women, and it is also the leading cause of death in female patients; the most common pathological type of BC is infiltrating duct carcinoma (IDC). Some nomograms have been developed to predict bone metastasis (BM) in patients with breast cancer. However, there are no studies on diagnostic and prognostic nomograms for BM in newly diagnosed IDC patients.<br><br>METHODS: IDC patients with newly diagnosed BM from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were reviewed. Multivariate logistic regression analysis was used to identify risk factors for BM in patients with IDC. Univariate and multivariate Cox proportional hazards regression analysis were used to explore the prognostic factors of BM in patients with IDC. We then constructed nomograms to predict the risk and prognosis of BM for patients with IDC. The results were validated using bootstrap resampling and retrospective research on 113 IDC patients with BM from 2015 to 2018 at the Affiliated Hospital of Chengde Medical University.<br><br>RESULTS: This study included 141,959 patients diagnosed with IDC in the SEER database, of whom 2383 cases were IDC patients with BM. The risk factors for BM in patients with IDC included sex, primary site, grade, T stage, N stage, liver metastasis, race, brain metastasis, breast cancer subtype, lung metastasis, insurance status, and marital status. The independent prognostic factors were brain metastases, race, grade, surgery, chemotherapy, age, liver metastases, breast cancer subtype, insurance status, and marital status. Through calibration, receiver operating characteristic curve and decision curve analyses, we found that the nomogram for predicting the prognosis of IDC patients with BM displayed great performance both internally and externally.<br><br>CONCLUSION: These nomograms are expected to be a precise and personalized tool for predicting the risk and prognosis for BM in patients with IDC. This will help clinicians develop more rational and effective treatment strategies.},
}
@article {pmid33238073,
year = {2021},
author = {Okada, K and Takahara, T and Suzuki, Y and Kohno, K and Sakakibara, A and Satou, A and Takahashi, E and Nakamura, S},
title = {Histiocytic and dendritic cell neoplasms: Reappraisal of a Japanese series based on t(14;18) and neoplastic PD-L1 expression.},
journal = {Pathology international},
volume = {71},
number = {1},
pages = {24-32},
doi = {10.1111/pin.13044},
pmid = {33238073},
issn = {1440-1827},
mesh = {Adolescent ; Adult ; Aged ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/analysis ; *Dendritic Cell Sarcoma, Follicular/immunology/metabolism/pathology ; Dendritic Cells/metabolism/pathology ; Female ; Histiocytes/metabolism/pathology ; *Histiocytic Sarcoma/immunology/metabolism/pathology ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Japan ; Langerhans Cell Sarcoma/immunology/metabolism/pathology ; Lymphoma, Follicular/immunology/metabolism/pathology ; Male ; Middle Aged ; Retrospective Studies ; T-Lymphocytes/metabolism ; },
abstract = {Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.},
}
@article {pmid33229203,
year = {2021},
author = {Madabhavi, I and Sarkar, M and Chavan, C and Trivedi, M},
title = {Maxillary bone metastasis, as an early sign of breast cancer; an unusual &amp; rare site of metastasis from the common cancer.},
journal = {Oral oncology},
volume = {115},
number = {},
pages = {105098},
doi = {10.1016/j.oraloncology.2020.105098},
pmid = {33229203},
issn = {1879-0593},
mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Maxilla/*pathology ; Maxillary Neoplasms/*secondary ; Neoplasm Metastasis ; },
abstract = {Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Due to their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. In this article we present a rare, unusual &amp; exceptional case of left maxillary mass which on further evaluation leading to diagnosis of left breast carcinoma with metastasis to isolated left maxillary bone. Sixty five year old postmenopausal woman of low socioeconomic status with good performance status presented with a 3 months history of progressive pain and swelling in the left maxillary region. Fine Needle Aspiration Cytology (FNAC) from the maxillary mass shows invasive ductal carcinoma. On further clinical, radiographic, and histopathological examination findings from the breast lesion confirmed the diagnosis of hormone receptor positive metastatic breast carcinoma. In view of painful metastatic maxillary lesion with breast disease she was managed with a palliative radiotherapy to the maxillary lesion and palliative chemotherapy with Doxorubicin-Cyclophosphamide and bhisphosphonate-Zolendronic acid. Patient responded very well to palliative radiotherapy and chemotherapy, in view of hormone receptor positive breast cancer, now she is on Tab. Anastrazole 1 mg once a day along with monthly Zolendronic acid injection since last 13 months without any symptoms of disease evolution. A high index of clinical thought of metastatic cancer to maxilla is necessary when evaluating patients who complain of maxillary pain and swelling without a history of pain or swelling in the head and neck &amp; non-head and neck region. To the best of our knowledge, this is the first reported case of a metastatic isolated solitary maxillary bone metastasis presenting as an early sign of breast cancer.},
}
@article {pmid33209168,
year = {2020},
author = {Fouhi, ME and Benider, A and Gaëtan, KZA and Mesfioui, A},
title = {[Epidemiological and anatomopathological profile of breast cancer at the Ibn Rochd University Hospital, Casablanca].},
journal = {The Pan African medical journal},
volume = {37},
number = {},
pages = {41},
pmid = {33209168},
issn = {1937-8688},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Delayed Diagnosis ; Female ; Hospitals, University ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Young Adult ; },
abstract = {The present study aims to determine the various epidemiological characteristics among newly diagnosed patients with breast cancer in Casablanca during 2018. During that period, 668 cases were collected, the average age was 51.6 years, the female was the most represented with 662 cases (99.1%) and men with 6 cases (0.9%), a sex ratio (M/F) of 0.009. The average age of menopause was 49.8 years and the average age of menarche was 13.5 years, 31.7% had a history of cancer (breast 14.1%, stomach and 9% liver 7%). The average diagnosis delay was 10 months, the thyroid disease was the most represented pathology, the left breast was diagnosed in 50.2% and the right breast in 44.7% and 1.3% in the bilateral location. The most common histological type was invasive ductal carcinoma (73.2%). The vascular and lymphatic invasion was observed in 42.2%, axillary nodes were affected in 71.1% of cases. The histological prognosis (SBR) revealed a predominance of grade II in 55.9% of cases. The Luminal B continues to be the most common phenotype (46%) followed by Triple Negative (15.3%) and Luminal A (14.2%) and HER2 (7.4%). The immediate prognosis is a cause for concern because of delayed diagnosis. It seems urgent to develop the health information policy and education.},
}
@article {pmid33204409,
year = {2020},
author = {Missori, G and Serra, F and Prestigiacomo, G and Ricciardolo, AA and Brugioni, L and Gelmini, R},
title = {Case Report: Metastatic breast cancer to the gallbladder.},
journal = {F1000Research},
volume = {9},
number = {},
pages = {343},
pmid = {33204409},
issn = {2046-1402},
mesh = {Aged, 80 and over ; Breast Neoplasms/*pathology/therapy ; *Cholecystitis, Acute/etiology/surgery ; Female ; *Gallbladder Neoplasms/secondary/surgery ; Humans ; },
abstract = {Cholecystitis is one of the leading causes of emergency surgical interventions; the occurrence of metastases to the gallbladder is rare and has only been reported in the literature exceptionally. Metastatic breast cancer to the gallbladder is even less frequent; in fact, breast cancer usually metastasizes to bone, lung, lymph nodes, liver and brain. We report the case of an 83-year-old female patient with a previous history of breast surgery with axillary dissection in 1997, followed by adjuvant chemotherapy due to invasive ductal carcinoma of the left breast. The patient was admitted at the emergency department for sepsis and an episode of acute kidney failure, anuria and fever. Right-upper quadrant abdominal pain triggered by food intake and abdominal tenderness was also present, placing the diagnostic suspicion of biliary sepsis due to acute cholecystitis. The histological examination of the surgical specimen highlighted the presence of metastasis from an infiltrating ductal breast carcinoma with positive hormone receptors. We also report here the results of a review of the literature looking at articles describing cases of gallbladder metastasis from breast cancer.},
}
@article {pmid33191115,
year = {2021},
author = {Shah, OS and Soran, A and Sahin, M and Knapick, BA and Ugras, S and Celik, E and Lucas, PC and Lee, AV},
title = {Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study.},
journal = {Clinical breast cancer},
volume = {21},
number = {3},
pages = {210-217},
pmid = {33191115},
issn = {1938-0666},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Lobular/genetics ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; },
abstract = {BACKGROUND: Identification of genomic alterations present in cancer patients may aid in cancer diagnosis, prognosis and therapeutic target discovery. In this study, we aimed to identify clinically actionable variants present in stage IV breast cancer (BC) samples.<br><br>MATERIALS AND METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples of BC (n&#xa0;= 41). DNA was sequenced using MammaSeq, a BC-specific next-generation sequencing panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data, and the resulting single nucleotide variants were annotated using the CRAVAT toolkit. Single nucleotide variations (SNVs) were filtered to remove common polymorphisms and germline variants. CNVkit was employed to identify copy number variations (CNVs). The Precision Medicine Knowledgebase (PMKB) and OncoKB Precision Oncology Database were used to associate clinical significance with the identified variants.<br><br>RESULTS: A total of 41 samples from Turkish patients with BC were sequenced (read depth of 94-13,340; median of 1529). These patients were diagnosed with various BC subtypes including invasive ductal carcinoma, invasive lobular carcinoma, apocrine BC, and micropapillary BC. In total, 59 different alterations (49 SNVs and 10 CNVs) were identified. From these, 8 alterations (3 CNVs - ERBB2, FGFR1, and AR copy number gains and 5 SNVs - IDH1.R132H, TP53.E204&#x2217;, PI3KCA.E545K, PI3KCA.H1047R, and PI3KCA.R88Q) were identified to have some clinical significance by PMKB and OncoKB. Moreover, the top 5 genes with the most SNVs included PIK3CA, TP53, MAP3K1, ATM, and NCOR1. Additionally, copy number gains and losses were found in ERBB2, GRB7, IGFR1, AR, FGFR1, MYC, and IKBKB, and BRCA2, RUNX1, and RB1, respectively.<br><br>CONCLUSION: We identified 59 unique alterations in 38 genes in 41 stage IV BC tissue samples using MammaSeq[TM]. Eight of these alterations were found to have some clinical significance by OncoKB and PKMB. This study highlights the potential use of cancer specific next-generation sequencing panels in clinic to get better insight into the patient-specific genomic alterations.},
}
@article {pmid33163280,
year = {2020},
author = {Zhang, J and Sun, M and Chang, E and Lu, CY and Chen, HM and Wu, SY},
title = {Pathologic response as predictor of recurrence, metastasis, and survival in breast cancer patients receiving neoadjuvant chemotherapy and total mastectomy.},
journal = {American journal of cancer research},
volume = {10},
number = {10},
pages = {3415-3427},
pmid = {33163280},
issn = {2156-6976},
abstract = {To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in breast invasive ductal carcinoma (IDC) patients receiving neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we used the pathologic response (PR) of primary breast diseases (T stages), nodal diseases (N stages), and combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) based on existing clinical and pathologic reports as predictors. We enrolled patients with IDC who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) of PR; other independent predictors were controlled for or stratified in the analysis. We analyzed 3654 IDC patients (1031, 1215, 1003, and 405 patients with clinical stages IIB, IIIA, IIIB, and IIIC, respectively) receiving NACT and TM. After multivariate Cox regression analyses, the adjusted HRs (aHRs) (95% CI) for all-cause mortality, LRR, and DM were noted to be 0.21 (0.13-0.34), 0.19 (0.08-0.48), and 0.33 (0.23-0.47), respectively, for pCR; 0.56 (0.48-0.65), 0.67 (0.51-0.89), and 0.61 (0.52-0.70), respectively, for AJCC downstaging; and 1.85 (1.56-2.18), 1.17 (0.84-1.62), and 1.61 (1.36-1.90), respectively, for AJCC upstaging. The PR parameters used in the study are easily applied because they are based on existing staging records, and they can strongly predict OS, LRR, and DM in IDC patients receiving NACT and TM, regardless of clinical stage. The results can be used to guide adjuvant treatment.},
}
@article {pmid33163131,
year = {2021},
author = {Chung, HL and Leung, JWT},
title = {Breast cancer recurrences in myocutaneous flap reconstruction.},
journal = {Radiology case reports},
volume = {16},
number = {1},
pages = {40-46},
pmid = {33163131},
issn = {1930-0433},
abstract = {Autologous flap reconstruction is widely used after skin sparing mastectomy to reconstruct the appearance of the breast. We present 2 cases of breast cancer recurrence in a deep inferior epigastric perforator reconstruction, including a 65-year-old female with history of papillary carcinoma and a 35-year-old female with history of a high grade invasive ductal carcinoma with extensive ductal carcinoma in situ. Differential imaging considerations of the post mastectomy patient are reviewed. Typical appearance of a deep inferior epigastric perforator flap reconstruction as well as location and timing of presentation may help differentiate a recurrence from the more commonly encountered postsurgical etiologies.},
}
@article {pmid33154304,
year = {2020},
author = {Oral, O and Unverdi, H and Kumcu, E and Turkbey, D and Dogan, S and Hucumenoglu, S},
title = {Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {63},
number = {4},
pages = {551-558},
doi = {10.4103/IJPM.IJPM_637_18},
pmid = {33154304},
issn = {0974-5130},
mesh = {Adenocarcinoma, Mucinous/genetics/pathology ; Adult ; Aged ; Breast Neoplasms/*genetics/*pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Mucin 5AC/*genetics ; Mucin-1/*genetics ; Mucin-2/*genetics ; Mucin-6/*genetics ; Prognosis ; },
abstract = {AIMS: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters.<br><br>MATERIALS AND METHODS: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas.<br><br>RESULTS: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion.<br><br>CONCLUSIONS: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.},
}
@article {pmid33148662,
year = {2021},
author = {Chen, F and Ding, K and Priedigkeit, N and Elangovan, A and Levine, KM and Carleton, N and Savariau, L and Atkinson, JM and Oesterreich, S and Lee, AV},
title = {Single-Cell Transcriptomic Heterogeneity in Invasive Ductal and Lobular Breast Cancer Cells.},
journal = {Cancer research},
volume = {81},
number = {2},
pages = {268-281},
pmid = {33148662},
issn = {1538-7445},
support = {F30 CA203154/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; },
mesh = {Antigens, CD/genetics/metabolism ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Cadherins/antagonists &amp; inhibitors/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Mutation ; Prognosis ; Single-Cell Analysis/*methods ; *Transcriptome ; Tumor Cells, Cultured ; },
abstract = {Invasive lobular breast carcinoma (ILC), one of the major breast cancer histologic subtypes, exhibits unique features compared with the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell RNA sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knockout (KO). Inspection of intracell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a preadaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membranous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFNγ-mediated growth inhibition via activation of IRF1. This study reveals single-cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance. SIGNIFICANCE: This study represents a key step towards understanding heterogeneity in cancer cell lines and the role of E-cadherin depletion in contributing to the molecular features of invasive lobular breast carcinoma.},
}
@article {pmid33148628,
year = {2022},
author = {Pareja, F and Vahdatinia, M and Marchio, C and Lee, SSK and Da Cruz Paula, A and Derakhshan, F and da Silva, EM and Selenica, P and Dopeso, H and Chandarlapaty, S and Wen, HY and Vincent-Salomon, A and Brogi, E and Weigelt, B and Reis-Filho, JS},
title = {Neuroendocrine tumours of the breast: a genomic comparison with mucinous breast cancers and neuroendocrine tumours of other anatomic sites.},
journal = {Journal of clinical pathology},
volume = {75},
number = {1},
pages = {10-17},
pmid = {33148628},
issn = {1472-4146},
support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA247749/CA/NCI NIH HHS/United States ; },
mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Chromosome Aberrations ; Female ; Genomics ; Humans ; Lung Neoplasms/*genetics/pathology ; Mutation ; Neuroendocrine Tumors/*genetics/pathology ; Pancreatic Neoplasms/*genetics/pathology ; Receptors, Estrogen/genetics ; Transcription Factors/genetics ; *Transcriptome ; Exome Sequencing ; },
abstract = {AIMS: Breast neuroendocrine tumours (NETs) constitute a rare histologic subtype of oestrogen receptor (ER)-positive breast cancer, and their definition according to the WHO classification was revised in 2019. Breast NETs display histologic and transcriptomic similarities with mucinous breast carcinomas (MuBCs). Here, we sought to compare the repertoire of genetic alterations in breast NETs with MuBCs and NETs from other anatomic origins.<br><br>METHODS: On histologic review applying the new WHO criteria, 18 breast tumours with neuroendocrine differentiation were reclassified as breast NETs (n=10) or other breast cancers with neuroendocrine differentiation (n=8). We reanalysed targeted sequencing or whole-exome sequencing data of breast NETs (n=10), MuBCs type A (n=12) and type B (n=11).<br><br>RESULTS: Breast NETs and MuBCs were found to be genetically similar, harbouring a lower frequency of PIK3CA mutations, 1q gains and 16q losses than ER-positive/HER2-negative breast cancers. 3/10 breast NETs harboured the hallmark features of ER-positive disease (ie, PIK3CA mutations and concurrent 1q gains/16q losses). Breast NETs showed an enrichment of oncogenic/likely oncogenic mutations affecting transcription factors compared with common forms of ER-positive breast cancer and with pancreatic and pulmonary NETs.<br><br>CONCLUSIONS: Breast NETs are heterogeneous and are characterised by an enrichment of mutations in transcription factors and likely constitute a spectrum of entities histologically and genomically related to MuBCs. While most breast NETs are distinct from ER-positive/HER2-negative IDC-NSTs, a subset of breast NETs appears to be genetically similar to common forms of ER-positive breast cancer, suggesting that some breast cancers may acquire neuroendocrine differentiation later in tumour evolution.},
}
@article {pmid33140128,
year = {2021},
author = {Chen, XY and Thike, AA and Koh, VCY and Nasir, NDM and Bay, BH and Tan, PH},
title = {Breast ductal Carcinoma in situ associated with microinvasion induces immunological response and predicts ipsilateral invasive recurrence.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {478},
number = {4},
pages = {679-686},
pmid = {33140128},
issn = {1432-2307},
support = {SHF/FG668S/2015//SingHealth Foundation/ ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*immunology/metabolism/*pathology/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*immunology/metabolism/*pathology/prevention &amp; control ; Prognosis ; Proportional Hazards Models ; },
abstract = {Although microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and established invasive ductal carcinoma, survival outcomes and biological behaviour of DCIS-Mi are still poorly understood. This study investigated the potential influence of Mi on disease-free survival (DFS) and assessed its correlations with clinicopathological parameters, prognosis, molecular, and immune markers. CD4, CD8, forkhead box P3 (FOXP3), CD68, CD163, programmed cell death protein 1 (PD-1), and its ligand (PD-L1) expression in pure DCIS and DCIS-Mi, from a cohort of 198 patients, were determined by immunohistochemistry. DFS, clinicopathological parameters, immune markers, and biomarker expression were correlated with presence of Mi. Twelve out of 198 DCIS cases were associated with Mi. DCIS-Mi was significantly linked with ipsilateral invasive recurrence (p = 0.032). Kaplan-Meier analysis revealed that DCIS-Mi had worse DFS for ipsilateral invasive recurrence (p = 0.011) and this was affirmed by multivariate Cox regression analysis (95% CI 1.181-9.010, HR = 3.262, p = 0.023). DCIS-Mi was associated with higher densities of immune infiltrates positive for CD4 (p = 0.037), FOXP3 (p = 0.037), CD163 (p = 0.01), and PD-L1 (p = 0.015). This study demonstrated that DCIS-Mi was correlated with high densities of immune infiltrates and predicted ipsilateral invasive recurrence.},
}
@article {pmid33135196,
year = {2021},
author = {Bishop, JA and Nakaguro, M and Whaley, RD and Ogura, K and Imai, H and Laklouk, I and Faquin, WC and Sadow, PM and Gagan, J and Nagao, T},
title = {Oncocytic intraductal carcinoma of salivary glands: a distinct variant with TRIM33-RET fusions and BRAF V600E mutations.},
journal = {Histopathology},
volume = {79},
number = {3},
pages = {338-346},
pmid = {33135196},
issn = {1365-2559},
support = {P01 CA240239/CA/NCI NIH HHS/United States ; //UT Southwestern Medical Center/ ; },
mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/genetics ; Carcinoma, Ductal/diagnosis/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Mutation ; Oncogene Fusion ; Oxyphil Cells/pathology ; Proto-Oncogene Proteins B-raf/*genetics ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/diagnosis/genetics/pathology ; Salivary Glands/pathology ; Sequence Analysis, RNA ; Transcription Factors/*genetics ; },
abstract = {AIMS: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC.<br><br>METHODS AND RESULTS: Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75&#xa0;years (mean, 63&#xa0;years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23&#xa0;months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations.<br><br>CONCLUSIONS: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.},
}
@article {pmid33132109,
year = {2021},
author = {Zong, Y and Montironi, R and Massari, F and Jiang, Z and Lopez-Beltran, A and Wheeler, TM and Scarpelli, M and Santoni, M and Cimadamore, A and Cheng, L},
title = {Intraductal Carcinoma of the Prostate: Pathogenesis and Molecular Perspectives.},
journal = {European urology focus},
volume = {7},
number = {5},
pages = {955-963},
doi = {10.1016/j.euf.2020.10.007},
pmid = {33132109},
issn = {2405-4569},
mesh = {*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Pelvis/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P), a clinicopathological entity characterized by malignant prostatic epithelial cells growing within ducts and/or acini, has a distinct architectural pattern, cytological features, and biological behavior. Whereas most IDC-P tumors could be derived from adjacent high-grade invasive cancer via retrograde spreading of cancer cells along benign ducts and acini, a small subset of IDC-P may arise from the transformation and intraductal proliferation of precancerous cells induced by various oncogenic events. These isolated IDC-P tumors possess a distinct mutational profile and may function as a carcinoma in situ lesion with de novo intraductal outgrowth of malignant cells. Further molecular characterization of these two types of IDC-P and better understanding of the mechanisms underlying IDC-P formation and progression could be translated into valuable biomarkers for differential diagnosis and actionable targets for therapeutic interventions. PATIENT SUMMARY: Intraductal carcinoma of the prostate is an aggressive type of prostate cancer associated with high risk for local recurrence and distant metastasis. In this review, we discussed pathogenesis, biomarkers, differential diagnoses, and therapeutic strategies for this tumor.},
}
@article {pmid33130707,
year = {2020},
author = {Kosaka, Y and Kikuchi, M and Nishimiya, H and Katoh, H and Kawaguchi, R and Araki, N and Shimazu, M and Tsumura, H and Waraya, M and Takada, F and Sengoku, N and Sangai, T},
title = {[In Situ Ductal Carcinoma with Hereditary Breast and Ovarian Cancer Syndrome in a Patient Who Received Contralateral Risk-Reducing Mastectomy-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {47},
number = {9},
pages = {1387-1389},
pmid = {33130707},
issn = {0385-0684},
mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Intraductal, Noninfiltrating ; Child ; Female ; *Hereditary Breast and Ovarian Cancer Syndrome/genetics/surgery ; Humans ; Mastectomy ; },
abstract = {A woman in her 30s presented to our hospital with the chief complaint of a right breast mass after the birth of her first child. She was diagnosed as having right invasive ductal carcinoma of Luminal-B type and T3N3cM0, stage Ⅲc. While undergoing neoadjuvant chemotherapy, she received genetic counseling and underwent genetic testing and was determined to have deleterious BRCA1 and BRCA2 mutations. After completing chemotherapy, she underwent a right total mastectomy and axillary lymph node dissection. Two years postoperatively, she requested to undergo a contralateral risk-reducing mastectomy(CRRM)of her left breast. Therefore, CT and breast MRI were performed to confirm the absence of contralateral lesions and distant metastases, and subsequently, CRRM was performed. Postoperative pathology results showed non-invasive ductal carcinoma lesions at 5 sites. In the case of hereditary breast and ovarian cancer syndrome such as in this study, lesions may be discovered at an early stage by performing risk-reducing mastectomy.},
}
@article {pmid33126344,
year = {2020},
author = {Liu, C and Wang, C and Du, Z and Xue, H and Liu, Z},
title = {Clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia.},
journal = {Medicine},
volume = {99},
number = {44},
pages = {e22904},
pmid = {33126344},
issn = {1536-5964},
mesh = {Age Factors ; Anticarcinogenic Agents/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; China/epidemiology ; Female ; Humans ; Imatinib Mesylate/*therapeutic use ; Incidence ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/diagnosis/epidemiology/pathology ; Male ; Middle Aged ; *Neoplasms, Multiple Primary/blood/diagnosis/epidemiology/pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Analysis ; Time Factors ; },
abstract = {This study was to investigate clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia (CML-DPMNs). Clinical data of thirteen CML-DPMN patients who were admitted to the First Hospital of Jilin University from May 2008 to December 2018 were collected and retrospectively analyzed. Female patients (9/13) were predominant in this cohort study. Nine patients were metachronous DPMNs (metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia) with 5 years median interval time from primary malignancy to secondary malignancy. The other 4 patients were diagnosed as synchronous CML-DPMNs. Seven of the metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia suffered from CML following many years of comprehensive anti-cancer therapy. Two of CML-MDPMN patients had invasive ductal carcinoma of breast after many years of treatment with imatinib. There was no difference between treatment-related CML group and non-treatment-related CML group in regard as the gender, age, white blood cell count, hemoglobin level, platelet count, and risk level. The median overall survival time of these thirteen patients with CML-DPMNs was not reached. In conclusion, female patients are more likely to suffer from the CML-DPMNs in the present article. Overall survival time of patients with DPMNs involving CML could be promising if timely and effective treatment therapy is adopted.},
}
@article {pmid33106505,
year = {2020},
author = {Tsai, HT and Huang, CS and Tu, CC and Liu, CY and Huang, CJ and Ho, YS and Tu, SH and Tseng, LM and Huang, CC},
title = {Multi-gene signature of microcalcification and risk prediction among Taiwanese breast cancer.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {18276},
pmid = {33106505},
issn = {2045-2322},
mesh = {Bayes Theorem ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Calcinosis/*diagnosis/genetics ; Early Detection of Cancer ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Taiwan ; Exome Sequencing ; },
abstract = {Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ[2]-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.},
}
@article {pmid33097605,
year = {2021},
author = {Kurley, SJ and Tischler, V and Bierie, B and Novitskiy, SV and Noske, A and Varga, Z and Zürrer-Härdi, U and Brandt, S and Carnahan, RH and Cook, RS and Muller, WJ and Richmond, A and Reynolds, AB},
title = {A requirement for p120-catenin in the metastasis of invasive ductal breast cancer.},
journal = {Journal of cell science},
volume = {134},
number = {6},
pages = {},
pmid = {33097605},
issn = {1477-9137},
support = {R01 CA200681/CA/NCI NIH HHS/United States ; IK6 BX005225/BX/BLRD VA/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P50 CA098131/CA/NCI NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; R01 CA055724/CA/NCI NIH HHS/United States ; P01 CA099031/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; P30 HD015052/HD/NICHD NIH HHS/United States ; R01 CA243326/CA/NCI NIH HHS/United States ; R01 CA111947/CA/NCI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; },
mesh = {Animals ; *Breast Neoplasms/genetics ; Cadherins/genetics ; Catenins/genetics ; Cell Adhesion ; Female ; Humans ; Mice ; Tumor Microenvironment ; Delta Catenin ; },
abstract = {We report here the effects of targeted p120-catenin (encoded by CTNND1; hereafter denoted p120) knockout (KO) in a PyMT mouse model of invasive ductal (mammary) cancer (IDC). Mosaic p120 ablation had little effect on primary tumor growth but caused significant pro-metastatic alterations in the tumor microenvironment, ultimately leading to a marked increase in the number and size of pulmonary metastases. Surprisingly, although early effects of p120-ablation included decreased cell-cell adhesion and increased invasiveness, cells lacking p120 were almost entirely unable to colonized distant metastatic sites in vivo The relevance of this observation to human IDC was established by analysis of a large clinical dataset of 1126 IDCs. As reported by others, p120 downregulation in primary IDC predicted worse overall survival. However, as in the mice, distant metastases were almost invariably p120 positive, even in matched cases where the primary tumors were p120 negative. Collectively, our results demonstrate a strong positive role for p120 (and presumably E-cadherin) during metastatic colonization of distant sites. On the other hand, downregulation of p120 in the primary tumor enhanced metastatic dissemination indirectly via pro-metastatic conditioning of the tumor microenvironment.},
}
@article {pmid33090732,
year = {2020},
author = {Morigny, P and Zuber, J and Haid, M and Kaltenecker, D and Riols, F and Lima, JDC and Simoes, E and Otoch, JP and Schmidt, SF and Herzig, S and Adamski, J and Seelaender, M and Berriel Diaz, M and Rohm, M},
title = {High levels of modified ceramides are a defining feature of murine and human cancer cachexia.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {11},
number = {6},
pages = {1459-1475},
pmid = {33090732},
issn = {2190-6009},
support = {J 4224/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {Animals ; *Cachexia/etiology ; *Ceramides/metabolism ; Humans ; Mice ; Muscular Atrophy ; *Neoplasms/complications ; Quality of Life ; },
abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial energy-wasting syndrome reducing the efficiency of anti-cancer therapies, quality of life, and survival of cancer patients. In the past years, most studies focused on the identification of tumour and host-derived proteins contributing to CCx. However, there is still a lack of studies addressing the changes in bioactive lipids. The aim of this study was to identify specific lipid species as a hallmark of CCx by performing a broad range lipid analysis of plasma from well-established CCx mouse models as well as cachectic and weight stable cancer patients.<br><br>METHODS: Plasma from non-cachectic (PBS-injected mice, NC26 tumour-bearing mice), pre-cachectic and cachectic mice (C26 and LLC tumour-bearing mice, Apc[Min/+] mutant mice), and plasma from weight stable and cachectic patients with gastrointestinal cancer, were analysed using the Lipidyzer&#x2122; platform. In total, 13 lipid classes and more than 1100 lipid species, including sphingolipids, neutral and polar glycerolipids, were covered by the analysis. Correlation analysis between specific lipid species and readouts of CCx were performed. Lipidomics data were confirmed by gene expression analysis of metabolic organs to analyse enzymes involved in sphingolipid synthesis and degradation.<br><br>RESULTS: A decrease in several lysophosphatidylcholine (LPC) species and an increase in numerous sphingolipids including sphingomyelins (SMs), ceramides (CERs), hexosyl-ceramides (HCERs) and lactosyl-ceramides (LCERs), were mutual features of CCx in both mice and cancer patients. Notably, sphingolipid levels gradually increased during cachexia development. Key enzymes involved in ceramide synthesis were elevated in liver but not in adipose, muscle, or tumour tissues, suggesting that ceramide turnover in the liver is a major contributor to elevated sphingolipid levels in CCx. LPC(16:1), LPC(20:3), SM(16:0), SM(24:1), CER(16:0), CER(24:1), HCER(16:0), and HCER(24:1) were the most consistently affected lipid species between mice and humans and correlated negatively (LPCs) or positively (SMs, CERs and HCERs) with the severity of body weight loss.<br><br>CONCLUSIONS: High levels of sphingolipids, specifically ceramides and modified ceramides, are a defining feature of murine and human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the inhibition of anabolic signals. The progressive increase in sphingolipids during cachexia development supports their potential as early biomarkers for CCx.},
}
@article {pmid33086236,
year = {2021},
author = {Bishop, JA and Rooper, LM and Sangoi, AR and Gagan, J and Thompson, LDR and Inagaki, H},
title = {The Myoepithelial Cells of Salivary Intercalated Duct-type Intraductal Carcinoma Are Neoplastic: A Study Using Combined Whole-slide Imaging, Immunofluorescence, and RET Fluorescence In Situ Hybridization.},
journal = {The American journal of surgical pathology},
volume = {45},
number = {4},
pages = {507-515},
doi = {10.1097/PAS.0000000000001605},
pmid = {33086236},
issn = {1532-0979},
mesh = {Aged ; Automation, Laboratory ; *Biomarkers, Tumor/analysis/genetics ; Calcium-Binding Proteins/*analysis ; *Carcinoma, Ductal/chemistry/genetics/pathology ; Female ; *Fluorescent Antibody Technique ; Gene Fusion ; Humans ; Image Interpretation, Computer-Assisted ; *In Situ Hybridization, Fluorescence ; Male ; Microfilament Proteins/*analysis ; Middle Aged ; Predictive Value of Tests ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/chemistry/genetics/pathology ; Calponins ; },
abstract = {Intraductal carcinoma (IDC) is a salivary gland tumor currently believed to be analogous to breast ductal carcinoma in situ, consisting of a complex neoplastic epithelial proliferation surrounded by a continuous layer of myoepithelial cells presumed to be native and non-neoplastic. Recent molecular insights have shown that there are at least 3 different types of IDC: (1) intercalated duct-like, with frequent NCOA4-RET fusions; (2) apocrine, with multiple mutations similar to salivary duct carcinoma; and (3) mixed intercalated duct-like and apocrine with frequent RET fusions, especially TRIM27-RET. Recent observations (eg, IDC occurring in lymph nodes) have challenged the notion that the myoepithelial cells of IDC are non-neoplastic. Five IDCs with known RET fusions by RNA sequencing were retrieved from the authors' archives, including 4 intercalated duct-like IDCs with NCOA4-RET, and 1 mixed intercalated duct-like/apocrine IDC with TRIM27-RET. A panel of immunohistochemistry antibodies (S100 protein, p63 or p40, mammaglobin, smooth muscle actin, calponin, androgen receptor) was tested. To precisely localize RET split-positive cells, each case was subjected to sequential retrieval of whole-slide imaging data of hematoxylin and eosin (HE) staining, immunofluorescence staining for calponin, and fluorescence in situ hybridization (FISH) for RET. Because NCOA4-RET is an inversion difficult to visualize on conventional RET FISH, a novel 3-color FISH technique was utilized to demonstrate it clearly. In all 5 cases, the proliferative ducts were completely surrounded by a layer of myoepithelial cells that were positive for p63 or p40, smooth muscle actin, and calponin. Using combined HE, calponin immunofluorescence, and RET FISH imaging, the positive signals were unmistakably identified in both calponin-negative ductal cells and peripheral, calponin-positive myoepithelial cells in all 5 cases. Utilizing combined HE, calponin immunofluorescence, and RET FISH imaging, we demonstrated that IDCs with RET fusions harbored this alteration in both the ductal and myoepithelial cells. This is compelling evidence that the myoepithelial cells of IDC are not mere bystanders, but are rather a component of the neoplasm itself, similar to other biphasic salivary gland neoplasms like pleomorphic adenoma and epithelial-myoepithelial carcinoma. This finding raises questions about the appropriate terminology, classification, and staging of IDC.},
}
@article {pmid33073677,
year = {2020},
author = {Qi, P and Bai, QM and Yao, QL and Yang, WT and Zhou, XY},
title = {Performance of Automated Dissection on Formalin-Fixed Paraffin-Embedded Tissue Sections for the 21-Gene Recurrence Score Assay.},
journal = {Technology in cancer research &amp; treatment},
volume = {19},
number = {},
pages = {1533033820960760},
pmid = {33073677},
issn = {1533-0338},
mesh = {Breast Neoplasms/*genetics/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/pathology ; Paraffin Embedding ; Real-Time Polymerase Chain Reaction/*methods ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Transcriptome/*genetics ; },
abstract = {This study aimed to compare the performance of MilliSect dissection and manual dissection. Twenty-five formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks were selected for comparison. Specific areas of interest (AOIs) in invasive carcinoma on tissue sections were transferred to dissection slides by manual macrodissection or the MilliSect instrument. The comparison criteria were 1) the time required for dissection; 2) RNA concentration and purity; 3) RNA quantity of 5 housekeeping genes (by RT-qPCR); and 4) ER, PR, HER2, Ki-67 and recurrence score (RS) values (by the 21-gene assay). Then, tumor-adjacent tissues, including fibrocollagenous and epithelial tissues, from the same selected tissue blocks of 8 of 25 patients were scraped using the mesodissection method, and their RS values were assessed to evaluate the influence of tumor-adjacent tissues on the target AOIs. Ultimately, 4 AOIs of invasive ductal carcinoma (IDC) from 1 tissue block of another 4 patients with lymph node (LN) metastases each, LN tissue and a mixture of IDC and LN tissue from the other tissue block of the same 4 patients were mesodissected to evaluate the influence of infiltrating lymphocyte levels on the RS values of AOIs. In our experience, the MilliSect instrument, which provides process management documentation, required more time than manual macrodissection (on average, approximately 9.1 min per sample versus 5.8 min per sample, respectively). The RNA yield and quality of the dissected tissues were comparable for the 2 methods. However, the tumor-adjacent tissues of the AOIs may influence the RS to some extent. Tumor-infiltrating lymphocytes (TILs) can dramatically increase RSs, far exceeding the influence of tumor-adjacent fibrocollagenous and epithelial tissues. In conclusion, MilliSect mesodissection is comparable to manual dissection. This mesodissection tool may facilitate AOI alignment and the dissection process for the 21-gene RS assay. Samples whose adjacent tissues are intermixed with TILs warrant special attention.},
}
@article {pmid33049657,
year = {2020},
author = {Zhang, J and Lu, CY and Qin, L and Chen, HM and Wu, SY},
title = {Breast-conserving surgery with or without irradiation in women with invasive ductal carcinoma of the breast receiving preoperative systemic therapy: A cohort study.},
journal = {Breast (Edinburgh, Scotland)},
volume = {54},
number = {},
pages = {139-147},
pmid = {33049657},
issn = {1532-3080},
mesh = {Adult ; Antineoplastic Protocols ; Breast/pathology ; Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/mortality/*therapy ; Chemotherapy, Adjuvant/methods/*mortality ; Cohort Studies ; Combined Modality Therapy ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy, Segmental/methods/*mortality ; Middle Aged ; Neoplasm Recurrence, Local/etiology/pathology ; Neoplasm Staging ; Neoplasm, Residual ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant/methods/*mortality ; Registries ; Regression Analysis ; Taiwan ; Treatment Outcome ; Young Adult ; },
abstract = {PURPOSE: To investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival.<br><br>PATIENTS AND METHODS: Patients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs).<br><br>RESULTS: Multivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2-4) or nodal (ypN2-3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03-0.81), 0.32 (0.16-0.64), 0.43 (0.23-0.79), 0.23 (0.13-0.42), 0.52 (0.20-1.33), and 0.34 (0.13-0.87) in the ypT0, ypT1, ypT2-4, ypN0, ypN1, and ypN2-3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00-4.07), 0.46 (0.26-0.83), 0.18 (0.06-0.51), 0.28 (0.06-1.34), 0.25 (0.10-0.63), 0.47 (0.23-0.88), and 0.32 in the cT0-1, cT2, cT3, cT4, cN0, cN1, and cN2-3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST.<br><br>CONCLUSION: WBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response.},
}
@article {pmid33047834,
year = {2021},
author = {Nishimoto, A and Kuwahara, H and Ohashi, R and Ansai, SI},
title = {Multicentric endocrine mucin-producing sweat gland carcinoma and mucinous carcinoma of the skin: A case report.},
journal = {Journal of cutaneous pathology},
volume = {48},
number = {1},
pages = {165-170},
doi = {10.1111/cup.13896},
pmid = {33047834},
issn = {1600-0560},
mesh = {Adenocarcinoma, Mucinous/*pathology ; Aged ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Humans ; Mucins ; Neoplasms, Multiple Primary/*pathology ; Skin Neoplasms/*pathology ; Sweat Gland Neoplasms/*pathology ; Uterine Neoplasms/pathology ; },
abstract = {Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade sweat gland carcinoma. EMPSGC is thought to be a precursor to mucinous carcinoma of the skin (MCS). Since the first description of EMPSGC in 1997, only a few cases have been reported, and its etiology and mechanisms remain unknown. In this report, we describe a 71-year-old Japanese woman with two isolated EMPSGC and one MCS lesion on her face. She was simultaneously diagnosed with invasive ductal carcinoma of the breast. She had a history of uterine cancer of unknown histopathological diagnosis 24 years previously. The presence of in situ lesions confirmed by myoepithelial cells suggested that the cutaneous lesions were primary tumors. To the best of our knowledge, this is the first case of multiple primary EMPSGC/MCS tumors. Additionally, this might be the first case with multiple primary carcinomas including adnexal cutaneous tumors, breast cancer, and uterine cancer, which may share the common feature of expressing female hormonal receptors. This case indicates that EMPSGC/MCS may be triggered by a hormonal receptor abnormality, perhaps because of genetic defects. A larger number of reports examining this issue may be necessary to further assess our initial observations.},
}
@article {pmid33039708,
year = {2020},
author = {Bitencourt, AGV and Gibbs, P and Rossi Saccarelli, C and Daimiel, I and Lo Gullo, R and Fox, MJ and Thakur, S and Pinker, K and Morris, EA and Morrow, M and Jochelson, MS},
title = {MRI-based machine learning radiomics can predict HER2 expression level and pathologic response after neoadjuvant therapy in HER2 overexpressing breast cancer.},
journal = {EBioMedicine},
volume = {61},
number = {},
pages = {103042},
pmid = {33039708},
issn = {2352-3964},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; *Biomarkers ; Breast Neoplasms/*diagnostic imaging/*genetics/therapy ; Female ; *Gene Expression ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; *Machine Learning ; *Magnetic Resonance Imaging/methods ; Middle Aged ; Neoadjuvant Therapy ; ROC Curve ; Receptor, ErbB-2/*genetics/metabolism ; Young Adult ; },
abstract = {BACKGROUND: To use clinical and MRI radiomic features coupled with machine learning to assess HER2 expression level and predict pathologic response (pCR) in HER2 overexpressing breast cancer patients receiving neoadjuvant chemotherapy (NAC).<br><br>METHODS: This retrospective study included 311 patients. pCR was defined as no residual invasive carcinoma in the breast or axillary lymph nodes (ypT0/isN0). Radiomics/statistical analysis was performed using MATLAB and CERR software. After ROC and correlation analysis, selected radiomics parameters were advanced to machine learning modelling alongside clinical MRI-based parameters (lesion type, multifocality, size, nodal status). For predicting pCR, the data was split into a training and test set (80:20).<br><br>FINDINGS: The overall pCR rate was 60.5% (188/311). The final model to predict HER2 heterogeneity utilised three MRI parameters (two clinical, one radiomic) for a sensitivity of 99.3% (277/279), specificity of 81.3% (26/32), and diagnostic accuracy of 97.4% (303/311). The final model to predict pCR included six MRI parameters (two clinical, four radiomic) for a sensitivity of 86.5% (32/37), specificity of 80.0% (20/25), and diagnostic accuracy of 83.9% (52/62) (test set); these results were independent of age and ER status, and outperformed the best model developed using clinical parameters only (p=0.029, comparison of proportion Chi-squared test).<br><br>INTERPRETATION: The machine learning models, including both clinical and radiomics MRI features, can be used to assess HER2 expression level and can predict pCR after NAC in HER2 overexpressing breast cancer patients.<br><br>FUNDING: NIH/NCI (P30CA008748), Susan G. Komen Foundation, Breast Cancer Research Foundation, Spanish Foundation Alfonso Martin Escudero, European School of Radiology.},
}
@article {pmid33027710,
year = {2021},
author = {Thongpiya, J and Sa-Nguanraksa, D and Samarnthai, N and Sarasombath, PT},
title = {Filariasis of the breast caused by Brugia pahangi: A concomitant finding with invasive ductal carcinoma.},
journal = {Parasitology international},
volume = {80},
number = {},
pages = {102203},
pmid = {33027710},
issn = {1873-0329},
mesh = {Animals ; Breast Diseases/*diagnosis/parasitology ; Breast Neoplasms/*pathology ; Brugia pahangi/classification/*isolation &amp; purification ; Carcinoma, Ductal, Breast/*pathology ; DNA, Ribosomal Spacer/analysis ; Female ; Filariasis/*diagnosis/parasitology ; Humans ; Middle Aged ; RNA, Helminth/analysis ; RNA, Ribosomal/analysis ; Thailand ; },
abstract = {Extralymphatic filariasis is an uncommon phenomenon that can be caused by several lymphatic filarial species, including zoonotic filaria of animal origins. In this study, we report a case of a 64-year-old Thai woman who presented with a lump in her left breast that was diagnosed with invasive ductal carcinoma. At the same time, a small nodule was found in her right breast, via imaging study, without any abnormal symptoms. A core needle biopsy of the right breast nodule revealed a filarial-like nematode compatible with the adult stage of Brugia sp. A molecular identification of the nematode partial mt 12rRNA gene and ITS1 suggested the causative species as closely related to Brugia pahangi, a zoonotic lymphatic filaria of animals such as cats and dogs. The sequence of the partial mt 12rRNA and ITS1 gene in this patient was 94% and 99% identical to the previously reported sequence of mt 12rRNA and ITS1 genes of B. pahangi. The sequence of ITS1 gene is 99% similar to B. pahangi microfilaria from infected dogs in Bangkok, which was highly suspected of having a zoonotic origin. As far as we know, this is the first case report of B. pahangi filariasis presented with a breast mass concomitantly found in a patient with invasive ductal carcinoma. This raised serious concern regarding the zoonotic transmission of filariasis from natural animal reservoirs.},
}
@article {pmid33027370,
year = {2020},
author = {Gewehr, DM and Salgueiro, GR and Noronha, L and Kubrusly, FB and Kubrusly, LF and Coltro, GA and Preto, PC and Bertoldi, AS and Vieira, HI},
title = {Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension.},
journal = {Arquivos brasileiros de cardiologia},
volume = {115},
number = {3},
pages = {480-490},
pmid = {33027370},
issn = {1678-4170},
mesh = {Animals ; Humans ; *Hypertension, Pulmonary/chemically induced ; Hypertrophy, Right Ventricular/chemically induced ; Male ; Monocrotaline/toxicity ; *Pulmonary Arterial Hypertension ; Rats ; Rats, Wistar ; },
abstract = {BACKGROUND: The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans.<br><br>OBJECTIVE: To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival.<br><br>METHODS: Fifty male Wistar rats were divided into one of the four groups - control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%.<br><br>RESULTS: In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000).<br><br>CONCLUSION: The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490).},
}
@article {pmid33024608,
year = {2020},
author = {Matich, A and Sud, S and Buxi, TBS and Dogra, V},
title = {Idiopathic Granulomatous Mastitis and its Mimics on Magnetic Resonance Imaging: A Pictorial Review of Cases from India.},
journal = {Journal of clinical imaging science},
volume = {10},
number = {},
pages = {53},
pmid = {33024608},
issn = {2156-7514},
abstract = {OBJECTIVES: Idiopathic granulomatous mastitis (IGM) is a rare inflammatory disease of the breast, which is benign but potentially morbid. Mammographic and sonographic findings have been well characterized, but magnetic resonance imaging (MRI) findings have been less thoroughly documented. The objective of this study was to demonstrate characteristic findings for IGM and its mimics via a retrospective review.<br><br>MATERIAL AND METHODS: Breast MRI examinations performed at Sir Ganga Ram Hospital in New Delhi, India between 2014 and 2019 were retrospectively reviewed to identify cases in which a pattern suggestive of granulomatous mastitis was seen. Cases of known malignancy were excluded. Any available breast pathology results were then obtained, and cases with presumptive or definitive diagnoses were compiled for analysis.<br><br>RESULTS: Overall, cases identified with characteristic imaging findings and confirmed diagnosis included seven cases of IGM, four cases of invasive ductal carcinoma, two cases of tuberculous mastitis, one case of non- tuberculous infectious mastitis, one case of foreign body mastitis, and one case of eosinophilc mastitis. One case of IGM with masses rather than of non-mass enhancement was also identified.<br><br>CONCLUSION: In our review, cases with clustered ring enhancement were found to have inflammatory, idiopathic, infectious and malignant etiologies. While, these etiologies can only be reliably differentiated on pathology, familiarity with the pattern and an awareness of the differential may lead to decreased morbidity due to delays in diagnosis.},
}
@article {pmid33023170,
year = {2020},
author = {Petre, AR and Craciunescu, R and Fratu, O},
title = {Design, Implementation and Simulation of a Fringing Field Capacitive Humidity Sensor.},
journal = {Sensors (Basel, Switzerland)},
volume = {20},
number = {19},
pages = {},
pmid = {33023170},
issn = {1424-8220},
support = {51675/09.07.2019, SMIS code 125125//Operational Programme Human Capital of the Ministry of European Funds through the Financial Agreement/ ; 33PCCDI/2018//Ministry of Innovation and Research, UEFISCDI, MultiMonD2 within PNCDI III/ ; },
abstract = {The world population is growing in an accelerated way urging the need for a more efficient and sustainable agricultural industry. Initially developed for smart cities which face the same challenges caused by an increasing population, Internet of Things (IoT) technologies have evolved rapidly over the last few years and are now moving successfully to agriculture. Wireless Sensor Networks (WSNs) have been reported to be used in the agri-food sector and could answer the call for a more optimized agricultural management. This paper investigates a PCB-made interdigited capacitive (IDC) soil humidity sensor as a low-price alternative to the existing ones on the market. An in-depth comparative study is performed on 30 design variations, part of them also manufactured for further investigations. By measurements and simulations, the influence of the aspect ratio and dielectric thickness on the sensitivity and capacitance of the sensor are studied. In the end, a Humidity and Temperature Measurement Wireless Equipment (HTMWE) for IoT agriculture applications is implemented with this type of sensor.},
}
@article {pmid33016589,
year = {2019},
author = {Merry, R and Butenhoff, K and Campbell, BW and Michno, JM and Wang, D and Orf, JH and Lorenz, AJ and Stupar, RM},
title = {Identification and Fine-Mapping of a Soybean Quantitative Trait Locus on Chromosome 5 Conferring Tolerance to Iron Deficiency Chlorosis.},
journal = {The plant genome},
volume = {12},
number = {3},
pages = {1-13},
doi = {10.3835/plantgenome2019.01.0007},
pmid = {33016589},
issn = {1940-3372},
mesh = {Genome-Wide Association Study ; *Iron Deficiencies ; *Plant Diseases ; Quantitative Trait Loci ; Glycine max/*genetics ; },
abstract = {CORE IDEAS: 'Fiskeby III' harbors a combination of abiotic stress traits, including iron deficiency chlorosis (IDC) tolerance. An IDC quantitative trait locus on chromosome Gm05 was identified in genome-wide association studies and biparental populations. Fine-mapping resolved a 137-kb interval containing strong candidate genes. Iron deficiency chlorosis (IDC) is an important nutrient stress for soybean [Glycine max (L.) Merr.] grown in high-pH soils. Despite numerous agronomic attempts to alleviate IDC, genetic tolerance remains the most effective preventative measure against symptoms. In this study, two association mapping populations and a biparental mapping population were used for genetic mapping of IDC tolerance. Quantitative trait loci (QTLs) were identified on chromosomes Gm03, Gm05, and Gm06. Heterogenous inbred families were developed to fine-map the Gm05 QTL, which was uniquely supported in all three mapping populations. Fine-mapping resulted in a QTL with an interval size of 137 kb on the end of the short arm of Gm05, which produced up to a 1.5-point reduction in IDC severity on a 1 to 9 scale in near isogenic lines.},
}
@article {pmid33011829,
year = {2021},
author = {Sadeghalvad, M and Mohammadi-Motlagh, HR and Rezaei, N},
title = {Immune microenvironment in different molecular subtypes of ductal breast carcinoma.},
journal = {Breast cancer research and treatment},
volume = {185},
number = {2},
pages = {261-279},
pmid = {33011829},
issn = {1573-7217},
support = {41086//Tehran University of Medical Sciences/ ; },
mesh = {Biomarkers, Tumor ; *Breast Neoplasms/genetics/immunology ; *Carcinoma, Ductal, Breast ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; *Immunity, Cellular ; Prognosis ; *Tumor Microenvironment ; },
abstract = {PURPOSE: Ductal breast carcinoma as a heterogeneous disease has different molecular subtypes associated with clinical prognosis and patients' survival. The role of immune system as a consistent part of the tumor microenvironment (TME) has been documented in progression of ductal breast carcinoma. Here, we aimed to describe the important immune cells and the immune system-associated molecules in Ductal Carcinoma In situ (DCIS) and Invasive Ductal Carcinoma (IDC) with special emphasis on their associations with different molecular subtypes and patients' prognosis.<br><br>RESULTS: The immune cells have a dual role in breast cancer (BC) microenvironment depending on the molecular subtype or tumor grade. These cells with different frequencies are present in the TME of DCIS and IDC. The presence of regulatory cells including Tregs, MDSC, Th2, Th17, M2 macrophages, HLADR[-] T cells, and T&#x3b3;&#x3b4; cells is related to more immunosuppressive microenvironment, especially in ER[-] and TN subtypes. In contrast, NK cells, CTL, Th, and Tfh cells are associated to the anti-tumor activity. These cells are higher in ER[+] BC, although in other subtypes such as TN or HER2[+] are associated with a favorable prognosis.<br><br>CONCLUSION: Determining the specific immune response in each subtype could be helpful in estimating the possible behavior of the tumor cells in TME. It is important to realize that different frequencies of immune cells in BC environment likely determine the patients' prognosis and their survival in each subtype. Therefore, elucidation of the distinct immune players in TME would be helpful toward developing targeted therapies in each subtype.},
}
@article {pmid33011180,
year = {2020},
author = {Roberts, WC and Everett, BP and Won, VS and Kondapalli, N},
title = {Diagnostic Usefulness of Histological Examination of the Left Ventricular "Core" Excised to Insert a Left Ventricular Assist Device in Patients With Severe Heart Failure.},
journal = {The American journal of cardiology},
volume = {137},
number = {},
pages = {71-76},
doi = {10.1016/j.amjcard.2020.09.038},
pmid = {33011180},
issn = {1879-1913},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Female ; Heart Failure/*diagnosis/physiopathology/therapy ; *Heart-Assist Devices ; Humans ; Male ; Middle Aged ; Myocardium/*pathology ; Severity of Illness Index ; Stroke Volume/*physiology ; Ventricular Function, Left/*physiology ; Young Adult ; },
abstract = {The left ventricular assist device (LVAD) has proven to be beneficial for patients with severe heart failure poorly responsive to anti heart failure medicine. To examine both grossly and histologically the portion of left ventricular (LV) free wall excised ("the left ventricular core") to insert a LVAD in 337 patients with severe heart failure from a variety of causes. We collected together all photographs of LV "cores" and the histologic sections prepared from them and reexamined both. Despite the fact that these LV cores usually weighed >100 times the quantity of myocardium available to examine compared with that available by biotome inserted via a transvenous catheter, the number in which histologic study allowed an unequivocal diagnosis was limited. Examination of the clinical records usually was required to establish the definitive diagnosis. Although the presence of a scarred myocardial wall usually suggested ischemic cardiomyopathy (IC), the scarring may not have involved the LV apex resulting in a nonscarred portion of myocardium simulating idiopathic dilated cardiomyopathy (IDC). Moreover, about 10% of the patients with IDC have myocardial scars thus simulating IC. Involvement of the LV core by amyloid, sarcoid, myocarditis, and acute infarction, of course, allowed a specific anatomic diagnosis. Despite the presence of ample tissue to secure a definitive diagnosis, the combination of clinical input and morphologic assessment was required to arrive at a definite diagnosis in most patients.},
}
@article {pmid32995936,
year = {2021},
author = {Doello, K and Conde, V and Perez, MC and Mendoza, I and Mesas, C and Prados, J},
title = {Unusual long survival in a case of heterotaxy and polysplenia.},
journal = {Surgical and radiologic anatomy : SRA},
volume = {43},
number = {4},
pages = {607-611},
pmid = {32995936},
issn = {1279-8517},
mesh = {Bone Neoplasms/diagnosis/secondary ; Breast Neoplasms/diagnosis/therapy ; Carcinoma, Ductal, Breast/diagnosis/therapy ; Chemoradiotherapy, Adjuvant ; Contrast Media/administration &amp; dosage ; Female ; Heterotaxy Syndrome/*diagnosis ; Humans ; Incidental Findings ; Liver Neoplasms/diagnosis/secondary ; Mastectomy, Segmental ; Middle Aged ; Spleen/*abnormalities/diagnostic imaging ; Time Factors ; Tomography, X-Ray Computed ; },
abstract = {Heterotaxy syndrome with polysplenia is an extremely rare congenital disorder caused by a disruption in the embryonic development that results in an abnormal arrangement of the abdominal and thoracic organs. We present the case of a 59-year-old female patient with invasive ductal carcinoma of the right breast (luminal A type) and CT findings of heterotaxy syndrome with polysplenia. The most remarkable anomalies identified were a left inferior vena cava draining into the hemiazygos vein, absent inferior vena cava at the thoracic level, and hepatic veins directly draining into the right atrium. Moreover, an atrial septal defect was identified, explaining the pulmonary hypertension of unknown cause previously detected in the patient. The relevance of this case lies in the unusual anatomical abnormalities found and the large patient survival, having in to account the great rate of heterotaxy syndrome mortality in the first years of life.},
}
@article {pmid32988889,
year = {2020},
author = {Yildirim, E and Bektas, S and Gundogar, O and Findik, D and Alcicek, S and Erdogan, KO and Yildiz, M},
title = {The Relationship of GATA3 and Ki-67 With Histopathological Prognostic Parameters, Locoregional Recurrence and Disease-free Survival in Invasive Ductal Carcinoma of the Breast.},
journal = {Anticancer research},
volume = {40},
number = {10},
pages = {5649-5657},
doi = {10.21873/anticanres.14578},
pmid = {32988889},
issn = {1791-7530},
mesh = {Adult ; Biomarkers, Tumor ; Carcinoma, Ductal, Breast/epidemiology/*genetics/pathology ; Disease-Free Survival ; Estrogens/genetics ; Female ; GATA3 Transcription Factor/*genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/*genetics ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*genetics/pathology ; Progesterone/genetics ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; },
abstract = {BACKGROUND: In recent years, GATA-binding protein 3 (GATA3) has been indicated as a marker showing good prognosis in breast cancer. In luminal breast cancer, which has good a prognosis, it shows more significant elevation in small-sized and low-grade tumors. In contrast, Ki-67 is defined as a poor prognostic factor. The aim of this study was to emphasise the prognostic importance of GATA3 and the inverse relationship with Ki-67.<br><br>MATERIALS AND METHODS: In our study, 90 patients with invasive ductal breast cancer were immunohistochemically evaluated for Ki-67 and GATA3 expression. The relationship between GATA3 and Ki-67 expression was examined. In addition, the relationship between these two factors with estrogen, progesterone, human epidermal growth factor 2 receptor antibodies and other prognostic parameters such as disease-free survival and local recurrence was investigated. We accepted the level of &#x2265;5% n&#xfc;clear reaction as positive for GATA 3. A Ki-67 cut-off value of 20% was accepted as positive.<br><br>RESULTS: In GATA3 positive breast cancers, good prognostic parameters were seen including high estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, small tumor size and low histological grade as well as low Ki-67 expression. In breast cancers showing high Ki-67 expression, ER, PR, and GATA3 positivity were lower and there was higher human epidermal growth factor receptor 2 (HER2) positivity and high histological grade while the tumor size was larger.<br><br>CONCLUSION: Our study has revealed that GATA3 has an inverse relationship with Ki-67, whereas it has a positive releationship with good prognostic factors.},
}
@article {pmid32980661,
year = {2020},
author = {Lou, B and Boger, M and Bennewitz, K and Sticht, C and Kopf, S and Morgenstern, J and Fleming, T and Hell, R and Yuan, Z and Nawroth, PP and Kroll, J},
title = {Elevated 4-hydroxynonenal induces hyperglycaemia via Aldh3a1 loss in zebrafish and associates with diabetes progression in humans.},
journal = {Redox biology},
volume = {37},
number = {},
pages = {101723},
pmid = {32980661},
issn = {2213-2317},
mesh = {*Aldehyde Dehydrogenase/genetics ; Aldehydes ; Animals ; *Diabetes Mellitus ; Gene Knockout Techniques ; Humans ; *Hyperglycemia/genetics ; *Zebrafish/genetics ; },
abstract = {Increased methylglyoxal (MG) formation is associated with diabetes and its complications. In zebrafish, knockout of the main MG detoxifying system Glyoxalase 1, led to limited MG elevation but significantly elevated aldehyde dehydrogenases (ALDH) activity and aldh3a1 expression, suggesting the compensatory role of Aldh3a1 in diabetes. To evaluate the function of Aldh3a1 in glucose homeostasis and diabetes, aldh3a1[-/-] zebrafish mutants were generated using CRISPR-Cas9. Vasculature and pancreas morphology were analysed by zebrafish transgenic reporter lines. Corresponding reactive carbonyl species (RCS), glucose, transcriptome and metabolomics screenings were performed and ALDH activity was measured for further verification. Aldh3a1[-/-] zebrafish larvae displayed retinal vasodilatory alterations, impaired glucose homeostasis, which can be aggravated via pdx1 silencing induced hyperglycaemia. Unexpectedly, MG was not altered, but 4-hydroxynonenal (4-HNE), another prominent lipid peroxidation RCS exhibited high affinity with Aldh3a1, was increased in aldh3a1 mutants. 4-HNE was responsible for the retinal phenotype via pancreas disruption induced hyperglycaemia and can be rescued via l-Carnosine treatment. Furthermore, in type 2 diabetic patients, serum 4-HNE was increased and correlated with disease progression. Thus, our data suggest impaired 4-HNE detoxification and elevated 4-HNE concentration as biomarkers but also the possible inducers for diabetes, from genetic susceptibility to the pathological progression.},
}
@article {pmid32975612,
year = {2020},
author = {Yoshida, Y and Matsumoto, I and Tanaka, T and Yamao, K and Hayashi, A and Kamei, K and Satoi, S and Takebe, A and Nakai, T and Takenaka, M and Takeyama, Y},
title = {Pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct leading to pancreatic pleural effusion: a case report.},
journal = {Surgical case reports},
volume = {6},
number = {1},
pages = {222},
pmid = {32975612},
issn = {2198-7793},
abstract = {BACKGROUND: Pancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion.<br><br>CASE PRESENTATION: A 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854&#xa0;IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15&#x2009;&#xd7;&#x2009;15&#xa0;mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor.<br><br>CONCLUSIONS: Differential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.},
}
@article {pmid38424901,
year = {2020},
author = {Samreen, N and Moy, L and Lee, CS},
title = {Architectural Distortion on Digital Breast Tomosynthesis: Management Algorithm and Pathological Outcome.},
journal = {Journal of breast imaging},
volume = {2},
number = {5},
pages = {424-435},
doi = {10.1093/jbi/wbaa034},
pmid = {38424901},
issn = {2631-6129},
abstract = {Architectural distortion on digital breast tomosynthesis (DBT) can occur due to benign and malignant causes. With DBT, there is an increase in the detection of architectural distortion compared with 2D digital mammography, and the positive predictive value is high enough to justify tissue sampling when imaging findings are confirmed. Workup involves supplemental DBT views and ultrasound, with subsequent image-guided percutaneous biopsy using the modality on which it is best visualized. If architectural distortion is subtle and/or questionable on diagnostic imaging, MRI may be performed for problem solving, with subsequent biopsy of suspicious findings using MRI or DBT guidance, respectively. If no suspicious findings are noted on MRI, a six-month follow-up DBT may be performed. On pathology, malignant cases are noted in 6.8%-50.7% of the cases, most commonly due to invasive ductal carcinoma, followed by invasive lobular carcinoma. Radial scars are the most common benign cause, with stromal fibrosis and sclerosing adenosis being much less common. As there is an increase in the number of benign pathological outcomes for architectural distortion on DBT compared with 2D digital mammography, concordance should be based on the level of suspicion of imaging findings. As discordant cases have upgrade rates of up to 25%, surgical consultation is recommended for discordant radiologic-pathologic findings.},
}
@article {pmid32957504,
year = {2020},
author = {Griffin, N and Marsland, M and Roselli, S and Oldmeadow, C and Attia, J and Walker, MM and Hondermarck, H and Faulkner, S},
title = {The Receptor Tyrosine Kinase TrkA Is Increased and Targetable in HER2-Positive Breast Cancer.},
journal = {Biomolecules},
volume = {10},
number = {9},
pages = {},
pmid = {32957504},
issn = {2218-273X},
support = {G1101013//Faculty of Health and Medicine, University of Newcastle Australia/International ; },
mesh = {Biomarkers, Tumor/antagonists &amp; inhibitors/*biosynthesis/genetics ; Breast Neoplasms/drug therapy/genetics/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/genetics/metabolism ; Carcinoma, Lobular/drug therapy/genetics/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunohistochemistry ; Middle Aged ; Molecular Targeted Therapy/methods ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Receptor, ErbB-2/*metabolism ; Receptor, trkA/antagonists &amp; inhibitors/*biosynthesis/genetics ; Survival Analysis ; },
abstract = {The tyrosine kinase receptor A (NTRK1/TrkA) is increasingly regarded as a therapeutic target in oncology. In breast cancer, TrkA contributes to metastasis but the clinicopathological significance remains unclear. In this study, TrkA expression was assessed via immunohistochemistry of 158 invasive ductal carcinomas (IDC), 158 invasive lobular carcinomas (ILC) and 50 ductal carcinomas in situ (DCIS). TrkA was expressed in cancer epithelial and myoepithelial cells, with higher levels of TrkA positively associated with IDC (39% of cases) (p < 0.0001). Interestingly, TrkA was significantly increased in tumours expressing the human epidermal growth factor receptor-2 (HER2), with expression in 49% of HER2-positive compared to 25% of HER2-negative tumours (p = 0.0027). A panel of breast cancer cells were used to confirm TrkA protein expression, demonstrating higher levels of TrkA (total and phosphorylated) in HER2-positive cell lines. Functional investigations using four different HER2-positive breast cancer cell lines indicated that the Trk tyrosine kinase inhibitor GNF-5837 reduced cell viability, through decreased phospho-TrkA (Tyr490) and downstream AKT (Ser473) activation, but did not display synergy with Herceptin. Overall, these data highlight a relationship between the tyrosine kinase receptors TrkA and HER2 and suggest the potential of TrkA as a novel or adjunct target for HER2-positive breast tumours.},
}
@article {pmid32947148,
year = {2020},
author = {Zhang, J and Lu, CY and Chen, CH and Chen, HM and Wu, SY},
title = {Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis.},
journal = {Breast (Edinburgh, Scotland)},
volume = {54},
number = {},
pages = {70-78},
pmid = {32947148},
issn = {1532-3080},
mesh = {Adult ; Breast/pathology ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Chemotherapy, Adjuvant ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Staging ; Postoperative Period ; Proportional Hazards Models ; *Radiotherapy, Adjuvant ; Registries ; Regression Analysis ; Taiwan ; Treatment Outcome ; Young Adult ; },
abstract = {PURPOSE: To use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).<br><br>PATIENTS AND METHODS: We enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.<br><br>RESULTS: After multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52-0.81, P&#xa0;<&#xa0;0.0001) and 0.58 (0.47-0.71, P&#xa0;<&#xa0;0.0001) in postchemotherapy pathologic tumor stages T2-4 (ypT3-4) and postchemotherapy pathologic nodal stages N2-3 (ypN2-3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38-0.69, P&#xa0;<&#xa0;0.0001), 0.60 (0.40-0.88, P&#xa0;=&#xa0;0.0096), and 0.64 (0.48-0.86, P&#xa0;=&#xa0;0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0-4, ypN0-3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.<br><br>CONCLUSION: For patients with breast cancer ypT3-4, ypN2-3, or pathologic stages IIIA-IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.},
}
@article {pmid32943456,
year = {2020},
author = {Richard, F and Majjaj, S and Venet, D and Rothé, F and Pingitore, J and Boeckx, B and Marchio, C and Clatot, F and Bertucci, F and Mariani, O and Galant, C and Eynden, GVD and Salgado, R and Biganzoli, E and Lambrechts, D and Vincent-Salomon, A and Pruneri, G and Larsimont, D and Sotiriou, C and Desmedt, C},
title = {Characterization of Stromal Tumor-infiltrating Lymphocytes and Genomic Alterations in Metastatic Lobular Breast Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {26},
number = {23},
pages = {6254-6265},
doi = {10.1158/1078-0432.CCR-20-2268},
pmid = {32943456},
issn = {1557-3265},
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/immunology/metabolism/*secondary ; Carcinoma, Lobular/genetics/immunology/metabolism/*secondary ; Female ; Follow-Up Studies ; Genomics/*methods ; Humans ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Stromal Cells/*immunology ; Survival Rate ; },
abstract = {PURPOSE: Invasive lobular carcinoma (ILC) represents the second most common histologic breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level.<br><br>EXPERIMENTAL DESIGN: We retrospectively assembled the multicentric EuroILC series of matched primary and metastatic samples from 94 patients with estrogen receptor (ER)-positive ILC. Stromal tumor-infiltrating lymphocytes (sTILs) were assessed by experienced pathologists. Targeted sequencing and low pass whole-genome sequencing were conducted to detect mutations and copy-number aberrations (CNAs). We compared the frequencies of the alterations in EuroILC with those from patients with ER-positive metastatic ILC (n = 135) and IDC (n = 563) from MSK-IMPACT.<br><br>RESULTS: Low sTIL levels were observed in ILC metastases, with higher levels in the mixed nonclassic histology. Considering ILC metastases from EuroILC and MSK-IMPACT, we observed that >50% of tumors harbor genomic alterations that have previously been associated with endocrine resistance. A matched primary/metastasis comparison in EuroILC revealed mutations (AKT1, ARID1A, ESR1, ERBB2, or NF1) and CNAs (PTEN or NF1 deletion, CYP19A1 amplification) associated with endocrine resistance that were private to the metastasis in 22% (7/32) and 19% (4/21) of patients, respectively. An increase in CDH1, ERBB2, FOXA1, and TBX3 mutations, in CDH1 deletions and a decrease in TP53 mutations was observed in ILC as compared with IDC metastases.<br><br>CONCLUSIONS: ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared with IDC metastases.},
}
@article {pmid32920553,
year = {2020},
author = {Bartlett, H and Elghobashy, M and Deshmukh, N and Rao, R and Shaaban, AM},
title = {Radiation-Associated Primary Osteosarcoma of the Breast.},
journal = {Pathobiology : journal of immunopathology, molecular and cellular biology},
volume = {87},
number = {5},
pages = {322-326},
doi = {10.1159/000509580},
pmid = {32920553},
issn = {1423-0291},
mesh = {Aged ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/*etiology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Osteosarcoma/*diagnostic imaging/*etiology/surgery ; Radiation Injuries/complications ; Radiotherapy/*adverse effects ; },
abstract = {INTRODUCTION: Non-epithelial primary mammary osteosarcomas are extremely rare. The differentials include metaplastic carcinoma and malignant phyllodes tumour. This is the first published case of primary breast osteosarcoma arising after local radiotherapy.<br><br>CASE PRESENTATION: A 73-year-old female presented with a right-sided breast lump. The same breast had been irradiated 11 years previously for invasive ductal carcinoma. Diagnostic excision revealed a highly cellular, malignant spindle-cell lesion merged with an osteoid matrix and foci of calcification and bone formation. Immunohistochemistry and molecular studies showed no lines of differentiation. Due to the lack of epithelial/glandular differentiation, in situ carcinoma or leaf-like pattern, the diagnosis of post-irradiation osteosarcoma was made. She underwent mastectomy and is disease-free at 8 months of follow-up.<br><br>CONCLUSION: Post-irradiation osteosarcoma should be considered in the differential diagnosis of breast lesions showing malignant osteoid. Extensive sampling and careful search for epithelial differentiation is required to guide management. Complete surgical excision is recommended.},
}
@article {pmid32884534,
year = {2020},
author = {Liu, IC and Giap, F and Mailhot-Vega, RB and Bradley, JA and Mendenhall, NP and Okunieff, P and Lu, L and Jantz, MA and Daily, K and Spiguel, L and Lockney, NA},
title = {Concomitant Radiation Recall Dermatitis and Organizing Pneumonia following Breast Radiotherapy: A Case Report.},
journal = {Case reports in oncology},
volume = {13},
number = {2},
pages = {875-882},
pmid = {32884534},
issn = {1662-6575},
abstract = {PURPOSE: Radiation recall dermatitis (RRD) is a rare complication that occurs after completion of radiation therapy (RT) and initiation of a precipitating agent, most commonly chemotherapeutic medications. Various theories attempt to explain the mechanism, including activation of the body's inflammatory pathways through nonimmune activation. Likewise, radiation-induced organizing pneumonia (RIOP) is an infrequent but potentially life-threatening complication of RT that, while not fully understood, is suspected to be partly an autoimmune reaction.<br><br>PATIENT: We present the case of a 71-year-old female with a history of type 2 diabetes mellitus, hypothyroidism, interstitial cystitis, and osteoarthritis who presented with clinical stage T1N0M0 ER+/PR-/HER2- invasive ductal carcinoma of the lower outer quadrant of the left breast, for which she underwent left segmental mastectomy and sentinel lymph node biopsy followed by completion axillary lymph node dissection. Her final pathologic stage was T1N1M0.<br><br>RESULT: The patient developed RRD and later RIOP following receipt of radiation and chemotherapy, which resolved with steroid administration.<br><br>CONCLUSIONS: The rarity of both RRD and RIOP occurring in a patient, as in our case, suggests a shared pathophysiology behind these two complications. As both reactions involve some degree of inflammation and respond to corticosteroids, it seems likely that the etiologies of RRD and RIOP lie within the inflammatory pathway. However, further investigation should evaluate the frequency, duration, and triggering of concomitant RRD and RIOP.},
}
@article {pmid32877689,
year = {2020},
author = {Rohm, M and Herzig, S},
title = {An Antibody Attack against Body Wasting in Cancer.},
journal = {Cell metabolism},
volume = {32},
number = {3},
pages = {331-333},
doi = {10.1016/j.cmet.2020.08.003},
pmid = {32877689},
issn = {1932-7420},
mesh = {Adipose Tissue ; Animals ; *Cachexia/etiology ; Growth Differentiation Factor 15 ; Humans ; Mice ; *Neoplasms/complications ; },
abstract = {Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben et al. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL axis that efficiently blocks tumor-induced body wasting in experimental animals.},
}
@article {pmid32876204,
year = {2020},
author = {Salim, TR and Andrade, TM and Klein, CH and Oliveira, GMM},
title = {Inequalities in Mortality Rates from Malformations of Circulatory System Between Brazilian Macroregions in Individuals Younger Than 20 Years.},
journal = {Arquivos brasileiros de cardiologia},
volume = {115},
number = {6},
pages = {1164-1173},
pmid = {32876204},
issn = {1678-4170},
mesh = {Brazil/epidemiology ; *Cardiovascular Diseases ; *Cardiovascular System ; Cause of Death ; Female ; *Heart Defects, Congenital ; Humans ; Male ; Mortality ; },
abstract = {BACKGROUND: Deaths from malformations of the circulatory system (MCS) have a major impact on mortality reduction. given that most cases are avoidable with correct diagnosis and treatment.<br><br>OBJECTIVES: To describe the distribution of mortality from MCS by sex. age. and macroregion in Brazil. in individuals under the age of 20. between 2000 and 2015.<br><br>METHODS: A descriptive study of mortality rates and proportional mortality (PM) from MCS. other congenital malformations (OCM). circulatory system disease (CSD). ill-defined causes (IDC). and external causes (EC) in Brazil.<br><br>RESULTS: There were 1.367.355 deaths from all causes in individuals younger than 20. 55.0% under 1 year of age. A total of 144.057 deaths were caused by congenital malformations. 39% of them by MCS. In both sexes. the annual mortality from MCS was 5.3/100.000. PM from MCS was 4.2%. CSD 2.2%. IDC 6.2% and EC 24.9%. Unspecified MCS showed the highest PM rates in both sexes and age groups. especially in the north and northeast regions (60%). Deaths from malformations occurred 5.7 times more frequently during the first year of life than in other ages (MCS: 5.0; OCM: 6.4).<br><br>CONCLUSIONS: MCS was the leading cause of death among all malformations. being twice as important as CSD. mainly under 1 year of age. The frequency of misdiagnosis of MCS as cause of death was high in all ages and both sexes. especially in the north and northeast regions. These findings highlight the need for the development of public health strategies focused on correct diagnosis and early treatment of congenital cardiopathies. leading to a reduction in mortality. (Arq Bras Cardiol. 2020; 115(6):1164-1173).},
}
@article {pmid32871469,
year = {2020},
author = {Molocea, CE and Tsokanos, FF and Herzig, S},
title = {Exploiting common aspects of obesity and cancer cachexia for future therapeutic strategies.},
journal = {Current opinion in pharmacology},
volume = {53},
number = {},
pages = {101-116},
doi = {10.1016/j.coph.2020.07.006},
pmid = {32871469},
issn = {1471-4973},
mesh = {Animals ; Appetite Regulation ; *Cachexia/etiology/immunology/metabolism/therapy ; Humans ; Inflammation Mediators/immunology ; Macrophages/immunology ; *Neoplasms/complications/immunology/metabolism/therapy ; *Obesity/immunology/metabolism/therapy ; },
abstract = {Obesity and cancer cachexia are diseases at opposite ends of the BMI. However, despite the apparent dichotomy, these pathologies share some common underlying mechanisms that lead to profound metabolic perturbations. Insulin resistance, adipose tissue lipolysis, skeletal muscle atrophy and systemic inflammation are key players in both diseases. Several strategies for pharmacological treatments have been employed in obesity and cancer cachexia but demonstrated only limited effects. Therefore, there is still a need to develop novel, more effective strategies. In this review we summarize existing therapies and discuss potential novel strategies that could arise by bridging common aspects between obesity and cachexia. We discuss the potential role of macrophage manipulation and the modulation of inflammation by targeting Nuclear Receptors (NRs) as potential novel therapeutic strategies.},
}
@article {pmid32868877,
year = {2020},
author = {Murray, AS and Hyland, TE and Sala-Hamrick, KE and Mackinder, JR and Martin, CE and Tanabe, LM and Varela, FA and List, K},
title = {The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy.},
journal = {Oncogene},
volume = {39},
number = {41},
pages = {6421-6436},
pmid = {32868877},
issn = {1476-5594},
support = {R25 GM058905/GM/NIGMS NIH HHS/United States ; F31 CA217148/CA/NCI NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; R01 CA160565/CA/NCI NIH HHS/United States ; R01 CA222359/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use ; Apoptosis/drug effects/genetics ; Breast/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Cell Line, Tumor ; Cell Survival/genetics ; Datasets as Topic ; Disease Progression ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Experimental/drug therapy/genetics/*pathology ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Serine Endopeptidases/genetics/*metabolism ; Triple Negative Breast Neoplasms/drug therapy/genetics/*pathology ; },
abstract = {Breast cancer progression is accompanied by increased expression of extracellular and cell-surface proteases capable of degrading the extracellular matrix as well as cleaving and activating downstream targets. The type II transmembrane serine proteases (TTSPs) are a family of cell-surface proteases that play critical roles in numerous types of cancers. Therefore, the aim of this study was to identify novel and uncharacterized TTSPs with differential expression in breast cancer and to determine their potential roles in progression. Systematic in silico data analysis followed by immunohistochemical validation identified increased expression of the TTSP family member, TMPRSS13 (transmembrane protease, serine 13), in invasive ductal carcinoma patient tissue samples compared to normal breast tissue. To test whether loss of TMPRSS13 impacts tumor progression, TMPRSS13 was genetically ablated in the oncogene-induced transgenic MMTV-PymT tumor model. TMPRSS13 deficiency resulted in a significant decrease in overall tumor burden and growth rate, as well as a delayed formation of detectable mammary tumors, thus suggesting a causal relationship between TMPRSS13 expression and the progression of breast cancer. Complementary studies using human breast cancer cell culture models revealed that siRNA-mediated silencing of TMPRSS13 expression decreases proliferation, induces apoptosis, and attenuates invasion. Importantly, targeting TMPRSS13 expression renders aggressive triple-negative breast cancer cell lines highly responsive to chemotherapy. At the molecular level, knockdown of TMPRSS13 in breast cancer cells led to increased protein levels of the tumor-suppressive protease prostasin. TMPRSS13/prostasin co-immunoprecipitation and prostasin zymogen activation experiments identified prostasin as a potential novel target for TMPRSS13. Regulation of prostasin levels may be a mechanism that contributes to the pro-oncogenic properties of TMPRSS13 in breast cancer. TMPRSS13 represents a novel candidate for targeted therapy in combination with standard of care chemotherapy agents in patients with hormone receptor-negative breast cancer or in patients with tumors refractory to endocrine therapy.},
}
@article {pmid32856854,
year = {2020},
author = {Chowdhury, SS and Khatun, M and Khan, TH and Laila, AB},
title = {Mutation in Exon2 of BRCA1 Gene in Adult Bengali Bangladeshi Female Patients with Breast Cancer: An Experience from Two Tertiary-Care Hospitals.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {21},
number = {8},
pages = {2265-2270},
pmid = {32856854},
issn = {2476-762X},
mesh = {Adult ; BRCA1 Protein/*genetics ; Bangladesh/epidemiology ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/epidemiology/genetics/*pathology ; Cross-Sectional Studies ; *Exons ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; *Mutation ; Prognosis ; Tertiary Care Centers ; },
abstract = {BACKGROUND: The occurrence rate of BRCA1 mutations is found to be high in South Asian countries where early onset of breast cancer is common. In Bangladesh, noticeable percentage of patients experience breast cancer in their reproductive ages. The objective of this study was to identify any mutation in exon2 of the BRCA1 gene in adult Bengali Bangladeshi female patients with breast cancer.<br><br>METHODS: In this cross-sectional descriptive study, the genomic DNA was extracted from the blood of adult fifty Bengali Bangladeshi female breast cancer patients. The whole region of exon2 of the BRCA1 gene was amplified and the amplified DNA products were sequenced using Sanger sequencing. The raw chromatogram data were analyzed using Chromas software, and analyzed sequences were compared with the NCBI RefSeq database by BLAST search. The resultant amino acid change was detected by MEGA X software.<br><br>RESULTS: We found the mean age at diagnosis 44.66 years, whereas 96% of patients were married, 90% were multiparous and 86% breastfed their children. All patients had unilateral breast cancer and among them 94% had invasive ductal carcinoma. Only 24.5% of the patients had associated omorbidity. The family history of breast cancer or other BRCA-associated cancer was positive only for 4% of patients. A total of five mutations were identified all of which caused by substitutions. Among them three were nonsynonymous and two were synonymous. Only 2.5% of the patients, within the age group of 18-50 years, were found to have mutations in their blood, whereas 26.66% of the patients above 50 years found to have mutations in this study.<br><br>CONCLUSIONS: Among this small sample size, we found five mutations in exon2 of the BRCA1 gene and this indicates the necessity to find out the mutation spectra of the BRCA1 gene in the Bangladeshi population.},
}
@article {pmid32853021,
year = {2021},
author = {Bakhtari, N and Mozdarani, H and Salimi, M and Omranipour, R},
title = {Association study of miR-22 and miR-335 expression levels and G2 assay related inherent radiosensitivity in peripheral blood of ductal carcinoma breast cancer patients.},
journal = {Neoplasma},
volume = {68},
number = {1},
pages = {190-199},
doi = {10.4149/neo_2020_200225N185},
pmid = {32853021},
issn = {0028-2685},
mesh = {Adult ; Biomarkers, Tumor/blood/genetics ; *Breast Neoplasms/blood/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/blood/genetics/radiotherapy ; Female ; Humans ; Leukocytes, Mononuclear/metabolism ; *MicroRNAs/biosynthesis/blood ; Middle Aged ; ROC Curve ; Radiation Tolerance ; },
abstract = {Identifying patient's cellular radiosensitivity before radiotherapy (RT) in breast cancer (BC) patients allows proper alternations in routinely used treatment programs and reduces the adverse side effects in exposed patients. This study was conducted on blood samples taken from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC (mean age: 47±9.93) and 30 healthy women (mean age: 44.43±6.7). The standard G2 assay was performed to predict cellular radiosensitivity. To investigate miR-22 and miR-335 expression levels in peripheral blood mononuclear cells (PBMCs), qPCR was performed. The sensitivity and specificity of the mentioned miRNAs were assessed by plotting the Receiver Operating Characteristic (ROC) curve. Binary logistic regression was performed to identify the miRNA involvement in BC and cellular radiosensitivity (CR) of BC patients. The frequency of spontaneous and radiation-induced chromatid breaks (CBs) was significantly different between control and patient groups (p<0.05). A cut-off value was determined to differentiate the patients with and without cellular radiosensitivity. miR-22 and miR-335 were significantly downregulated in BC patients. miRNAs expression levels were directly associated with CR. ROC curve assessment identified that both miRNAs had acceptable specificity and sensitivity in the prediction of BC and CR of BC patients. Binary logistic regression showed that both miRNAs could also predict BC successfully. Although only miR-22 was shown potent to predict CR of BC patients, both miR-22 and miR-335 might act as tumor suppressor miRNAs in BC. miR-22 and miR-335 may be promising potential biomarkers in BC prediction along with other important biomarkers. Moreover, mirR-22 might be a potential biomarker for the prediction of CR in BC patients.},
}
@article {pmid32846803,
year = {2020},
author = {Li, G and Yao, J and Wu, T and Chen, Y and Wang, Z and Wang, Y and Wang, F and Zhong, R and Yang, S},
title = {Triple metachronous primary cancer of uterus, colon, and breast cancer: A case report and review of the literature.},
journal = {Medicine},
volume = {99},
number = {34},
pages = {e21764},
pmid = {32846803},
issn = {1536-5964},
mesh = {Aged ; Breast Neoplasms/*complications/pathology/therapy ; Colonic Neoplasms/*complications ; Female ; Humans ; Mammography ; Mastectomy ; Sentinel Lymph Node Biopsy ; Uterine Neoplasms/*complications ; },
abstract = {RATIONALE: Triple or more primary malignancies are rare, with only 23 previous cases including breast cancer reported in the English language studies between January 1990 and December 2019.<br><br>PATIENT CONCERNS: The patient was a 67-year-old woman with a mass in her right breast. She had a previous history of uterine and colon cancer. Both ultrasonography and mammography revealed a Breast Imaging Reporting and Data System (BI-RADS) category 3 breast lesion, in which proliferative nodules are more likely. Given her previous history of 2 malignancies, her doctors strongly recommended a biopsy.<br><br>DIAGNOSIS AND INTERVENTIONS: The biopsy pathology suggested intraductal breast cancer. Mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological diagnosis was invasive ductal carcinoma, grade II, stage I. The sample was positive for estrogen receptor and progesterone receptor and negative for cerbB-2. No radiotherapy or chemotherapy was administered except for endocrine therapy. A follow-up at 19 months showed no breast recurrence or distant metastases.<br><br>OUTCOMES: No recurrence or distant metastasis occurred within the 19-month, 11-year, and 20-year follow-ups for breast, colon, and uterine cancers, respectively.<br><br>LESSONS: To our knowledge, this is the first review of triple or more primary malignancies including breast cancer. These malignancies occur predominantly in older female patients. The most prevalent tumors of triple or more primary malignancies including breast cancer occur in the colon, uterus, and lung. A favorable prognosis is associated with early-stage malignancies.},
}
@article {pmid32816842,
year = {2020},
author = {Vaidya, JS and Bulsara, M and Baum, M and Wenz, F and Massarut, S and Pigorsch, S and Alvarado, M and Douek, M and Saunders, C and Flyger, HL and Eiermann, W and Brew-Graves, C and Williams, NR and Potyka, I and Roberts, N and Bernstein, M and Brown, D and Sperk, E and Laws, S and Sütterlin, M and Corica, T and Lundgren, S and Holmes, D and Vinante, L and Bozza, F and Pazos, M and Le Blanc-Onfroy, M and Gruber, G and Polkowski, W and Dedes, KJ and Niewald, M and Blohmer, J and McCready, D and Hoefer, R and Kelemen, P and Petralia, G and Falzon, M and Joseph, DJ and Tobias, JS},
title = {Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial.},
journal = {BMJ (Clinical research ed.)},
volume = {370},
number = {},
pages = {m2836},
pmid = {32816842},
issn = {1756-1833},
support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; 14/49/13/DH_/Department of Health/United Kingdom ; HTA/14/49/13/DH_/Department of Health/United Kingdom ; },
mesh = {Aged ; Breast Neoplasms/mortality/*radiotherapy/*surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; Intraoperative Care ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prospective Studies ; Radiotherapy Dosage ; Survival Rate ; },
abstract = {OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.<br><br>DESIGN: Prospective, open label, randomised controlled clinical trial.<br><br>SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.<br><br>PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).<br><br>INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients).<br><br>MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes.<br><br>RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005).<br><br>CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned.<br><br>TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.},
}
@article {pmid32811533,
year = {2020},
author = {Chao, X and Liu, L and Sun, P and Yang, X and Li, M and Luo, R and Huang, Y and He, J and Yun, J},
title = {Immune parameters associated with survival in metaplastic breast cancer.},
journal = {Breast cancer research : BCR},
volume = {22},
number = {1},
pages = {92},
pmid = {32811533},
issn = {1465-542X},
mesh = {Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/*immunology/metabolism ; Biomarkers, Tumor/*immunology/metabolism ; Breast Neoplasms/*immunology/*mortality/pathology/therapy ; CD8-Positive T-Lymphocytes/*immunology ; Carcinoma, Squamous Cell/immunology/mortality/pathology/therapy ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Programmed Cell Death 1 Receptor/*immunology/metabolism ; Survival Rate ; Tumor Microenvironment/*immunology ; },
abstract = {BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis.<br><br>METHODS: A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm[2]) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm[2]), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A &#x2265;&#x2009;1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression.<br><br>RESULTS: We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p&#x2009;=&#x2009;0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p&#x2009;<&#x2009;0.001). Thirty (50%) patients exhibited positive (&#x2265;&#x2009;1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (&#x2265;&#x2009;1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (&#x2265;&#x2009;1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (&#x2265;&#x2009;1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (>&#x2009;300/mm[2], 20%), CD4+ TILs (>&#x2009;250/mm[2]), and CD8+ TILs (>&#x2009;70/mm[2]) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (&#x2265;&#x2009;1%) and PD1 in stromal cells (&#x2265;&#x2009;1%) were also associated with longer survival.<br><br>CONCLUSIONS: The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.},
}
@article {pmid32789812,
year = {2021},
author = {Wakefield, B and Diko, S and Gilmer, R and Connell, KA and DeWitt, PE and Hurt, KJ},
title = {Accuracy of obstetric laceration diagnoses in the electronic medical record.},
journal = {International urogynecology journal},
volume = {32},
number = {7},
pages = {1907-1915},
pmid = {32789812},
issn = {1433-3023},
mesh = {Anal Canal/injuries ; Delivery, Obstetric ; Electronic Health Records ; Female ; Humans ; *Lacerations/diagnosis/epidemiology ; Perineum/injuries ; Pregnancy ; Retrospective Studies ; Risk Factors ; },
abstract = {INTRODUCTION AND HYPOTHESIS: Patient safety data including rates of obstetric anal sphincter injury (OASI) are often derived from hospital discharge codes. With the transition to electronic medical records (EMRs), we hypothesized that electronic provider-entered delivery data would more accurately document obstetric perineal injury than traditional billing/diagnostic codes.<br><br>METHODS: We evaluated the accuracy of perineal laceration diagnoses after singleton vaginal deliveries during one calendar year at an American tertiary academic medical center. We reviewed the entire hospital chart to determine the most likely laceration diagnosis and compared that expert review diagnosis (ExpRD) with documentation in the EMR delivery summary (EDS) and ICD-9 diagnostic codes (IDCs).<br><br>RESULTS: We retrospectively selected 354 total delivery records. OASI complicated 56 of those. 303 records (86%) were coded identically by the EDS and IDCs. Diagnoses from the IDCs and the EDS were mostly correct compared with ExpRD (sensitivity&#x2009;=&#x2009;96%, specificity&#x2009;=&#x2009;100%). There was no systematic over- or under-diagnosis of OASI for either the EDS (p&#x2009;=&#x2009;0.070) or the IDCs (p&#x2009;=&#x2009;0.447). When considering all laceration types the EDS was correct for 21 (5.9%) lacerations that were incorrect according to the IDCs. Overall, the EDS was more accurate (p&#x2009;<&#x2009;0.05) owing to errors in IDC minor laceration diagnoses.<br><br>CONCLUSIONS: Electronic medical record delivery summary data and EMR-derived diagnostic codes similarly characterize OASI. The EDS does not improve OASI reporting, but may be more accurate when considering all perineal lacerations. This assumes that providers have correctly identified and categorized the lacerations that they record in the EMR.},
}
@article {pmid32785515,
year = {2020},
author = {Souza, TO and Souza, ER and Pinto, LW},
title = {Analysis of the correlation of socioeconomic, sanitary, and demographic factors with homicide deaths - Bahia, Brazil, 2013-2015.},
journal = {Revista brasileira de enfermagem},
volume = {73},
number = {6},
pages = {e20190346},
doi = {10.1590/0034-7167-2019-0346},
pmid = {32785515},
issn = {1984-0446},
mesh = {Brazil/epidemiology ; Demography ; Educational Status ; *Homicide ; Humans ; Socioeconomic Factors ; },
abstract = {OBJECTIVE: To analyze the correlation of socioeconomic, sanitary, and demographic factors with homicides in Bahia, from 2013 to 2015.<br><br>METHODS: Ecological study, using data from the Information System on Mortality and from the Superintendence of Economic and Social Studies. The depending variable is the corrected homicide rate. Explanatory variables were categorized in four axes. Simple and multiple negative binomial regression models were used.<br><br>RESULTS: Positive associations were found between homicides and the Index of Economy and Finances (IEF), the Human Development Index, the Gini Index, population density, and legal intervention death rates (LIDR). The variables Index of Education Levels (IEL), rates of death with undetermined intentions (RDUI), and the proportion of ill-defined causes (IDC) presented a negative association with the homicide rates.<br><br>CONCLUSION: The specific features of the context of each community, in addition to broader socioeconomic municipal factors, directly interfere in life conditions and increase the risk of dying by homicide.},
}
@article {pmid32783993,
year = {2020},
author = {Domínguez-de-la-Cruz, E and Muñoz, ML and Pérez-Muñoz, A and García-Hernández, N and Moctezuma-Meza, C and Hinojosa-Cruz, JC},
title = {Reduced mitochondrial DNA copy number is associated with the haplogroup, and some clinical features of breast cancer in Mexican patients.},
journal = {Gene},
volume = {761},
number = {},
pages = {145047},
doi = {10.1016/j.gene.2020.145047},
pmid = {32783993},
issn = {1879-0038},
mesh = {Adult ; Breast Neoplasms/*genetics/metabolism ; Case-Control Studies ; DNA Copy Number Variations/*genetics ; DNA, Mitochondrial/*genetics ; Female ; Genetic Predisposition to Disease ; Haplotypes/genetics ; Humans ; Mexico/epidemiology ; Middle Aged ; Mitochondria/genetics ; },
abstract = {Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p = 0.010); it was significantly decreased in BCT and NAT in women > 50 years of age, compared with NAT in women < 50 years of age (p = 0.032 and p = 0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p = 0.011, p = 0.010 and, p = 0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p = 0.025, p = 0.022 and p = 0.031 and p = 0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p = 0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p = 0.006) and with BCT patients belonging to haplogroups A2 and D1 (p = 0.01 and p = 0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p = 0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p = 0.021, =0.048, and = 0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.},
}
@article {pmid32782013,
year = {2020},
author = {Kurozumi, S and Alsaleem, M and Monteiro, CJ and Bhardwaj, K and Joosten, SEP and Fujii, T and Shirabe, K and Green, AR and Ellis, IO and Rakha, EA and Mongan, NP and Heery, DM and Zwart, W and Oesterreich, S and Johnston, SJ},
title = {Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets.},
journal = {Breast cancer research : BCR},
volume = {22},
number = {1},
pages = {85},
pmid = {32782013},
issn = {1465-542X},
support = {/WT_/Wellcome Trust/United Kingdom ; AAM127669/WT_/Wellcome Trust/United Kingdom ; SAC160073/KOMEN/Susan G. Komen/United States ; },
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Computer Simulation ; Databases, Genetic/statistics &amp; numerical data ; Female ; Humans ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 10-15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets.<br><br>METHODS: We performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I-III primary ILC (N&#x2009;=&#x2009;279) and invasive ductal carcinoma (IDC, N&#x2009;=&#x2009;1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBB2 mutation and amplification status was performed using weighted average differences and an in silico model of response to neratinib derived from breast cancer cell lines.<br><br>RESULTS: ILC tumors comprised 17.7% of all cases in the dataset but accounted for 47.1% of ERBB2-mutated cases. Mutations in ERBB2 were enriched in ILC vs. IDC cases (5.7%, N&#x2009;=&#x2009;16 vs. 1.4%, N&#x2009;=&#x2009;18, p&#x2009;<&#x2009;0.0001) and clustered in the tyrosine kinase domain of HER2. ERBB3 mutations were not enriched in ILC (1.1%, N&#x2009;=&#x2009;3 vs. 1.8%, N&#x2009;=&#x2009;23; p&#x2009;=&#x2009;0.604). Median OS for patients with ERBB2-mutant ILC tumors was 66&#x2009;months vs. 211&#x2009;months for ERBB2 wild-type (p&#x2009;=&#x2009;0.0001), and 159 vs. 166&#x2009;months (p&#x2009;=&#x2009;0.733) for IDC tumors. Targetable ERBB2 mutational status was an independent prognostic marker of 10-year OS-but only in ILC (hazard ratio, HR&#x2009;=&#x2009;3.7, 95% CI 1.2-11.0; p&#x2009;=&#x2009;0.021). Findings were validated using a novel ERBB2 mutation gene enrichment score (HR for 10-year OS in ILC&#x2009;=&#x2009;2.3, 95% CI 1.04-5.05; p&#x2009;=&#x2009;0.040).<br><br>CONCLUSIONS: Targetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.},
}
@article {pmid32781417,
year = {2020},
author = {Lu, K and Wang, X and Zhang, W and Ye, H and Lao, L and Zhou, X and Yao, S and Lv, F},
title = {Clinicopathological and genomic features of breast mucinous carcinoma.},
journal = {Breast (Edinburgh, Scotland)},
volume = {53},
number = {},
pages = {130-137},
pmid = {32781417},
issn = {1532-3080},
mesh = {Adenocarcinoma, Mucinous/*genetics/*pathology ; Adult ; Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cohort Studies ; Female ; Gene Expression Profiling ; Genome ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prospective Studies ; SEER Program ; Young Adult ; },
abstract = {INTRODUCTION: Mucinous carcinoma (MC) of the breast is a special histological type of breast cancer. Clinicopathological characteristics and genomic features of MC is not fully understood.<br><br>MATERIALS AND METHODS: 186,497 primary breast cancer patients from SEER database diagnosed with invasive ductal carcinoma (IDC) or MC were included. 801 primary IDC or MC patients from TCGA cohort were included for transcriptomic and genomic analysis.<br><br>RESULTS: MC patients were older, had lower tumor grade and T and N stage, higher hormone receptor positive proportions and lower HER2 positive proportions than IDC patients. Kaplan-Meier plots showed that the breast cancer-specific survival (BCSS) of MC patients was significantly better than IDC patients (P&#xa0;<&#xa0;0.001). However, after adjusting for clinicopathological factors, survival advantage of MC disappeared. In terms of genomic features of MC, representative upregulated genes of MC in transcriptomic level were MUC2, TFF1 and CARTPT. Upregulated pathways of MC included neurotransmitter-related pathways. Moreover, MC was featured by the amplification of 6p25.2, 6q12 and 11q12.3.<br><br>CONCLUSION: MC is a distinct histological subtype compared with IDC in terms of clinicopathological characteristics and genomic features. Further investigation need to be conducted to explore the formation of this specific histological subtype.},
}
@article {pmid32776387,
year = {2020},
author = {Takahara, T and Satou, A and Sugie, M and Watanabe, M and Kanao, K and Sumitomo, M and Tsuzuki, T},
title = {Prognostic significance of p16 expression in high-grade prostate adenocarcinoma.},
journal = {Pathology international},
volume = {70},
number = {10},
pages = {743-751},
doi = {10.1111/pin.12997},
pmid = {32776387},
issn = {1440-1827},
mesh = {Adenocarcinoma/*diagnosis/drug therapy/metabolism/pathology ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate/metabolism/pathology ; Prostatic Neoplasms, Castration-Resistant/*diagnosis/drug therapy/metabolism/pathology ; },
abstract = {Management of advanced hormone-naïve prostate cancer (HNPC) is a critical public health issue. Useful prognostic markers are thus needed to select patients who will benefit from recently introduced upfront therapies. p16 expression is an adverse prognostic marker in prostate cancer. The present study aimed to determine whether p16 expression would serve as an adverse prognostic marker in advanced HNPC. A total of 79 patients diagnosed by needle biopsy with adenocarcinoma Gleason score ≥8 between 2010 and 2013 at Aichi Medical University were included in this study. The median patient age was 73 (range 52-87) years. The median follow-up was 62 months (range 2-98). Fourteen patients had p16-positive samples. Fifteen patients died from prostate cancer, 10 of whom were in the p16-positive group. p16 positivity was associated with clinical T stage (P < 0.001), presence of IDC-P (P < 0.001), distant metastasis (P < 0.001) and lymph node metastasis (P < 0.001). These results indicate that p16 expression is associated with adverse prognostic factor of prostate cancer and suggest that p16 expression may provide useful information for treatment planning and identifying suitable candidates for upfront chemotherapy or androgen receptor axis-targeted therapy.},
}
@article {pmid32758491,
year = {2020},
author = {Sechrist, H and Glasgow, A and Bomeisl, P and Gilmore, H and Harbhajanka, A},
title = {Concordance of breast cancer biomarker status between routine immunohistochemistry/in situ hybridization and Oncotype DX qRT-PCR with investigation of discordance, a study of 591 cases.},
journal = {Human pathology},
volume = {104},
number = {},
pages = {54-65},
doi = {10.1016/j.humpath.2020.07.022},
pmid = {32758491},
issn = {1532-8392},
mesh = {Aged ; *Biomarkers, Tumor/analysis/genetics ; Breast Neoplasms/*chemistry/*genetics/pathology/therapy ; Clinical Decision-Making ; Female ; *Gene Expression Profiling ; Humans ; *Immunohistochemistry ; *In Situ Hybridization ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Receptor, ErbB-2/analysis/genetics ; Receptors, Estrogen/analysis/genetics ; Receptors, Progesterone/analysis/genetics ; Retrospective Studies ; *Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Risk Factors ; Transcriptome ; Treatment Outcome ; },
abstract = {Patients with estrogen receptor (ER)+/human epidermal growth factor receptor (HER)2-, lymph node- breast cancer with high recurrence risk benefit from adjuvant chemotherapy in addition to hormonal therapy. This study compares ER, progesterone receptor (PR), and HER2 status between routine immunohistochemistry (IHC)/in situ hybridization (ISH) and Oncotype DX (ODX) in 591 cases. ODX recurrence score (RS) and clinicopathologic features were compared between ER/PR-concordant and discordant cases. Hematoxylin and eosin (H&amp;E) slides from ER discordant cases were reexamined. Concordance was high between ODX and IHC for ER status (580/591, 98.1%) and moderate for PR status (512/591, 86.6%). All 11 ER discordant cases were ER+ by IHC but ER- by ODX and high risk by ODX. Histologically, all of these cases were grade III invasive ductal carcinoma (IDC), except one case diagnosed as IDC with apocrine features. Although this case was grade I and ER/PR+ by IHC, this patient received chemotherapy because of high RS. Of 79 PR discordant cases, 60 were PR+ by IHC but PR- by ODX. Five hundred eighty-four cases had available HER2 data, with high negative agreement (580/582, 99.7%). However, both HER2+ cases by ISH were HER2- by ODX. Mean RS was higher for ER discordant than concordant cases (48.0 versus 17.1, P < 0.0001) and for PR discordant (IHC+/ODX-) than concordant cases (27.2 versus 16.7, P < 0.0001) with no significant differences in recurrence or metastasis. Overall, detection was more sensitive by IHC, and high RS of discordant cases suggests possible risk overestimation. Therapeutic decisions for discordant cases should continue to be based on clinicopathologic correlation and not oncotype alone.},
}
@article {pmid32753069,
year = {2020},
author = {Choridah, L and Sari, WK and Dwianingsih, EK and Widodo, I and Suwardjo, and Anwar, SL},
title = {Advanced lesions of synchronous bilateral mammary Paget's disease: a case report.},
journal = {Journal of medical case reports},
volume = {14},
number = {1},
pages = {119},
pmid = {32753069},
issn = {1752-1947},
support = {PPUPT 2274/2019//Kementerian Riset, Teknologi dan Pendidikan Tinggi/ ; Dana Masyarakat 1499/2019//Universitas Gadjah Mada/ ; RTA Nr 133/2607-2020//Universitas Gadjah Mada/ ; 1/2018//NUS-UGM-Tahir Foundation/ ; },
mesh = {*Breast Neoplasms/diagnosis/surgery ; Female ; Humans ; Indonesia ; Mastectomy ; Middle Aged ; Nipples ; *Paget's Disease, Mammary/diagnostic imaging/surgery ; },
abstract = {BACKGROUND: Mammary Paget's disease is an eczematous eruption on the nipple and areola with underlying breast malignancy. It is often misinterpreted as chronic dermatitis or psoriasis causing a delayed diagnosis. Synchronous bilateral mammary Paget's disease is exceptionally rare and an advanced case with underlying invasive carcinoma might require long-term treatment and follow-up that could affect a patient's physical, psychological, and social aspects of well-being.<br><br>CASE PRESENTATION: A 54-year-old Javanese woman presented in our clinic with a 2-year history of itching and chronic eczema in both areolae. Bilateral nipple retraction and retro-areolar palpable lumps were observed during the first presentation. Breast ultrasound revealed hypoechoic lesions in her left and right breasts. Mammograms showed an irregular hyperdense lesion and multiple microcalcifications. Histopathology from biopsy and bilateral mastectomy demonstrated infiltration of large Paget's cells in the epidermis of the areola with underlying lesions of invasive ductal carcinoma, diagnosed solid type with high nuclear grade and negative expression of estrogen receptor and progesterone receptor, with positive expression of human epidermal growth receptor-2(HER2) and Ki-67 (45%).<br><br>CONCLUSIONS: In a patient with suspicious chronic inflammation of the nipple and areolae, prompt biopsy should be performed to avoid a delayed diagnosis of any malignant breast lesion.},
}
@article {pmid32748295,
year = {2020},
author = {Kato, M and Hirakawa, A and Kobayashi, Y and Yamamoto, A and Naito, Y and Tochigi, K and Sano, T and Ishida, S and Funahashi, Y and Fujita, T and Matsukawa, Y and Hattori, R and Tsuzuki, T},
title = {Effect of core needle biopsy number on intraductal carcinoma of the prostate (IDC-P) diagnosis in patients with metastatic hormone-sensitive prostate cancer.},
journal = {International journal of clinical oncology},
volume = {25},
number = {12},
pages = {2130-2137},
pmid = {32748295},
issn = {1437-7772},
mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/*methods ; Bone Neoplasms/secondary ; Carcinoma, Ductal/mortality/*pathology ; Hormones ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/mortality/*pathology ; Retrospective Studies ; },
abstract = {BACKGROUND: The number of core needle biopsies in metastatic prostate cancer cases are sometimes reduced to avoid various complications. We analyzed whether core needle biopsy number influence IDC-P detection rate in patients with metastatic castration-sensitive prostate cancer (mHSPC).<br><br>METHODS: We retrospectively evaluated data from 150 patients diagnosed with mHSPC. Subjects were allocated to three groups according to the number of core biopsies performed:&#x2009;&#x2264;&#x2009;5, 6-9, and&#x2009;&#x2265;&#x2009;10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates.<br><br>RESULTS: For patients who underwent&#x2009;&#x2265;&#x2009;10 core biopsies, a significant difference on CSS was detected between with or without IDC-P (P&#x2009;=&#x2009;0.016). On the other hand, the difference decreased as the number of core biopsies became smaller (6-9; P&#x2009;=&#x2009;0.322 and&#x2009;&#x2264;&#x2009;5; P&#x2009;=&#x2009;0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent&#x2009;&#x2265;&#x2009;10 and 6-9 core needle biopsies (P&#x2009;=&#x2009;0.0002 and 0.017, respectively), but not in those who underwent&#x2009;&#x2264;&#x2009;5 core biopsies (P&#x2009;=&#x2009;0.341). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis for patients had&#x2009;&#x2265;&#x2009;10 core biopsies (P&#x2009;=&#x2009;0.016, and P&#x2009;=&#x2009;0.0014, respectively).<br><br>CONCLUSIONS: Given the IDC-P detection and its value as a prognostic marker, we propose the performance of&#x2009;&#x2265;&#x2009;10 core biopsy procedures in patients diagnosed with mHSPC to minimize the sampling error of the IDC-P.},
}
@article {pmid32745951,
year = {2020},
author = {Altinoz, A and Al Ameri, M and Qureshi, W and Boush, N and Nair, SC and Abdel-Aziz, A},
title = {Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates.},
journal = {Breast (Edinburgh, Scotland)},
volume = {53},
number = {},
pages = {119-124},
pmid = {32745951},
issn = {1532-3080},
mesh = {Adult ; Arabs/genetics ; Breast Neoplasms/ethnology/*genetics/pathology ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Predisposition to Disease/*epidemiology/ethnology/genetics ; Genetic Testing/statistics &amp; numerical data ; Hereditary Breast and Ovarian Cancer Syndrome/ethnology/*genetics/pathology ; Humans ; Middle Aged ; Prevalence ; Retrospective Studies ; United Arab Emirates/epidemiology ; },
abstract = {INTRODUCTION: Breast cancer is the most prevalent cancer in the United Arab Emirates (UAE). This is the first study to provide data on predisposition of breast cancer susceptibility genes with associated clinical and pathological aspects in the UAE.<br><br>MATERIAL &amp; METHODS: A retrospective chart review for breast cancer patients undergoing genetic testing from 2016 to 2018. According to National Comprehensive Cancer Network (NCCN) guidelines genetic testing was offered. The analyzed data included; age, ethnicity, family cancer history, pathogenic variant, histopathology, stage, molecular subtype and proliferation.<br><br>RESULTS: 309 patients underwent genetic testing with a positive result in 130 patients (11.9%) over a period of 36 months. In 34.6% pathogenic and likely pathogenic variants were identified. BRCA2 was the most common gene identified. The mean age was 42.9 years (&#xb1;9.01). Positive family history was identified in 66 patients (50.7%). Majority had stage 1 or 2 disease (66.2%), invasive ductal carcinoma (81.5%) and hormone receptor positive cancer (45.3%).<br><br>CONCLUSIONS: This is the first study in the UAE to describe the clinical and pathological characteristics of hereditary breast cancer in a mixed ethnic group with dominant Arabic population. Further genetic studies will be required in the UAE population, as the prevalence of breast cancer continues to rise.},
}
@article {pmid32740271,
year = {2020},
author = {Granek, L and Nakash, O},
title = {Prevalence and risk factors for suicidality in cancer patients and oncology healthcare professionals strategies in identifying suicide risk in cancer patients.},
journal = {Current opinion in supportive and palliative care},
volume = {14},
number = {3},
pages = {239-246},
pmid = {32740271},
issn = {1751-4266},
mesh = {Age Factors ; Cancer Care Facilities/organization &amp; administration ; Health Personnel/education/*organization &amp; administration ; Humans ; Inservice Training ; Mass Screening/organization &amp; administration ; Neoplasms/pathology/*psychology ; Prevalence ; Risk Factors ; Sex Factors ; Socioeconomic Factors ; Suicide/*statistics &amp; numerical data ; },
abstract = {PURPOSE OF REVIEW: The aim of this study was to summarize the literature on prevalence and risk factors for suicidality in cancer patients and to document the research on oncology healthcare professionals' strategies in identifying this risk.<br><br>RECENT FINDINGS: Cancer patients exhibit increased risk of suicidality compared with the general population. Various risk factors have been identified including sociodemographic factors such as poverty, being male and elderly as well as disease-related attributes such as cancer type and stage. The literature on how healthcare professionals identify suicide risk is sparse. Ten articles were found that focused on two main themes. These included information on systematic strategies in identifying suicide risk and factors that affect healthcare professionals' ability to identify risk in their patients.<br><br>SUMMARY: Although there is an immense amount of literature documenting the problem of suicidality among patients, the research on how healthcare professionals identify and respond to these indications in patients is nearly nonexistent. Cancer centres should implement standardized and systematic screening of cancer patients for suicidality and research on this patient population should collect and report these data. Ongoing training and education for healthcare professionals who work in the oncology setting on how to identify and respond to suicide risk among cancer patients is urgently needed.},
}
@article {pmid32738354,
year = {2021},
author = {Camacho Londoño, JE and Kuryshev, V and Zorn, M and Saar, K and Tian, Q and Hübner, N and Nawroth, P and Dietrich, A and Birnbaumer, L and Lipp, P and Dieterich, C and Freichel, M},
title = {Transcriptional signatures regulated by TRPC1/C4-mediated Background Ca[2+] entry after pressure-overload induced cardiac remodelling.},
journal = {Progress in biophysics and molecular biology},
volume = {159},
number = {},
pages = {86-104},
doi = {10.1016/j.pbiomolbio.2020.07.006},
pmid = {32738354},
issn = {1873-1732},
support = {Z01 ES101684/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Animals ; Biomechanical Phenomena/physiology ; Calcium/*metabolism ; Calcium Signaling ; Cardiomegaly/metabolism ; Gene Expression Regulation ; Humans ; Ion Channels/genetics/metabolism ; Male ; Mice ; Mice, Knockout ; Myocytes, Cardiac/*metabolism ; TRPC Cation Channels/*metabolism ; Transcriptional Activation/physiology ; Ventricular Remodeling/*physiology ; },
abstract = {AIMS: After summarizing current concepts for the role of TRPC cation channels in cardiac cells and in processes triggered by mechanical stimuli arising e.g. during pressure overload, we analysed the role of TRPC1 and TRPC4 for background Ca[2+] entry (BGCE) and for cardiac pressure overload induced transcriptional remodelling.<br><br>METHODS AND RESULTS: Mn[2+]-quench analysis in cardiomyocytes from several Trpc-deficient mice revealed that both TRPC1 and TRPC4 are required for BGCE. Electrically-evoked cell shortening of cardiomyocytes from TRPC1/C4-DKO mice was reduced, whereas parameters of cardiac contractility and relaxation assessed in&#xa0;vivo were unaltered. As pathological cardiac remodelling in mice depends on their genetic background, and the development of cardiac remodelling was found to be reduced in TRPC1/C4-DKO mice on a mixed genetic background, we studied TRPC1/C4-DKO mice on a C57BL6/N genetic background. Cardiac hypertrophy was reduced in those mice after chronic isoproterenol infusion (-51.4%) or after one week of transverse aortic constriction (TAC;&#xa0;-73.0%). This last manoeuvre was preceded by changes in the pressure overload induced transcriptional program as analysed by RNA sequencing. Genes encoding specific collagens, the Mef2 target myomaxin and the gene encoding the mechanosensitive channel Piezo2 were up-regulated after TAC in wild type but not in TRPC1/C4-DKO hearts.<br><br>CONCLUSIONS: Deletion of the TRPC1 and TRPC4 channel proteins protects against development of pathological cardiac hypertrophy independently of the genetic background. To determine if the TRPC1/C4-dependent changes in the pressure overload induced alterations in the transcriptional program causally contribute to cardio-protection needs to be elaborated in future studies.},
}
@article {pmid32719289,
year = {2020},
author = {Dhia, SB and Belaid, I and Stita, W and Hochlaf, M and Ezzairi, F and Ahmed, SB},
title = {Bilateral parotid gland metastasis from a breast invasive ductal carcinoma.},
journal = {Journal of cancer research and therapeutics},
volume = {16},
number = {3},
pages = {672-674},
doi = {10.4103/jcrt.JCRT_1047_17},
pmid = {32719289},
issn = {1998-4138},
mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*pathology/therapy ; Palliative Care ; Parotid Neoplasms/*secondary/therapy ; },
abstract = {Metastases to the parotid gland are very rare. We report the second case of bilateral metastases to the parotid gland from a breast invasive ductal carcinoma. A 50-year-old female was treated for an early left breast cancer in 2007. A pulmonary metastatic relapse was diagnosed in 2013. A metastatic skin extension required several lines of treatment from June 2014 to July 2016. Bilateral parotid gland metastases from a breast invasive ductal carcinoma were confirmed in December 2016. The patient died on May 2017 from cerebral metastases. Only 16 cases of metastasis to the parotid gland from breast cancer have been reported in the literature. Only one case had a bilateral involvement. Prognosis is poor, and there are no specific guidelines for the treatment.},
}
@article {pmid32710711,
year = {2020},
author = {Jones, B and Thomas, G and Sprenger, J and Nofech-Mozes, S and Khorasani, M and Vitkin, A},
title = {Peri-tumoural stroma collagen organization of invasive ductal carcinoma assessed by polarized light microscopy differs between OncotypeDX risk group.},
journal = {Journal of biophotonics},
volume = {13},
number = {11},
pages = {e202000188},
doi = {10.1002/jbio.202000188},
pmid = {32710711},
issn = {1864-0648},
support = {PJT-156110//CIHR/Canada ; },
mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/genetics ; Collagen ; Female ; Humans ; Microscopy, Polarization ; Risk Factors ; },
abstract = {A commercially available genomic test, OncotypeDX has emerged as a useful postsurgical treatment guide for early stage breast cancer. Despite widespread clinical adoption, there remain logistical issues with its implementation. Collagenous stromal architecture has been shown to hold prognostic value that may complement OncotypeDX. Polarimetric analysis of breast cancer surgical samples allows for the quantification of collagenous stroma abundance and organization. We examine intratumoural collagen abundance and alignment along the tumor-host interface for 45 human samples of invasive ductal carcinoma categorized as low or higher risk by OncotypeDX. Furthermore, we probe the separatory power of collagen alignment patterns to classify unlabeled samples as low or higher OncotypeDX risk group using a linear discriminant (LD) model. No significant difference in mean collagen abundance was found between the two risk groups. However, collagen alignment along the tumor boundary was found to be significantly lower in higher risk samples. The LD model achieved a 71% total accuracy and 81% sensitivity to higher risk samples. Prognostic information extracted from the stromal morphology has potential to complement OncotypeDX as an easy-to-implement prescreening methodology.},
}
@article {pmid32700071,
year = {2020},
author = {Richards, D and Ayala, AA and Wu, Y and Middleton, LP},
title = {Carcinoma In Situ Involving Sclerosing Adenosis on Core Biopsy: Diagnostic Pearls to Aid the Practicing Clinician and Avoid Overtreatment.},
journal = {Oncology and therapy},
volume = {8},
number = {1},
pages = {81-89},
pmid = {32700071},
issn = {2366-1089},
abstract = {INTRODUCTION: Involvement of pre-existing benign lesions by ductal carcinoma in situ (DCIS) or lobular neoplasia (LN) can present difficult diagnostic challenges, and can easily cause misdiagnosis of invasive carcinoma and over-management of localized disease. Our objective was to gather the largest case series of DCIS and LN involving sclerosing adenosis (SA), and to report the characteristic features of these lesions, in order to provide histologic criteria for the diagnostician.<br><br>METHODS: Our database was searched for core biopsy material diagnosed as carcinoma in situ involving adenosis. Glass slides and pathology reports were reviewed. The cases were studied for salient features, and clinical follow-up was also obtained.<br><br>RESULTS: Thirty-one cases of DCIS or LN involving SA were obtained (12 cases of DCIS, 19 cases of LN including LCIS and ALH). Histomorphologic features commonly seen with DCIS or LN involving SA included lobulocentric architecture (31/31, 100%), myoepithelial cells visible by H&amp;E at least focally (31/31, 100%), and separate areas of SA not involved by neoplasia (29/31, 93.5%). Features that were sometimes seen included hyaline basement membranes surrounding the lesion (14/31, 45.2%), DCIS/LN apart from the area of involvement by SA (16/31, 51.6%), and calcifications associated with DCIS/LN/SA (12/31, 38.7%). Features that were not commonly seen included desmoplasia (6/31, 19.4%), dense inflammation (4/31, 12.9%), and single epithelial cells enveloped by flattened myoepithelial cells (6/31, 19.4%). Of the ten cases of DCIS with known follow-up, four showed DCIS involving either SA or a complex SA on excision (4/10, 40%), four had only DCIS (4/10, 40%), one had DCIS with a small 1.8-mm focus of predominantly tubular carcinoma (1/10, 10%), and one showed invasive ductal carcinoma on excision (1/10, 10%). The latter case of invasive ductal carcinoma occurred in a patient who had a delay of 3&#xa0;years from diagnosis to surgical resection. Of the eight cases of LN with surgical follow-up, seven had LCIS (7/8, 87.5%), and one showed only fibroadenoma and SA with no residual LN in the excised specimen (1/8, 12.5%). Importantly, no invasive carcinoma was identified in any of the resections for LN involving SA.<br><br>CONCLUSIONS: In our series of carcinoma in situ (CIS) involving sclerosing adenosis diagnosed on core biopsy, lobular lesions involving SA were more common than ductal lesions. Ductal and lobular carcinoma in situ involving adenosis were best diagnosed by the low-power appearance of a lobulocentric pattern of growth. The most helpful diagnostic feature was the observation of additional foci of carcinoma in situ away from the adenosis. Immunohistochemical stains for myoepithelial cells were useful in particularly difficult cases. The presence of stromal desmoplasia does not preclude the diagnosis of carcinoma in situ involving adenosis. Knowledge of these diagnostic pearls can reduce over-interpretation of CIS on core biopsy and subsequent overtreatment.},
}
@article {pmid32694843,
year = {2019},
author = {Seitz, S and Kwon, Y and Hartleben, G and Jülg, J and Sekar, R and Krahmer, N and Najafi, B and Loft, A and Gancheva, S and Stemmer, K and Feuchtinger, A and Hrabe de Angelis, M and Müller, TD and Mann, M and Blüher, M and Roden, M and Berriel Diaz, M and Behrends, C and Gilleron, J and Herzig, S and Zeigerer, A},
title = {Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity.},
journal = {Nature metabolism},
volume = {1},
number = {10},
pages = {1009-1026},
pmid = {32694843},
issn = {2522-5812},
mesh = {Adiposity ; Adult ; Animals ; Autophagy ; Blood Glucose/*metabolism ; Cholesterol/blood ; Female ; Homeostasis ; Humans ; Lipid Metabolism/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria, Liver/*metabolism ; Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/metabolism ; Up-Regulation ; rab GTP-Binding Proteins/genetics/*metabolism ; },
abstract = {Non-alcoholic fatty liver disease (NAFLD) represents a key feature of obesity-related type 2 diabetes with increasing prevalence worldwide. To our knowledge, no treatment options are available to date, paving the way for more severe liver damage, including cirrhosis and hepatocellular carcinoma. Here, we show an unexpected function for an intracellular trafficking regulator, the small Rab GTPase Rab24, in mitochondrial fission and activation, which has an immediate impact on hepatic and systemic energy homeostasis. RAB24 is highly upregulated in the livers of obese patients with NAFLD and positively correlates with increased body fat in humans. Liver-selective inhibition of Rab24 increases autophagic flux and mitochondrial connectivity, leading to a strong improvement in hepatic steatosis and a reduction in serum glucose and cholesterol levels in obese mice. Our study highlights a potential therapeutic application of trafficking regulators, such as RAB24, for NAFLD and establishes a conceptual functional connection between intracellular transport and systemic metabolic dysfunction.},
}
@article {pmid32686908,
year = {2020},
author = {Ma, L and Qi, L and Li, S and Yin, Q and Liu, J and Wang, J and She, C and Li, P and Liu, Q and Wang, X and Li, W},
title = {Aberrant HDAC3 expression correlates with brain metastasis in breast cancer patients.},
journal = {Thoracic cancer},
volume = {11},
number = {9},
pages = {2493-2505},
pmid = {32686908},
issn = {1759-7714},
support = {81702481//National Natural Science Foundation of China/ ; 15JCQNJC44800//Natural Science Foundation of Tianjin City/ ; 18JCYBJC27600//Natural Science Foundation of Tianjin City/ ; },
mesh = {Brain Neoplasms/*enzymology/*secondary ; Breast Neoplasms/*complications/*enzymology/pathology ; Female ; Histone Deacetylases/*metabolism ; Humans ; Middle Aged ; },
abstract = {BACKGROUND: Brain metastasis is an unsolved clinical problem in breast cancer patients due to its poor prognosis and high fatality rate. Although accumulating evidence has shown that some pan-histone deacetylase (HDAC) inhibitors can relieve breast cancer brain metastasis, the specific HDAC protein involved in this process is unclear. Thus, identifying a specific HDAC protein closely correlated with breast cancer brain metastasis will not only improve our understanding of the functions of the HDAC family but will also help develop a novel target for precision cancer therapy.<br><br>METHODS: Immunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 samples from breast invasive ductal carcinoma patients, including 63 patients with brain metastasis, was performed using the standard streptavidin-peroxidase method. The relationships between HDAC1, HDAC2, and HDAC3 and overall survival/brain metastasis-free survival/post-brain metastatic survival were evaluated using Kaplan-Meier curves and Cox regression analyses.<br><br>RESULTS: HDAC1, HDAC2, and cytoplasmic HDAC3 all displayed typical oncogenic characteristics and were independent prognostic factors for the overall survival of breast cancer patients. Only cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis-free survival. Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumors, while nuclear expression was downregulated. The HDAC1, HDAC2, and HDAC3 expression levels in the brain metastases were not correlated with survival post-brain metastasis.<br><br>CONCLUSIONS: Our studies first demonstrate a critical role for HDAC3 in the brain metastasis of breast cancer patients and it may serve as a promising therapeutic target for the vigorously developing field of precision medicine.<br><br>KEY POINTS: Significant findings of the study Cytoplasmic HDAC3 is an independent prognostic factor for the overall survival and brain metastasis-free survival of breast cancer patients. What this study adds Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumours, while nuclear expression was downregulated.},
}
@article {pmid32665190,
year = {2020},
author = {Escott, CE and Zaenger, D and Switchencko, JM and Lin, JY and Abugideiri, M and Arciero, CA and Pfister, NT and Xu, KM and Meisel, JL and Subhedar, P and Torres, M and Curran, WJ and Patel, PR},
title = {The Influence of Histologic Grade on Outcomes of Elderly Women With Early Stage Breast Cancer Treated With Breast Conserving Surgery With or Without Radiotherapy.},
journal = {Clinical breast cancer},
volume = {20},
number = {6},
pages = {e701-e710},
pmid = {32665190},
issn = {1938-0666},
support = {P30 CA138292/CA/NCI NIH HHS/United States ; },
mesh = {Aged ; Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/diagnosis/mortality/pathology/*therapy ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental/*statistics &amp; numerical data ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant/statistics &amp; numerical data ; SEER Program/statistics &amp; numerical data ; Treatment Outcome ; },
abstract = {BACKGROUND: Two large randomized trials, CALGB 9343 and PRIME II, support omission of radiotherapy after breast conserving surgery (BCS) in elderly women with favorable-risk early stage breast cancer intending to take endocrine therapy. However, patients with grade 3 histology were underrepresented on these trials. We hypothesized that high-grade disease may be unsuitable for treatment de-escalation and report the oncologic outcomes for elderly women with favorable early stage breast cancer treated with BCS with or without radiotherapy.<br><br>MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for women between 70 and 79 years of age with invasive ductal carcinoma diagnosed between 1998 and 2007. This cohort was narrowed to women with T1mic-T1c, N0, estrogen receptor-positive, invasive ductal carcinoma treated with BCS with or without external beam radiation (EBRT). The primary endpoints were 5- and 10-year cause-specific survival (CSS). Univariate and multivariate analyses were performed. Propensity-score matching of T-stage, year of diagnosis, and age was utilized to reduce selection bias while comparing treatment arms within the grade 3 subgroup.<br><br>RESULTS: A total of 12,036 women met inclusion criteria, and the median follow-up was 9.4 years. EBRT was omitted in 22% of patients, including 21% with grade 3 disease. Patients in the EBRT cohort were slightly younger (median, 74 vs. 75 years; P&#xa0;< .01) and had fewer T1a tumors (11% vs. 13%; P&#xa0;= .02). Histologic grades 1, 2, and 3 comprised 36%, 50%, and 14% of the cohort, respectively, and there were no differences in EBRT utilization by grade. Utilization of EBRT decreased following the publication of the CALGB trial in 2004 decreasing from 82% to 85% in 1998 to 2000 to 73% to 75% in 2005 to 2007 (P&#xa0;< .01). Unadjusted outcomes showed that in grade 1 disease, there were no differences in CSS with or without EBRT at 5 (99%) and 10 years (95%-96%). EBRT was associated with an improvement in CSS in grade 2 histology at 5 years (97% vs. 98%) and 10 years (92% vs. 95%) (P&#xa0;= .004). The benefit was more pronounced in grade 3 disease with CSS increasing from 93% to 96% at 5 years and from 87% to 92% at 10 years (P&#xa0;= .02) with EBRT. In the grade 3 subgroup, propensity-score matching confirmed EBRT was associated with superior CSS compared with surgery alone (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P&#xa0;= .043).<br><br>CONCLUSION: In this database analysis, omission of radiotherapy after BCS in elderly women with favorable-risk, early stage, grade 3 breast cancer was associated with inferior CSS. Further prospective data in this patient population are needed to confirm our findings and conclusions.},
}
@article {pmid32662684,
year = {2020},
author = {Shan, Z and Liu, L and Shen, J and Hao, H and Zhang, H and Lei, L and Liu, F and Wang, Z},
title = {Enhanced UV Resistance Role of Death Domain-Associated Protein in Human MDA-MB-231 Breast Cancer Cells by Regulation of G2 DNA Damage Checkpoint.},
journal = {Cell transplantation},
volume = {29},
number = {},
pages = {963689720920277},
pmid = {32662684},
issn = {1555-3892},
mesh = {Adult ; Breast Neoplasms/*genetics ; Cell Proliferation ; DNA Damage/*genetics ; Death Domain/*genetics ; Female ; G2 Phase Cell Cycle Checkpoints ; Humans ; Immunohistochemistry/*methods ; Middle Aged ; },
abstract = {PURPOSE: Death domain-associated protein (DAXX) is a multifunctional nuclear protein involved in apoptosis, transcription, deoxyribonucleic acid damage response, and tumorigenesis. However, the role of DAXX in breast cancer development and progression remains elusive. In this study, we examined the expression patterns and function of DAXX in human breast cancer samples and cell lines.<br><br>METHODS: Immunohistochemistry was used to analyze the expression and localization patterns of DAXX. Additionally, we investigated whether DAXX played an intrinsic role in the cellular response to damage induced by ultraviolet (UV) irradiation in MDA-MB-231 breast cancer cells (isolated at M D Anderson from a pleural effusion of a patient with invasive ductal carcinoma).<br><br>RESULTS: Our results showed that nucleus size, chromatin organization, and DAXX localization were altered in breast cancer tissues compared with those in control tissues. Compared with cytoplasmic and nuclear expression in benign breast tissues, DAXX was colocalized with promyelocytic leukemia in nuclei with a granular distribution. Endogenous DAXX messenger ribonucleic acid levels were upregulated upon UV radiation in MDA-MB-231 cells. DAXX-deficient cells tended to be more sensitive to irradiation than control cells. Conversely, DAXX-overexpressing cells exhibited reduced&#xa0;phosphorylated histone H2AX (&#x3b3;-H2AX) accumulation, increased cell survival, and resistance to UV-induced damage. The protective effects of DAXX may be related to the activation of the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (ATM-CHK2)-cell division cycle 25c (CDC25c) signaling pathways in Gap2/Mitosis (G2/M) checkpoint and ultimately cell cycle arrest at G2/M phase.<br><br>CONCLUSIONS: Taken together, these results suggested that DAXX may be an essential component in breast cancer initiation, malignant progression, and radioresistance.},
}
@article {pmid32661669,
year = {2021},
author = {Rooper, LM and Thompson, LDR and Gagan, J and Oliai, BR and Weinreb, I and Bishop, JA},
title = {Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion.},
journal = {Head and neck pathology},
volume = {15},
number = {1},
pages = {179-185},
pmid = {32661669},
issn = {1936-0568},
mesh = {Aged ; Aged, 80 and over ; Carcinoma, Ductal/genetics/*pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Male ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Parotid Neoplasms/genetics/*pathology ; },
abstract = {Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.},
}
@article {pmid32661241,
year = {2020},
author = {Tasdemir, N and Ding, K and Savariau, L and Levine, KM and Du, T and Elangovan, A and Bossart, EA and Lee, AV and Davidson, NE and Oesterreich, S},
title = {Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {11487},
pmid = {32661241},
issn = {2045-2322},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; 5F30CA203154/NH/NIH HHS/United States ; K99CA237736/NH/NIH HHS/United States ; 1F31CA203055-01/NH/NIH HHS/United States ; F31 CA203055/CA/NCI NIH HHS/United States ; K99 CA237736/CA/NCI NIH HHS/United States ; },
mesh = {Autoantigens/genetics ; Breast Neoplasms/*genetics/pathology ; Cadherins/genetics ; Carcinoma, Lobular/*genetics/pathology ; Cell Differentiation/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Inhibitor of Differentiation Protein 1/genetics ; Inhibitor of Differentiation Proteins/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Membrane Proteins/genetics ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Proteins/genetics ; Phosphatidylinositol 3-Kinases/genetics ; *Proteomics ; Proto-Oncogene Proteins c-akt/genetics ; Ribosomal Protein S6 Kinases, 90-kDa/genetics ; Signal Transduction/genetics ; Transcriptome/*genetics ; },
abstract = {Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further transcriptional profiling uncovered unique upregulation of the inhibitors of differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.},
}
@article {pmid32650989,
year = {2020},
author = {Kaviani, A and Tabary, M and Zand, S and Araghi, F and Patocskai, E and Nouraie, M},
title = {Oncoplastic Repair in Breast Conservation: Comprehensive Evaluation of Techniques and Oncologic Outcomes of 937 Patients.},
journal = {Clinical breast cancer},
volume = {20},
number = {6},
pages = {511-519},
doi = {10.1016/j.clbc.2020.05.016},
pmid = {32650989},
issn = {1938-0666},
mesh = {Adult ; Breast/pathology/surgery ; Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Chemotherapy, Adjuvant/statistics &amp; numerical data ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Iran/epidemiology ; Mammaplasty/*adverse effects/methods/statistics &amp; numerical data ; Margins of Excision ; Mastectomy, Segmental/*adverse effects/statistics &amp; numerical data ; Middle Aged ; Neoadjuvant Therapy/methods/statistics &amp; numerical data ; Neoplasm Recurrence, Local/*epidemiology ; Neoplasm Staging ; Postoperative Complications/*epidemiology/etiology ; Prospective Studies ; Reoperation/statistics &amp; numerical data ; Retrospective Studies ; },
abstract = {BACKGROUND: Breast-conserving surgery, especially with oncoplastic breast surgery (OBS), is becoming the standard of care in the surgical management of breast cancer. We investigated the applied technique of OBS and oncologic outcomes in a large series of patients.<br><br>PATIENTS AND METHODS: This study was conducted between January 2008 and June 2018 in two centers in Iran. Patients underwent OBS. Early and late postoperative complications, oncologic outcomes, and follow-up data were documented.<br><br>RESULTS: Nine hundred thirty-seven patients with a mean &#xb1; standard deviation age of 48.1 &#xb1; 11.3 underwent OBS. Most of the patients were diagnosed with early-stage disease, of which the most common pathology was invasive ductal carcinoma (83.3%). Lateral oncoplasty was the most commonly used OBS technique (324 cases, 34.6%). The most common complication was seroma formation. Reduction-type OBS technique had the highest rate of complications (13.1%). Thirty-four patients (5.4%) experienced local recurrence, with a median recurrence time of 26.4 months. Nine patients (1.3%) died from cancer recurrence.<br><br>CONCLUSION: OBS is a safe procedure with minor complications and good oncologic outcomes. These techniques can be applied to most patients who are candidates for breast-conserving surgery.},
}
@article {pmid32637252,
year = {2020},
author = {Jones, B and Thomas, G and Westreich, J and Nofech-Mozes, S and Vitkin, A and Khorasani, M},
title = {Novel quantitative signature of tumor stromal architecture: polarized light imaging differentiates between myxoid and sclerotic human breast cancer stroma.},
journal = {Biomedical optics express},
volume = {11},
number = {6},
pages = {3246-3262},
pmid = {32637252},
issn = {2156-7085},
abstract = {As a leading cause of death in women, breast cancer is a global health concern for which personalized therapy remains largely unrealized, resulting in over- or under-treatment. Recently, tumor stroma has been shown to carry important prognostic information, both in its relative abundance and morphology, but its current assessment methods are few and suboptimal. Herein, we present a novel stromal architecture signature (SAS) methodology based on polarized light imaging that quantifies patterns of tumor connective tissue. We demonstrate its ability to differentiate between myxoid and sclerotic stroma, two pathology-derived categories associated with significantly different patient outcomes. The results demonstrate a 97% sensitivity and 88% specificity for myxoid stroma identification in a pilot study of 102 regions of interest from human invasive ductal carcinoma breast cancer surgical specimens (20 patients). Additionally, the SAS numerical score is indicative of the wide range of stromal characteristics within these binary classes and highlights ambiguous mixed-morphology regions prone to misclassification. The enabling polarized light microscopy technique is inexpensive, fast, fully automatable, applicable to fresh or embedded tissue without the need for staining and thus potentially translatable into research and/or clinical settings. The SAS metric yields quantifiable and objective stromal characterization with promise for prognosis in many types of cancers beyond breast carcinoma, enabling researchers and clinicians to further investigate the emerging and important role of stromal architectural patterns in solid tumors.},
}
@article {pmid32636849,
year = {2020},
author = {Siegers, GM and Dutta, I and Kang, EY and Huang, J and Köbel, M and Postovit, LM},
title = {Aberrantly Expressed Embryonic Protein NODAL Alters Breast Cancer Cell Susceptibility to γδ T Cell Cytotoxicity.},
journal = {Frontiers in immunology},
volume = {11},
number = {},
pages = {1287},
pmid = {32636849},
issn = {1664-3224},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Intraepithelial Lymphocytes/*immunology ; Middle Aged ; Nodal Protein/*immunology/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Triple Negative Breast Neoplasms/*immunology/metabolism ; Tumor Escape/*immunology ; Tumor Microenvironment/*immunology ; },
abstract = {Gamma delta (γδ) T cells kill transformed cells, and increased circulating γδ T cells levels correlate with improved outcome in cancer patients; however, their function within the breast tumor microenvironment (TME) remains controversial. As tumors progress, they begin to express stem-cell associated proteins, concomitant with the emergence of therapy resistant metastatic disease. For example, invasive breast cancers often secrete the embryonic morphogen, NODAL. NODAL has been shown to promote angiogenesis, therapy resistance and metastasis in breast cancers. However, to date, little is known about how this secreted protein may interact with cells in the TME. Herein we explore how NODAL in the TME may influence γδ T cell function. We have assessed the proximity of γδ T cells to NODAL in a cohort of triple negative breast tumors. In all cases in which γδ T cells could be identified in these tumors, γδ T cells were found in close proximity to NODAL-expressing tumor cells. Migration of γδ and αβ T cells was similar toward MDA-MB-231 cells in which NODAL had been knocked down (shN) and MDA-MB-231 scrambled control cells (shC). Furthermore, Vδ1 γδ T cells did not migrate preferentially toward conditioned medium from these cell lines. While 24-h exposure to NODAL did not impact CD69, PD-1, or T cell antigen receptor (TCR) expression on γδ T cells, long term exposure resulted in decreased Vδ2 TCR expression. Maturation of γδ T cells was not significantly influenced by NODAL stimulation. While neither short- nor long-term NODAL stimulation impacted the ability of γδ T cells to kill MCF-7 breast cancer cells, the absence of NODAL resulted in greater sensitivity of targets to γδ T cell cytotoxicity, while overexpression of NODAL conferred resistance. This appeared to be at least in part due to an inverse correlation between NODAL and surface MICA/B expression on breast cancer target lines. As such, it appears that NODAL may play a role in strategies employed by breast cancer cells to evade γδ T cell targeting, and this should be considered in the development of safe and effective γδ T cell immunotherapies.},
}
@article {pmid32619221,
year = {2020},
author = {Escoter-Torres, L and Greulich, F and Quagliarini, F and Wierer, M and Uhlenhaut, NH},
title = {Anti-inflammatory functions of the glucocorticoid receptor require DNA binding.},
journal = {Nucleic acids research},
volume = {48},
number = {15},
pages = {8393-8407},
pmid = {32619221},
issn = {1362-4962},
mesh = {Animals ; DNA/*genetics/metabolism ; DNA-Binding Proteins/*genetics ; Gene Expression Regulation/genetics ; Glucocorticoids/genetics/metabolism ; Humans ; Inflammation/*genetics/pathology ; Mice ; Protein Interaction Domains and Motifs/genetics ; RNA-Seq ; Receptors, Glucocorticoid/*genetics ; Transcriptional Activation/genetics ; },
abstract = {The glucocorticoid receptor is an important immunosuppressive drug target and metabolic regulator that acts as a ligand-gated transcription factor. Generally, GR's anti-inflammatory effects are attributed to the silencing of inflammatory genes, while its adverse effects are ascribed to the upregulation of metabolic targets. GR binding directly to DNA is proposed to activate, whereas GR tethering to pro-inflammatory transcription factors is thought to repress transcription. Using mice with a point mutation in GR's zinc finger, that still tether via protein-protein interactions while being unable to recognize DNA, we demonstrate that DNA binding is essential for both transcriptional activation and repression. Performing ChIP-Seq, RNA-Seq and proteomics under inflammatory conditions, we show that DNA recognition is required for the assembly of a functional co-regulator complex to mediate glucocorticoid responses. Our findings may contribute to the development of safer immunomodulators with fewer side effects.},
}
@article {pmid32618211,
year = {2020},
author = {Bhattad, PB and Jain, V},
title = {Diffuse Sarcoidosis Masquerading as Widespread Malignant Disease: A Rare Case Report and Literature Review.},
journal = {Journal of investigative medicine high impact case reports},
volume = {8},
number = {},
pages = {2324709620938942},
pmid = {32618211},
issn = {2324-7096},
mesh = {Biopsy ; Breast Neoplasms/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Lung/*pathology ; Lymph Nodes/*pathology ; Lymphoma/*pathology ; Magnetic Resonance Imaging ; Mediastinum/*pathology ; Middle Aged ; Neoplasm Metastasis/diagnosis ; Positron Emission Tomography Computed Tomography ; Sarcoidosis/complications/*diagnosis ; },
abstract = {Sarcoidosis is a multisystem granulomatous disease commonly involving the lungs and mediastinal lymph nodes with the exact etiology being unclear. The simultaneous presence of malignant disease such as breast cancer and sarcoidosis has been reported. Sarcoidosis preceding a diagnosis of malignancy and that occurring years after treatment of malignant disease has been noted in the past. The presence of sarcoidosis in the setting of malignant disease carries a high risk of misdiagnosis. In this article, we report the case of a 45-year-old female with stage IA invasive ductal carcinoma of left breast that was in remission for 2 years; however, radiological imaging including magnetic resonance imaging of thoracic spine and positron emission tomography-computed tomography scanning were highly suspicious for malignant disease metastasis versus lymphoma with the widespread lymphadenopathy. Multiple tissue biopsies with histopathological evaluation allowed us to definitively exclude malignant disease metastasis and to correctly diagnose her atypical presentation of sarcoidosis.},
}
@article {pmid32617838,
year = {2021},
author = {Hashinokuchi, A and Akamine, T and Kometani, T and Shikada, Y and Nozoe, T and Kato, S},
title = {Spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer: a case report and literature review.},
journal = {General thoracic and cardiovascular surgery},
volume = {69},
number = {1},
pages = {137-141},
pmid = {32617838},
issn = {1863-6713},
mesh = {Aged ; *Breast Neoplasms ; Female ; Humans ; Neoplasm Recurrence, Local ; Pleurodesis ; *Pneumothorax/etiology/therapy ; Quality of Life ; Recurrence ; Thoracic Surgery, Video-Assisted ; },
abstract = {We report a 69-year-old woman with spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer. She was treated for right breast cancer (invasive ductal carcinoma, ypT4bN1M0, stage IIIB) 2 years earlier, and was admitted for right pneumothorax and chest computed tomography, which showed multiple small cavitating lesions in bilateral lungs. The pneumothorax was treated conservatively with chest drainage, but subsequently recurred ipsilaterally. During video-assisted thoracic surgery, we detected small white nodules with visceral pleural rupture; therefore, we performed partial lung resection. The pathological findings revealed metastatic breast cancer with pleural invasion. Forty days later, ipsilateral pneumothorax recurred, and chemical pleurodesis was performed, which resolved the pneumothorax and prevented subsequent recurrence. Early diagnosis and definitive treatment, including pleurodesis, should be considered to prevent recurrence of spontaneous pneumothorax and improve patients' quality of life, even in patients with advanced malignancy.},
}
@article {pmid32609836,
year = {2020},
author = {Sreekumar, S and Levine, KM and Sikora, MJ and Chen, J and Tasdemir, N and Carter, D and Dabbs, DJ and Meier, C and Basudan, A and Boone, D and McAuliffe, PF and Jankowitz, RC and Lee, AV and Atkinson, JM and Oesterreich, S},
title = {Differential Regulation and Targeting of Estrogen Receptor α Turnover in Invasive Lobular Breast Carcinoma.},
journal = {Endocrinology},
volume = {161},
number = {9},
pages = {},
pmid = {32609836},
issn = {1945-7170},
support = {R00 CA193734/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; K99 CA193734/CA/NCI NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; K99 CA237736/CA/NCI NIH HHS/United States ; },
mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; Cell Line, Tumor ; Estradiol/pharmacology ; Estrogen Receptor alpha/*genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MCF-7 Cells ; Neoplasm Invasiveness ; Protein Processing, Post-Translational/drug effects ; Proteolysis/drug effects ; Ubiquitination/drug effects ; },
abstract = {Invasive lobular breast carcinoma (ILC) accounts for 10% to 15% of breast cancers diagnosed annually. Evidence suggests that some aspects of endocrine treatment response might differ between invasive ductal carcinoma (IDC) and ILC, and that patients with ILC have worse long-term survival. We analyzed The Cancer Genome Atlas dataset and observed lower levels of ESR1 mRNA (P = 0.002) and ERα protein (P = 0.038) in ER+ ILC (n = 137) compared to IDC (n = 554), and further confirmed the mRNA difference in a local UPMC cohort (ILC, n = 143; IDC, n = 877; P < 0.005). In both datasets, the correlation between ESR1 mRNA and ERα protein was weaker in ILC, suggesting differential post-transcriptional regulation of ERα. In vitro, 17β-estradiol (E2) decreased the rate of degradation and increased the half-life of ERα in ILC cell lines, whereas the opposite was observed in IDC cell lines. Further, E2 failed to induce robust ubiquitination of ERα in ILC cells. To determine the potential clinical relevance of these findings, we evaluated the effect of 2 selective estrogen receptor downregulators (SERDs), ICI 182,780 and AZD9496, on ERα turnover and cell growth. While ICI 182,780 and AZD9496 showed similar effects in IDC cells, in ILC cell lines, AZD9496 was not as effective as ICI 182,780 in decreasing ERα stability and E2-induced proliferation. Furthermore, AZD9496 exhibited partial agonist activity in growth assays in ILC cell lines. Our study provides evidence for a distinct ERα regulation by SERDs in ILC cell lines, and therefore it is important to include ILC models into preclinical and clinical testing of novel SERDs.},
}
@article {pmid32599083,
year = {2020},
author = {Grabenstetter, A and Mohanty, AS and Rana, S and Zehir, A and Brannon, AR and D'Alfonso, TM and DeLair, DF and Tan, LK and Ross, DS},
title = {E-cadherin immunohistochemical expression in invasive lobular carcinoma of the breast: correlation with morphology and CDH1 somatic alterations.},
journal = {Human pathology},
volume = {102},
number = {},
pages = {44-53},
pmid = {32599083},
issn = {1532-8392},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Antigens, CD/biosynthesis/*genetics ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/genetics/*pathology ; Cadherins/biosynthesis/*genetics ; Carcinoma, Lobular/diagnosis/genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Immunohistochemistry ; Mutation ; },
abstract = {E-cadherin (ECAD) immunohistochemical (IHC) expression is lost in ∼90% of invasive lobular carcinomas (ILCs) owing to genomic alterations of CDH1. We examined morphologic features and ECAD IHC expression in invasive breast carcinomas (BCs) with known CDH1 alterations. Between January 2014 and May 2018, 202 cases of BC with a CDH1 somatic alteration were identified. ECAD expression was lost in 77% (155/202) of cases and was retained in 23% (47/202) cases. Most (90%, 139/155) ECAD-negative cases were morphologically classified as ILC, while the remaining (10%, 16/155) were invasive mammary carcinoma with mixed ductal and lobular features (IMC). Of 47 cases with ECAD staining, 62% (29/47) were classified as ILC, 23% (11/47) were classified as IMC, and 15% (7/47) were classified as invasive ductal carcinoma (IDC). Of note, 51% (24/47) of ECAD-positive cases were initially diagnosed as IDC or IMC based on ECAD expression alone. For ECAD-negative BCs, 98% (152/155) of CDH1 alterations were truncating, and 2% (3/155) were variants of unknown significance (VUS). Truncating CDH1 alterations were identified in the majority of ECAD-positive BCs (72%, 34/47); however, VUS-type CDH1 alterations were more prevalent (28%, 13/47) in ECAD-positive BCs than in ECAD-negative BCs. Although 90% of ECAD-negative tumors were compatible with ILC in this study, 17% (29/168) of ILC cases were ECAD positive. In addition, CDH1 truncating alterations were seen in ECAD-positive ILC, supporting the notion of aberrant ECAD staining. Therefore, ECAD IHC expression must be interpreted in conjunction with morphology, and BC with classic histologic features of ILC should not be reclassified as IDC/IMC based solely on the status of ECAD IHC expression.},
}
@article {pmid32589068,
year = {2021},
author = {Epstein, JI and Amin, MB and Fine, SW and Algaba, F and Aron, M and Baydar, DE and Beltran, AL and Brimo, F and Cheville, JC and Colecchia, M and Comperat, E and da Cunha, IW and Delprado, W and DeMarzo, AM and Giannico, GA and Gordetsky, JB and Guo, CC and Hansel, DE and Hirsch, MS and Huang, J and Humphrey, PA and Jimenez, RE and Khani, F and Kong, Q and Kryvenko, ON and Kunju, LP and Lal, P and Latour, M and Lotan, T and Maclean, F and Magi-Galluzzi, C and Mehra, R and Menon, S and Miyamoto, H and Montironi, R and Netto, GJ and Nguyen, JK and Osunkoya, AO and Parwani, A and Robinson, BD and Rubin, MA and Shah, RB and So, JS and Takahashi, H and Tavora, F and Tretiakova, MS and True, L and Wobker, SE and Yang, XJ and Zhou, M and Zynger, DL and Trpkov, K},
title = {The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer.},
journal = {Archives of pathology &amp; laboratory medicine},
volume = {145},
number = {4},
pages = {461-493},
doi = {10.5858/arpa.2020-0015-RA},
pmid = {32589068},
issn = {1543-2165},
mesh = {Biomarkers, Tumor/analysis/genetics ; Biopsy, Needle/standards ; Consensus ; Humans ; Image-Guided Biopsy/standards ; Immunohistochemistry/standards ; Magnetic Resonance Imaging/standards ; Male ; Molecular Diagnostic Techniques/standards ; Neoplasm Grading/*standards ; Pathology/*standards ; Predictive Value of Tests ; Prostatic Neoplasms/chemistry/genetics/*pathology ; },
abstract = {CONTEXT.&#x2014;: Controversies and uncertainty persist in prostate cancer grading.<br><br>OBJECTIVE.&#x2014;: To update grading recommendations.<br><br>DATA SOURCES.&#x2014;: Critical review of the literature along with pathology and clinician surveys.<br><br>CONCLUSIONS.&#x2014;: Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.},
}
@article {pmid32586354,
year = {2020},
author = {Blohmer, M and Zhu, L and Atkinson, JM and Beriwal, S and Rodríguez-López, JL and Rosenzweig, M and Brufsky, AM and Tseng, G and Lucas, PC and Lee, AV and Oesterreich, S and Jankowitz, RC},
title = {Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology.},
journal = {Breast cancer research : BCR},
volume = {22},
number = {1},
pages = {70},
pmid = {32586354},
issn = {1465-542X},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; CCR14300865/KOMEN/Susan G. Komen/United States ; U24 CA180921/CA/NCI NIH HHS/United States ; SAC150021/KOMEN/Susan G. Komen/United States ; SAC160073/KOMEN/Susan G. Komen/United States ; },
mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/*pathology/*radiotherapy ; Carcinoma, Ductal, Breast/metabolism/pathology/radiotherapy ; Carcinoma, Lobular/metabolism/*mortality/pathology/radiotherapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Orbital Neoplasms/metabolism/radiotherapy/*secondary ; Prognosis ; Radiotherapy, Intensity-Modulated ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; },
abstract = {BACKGROUND: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival.<br><br>METHODS: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed.<br><br>RESULTS: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p&#x2009;=&#x2009;0.007). Median time to first OM in the OM cohort was 46.7&#x2009;months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4&#x2009;months) was significantly shorter than that of patients with IDC (55.3&#x2009;months, p&#x2009;=&#x2009;0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p&#x2009;=&#x2009;0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM.<br><br>CONCLUSIONS: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.},
}
@article {pmid32585364,
year = {2020},
author = {Erener, S},
title = {Diabetes, infection risk and COVID-19.},
journal = {Molecular metabolism},
volume = {39},
number = {},
pages = {101044},
pmid = {32585364},
issn = {2212-8778},
mesh = {Adult ; Aged ; Animals ; *Betacoronavirus ; COVID-19 ; Child ; Comorbidity ; Coronavirus Infections/*epidemiology/immunology/pathology/virology ; Cytokines/metabolism ; Diabetes Mellitus, Type 1/*epidemiology/immunology ; Diabetes Mellitus, Type 2/*epidemiology/immunology ; Female ; Humans ; Immunity, Cellular ; Immunity, Innate ; Incidence ; Male ; Mice ; Middle Aged ; Pandemics ; Pneumonia, Viral/*epidemiology/immunology/pathology/virology ; Risk Factors ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial, and fungal infections. The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries and claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19.<br><br>SCOPE OF REVIEW: In this review, I summarize the clinical data on the risk for infectious diseases in individuals with diabetes while highlighting the mechanisms for altered immune regulation. The focus is on coronaviruses. Based on the new clinical data obtained from COVID-19 patients, a discussion of mechanisms, such as cytokine storm, pulmonary and endothelial dysfunction, and hypercoagulation, that may render individuals with diabetes more vulnerable to COVID-19 is provided.<br><br>MAJOR CONCLUSIONS: Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and the pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to designing tailored treatments and clinical management of individuals affected by diabetes.},
}
@article {pmid32581209,
year = {2020},
author = {Lan, T and Lu, Y and Luo, H and He, J and He, J and Hu, Z and Xu, H},
title = {Effects of Marital Status on Prognosis in Women with Infiltrating Ductal Carcinoma of the Breast: A Real-World 1: 1 Propensity-Matched Study.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {26},
number = {},
pages = {e923630},
pmid = {32581209},
issn = {1643-3750},
mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal/mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Marital Status/*statistics &amp; numerical data ; Middle Aged ; Multivariate Analysis ; Prognosis ; Propensity Score ; Proportional Hazards Models ; Protective Factors ; Risk Factors ; SEER Program ; United States/epidemiology ; },
abstract = {BACKGROUND The effects of marital status on infiltrating ductal carcinoma of breast cancer (IDC) have not been studied in detail. This study investigated the impact of marital status on IDC patients. MATERIAL AND METHODS SEER databases were searched from 2010 to 2015 for subjects who were married, divorced, single, and widowed. The influence of marital status on breast cancer-specific survival (BCSS) and overall survival (OS) of IDC patients was investigated through multivariate Cox regression analysis and Kaplan-Meier analysis. To prevent bias, propensity score matching (PSM) analysis was performed. RESULTS The 5-year OS was 89.6%in married patients, 84.9% in divorced patients, 83.5% in single patients, and 71.3% in widowed patients (p<0.001). The 5-year BCSS were 92.9%, 90.2%, 87.6%, and 86.4%, respectively (p<0.001). Multivariate Cox regression analysis revealed that marriage was a protective factor for patients with IDC in terms of OS (divorced: HR, 1.27; 95% CI, 1.21-1.32; p<0.001; single: HR, 1.36; 95% CI, 1.31-1.42; p<0.001; widowed: HR, 1.42; 95% CI, 1.36-1.48; p<0.001) and BCSS (divorced: HR, 1.15; 95% CI, 1.09-1.21; p<0.001; single: HR, 1.27; 95% CI, 1.21-1.33; p<0.001; widowed: HR, 1.32; 95% CI, 1.25-1.40; p<0.001). Following subgroup and PSM analysis, married patients were shown to have better OS and BCSS as opposed to divorced, single, or widowed patients. CONCLUSIONS We identify marital status as a predictor of survival in those with IDC. Widowed patients showed the highest mortality risk.},
}
@article {pmid32580398,
year = {2020},
author = {Kim, HM and Koo, JS},
title = {Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes.},
journal = {International journal of molecular sciences},
volume = {21},
number = {12},
pages = {},
pmid = {32580398},
issn = {1422-0067},
support = {2016 (6-2016-0163)//faculty research grant from Yonsei University College of Medicine/ ; },
mesh = {Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/immunology/metabolism/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; Forkhead Transcription Factors/metabolism ; Humans ; Lymphocytes, Tumor-Infiltrating/*classification/*immunology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; STAT6 Transcription Factor/metabolism ; Survival Rate ; CD163 Antigen ; },
abstract = {The clinical significance of immune cell subtypes in breast cancer remains poorly understood. To identify tumor-infiltrating immune cell subtypes in breast cancer and investigate their implications, tissue microarrays were constructed using 334 cases of invasive ductal carcinoma (luminal A type: 162 (48.5%), luminal B type: 96 (28.7%), HER-2 type: 21 (6.3%), and triple negative breast cancer: 55 (16.5%)). Hormone receptors (ER, PR, and HER-2), Ki-67, and immune cell subtype-related proteins (STAT4, STAT6, FOXP3, CD8, CD68, and CD163) were assessed immunohistochemically. The proportion of highly expressed STAT6, FOXP3, CD8, CD68, and CD163 proteins was found to be lowest in luminal A type but highest in the HER-2 type. Additionally, high-level STAT6, FOXP3, CD68, and CD163 protein expression was associated with higher histologic grade. ER negativity was associated with high STAT6, FOXP3, and CD163 expression levels, whereas PR negativity and high Ki-67 labeling index were associated with high CD163 expression. Univariate (p = 0.003) and multivariate Cox (hazard ratio: 2.435, 95% CI: 1.110-5.344, p = 0.049) analyses showed that high CD8 expression is an independent factor associated with shorter disease-free survival. Immune cell subtype-related protein expression is dependent on breast cancer molecular subtypes, and CD8 expression is associated with patient prognosis.},
}
@article {pmid32563094,
year = {2020},
author = {Yoneyama, K and Nakagawa, M and Hara, A},
title = {Local recurrence of breast cancer caused by core needle biopsy: Case report and review of the literature.},
journal = {International journal of surgery case reports},
volume = {72},
number = {},
pages = {318-321},
pmid = {32563094},
issn = {2210-2612},
abstract = {INTRODUCTION: Needle tract seeding is the implantation of tumor cells at the site of needle passage during needle biopsy. Histopathological examination of resected specimens after biopsy shows an incidence of 22%-50%. However, reports of actual local recurrence are extremely rare. Here we report such a case.<br><br>PRESENTATION OF CASE: A 67-year-old woman was diagnosed with ductal carcinoma by histopathology and underwent right mastectomy and sentinel lymph node biopsy. Histopathological examination revealed non-invasive ductal carcinoma. One year after the first operation, a mass was found at the site of the core needle biopsy (CNB) scar near the previous surgical wound on the right chest. Histological examination revealed the tumor as adenocarcinoma, and a skin lesion resection was performed. After surgery, radiation therapy and endocrine therapy were performed. She remains relapse-free as of this writing, 9 months after resection.<br><br>DISCUSSION: Reports of local recurrence due to needle tract seeding are extremely rare. We found nine cases of mastectomy and seven cases of partial resection performed for the first surgery; six patients received radiation therapy and 10 did not. Histological diagnosis at the time of the first operation was invasive carcinoma in all cases.<br><br>CONCLUSION: The risk of seeding is high with multiple punctures in CNB, in cases with a short period until surgery, and in mucinous carcinoma. Considering these factors, CNB puncture should preferably be at a site that is included in the resection area during surgery. If not resected, close follow-up is necessary considering the possibility of local recurrence.},
}
@article {pmid32561662,
year = {2020},
author = {Sestak, I and Filipits, M and Buus, R and Rudas, M and Balic, M and Knauer, M and Kronenwett, R and Fitzal, F and Cuzick, J and Gnant, M and Greil, R and Dowsett, M and Dubsky, P},
title = {Prognostic Value of EndoPredict in Women with Hormone Receptor-Positive, HER2-Negative Invasive Lobular Breast Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {26},
number = {17},
pages = {4682-4687},
doi = {10.1158/1078-0432.CCR-20-0260},
pmid = {32561662},
issn = {1557-3265},
support = {16891/CRUK_/Cancer Research UK/United Kingdom ; 5032/CRUK_/Cancer Research UK/United Kingdom ; C569/A16891/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast/*pathology/surgery ; Breast Neoplasms/genetics/*mortality/pathology/therapy ; Carcinoma, Lobular/genetics/*mortality/pathology/therapy ; Chemotherapy, Adjuvant/methods ; Clinical Trials, Phase III as Topic ; Datasets as Topic ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/genetics/pathology ; Prognosis ; Randomized Controlled Trials as Topic ; Receptor, ErbB-2/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Risk Assessment/methods ; },
abstract = {PURPOSE: Invasive lobular carcinoma (ILC) accounts for approximately 5%-15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients with invasive ductal carcinoma (IDC) or without distinction between the subtypes. Here, we investigate the prognostic value of EndoPredict (EPclin) in a large cohort of ILCs pooled from three phase III randomized trials (ABCSG-6, ABCSG-8, TransATAC).<br><br>EXPERIMENTAL DESIGN: The primary objective of this analysis was to determine the prognostic value of EPclin for distant recurrence (DR) in years 0-10 in postmenopausal women with ILC. The primary outcome was DR.<br><br>RESULTS: 470 women (17.9%) presented with ILC, 1,944 (73.9%) with IDC, and 216 (8.2%) with other histologic types. EPclin was highly prognostic in women with ILC [HR = 3.32 (2.54-4.34)] and provided more prognostic value than the Clinical Treatment Score [CTS; HR = 2.17 (1.73-2.72)]. 63.4% of women were categorized into the low EPclin risk group and they had a 10-year DR of 4.8% (2.7-8.4) compared with 36.6% of women in the high-risk group with a 10-year DR risk of 26.6% (20.0-35.0). EPclin also provided highly prognostic information in women with node-negative disease [HR = 2.56 (1.63-4.02)] and node-positive disease [HR = 3.70 (2.49-5.50)].<br><br>CONCLUSIONS: EPclin provided highly significant prognostic value and significant risk stratification for women with ILC. Ten-year DR risk in the EPclin low-risk groups were similar between ILC and IDC. Our results show that EPclin is informative in women with ILC and suggest that it is equally valid in both histologic subtypes.},
}
@article {pmid32551954,
year = {2020},
author = {Bosso, G and Valvano, A and Apuzzi, V and Mercurio, V and Di Simone, V and Cittadini, A and Napoli, R and Oliviero, U},
title = {Peripheral Vascular Function in Dilated Cardiomyopathy of Different Etiology.},
journal = {Angiology},
volume = {71},
number = {8},
pages = {726-733},
doi = {10.1177/0003319720932803},
pmid = {32551954},
issn = {1940-1574},
mesh = {Aged ; Brachial Artery/diagnostic imaging/*physiopathology ; Cardiomyopathy, Dilated/diagnostic imaging/*etiology/*physiopathology ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*complications/diagnosis/physiopathology ; Prognosis ; Risk Assessment ; Risk Factors ; *Vascular Stiffness ; *Vasodilation ; },
abstract = {Vascular function in dilated cardiomyopathy of different etiology has been poorly investigated. Moreover, reference values of flow-mediated dilation (FMD) in chronic heart failure (CHF) need to be updated according to the new standardized protocols. We characterized the vascular impairment in different stages of post-ischemic dilated cardiomyopathy (PI-DC) or idiopathic dilated cardiomyopathy (I-DC). Eighty consecutive outpatients with CHF in different New York Heart Association (NYHA) classes (45 PI-DC, 35 I-DC) and 50 control subjects underwent FMD and brachial distensibility coefficient measurement. Patients with CHF showed a marked impairment in FMD compared with controls that worsened from classes NYHA I-II to III-IV, independently of etiology (P < .05). New York Heart Association I-II PI-DC patients showed a worse FMD compared with NYHA I-II I-DC patients (P < .05). Brachial distensibility coefficient values were significantly lower in patients with CHF compared with controls (P < .001) without differences between PI-DC and I-DC. In conclusion, advanced CHF is characterized by vascular impairment that is independent of etiology. In the early stages of CHF, endothelial dysfunction is more severe in patients with PI-DC compared with I-DC probably due to the high cardiovascular risk profile. In I-DC, vascular function impairment is independent of cardiovascular risk factors and could participate in the pathogenesis of I-DC.},
}
@article {pmid32548206,
year = {2020},
author = {Arensman, K and Dela-Pena, J and Miller, JL and LaChance, E and Beganovic, M and Anderson, M and Rivelli, A and Wieczorkiewicz, SM},
title = {Impact of Mandatory Infectious Diseases Consultation and Real-time Antimicrobial Stewardship Pharmacist Intervention on Staphylococcus aureus Bacteremia Bundle Adherence.},
journal = {Open forum infectious diseases},
volume = {7},
number = {6},
pages = {ofaa184},
pmid = {32548206},
issn = {2328-8957},
abstract = {BACKGROUND: The purpose of this study was to evaluate the impact of infectious diseases consultation (IDC) and a real-time antimicrobial stewardship (AMS) review on the management of Staphylococcus aureus bacteremia (SAB).<br><br>METHODS: This retrospective study included adult inpatients with SAB from January 2016 to December 2018 at 7 hospitals. Outcomes were compared between 3 time periods: before mandatory IDC and AMS review (period 1), after mandatory IDC and before AMS review (period 2), and after mandatory IDC and AMS review (period 3). The primary outcome was bundle adherence, defined as appropriate intravenous antimicrobial therapy, appropriate duration of therapy, appropriate surveillance cultures, echocardiography, and removal of indwelling intravenous catheters, if applicable. Secondary end points included individual bundle components, source control, length of stay (LOS), 30-day bacteremia-related readmission, and in-hospital all-cause mortality.<br><br>RESULTS: A total of 579 patients met inclusion criteria for analysis. Complete bundle adherence was 65% in period 1 (n&#x2005;=&#x2005;241/371), 54% in period 2 (n&#x2005;=&#x2005;47/87), and 76% in period 3 (n&#x2005;=&#x2005;92/121). Relative to period 3, bundle adherence was significantly lower in period 1 (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.37-0.93; P&#x2005;=&#x2005;.02) and period 2 (OR, 0.37; 95% CI, 0.20-0.67; P&#x2005;=&#x2005;.0009). No difference in bundle adherence was noted between periods 1 and 2. Significant differences were seen in obtaining echocardiography (91% vs 83% vs 100%; P&#x2005;<&#x2005;.001), source control (34% vs 45% vs 45%; P&#x2005;=&#x2005;.04), and hospital LOS (10.5 vs 8.9 vs 12.0 days; P&#x2005;=&#x2005;.01). No differences were noted for readmission or mortality.<br><br>CONCLUSIONS: The addition of AMS pharmacist review to mandatory IDC was associated with significantly improved quality care bundle adherence.},
}
@article {pmid32544183,
year = {2020},
author = {Moon, HR and Ospina-Muñoz, N and Noe-Kim, V and Yang, Y and Elzey, BD and Konieczny, SF and Han, B},
title = {Subtype-specific characterization of breast cancer invasion using a microfluidic tumor platform.},
journal = {PloS one},
volume = {15},
number = {6},
pages = {e0234012},
pmid = {32544183},
issn = {1932-6203},
support = {HHSN261201400021C/CA/NCI NIH HHS/United States ; P30 CA023168/CA/NCI NIH HHS/United States ; UL1 TR000006/TR/NCATS NIH HHS/United States ; },
mesh = {CD24 Antigen/metabolism ; Carcinoma, Ductal, Breast/classification/genetics/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Humans ; Microfluidics/methods ; Neoplasm Invasiveness ; Neoplasm Staging ; Triple Negative Breast Neoplasms/classification/genetics/*pathology ; *Tumor Microenvironment ; },
abstract = {Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.},
}
@article {pmid32532588,
year = {2020},
author = {Brings, S and Fleming, T and Herzig, S and Nawroth, PP and Kopf, S},
title = {Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study.},
journal = {Journal of diabetes and its complications},
volume = {34},
number = {9},
pages = {107648},
doi = {10.1016/j.jdiacomp.2020.107648},
pmid = {32532588},
issn = {1873-460X},
mesh = {*Albuminuria/diagnosis/etiology ; Cathepsin D/urine ; Cathepsin L/*urine ; Cohort Studies ; *Diabetes Mellitus, Type 2/complications/diagnosis ; *Glycation End Products, Advanced/urine ; Humans ; Tandem Mass Spectrometry ; },
abstract = {AIMS: Cathepsin D (CTSD) and L (CTSL) are lysosomal proteases which degrade and detoxify advanced glycation end product (AGE)-modified proteins which are predictive of the development of diabetic nephropathy. We aimed to quantify cathepsin levels in urine from patients with type 2 diabetes and to relate these to the amount of urinary free AGEs at baseline and with kidney function after four years of follow-up in this closed cohort study.<br><br>METHODS: We established and validated a LC MS/MS method for the quantification of CTSD and CTSL in urine. Patients with type 2 diabetes were screened for diabetic kidney disease and 141 patients were seen at baseline and after four years. CTSD and CTSL and free AGEs were quantified in urine by LC MS/MS at baseline in these patients.<br><br>RESULTS: The detection limit of CTSD and CTSL in urine was 2.4&#x202f;ng/l and 19.1&#x202f;ng/l, respectively. CTSD (p&#x202f;<&#x202f;0.0001, r&#x202f;=&#x202f;0.555) and CTSL (p&#x202f;<&#x202f;0.0001, r&#x202f;=&#x202f;0.608) correlated positively with albuminuria at time of recruitment. In addition levels of the proteases but not albuminuria correlated with urinary levels of the major cross-linking AGE glucosepane (CTSD: p&#x202f;=&#x202f;0.012, r&#x202f;=&#x202f;0.225; CTSL: p&#x202f;<&#x202f;0.001, r&#x202f;=&#x202f;0.376). A strong non-linear association between CTSD (r&#x202f;=&#x202f;0.568), CTSL (r&#x202f;=&#x202f;0.588) and change in albuminuria over four years was present. High levels of CTSL (p&#x202f;=&#x202f;0.007, beta&#x202f;=&#x202f;-0.366) were associated with an improvement of albuminuria after four years.<br><br>CONCLUSIONS: A sensitive LC MS/MS assay for the quantification of CTSD and CTSL in urine was established. High CTSL baseline levels were associated with an improvement in albuminuria at follow-up. An increased excretion and thus detoxification of the free form of the pathogenic cross-linking AGE glucosepane could explain the positive predictive value of high CTSL levels on albuminuria.},
}
@article {pmid32511899,
year = {2020},
author = {Yamaguchi, T and Akahane, T and Harada, O and Kato, Y and Aimono, E and Takei, H and Tasaki, T and Noguchi, H and Nishihara, H and Kamata, H and Tanimoto, A},
title = {Next-generation sequencing in residual liquid-based cytology specimens for cancer genome analysis.},
journal = {Diagnostic cytopathology},
volume = {48},
number = {11},
pages = {965-971},
doi = {10.1002/dc.24511},
pmid = {32511899},
issn = {1097-0339},
mesh = {Carcinoma/*genetics ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Gene Frequency/genetics ; Genome/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lymph Nodes/pathology ; Mutation/genetics ; Neoplasms/*genetics ; Sequence Analysis, DNA/methods ; Thyroid Gland/pathology ; },
abstract = {BACKGROUND: Cancer genome profiling of cytology specimens using next-generation sequencing (NGS) requires adequate and good-quality DNA. Genomic examination of cytology samples was conventionally performed on cell block (CB) or smear specimens than on residual liquid-based cytology (LBC) specimens, which are high-quality DNA sources even after long-term storage.<br><br>METHODS: We estimated tumor fractions of 37 residual LBC specimens, including 30 fine needle aspiration (FNA) samples from the thyroid (12 papillary thyroid carcinomas and two malignant lymphomas), lymph node (13 metastatic carcinomas and one malignant lymphoma), and breast cancer (one phyllodes tumor and one invasive ductal carcinoma), two pancreatic carcinoma samples, and five liquid (ascites, pleural effusion, and cerebrospinal fluid) samples. The DNA was extracted from all samples and subjected to NGS using a customized cancer gene panel comprising 28 cancer-related genes.<br><br>RESULTS: NGS analysis revealed somatic mutations corresponding to pathological diagnosis with adequate variant allele frequency (VAF) in 24 LBC specimens, which had significantly higher tumor fraction (72.5%&#x2009;&#xb1;&#x2009;4.9%). Ten cases, including the five fluid samples, had very small tumor fractions (7.5%&#x2009;&#xb1;&#x2009;2.3%) to obtain sufficient VAF. Other two samples had high tumor fractions but showed very low VAF, indicating the presence of fusion genes. The remaining one sample yielded no DNA recovery.<br><br>CONCLUSION: The residual LBC specimens collected by FNA from the thyroid gland and lymph node were verified to carry high tumor fraction and could serve as an alternate source for molecular testing to screen and diagnose cancers without the use of CB or smears.},
}
@article {pmid32509097,
year = {2020},
author = {Lv, X and Ye, J and Jiang, G and Wang, Y and Lv, J and Wang, Y},
title = {Simultaneous multiple primary cancers with concomitant inflammatory myofibroblastic tumor: a case report.},
journal = {International journal of clinical and experimental pathology},
volume = {13},
number = {5},
pages = {1212-1215},
pmid = {32509097},
issn = {1936-2625},
abstract = {Multiple primary cancers are of rare occurrence. Most multiple primary cancers are metachronous multiple primary cancers, while simultaneous multiple primary cancers are rare. Inflammatory myofibroblastic tumors are rare. Inflammatory myofibroblastic tumor occurs most frequently in children and young adults. Herein, we report a rare case of simultaneous multiple primary cancers and inflammatory myofibroblastic tumor. A 44-year-old woman was admitted for a breast mass evaluation. The patient was positive for antinuclear, anti-mitochondrial, and anti-RO52 antibodies. Breast magnetic resonance imaging revealed a right breast mass. After neoadjuvant chemotherapy, modified radical mastectomy was performed. Postoperative histopathology revealed an invasive ductal carcinoma. Two months later, computed tomography revealed a nodule in the right upper lobe and ground-glass opacity in the lower lobe of the lungs. Lobectomy and lobe biopsy were performed. Postoperative histopathology revealed that the mass in the right upper lobe was an inflammatory myofibroblastic tumor and the right lower lobe lesion was an invasive adenocarcinoma. Immunohistochemistry of the inflammatory myofibroblastic tumor revealed negativity for anaplastic lymphoma kinase. At the 4-month follow-up, the patient showed good recovery. The etiology of multiple primary cancers and inflammatory myofibroblastic tumors is still unknown; in this case, we believe that autoimmune factors are the main cause of multiple primary cancers with concomitant inflammatory myofibroblastic tumor. Tissue biopsy is needed to ensure correct diagnosis of multiple primary cancers and inflammatory myofibroblastic tumor. Surgery-based comprehensive therapy is recommended. The prognosis is favorable and regular follow-up is necessary.},
}
@article {pmid32488076,
year = {2020},
author = {Subudhi, AK and O'Donnell, AJ and Ramaprasad, A and Abkallo, HM and Kaushik, A and Ansari, HR and Abdel-Haleem, AM and Ben Rached, F and Kaneko, O and Culleton, R and Reece, SE and Pain, A},
title = {Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms.},
journal = {Nature communications},
volume = {11},
number = {1},
pages = {2763},
pmid = {32488076},
issn = {2041-1723},
support = {/WT_/Wellcome Trust/United Kingdom ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Animals ; Caenorhabditis elegans Proteins ; Circadian Rhythm/*physiology ; Disease Models, Animal ; Erythropoiesis/*physiology ; Female ; Gene Expression ; Host-Parasite Interactions/genetics/*physiology ; Humans ; Malaria/*metabolism/parasitology ; Mice ; Mice, Knockout ; Plasmodium chabaudi/genetics/growth &amp; development ; Plasmodium falciparum/genetics/growth &amp; development ; Protozoan Proteins/genetics/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Rodentia ; Secologanin Tryptamine Alkaloids/*metabolism ; Transcriptome ; },
abstract = {Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.},
}
@article {pmid32480118,
year = {2020},
author = {Chan, SJ and Ein-Dor, T and Mayopoulos, PA and Mesa, MM and Sunda, RM and McCarthy, BF and Kaimal, AJ and Dekel, S},
title = {Risk factors for developing posttraumatic stress disorder following childbirth.},
journal = {Psychiatry research},
volume = {290},
number = {},
pages = {113090},
doi = {10.1016/j.psychres.2020.113090},
pmid = {32480118},
issn = {1872-7123},
mesh = {Adult ; Delivery, Obstetric/*psychology/statistics &amp; numerical data ; Female ; Humans ; Labor, Obstetric/*psychology ; Mental Health ; Parturition/*psychology ; Postpartum Period/*psychology ; Pregnancy ; Pregnancy Complications/*epidemiology ; Pregnancy Outcome/epidemiology/psychology ; Prevalence ; Risk Factors ; Stress Disorders, Post-Traumatic/*epidemiology ; Surveys and Questionnaires ; },
abstract = {Women can develop childbirth-related posttraumatic stress disorder (CB-PTSD) in at-term delivery with healthy baby outcome as well as following pre-term delivery and neonatal complications, a potential added stressor. No study compares risk factors of CB-PTSD associated with different infant outcomes. We investigated CB-PTSD risk factors by comparing women with or without neonatal complications. Analysis reveals the importance of antepartum and birth-related risk factors in CB-PTSD above and beyond child outcomes, suggesting childbirth is an independent stressor capable of evoking CB-PTSD.},
}
@article {pmid32467291,
year = {2020},
author = {Shan, NL and Minden, A and Furmanski, P and Bak, MJ and Cai, L and Wernyj, R and Sargsyan, D and Cheng, D and Wu, R and Kuo, HD and Li, SN and Fang, M and Maehr, H and Kong, AN and Suh, N},
title = {Analysis of the Transcriptome: Regulation of Cancer Stemness in Breast Ductal Carcinoma In Situ by Vitamin D Compounds.},
journal = {Cancer prevention research (Philadelphia, Pa.)},
volume = {13},
number = {8},
pages = {673-686},
pmid = {32467291},
issn = {1940-6215},
support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 AT007036/AT/NCCIH NIH HHS/United States ; R01 AT009152/AT/NCCIH NIH HHS/United States ; R01 CA127645/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology/*prevention &amp; control ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; DNA Methylation/drug effects ; Datasets as Topic ; Disease Progression ; Down-Regulation/drug effects ; Epithelial-Mesenchymal Transition/drug effects/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Neoplasm Invasiveness/pathology/prevention &amp; control ; Neoplastic Stem Cells/*drug effects/pathology ; RNA-Seq ; Signal Transduction/drug effects/genetics ; Up-Regulation/drug effects ; Vitamin D/*administration &amp; dosage/analogs &amp; derivatives ; },
abstract = {Ductal carcinoma in situ (DCIS), which accounts for one out of every five new breast cancer diagnoses, will progress to potentially lethal invasive ductal carcinoma (IDC) in about 50% of cases. Vitamin D compounds have been shown to inhibit progression to IDC in the MCF10DCIS model. This inhibition appears to involve a reduction in the cancer stem cell-like population in MCF10DCIS tumors. To identify genes that are involved in the vitamin D effects, a global transcriptomic analysis was undertaken of MCF10DCIS cells grown in mammosphere cultures, in which cancer stem-like cells grow preferentially and produce colonies by self-renewal and maturation, in the presence and absence of 1α25(OH)2D3 and a vitamin D analog, BXL0124. Using next-generation RNA-sequencing, we found that vitamin D compounds downregulated genes involved in maintenance of breast cancer stem-like cells (e.g., GDF15), epithelial-mesenchymal transition, invasion, and metastasis (e.g., LCN2 and S100A4), and chemoresistance (e.g., NGFR, PPP1R1B, and AGR2), while upregulating genes associated with a basal-like phenotype (e.g., KRT6A and KRT5) and negative regulators of breast tumorigenesis (e.g., EMP1). Gene methylation status was analyzed to determine whether the changes in expression induced by vitamin D compounds occurred via this mechanism. Ingenuity pathway analysis was performed to identify upstream regulators and downstream signaling pathway genes differentially regulated by vitamin D, including TP63 and vitamin D receptor -mediated canonical pathways in particular. This study provides a global profiling of changes in the gene signature of DCIS regulated by vitamin D compounds and possible targets for chemoprevention of DCIS progression to IDC in patients.},
}
@article {pmid32457515,
year = {2020},
author = {Goodes, LM and King, GK and Goodwin, DM and Watts, A and Bardsley, J and Middleton, J and Bragge, P and Dunlop, SA},
title = {Barriers and facilitators to optimising inpatient bladder management after spinal cord injury.},
journal = {Spinal cord},
volume = {58},
number = {12},
pages = {1291-1300},
pmid = {32457515},
issn = {1476-5624},
mesh = {Humans ; Inpatients ; Longitudinal Studies ; *Spinal Cord Injuries/therapy ; *Urinary Bladder, Neurogenic/etiology/therapy ; },
abstract = {STUDY DESIGN: Qualitative survey.<br><br>OBJECTIVES: Examine clinicians' perspectives on adherence to published evidence-based guidelines and clinician-perceived barriers, and facilitators to optimising inpatient bladder management within one Spinal Cord Injury (SCI) service.<br><br>SETTING: Surgical Hospital (acute care) and SCI Unit (sub-acute, rehabilitation) in Western Australia (WA).<br><br>METHODS: Clinicians reviewed an 'Evidence Matrix' summarising published clinical practice guidelines and recommendations for SCI bladder management. Focus groups examined the extent to which current practice adhered to recommendations and identified perceived barriers and facilitators to optimal management. Data were analysed thematically using a deductive approach.<br><br>RESULTS: Current management closely mirrors published recommendations. Key facilitators included long-standing prioritisation of rapid progression from urethral indwelling (IDC) to a 6&#x2009;hourly intermittent catheterisation (IC) protocol; regular competency audits of catheterisation technique; and a Spinal Urology Clinical Nurse Consultant (CNC) position. Barriers included limited resources/staffing; restricted access to Neuro-urology consultation; inter-disciplinary communication gaps; and delays in determining and implementing long-term bladder management.<br><br>CONCLUSIONS: Inpatient SCI bladder care in WA closely emulates published evidence, although adherence at other sites may reveal different practices. Bladder management was found to have been facilitated by a strong culture of practice led by Neuro-urologists, informed by evidence and embraced by Senior Clinicians. Further reduction in duration of initial IDC, provision of early and ongoing Neuro-urology consultations as part of standard care, increased interdisciplinary communication and dedicated SCI Urology theatre lists would further optimise management.},
}
@article {pmid32439746,
year = {2020},
author = {Bacorn, C and Kim, E and Borowsky, AD and Lin, LK},
title = {Previously undiagnosed neuroendocrine tumour mimicking breast cancer metastasis to the orbit.},
journal = {BMJ case reports},
volume = {13},
number = {5},
pages = {},
pmid = {32439746},
issn = {1757-790X},
mesh = {Adenocarcinoma/*pathology/therapy ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/*secondary/therapy ; Diplopia ; Female ; Humans ; Intestinal Neoplasms/*pathology/therapy ; Neuroendocrine Tumors/*pathology/therapy ; Octreotide/therapeutic use ; Orbit ; Orbital Neoplasms/*secondary/therapy ; Pancreatic Neoplasms/*pathology/therapy ; Stomach Neoplasms/*pathology/therapy ; },
abstract = {Metastatic neuroendocrine neoplasms to the breast are rare and histopathologic overlap with mammary carcinomas has led to misdiagnosis. We present a case of a middle-aged woman with diplopia and a right medial rectus mass. Metastatic breast cancer was initially suspected based on a history of invasive ductal carcinoma. Detailed immunohistochemistry of the orbital biopsy, gallium-68 dotatate positron emission tomography-CT, and reevaluation of her prior breast specimen, demonstrated that her initial breast carcinoma diagnosis was in error and she was ultimately diagnosed with a previously unknown gastrointestinal neuroendocrine tumour metastatic to both the orbit and breast. This case highlights the challenges of differentiating between metastatic neuroendocrine tumours and invasive mammary carcinomas with neuroendocrine differentiation both in the breast and in the orbit. It is important to recognise the overlap so that a primary neuroendocrine neoplasm is not missed, or treatment significantly delayed.},
}
@article {pmid32438745,
year = {2020},
author = {Moran Lauter, AN and Rutter, L and Cook, D and O'Rourke, JA and Graham, MA},
title = {Examining Short-Term Responses to a Long-Term Problem: RNA-Seq Analyses of Iron Deficiency Chlorosis Tolerant Soybean.},
journal = {International journal of molecular sciences},
volume = {21},
number = {10},
pages = {},
pmid = {32438745},
issn = {1422-0067},
support = {Project 5030-21220-006-00D//Agricultural Research Service/ ; },
mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant ; Gene Ontology ; *Iron Deficiencies ; Plant Leaves/genetics ; Plant Necrosis and Chlorosis/*genetics ; Plant Roots/genetics ; *RNA-Seq ; Signal Transduction ; Glycine max/*genetics ; Stress, Physiological/genetics ; Transcription Factors/metabolism ; },
abstract = {Iron deficiency chlorosis (IDC) is a global crop production problem, significantly impacting yield. However, most IDC studies have focused on model species, not agronomically important crops. Soybean is the second largest crop grown in the United States, yet the calcareous soils across most of the upper U.S. Midwest limit soybean growth and profitability. To understand early soybean iron stress responses, we conducted whole genome expression analyses (RNA-sequencing) of leaf and root tissue from the iron efficient soybean (Glycine max) cultivar Clark, at 30, 60 and 120 min after transfer to iron stress conditions. We identified over 10,000 differentially expressed genes (DEGs), with the number of DEGs increasing over time in leaves, but decreasing over time in roots. To investigate these responses, we clustered our expression data across time to identify suites of genes, their biological functions, and the transcription factors (TFs) that regulate their expression. These analyses reveal the hallmarks of the soybean iron stress response (iron uptake and homeostasis, defense, and DNA replication and methylation) can be detected within 30 min. Furthermore, they suggest root to shoot signaling initiates early iron stress responses representing a novel paradigm for crop stress adaptations.},
}
@article {pmid32424149,
year = {2020},
author = {Cheung, SM and Husain, E and Masannat, Y and Miller, ID and Wahle, K and Heys, SD and He, J},
title = {Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy.},
journal = {British journal of cancer},
volume = {123},
number = {2},
pages = {261-267},
pmid = {32424149},
issn = {1532-1827},
support = {28312/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Female ; Glycolysis/genetics ; Humans ; Lactate Dehydrogenase 5/genetics/metabolism ; Lactic Acid/isolation &amp; purification/*metabolism ; Magnetic Resonance Spectroscopy ; Middle Aged ; *Prognosis ; Receptors, Estrogen/genetics/*metabolism ; },
abstract = {BACKGROUND: Precision medicine in breast cancer demands markers sensitive to early treatment response. Aerobic glycolysis (AG) upregulates lactate dehydrogenase A (LDH-A) with elevated lactate production; however, existing approaches for lactate quantification are either invasive or impractical clinically.<br><br>METHODS: Thirty female patients (age 39-78 years, 15 grade II and 15 grade III) with invasive ductal carcinoma were enrolled. Lactate concentration was quantified from freshly excised whole tumours with double quantum filtered (DQF) magnetic resonance spectroscopy (MRS), and Nottingham Prognostic Index (NPI), LDH-A and proliferative marker Ki-67 were assessed histologically.<br><br>RESULTS: There was a significantly higher lactate concentration (t&#x2009;=&#x2009;2.2224, p&#x2009;=&#x2009;0.0349) in grade III (7.7&#x2009;&#xb1;&#x2009;2.9&#x2009;mM) than in grade II (5.5&#x2009;&#xb1;&#x2009;2.4&#x2009;mM). Lactate concentration was correlated with NPI (&#x3c1;&#x2009;=&#x2009;0.3618, p&#x2009;=&#x2009;0.0495), but not with Ki-67 (&#x3c1;&#x2009;=&#x2009;0.3041, p&#x2009;=&#x2009;0.1023) or tumour size (r&#x2009;=&#x2009;0.1716, p&#x2009;=&#x2009;0.3645). Lactate concentration was negatively correlated with LDH-A (&#x3c1;&#x2009;=&#x2009;-0.3734, p&#x2009;=&#x2009;0.0421).<br><br>CONCLUSION: Our results showed that lactate concentration in whole breast tumour from DQF MRS is sensitive to tumour grades and patient prognosis.},
}
@article {pmid32423910,
year = {2020},
author = {O'Connor, P and Bhadbhade, P and Khan, Q and Williamson, S},
title = {Acral vascular syndrome during an immune checkpoint inhibitor.},
journal = {BMJ case reports},
volume = {13},
number = {5},
pages = {},
pmid = {32423910},
issn = {1757-790X},
mesh = {Black or African American ; Diagnosis, Differential ; Female ; Fingers/blood supply/pathology ; Gangrene/chemically induced/*diagnostic imaging/*pathology/surgery ; Humans ; Immune Checkpoint Inhibitors/*adverse effects ; Middle Aged ; Raynaud Disease/chemically induced/*diagnostic imaging/*pathology/surgery ; Thrombosis ; Vasculitis ; },
abstract = {Immune checkpoint inhibitors, including antiprogrammed death cell protein 1 (anti-PD-1) and anti cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), have been associated with a range of autoimmune-related side effects since their introduction in cancer treatment. Small vessel digital necrosis, referred to as the acral vascular syndrome, is a rare but serious complication that can result in loss of digits. Here we present a case report of acral vascular syndrome and review possible aetiologies. A 45- year-old woman with invasive ductal carcinoma of the left breast presented to the emergency department during neoadjuvant treatment with carboplatin, docetaxel and pembrolizumab with complaints of severe pain in her right third digit. She had physical findings consistent with ischaemic necrosis and gangrene of the distal phalanx. Angiography demonstrated Raynaud's phenomenon in the distal portion of the digits. Laboratory testing showed a weakly positive RNA polymerase III antibody level. Her case resulted in surgical amputation of her affected digit after partial resolution of symptoms with prednisone, vasodilators and antibiotics.},
}
@article {pmid32416533,
year = {2020},
author = {Syed, AP and Greulich, F and Ansari, SA and Uhlenhaut, NH},
title = {Anti-inflammatory glucocorticoid action: genomic insights and emerging concepts.},
journal = {Current opinion in pharmacology},
volume = {53},
number = {},
pages = {35-44},
doi = {10.1016/j.coph.2020.03.003},
pmid = {32416533},
issn = {1471-4973},
mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Genomics ; Glucocorticoids/*pharmacology ; Humans ; RNA, Untranslated ; Receptors, Glucocorticoid/genetics ; Transcription, Genetic ; },
abstract = {Glucocorticoids (GCs) are widely used immunomodulators. They regulate gene expression by binding and activating the Glucocorticoid Receptor (GR), but underlying transcriptional mechanisms remain enigmatic. This review summarizes recent findings identifyingspecific GR-bound DNA sequences whose configuration may affect transcriptional output. Additional factors affecting GR's anti-inflammatory actions, including different chromatin states such as DNAse hypersensitive regions and histone marks will be discussed, together with the relevant transcriptional co-regulators and promoter/enhancer features. Furthermore, the involvement of non-coding RNAs such as lncRNAs, miRNAs and eRNAs adds another level of regulation to the GR's transcriptional activity. Characterizing and understanding these multiple mechanisms will be crucial for developing more targeted immunomodulatory therapies with reduced adverse effects such as obesity, diabetes and osteoporosis.},
}
@article {pmid32408395,
year = {2020},
author = {Solagna, F and Nogara, L and Dyar, KA and Greulich, F and Mir, AA and Türk, C and Bock, T and Geremia, A and Baraldo, M and Sartori, R and Farup, J and Uhlenhaut, H and Vissing, K and Krüger, M and Blaauw, B},
title = {Exercise-dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF-SRF signalling.},
journal = {Acta physiologica (Oxford, England)},
volume = {230},
number = {1},
pages = {e13496},
pmid = {32408395},
issn = {1748-1716},
mesh = {Animals ; Chromatin/*chemistry ; Exercise ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*metabolism ; *Physical Conditioning, Animal ; Protein Biosynthesis ; *Serum Response Factor/genetics/metabolism ; *Signal Transduction ; Transcription Factors/*metabolism ; },
abstract = {AIM: Resistance exercise increases muscle mass over time. However, the early signalling events leading to muscle growth are not yet well-defined. Here, we aim to identify new signalling pathways important for muscle remodelling after exercise.<br><br>METHODS: We performed a phosphoproteomics screen after a single bout of exercise in mice. As an exercise model we used unilateral electrical stimulation in vivo and treadmill running. We analysed muscle biopsies from human subjects to verify if our findings in murine muscle also translate to exercise in humans.<br><br>RESULTS: We identified a new phosphorylation site on Myocardin-Related Transcription Factor B (MRTF-B), a co-activator of serum response factor (SRF). Phosphorylation of MRTF-B is required for its nuclear translocation after exercise and is accompanied by the transcription of the SRF target gene Fos. In addition, high-intensity exercise also remodels chromatin at specific SRF target gene loci through the phosphorylation of histone 3 on serine 10 in myonuclei of both mice and humans. Ablation of the MAP kinase member MSK1/2 is sufficient to prevent this histone phosphorylation, reduce induction of SRF-target genes, and prevent increases in protein synthesis after exercise.<br><br>CONCLUSION: Our results identify a new exercise signalling fingerprint in vivo, instrumental for exercise-induced protein synthesis and potentially muscle growth.},
}
@article {pmid32408270,
year = {2020},
author = {Pedro, J and Cunha, FM and Neto, V and Hespanhol, V and Martins, DF and Guimarães, S and Varela, A and Carvalho, D},
title = {Coexistence of DIPNECH and carotid body paraganglioma: is it just a coincidence?.},
journal = {Endocrinology, diabetes &amp; metabolism case reports},
volume = {2020},
number = {},
pages = {},
pmid = {32408270},
issn = {2052-0573},
abstract = {SUMMARY: We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up.<br><br>LEARNING POINTS: The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology. To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma. The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.},
}
@article {pmid32404955,
year = {2020},
author = {Tille, JC and Vieira, AF and Saint-Martin, C and Djerroudi, L and Furhmann, L and Bidard, FC and Kirova, Y and Tardivon, A and Reyal, F and Carton, M and Vincent-Salomon, A},
title = {Tumor-infiltrating lymphocytes are associated with poor prognosis in invasive lobular breast carcinoma.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {33},
number = {11},
pages = {2198-2207},
pmid = {32404955},
issn = {1530-0285},
mesh = {Age Factors ; Breast Neoplasms/immunology/metabolism/mortality/*pathology ; Carcinoma, Lobular/immunology/metabolism/mortality/*pathology ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology/*pathology ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; },
abstract = {The prognostic impact of tumor-infiltrating lymphocytes (TILs) within invasive lobular carcinoma (ILC) remains to be better characterized. In estrogen receptor (ER)-negative invasive ductal carcinomas of no special type (IDC-NST), TILs are associated with good prognosis. The aim of this study was to examine TILs in ILC, with particular focus on prognostic and clinicopathologic features. A cohort comprising 459 consecutive ILCs diagnosed in a single institution from 2005 to 2008 met the eligibility criteria for this study. The percentage of tumor area occupied by TILs was quantified by two breast pathologists and categorized into three groups: no TILs, ≤5%, >5%. Clinicopathologic features were tested by Fisher's exact tests or Chi[2] tests. Overall survival (OS) and invasive disease-free survival (iDFS) were estimated by Kaplan-Meier and Cox proportional hazard statistics. There were 239 TIL-negative cases, 185 cases with ≤5% TILs, and 35 cases with >5% TILs. TILs were associated with younger age, larger tumors, lymph node involvement, poor Nottingham prognostic index, HER2 amplification, multinucleation, and prominent nucleoli (p < 0.05). Poor OS was significantly associated with increasing TILs in the univariate Cox proportional hazards model (p < 0.001) and Kaplan-Meier estimator (p < 0.05, log-rank test). Similar results were observed for iDFS (p = 0.004 for Cox univariate and p = 0.005 for log-rank test). Notably, TILs can identify a subset of ILC patients with poor OS independently of molecular subtype and lymph node metastases (multivariate Cox, p < 0.001, OS hazard ratio (HR) = 4.38 and HR = 6.15, for ≤5% and >5% TILs, respectively, vs. absence of TILs). Prominent nucleoli was the only nuclear feature associated with poor OS (p = 0.05) and iDFS (p = 0.05) in univariate Cox survival analysis. TILs represent a promising new morphologic biomarker associated with poor outcome of ILC, in contrast with that observed in ER-negative IDC-NST.},
}
@article {pmid32381867,
year = {2020},
author = {Tamaoki, M and Nio, Y and Tamaoki, M and Sakamoto, M and Uesugi, K and Sakamoto, T and Imai, S and Maruyama, R},
title = {[Radiation-Associated Angiosarcoma That Developed in the Irradiated Residual Breast after Breast-Conserving Surgery for Breast Cancer-A Case Report and Review of the Literature].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {47},
number = {1},
pages = {77-81},
pmid = {32381867},
issn = {0385-0684},
mesh = {Aged ; *Breast Neoplasms/radiotherapy ; Female ; *Hemangiosarcoma/etiology ; Humans ; Japan ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Recurrence, Local ; *Neoplasms, Radiation-Induced ; *Skin Neoplasms ; },
abstract = {We report a radiation-associated angiosarcoma(RAAS)of the breast, which is a rare but important complication after breast-conserving surgery(BCS)and radiotherapy(RT)for breast cancer. A7 2-year-old woman had undergone BCS for invasive ductal carcinoma of the right breast(pT2pN1M0, StageⅡB), followed by RT of 50 Gy; she was treated with doxifluridine and anastrozole for 5 year. She noticed a bloody cutaneous bulla in the right breast 64 months later, and the skin lesions gradually expanded. She was brought to our clinic for the treatment of massive bleeding from the skin lesions. Ulcer biopsy revealed cutaneous AS(cells were CD31[+], CD34[+], VEGF[-], and VEGF-R[+]). She underwent mastectomy and latissimus dorsal flap surgery. She died of local recurrence and liver metastasis 13 months later. RAAS is rare, but it should be considered in patients with skin lesions, such as erosion and bloody bulla, after BCS and RT for breast cancer. To our knowledge, only 12 cases of RAAS, including the present case, have been reported in Japan, and we reviewed the Japanese RAAS cases in comparison with those reported in the Western literature.},
}
@article {pmid36133137,
year = {2019},
author = {Amiri, A and Hastert, F and Stühn, L and Dietz, C},
title = {Structural analysis of healthy and cancerous epithelial-type breast cells by nanomechanical spectroscopy allows us to obtain peculiarities of the skeleton and junctions.},
journal = {Nanoscale advances},
volume = {1},
number = {12},
pages = {4853-4862},
pmid = {36133137},
issn = {2516-0230},
abstract = {The transition of healthy epithelial cells to carcinoma is associated with an alteration in the structure and organization of the cytoskeleton of the cells. A comparison of the mechanical properties of cancerous and healthy cells indicated a higher deformability of the cancer cells based on averaging the mechanical properties of single cells. However, the exact reason for softening of the cancerous cells compared to their counterparts remains unclear. Here, we focused on nanomechanical spectroscopy of healthy and cancerous ductal epithelial-type breast cells by means of atomic force microscopy with high lateral and depth precision. As a result, based on atomic force microscopy measurements formation of significantly fewer microtubules in cancerous cells which was observed in our study is most likely one of the main causes for the overall change in mechanical properties without any phenotypic shift. Strikingly, in a confluent layer of invasive ductal carcinoma cells, we observed the formation of cell-cell junctions that have the potential for signal transduction among neighboring cells such as desmosomes and adherens junctions. This increases the possibility of cancerous cell collaboration in malignancy, infiltration or metastasis phenomena.},
}
@article {pmid34191158,
year = {2019},
author = {Aarstad, EM and Nordhaug, P and Naghavi-Behzad, M and Larsen, LB and Gerke, O and Hildebrandt, MG},
title = {Prevalence of focal incidental breast uptake on FDG-PET/CT and risk of malignancy: a systematic review and meta-analysis.},
journal = {European journal of hybrid imaging},
volume = {3},
number = {1},
pages = {16},
pmid = {34191158},
issn = {2510-3636},
support = {//Danmarks Frie Forskningsfond/ ; //Syddansk Universitet/ ; },
abstract = {BACKGROUND: FDG-PET/CT is increasingly used for oncologic and inflammatory diseases. Focal incidental FDG uptake occurs rarely in breast tissue but has often significant consequences. This study aimed to systematically review literature regarding focal incidental breast uptake (FIBU) on FDG-PET/CT in order to yield an update on the prevalence and risk of malignancy for FIBU.<br><br>METHODS: A systematic search for relevant articles published between 2012 and 2018 was performed through MEDLINE, Embase, and Cochrane databases. Studies addressing the detection of FIBU in patients without a previous history of breast malignancy were included. The QUADAS-2 was used for quality assessment, and eligible data were pooled using a fixed-effects model. I[2] was calculated for the heterogeneity between studies.<br><br>RESULTS: Eight studies containing 180,002 scans were included in the systematic review. The median prevalence of FIBU for both genders was 0.52% (range 0.18-22.5%). Prevalence for women was mentioned separately in five studies and varied from 0.51 to 23.5%. One study reporting a high prevalence was based on patients being staged for known malignancy, and the word "breast" was used in the search, which may have caused selection bias. Data from four studies were eligible for meta-analysis. A high degree of heterogeneity was observed for prevalence data (I[2] of 97.5%), while moderate heterogeneity was observed for data on malignancy risk assessment (I[2] of 62.8%). The pooled prevalence of FIBU in women was 0.61% (range 0.56-0.66%), and the pooled prevalence of malignancy of FIBUs was 38.7% (range 34.4-43.0%). The most commonly detected malignancy was invasive ductal carcinoma.<br><br>CONCLUSION: FIBU occurs rarely on FDG-PET/CT for female patients but yields a high risk of malignancy according to the results of published papers. Therefore, it should be considered relevant to further elucidate patients with incidentally detected FDG uptake in breast in clinical practice.},
}
@article {pmid36338780,
year = {2019},
author = {Lam, JC and Gregson, DB and Robinson, S and Somayaji, R and Welikovitch, L and Conly, JM and Parkins, MD},
title = {Infectious diseases consultation improves key performance metrics in the management of Staphylococcus aureus bacteremia: A multicentre cohort study.},
journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada},
volume = {4},
number = {1},
pages = {24-32},
pmid = {36338780},
issn = {2371-0888},
abstract = {BACKGROUND: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. We sought to identify factors associated with infectious diseases consultation (IDC) and understand how IDC associates with SAB patient management and outcomes.<br><br>METHODS: A multicentre retrospective study was performed between 2012 and 2014 in a large Canadian Health Zone in order to determine factors associated with IDC and performance of key quality of care determinants in SAB management and clinical outcomes. Factors subject to quality of care determinants were established a priori and studied for associations with IDC and 30-day all-cause mortality using multivariable analysis.<br><br>RESULTS: Of 961 SAB episodes experienced by 892 adult patients, 605 episodes received an IDC. Patients receiving IDC were more likely to have prosthetic valves and joints and to have community-acquired and known sources of SAB, but increasing age decreased IDC occurrence. IDC was the strongest independent predictor for quality of care performance metrics, including repeat blood cultures and echocardiography. Mortality at 30 days was 20% in the cohort, and protective factors included IDC, achievement of source control, targeted therapy within 48 hours, and follow-up blood cultures but not the performance of echocardiography.<br><br>CONCLUSIONS: There were significant gaps between the treatments and investigations that patients actually received for SAB and what is considered the optimal management of their condition. IDC is associated with improved attainment of targeted SAB quality of care determinants and reduced mortality rates. Based on our findings, we propose a policy of mandatory IDC for all cases of SAB to improve patient management and outcomes.},
}
@article {pmid32380439,
year = {2020},
author = {Rodriguez-Ibarria, NG and Pinar, MB and García, L and Cabezón, MA and Lloret, M and Rey-Baltar, MD and Rdguez-Melcón, JI and Lara, PC},
title = {Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer.},
journal = {Breast (Edinburgh, Scotland)},
volume = {52},
number = {},
pages = {45-49},
pmid = {32380439},
issn = {1532-3080},
mesh = {Aged ; Brachytherapy/*methods ; Breast Neoplasms/*radiotherapy ; Carcinoma, Ductal, Breast/*radiotherapy ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*radiotherapy ; Radiotherapy Dosage ; },
abstract = {Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008-December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3-1.9) and 98.3% (95% CI 97.3-99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.},
}
@article {pmid32371885,
year = {2020},
author = {Schwarz, D and Hidmark, AS and Sturm, V and Fischer, M and Milford, D and Hausser, I and Sahm, F and Breckwoldt, MO and Agarwal, N and Kuner, R and Bendszus, M and Nawroth, PP and Heiland, S and Fleming, T},
title = {Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {7593},
pmid = {32371885},
issn = {2045-2322},
mesh = {Animals ; Biopsy ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 1/complications ; Diabetic Neuropathies/*diagnostic imaging/etiology/*pathology ; Disease Models, Animal ; Humans ; Image Processing, Computer-Assisted ; *Magnetic Resonance Imaging/methods/standards ; Mice ; Microscopy ; Microscopy, Electron ; },
abstract = {In light of the limited treatment options of diabetic polyneuropathy (DPN) available, suitable animal models are essential to investigate pathophysiological mechanisms and to identify potential therapeutic targets. In vivo evaluation with current techniques, however, often provides only restricted information about disease evolution. In the study of patients with DPN, magnetic resonance neurography (MRN) has been introduced as an innovative diagnostic tool detecting characteristic lesions within peripheral nerves. We developed a novel multicontrast ultra high field MRN strategy to examine major peripheral nerve segments in diabetic mice non-invasively. It was first validated in a cross-platform approach on human nerve tissue and then applied to the popular streptozotocin(STZ)-induced mouse model of DPN. In the absence of gross morphologic alterations, a distinct MR-signature within the sciatic nerve was observed mirroring subtle changes of the nerves' fibre composition and ultrastructure, potentially indicating early re-arrangements of DPN. Interestingly, these signal alterations differed from previously reported typical nerve lesions of patients with DPN. The capacity of our approach to non-invasively assess sciatic nerve tissue structure and function within a given mouse model provides a powerful tool for direct translational comparison to human disease hallmarks not only in diabetes but also in other peripheral neuropathic conditions.},
}
@article {pmid32365829,
year = {2020},
author = {Cortes-Urrea, C and Bueno-Gutiérrez, F and Solarte, M and Guevara-Burbano, M and Tobar-Tosse, F and Vélez-Varela, PE and Bonilla, JC and Barreto, G and Velasco-Medina, J and Moreno, PA and Rivas, JL},
title = {Exomes of Ductal Luminal Breast Cancer Patients from Southwest Colombia: Gene Mutational Profile and Related Expression Alterations.},
journal = {Biomolecules},
volume = {10},
number = {5},
pages = {},
pmid = {32365829},
issn = {2218-273X},
support = {PI18/00591//Instituto de Salud Carlos III/International ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; *Exome ; Female ; Humans ; Middle Aged ; *Mutation ; Oncogenes ; },
abstract = {Cancer is one of the leading causes of mortality worldwide. Breast cancer is the most frequent cancer in women, and in recent years it has become a serious public health problem in Colombia. The development of large-scale omic techniques allows simultaneous analysis of all active genes in tumor cells versus normal cells, providing new ways to discover the drivers of malignant transformations. Whole exome sequencing (WES) was obtained to provide a deep view of the mutational genomic profile in a set of cancer samples from Southwest Colombian women. WES was performed on 52 tumor samples from patients diagnosed with invasive breast cancer, which in most cases (33/52) were ductal luminal breast carcinomas (IDC-LM-BRCA). Global variant call was calculated, and six different algorithms were applied to filter out false positives and identify pathogenic variants. To compare and expand the somatic tumor variants found in the Colombian cohort, exome mutations and genome-wide expression alterations were detected in a larger set of tumor samples of the same breast cancer subtype from TCGA (that included DNA-seq and RNA-seq data). Genes with significant changes in both the mutational and expression profiles were identified, providing a set of genes and mutations associated with the etiology of ductal luminal breast cancer. This set included 19 single mutations identified as tumor driver mutations in 17 genes. Some of the genes (ATM, ERBB3, ESR1, TP53) are well-known cancer genes, while others (CBLB, PRPF8) presented driver mutations that had not been reported before. In the case of the CBLB gene, several mutations were identified in TCGA IDC-LM-BRCA samples associated with overexpression of this gene and repression of tumor suppressive activity of TGF-β pathway.},
}
@article {pmid32362500,
year = {2020},
author = {Dianatinasab, M and Rezaian, M and HaghighatNezad, E and Bagheri-Hosseinabadi, Z and Amanat, S and Rezaeian, S and Masoudi, A and Ghiasvand, R},
title = {Dietary Patterns and Risk of Invasive Ductal and Lobular Breast Carcinomas: A Systematic Review and Meta-analysis.},
journal = {Clinical breast cancer},
volume = {20},
number = {4},
pages = {e516-e528},
doi = {10.1016/j.clbc.2020.03.007},
pmid = {32362500},
issn = {1938-0666},
mesh = {Breast Neoplasms/*epidemiology/etiology ; Carcinoma, Ductal, Breast/*epidemiology/etiology ; Carcinoma, Lobular/*epidemiology/etiology ; Case-Control Studies ; Diet Surveys/*statistics &amp; numerical data ; *Feeding Behavior ; Female ; Humans ; Risk Assessment/statistics &amp; numerical data ; Risk Factors ; },
abstract = {The histopathologic subtypes of breast cancer, including invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in terms of risk factors, progression, and response to treatment. The PubMed/Medline, Web of Science, and Scopus databases were searched up to February 2020 for published studies on the association between dietary patterns (Western diet [WD] or Mediterranean diet [WD]) and the risk of IDC/ILC of breast. Multivariable adjusted relative risk (RR) and 95% confidence intervals (CIs) comparing the highest and lowest categories of WD and MD patterns were combined by using the random-effects meta-analyses. After searching the databases, 10 eligible studies on the association of diet and IDC (7 articles) and ILC (3 articles) were included in the analysis. A statistically significant adverse association was observed between MD and IDC in case-control studies (RR = 0.47; 95% CI, 0.39-0.55; I[2] = 85.1%; P < .001). However, the association was nonsignificant in cohort studies (RR = 0.98; 95% CI, 0.92-1.05; I[2] = 88.8%; P = .003). The pooled analysis also suggested a significant and direct association between the WD and the risk of IDC (RR = 1.36; 95% CI, 1.18-1.53; I[2] = 63.7%; P = .017). The risk of ILC for the highest compared to the lowest category of MD was highly protective (RR = 0.76; 95% CI, 0.64-0.87; I[2] = 89.2%; P < .001), and a marginally significant association was found between the WD and risk of ILC (RR = 1.45; 95% CI, 1.04-1.86), with no heterogeneity (I[2] = 0; P = .52). This meta-analysis provides supporting evidence for the association between MD decreased risk of IDC and ILC of the breast and the association between WD and increased risk of IDC and ILC. Further investigations are needed to better understand the reasons behind the etiologic mechanisms of how dietary patterns affect patients differently by common breast cancer subtypes, including IDC and ILC.},
}
@article {pmid32354932,
year = {2020},
author = {Fujii, T and Tokuda, S and Nakazawa, Y and Kurozumi, S and Obayashi, S and Yajima, R and Shirabe, K},
title = {Relationship Between FDG Uptake and the Platelet/lymphocyte Ratio in Patients With Breast Invasive Ductal Cancer.},
journal = {In vivo (Athens, Greece)},
volume = {34},
number = {3},
pages = {1365-1369},
pmid = {32354932},
issn = {1791-7549},
mesh = {Aged ; Biomarkers, Tumor ; Breast Neoplasms/*diagnostic imaging/etiology/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Leukocyte Count ; *Lymphocyte Count ; Middle Aged ; Neutrophils ; *Platelet Count ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Tumor Microenvironment ; },
abstract = {BACKGROUND/AIM: We investigated the relationship between F18-fluorodeoxyglucose (FDG) uptake and the platelet/lymphocyte ratio (PLR), as both represent inflammation.<br><br>PATIENTS AND METHODS: We retrospectively analyzed the cases of 143 consecutive invasive ductal carcinoma patients who had undergone preoperative FDG-PET and surgery. We divided the patients into groups based on their maximum standardized uptake value (SUVmax) values: low (<2.5) and high (&#x2265;2.5) and based on their PLRs: low (<130) and high (&#x2265;130). We determined the relationships between the SUVmax or PLR and clinicopathological features.<br><br>RESULTS: Seventy-three patients (51.0%) had a high SUVmax in their primary tumor. There were significant associations between SUVmax and the PLR. A multivariate analysis revealed that high PLR, but not NLR, was independent factor associated with a high SUVmax. Seventy-four patients (51.7%) had a high PLR; The factors significantly associated with high PLR were large tumor size, presence of node metastasis, presence of vascular invasion, high NLR, and high SUVmax.<br><br>CONCLUSION: In breast cancer patients, the PLR is independently associated with the SUVmax, but not with recurrent disease. In breast cancer patients with a high SUVmax and/or PLR, these values may reflect the tumor microenvironment.},
}
@article {pmid32343605,
year = {2021},
author = {Liu, CR and Meng, FH},
title = {DNASE1L2, as a Carcinogenic Marker, Affects the Phenotype of Breast Cancer Cells Via Regulating Epithelial-Mesenchymal Transition Process.},
journal = {Cancer biotherapy &amp; radiopharmaceuticals},
volume = {36},
number = {2},
pages = {180-188},
doi = {10.1089/cbr.2019.3504},
pmid = {32343605},
issn = {1557-8852},
mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Proliferation/physiology ; Deoxyribonuclease I/*metabolism ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Middle Aged ; Phenotype ; Prognosis ; Transfection ; },
abstract = {Purpose: The authors explore the role of DNASE1L2 in breast cancer (BC) and its affect on the cell phenotype. Methods: Breast invasive ductal carcinoma RNA-Seq data set was downloaded from The Cancer Genome Atlas database for analyzing DNASE1L2 levels. Overall survival curve was plotted by Kaplan-Meier methods. The correlations between DNASE1L2 expression and clinical characteristics were analyzed by chi-square tests. Cox regression models were implemented for analyzing the potential prognosticators of BC. Small interference RNA-DNASE1L2 and pcDNA3.1-DNASE1L2 were transfected into BC cells to silence and overexpress DNASE1L2, respectively. Relative mRNA and protein levels were determined by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. Cell counting Kit-8, clone formation, and Transwell assays were employed to measure the proliferative, invasive, and migratory abilities. Results: Bioinformatics analysis showed that the levels of DNASE1L2 were found to be elevated in BC tissues, which was further proved by qRT-PCR tests. Besides, high expression of DNASE1L2 was dramatically led to a poor overall survival. Furthermore, DNASE1L2 expression was remarkably associated with age and pathologic-stage. Silencing DNASE1L2 showed an inhibitory effect on the proliferation, invasion, and migration of MCF7 cells, whereas overexpression of DNASE1L2 in BT549 cells presented the opposite results. Mechanistically, downregulation of DNASE1L2 could significantly enhance the levels of E-cadherin, as well as suppress the levels of Vimentin, N-cadherin and Snail, whereas upregulation of DNASE1L2 showed the reverse outcomes. Conclusion: This study for the first time demonstrated that DNASE1L2 was upregulated in BC cells, and acted as an oncogene to affect the phenotype of BC cells by modulating the epithelial-mesenchymal transition process, which suggested that DNASE1L2 might be considered as a useful biomarker for BC therapeutics.},
}
@article {pmid32338774,
year = {2020},
author = {Kumar, V and Agrawal, R and Pandey, A and Kopf, S and Hoeffgen, M and Kaymak, S and Bandapalli, OR and Gorbunova, V and Seluanov, A and Mall, MA and Herzig, S and Nawroth, PP},
title = {Compromised DNA repair is responsible for diabetes-associated fibrosis.},
journal = {The EMBO journal},
volume = {39},
number = {11},
pages = {e103477},
pmid = {32338774},
issn = {1460-2075},
support = {R37 AG046320/AG/NIA NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; //Helmholtz Cross Program Topic Metabolic Dysfunction/ ; //Foundation for Diabetes Research/ ; GRK 1874-DIAMICOM//Deutsche Forschungsgemeinschaft (DFG)/ ; R01 AG027237/AG/NIA NIH HHS/United States ; P01 AG051449/AG/NIA NIH HHS/United States ; SFB1118//Deutsche Forschungsgemeinschaft (DFG)/ ; },
mesh = {A549 Cells ; *DNA End-Joining Repair ; Diabetes Mellitus, Type 1/genetics/*metabolism/pathology ; Diabetes Mellitus, Type 2/genetics/*metabolism/pathology ; Fibrosis ; HEK293 Cells ; Humans ; },
abstract = {Diabetes-associated organ fibrosis, marked by elevated cellular senescence, is a growing health concern. Intriguingly, the mechanism underlying this association remained unknown. Moreover, insulin alone can neither reverse organ fibrosis nor the associated secretory phenotype, favoring the exciting notion that thus far unknown mechanisms must be operative. Here, we show that experimental type 1 and type 2 diabetes impairs DNA repair, leading to senescence, inflammatory phenotypes, and ultimately fibrosis. Carbohydrates were found to trigger this cascade by decreasing the NAD[+] /NADH ratio and NHEJ-repair in vitro and in diabetes mouse models. Restoring DNA repair by nuclear over-expression of phosphomimetic RAGE reduces DNA damage, inflammation, and fibrosis, thereby restoring organ function. Our study provides a novel conceptual framework for understanding diabetic fibrosis on the basis of persistent DNA damage signaling and points to unprecedented approaches to restore DNA repair capacity for resolution of fibrosis in patients with diabetes.},
}
@article {pmid32317515,
year = {2020},
author = {Pyla, RD and Potekar, RM and Patil, VS and Reddy, AK and Sathyashree, KV},
title = {Quantitative mast cell analysis and hormone receptor study (ER, PR and HER2/neu) in invasive carcinoma of breast.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {63},
number = {2},
pages = {200-204},
doi = {10.4103/IJPM.IJPM_155_19},
pmid = {32317515},
issn = {0974-5130},
mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/*pathology ; Female ; Humans ; Immunohistochemistry ; Mast Cells/immunology/*pathology ; Middle Aged ; Prospective Studies ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tumor Microenvironment/*immunology ; },
abstract = {CONTEXT: Breast cancer constitutes nearly one third of cancers among women. Immune responses caused by neoplastic cells lead to the accumulation of inflammatory cells like mast cells (MCs), macrophages, lymphocytes, and plasma cells around the tumor tissue forming the tumor microenvironment.<br><br>AIM: The study aims at quantifying the role of MCs in different grades of invasive carcinoma of breast with respect to estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2/neu).<br><br>MATERIALS AND METHODS: This study included 60 cases of invasive carcinoma of breast. Toluidine blue staining was used for quantitative MC analysis and correlated with immunohistochemistry analysis for hormonal markers' positivity-ER, PR and HER2/neu.<br><br>RESULTS: The mean age was 52 years (range: 25-75 years). The average number of MCs in Grade I, II, and III were 24.05, 18.4, and 7.9, respectively, with a significant P value. ER, PR, and HER2/neu positivity was found in 60%, 55%, and 32% of the cases, respectively. ER positivity with mean MC count of 23.55 was found in 36 cases, and 33 cases were positive for PR with a mean MC count of 24.18 and a significant P value. HER2 positive cases were 28 with a mean MC count of 20.82.<br><br>CONCLUSION: The presence of MCs in breast cancer is inversely proportional to the grade of tumor, i.e., a maximum number of MCs were seen in low grade tumors. In addition, there is a positive correlation between ER and PR receptor positivity with the presence of MCs in the stroma of breast cancer.},
}
@article {pmid32310154,
year = {2020},
author = {Suhani, S and Kazi, M and Parshad, R and Seenu, V and Verma, E and Mathur, S and Gupta, SD and Haresh, KP},
title = {An audit of over 1000 breast cancer patients from a tertiary care center of Northern India.},
journal = {Breast disease},
volume = {39},
number = {2},
pages = {91-99},
doi = {10.3233/BD-190435},
pmid = {32310154},
issn = {1558-1551},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/physiopathology ; Breast Neoplasms, Male/*epidemiology/physiopathology ; Female ; Humans ; India/epidemiology ; Male ; *Medical Audit ; Middle Aged ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers/*statistics &amp; numerical data ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer is the commonest cancer among women. India along with United States and China collectively account for one third of the global burden. The present study reports the clinico-epidemiological data of our patient population. This may help in better understanding of the disease in our population and also form ground for conducting further breast cancer research in India.<br><br>METHODS: The study was conducted at an apex teaching and medical research institution in India from September 2013 to April 2015 as a retrospective review of prospectively collected data of breast cancer patients. The socio-demographic characteristics, reproductive risk factors, clinical presentation, TNM staging and histopathological characteristics for breast cancer in these patients were recorded. The data was recorded on an Xcel spreadsheet and analyzed using IBM SPSS 21.<br><br>RESULTS: The study comprised of 1310 breast cancer patients with males comprising 1.1%. The median age of presentation was 47 years, and menarche 14 years. Most of women were married and multiparous. More than half of the women were postmenopausal at presentation. All patients were symptomatic at presentation with median duration of symptom of 5 months and median lump size of 5&#xa0;cm. Most common stage at presentation was Stage II and most common histopathology was Invasive ductal carcinoma. 61.9% tumors were hormone receptor positive. Triple negative cancers formed one third of all tumors.<br><br>CONCLUSION: Breast cancer in the Indian scenario is a disease of younger woman who lack the characteristic reproductive and demographic risk factors. This calls for a need to study the clinico-demographic risk factors and characteristics of our own population.},
}
@article {pmid32299754,
year = {2020},
author = {El Abbass, KA and Abdellateif, MS and Gawish, AM and Zekri, AN and Malash, I and Bahnassy, AA},
title = {The Role of Breast Cancer Stem Cells and Some Related Molecular Biomarkers in Metastatic and Nonmetastatic Breast Cancer.},
journal = {Clinical breast cancer},
volume = {20},
number = {4},
pages = {e373-e384},
doi = {10.1016/j.clbc.2019.11.008},
pmid = {32299754},
issn = {1938-0666},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast/*pathology/surgery ; Breast Neoplasms/diagnosis/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*genetics/secondary/therapy ; Case-Control Studies ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Healthy Volunteers ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplastic Stem Cells/*pathology ; Primary Cell Culture ; Retrospective Studies ; Signal Transduction/genetics ; Tumor Cells, Cultured ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer stem cells (BCSCs) play important role(s) in the development and progression of invasive duct carcinoma (IDC). We assessed the role of BCSC marker expression and the number of mammospheres in cultures of breast cancer (BC) tissues and correlated these data to relevant clinicopathologic features of the patients and overall survival (OS).<br><br>METHODS: Fresh tumor tissue samples were collected from 44 Egyptian female patients with IDC of the breast and 25 healthy women undergoing reduction mammoplasty as a control. The mammosphere number and the RNA expression levels of some cancer stem cell-related genes (PTEN, PI3K, AKT, Wnt, and &#x3b2;-catenin) were assessed by reverse-transcriptase polymerase chain reaction at different stages of BCSC differentiation compared with control samples.<br><br>RESULTS: The number of CD44[+]CD24[-/low] cells associated significantly at the end of culture with the expression level of Wnt, &#x3b2;-catenin, and distant metastasis (P&#xa0;< .001, P&#xa0;= .015 and P&#xa0;= .003, respectively). There was significant association between the mammosphere number and CD44[+]CD24[-/low] cells as well as AKT expression (P&#xa0;= .040 and .021, respectively). PTEN messenger RNA expressed significantly in BC (P&#xa0;< .05). Wnt-RNA expression associated significantly with high tumor stage, positive lymph node status, Her2-neu overexpression, and metastasis (P&#xa0;= .009, .012, .026, and .001, respectively), whereas OS associated significantly with distant metastasis, Wnt, and PTEN expressions (P&#xa0;< .001, P&#xa0;= .001, P&#xa0;= .014, respectively).<br><br>CONCLUSION: BCSCs and their related genes (PTEN, PI3K, AKT, Wnt, and &#x3b2;-catenin) play important roles in the development and progression of BC and they can be used as potential prognostic and predictive biomarkers for patients with BC or as target therapy.},
}
@article {pmid32279596,
year = {2020},
author = {Duman, B and Kuşman, A and Çolak, B and Şenler, F&#xc7; and Kumbasar, H},
title = {Tamoxifen-induced acute mania: A case report.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {26},
number = {8},
pages = {2025-2027},
doi = {10.1177/1078155220915959},
pmid = {32279596},
issn = {1477-092X},
mesh = {Acute Disease ; Antineoplastic Agents, Hormonal/*adverse effects ; Breast Neoplasms/*drug therapy ; Female ; Humans ; Mania/*chemically induced ; Middle Aged ; Tamoxifen/*adverse effects ; },
abstract = {INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer, osteoporosis, and post-menopausal symptoms. Also, tamoxifen is currently under investigation for its anti-manic properties. In this article, we report a case who developed manic episode following the initiation of tamoxifen and remitted with discontinuation of the medication.<br><br>CASE REPORT: A 58-year-old woman was diagnosed with breast cancer. Pathologic diagnosis was invasive ductal carcinoma. Following bilateral total mastectomy operation, trastuzumab was initiated with intervals of 21&#x2009;days. Five days before the fourth application of trastuzumab, tamoxifen was added. On the sixth day following the initiation of tamoxifen, manic symptoms were developed and she was diagnosed as acute mania.<br><br>MANAGEMENT AND OUTCOME: The oncology department suggested withdrawing tamoxifen due to a possible association between tamoxifen initiation and behavioral symptoms. Manic symptoms were rapidly (approximately 24&#x2009;h) improved following cessation of tamoxifen. Psychiatric evaluation on the fifth day following cessation of tamoxifen revealed no manic symptoms. An aromatase inhibitor-exemestane was initiated and she showed no side effects with this medication since then.<br><br>DISCUSSION: To our knowledge, this is the first case report of probable tamoxifen-induced mania. Our case report at least indicates that there were possibly some patients who were sensitive to the tamoxifen's nervous system effects, mainly to manic effects. In conclusion, clinicians should be aware of these rare behavioral adverse effects of tamoxifen.},
}
@article {pmid32272928,
year = {2020},
author = {Sutham, K and Khuwuthyakorn, P and Thinnukool, O},
title = {Thailand medical mobile application for patients triage base on criteria based dispatch protocol.},
journal = {BMC medical informatics and decision making},
volume = {20},
number = {1},
pages = {66},
pmid = {32272928},
issn = {1472-6947},
mesh = {*Emergency Medical Services ; Humans ; *Mobile Applications ; Patients ; Reproducibility of Results ; Retrospective Studies ; Thailand ; Triage ; },
abstract = {BACKGROUND: Before patients are admitted into the emergency department, it is important to undertake a pre-hospital process, both in terms of treatment performance and a request for resources from an emergency unit. The existing system to triage patients in Thailand is not functioning to its full capacity in either the primary medical system or pre-hospital treatment with shortcomings in the areas of speed, features, and appropriate systems. There is a high possibility of issuing a false Initial Dispatch Code (IDC), which will cause the over or underutilisation of emergency resources, such as rescue teams, community hospitals and emergency medical volunteers.<br><br>METHODS: A usability system design, together with a reliability test, was applied to develop an application to optimise the pre-hospital process, specifically to sort patients, using an IDC to improve the request for emergency resources. The triage mobile application was developed on both iOS and Android operating systems to support patient triage based on Criteria Based Dispatch (CBD). The 25 main symptom categories covered by CBD were used to design and develop the application, and 12 emergency medical staff, including doctors and nurses, were asked to test the system in the aspects of triage protocol correction, triage reliability, usability and user satisfaction.<br><br>RESULTS: The results of testing the proposed triage application were compared with the time used to triage by experienced staff and it was found that, in non-trauma cases, it was faster and more effective to use the application for emergency operations and to correct the IDC code representation.<br><br>CONCLUSIONS: The triage application will be utilised to support the pre-hospital process and to classify patients' conditions before they are admitted to the Emergency Department (ED). The application is suitable for users who are not medical emergency staff. Patients with non-trauma symptoms may be a suitable group to use the application in terms of time used to identify IDC for their own symptoms. The use of the application can be beneficial for those who wish to self-identify their symptoms before requesting medical services.},
}
@article {pmid32269189,
year = {2020},
author = {Lee, YH and Kwon, MJ and Park, JH and Jeong, SJ and Kim, TH and Jeong, HW and Lee, SH},
title = {Neurofibromatosis Type 1 with the Development of Pheochromocytoma and Breast Cancer.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {59},
number = {13},
pages = {1665-1669},
pmid = {32269189},
issn = {1349-7235},
mesh = {Adrenal Gland Neoplasms/*complications/surgery ; Adrenalectomy ; Adult ; Biopsy ; Breast Neoplasms/*complications/therapy ; Cafe-au-Lait Spots/pathology ; Female ; Humans ; Incidental Findings ; Neurofibromatosis 1/*complications ; Pheochromocytoma/*complications ; Skin Neoplasms/pathology ; },
abstract = {A 40-year-old woman presented with a left adrenal incidentaloma. Based on the presence of café-au-lait spots, cutaneous neurofibroma, and family history, she was diagnosed with neurofibromatosis type 1 (NF1). Adrenal incidentaloma screening showed an elevated normetanephrine level; the left adrenal mass showed the uptake of I-123 meta-iodobenzylguanidine. She underwent left adrenalectomy, and pheochromocytoma was diagnosed. One year later, the results of a biopsy of a palpable mass in the left breast suggested invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy followed by left breast-conserving surgery. We herein report a rare case of an NF1 patient who developed both pheochromocytoma and breast cancer.},
}
@article {pmid32266446,
year = {2020},
author = {Zong, L and Mo, S and Yu, S and Zhou, Y and Zhang, M and Chen, J and Xiang, Y},
title = {Expression of the immune checkpoint VISTA in breast cancer.},
journal = {Cancer immunology, immunotherapy : CII},
volume = {69},
number = {8},
pages = {1437-1446},
pmid = {32266446},
issn = {1432-0851},
support = {81672648//National Natural Science Foundation of China/International ; 81971475//National Natural Science Foundation of China/International ; CAMS-2017-I2M-1-002//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; CAMS-2016-I2M-1-001//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; B7 Antigens/*metabolism ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/*metabolism/pathology ; Carcinoma, Ductal, Breast ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/*metabolism ; Survival Rate ; },
abstract = {V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint that is an emerging target for cancer immunotherapy. This study aimed to investigate the expression of VISTA and its association with clinicopathologic parameters as well as with the key immune markers including programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) in invasive ductal carcinoma (IDC) of the breast [corrected]. Immunohistochemistry was used to detect VISTA, PD-1, PD-L1, and CD8 in tissue microarrays from 919 patients with IDC (N = 341 in the exploratory cohort and = 578 in the validation cohort). VISTA was expressed on the immune cells of 29.1% (267/919) of the samples and on the tumor cells of 8.2% (75/919). VISTA was more frequently expressed in samples that were estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2-positive, poorly differentiated, human epidermal growth factor receptor 2-enriched, and consisting of basal-like tumors. VISTA on immune cells correlated with PD-1, PD-L1, stromal CD8, and tumor-infiltrating lymphocyte expression and was an independent prognostic factor for improved relapse-free and disease-specific survival in patients with estrogen receptor-negative, progesterone receptor-negative, and basal-like IDC. These findings support therapeutic strategies that modulate VISTA expression, perhaps in combination with PD-1/PD-L1 blockade, in human breast cancer immunotherapy.},
}
@article {pmid32246378,
year = {2020},
author = {Le, AN and Harton, J and Desai, H and Powers, J and Zelley, K and Bradbury, AR and Nathanson, KL and Shah, PD and Doucette, A and Freedman, GM and Gabriel, P and Domchek, SM and MacFarland, SP and Maxwell, KN},
title = {Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome.},
journal = {Breast cancer research and treatment},
volume = {181},
number = {1},
pages = {181-188},
pmid = {32246378},
issn = {1573-7217},
support = {K08 CA215312/CA/NCI NIH HHS/United States ; K08CA21531//National Cancer Institute (US)/ ; ITMAT MHB//University of Pennsylvania/ ; 1017184//Burroughs Wellcome Fund/ ; },
mesh = {Adolescent ; Adult ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/pathology/*radiotherapy ; Carcinoma, Lobular/pathology/*radiotherapy ; Female ; Follow-Up Studies ; Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/*complications ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Neoplasms, Radiation-Induced/*etiology/pathology ; Prognosis ; Radiotherapy, Adjuvant/*adverse effects ; Retrospective Studies ; Survival Rate ; Tumor Suppressor Protein p53/genetics ; Young Adult ; },
abstract = {PURPOSE: Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy.<br><br>METHODS: A single-institution retrospective chart review was conducted for female breast cancer patients with confirmed germline TP53 mutation. The frequency of radiation-induced malignancies in LFS patients was compared to non-LFS breast cancer cases reported in the Penn Medicine Cancer Registry via statistical analyses.<br><br>RESULTS: We identified 51 female LFS breast cancer patients with 74 primary diagnoses. Fifty-seven% had a history of breast cancer only, and 25% had breast cancer as their presenting diagnosis of LFS. LFS-associated breast cancers were predominantly invasive ductal carcinoma (48%) and HER2+&#x2009;(58%). Twenty patients underwent adjuvant radiotherapy with a median follow-up of 12.5 (2-20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer, and one (6%) patient developed sarcoma in the radiation field. This risk for radiation-induced malignancy associated with LFS was higher for both sarcoma and thyroid cancer in comparison with the&#xa0;control cohort.<br><br>CONCLUSIONS: We found a lower risk of radiation-induced secondary malignancies in LFS breast cancer patients than previously reported in the literature (33% risk of radiation-induced sarcoma). These findings suggest that LFS may not be an absolute contraindication for radiotherapy in breast cancer. The potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies in consideration of adjuvant radiotherapy for LFS breast cancer patients.},
}
@article {pmid32239879,
year = {2023},
author = {Zheng, X and Yin, J},
title = {Efficacy of texture analysis in determining the gene amplification status of HER2 2+ for invasive ductal carcinoma cases.},
journal = {Minerva medica},
volume = {114},
number = {6},
pages = {832-838},
doi = {10.23736/S0026-4806.20.06536-2},
pmid = {32239879},
issn = {1827-1669},
mesh = {Humans ; Female ; Gene Amplification ; Magnetic Resonance Imaging/methods ; In Situ Hybridization, Fluorescence ; Contrast Media ; *Carcinoma, Ductal/genetics ; *Breast Neoplasms/diagnostic imaging/genetics ; Receptor, ErbB-2/genetics/metabolism ; },
abstract = {BACKGROUND: Gene amplification of human epidermal growth factor receptor2 (HER2) 2+ is essential to be determined for treatment planning. A search of the PubMed database indicates that the correlation between texture features from dynamic contrast enhanced (DCE)-MRI and HER2 2+ status has not been investigated extensively in invasive ductal carcinoma cases.<br><br>METHODS: Seventy-one DCE-MRI cases of HER2 2+ status verified using fluorescence in-situ hybridization (FISH) were selected, including 36 positive and 35 negative cases. Overall, 279 texture features were derived from lesion regions of interest manually drawn onto the subtraction images between pre- and post-contrast agent. Fisher coefficient, mutual information, minimization of both classification error probability and average correlation coefficients as well as a combination of all three methods (MPF) were independently used to reduce the dimensionality of texture parameters. A popular machine learning algorithm, the Support Vector Machine, was further applied to determine HER2 2+ status. Receiver operating characteristic (ROC) analysis was conducted to evaluate the classification performance.<br><br>RESULTS: Diagnostic accuracy was optimal when the most significant discriminatory features were selected using MPF. The area under ROC curve reached 0.863 with corresponding accuracy, sensitivity and specificity rates of 81.80%, 85.71% and 77.78%, respectively.<br><br>CONCLUSIONS: Texture analysis based on breast MRI delivered consistently high performance with FISH detection and may serve as a useful supplementary tool for determining the gene amplification status of HER2 2+ for cases with invasive ductal carcinoma.},
}
@article {pmid32239352,
year = {2020},
author = {Maggi, G and D'Iorio, A and Di Meglio, D and Vinciguerra, A and Amboni, M and Vitale, C and Santangelo, G},
title = {The role of the motor subtypes on the relationship between anxiety and cognitive dysfunctions in Parkinson's disease.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {127},
number = {6},
pages = {893-898},
doi = {10.1007/s00702-020-02179-x},
pmid = {32239352},
issn = {1435-1463},
mesh = {Anxiety/etiology ; *Cognitive Dysfunction/etiology ; *Gait Disorders, Neurologic ; Humans ; Neuropsychological Tests ; *Parkinson Disease/complications ; },
abstract = {Anxiety is a common neuropsychiatric symptom in Parkinson's disease (PD). Until now, anxiety has been consistently related to cognitive deficits and severity of motor symptoms, whereas the association between anxiety and motor subtypes (TD-PD, tremor dominant and PIGD-PD, postural instability/gait disturbances dominant) revealed contrasting results. The present study aims to investigate the relationship between PD motor subtypes and anxiety and to explore whether the relationship between anxiety and cognitive deficits occurs in a specific PD motor subtype. Consecutive PD outpatients were recruited and divided into TD-PD and PIGD-PD groups according to Jankovic et al.'s criteria. All participants underwent a neuropsychological battery to evaluate anxiety, apathy, the global cognitive functioning, memory abilities, executive and visuo-constructional functions. Thirty-six patients with TD-PD and 35 patients with PIGD-PD were enrolled. The two groups did not differ on demographical and clinical variables. As for the severity of anxiety, no significant difference between the two groups was found. Regression analysis revealed that higher anxiety score was associated with poorer performance on constructional visuospatial test in both TD-PD and PIGD-PD. Clinical variables were not associated with anxiety in the two groups. Our findings indicated that the severity of anxiety was not associated with any PD motor subtypes. Moreover, regression analysis revealed that impaired visuo-constructional abilities are related to anxiety independently of PD motor subtypes. Since altered fronto-parietal network might be one of the pathogenetic mechanisms underpinning anxiety and constructional visuospatial deficits, the treatment of cognitive dysfunctions might reduce anxious symptoms.},
}
@article {pmid32236595,
year = {2020},
author = {Gao, X and Bao, H and Liu, L and Zhu, W and Zhang, L and Yue, L},
title = {Systematic analysis of lysine acetylome and succinylome reveals the correlation between modification of H2A.X complexes and DNA damage response in breast cancer.},
journal = {Oncology reports},
volume = {43},
number = {6},
pages = {1819-1830},
pmid = {32236595},
issn = {1791-2431},
mesh = {Acetylation ; Adult ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Case-Control Studies ; Cell Line, Tumor ; Cell Survival ; *DNA Damage ; Female ; Gene Expression Regulation, Neoplastic ; Histones/*metabolism ; Humans ; Lysine/*chemistry ; MCF-7 Cells ; Middle Aged ; Nuclear Proteins/metabolism ; Nucleophosmin ; Proteomics/*methods ; Succinic Acid/chemistry ; Up-Regulation ; },
abstract = {Abnormal protein acetylation and succinylation in lysine residues can cause the initiation and development of numerous different types of tumors. However, to the best of our knowledge, there is currently a lack of systematic investigation in breast cancer. Using proteomic techniques, the present study systematically investigated the two modifications of all proteins in invasive ductal carcinoma tissues to identify potential targets. The results revealed significantly higher modification levels for the majority of proteins in breast cancer tissue when compared with para‑carcinomous normal tissue. The bioinformatic analysis demonstrated that either highly acetylated or succinylated proteins were significantly enriched in histone H2A.X (H2A.X) complexes and nucleophosmin (NPM1) may be the key member among them. The results of further analyses revealed that H2A.X complexes were associated with DNA damage response (DDR), and the proteomic results for protein quantification provided further evidence for the abnormal DDR condition in breast cancer tissues. Later, the western blotting results validated the high acetylation and succinylation levels of the majority of proteins, including the modification of NPM1 and its correlation with cell viability. Finally, the upregulation of H2A.X in breast cancer tissues further demonstrated the association between H2A.X complex modification and DDR in breast cancer. Overall, the present study systematically investigated the protein acetylation and succinylation in breast cancer and provided evidence to support H2A.X complexes as potential targets. These results broaden the horizon for breast cancer investigation and link it with epigenetics.},
}
@article {pmid32220886,
year = {2020},
author = {Pareja, F and Brown, DN and Lee, JY and Da Cruz Paula, A and Selenica, P and Bi, R and Geyer, FC and Gazzo, A and da Silva, EM and Vahdatinia, M and Stylianou, AA and Ferrando, L and Wen, HY and Hicks, JB and Weigelt, B and Reis-Filho, JS},
title = {Whole-Exome Sequencing Analysis of the Progression from Non-Low-Grade Ductal Carcinoma In Situ to Invasive Ductal Carcinoma.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {26},
number = {14},
pages = {3682-3693},
pmid = {32220886},
issn = {1557-3265},
support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Breast/pathology ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; DNA Copy Number Variations ; DNA Mutational Analysis ; Disease Progression ; Female ; *Genetic Heterogeneity ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/diagnosis/*genetics/pathology ; Exome Sequencing ; },
abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive breast cancer. Here, we sought to investigate the level of intralesion genetic heterogeneity in DCIS and the patterns of clonal architecture changes in the progression from DCIS to invasive disease.<br><br>EXPERIMENTAL DESIGN: Synchronous DCIS (n = 27) and invasive ductal carcinomas of no special type (IDC-NSTs; n = 26) from 25 patients, and pure DCIS (n = 7) from 7 patients were microdissected separately and subjected to high-depth whole-exome (n = 56) or massively parallel sequencing targeting &#x2265;410 key cancer-related genes (n = 4). Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic analyses were defined using validated computational methods.<br><br>RESULTS: DCIS revealed genetic alterations similar to those of synchronously diagnosed IDC-NSTs and of non-related IDC-NSTs from The Cancer Genome Atlas (TCGA), whereas pure DCIS lacked PIK3CA mutations. Clonal decomposition and phylogenetic analyses based on somatic mutations and copy number alterations revealed that the mechanisms of progression of DCIS to invasive carcinoma are diverse, and that clonal selection might have constituted the mechanism of progression from DCIS to invasive disease in 28% (7/25) of patients. DCIS displaying a pattern of clonal selection in the progression to invasive cancer harbored higher levels of intralesion genetic heterogeneity than DCIS where no clonal selection was observed.<br><br>CONCLUSIONS: Intralesion genetic heterogeneity is a common feature in DCIS synchronously diagnosed with IDC-NST. DCIS is a nonobligate precursor of IDC-NST, whose mechanisms of progression to invasive breast cancer are diverse and vary from case to case.},
}
@article {pmid32212794,
year = {2020},
author = {Rasmy, A and Sorour, Y},
title = {Effect of Obesity on Neoadjuvant Systemic Therapy Outcomes in Patients with Early Breast Cancer: A Retrospective Institutional Study.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {21},
number = {3},
pages = {683-691},
pmid = {32212794},
issn = {2476-762X},
mesh = {Adult ; Aged ; Body Mass Index ; Breast Neoplasms/complications/*therapy ; Female ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Obesity/*complications ; Retrospective Studies ; Treatment Outcome ; },
abstract = {BACKGROUND: Obesity and overweight are usually considered as poor prognostic factors in early breast cancer. Body mass index (BMI) is a significant predictive factor for lower pathologic complete response (pCR) rates after neo-adjuvant systemic therapy (NST). The relationship between obesity and breast cancer prognosis varies according to patient and tumor characteristics such as menopausal status and tumor subtype, respectively.<br><br>PATIENTS AND METHODS: Between March 2010 and October 2013, 80 patients with early breast cancer who had received standard NST from KFSH Saudi Arabia were included in this study. For statistical analysis, the study participants were categorized into two groups based on their BMI, as normal (BMI < 25 kg/m2) and obese groups (BMI &#x2265; 25 kg/m2). pCR was defined as non-invasive cancer in the breast/axillary tissue.<br><br>RESULTS: The median age of our patients was 48 (range, 38-68) years. Invasive ductal carcinoma (IDC) subtype was identified in 93.8% of the cases. Additionally, 26 (32.5%) and 33 (41.25%) patients were diagnosed with stage II and stage IIIA breast cancer, respectively. Lymphovascular invasion was detected in 32.5%, whereas intermediate and high-grade malignancy were found in 61.25% and 32.5% of the patients, respectively. Forty-four patients (55%) were obese. pCR was achieved in 56 patients (70%), and the comparison between patients with and without pCR revealed that those in the former group had significantly lower tumor grades. Significantly, lower relapse and mortality rates were distinguished in patients who achieved pCR than in those who did not. Additionally, comparison between normal and obese patients revealed that a high number of patients in both groups were post-menopausal (p = 0.001). However, survival analysis indicated the absence of significant differences in disease-free survival between the two groups based on BMI (p = 0.19). Conversely, patients with normal BMI had significantly better overall survival than obese patients (p = 0.029), with a higher mortality rate noted in the obese group (16.7% vs 2.3%, p = 0.037).<br><br>CONCLUSIONS: In the present study, 58.3% of patients that failed to achieve pCR had BMI above the normal level; they moreover had higher relapse rates and lower survival compared with normal BMI patients. This finding needs to be verified through further prospective studies to determine if BMI is a risk factor for breast cancer.},
}
@article {pmid32209879,
year = {2020},
author = {Liu, Q and Zhang, J and Kulkarni, HR and Baum, RP},
title = {177Lu-DOTATOC Peptide Receptor Radionuclide Therapy in a Patient With Neuroendocrine Breast Carcinoma and Breast Invasive Ductal Carcinoma.},
journal = {Clinical nuclear medicine},
volume = {45},
number = {5},
pages = {e232-e235},
doi = {10.1097/RLU.0000000000003005},
pmid = {32209879},
issn = {1536-0229},
mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/pathology/*radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Neuroendocrine Tumors/diagnostic imaging/metabolism/pathology/*radiotherapy ; Octreotide/*analogs &amp; derivatives/therapeutic use ; Positron Emission Tomography Computed Tomography ; Receptors, Somatostatin/*metabolism ; Treatment Outcome ; },
abstract = {Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)-targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on Ga-DOTATOC PET/CT, and remarkably partial remission after Lu-DOTATOC PRRT.},
}
@article {pmid32202536,
year = {2020},
author = {Szentirmai, E and Giannico, GA},
title = {Intraductal carcinoma of the prostate.},
journal = {Pathologica},
volume = {112},
number = {1},
pages = {17-24},
pmid = {32202536},
issn = {1591-951X},
mesh = {Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Prostatectomy/trends ; Prostatic Neoplasms/*diagnosis/*genetics/therapy ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) is a diagnostic entity characterized by architecturally or cytologically malignant-appearing prostatic glandular epithelium confined to prostatic ducts. Despite its apparent in situ nature, this lesion is associated with aggressive prostatic adenocarcinoma and is a predictor for poor prognosis when identified on biopsy or radical prostatectomy. This review discusses diagnosis, clinical features, histogenesis, and management of IDC-P, as well as current research and controversies surrounding this entity.},
}
@article {pmid32190711,
year = {2020},
author = {Lee, RA and Vo, DT and Zurko, JC and Griffin, RL and Rodriguez, JM and Camins, BC},
title = {Infectious Diseases Consultation Is Associated With Decreased Mortality in Enterococcal Bloodstream Infections.},
journal = {Open forum infectious diseases},
volume = {7},
number = {3},
pages = {ofaa064},
pmid = {32190711},
issn = {2328-8957},
abstract = {BACKGROUND: Enterococcus species frequently cause health care-associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown.<br><br>METHODS: This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients&#x2005;>18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture.<br><br>RESULTS: Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P&#x2005;<&#x2005;.001), echocardiography (79% vs 45%; P&#x2005;<&#x2005;.001), surgical intervention (20% vs 7%; P&#x2005;=&#x2005;0.01), and have appropriate antibiotic duration (90% vs 46%; P&#x2005;<&#x2005;.001). Thirty-day mortality was significantly higher in the no-IDC group (27 % vs 12 %; P&#x2005;<&#x2005;.007). In multivariate analysis, 30-day in-hospital mortality was associated with both E. faecium bacteremia (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.09-5.23) and IDC (aOR, 0.35; 95% CI, 0.16-0.76).<br><br>CONCLUSIONS: Patients who received IDC for Enterococcus bacteremia had significantly lower 30-day mortality. Further prospective studies are necessary to determine if these outcomes can be validated in other institutions for patients who receive IDC with Enterococcus bacteremia.},
}
@article {pmid32161717,
year = {2020},
author = {Guo, T and Chen, Z and Xu, J and Zhang, Y},
title = {Change of Pathological Type to Metaplastic Squamous Cell Carcinoma of the Breast During Disease Recurrence: Case Report and Literature Review.},
journal = {Frontiers in oncology},
volume = {10},
number = {},
pages = {32},
pmid = {32161717},
issn = {2234-943X},
abstract = {Background: Metaplastic squamous cell carcinoma (SCC) of the breast is a rare and heterogeneous group of primary breast malignancies. The etiology, pathogenesis, and proper treatment for this kind rare breast cancer are still unclear. Case presentation: We reported a case of a 55-year-old woman with a palpable lump in the inner quadrant of the right breast. She underwent a right breast mass resection and sentinel lymph node biopsy, which revealed that the tumor was an invasive ductal carcinoma, followed by four cycles of doxorubicin plus cyclophosphamide and four cycles of docetaxel as adjuvant chemotherapy, and then simultaneous integrated boost intensity modulated radiotherapy to the whole right breast. After 2 years' follow-up, she had biopsy-proven disease recurrence in the right breast, which revealed SCC, and a mammogram showed abnormalities in the lower inner quadrant of the right breast and left axillary lymph nodes. Then we performed bilateral breast modified radical mastectomy, which confirmed that the recurrent tumors were metaplastic SCC, followed by adjuvant chemotherapy and adjuvant radiotherapy of the left supraclavicular and apical axillary regions. There has been no recurrent or metastatic evidence in the 16 months' follow-up since the second surgery. Conclusion: This case report shows that evolution of pathology type in recurrent breast cancer after initial treatment is possible. Detailed pathologic and immunohistochemical analyses are needed for identification of this change. Surgery and adjuvant radiation and chemotherapy are appropriate treatments for recurrent primary SCC of the breast.},
}
@article {pmid32157060,
year = {2019},
author = {Egawa, C and Yanai, A and Yanagawa, T and Takatsuka, Y and Takeno, A and Masuzawa, T and Hata, T and Kagawa, Y and Ohmura, Y and Katsura, Y and Murakami, K and Sakamoto, T and Kawai, K and Takeda, Y and Murata, K},
title = {[Long-Term Survival in a Case of Breast Cancer with Brain Metastases and No Other Distant Metastases Treated by Surgical Removal and Gamma Knife Radiosurgery].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {46},
number = {13},
pages = {2063-2065},
pmid = {32157060},
issn = {0385-0684},
mesh = {Adult ; *Brain Neoplasms/radiotherapy/secondary ; *Breast Neoplasms/radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; *Radiosurgery ; },
abstract = {A 44-year-oldwoman was diagnosedwith right breast cancer andund erwent mastectomy andaxillary lymph node dissection in February 2006. She was pathologically diagnosed with invasive ductal carcinoma without lymph node metastasis. Immunohistochemical examination showedthat the tumor was estrogen receptor positive, progesterone receptor negative, andhada HER2 status score of 0. She received 4 cycles of AC, followedby leuprorelin andtamoxifen. Several metastases were identified in the right supraclavicular lymph nodes in August 2008 during the endocrine therapy. Then, she received S-1 as the first-line chemotherapy. Although metastases showed complete response, she developed an eye disorder caused by S-1 and thus the treatment agent was changedto leuprorelin andanastrozole. She complainedof headache andright homonymous hemianopsia in November 2013. MRI showeda 42mm diameter tumor in the left occipital lobe, suspectedto be brain metastasis from breast cancer. Craniotomy was performedto remove the brain tumor, which was pathologically diagnosedas metastasis from breast cancer. In the brain tumor, the estrogen receptor status hadchangedto negative, but the HER2 status remained unchanged, showing a score of 0. Vinorelbine was administered after the brain surgery. Unfortunately, brain metastasis was foundin the dura mater near the surgical cavity, andgamma knife radiosurgery was performedin January 2014. Thereafter, brain metastases were repeatedly found, and gamma knife radiosurgery was again performed in January 2015, September 2016, and February 2017. In addition, a large tumor appearedin the left occipital lobe andwas surgically removed in June 2016. No other distant metastases were found, andvinorelbine was continueduntil February 2018. Because the patient developed dyslexia caused by gamma knife-induced radiation necrosis, bevacizumab was administered between November 2018 and April 2019. MRI showed that the edema due to radiation necrosis reduced and dyslexia symptoms improved. As of now, she has survivedfor 5 years and 6 months after the diagnosis of brain metastases.},
}
@article {pmid32156965,
year = {2019},
author = {Kinoshita, H and Teraoka, H and Mori, T and Hasegawa, T and Noda, E and Takashima, T and Hirakawa, K and Ohira, M},
title = {[A Case of Breast Cancer Liver Metastases with Jaundice Responding to Chemotherapy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {46},
number = {13},
pages = {2461-2463},
pmid = {32156965},
issn = {0385-0684},
mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy/secondary ; Female ; Humans ; *Jaundice/etiology ; *Liver Neoplasms/drug therapy/secondary ; Middle Aged ; Paclitaxel ; },
abstract = {A 50-year-old woman was referred to our hospital due to breast cancer with multiple liver metastasis diagnosed by CT scan. Laboratory findings showed liver dysfunction(T-Bil 7.6mg/dL)with marked elevation of tumor markers(CEA 727.9 ng/mL). Breast tumor biopsy showed an invasive ductal carcinoma(scirrhous type), ER(+), PgR(-), and HER2(3+). Combination therapy with docetaxel, carboplatin and, trastuzumab was administered after the end of 1 course of weekly paclitaxel plus bevacizumab regimen. The patient maintained a good condition without liver dysfunction 8 months after the first visit. Follow-up CT scan showed partial response of breast and hepatic tumors. Our case suggests that careful chemotherapy can improve the prognosis of breast cancer with liver metastasis even if a patient is in an icteric condition.},
}
@article {pmid32156942,
year = {2019},
author = {Morisaki, T and Takashima, T and Asano, Y and Kashiwagi, S and Noda, S and Onoda, N and Ohira, M},
title = {[Two Cases of Orbital Metastasis from Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {46},
number = {13},
pages = {2392-2394},
pmid = {32156942},
issn = {0385-0684},
mesh = {Adult ; *Breast Neoplasms ; Eye Neoplasms/*secondary ; Female ; Humans ; *Liver Neoplasms ; Magnetic Resonance Imaging ; },
abstract = {Orbital metastasis from breast cancer is a rare condition. Here, we describe 2 cases of orbital metastasis from breast cancer. The first patient was a 26-year-old woman diagnosed with triple-negative invasive ductal carcinoma. She underwent surgery after neoadjuvant chemotherapy. One year after surgery, she had multiple bone metastases and then multiple liver metastases developed. During chemotherapy for metastatic disease, she complained ofheadaches and visual disturbances. Findings ofa MRI scan suggested a metastatic tumor in the left orbit. A total of 30 Gy of radiation therapy was administered, but she died a month after the orbital metastasis was discovered. The second patient was a 42-year-old woman, who had advanced breast cancer with bone metastasis. Diplopia developed 8 months after initiation of chemotherapy. Meningeal dissemination was suspected because ophthalmological examination revealed swelling ofbilateral optic discs. She lost her sight within a month. She died 2 months after the diagnosis oforbital metastasis. There was no evidence ofcentral nervous system metastasis in either case. Loss ofvision severely impairs patients' quality oflif e. It is important to know that there is rarely such a rapid progression ofdisease, especially in young patients with triple-negative disease.},
}
@article {pmid32156914,
year = {2019},
author = {Nakama, Y and Maruyama, Y and Hisaka, T and Yasumoto, M and Okabe, Y and Naito, Y and Yamaguchi, M and Tanaka, M and Tanaka, H and Akagi, Y and Okuda, K},
title = {[A Vesected Case of Pancreatic Metastasis from Breast Cancer Which Recurred Six Years after Breast Surgery].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {46},
number = {13},
pages = {2309-2311},
pmid = {32156914},
issn = {0385-0684},
mesh = {*Adenocarcinoma/secondary/surgery ; Adult ; *Breast Neoplasms/surgery ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/secondary ; },
abstract = {A 43-year-old woman who underwent surgical resection of invasive ductal carcinoma in the left breast at the age of 37 years old presented at our hospital for evaluation of pancreatic tumor. The original tumor was estrogen receptor(ER)progesterone receptor(PgR)and HER2 positive. At that time, she underwent radical mastectomy with no evident nodal disease. Postoperatively, the patient was placed on adjuvant tamoxifen therapy for several years. Six years following the original diagnosis of breast cancer, she was referred to the hospital for routine check-up while asymptomatic. Follow-up examination showed a solitary hypodense mass approximately 0.9 cm in size in the pancreas body on dynamic CT scan. The patient underwent a standard distal pancreatectomy with standard regional lymphadenectomy. Histopathological examination and immunohistochemical features revealed that the tumor was compatible with metastatic pancreatic adenocarcinoma from breast cancer.},
}
@article {pmid32139710,
year = {2020},
author = {Roy, S and Kumar, R and Mittal, V and Gupta, D},
title = {Classification models for Invasive Ductal Carcinoma Progression, based on gene expression data-trained supervised machine learning.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {4113},
pmid = {32139710},
issn = {2045-2322},
support = {SRF//Council of Scientific and Industrial Research (CSIR)/International ; SRF//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/PR6963/BID/7/427/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/BI/25/066/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; },
mesh = {Algorithms ; Breast Neoplasms/*classification/genetics ; Carcinoma, Ductal, Breast/*classification/genetics ; Databases, Genetic ; Datasets as Topic ; Early Detection of Cancer ; Female ; Gene Ontology ; Humans ; Machine Learning ; Microarray Analysis ; Models, Biological ; Neoplasm Staging ; Protein Interaction Maps ; RNA, Neoplasm ; RNA-Seq ; Reproducibility of Results ; *Supervised Machine Learning ; *Transcriptome ; },
abstract = {Early detection of breast cancer and its correct stage determination are important for prognosis and rendering appropriate personalized clinical treatment to breast cancer patients. However, despite considerable efforts and progress, there is a need to identify the specific genomic factors responsible for, or accompanying Invasive Ductal Carcinoma (IDC) progression stages, which can aid the determination of the correct cancer stages. We have developed two-class machine-learning classification models to differentiate the early and late stages of IDC. The prediction models are trained with RNA-seq gene expression profiles representing different IDC stages of 610 patients, obtained from The Cancer Genome Atlas (TCGA). Different supervised learning algorithms were trained and evaluated with an enriched model learning, facilitated by different feature selection methods. We also developed a machine-learning classifier trained on the same datasets with training sets reduced data corresponding to IDC driver genes. Based on these two classifiers, we have developed a web-server Duct-BRCA-CSP to predict early stage from late stages of IDC based on input RNA-seq gene expression profiles. The analysis conducted by us also enables deeper insights into the stage-dependent molecular events accompanying IDC progression. The server is publicly available at http://bioinfo.icgeb.res.in/duct-BRCA-CSP.},
}
@article {pmid32138738,
year = {2020},
author = {Sun, T and Yang, W and Toprani, SM and Guo, W and He, L and DeLeo, AB and Ferrone, S and Zhang, G and Wang, E and Lin, Z and Hu, P and Wang, X},
title = {Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram.},
journal = {Cell communication and signaling : CCS},
volume = {18},
number = {1},
pages = {36},
pmid = {32138738},
issn = {1478-811X},
support = {R01 CA226981/CA/NCI NIH HHS/United States ; R03 CA216114/CA/NCI NIH HHS/United States ; },
mesh = {*Antineoplastic Agents/administration &amp; dosage/pharmacology ; Breast Neoplasms/*drug therapy/pathology/radiotherapy ; Cell Line, Tumor ; *Disulfiram/administration &amp; dosage/pharmacology ; *Drug Repositioning ; Female ; Humans ; Immunogenic Cell Death/*drug effects ; Neoplastic Stem Cells ; Radiation Tolerance/*drug effects ; },
abstract = {BACKGROUND: The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response.<br><br>METHODS: High aldehyde dehydrogenase activity (ALDH)[bright] and CD44[+]/CD24[-]/ESA[+] cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors.<br><br>CONCLUSION: DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.},
}
@article {pmid32135221,
year = {2020},
author = {Shete, A and Kurle, S and Dhayarkar, S and Patil, A and Kulkarni, S and Ghate, M and Sangale, S and Medhe, U and Rajan, S and Verma, V and Gangakhedkar, R},
title = {High IL-5 levels possibly contributing to HIV viremia in virologic non-responders at one year after initiation of anti-retroviral therapy.},
journal = {Microbial pathogenesis},
volume = {143},
number = {},
pages = {104117},
doi = {10.1016/j.micpath.2020.104117},
pmid = {32135221},
issn = {1096-1208},
mesh = {Adolescent ; Adult ; Anti-HIV Agents/*therapeutic use ; CD4-CD8 Ratio ; Drug Resistance, Viral/genetics ; Female ; HIV Infections/*drug therapy/virology ; Humans ; Interleukin-5/*blood ; Male ; Middle Aged ; Treatment Failure ; Viremia/blood/*drug therapy ; Young Adult ; },
abstract = {Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40). They were assessed for HIV drug resistance by sequencing, plasma cytokines by luminex assay, T cell activation status by flow cytometry and total IgE levels by ELISA. VNR and failure patients had significantly lower median baseline CD4 counts than the responders. VNRs had significantly higher CD4 counts but lower viral load than treatment failures at one year of ART. VNRs had the highest eosinophil counts and the highest IL-5 levels among all the groups. IL-5 levels in them correlated with their viral load values. Frequency of Treg cells was also highest among the VNR group participants. More than 60% of the viremic patients irrespective of their groups harboured multiple HIV drug resistance mutations and mutation pattern did not differ between the groups. Low baseline CD4 counts and presence of multiple drug resistance mutations in the viremic groups highlighted the importance of early ART initiation and viral load monitoring irrespective of presence of immunologic failure. High IL-5 levels in VNR group indicated a need for investigating causal relationship between IL-5 and viral replication to devise therapeutic strategies to control viremia.},
}
@article {pmid32119669,
year = {2020},
author = {Rangel, GW and Clark, MA and Kanjee, U and Goldberg, JM and MacInnis, B and José Menezes, M and Ferreira, MU and Duraisingh, MT},
title = {Plasmodium vivax transcriptional profiling of low input cryopreserved isolates through the intraerythrocytic development cycle.},
journal = {PLoS neglected tropical diseases},
volume = {14},
number = {3},
pages = {e0008104},
pmid = {32119669},
issn = {1935-2735},
support = {R01 AI140751/AI/NIAID NIH HHS/United States ; R01 HL139337/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U19 AI089681/AI/NIAID NIH HHS/United States ; },
mesh = {Adolescent ; Child ; Child, Preschool ; Culture Media/chemistry ; Erythrocytes/*parasitology ; Female ; *Gene Expression Profiling ; *Host-Pathogen Interactions ; Humans ; Infant ; Infant, Newborn ; Malaria, Vivax/*parasitology ; Male ; Parasitology/methods ; Plasmodium vivax/genetics/*growth &amp; development ; Sequence Analysis, RNA ; },
abstract = {Approximately one-third of the global population is at risk of Plasmodium vivax infection, and an estimated 7.51 million cases were reported in 2017. Although, P. vivax research is currently limited by the lack of a robust continuous in vitro culture system for this parasite, recent work optimizing short-term ex vivo culture of P. vivax from cryopreserved isolates has facilitated quantitative assays on synchronous parasites. Pairing this improved culture system with low-input Smart-seq2 RNAseq library preparation, we sought to determine whether transcriptional profiling of P. vivax would provide insight into the differential survival of parasites in different culture media. To this end we probed the transcriptional signature of three different ex vivo P. vivax samples in four different culture media using only 1000 cells for each time point taken during the course of the intraerythrocytic development cycle (IDC). Using this strategy, we achieved similar quality transcriptional data to previously reported P. vivax transcriptomes. We found little effect with varying culture media on parasite transcriptional signatures, identified many novel gametocyte-specific genes from transcriptomes of FACS-isolated gametocytes, and determined invasion ligand expression in schizonts in biological isolates and across the IDC. In total, these data demonstrate the feasibility and utility of P. vivax RNAseq-based transcriptomic studies using minimal biomass input to maximize experimental capacity.},
}
@article {pmid32103749,
year = {2020},
author = {Tewari, SG and Swift, RP and Reifman, J and Prigge, ST and Wallqvist, A},
title = {Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite.},
journal = {Malaria journal},
volume = {19},
number = {1},
pages = {94},
pmid = {32103749},
issn = {1475-2875},
support = {R01 AI125534/AI/NIAID NIH HHS/United States ; R01 AI065853/NH/NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; W81XWH-15-C-0061//U.S. Army Medical Research and Development Command/ ; },
mesh = {Erythrocytes/*metabolism/parasitology ; Malaria, Falciparum/*metabolism/parasitology ; Parasitemia/*metabolism/parasitology ; Plasmodium falciparum/*growth &amp; development ; },
abstract = {BACKGROUND: Human blood cells (erythrocytes) serve as hosts for the malaria parasite Plasmodium falciparum during its 48-h intraerythrocytic developmental cycle (IDC). Established in vitro protocols allow for the study of host-parasite interactions during this phase and, in particular, high-resolution metabolomics can provide a window into host-parasite interactions that support parasite development.<br><br>METHODS: Uninfected and parasite-infected erythrocyte cultures were maintained at 2% haematocrit for the duration of the IDC, while parasitaemia was maintained at 7% in the infected cultures. The parasite-infected cultures were synchronized to obtain stage-dependent information of parasite development during the IDC. Samples were collected in quadruplicate at six time points from the uninfected and parasite-infected cultures and global metabolomics was used to analyse cell fractions of these cultures.<br><br>RESULTS: In uninfected and parasite-infected cultures during the IDC, 501 intracellular metabolites, including 223 lipid metabolites, were successfully quantified. Of these, 19 distinct metabolites were present only in the parasite-infected culture, 10 of which increased to twofold in abundance during the IDC. This work quantified approximately five times the metabolites measured in previous studies of similar research scope, which allowed for more detailed analyses. Enrichment in lipid metabolism pathways exhibited a time-dependent association with different classes of lipids during the IDC. Specifically, enrichment occurred in sphingolipids at the earlier stages, and subsequently in lysophospholipid and phospholipid metabolites at the intermediate and end stages of the IDC, respectively. In addition, there was an accumulation of 18-, 20-, and 22-carbon polyunsaturated fatty acids, which produce eicosanoids and promote gametocytogenesis in infected erythrocyte cultures.<br><br>CONCLUSIONS: The current study revealed a number of heretofore unidentified metabolic components of the host-parasite system, which the parasite may exploit in a time-dependent manner to grow over the course of its development in the blood stage. Notably, the analyses identified components, such as precursors of immunomodulatory molecules, stage-dependent lipid dynamics, and metabolites, unique to parasite-infected cultures. These conclusions are reinforced by the metabolic alterations that were characterized during the IDC, which were in close agreement with those known from previous studies of blood-stage infection.},
}
@article {pmid32088208,
year = {2020},
author = {Guillet, C and Rechsteiner, M and Bellini, E and Choschzick, M and Moskovszky, L and Dedes, K and Papassotiropoulos, B and Varga, Z},
title = {Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations.},
journal = {Human pathology},
volume = {98},
number = {},
pages = {64-73},
doi = {10.1016/j.humpath.2020.02.002},
pmid = {32088208},
issn = {1532-8392},
mesh = {Adult ; Age of Onset ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/surgery ; Class I Phosphatidylinositol 3-Kinases/*genetics ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; Heredity ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; *Mutation ; Papilloma/*genetics/pathology/surgery ; Pedigree ; Phenotype ; Proto-Oncogene Proteins c-akt/*genetics ; },
abstract = {Juvenile papillomatosis (JP), the so-called Swiss cheese disease, is a rare benign breast disease of young adults. An association (up to 28%) with breast cancer within the family of affected patients has been reported. A multinodular cystic breast mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal papillomas, usual ductal hyperplasia, ductectasias, perifocal sclerosing adenosis, and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family history in context with a comprehensive review of the JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were women with a median age of 38 years (26-50 years). Follow-up information was available for 11 of 13 patients. Sufficient paraffin-embedded tissue and good DNA quality for next-generation sequencing (NGS) was available for 10 patients. Paraffin blocks were microdissected in the area of intraductal proliferative disease; the tissue cores underwent NGS analysis using the Oncomine Comprehensive Panel. In 5 of 10 patients, we found PIK3CA mutations; in 2 of 10 patients, we found AKT1 mutations in known hot spot regions. Further mutations in MET, FGFR3, PTEN, ATM, NF1, and GNAS genes were detected in individual patients. Some of these mutations were present at high allele frequencies suggesting germ line mutations. Two of 3 patients with positive family history had PIK3CA mutation; one patient with positive family history had an AKT1 mutation. One patient who subsequently developed invasive ductal carcinoma in the contralateral breast possibly had a germ line ATM mutation. Our results confirm hot spot mutations in PIK3CA and AKT1 genes in JP associated with positive family history for breast cancer, although these mutations are not specific for JP. The genetic link between JP, positive family history, and subsequent risk of breast cancer needs to be analyzed in further studies.},
}
@article {pmid32086991,
year = {2020},
author = {Luo, Y and Kishi, S and Sasaki, T and Ohmori, H and Fujiwara-Tani, R and Mori, S and Goto, K and Nishiguchi, Y and Mori, T and Kawahara, I and Kondoh, M and Kuniyasu, H},
title = {Targeting claudin-4 enhances chemosensitivity in breast cancer.},
journal = {Cancer science},
volume = {111},
number = {5},
pages = {1840-1850},
pmid = {32086991},
issn = {1349-7006},
support = {17KJB320010//Natural Science Foundation of Jiangsu Education Department Project/ ; 16H05164//Ministry of Education, Culture, Sports, Science and Technology/ ; 17K19923//Ministry of Education, Culture, Sports, Science and Technology/ ; 81702723//National Natural Science Foundation of China/ ; },
mesh = {Animals ; Antibodies/pharmacology/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Claudin-1 ; Claudin-4/chemistry/genetics/*immunology ; Drug Synergism ; Female ; Humans ; MCF-7 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Paclitaxel/pharmacology/therapeutic use ; Tamoxifen/pharmacology/therapeutic use ; Triple Negative Breast Neoplasms/drug therapy/metabolism/pathology ; Tumor Microenvironment/drug effects ; Xenograft Model Antitumor Assays ; },
abstract = {Triple negative breast cancer (TNBC) is characterized by highly aggressive phenotype, limited treatment options and a poor prognosis. In the present study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDC (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and was correlated with histological grade. In contrast, expression of CLDN4 was correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors and increased the intratumoral pH. Moreover, concurrent treatment with 4D3, PTX and tamoxifen, or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in a bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects.},
}
@article {pmid32079470,
year = {2020},
author = {Yin, S and Fan, Y and He, X and Wei, G and Wen, Y and Zhao, Y and Shi, M and Wei, J and Chen, H and Han, J and Jiang, L and Zhang, Q},
title = {The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum.},
journal = {RNA biology},
volume = {17},
number = {6},
pages = {828-842},
pmid = {32079470},
issn = {1555-8584},
mesh = {Computational Biology/methods ; Erythrocytes/parasitology ; Exosome Multienzyme Ribonuclease Complex ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Ontology ; Humans ; Life Cycle Stages ; Malaria, Falciparum/*parasitology ; Plasmodium falciparum/*genetics/*growth &amp; development ; *RNA Splicing ; RNA Stability ; RNA, Messenger/genetics ; RNA, Protozoan/*genetics ; RNA, Untranslated/genetics ; },
abstract = {The tight gene expression regulation controls the development and pathogenesis of human malaria parasite Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in the dynamic gene expression. However, the landscape and related biological functions of nascent non-coding RNAs (ns-ncRNAs) are still poorly explored. Here we profiled the transcription dynamics of nascent RNAs by rRNA-depleted and stranded RNA sequencing over the course of 48-h intraerythrocytic developmental cycle (IDC). We identified the genome-wide sources of a total of 2252 ns-ncRNAs, mostly originating from intergenic and untranslated regions of annotated genes. By integrating the nascent RNA abundances with ATAC-seq and ChIP-seq analysis, we uncovered the euchromatic microenvironment surrounding the ns-ncRNA loci, and revealed a positive correlation between ns-ncRNAs and corresponding mRNA abundances. Finally, by gene knock-down strategy, we showed that the cooperation of RNA exosome catalytic subunit PfDis3 and PfMtr4 cofactor played a major role in ns-ncRNAs degradation. Collectively, this study contributes to understanding of the potential roles of short-lived nascent ncRNAs in regulating gene expression in malaria parasites.},
}
@article {pmid32063604,
year = {2020},
author = {Granados, K and Hüser, L and Federico, A and Sachindra, S and Wolff, G and Hielscher, T and Novak, D and Madrigal-Gamboa, V and Sun, Q and Vierthaler, M and Larribère, L and Umansky, V and Utikal, J},
title = {T-type calcium channel inhibition restores sensitivity to MAPK inhibitors in de-differentiated and adaptive melanoma cells.},
journal = {British journal of cancer},
volume = {122},
number = {7},
pages = {1023-1036},
pmid = {32063604},
issn = {1532-1827},
support = {OAICE-CAB-09-133-2015//Universidad de Costa Rica (University of Costa Rica)/International ; PED-054-2015-2//Ministerio de Ciencia Tecnolog&#xed;a y Telecomunicaciones (Ministerio de Ciencia Tecnolog&#xed;a y Telecomunicaciones de Costa Rica)/International ; 259332240 / RTG 2099//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; },
mesh = {Animals ; Calcium Channels, T-Type/*genetics ; Disease Models, Animal ; Female ; Humans ; Melanoma/*drug therapy/pathology ; Mice ; Protein Kinase Inhibitors/pharmacology/*therapeutic use ; Proto-Oncogene Mas ; },
abstract = {BACKGROUND: Drug resistance remains as one of the major challenges in melanoma therapy. It is well known that tumour cells undergo phenotypic switching during melanoma progression, increasing melanoma plasticity and resistance to mitogen-activated protein kinase inhibitors (MAPKi).<br><br>METHODS: We investigated the melanoma phenotype switching using a partial reprogramming model to de-differentiate murine melanoma cells and target melanoma therapy adaptation against MAPKi.<br><br>RESULTS: Here, we show that partially reprogrammed cells are a less proliferative and more de-differentiated cell population, expressing a gene signature for stemness and suppressing melanocyte-specific markers. To investigate adaptation to MAPKi, cells were exposed to B-Raf Proto-Oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors. De-differentiated cells became less sensitive to MAPKi, showed increased cell viability and decreased apoptosis. Furthermore, T-type calcium channels expression increased in adaptive murine cells and in human adaptive melanoma cells. Treatment with the calcium channel blocker mibefradil induced cell death, differentiation and susceptibility to MAPKi in vitro and in vivo.<br><br>CONCLUSION: In summary, we show that partial reprogramming of melanoma cells induces de-differentiation and adaptation to MAPKi. Moreover, we postulated a calcium channel blocker such as mibefradil, as a potential candidate to restore sensitivity to MAPKi in adaptive melanoma cells.},
}
@article {pmid32062352,
year = {2020},
author = {Kanwar, N and Carmine-Simmen, K and Nair, R and Wang, C and Moghadas-Jafari, S and Blaser, H and Tran-Thanh, D and Wang, D and Wang, P and Wang, J and Pasculescu, A and Datti, A and Mak, T and Lewis, JD and Done, SJ},
title = {Amplification of a calcium channel subunit CACNG4 increases breast cancer metastasis.},
journal = {EBioMedicine},
volume = {52},
number = {},
pages = {102646},
pmid = {32062352},
issn = {2352-3964},
mesh = {Animals ; Breast Neoplasms/*genetics/metabolism/*pathology ; Calcium/metabolism ; Calcium Channels/chemistry/*genetics/metabolism ; Calcium Signaling ; Cell Line ; Cell Movement/genetics ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/genetics/metabolism ; Disease Progression ; Female ; *Gene Amplification ; Gene Expression ; Humans ; Immunohistochemistry ; Mice ; Models, Biological ; Neoplasm Metastasis ; Neoplasm Staging ; Protein Interaction Domains and Motifs ; },
abstract = {BACKGROUND: Previously, we found that amplification of chromosome 17q24.1-24.2 is associated with lymph node metastasis, tumour size, and lymphovascular invasion in invasive ductal carcinoma. A gene within this amplicon, CACNG4, an L-type voltage-gated calcium channel gamma subunit, is elevated in breast cancers with poor prognosis. Calcium homeostasis is achieved by maintaining low intracellular calcium levels. Altering calcium influx/efflux mechanisms allows tumour cells to maintain homeostasis despite high serum calcium levels often associated with advanced cancer (hypercalcemia) and aberrant calcium signaling.<br><br>METHODS: In vitro 2-D and 3-D assays, and intracellular calcium influx assays were utilized to measure tumourigenic activity in response to altered CANCG4 levels and calcium channel blockers. A chick-CAM model and mouse model for metastasis confirmed these results in vivo.<br><br>FINDINGS: CACNG4 alters cell motility in vitro, induces malignant transformation in 3-dimensional culture, and increases lung-specific metastasis in vivo. CACNG4 functions by closing the channel pore, inhibiting calcium influx, and altering calcium signaling events involving key survival and metastatic pathway genes (AKT2, HDAC3, RASA1 and PKC&#x3b6;).<br><br>INTERPRETATION: CACNG4 may promote homeostasis, thus increasing the survival and metastatic ability of tumour cells in breast cancer. Our findings suggest an underlying pathway for tumour growth and dissemination regulated by CACNG4 that is significant with respect to developing treatments that target these channels in tumours with aberrant calcium signaling.<br><br>FUNDING: Canadian Breast Cancer Foundation, Ontario; Canadian Institutes of Health Research.},
}
@article {pmid32051475,
year = {2020},
author = {Beetch, M and Harandi-Zadeh, S and Yang, T and Boycott, C and Chen, Y and Stefanska, B and Mohammed, SI},
title = {DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {2415},
pmid = {32051475},
issn = {2045-2322},
mesh = {Animals ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/*veterinary ; *DNA Methylation ; Disease Progression ; Dog Diseases/*genetics/pathology ; Dogs/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Triple Negative Breast Neoplasms/genetics/pathology/*veterinary ; },
abstract = {Triple-negative breast cancer (TNBC) is a subtype of breast cancer unresponsive to traditional receptor-targeted treatments, leading to a disproportionate number of deaths. Invasive breast cancer is believed to evolve from non-invasive ductal carcinoma in situ (DCIS). Detection of triple-negative DCIS (TN-DCIS) is challenging, therefore strategies to study molecular events governing progression of pre-invasive TN-DCIS to invasive TNBC are needed. Here, we study a canine TN-DCIS progression and investigate the DNA methylation landscape of normal breast tissue, atypical ductal hyperplasia (ADH), DCIS and invasive breast cancer. We report hypo- and hypermethylation of genes within functional categories related to cancer such as transcriptional regulation, apoptosis, signal transduction, and cell migration. DNA methylation changes associated with cancer-related genes become more pronounced at invasive breast cancer stage. Importantly, we identify invasive-only and DCIS-specific DNA methylation alterations that could potentially determine which lesions progress to invasive cancer and which could remain as pre-invasive DCIS. Changes in DNA methylation during TN-DCIS progression in this canine model correspond with gene expression patterns in human breast tissues. This study provides evidence for utilizing methylation status of gene candidates to define late-stage (DCIS and invasive), invasive stage only or DCIS stage only of TN-DCIS progression.},
}
@article {pmid32050925,
year = {2020},
author = {Dettogni, RS and Stur, E and Laus, AC and da Costa Vieira, RA and Marques, MMC and Santana, IVV and Pulido, JZ and Ribeiro, LF and de Jesus Parmanhani, N and Agostini, LP and Dos Reis, RS and de Vargas Wolfgramm Dos Santos, E and Alves, LNR and Garcia, FM and Santos, JA and do Prado Ventorim, D and Reis, RM and Louro, ID},
title = {Potential biomarkers of ductal carcinoma in situ progression.},
journal = {BMC cancer},
volume = {20},
number = {1},
pages = {119},
pmid = {32050925},
issn = {1471-2407},
support = {0468/2015//Funda&#xe7;&#xe3;o Estadual de Amparo &#xe0; Pesquisa do Estado do Esp&#xed;rito Santo/ ; 66141494/2014//Funda&#xe7;&#xe3;o Estadual de Amparo &#xe0; Pesquisa do Estado do Esp&#xed;rito Santo/ ; 66271126/2014//Funda&#xe7;&#xe3;o Estadual de Amparo &#xe0; Pesquisa do Estado do Esp&#xed;rito Santo/ ; 0698/2015//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Espirito Santo-Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior (FAPES-CAPES)/ ; },
mesh = {Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Carcinoma, Ductal, Breast/*diagnosis/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics/metabolism ; Computational Biology ; Disease Progression ; Disease Susceptibility ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Protein Interaction Mapping ; Protein Interaction Maps ; Transcriptome ; },
abstract = {BACKGROUND: Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.<br><br>METHODS: In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter&#xae; PanCancer Pathways panel of NanoString Technologies.<br><br>RESULTS: The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis.<br><br>CONCLUSIONS: We propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.},
}
@article {pmid32050826,
year = {2020},
author = {Mostyka, M and Jessurun, J and Matrai, C},
title = {Sarcoid-Like Granulomatosis in a Patient With Breast Cancer Mimicking Refractory Metastatic Disease.},
journal = {International journal of surgical pathology},
volume = {28},
number = {6},
pages = {668-671},
doi = {10.1177/1066896920905887},
pmid = {32050826},
issn = {1940-2465},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Female ; Granuloma, Respiratory Tract/chemically induced/*pathology ; Humans ; Lung/pathology ; Pulmonary Fibrosis/chemically induced/pathology ; },
abstract = {Sarcoid-like granulomatosis is a known but rare adverse reaction to immune checkpoint inhibitors and chemotherapy in the treatment of advanced solid tumors. We present a case of a 29-year-old female with a pathologically confirmed poorly differentiated invasive ductal carcinoma of the breast with presumed metastases to the lungs, hilar lymph nodes, liver, and spleen. Despite appropriate chemotherapy, the patient developed pulmonary lesions that were interpreted on imaging studies as progression of malignancy. Autopsy revealed disseminated sarcoid-like granulomatosis with multiple noncaseating granulomata with associated fibrosis in the lungs, liver, and spleen. No residual invasive carcinoma or metastatic disease was identified. This case illustrates the difficulty in differentiating this nonneoplastic process from progressive disease in the clinical setting.},
}
@article {pmid32043593,
year = {2020},
author = {Shahir, M and Mahmoud Hashemi, S and Asadirad, A and Varahram, M and Kazempour-Dizaji, M and Folkerts, G and Garssen, J and Adcock, I and Mortaz, E},
title = {Effect of mesenchymal stem cell-derived exosomes on the induction of mouse tolerogenic dendritic cells.},
journal = {Journal of cellular physiology},
volume = {235},
number = {10},
pages = {7043-7055},
pmid = {32043593},
issn = {1097-4652},
mesh = {Animals ; Biomarkers/metabolism ; Cell Communication/immunology ; Cell Proliferation/physiology ; Cells, Cultured ; Cytokines/immunology/metabolism ; Dendritic Cells/*immunology/metabolism ; Exosomes/*immunology/metabolism ; Female ; Immune Tolerance/*immunology ; Immunity/immunology ; Inflammation/immunology/metabolism ; Lymphocytes/immunology/metabolism ; Mesenchymal Stem Cells/*immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; },
abstract = {Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T-cell activation via direct cell-cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T-cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC-derived exosomes on the induction of mouse tolDCs, murine adipose-derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick-TC kits. BM-derived DCs (BMDCs) were prepared and cocultured with MSCs-derived exosomes (100 μg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1μg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester-labeled BALB/C-derived splenocytes p. Interleukin-6 (IL-6), IL-10, and transforming growth factor-β (TGF-β) release were measured by enzyme-linked immunosorbent assay. MSC-derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells (≤ .05). MSC-derived exosomes decrease IL-6 release but augment IL-10 and TGF-β release (p ≤ .05). Lymphocyte proliferation was decreased (p ≤ .05) in the presence of DCs treated with MSC-derived exosomes. CMSC-derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC-induced immune responses.},
}
@article {pmid32031117,
year = {2020},
author = {Söyleyici, NA and Aslan, F and Avcýkurt, AS and Akgün, GA},
title = {Importance of MACC1 expression in breast cancer and its relationship with pathological prognostic markers.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {63},
number = {1},
pages = {19-24},
doi = {10.4103/IJPM.IJPM_658_19},
pmid = {32031117},
issn = {0974-5130},
mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/surgery ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Middle Aged ; Prognosis ; Trans-Activators/*genetics ; Vascular Endothelial Growth Factor A/genetics ; },
abstract = {BACKGROUND: Metastasis associated colon cancer gene 1 (MACC1) is a gene that was first described as a c-Met transcription regulator causing the progression of colon cancer. In this study, protein and messenger RNA (mRNA) expression of MACC1 in breast cancer and its relationship with clinicopathological prognostic parameters were investigated.<br><br>METHODS: Sixty-six cases with tumors underwent radical mastectomy for invasive ductal carcinoma and 25 control cases operated for mammoplasty were included in the study. In paraffin blocks of tumor and control tissues, MACC1 expression was investigated by the immunohistochemical method and Real-time polymerase chain reaction (Real-Time PCR). In addition, vascular endothelial growth factor (VEGF) expression was examined immunohistochemically in tumor tissues. The relationship between MACC1 expression in tumor tissues, clinicopathological prognostic parameters, and VEGF was investigated.<br><br>RESULTS: In this study, protein and mRNA expressions of MACC1 were found to be higher in tumor tissues compared with normal breast tissues. MACC1 protein expression was also associated with significant poor prognostic markers, such as high histologic grade, ER negativity, and HER2 positivity. However, there was no correlation between MACC1 expression and VEGF.<br><br>CONCLUSION: According to these results, MACC1 expression may be a marker of breast carcinoma as well as an independent predictor of poor prognosis. In addition, MACC1 may not affect angiogenesis in breast cancer or even if it has an effect, it may not be associated with VEGF. However, it would be appropriate to support these results in a larger series by investigating in vivo and in vitro studies.},
}
@article {pmid32031116,
year = {2020},
author = {Varma, K and Chauhan, A and Bhargava, M and Misra, V and Srivastava, S},
title = {Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {63},
number = {1},
pages = {13-18},
doi = {10.4103/IJPM.IJPM_419_19},
pmid = {32031116},
issn = {0974-5130},
mesh = {Breast Neoplasms/classification/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cyclin D1/*genetics ; Female ; Genetic Association Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; beta Catenin/*genetics ; },
abstract = {BACKGROUND: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet.<br><br>MATERIALS AND METHODS: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association.<br><br>RESULTS: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns.<br><br>CONCLUSION: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.},
}
@article {pmid32029638,
year = {2020},
author = {Aminian, A and Zajichek, A and Arterburn, DE and Wolski, KE and Brethauer, SA and Schauer, PR and Nissen, SE and Kattan, MW},
title = {Predicting 10-Year Risk of End-Organ Complications of Type 2 Diabetes With and Without Metabolic Surgery: A Machine Learning Approach.},
journal = {Diabetes care},
volume = {43},
number = {4},
pages = {852-859},
pmid = {32029638},
issn = {1935-5548},
support = {R01 DK105960/DK/NIDDK NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Bariatric Surgery/statistics &amp; numerical data ; Computer Simulation ; Diabetes Complications/*diagnosis/epidemiology/pathology ; Diabetes Mellitus, Type 2/*complications/*diagnosis/epidemiology/*surgery ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; *Machine Learning ; Male ; Middle Aged ; Organs at Risk/pathology ; Prognosis ; Retrospective Studies ; Time Factors ; Young Adult ; },
abstract = {OBJECTIVE: To construct and internally validate prediction models to estimate the risk of long-term end-organ complications and mortality in patients with type 2 diabetes and obesity that can be used to inform treatment decisions for patients and practitioners who are considering metabolic surgery.<br><br>RESEARCH DESIGN AND METHODS: A total of 2,287 patients with type 2 diabetes who underwent metabolic surgery between 1998 and 2017 in the Cleveland Clinic Health System were propensity-matched 1:5 to 11,435 nonsurgical patients with BMI &#x2265;30 kg/m[2] and type 2 diabetes who received usual care with follow-up through December 2018. Multivariable time-to-event regression and random forest machine learning models were built and internally validated using fivefold cross-validation to predict the 10-year risk for four outcomes of interest. The prediction models were programmed to construct user-friendly web-based and smartphone applications of Individualized Diabetes Complications (IDC) Risk Scores for clinical use.<br><br>RESULTS: The prediction tools demonstrated the following discrimination ability based on the area under the receiver operating characteristic curve (1 = perfect discrimination and 0.5 = chance) at 10 years in the surgical and nonsurgical groups, respectively: all-cause mortality (0.79 and 0.81), coronary artery events (0.66 and 0.67), heart failure (0.73 and 0.75), and nephropathy (0.73 and 0.76). When a patient's data are entered into the IDC application, it estimates the individualized 10-year morbidity and mortality risks with and without undergoing metabolic surgery.<br><br>CONCLUSIONS: The IDC Risk Scores can provide personalized evidence-based risk information for patients with type 2 diabetes and obesity about future cardiovascular outcomes and mortality with and without metabolic surgery based on their current status of obesity, diabetes, and related cardiometabolic conditions.},
}
@article {pmid32019280,
year = {2020},
author = {Wu, J and Ding, S and Lin, L and Fei, X and Lin, C and Andriani, L and Goh, C and Huang, J and Hong, J and Gao, W and Zhu, S and Wang, H and Huang, O and Chen, X and He, J and Li, Y and Shen, K and Chen, W and Zhu, L},
title = {Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study.},
journal = {Cancer research and treatment},
volume = {52},
number = {3},
pages = {671-679},
pmid = {32019280},
issn = {2005-9256},
support = {81572581//National Natural Science Foundation of China/ ; 81772797//National Natural Science Foundation of China/ ; 14411950200//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 14411950201//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 16411966- 900//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 201840323//Grant of Shanghai municipal commission of health and family planning/ ; },
mesh = {Adenocarcinoma, Mucinous/metabolism/pathology/*therapy ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/metabolism/pathology/*therapy ; Carcinoma, Ductal, Breast/metabolism/pathology/*therapy ; China/epidemiology ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis/epidemiology/genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; *Transcriptome ; },
abstract = {PURPOSE: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).<br><br>MATERIALS AND METHODS: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase-polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.<br><br>RESULTS: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).<br><br>CONCLUSION: RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.},
}
@article {pmid32007118,
year = {2019},
author = {Komaei, I and Guccione, F and Sarra, F and Palmeri, E and Ieni, A and Cardia, R and Currò, G and Navarra, G and Palmeri, R},
title = {Radiation-induced undifferentiated pleomorphic sarcoma of the breast: a rare but serious complication following breast-conserving therapy. A case report and literature review.},
journal = {Il Giornale di chirurgia},
volume = {40},
number = {6},
pages = {544-550},
pmid = {32007118},
issn = {1971-145X},
mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/*etiology/pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/drug therapy/*radiotherapy/surgery ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide/administration &amp; dosage ; Diagnosis, Differential ; Epirubicin/administration &amp; dosage ; Female ; Humans ; Letrozole/administration &amp; dosage ; Mastectomy ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis ; Neoplasms, Radiation-Induced/diagnosis/*etiology/pathology/therapy ; Photons ; Radiotherapy, High-Energy/*adverse effects ; Sarcoma/diagnosis/*etiology/pathology/therapy ; Ultrasonography, Mammary ; },
abstract = {BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) of the breast is an extremely rare, but aggressive subtype of sarcoma that can develop in radiotherapy (RT)-treated breast cancer patients. Due to the low incidence, there are many uncertainties regarding the adequate management of these tumors. We present a rare case of radiation-induced UPS in a 63-year-old woman who had undergone breast conserving therapy for invasive ductal carcinoma of the left breast, six years prior to presentation.<br><br>CASE PRESENTATION: A 63-year-old woman presented with a rapidly growing left breast mass. She had been diagnosed with invasive ductal carcinoma of the left breast for which she underwent a left upper outer quadrantectomy and ipsilateral axillary dissection followed by RT, six years previously. During her routine oncologic follow-up, the mammography revealed a dense, nodular opacity with microcalcifications. The breast ultrasound (US) confirmed the presence of the nodule. US-guided fine needle aspiration biopsy was performed and the diagnosis of UPS was made, the reason for which the patient underwent wide local excision of the left breast.<br><br>CONCLUSION: The diagnosis of RT-induced UPS is challenging and often missed due to the low incidence, long latency period, unspecific imaging findings, and difficulties in clinical and histological detection of these lesions. These tumors should be considered in differential diagnoses of rapidly-growing breast masses in previously RT-treated breast cancer patients, as they can mimic the local recurrence of the primary tumor. Since the prevalence of breast-conserving surgery followed by RT has been increasing, the careful monitoring of at risk patients is of utmost importance, as UPSs are highly aggressive tumors associated with very poor outcomes.},
}
@article {pmid31992198,
year = {2020},
author = {Assefa, T and Zhang, J and Chowda-Reddy, RV and Moran Lauter, AN and Singh, A and O'Rourke, JA and Graham, MA and Singh, AK},
title = {Deconstructing the genetic architecture of iron deficiency chlorosis in soybean using genome-wide approaches.},
journal = {BMC plant biology},
volume = {20},
number = {1},
pages = {42},
pmid = {31992198},
issn = {1471-2229},
support = {NA//Iowa Soybean Association/ ; NA//Iowa State University/ ; NA//North Central Soybean Research Program (US)/ ; NA//Agricultural Research Service/ ; NA//National Institute of Food and Agriculture/ ; },
mesh = {Epistasis, Genetic ; Gene Expression Profiling ; Genes, Plant ; Genome, Plant ; *Genome-Wide Association Study ; Iron/*metabolism ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Seed Bank ; Glycine max/*genetics ; Stress, Physiological/*genetics ; },
abstract = {BACKGROUND: Iron (Fe) is an essential micronutrient for plant growth and development. Iron deficiency chlorosis (IDC), caused by calcareous soils or high soil pH, can limit iron availability, negatively affecting soybean (Glycine max) yield. This study leverages genome-wide association study (GWAS) and a genome-wide epistatic study (GWES) with previous gene expression studies to identify regions of the soybean genome important in iron deficiency tolerance.<br><br>RESULTS: A GWAS and a GWES were performed using 460 diverse soybean PI lines from 27 countries, in field and hydroponic iron stress conditions, using more than 36,000 single nucleotide polymorphism (SNP) markers. Combining this approach with available RNA-sequencing data identified significant markers, genomic regions, and novel genes associated with or responding to iron deficiency. Sixty-nine genomic regions associated with IDC tolerance were identified across 19 chromosomes via the GWAS, including the major-effect quantitative trait locus (QTL) on chromosome Gm03. Cluster analysis of significant SNPs in this region deconstructed this historically prominent QTL into four distinct linkage blocks, enabling the identification of multiple candidate genes for iron chlorosis tolerance. The complementary GWES identified SNPs in this region interacting with nine other genomic regions, providing the first evidence of epistatic interactions impacting iron deficiency tolerance.<br><br>CONCLUSIONS: This study demonstrates that integrating cutting edge genome wide association (GWA), genome wide epistasis (GWE), and gene expression studies is a powerful strategy to identify novel iron tolerance QTL and candidate loci from diverse germplasm. Crops, unlike model species, have undergone selection for thousands of years, constraining and/or enhancing stress responses. Leveraging genomics-enabled approaches to study these adaptations is essential for future crop improvement.},
}
@article {pmid31992119,
year = {2020},
author = {Billena, C and Padia, S and O'Brien, B and Knoble, J and Gokhale, A and Rajagopalan, M},
title = {Radiation recall dermatitis after treatment of stage IV breast cancer with nivolumab: a case report.},
journal = {Immunotherapy},
volume = {12},
number = {2},
pages = {123-130},
doi = {10.2217/imt-2019-0020},
pmid = {31992119},
issn = {1750-7448},
mesh = {Aged ; Antineoplastic Agents, Immunological/*therapeutic use ; Breast Neoplasms/complications/*drug therapy/*radiotherapy ; Carcinoma, Ductal, Breast/complications/*drug therapy/*radiotherapy ; Female ; Humans ; Nivolumab/*therapeutic use ; Radiodermatitis/complications/*etiology ; Radiotherapy, Adjuvant ; },
abstract = {Radiation recall dermatitis (RRD) is an uncommon dermatologic reaction provoked notably by chemotherapy in an area of skin irradiated weeks to years prior. We report a case of RRD with nivolumab in a woman with breast cancer. The patient was diagnosed with invasive ductal carcinoma of the left breast with an isolated spinal metastasis approached in an oligometastatic fashion with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant radiotherapy. Unfortunately, after progression of bony metastases treated with radiotherapy, the patient received nivolumab and subsequently developed a rash corresponding to the adjuvant radiation field. This case highlights the unpredictable nature and characteristic rash of RRD. It is an important differential diagnosis for multidisciplinary teams who also see chemotherapy-induced dermatitis and immune-related adverse events.},
}
@article {pmid31980982,
year = {2020},
author = {Zhao, Y and Wang, Y and Zhu, F and Zhang, J and Ma, X and Zhang, D},
title = {Gene expression profiling revealed MCM3 to be a better marker than Ki67 in prognosis of invasive ductal breast carcinoma patients.},
journal = {Clinical and experimental medicine},
volume = {20},
number = {2},
pages = {249-259},
pmid = {31980982},
issn = {1591-9528},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/*genetics/pathology/therapy ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/*genetics ; Middle Aged ; Minichromosome Maintenance Complex Component 3/*genetics ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; },
abstract = {Invasive ductal carcinoma (IDC) is the most common breast cancer. Our study used gene microarray data to select differentially expressed genes between normal and IDC mammary tissues. From these, we selected genes related to the proliferation of tumor cells and compared their prognostic value with known biomarker Ki67 for IDC. Analysis of publicly available Gene Expression Omnibus (GEO) data revealed 24 differentially expressed genes (DEGs) in normal and 31 DEGS in IDC tissues that were used for further analyses. Gene chip analysis software was used to identify DEGs. DEG profiles were confirmed using quantitative PCR (qPCR). DEG functions where shown to be related to cell proliferation. We confirmed MCM3 expression using immunohistochemical staining in 45 IDC patients. The relationship between MCM3 expression and survival was investigated using Kaplan-Meier survival curves and Cox proportional hazard regression models. A total of 1307 differentially expressed genes were identified between IDC and normal tissues, which were enriched in 32 Gene Ontology (GO) terms and 9 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. qPCR demonstrated that both COL1A1 and MCM3 were significantly up-regulated in IDC tissues, of which only MCM3 was related to cell proliferation. Ki67 is closely associated with the tumor grade, ER status, PR status and HER2 status, while MCM3 was shown to relate to tumor size, lymph node, and PR status. There was significant association between survival and MCM3, but not for Ki67. High MCM3 expression demonstrated statistically significant associations with poor prognosis in IDC patients. Findings from the gene microarray data analysis confirmed that MCM3 is associated with the response to cell proliferation. MCM3 represents a better proliferation marker than Ki67 making it a valuable prognostic tool that is independent of ER and HER2 status.},
}
@article {pmid31941968,
year = {2020},
author = {Elmetwali, T and Salman, A and Wei, W and Hussain, SA and Young, LS and Palmer, DH},
title = {CD40L membrane retention enhances the immunostimulatory effects of CD40 ligation.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {342},
pmid = {31941968},
issn = {2045-2322},
mesh = {Antigens, CD/metabolism ; Antigens, Neoplasm/metabolism ; Apoptosis/drug effects ; CD40 Antigens/metabolism ; CD40 Ligand/genetics/*metabolism/pharmacology ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Line, Tumor ; Cell Membrane/*metabolism ; Cell Proliferation ; Dendritic Cells/cytology/immunology/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Genetic Vectors/genetics/metabolism ; Humans ; Immunoglobulins/metabolism ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Leukocytes, Mononuclear/cytology/metabolism ; Membrane Glycoproteins/metabolism ; T-Lymphocytes/cytology/*immunology/metabolism ; Urinary Bladder Neoplasms/immunology/metabolism/pathology ; CD83 Antigen ; },
abstract = {In carcinomas, the nature of CD40 ligand shapes the outcome of CD40 ligation. To date, the consequences of membrane-bound CD40L (mCD40L) on its immune-stimulatory function are unknown. Here, we examined the impact of mCD40L versus soluble CD40L (sCD40L) on T24 bladder carcinoma gene expression profiling. Of 410 differentially expressed genes, 286 were upregulated and 124 downregulated by mCD40L versus sCD40L. Gene ontology enrichment analysis revealed immune-stimulatory function as the most significant enriched biological process affected by upregulated transcripts, while those downregulated were critical for cell growth and division. Furthermore, immature dendritic cells (iDC) responded to mCD40L with enhanced maturation and activation over sCD40L evidenced by higher expression levels of CD83, CD86, HLA-DR and CD54, increased secretion of IL12 and IL10 and higher tumour-antigen (TA) uptake capacity. Furthermore, autologus CD3+ T cells responded to TA-loaded mCD40L-activated DC with increased proliferation and cytotoxic response (CD107a and IFN-γ-producing CD3+ CD8+ T cells) to the tumour-loaded autologous PBMCs compared to sCD40L. Thus, these data indicate that mCD40L enhances the immunostimulatory capacity over sCD40L. Furthermore, the ability of mCD40L to also directly induce cell death in CD40-expressing carcinomas, subsequently releasing tumour-specific antigens into the tumour microenvironment highlights the potential for mCD40L as a multi-faceted anti-cancer immunotherapeutic.},
}
@article {pmid31937300,
year = {2020},
author = {Westwood, ML and O'Donnell, AJ and Schneider, P and Albery, GF and Prior, KF and Reece, SE},
title = {Testing possible causes of gametocyte reduction in temporally out-of-synch malaria infections.},
journal = {Malaria journal},
volume = {19},
number = {1},
pages = {17},
pmid = {31937300},
issn = {1475-2875},
support = {/WT_/Wellcome Trust/United Kingdom ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Animals ; *Circadian Rhythm/immunology ; Erythrocytes/*parasitology ; Female ; Flow Cytometry ; Gametogenesis/physiology ; Linear Models ; Malaria/blood/immunology/*parasitology ; Male ; Merozoites/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Plasmodium chabaudi/genetics/growth &amp; development/immunology/*physiology ; Random Allocation ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Tumor Necrosis Factor-alpha/*administration &amp; dosage/blood/immunology ; },
abstract = {BACKGROUND: The intraerythrocytic development cycle (IDC) of the rodent malaria Plasmodium chabaudi is coordinated with host circadian rhythms. When this coordination is disrupted, parasites suffer a 50% reduction in both asexual stages and sexual stage gametocytes over the acute phase of infection. Reduced gametocyte density may not simply follow from a loss of asexuals because investment into gametocytes ("conversion rate") is a plastic trait; furthermore, the densities of both asexuals and gametocytes are highly dynamic during infection. Hence, the reasons for the reduction of gametocytes in infections that are out-of-synch with host circadian rhythms remain unclear. Here, two explanations are tested: first, whether out-of-synch parasites reduce their conversion rate to prioritize asexual replication via reproductive restraint; second, whether out-of-synch gametocytes experience elevated clearance by the host's circadian immune responses.<br><br>METHODS: First, conversion rate data were analysed from a previous experiment comparing infections of P. chabaudi that were in-synch or 12&#xa0;h out-of-synch with host circadian rhythms. Second, three new experiments examined whether the inflammatory cytokine TNF varies in its gametocytocidal efficacy according to host time-of-day and gametocyte age.<br><br>RESULTS: There was no evidence that parasites reduce conversion or that their gametocytes become more vulnerable to TNF when out-of-synch with host circadian rhythms.<br><br>CONCLUSIONS: The factors causing the reduction of gametocytes in out-of-synch infections remain mysterious. Candidates for future investigation include alternative rhythmic factors involved in innate immune responses and the rhythmicity in essential resources required for gametocyte development. Explaining why it matters for gametocytes to be synchronized to host circadian rhythms might suggest novel approaches to blocking transmission.},
}
@article {pmid31932496,
year = {2020},
author = {Jelacic, TM and Ribot, WJ and Chua, J and Boyer, AE and Woolfitt, AR and Barr, JR and Friedlander, AM},
title = {Human Innate Immune Cells Respond Differentially to Poly-γ-Glutamic Acid Polymers from Bacillus anthracis and Nonpathogenic Bacillus Species.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {204},
number = {5},
pages = {1263-1273},
pmid = {31932496},
issn = {1550-6606},
support = {CC999999/ImCDC/Intramural CDC HHS/United States ; },
mesh = {Bacillus anthracis/*immunology ; Bacillus licheniformis/*immunology ; Bacillus subtilis/*immunology ; Cytokines/immunology ; Dendritic Cells/*immunology ; Female ; Humans ; *Immunity, Innate ; Macrophages/*immunology ; Male ; Monocytes/*immunology ; Polyglutamic Acid/*immunology ; },
abstract = {The poly-γ-glutamic acid (PGA) capsule produced by Bacillus anthracis is composed entirely of d-isomer glutamic acid, whereas nonpathogenic Bacillus species produce mixed d-, l-isomer PGAs. To determine if B. anthracis PGA confers a pathogenic advantage over other PGAs, we compared the responses of human innate immune cells to B. anthracis PGA and PGAs from nonpathogenic B. subtilis subsp. chungkookjang and B. licheniformis Monocytes and immature dendritic cells (iDCs) responded differentially to the PGAs, with B. anthracis PGA being least stimulatory and B. licheniformis PGA most stimulatory. All three elicited IL-8 and IL-6 from monocytes, but B. subtilis PGA also elicited IL-10 and TNF-α, whereas B. licheniformis PGA elicited all those plus IL-1β. Similarly, all three PGAs elicited IL-8 from iDCs, but B. subtilis PGA also elicited IL-6, and B. licheniformis PGA elicited those plus IL-12p70, IL-10, IL-1β, and TNF-α. Only B. licheniformis PGA induced dendritic cell maturation. TLR assays also yielded differential results. B. subtilis PGA and B. licheniformis PGA both elicited more TLR2 signal than B. anthracis PGA, but only responses to B. subtilis PGA were affected by a TLR6 neutralizing Ab. B. licheniformis PGA elicited more TLR4 signal than B. anthracis PGA, whereas B. subtilis PGA elicited none. B. anthracis PGA persisted longer in high m.w. form in monocyte and iDC cultures than the other PGAs. Reducing the m.w. of B. anthracis PGA reduced monocytes' cytokine responses. We conclude that B. anthracis PGA is recognized less effectively by innate immune cells than PGAs from nonpathogenic Bacillus species, resulting in failure to induce a robust host response, which may contribute to anthrax pathogenesis.},
}
@article {pmid31931856,
year = {2020},
author = {Yoosuf, N and Navarro, JF and Salmén, F and Ståhl, PL and Daub, CO},
title = {Identification and transfer of spatial transcriptomics signatures for cancer diagnosis.},
journal = {Breast cancer research : BCR},
volume = {22},
number = {1},
pages = {6},
pmid = {31931856},
issn = {1465-542X},
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/classification/*diagnosis/genetics ; Carcinoma, Ductal, Breast/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Female ; Humans ; *Machine Learning ; Molecular Typing/*methods ; ROC Curve ; Spatial Analysis ; *Transcriptome ; },
abstract = {BACKGROUND: Distinguishing ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) regions in clinical biopsies constitutes a diagnostic challenge. Spatial transcriptomics (ST) is an in situ capturing method, which allows quantification and visualization of transcriptomes in individual tissue sections. In the past, studies have shown that breast cancer samples can be used to study their transcriptomes with spatial resolution in individual tissue sections. Previously, supervised machine learning methods were used in clinical studies to predict the clinical outcomes for cancer types.<br><br>METHODS: We used four publicly available ST breast cancer datasets from breast tissue sections annotated by pathologists as non-malignant, DCIS, or IDC. We trained and tested a machine learning method (support vector machine) based on the expert annotation as well as based on automatic selection of cell types by their transcriptome profiles.<br><br>RESULTS: We identified expression signatures for expert annotated regions (non-malignant, DCIS, and IDC) and build machine learning models. Classification results for 798 expression signature transcripts showed high coincidence with the expert pathologist annotation for DCIS (100%) and IDC (96%). Extending our analysis to include all 25,179 expressed transcripts resulted in an accuracy of 99% for DCIS and 98% for IDC. Further, classification based on an automatically identified expression signature covering all ST spots of tissue sections resulted in prediction accuracy of 95% for DCIS and 91% for IDC.<br><br>CONCLUSIONS: This concept study suggest that the ST signatures learned from expert selected breast cancer tissue sections can be used to identify breast cancer regions in whole tissue sections including regions not trained on. Furthermore, the identified expression signatures can classify cancer regions in tissue sections not used for training with high accuracy. Expert-generated but even automatically generated cancer signatures from ST data might be able to classify breast cancer regions and provide clinical decision support for pathologists in the future.},
}
@article {pmid31929965,
year = {2019},
author = {Lin, L and Wang, X and Tang, C and Liang, J},
title = {Clinical Characteristics and Prognosis of Gastrointestinal Metastases in Solid Tumor Patients: A Retrospective Study and Review of Literatures.},
journal = {Analytical cellular pathology (Amsterdam)},
volume = {2019},
number = {},
pages = {4508756},
pmid = {31929965},
issn = {2210-7185},
mesh = {Adenocarcinoma/mortality/pathology/*secondary ; Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal/mortality/pathology/*secondary ; Female ; Gastrointestinal Neoplasms/mortality/*secondary ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*pathology ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms/mortality/*pathology ; },
abstract = {BACKGROUND: According to the literature and our experience, patients with gastrointestinal metastases are relatively rare. Numerous case reports and literature reviews have been reported. We present one of the larger case series of gastrointestinal metastases.<br><br>OBJECTIVES: To explore the clinical characteristics and prognosis of patients with gastrointestinal tract metastases, which are rare metastatic sites.<br><br>METHODS: Patients with gastrointestinal metastases in the setting of stage IV primary carcinomas treated at Beijing Ditan Hospital and Peking University International Hospital from November 1992 to August 2017 were included in this study. The diagnosis of gastrointestinal tract metastases was based on histopathology.<br><br>RESULTS: 30 patients (median age 56 years, 56.7% female) were included. The most common primary carcinomas associated with gastrointestinal metastases were breast (11 patients, 36.7%), stomach (9 patients, 30.0%), and lung (4 patients, 13.3%) cancer. The major pathological types were adenocarcinoma (16 patients, 53.3%) and ductal carcinoma (9 patients, 30.0%). Ten patients (33.3%) underwent local gastrointestinal treatment, and 20 patients (66.7%) underwent nonlocal treatment (involving chemotherapy alone or best supportive care). For breast cancer patients and gastric cancer patients who underwent local therapy, a significant survival advantage was observed (p = 0.001 and p = 0.012, respectively). The presence of other common metastases was identified as an independent poor prognostic factor through multivariate analysis with a HR (hazard ratio) of survival of 0.182 (95% confidence interval (CI) 0.11-0.523, p = 0.031).<br><br>CONCLUSION: Gastrointestinal metastases are most frequently from breast invasive ductal carcinoma. The presentation of other common metastases with gastrointestinal metastasis indicates poor prognosis, and selected patients may benefit from surgical intervention.},
}
@article {pmid31929443,
year = {2020},
author = {Eckert, L and Mattia, L and Patel, S and Okumura, R and Reynolds, P and Stuiver, I},
title = {Reducing the Risk of Indwelling Catheter-Associated Urinary Tract Infection in Female Patients by Implementing an Alternative Female External Urinary Collection Device: A Quality Improvement Project.},
journal = {Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society},
volume = {47},
number = {1},
pages = {50-53},
doi = {10.1097/WON.0000000000000601},
pmid = {31929443},
issn = {1528-3976},
mesh = {Adult ; California ; Catheter-Related Infections/prevention &amp; control ; Catheters, Indwelling/*adverse effects/microbiology ; Female ; Humans ; Quality Improvement ; Urinary Tract Infections/*prevention &amp; control ; Urine Specimen Collection/methods/*standards/statistics &amp; numerical data ; },
abstract = {PURPOSE: The purpose of this quality improvement project was to reduce catheter-associated urinary tract infection (CAUTI) risk for female patients by implementing a female external urinary collection (FEUC) device with suction as an alternative to indwelling catheter (IDC).<br><br>PARTICIPANTS AND SETTING: Participants were female patients admitted to our 386-bed community hospital in Southern California and who required urinary management.<br><br>APPROACH: We implemented a comprehensive CAUTI prevention program in 2014 that was in place for 1.5 years before this project was started. The CAUTI prevention program was based on the US Center for Disease Control and Prevention's CAUTI prevention recommendations. To supplement our CAUTI prevention efforts in our female patients, we implemented the FEUC device in our intensive care, telemetry, medical-surgical, orthopedic, and acute rehabilitations inpatient care units. Indwelling catheter use and CAUTI cases were identified by our Infection Prevention department.<br><br>OUTCOMES: Prior to introduction of the FEUC device, in 2015, the baseline female IDC utilization rate was 31.7% (7181 IDC device-days/22,656 patient-days) and the female CAUTI rate was 1.11 (8 cases/7181 IDC device-days) per 1000 days. Following introduction of the device, both rates declined. In 2016, the IDC utilization rate was 29.7% (P = .000) and the CAUTI rate was 0% (P =.005). We continued to observe a reduction in 2017 IDC utilization rates of 26% (P = .000); the 2017 CAUTI rate of 0.90 was not significantly different to our prior year rate (P = .726).<br><br>IMPLICATIONS FOR PRACTICE: We found that the introduction of the FEUC device reduced the risk for CAUTI. We will continue to prioritize the use of external devices for urinary management to help reduce the risk of our patients developing CAUTI.},
}
@article {pmid31927471,
year = {2020},
author = {Mema, E and Schnabel, F and Chun, J and Kaplowitz, E and Price, A and Goodgal, J and Moy, L},
title = {The relationship of breast density in mammography and magnetic resonance imaging in women with triple negative breast cancer.},
journal = {European journal of radiology},
volume = {124},
number = {},
pages = {108813},
doi = {10.1016/j.ejrad.2020.108813},
pmid = {31927471},
issn = {1872-7727},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Breast Density/*physiology ; Cohort Studies ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Middle Aged ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/*diagnostic imaging ; Young Adult ; },
abstract = {PURPOSE: To evaluate the relationship between mammographic density, background parenchymal enhancement and fibroglandular tissue on MRI in women with triple negative breast cancer (TNBC) compared to women with non-triple negative breast cancer (non-TNBC).<br><br>METHODS: The institutional Breast Cancer Database was queried to identify the clinicopathologic and imaging characteristics among women who underwent mammography and breast MRI between 2010-2018. Statistical analyses included Pearson's Chi Square, Wilcoxon Rank-Sum and logistic regression.<br><br>RESULTS: Of 2995 women, 225 (7.5 %) had TNBC with a median age of 60 years (23-96) and median follow-up of 5.69 years. Compared to women with non-TNBC, TNBC was associated with African-American race 36/225 (16 %), BRCA1,2 positivity 34/225 (15.1 %), previous history of breast cancer 35/225 (15.6 %), presenting on breast exam 126/225 (56 %) or MRI 13/225 (5.8 %), palpability 133/225 (59.1 %), more invasive ductal carcinoma (IDC) 208/225 (92.4 %), higher stage (stage III) 37/225 (16.5 %), higher grade (grade 3) 186/225 (82.7 %) (all p < 0.001), lower mammographic breast density (MBD) 18/225 (8 %) (p = 0.04), lower fibroglandular tissue (FGT) 17/225 (7.6 %) (p = 0.01), and lower background parenchymal enhancement (BPE) 89/225 (39.8 %) (p = 0.02). Nine of 225 (4 %) women with TNBC experienced recurrence with no significant association with MBD, FGT, or BPE. There was no significant difference in median age of our TNBC and non-TNBC cohorts.<br><br>CONCLUSIONS: The higher proportion of women with lower MBD, FGT and BPE in women with TNBC suggests that MBD, amount of FGT and degree of BPE may be associated with breast cancer risk in women with TNBC.},
}
@article {pmid31907974,
year = {2020},
author = {DeVaux, RS and Ropri, AS and Grimm, SL and Hall, PA and Herrera, EO and Chittur, SV and Smith, WP and Coarfa, C and Behbod, F and Herschkowitz, JI},
title = {Long noncoding RNA BHLHE40-AS1 promotes early breast cancer progression through modulating IL-6/STAT3 signaling.},
journal = {Journal of cellular biochemistry},
volume = {121},
number = {7},
pages = {3465-3478},
pmid = {31907974},
issn = {1097-4644},
support = {R01 CA207445/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R21 CA185460/CA/NCI NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; },
mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Interleukin-6/*genetics ; Neoplasm Invasiveness ; RNA, Antisense/*genetics ; RNA, Long Noncoding/*genetics ; STAT3 Transcription Factor/*metabolism ; Signal Transduction ; Tumor Microenvironment ; },
abstract = {Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive breast cancer. Only a small percentage of DCIS cases are predicted to progress; however, there is no method to determine which DCIS lesions will remain innocuous from those that will become invasive disease. Therefore, DCIS is treated aggressively creating a current state of overdiagnosis and overtreatment. There is a critical need to identify functional determinants of progression of DCIS to invasive ductal carcinoma (IDC). Interrogating biopsies from five patients with contiguous DCIS and IDC lesions, we have shown that expression of the long noncoding RNA BHLHE40-AS1 increases with disease progression. BHLHE40-AS1 expression supports DCIS cell proliferation, motility, and invasive potential. Mechanistically, BHLHE40-AS1 modulates interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) activity and a proinflammatory cytokine signature, in part through interaction with interleukin enhancer-binding factor 3. These data suggest that BHLHE40-AS1 supports early breast cancer progression by engaging STAT3 signaling, creating an immune-permissive microenvironment.},
}
@article {pmid31902979,
year = {2019},
author = {Sultan, G and Zubair, S and Tayubi, IA and Dahms, HU and Madar, IH},
title = {Towards the early detection of ductal carcinoma (a common type of breast cancer) using biomarkers linked to the PPAR(γ) signaling pathway.},
journal = {Bioinformation},
volume = {15},
number = {11},
pages = {799-805},
pmid = {31902979},
issn = {0973-2063},
abstract = {Breast cancer is a leading cause of morbidity and mortality among women comprising about 12% females worldwide. The underlying alteration in the gene expression, molecular mechanism and metabolic pathways responsible for incidence and progression of breast tumorigenesis are yet not completely understood. In the present study, potential biomarker genes involved in the early progression for early diagnosis of breast cancer has been detailed. Regulation and Gene profiling of Ductal Carcinoma In-situ (DCIS), Invasive Ductal Carcinoma (IDC) and healthy samples have been analyzed to follow their expression pattern employing normalization, statistical calculation, DEGs annotation and Protein-Protein Interaction (PPI) network. We have performed a comparative study on differentially expressed genes among Healthy vs DCIS, Healthy vsIDC and DCIS vs IDC. We found MCM102 and SLC12A8as consistently over-expressed and LEP, SORBS1, SFRP1, PLIN1, FABP4, RBP4, CD300LG, ID4, CRYAB, ECRG4, G0S2, FMO2, ADAMTS5, CAV1, CAV2, ABCA8, MAMDC2, IGFBP6, CLDN11, TGFBR3as under-expressed genes in all the 3 conditions categorized for pre-invasive and invasive ductal breast carcinoma. These genes were further studied for the active pathways where PPAR(γ) signaling pathway was found to be significantly involved. The gene expression profile database can be a potential tool in the early diagnosis of breast cancer.},
}
@article {pmid31902119,
year = {2020},
author = {Acun, T and Senses, KM},
title = {Downregulation of DNAJC10 (ERDJ5) is associated with poor survival in breast cancer.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {27},
number = {3},
pages = {483-489},
pmid = {31902119},
issn = {1880-4233},
support = {2017-50737594-02//B&#xfc;lent Ecevit &#xdc;niversitesi/ ; 217S251//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;tirma Kurumu/ ; },
mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*mortality/pathology ; DNA Copy Number Variations ; *DNA Methylation ; Down-Regulation ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; HSP40 Heat-Shock Proteins/genetics/*metabolism ; Humans ; *Mutation ; Prognosis ; Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; Survival Rate ; },
abstract = {BACKGROUND: DNAJC10 (ERDJ5), a member of HSP40 family, was considered as an anti-oncogenic gene in neuroblastoma, prostate and colon cancers. But, the role and importance of DNAJC10 gene in breast cancer is currently unknown. In this study, in vitro/in vivo expression, biomarker potential and genetic/epigenetic alterations of DNAJC10 were analyzed in breast cancer.<br><br>METHODS: Real-time qRT-PCR and immunohistochemistry methods were used to determine the expression level of DNAJC10 gene in breast cancer cell lines and clinical samples. The Kaplan-Meier plotter was used to evaluate the survival prognostic value of DNAJC10 mRNA expression in breast cancer patients. Mutation screening software and methylation-specific PCR were used to screen genetic alterations and methylation status of DNAJC10 promoter regions, respectively.<br><br>RESULTS: DNAJC10 mRNA expression was significantly reduced in 3 out of 4 breast cancer cell lines compared to the nontumorigenic mammary epithelial cell line (MCF 10A). DNAJC10 protein expression was significantly less frequent in invasive ductal carcinoma samples (n&#x2009;=&#x2009;121) compared with adjacent normal breast tissues (n&#x2009;=&#x2009;32) (p&#x2009;<&#x2009;0.0001). Downregulation of DNAJC10 mRNA was associated with poor overall survival (OS) (n&#x2009;=&#x2009;626) (p&#x2009;=&#x2009;0.0096) and relapse-free survival (n&#x2009;=&#x2009;1764) (p&#x2009;=&#x2009;5.3e-12). According to the COSMIC and cBioPortal databases, point mutations and copy number variations of DNAJC10 were very rare in breast cancer samples. Besides, no genetic alterations on the experimentally validated promoter regions were found in breast cell lines. CpG island located in the promoter regions of DNAJC10 gene was found to be frequently hypomethylated in breast cell lines.<br><br>CONCLUSIONS: In the light of previous knowledge regarding the role of DNAJC10 in carcinogenesis, findings of this study suggest that DNAJC10 is a potential diagnostic/prognostic biomarker and tumor suppressor candidate for breast cancer. Epigenetic factors other than promoter methylation could contribute to the downregulation of DNAJC10 expression.},
}
@article {pmid31894281,
year = {2020},
author = {Zhao, C and Zheng, S and Yan, Z and Deng, Z and Wang, R and Zhang, B},
title = {CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2.},
journal = {Oncology reports},
volume = {43},
number = {2},
pages = {571-580},
doi = {10.3892/or.2019.7426},
pmid = {31894281},
issn = {1791-2431},
mesh = {Adult ; Aged ; Animals ; Annexin A2/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Chemokines, CC/*metabolism ; Disease Progression ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/metabolism/*pathology/*secondary ; MCF-7 Cells ; Mice ; Middle Aged ; Neoplasm Transplantation ; Tumor Burden ; },
abstract = {Chemokine (C‑C motif) ligand 18 (CCL18) is derived from breast tumor‑associated macrophages (TAMs), which are primarily a macrophage subpopulation with an M2 phenotype. CCL18 binds to its receptor, PYK2 N‑terminal domain interacting receptor 1 (Nir1), and promotes tumor progression and metastasis by inducing epithelial‑mesenchymal transition (EMT) via the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer cells. Recent research shows that Annexin A2 (AnxA2) plays a significant role in the invasion, metastasis, angiogenesis, proliferation, F‑actin polymerization and multidrug resistance to chemotherapy of breast cancer. The present study aimed to elucidate the molecular mechanisms by which CCL18 promotes breast cancer progression through AnxA2 which are not fully understood. Western blot analysis showed that the expression of AnxA2 was upregulated in highly invasive breast cancer cell lines and invasive ductal carcinoma. Furthermore, through chemotaxis, scratch, Matrigel invasion, and spontaneous metastasis assays, it was demonstrated that AnxA2 enhanced the invasion of breast cancer cells and the metastasis of human breast cancer cells to lungs of SCID mice with CCL18 stimulation. Cellular F‑actin measurement assay showed that reduction of AnxA2 suppressed CCL18‑induced F‑actin polymerization though phosphorylation of integrin β1 in breast cancer cells. Immunofluorescence and western blot analysis revealed that AnxA2 promoted CCL18‑induced EMT via the PI3K/Akt/GSK3β/Snail signaling pathway, and LY294002 inhibited the phosphorylation of AnxA2 in vitro. In brief, AnxA2, as a downstream molecule of Nir 1 binding to CCL18, promotes invasion and metastasis by EMT through the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer. This study suggests that AnxA2 is a potential anti‑invasion/metastasis target for therapeutic intervention in breast cancer.},
}
@article {pmid31876826,
year = {2020},
author = {Phan Sy, O and Rouchy, RC and De Leiris, N and Nika, E and Djaileb, L},
title = {FDG PET/CT of a Supraclavicular Silicone Granuloma at Follow-up of a Breast Carcinoma.},
journal = {Clinical nuclear medicine},
volume = {45},
number = {3},
pages = {e169-e170},
doi = {10.1097/RLU.0000000000002894},
pmid = {31876826},
issn = {1536-0229},
mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/complications/*surgery ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Granuloma/*diagnostic imaging/*etiology/pathology ; Humans ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Silicones/*adverse effects ; },
abstract = {We report herein the case of a 33-year-old woman who was referred for FDG PET/CT staging prior to pregnancy after a 4-year lost to follow-up for a breast invasive ductal carcinoma (pT2N1 SBRII). FDG PET/CT revealed right supraclavicular lymphadenopathy potentially caused by breast carcinoma recurrence. No additional site was involved. Supraclavicular ultrasonography showed typical "snowstorm" appearance. MRI revealed signs of breast implant intracapsular rupture and signal intensity of silicone within a supraclavicular node. Fine-needle aspiration and microbiopsy of adenopathy finally confirmed silicone granuloma and ruled out breast cancer recurrence.},
}
@article {pmid31871301,
year = {2020},
author = {Chen, G and Ding, XF and Pressley, K and Bouamar, H and Wang, B and Zheng, G and Broome, LE and Nazarullah, A and Brenner, AJ and Kaklamani, V and Jatoi, I and Sun, LZ},
title = {Everolimus Inhibits the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer Via Downregulation of MMP9 Expression.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {26},
number = {6},
pages = {1486-1496},
pmid = {31871301},
issn = {1557-3265},
support = {P30 CA054174/CA/NCI NIH HHS/United States ; R01 CA192564/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Down-Regulation ; Everolimus/*pharmacology ; Female ; Humans ; Matrix Metalloproteinase 9/chemistry/*metabolism ; Mice ; Mice, Nude ; Mice, Transgenic ; Receptor, ErbB-2/genetics/metabolism ; Spheroids, Cellular/drug effects/metabolism/pathology ; Xenograft Model Antitumor Assays ; },
abstract = {PURPOSE: We evaluated the role of everolimus in the prevention of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) progression.<br><br>EXPERIMENTAL DESIGN: The effects of everolimus on breast cancer cell invasion, DCIS formation, and DCIS progression to IDC were investigated in a 3D cell culturing model, intraductal DCIS xenograft model, and spontaneous MMTV-Her2/neu mouse model. The effect of everolimus on matrix metalloproteinase 9 (MMP9) expression was determined with Western blotting and IHC in these models and in patients with DCIS before and after a window trial with rapamycin. Whether MMP9 mediates the inhibition of DCIS progression to IDC by everolimus was investigated with knockdown or overexpression of MMP9 in breast cancer cells.<br><br>RESULTS: Everolimus significantly inhibited the invasion of human breast cancer cells in vitro. Daily intragastric treatment with everolimus for 7 days significantly reduced the number of invasive lesions from intraductal DCIS foci and inhibited DCIS progression to IDC in the MMTV-Her2/neu mouse mammary tumor model. Mechanistically, everolimus treatment decreased the expression of MMP9 in the in vitro and in vivo models, and in breast tissues from patients with DCIS treated with rapamycin for 1 week. Moreover, overexpression of MMP9 stimulated the invasion, whereas knockdown of MMP9 inhibited the invasion of breast cancer cell-formed spheroids in vitro and DCIS in vivo. Knockdown of MMP9 also nullified the invasion inhibition by everolimus in vitro and in vivo.<br><br>CONCLUSIONS: Targeting mTORC1 can inhibit DCIS progression to IDC via MMP9 and may be a potential strategy for DCIS or early-stage IDC therapy.},
}
@article {pmid31861274,
year = {2019},
author = {Micus, S and Kirsten, I and Haupt, M and Gresser, GT},
title = {Analysis of Hot Bar Soldering, Insulation Displacement Connections (IDC), and Anisotropic Conductive Adhesives (ACA), for the Automated Production of Smart Textiles.},
journal = {Sensors (Basel, Switzerland)},
volume = {20},
number = {1},
pages = {},
pmid = {31861274},
issn = {1424-8220},
abstract = {Despite all the growth forecasts of the smart textiles market, there is no stable automated manufacturing process for attaching classic electronics to textiles. The great amount of manual production steps causes high prices, which slow down market growth. During the production process, the contacting step offers the greatest potential to reduce manual manufacturing steps. For this reason, we have analyzed various contacting methods for electronic parts on conductive yarns that have a high potential for automation. The chosen methods were thermode soldering, insulation-displacement connectors and anisotropic conductive adhesives. In order to ensure reliable mechanical contacting, the samples were tested in a peeling experiment. The examination of the contact resistances took place in the context of a resistance test using four-wire measuring technology.},
}
@article {pmid31856858,
year = {2019},
author = {Wan, L and Liu, T and Hong, Z and Pan, Y and Sizemore, ST and Zhang, J and Ma, Z},
title = {NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis.},
journal = {Breast cancer research : BCR},
volume = {21},
number = {1},
pages = {148},
pmid = {31856858},
issn = {1465-542X},
mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Nedd4 Ubiquitin Protein Ligases/*genetics/metabolism ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Receptor, IGF Type 1/metabolism ; Young Adult ; },
abstract = {BACKGROUND: A role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the growth and progression of breast cancer (BC) and to evaluate the clinicopathologic and prognostic significance of NEDD4.<br><br>METHODS: The impact of NEDD4 expression in BC cell growth was determined by Cell Counting Kit-8 and colony formation assays. Formalin-fixed paraffin-embedded specimens were collected from 133 adjacent normal tissues (ANTs), 445&#x2009;BC cases composed of pre-invasive ductal carcinoma in situ (DCIS, n&#x2009;=&#x2009;37), invasive ductal carcinomas (IDC, n&#x2009;=&#x2009;408, 226 without and 182 with lymph node metastasis), and 116 invaded lymph nodes. The expression of NEDD4 was analyzed by immunohistochemistry. The association between NEDD4 expression and clinicopathological characteristics was analyzed by chi-square test. Survival was evaluated using the Kaplan-Meier method, and curves were compared using a log-rank test. Univariate and multivariate analyses were performed using the Cox regression method.<br><br>RESULTS: NEDD4 promoted BC growth in vitro. In clinical retrospective studies, 16.5% of ANTs (22/133) demonstrated positive NEDD4 staining. Strikingly, the proportion of cases showing NEDD4-positive staining increased to 51.4% (19/37) in DCIS, 58.4% (132/226) in IDC without lymph node metastasis, and 73.1% (133/182) in BC with lymph node metastasis (BCLNM). In addition, NEDD4-positive staining was associated with clinical parameters, including tumor size (P&#x2009;=&#x2009;0.030), nodal status (P&#x2009;=&#x2009;0.001), estrogen receptor status (P&#x2009;=&#x2009;0.035), and progesterone receptor status (P&#x2009;=&#x2009;0.023). Moreover, subset analysis in BCLNM revealed that high NEDD4 expression correlated with an elevated risk of relapse (P&#x2009;=&#x2009;0.0276). Further, NEDD4 expression was an independent prognostic predictor. Lastly, the rates for 10-year overall survival and disease-free survival were significantly lower in patients with positive NEDD4 staining than those in BC patients with negative NEDD4 staining BC (P&#x2009;=&#x2009;0.0024 and P&#x2009;=&#x2009;0.0011, respectively).<br><br>CONCLUSIONS: NEDD4 expression is elevated in BC and is associated with BC growth. NEDD4 correlated with clinicopathological parameters and predicts a poor prognosis. Thus, NEDD4 is a potential biomarker of poor prognosis and a potential therapeutic target for BC treatment.},
}
@article {pmid31856344,
year = {2020},
author = {Giles, M and Graham, L and Ball, J and King, J and Watts, W and Harris, A and Oldmeadow, C and Ling, R and Paul, M and O'Brien, A and Parker, V and Wiggers, J and Foureur, M},
title = {Implementation of a multifaceted nurse-led intervention to reduce indwelling urinary catheter use in four Australian hospitals: A pre- and postintervention study.},
journal = {Journal of clinical nursing},
volume = {29},
number = {5-6},
pages = {872-886},
doi = {10.1111/jocn.15142},
pmid = {31856344},
issn = {1365-2702},
support = {//NSW Ministry of Health Translational Research Grants Scheme/ ; },
mesh = {Adult ; Catheter-Related Infections/etiology/*prevention &amp; control ; Catheters, Indwelling/*adverse effects ; Controlled Before-After Studies ; Female ; Humans ; Male ; New South Wales ; Patient Care Bundles/*nursing ; Practice Patterns, Nurses' ; Urinary Catheters/*adverse effects ; Urinary Tract Infections/etiology/*prevention &amp; control ; },
abstract = {AIMS AND OBJECTIVES: This study aimed to reduce indwelling urinary catheter (IDC) use and duration through implementation of a multifaceted "bundled" care intervention.<br><br>BACKGROUND: Indwelling urinary catheters present a risk for patients through the potential development of catheter-associated urinary tract infection (CAUTI), with duration of IDC a key risk factor. Catheter-associated urinary tract infection is considered preventable yet accounts for over a third of all hospital-acquired infections. The most effective CAUTI reduction strategy is to avoid IDC use where ever possible and to remove the IDC as early as appropriate.<br><br>DESIGN: A cluster-controlled pre- and poststudy at a facility level with a phased intervention implementation approach.<br><br>METHODS: A multifaceted intervention involving a "No CAUTI" catheter care bundle was implemented, in 4 acute-care hospitals, 2 in metropolitan and 2 in rural locations, in New South Wales, Australia. Indwelling urinary catheter point prevalence and duration data were collected at the bedside on 1,630 adult inpatients at preintervention and 1,677 and 1,551 at 4 and 9&#xa0;months postintervention. This study is presented in line with the StaRI checklist (see Appendix S1).<br><br>RESULTS: A nonsignificant trend towards reduction in IDC prevalence was identified, from 12% preintervention to 10% of all inpatients at 4 and 9&#xa0;months. Variability in preintervention IDC prevalence existed across hospitals (8%-16%). Variability in reduction was evident across hospitals at 4&#xa0;months (between -2% and 4%) and 9&#xa0;months (between 0%-8%). Hospitals with higher preintervention prevalence showed larger decreases, up to 50% when preintervention prevalence was 16%. Indwelling urinary catheter duration increased as more of the short-term IDC placements were avoided.<br><br>CONCLUSIONS: Implementation of a multifaceted intervention resulted in reduced IDC use in four acute-care hospitals in Australia. This result was not statistically significant but did reflect a positive trend of reduction. There was a significant reduction in short-term IDC use at 9&#xa0;months postintervention.<br><br>Clinical nurse leaders can effectively implement change strategies that influence patient outcomes. Implementation of the evidence-based "No CAUTI" bundle increased awareness of appropriate indications and provided nurses with the tools to inform decision-making related to insertion and removal of IDCs in acute inpatient settings. Working in partnership with inpatients and the multidisciplinary team is essential in minimising acute-care IDC use.},
}
@article {pmid31856180,
year = {2019},
author = {Walzer, KA and Fradin, H and Emerson, LY and Corcoran, DL and Chi, JT},
title = {Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging.},
journal = {PLoS genetics},
volume = {15},
number = {12},
pages = {e1008506},
pmid = {31856180},
issn = {1553-7404},
mesh = {Gene Expression Profiling ; Gene Expression Regulation, Developmental ; In Situ Hybridization, Fluorescence/*methods ; Life Cycle Stages ; Microfluidic Analytical Techniques ; Multigene Family ; Plasmodium falciparum/genetics/*growth &amp; development ; Protozoan Proteins/*genetics ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; },
abstract = {Malaria parasites follow a complex life cycle that consists of multiple stages that span from the human host to the mosquito vector. Among the species causing malaria, Plasmodium falciparum is the most lethal, with clinical symptoms manifesting during the intraerythrocytic developmental cycle (IDC). During the IDC, P. falciparum progresses through a synchronous and continuous cascade of transcriptional programming previously established using population analyses. While individual parasites are known to exhibit transcriptional variations to evade the host immune system or commit to a sexual fate, such rare expression heterogeneity is largely undetectable on a population level. Therefore, we combined single-cell RNA-sequencing (scRNA-seq) on a microfluidic platform and fluorescence imaging to delineate the transcriptional variations among individual parasites during late asexual and sexual stages. The comparison between asexual and sexual parasites uncovered a set of previously undefined sex-specific genes. Asexual parasites were segregated into three distinct clusters based on the differential expression of genes encoding SERAs, rhoptry proteins, and EXP2 plus transporters. Multiple pseudotime analyses revealed that these stage-specific transitions are distinct. RNA fluorescent in situ hybridization of cluster-specific genes validated distinct stage-specific expression and transitions during the IDC and defined the highly variable transcriptional pattern of EXP2. Additionally, these analyses indicated huge variations in the stage-specific transcript levels among parasites. Overall, scRNA-seq and RNA-FISH of P. falciparum revealed distinct stage transitions and unexpected degrees of heterogeneity with potential impact on transcriptional regulation during the IDC and adaptive responses to the host.},
}
@article {pmid31849934,
year = {2019},
author = {Alexia, C and Cren, M and Louis-Plence, P and Vo, DN and El Ahmadi, Y and Dufourcq-Lopez, E and Lu, ZY and Hernandez, J and Shamilov, F and Chernysheva, O and Vasilieva, M and Vorotnikov, I and Vishnevskay, Y and Tupitsyn, N and Rossi, JF and Villalba, M},
title = {Polyoxidonium[®] Activates Cytotoxic Lymphocyte Responses Through Dendritic Cell Maturation: Clinical Effects in Breast Cancer.},
journal = {Frontiers in immunology},
volume = {10},
number = {},
pages = {2693},
pmid = {31849934},
issn = {1664-3224},
mesh = {Adenocarcinoma/*drug therapy/immunology ; Adjuvants, Immunologic/*therapeutic use ; Adult ; Aged ; Breast Neoplasms/*drug therapy/immunology ; Cell Differentiation/drug effects/immunology ; Chemotherapy, Adjuvant/methods ; Dendritic Cells/*drug effects/immunology ; Female ; Humans ; Killer Cells, Natural/drug effects/immunology ; Lymphocyte Activation/drug effects/immunology ; Lymphocytes, Tumor-Infiltrating/drug effects/immunology ; Middle Aged ; Neoadjuvant Therapy/methods ; Piperazines/*therapeutic use ; Polymers/*therapeutic use ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; },
abstract = {Immunotherapy, which is seen as a major tool for cancer treatment, requires, in some cases, the presence of several agents to maximize its effects. Adjuvants can enhance the effect of other agents. However, despite their long-time use, only a few adjuvants are licensed today, and their use in cancer treatment is rare. Azoximer bromide, marketed under the trade name Polyoxidonium® (PO), is a copolymer of N-oxidized 1,4-ethylenepiperazine and (N-carboxyethyl)-1,4-ethylene piperazinium bromide. It has been described as an immune adjuvant and immunomodulator that is clinically used with excellent tolerance. PO is used in the treatment and prophylaxis of diseases connected with damage to the immune system, and there is interest in testing it in antitumor therapy. We show here that PO treatment for 1 week induced positive pathological changes in 6 out of 20 patients with breast cancer, including complete response in a triple-negative patient. This correlated with an increased tumor CD4[+] T-lymphocyte infiltration. The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. We reveal that PO increases T-cell proliferation in vitro without negative effects on any activation marker. PO does not affect dendritic cell (DC) viability and increases the expansion of immature DC (iDC) and mature DC (mDC) at 100 μg/ml, and it stimulates expression of several DC co-stimulatory molecules, inducing the proliferation of allogeneic T cells. In contrast, PO decreases DC viability when added at day 5 post-expansion. PO is not toxic for NK cells at doses up to 100 μM and does not affect their activation, maturation, and cytotoxicity but tends to increase degranulation. This could be beneficial against target cells that show low sensitivity to NK cells, e.g., solid tumor cells. Finally, we have found great variability in PO response between donors. In summary, our in vitro results show that PO increases the number of costimulatory molecules on DC that prime T cells, favoring the production of effector T cells. This may support the future clinical development of PO in cancer treatment.},
}
@article {pmid31849088,
year = {2020},
author = {Arispe Angulo, KR and Jawa, Z and Visotcky, A and Majidi, SS and Chitambar, CR and Jorns, JM},
title = {A high mitotic score in breast cancer after neoadjuvant chemotherapy is predictive of outcome and associated with a distinct morphology.},
journal = {Histopathology},
volume = {76},
number = {5},
pages = {661-670},
doi = {10.1111/his.14049},
pmid = {31849088},
issn = {1365-2559},
mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology ; Chemotherapy, Adjuvant/methods ; Female ; Humans ; Middle Aged ; Mitotic Index ; Neoadjuvant Therapy/methods ; Retrospective Studies ; Treatment Outcome ; },
abstract = {AIMS: Neoadjuvant chemotherapy (NAC) is frequently used for the treatment of breast cancer. We sought to analyse the clinical, morphological and immunohistochemical features of tumours from patients who did not achieve pathological complete response following NAC.<br><br>METHODS AND RESULTS: We identified stage I-III post-NAC breast cancers from surgical resections (2000-2016) with evaluable residual invasive carcinoma [ypT1a(m) or greater and &#x2265;15% tumour cellularity]. One hundred and forty-three tumours from 142 patients were included. On univariable analysis, a high (score 3) post-NAC mitotic score (as compared with 1 or 2) was significantly associated with invasive ductal carcinoma (IDC) subtype (P&#xa0;=&#xa0;0.023), high grade, pushing borders with zones of necrosis, hormone receptor and triple-negative status, lack of hormonal therapy, higher cellularity (P&#xa0;<&#xa0;0.001), and a higher percentage of tumour-infiltrating lymphocytes (P&#xa0;=&#xa0;0.016). Multivariable analysis showed a high post-NAC mitotic score to be significantly associated with recurrence, distant metastasis, and shortened survival (hazard ratios of 5.73, 4.49, and 3.68, respectively). High post-NAC mitotic score tumours (n&#xa0;=&#xa0;32) were IDC and had a high Ki67 proliferation index (median, 55%). Of these, 24 (75%) had pushing borders with zones of necrosis; 19 (79.2%) of these had necrosis on preoperative imaging, and 24 (75%), 15 (46.9%) and four (12.5%) lacked androgen receptor, GATA-3 and cytokeratin 18 expression, respectively.<br><br>CONCLUSIONS: High post-NAC mitotic score breast cancers cause high morbidity and mortality, frequently have pushing borders and zones of necrosis, and may show loss of common 'breast cancer markers'. Our findings support that necrosis in pretreatment studies and post-NAC mitotic score should be routinely reported, as they offer significant additional prognostic information to guide management.},
}
@article {pmid31844635,
year = {2019},
author = {Redell, M and Sierra-Hoffman, M and Assi, M and Bochan, M and Chansolme, D and Gandhi, A and Sheridan, K and Soosaipillai, I and Walsh, T and Massey, J},
title = {The CHROME Study, a Real-world Experience of Single- and Multiple-Dose Oritavancin for Treatment of Gram-Positive Infections.},
journal = {Open forum infectious diseases},
volume = {6},
number = {11},
pages = {ofz479},
pmid = {31844635},
issn = {2328-8957},
abstract = {BACKGROUND: Oritavancin (ORI) is a long-acting lipoglycopeptide indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible Gram-positive (GP) pathogens.<br><br>METHODS: Data collected from a retrospective observational program (2014-2017), Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME), describe the utilization, outcomes, and adverse events (AEs) associated with ORI in 440 patients treated at 26 US sites for ABSSSI and other GP infections.<br><br>RESULTS: Clinical success in evaluable patients receiving at least 1 dose of oritavancin was 88.1% (386/438). In a subgroup of patients who received ORI for skin and soft tissue infections (n = 401) and bacteremia (n = 7), clinical success was achieved in 89.0% and 100%, respectively. A cohort of 32 patients received 2-10 ORI doses separated by no more than 14 days for complicated GP infections. Clinical success was observed in 30 of 32 patients (93.8%), including 10 of 11 (90.9%) patients with bone and joint infections and 7 of 8 (87.5%) patients with osteomyelitis. In the safety evaluable population, the overall rate of AEs was 6.6%.<br><br>CONCLUSIONS: We describe results from a real-world program that includes the largest multicenter, retrospective, observational study in patients who received at least 1 dose of ORI for the treatment of GP infections. This study confirms that ORI is an effective, well-tolerated antibiotic used in single and multiple doses for the treatment of ABSSSIs and complicated GP infections.},
}
@article {pmid31844357,
year = {2019},
author = {Amadi, OF and Okeke, IB and Ndu, IK and Ekwochi, U and Nduagubam, OC and Ezenwosu, OU and Asinobi, IN and Osuorah, CD},
title = {Cancer Mortality in the Niger Delta Region of Nigeria: A Case Study of the University of Port Harcourt Teaching Hospital.},
journal = {Nigerian medical journal : journal of the Nigeria Medical Association},
volume = {60},
number = {5},
pages = {262-267},
pmid = {31844357},
issn = {0300-1652},
abstract = {AIM: The aim of this study is to determine the pattern of cancer mortality (CM) seen in the University of Port Harcourt Teaching Hospital (UPTH) which is a cancer reference center in the Niger Delta Region.<br><br>METHODOLOGY: This is a 6-year retrospective study of cancer-related deaths in UPTH using patients' admission registers in all the wards and emergency units. Furthermore, the death certificates of cases were reviewed.<br><br>RESULTS: Three hundred and sixteen cases of cancer-related deaths occurred, involving 174 females and 142 males, in a female-to-male sex ratio of 1.2:1. All age groups were affected, with age group 40-49 years accounting for the majority (20.6%). CM was seen in all the systems, except the central nervous system. Cancers of the gastrointestinal tract and its accessory organs (liver and gall bladder) caused most mortality (27.9%), in a female-to-male ratio of 0.8:1. The single most involved organ in CM is the female breast (20.6%), distantly followed by mortality due to prostate cancers and hematolymphoid cancers which accounted for 9.2% each. Colorectal cancers accounted for 7.3% of cancer deaths and ranked 4[th]. Cancers of both cervix and stomach each accounted for 5.7% of mortality. The major histologic diagnoses were carcinomas (adenocarcinoma; 36.7%, invasive ductal carcinoma; 20.3%, squamous cell carcinomas; 8.2% and hepatocellular carcinomas; 4.4%). Leukemias and lymphomas accounted for 9.2% of cases, whereas sarcomas accounted for 5.1% of cases.<br><br>CONCLUSION: Infection-related and noninfection-related cancers cause most mortality in UPTH. The 5[th] decade was the most commonly affected, while female breast was the single most involved organ. Breast, prostate and hematolymphoid malignancies are common causes of CM with death from breast occurring earliest. Majority of the deceased were educated, working-class urban dwellers. More advocacies on public acceptance of cancer screening and cancer preventive lifestyles as well as governments' improvement on workforce training and treatment infrastructure will improve the current CM profile in Port Harcourt.},
}
@article {pmid31814295,
year = {2020},
author = {Li, Y and Su, P and Wang, Y and Zhang, H and Liang, Y and Zhang, N and Song, X and Li, X and Li, J and Yang, Q},
title = {Impact of histotypes on preferential organ-specific metastasis in triple-negative breast cancer.},
journal = {Cancer medicine},
volume = {9},
number = {3},
pages = {872-881},
pmid = {31814295},
issn = {2045-7634},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*epidemiology/secondary ; Brain Neoplasms/*epidemiology/secondary ; Breast/pathology ; Carcinoma, Ductal, Breast/*epidemiology/secondary ; Carcinoma, Lobular/*epidemiology/secondary ; Female ; Humans ; Liver Neoplasms/*epidemiology/secondary ; Lung Neoplasms/*epidemiology/secondary ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; SEER Program/statistics &amp; numerical data ; Triple Negative Breast Neoplasms/mortality/*pathology ; Young Adult ; },
abstract = {BACKGROUND: The distant metastasis was the most predictive characters of poor prognosis for triple-negative breast cancer (TNBC). We aimed to evaluate the correlation between patient characters and preferential distant metastatic sites (DMS) and its effects on prognosis.<br><br>METHODS: Using the 2010-2014 Surveillance, Epidemiology, and End Results Program (SEER) data, patients with TNBC were classified into eight histologic subtypes. Patient characters were compared using a chi-squared test. Logistic regression was used for identification of predictive factors. The log-rank testing was utilized with disease-specific survival (DSS) and overall survival (OS) as the primary outcomes.<br><br>RESULTS: A total of 23&#xa0;270 patients with TNBC were involved, including 1544 patients with distant metastatic cancer. Bone metastasis was diagnosed in 559 cases, brain metastasis in 124 cases, liver metastasis found in 369 cases and lung metastasis in 492 cases. Histologic subtypes including metaplastic breast carcinoma and invasive lobular carcinoma showed significant differences in preferential DMS compared with invasive ductal carcinoma. Furthermore, we found different histologic subtypes with specific DMS showed various prognosis. We also evaluated different DMS of specific histologic subtypes showed different prognosis.<br><br>CONCLUSION: Certain histologic subtypes of breast cancer are associated with preferential DMS and prognosis; this knowledge may help to further understand the mechanism of breast cancer metastasis and to monitor the prognosis of patients with TNBC.},
}
@article {pmid31809502,
year = {2019},
author = {Pick, FC and Fish, KE and Biggs, CA and Moses, JP and Moore, G and Boxall, JB},
title = {Application of enhanced assimilable organic carbon method across operational drinking water systems.},
journal = {PloS one},
volume = {14},
number = {12},
pages = {e0225477},
pmid = {31809502},
issn = {1932-6203},
mesh = {Carbon/*analysis/metabolism ; Drinking Water/chemistry/microbiology/*standards ; Flow Cytometry/methods ; Organic Chemicals/*analysis/metabolism ; Pseudomonas fluorescens/metabolism ; Reproducibility of Results ; Spirillum/metabolism ; Water Microbiology/*standards ; Water Purification ; Water Quality/*standards ; },
abstract = {Assimilable organic carbon (AOC) is known to correlate with microbial growth, which can consequently degrade drinking water quality. Despite this, there is no standardised AOC test that can be applied to drinking water distribution systems (DWDS). Herein we report the development of a quick, robust AOC that incorporates known strains Pseudomonas fluorescens strain P-17 and Spirillum strain NOX, a higher inoculum volume and enumeration using flow cytometry to generate a quicker (total test time reduced from 14 to 8 days), robust method. We apply the developed AOC test to twenty drinking water treatment works (WTW) to validate the method reproducibility and resolution across a wide range of AOC concentrations. Subsequently, AOC was quantified at 32 sample points, over four DWDS, for a year in order to identify sinks and sources of AOC in operative networks. Application of the developed AOC protocol provided a previously unavailable insight and novel evidence of pipes and service reservoirs exhibiting different AOC and regrowth behaviour. Observed correlations between AOC and microbial growth highlight the importance of monitoring AOC as an integral part of managing drinking water quality at the consumers tap.},
}
@article {pmid31791269,
year = {2019},
author = {Lee, CH and Hsieh, JC and Wu, TM and Yeh, TS and Wang, HM and Lin, YC and Chen, JS and Lee, CL and Huang, WK and Hung, TM and Yen, TT and Chan, SC and Chou, WC and Kuan, FC and Hu, CC and Chang, PH},
title = {Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.},
journal = {BMC cancer},
volume = {19},
number = {1},
pages = {1167},
pmid = {31791269},
issn = {1471-2407},
support = {CMRPG2D0171, CMRPG2D0172, CMRPG2G0681, CMRPG2G0682//Chang Gung Memorial Hospital/ ; CMRPG2D0173//Chang Gung Memorial Hospital/ ; PMRPG3G0791, CMRPG3G0771, CORPG3F0731, CMRPG3E1631-33//Chang Gung Memorial Hospital/ ; CMRPG3G1131-1133, CMRPG3H0871-73//Chang Gung Memorial Hospital/ ; MOST-108-2628-B-182A-001//Ministry of Science and Technology, Taiwan/ ; MOST-107-2314-B-182-053, MOST-104-2314-B-182-031-MY3//Ministry of Science and Technology, Taiwan/ ; },
mesh = {AC133 Antigen/immunology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*mortality/pathology ; Carcinoma, Ductal, Breast/drug therapy/*mortality/pathology ; Cell Count ; Female ; Humans ; Liquid Biopsy ; Middle Aged ; Neoplastic Cells, Circulating/immunology/*pathology ; Neoplastic Stem Cells/immunology/*pathology ; Prognosis ; Prospective Studies ; Survival Analysis ; Treatment Outcome ; },
abstract = {BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy.<br><br>METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM[+]Hoechst[+]CD45[-] cells and cCSCs as CD133[+]EpCAM[+]Hoechst[+]CD45[-] cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses.<br><br>RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p&#xa0;<&#x2009;0.001), overall survival (OS; median: 27.7&#x2009;months vs. not reached, p&#x2009;<&#x2009;0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0&#x2009;months, p&#x2009;<&#x2009;0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS.<br><br>CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.},
}
@article {pmid31789065,
year = {2020},
author = {Tijani, S and Sharma, K and Yuen, H and Shaaban, A},
title = {Metastatic "Ductal Carcinoma In Situ-Like" Lobular Carcinoma in a Lymph Node: A Case Report and Review of the Literature.},
journal = {International journal of surgical pathology},
volume = {28},
number = {4},
pages = {436-439},
doi = {10.1177/1066896919888744},
pmid = {31789065},
issn = {1940-2465},
mesh = {Axilla ; Biomarkers, Tumor/analysis/metabolism ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/secondary/surgery ; Carcinoma, Lobular/*diagnosis/secondary/surgery ; Diagnosis, Differential ; Diagnostic Errors/prevention &amp; control ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy ; Middle Aged ; },
abstract = {Metastatic breast cancer resembling ductal carcinoma in situ (DCIS) is a rare phenomenon. In this article, we present a unique case of metastatic lobular carcinoma with DCIS-like morphology in the left axillary lymph nodes of a 52-year-old female. She presented with 2 lesions in the left breast on mammography, and a mastectomy with axillary lymph node dissection was performed. Gross examination showed a 3.5 × 2.5 × 1.0 cm indistinct tumor in the lower outer quadrant and a 2.5 × 2.5 × 1.8 cm tumor in the upper outer quadrant. Microscopic assessment revealed a pleomorphic lobular carcinoma in the lower outer quadrant and a grade 2 invasive ductal carcinoma in the upper outer quadrant. Sixteen of the 17 axillary lymph nodes showed metastatic lobular carcinoma with foci of solid and comedo-type DCIS-like features. Immunohistochemical analysis of the primary and metastatic lobular carcinoma showed no expression of E-cadherin and p63 antibodies. To our knowledge, metastatic lobular carcinoma exhibiting this pattern has not been reported. The case suggests that lobular carcinoma can morphologically recreate a primary microenvironment at a distant site and simulate in situ growth. Recognition of this pattern is important to avoid misdiagnosis.},
}
@article {pmid31779581,
year = {2019},
author = {Luo, K and Wang, S and Fu, Y and Zhou, P and Huang, X and Gu, Q and Li, W and Wang, Y and Hu, F and Liu, S},
title = {Rapid genomic DNA variation in newly hybridized carp lineages derived from Cyprinus carpio (♀) × Megalobrama amblycephala (♂).},
journal = {BMC genetics},
volume = {20},
number = {1},
pages = {87},
pmid = {31779581},
issn = {1471-2156},
mesh = {Animals ; Carps/genetics/*physiology ; Evolution, Molecular ; Female ; Fish Proteins/genetics ; *Genetic Variation ; Goldfish/genetics/*physiology ; Homeodomain Proteins/*genetics ; Hybridization, Genetic ; Male ; Multigene Family ; Sequence Analysis, DNA/veterinary ; },
abstract = {BACKGROUND: Distant hybridization can generate changes in phenotypes and genotypes that lead to the formation of new hybrid lineages with genetic variation. In this study, the establishment of two bisexual fertile carp lineages, including the improved diploid common carp (IDC) lineage and the improved diploid scattered mirror carp (IDMC) lineage, from the interspecific hybridization of common carp (Cyprinus carpio, 2n = 100) (♀) × blunt snout bream (Megalobrama amblycephala, 2n = 48) (♂), provided a good platform to investigate the genetic relationship between the parents and their hybrid progenies.<br><br>RESULT: In this study, we investigated the genetic variation of 12 Hox genes in the two types of improved&#xa0;carp lineages derived from common carp (&#x2640;)&#x2009;&#xd7;&#x2009;blunt snout bream (&#x2642;). Hox gene clusters were abundant in the first generation of IDC, but most were not stably inherited in the second generation. In contrast, we did not find obvious mutations in Hox genes in the first generation of IDMC, and almost all the Hox gene clusters were stably inherited from the first generation to the second generation of IDMC. Interestingly, we found obvious recombinant clusters of Hox genes in both&#xa0;improved carp lineages, and partially recombinant clusters of Hox genes were stably inherited from the first generation to the second generation in both types of improved&#xa0;carp lineages. On the other hand, some Hox genes were gradually becoming pseudogenes, and some genes were completely pseudogenised in IDC or IDMC.<br><br>CONCLUSIONS: Our results provided important evidence that distant hybridization produces rapid genomic DNA changes that may or may not be stably inherited, providing novel insights into the function of hybridization in the establishment of improved lineages used as new fish resources for aquaculture.},
}
@article {pmid31765735,
year = {2020},
author = {Morimoto, M and Horikoshi, Y and Nakaso, K and Kurashiki, T and Kitagawa, Y and Hanaki, T and Sakamoto, T and Honjo, S and Umekita, Y and Fujiwara, Y and Matsura, T},
title = {Oncogenic role of TYRO3 receptor tyrosine kinase in the progression of pancreatic cancer.},
journal = {Cancer letters},
volume = {470},
number = {},
pages = {149-160},
doi = {10.1016/j.canlet.2019.11.028},
pmid = {31765735},
issn = {1872-7980},
mesh = {Aged ; Animals ; Carcinogenesis ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; MAP Kinase Signaling System ; Male ; Mice ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Pancreas/pathology ; Pancreatic Neoplasms/mortality/*pathology ; Phosphorylation ; Prognosis ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/*metabolism ; Xenograft Model Antitumor Assays ; },
abstract = {The expression and functions of TYRO3, a member of the TAM receptor tyrosine kinase family, in pancreatic cancer (PC) have not been specifically elucidated. In this study, we confirmed TYRO3 expression in five human PC cell lines (PANC-1, MIA PaCa-2, BxPC-3, AsPC-1, and PK-9) using Western blotting. TYRO3 silencing and overexpression studies have revealed that TYRO3 promotes cell proliferation and invasion in PC via phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK). Using a mouse xenograft model, we showed that tumor growth was significantly suppressed in mice subcutaneously inoculated with TYRO3-knockdown PC cells compared with mice inoculated with control PC cells. Furthermore, TYRO3 expression was examined in PC tissues obtained from 106 patients who underwent pancreatic resection for invasive ductal carcinoma through immunohistochemical staining. TYRO3-positive patients had poor prognoses for overall survival and disease-specific survival compared with TYRO3-negative patients. Multivariate analysis revealed that TYRO3 expression is an independent prognostic factor for overall survival. Our study demonstrates the critical role of TYRO3 in PC progression through Akt and ERK activation and suggests TYRO3 as a novel promising target for therapeutic strategies against PC.},
}
@article {pmid31748977,
year = {2020},
author = {Petry, V and Bonadio, RC and Cagnacci, AQC and Senna, LAL and Campos, RDNG and Cotti, GC and Hoff, PM and Fragoso, MCBV and Estevez-Diz, MDP},
title = {Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li-Fraumeni syndrome).},
journal = {Familial cancer},
volume = {19},
number = {1},
pages = {47-53},
pmid = {31748977},
issn = {1573-7292},
mesh = {Adult ; Brazil/epidemiology ; Breast Neoplasms/genetics/*radiotherapy ; Female ; Fibrosarcoma/epidemiology ; Follow-Up Studies ; *Genes, p53 ; *Germ-Line Mutation ; Humans ; Leiomyosarcoma/epidemiology ; Li-Fraumeni Syndrome/*genetics ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Radiation-Induced/*epidemiology ; Radiotherapy, Adjuvant/adverse effects ; Retrospective Studies ; Young Adult ; },
abstract = {The risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li-Fraumeni syndrome (LFS) or Li-Fraumeni Like (LFL) patients. However, the type of TP53 pathogenic germline variant may possibly influence this risk. TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenic TP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germline TP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were followed by the Hereditary Cancer Group of an academic cancer center. Our primary objective was to evaluate the occurrence of RIMs after adjuvant radiotherapy. Sixteen patients were evaluated; 10 (62.5%) had a germline TP53 p.R337H pathogenic variant. Median age was 39.8 years. Thirteen patients had invasive ductal carcinoma: 8 (61.5%) were hormone receptor-positive; 6 (46.1%), human epithelial growth factor receptor 2 (HER2)-amplified. Three patients had ductal carcinoma in situ. Most patients (N = 12/16, 75%) received adjuvant radiotherapy. After a median follow-up of 52.5 months, 2 patients (2/12, 16.6%) had RIMs. One had a fibrosarcoma and the other, a low-grade leiomyosarcoma. In the group treated with radiotherapy, one distant recurrence was diagnosed (1/12), and no loco-regional recurrence occurred. Among 4 patients who did not receive radiotherapy, 2 presented with loco-regional recurrence. In this cohort of patients with LFS enriched in TP53 p.R337H pathogenic variant, the incidence of RIMs after treatment of localized breast cancer was lower than previous literature. Nevertheless, rates of RIMs were still alarming. Early molecular diagnosis and careful evaluation of treatment risks and benefits are essential for these patients.},
}
@article {pmid31744918,
year = {2019},
author = {Xie, M and Leroy, H and Mascarau, R and Woottum, M and Dupont, M and Ciccone, C and Schmitt, A and Raynaud-Messina, B and Vérollet, C and Bouchet, J and Bracq, L and Benichou, S},
title = {Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction.},
journal = {mBio},
volume = {10},
number = {6},
pages = {},
pmid = {31744918},
issn = {2150-7511},
mesh = {CD4-Positive T-Lymphocytes/metabolism/virology ; Dendritic Cells/metabolism/virology ; HIV Infections/*metabolism/*virology ; HIV-1/*physiology ; Humans ; Macrophages/metabolism/virology ; Myeloid Cells/metabolism/virology ; SAM Domain and HD Domain-Containing Protein 1/*metabolism ; *Viral Tropism ; *Virus Replication ; },
abstract = {Dendritic cells (DCs) and macrophages as well as osteoclasts (OCs) are emerging as target cells of HIV-1 involved in virus transmission, dissemination, and establishment of persistent tissue virus reservoirs. While these myeloid cells are poorly infected by cell-free viruses because of the high expression levels of cellular restriction factors such as SAMHD1, we show here that HIV-1 uses a specific and common cell-to-cell fusion mechanism for virus transfer and dissemination from infected T lymphocytes to the target cells of the myeloid lineage, including immature DCs (iDCs), OCs, and macrophages, but not monocytes and mature DCs. The establishment of contacts with infected T cells leads to heterotypic cell fusion for the fast and massive transfer of viral material into OC and iDC targets, which subsequently triggers homotypic fusion with noninfected neighboring OCs and iDCs for virus dissemination. These two cell-to-cell fusion processes are not restricted by SAMHD1 and allow very efficient spreading of virus in myeloid cells, resulting in the formation of highly virus-productive multinucleated giant cells. These results reveal the cellular mechanism for SAMHD1-independent cell-to-cell spreading of HIV-1 in myeloid cell targets through the formation of the infected multinucleated giant cells observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients.IMPORTANCE We demonstrate that HIV-1 uses a common two-step cell-to-cell fusion mechanism for massive virus transfer from infected T lymphocytes and dissemination to myeloid target cells, including dendritic cells and macrophages as well as osteoclasts. This cell-to-cell infection process bypasses the restriction imposed by the SAMHD1 host cell restriction factor for HIV-1 replication, leading to the formation of highly virus-productive multinucleated giant cells as observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients. Since myeloid cells are emerging as important target cells of HIV-1, these results contribute to a better understanding of the role of these myeloid cells in pathogenesis, including cell-associated virus sexual transmission, cell-to-cell virus spreading, and establishment of long-lived viral tissue reservoirs.},
}
@article {pmid31737920,
year = {2020},
author = {Taylor, AS and Morgan, TM and Wallington, DG and Chinnaiyan, AM and Spratt, DE and Mehra, R},
title = {Correlation between cribriform/intraductal prostatic adenocarcinoma and percent Gleason pattern 4 to a 22-gene genomic classifier.},
journal = {The Prostate},
volume = {80},
number = {2},
pages = {146-152},
pmid = {31737920},
issn = {1097-0045},
support = {P50 CA069568/CA/NCI NIH HHS/United States ; P50 CA186786/CA/NCI NIH HHS/United States ; },
mesh = {Adenocarcinoma/*genetics/*pathology ; Aged ; Biomarkers, Tumor/genetics ; Carcinoma, Ductal/*genetics/*pathology ; Cell Growth Processes/genetics ; Cohort Studies ; Genetic Predisposition to Disease ; Genomics/methods ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/*pathology ; RNA, Neoplasm/*genetics ; },
abstract = {BACKGROUND: The Decipher test measures expression of 22 RNA biomarkers associated with aggressive prostate cancer used to improve risk stratification of patients to help guide management. To date, Decipher's genomic classification has not been extensively correlated with specific histologic growth patterns in prostatic adenocarcinoma. With a growing understanding of the clinical aggressiveness associated with cribriform growth pattern (CF), intraductal carcinoma (IDC), and percent Gleason pattern 4 (G4%), we sought to determine if their presence was associated with an increased genomic risk as measured by the Decipher assay.<br><br>DESIGN: Clinical use of the Decipher assay was performed on the highest Gleason score (GS) tumor nodule of prostatectomy specimens from a prospective cohort of 48 patients, with GS varying from 7 through 9 to help guide clinical risk stratification. The tumors were reviewed for CF, IDC, and G4%, which were then compared to the Decipher score (0-1) and risk stratification (high vs not high).<br><br>RESULTS: The presence of CF/IDC was significantly associated with Decipher risk score (P&#x2009;=&#x2009;.007), with a high-risk Decipher score in 22% vs 56% of patients without or with CF/IDC. On binary logistic regression analysis, G4% (odds ratio [OR]&#xa0;1.04 per percent increase&#xa0;[95% confidence interval [CI], 1.02-1.06];&#xa0;P&#x2009;=&#x2009;.0004) and CF predominant (OR, 9.60&#xa0;[95%CI, 1.48-62.16];&#xa0;P&#x2009;=&#x2009;.02) were significantly associated with a high-risk GC score. IDC did not reach significance (OR, 1.92&#xa0;[95%CI, 0.65-5.67];&#xa0;P&#x2009;=&#x2009;.24).<br><br>CONCLUSIONS: Our findings add to an expanding knowledge base that supports G4% and CF/IDC as molecularly unique and clinically relevant features in prostatic adenocarcinoma. These histologic features should be standardly reported as they are associated with more aggressive prostate cancer. Future work should determine the independent information of these histologic findings that are&#xa0;relative to genomic assessment on long-term outcomes.},
}
@article {pmid31734782,
year = {2020},
author = {Kim, K and Kim, IJ and Pak, K and Kim, SJ and Choi, SJ and Park, H and Kang, T and Kong, IJ and Shin, YB and Kim, H and Yoon, JA},
title = {The feasibility of quantitative parameters of lymphoscintigraphy without significant dermal backflow for the evaluation of lymphedema in post-operative patients with breast cancer.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {47},
number = {5},
pages = {1094-1102},
pmid = {31734782},
issn = {1619-7089},
mesh = {Axilla ; *Breast Neoplasms/diagnostic imaging/surgery ; Feasibility Studies ; Humans ; Lymph Node Excision ; *Lymphedema/diagnostic imaging/etiology ; Lymphoscintigraphy ; Mastectomy ; },
abstract = {PURPOSE: We aimed to evaluate the potential role of quantitative methods associated with lymphoscintigraphy for the assessment of severity of lymphedema post-operatively in patients with breast cancer who did not show definite dermal backflow activity on the lymphoscintigraphy.<br><br>METHODS: We evaluated 47 lymphoscintigraphies without dermal backflow in patients with lymphedema who received a mastectomy and axillary dissection or sentinel lymph node dissection for invasive ductal carcinoma of the breast. The quantitative asymmetry indices (QAIs) of both arms were calculated for each axilla, upper arm, forearm, and the whole arm. The QAI was defined as the radiopharmaceutical uptake ratio of the affected side to the unaffected side. Arm circumference was measured at four locations per arm to identify the maximal circumference difference (MCD) between affected and unaffected sides.<br><br>RESULTS: The total and forearm QAIs of each side arm were significantly higher in the group with above moderate stage lymphedema compared with the mild stage group. Previous radiotherapy also had a significant effect on radiotracer retention expressed as QAI. The MCD was significantly correlated with QAI values of the forearm and the whole arm. The QAI of axillary areas was not significantly correlated with circumferential measurements of the arm.<br><br>CONCLUSIONS: The QAIs have significant value for the diagnosis and severity of lymphedema and may therefore potentially be used as an objective tool for the assessment of lymphedema.},
}
@article {pmid31711023,
year = {2019},
author = {Zhou, J and Tan, H and Bai, Y and Li, J and Lu, Q and Chen, R and Zhang, M and Feng, Q and Wang, M},
title = {Evaluating the HER-2 status of breast cancer using mammography radiomics features.},
journal = {European journal of radiology},
volume = {121},
number = {},
pages = {108718},
doi = {10.1016/j.ejrad.2019.108718},
pmid = {31711023},
issn = {1872-7727},
mesh = {Area Under Curve ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging/*genetics ; Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics ; China ; Female ; Genes, erbB-2/*genetics ; Humans ; Mammography/*methods ; Middle Aged ; Preoperative Care ; ROC Curve ; Sensitivity and Specificity ; Support Vector Machine ; },
abstract = {PURPOSE: The aim of our study was to evaluate the HER-2 status in breast cancer patients using mammography (MG) radiomics features.<br><br>METHODS: A total of 306 Chinese female patients with invasive ductal carcinoma of no special type (IDC-NST) enrolled from January 2013 to July 2018 were divided into a training set (n&#x202f;=&#x202f;244) and a testing set (n&#x202f;=&#x202f;62). One hundred and eighty-six radiomics features were extracted from digital MG images based on the training set. The least absolute shrinkage and selection operator (LASSO) method was used to select the optimal predictive features for HER-2 status from the training set. Both support vector machine (SVM) and logistic regression models were employed based on the selected features. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training set and testing set were used to evaluate the predictive performance of the models.<br><br>RESULTS: Compared with the SVM model, the performance of the logistic regression model using a combination of cranial caudal (CC) and mediolateral oblique (MLO) MG views was optimal. In the training set, the sensitivity, specificity, accuracy and area under the curve (AUC) values of the logistic regression model for evaluating HER-2 status based on quantitative radiomics features were 87.29%, 58.73%, 80.00% and 0.846 (95% confidence interval (CI), 0.800-0.887), respectively, and in the testing set, the values were 73.91%, 68.75%, 77.00% and 0.787 (95% CI, 0.673-0.885), respectively.<br><br>CONCLUSIONS: Radiomics features could be an efficient tool for the preoperative evaluation of HER-2 status in patients with breast cancer.},
}
@article {pmid31710002,
year = {2020},
author = {Zhu, S and Zhao, JG and Chen, JR and Liu, ZH and Sun, GX and Wang, ZP and Ni, YC and Dai, JD and Shen, PF and Zeng, H},
title = {Intraductal carcinoma of the prostate in prostate biopsy samples: correlation with aggressive pathological features after radical prostatectomy and prognostic value in high-risk prostate cancer.},
journal = {Asian journal of andrology},
volume = {22},
number = {5},
pages = {519-525},
pmid = {31710002},
issn = {1745-7262},
mesh = {Aged ; Biopsy ; Carcinoma, Ductal/blood/*pathology/surgery ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Nomograms ; Prognosis ; Proportional Hazards Models ; Prostate/pathology ; Prostate-Specific Antigen/*blood ; Prostatectomy ; Prostatic Neoplasms/blood/*pathology/surgery ; Risk Factors ; Seminal Vesicles/pathology ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive pathological pattern of prostate cancer (PCa). We investigated the association of IDC-P in prostate biopsy (PBx) with several pathological features after radical prostatectomy (RP) and its prognostic value in high-risk PCa. A total of 418 patients with high-risk PCa after RP were included in this study. IDC-P and its architectural patterns were identified according to the 2016 World Health Organization Classification. Chi-squared test and logistic regression were used to investigate the correlation between IDC-P and post-RP pathological features. Kaplan-Meier curves and Cox regression were applied to explore the prognostic value of IDC-P. IDC-P was identified in PBx in 36/418 (8.6%) patients. Logistic regression indicated that IDC-P in PBx was independently associated with several pathological features of RP, including Gleason score 8-10 (P < 0.001), seminal vesicular invasion (P < 0.001), and pathological T (pT) 3a (P = 0.043). Patients with IDC-P in PBx manifested poorer biochemical-free survival (BFS) than those without IDC-P (37.47 months vs not reached, P < 0.001). The addition of IDC-P in several prognostic nomograms could improve the predictive accuracy of these tools. We conclude that IDC-P in PBx is positively associated with several aggressive pathological features after RP in high-risk PCa. In addition, IDC-P in PBx could effectively predict the BFS of high-risk PCa patients after RP.},
}
@article {pmid31706703,
year = {2019},
author = {Quagliarini, F and Mir, AA and Balazs, K and Wierer, M and Dyar, KA and Jouffe, C and Makris, K and Hawe, J and Heinig, M and Filipp, FV and Barish, GD and Uhlenhaut, NH},
title = {Cistromic Reprogramming of the Diurnal Glucocorticoid Hormone Response by High-Fat Diet.},
journal = {Molecular cell},
volume = {76},
number = {4},
pages = {531-545.e5},
pmid = {31706703},
issn = {1097-4164},
support = {K99 CA154887/CA/NCI NIH HHS/United States ; R00 CA154887/CA/NCI NIH HHS/United States ; R01 DK108987/DK/NIDDK NIH HHS/United States ; },
mesh = {Animals ; Blood Glucose/metabolism ; Chromatin/*metabolism ; *Circadian Clocks/genetics ; *Circadian Rhythm/genetics ; *Diet, High-Fat ; Dietary Fats/administration &amp; dosage/blood/*metabolism ; Disease Models, Animal ; *Energy Metabolism/genetics ; Fasting/metabolism ; Gene Expression Regulation ; Glucocorticoids/metabolism ; Gluconeogenesis ; Ligands ; Liver/*metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/blood/genetics/*metabolism ; PPAR alpha/genetics/metabolism ; Postprandial Period ; Receptors, Glucocorticoid/deficiency/genetics/*metabolism ; STAT5 Transcription Factor/genetics/metabolism ; Secretory Pathway ; Signal Transduction ; Time Factors ; Transcription, Genetic ; Triglycerides/blood ; },
abstract = {The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. We show how GR partitions metabolic processes by time-dependent target gene regulation and controls circulating glucose and triglycerides differentially during feeding and fasting. Highlighting the dominant role GR plays in synchronizing circadian amplitudes, we find that the majority of oscillating genes are bound by and depend on GR. This rhythmic pattern is altered by high-fat diet in a ligand-independent manner. We find that the remodeling of oscillatory gene expression and postprandial GR binding results from a concomitant increase of STAT5 co-occupancy in obese mice. Altogether, our findings highlight GR's fundamental role in the rhythmic orchestration of hepatic metabolism.},
}
@article {pmid31677352,
year = {2020},
author = {Chen, HH and Chen, DY and Huang, LG and Chen, YM and Hsieh, CW and Hung, WT and Tang, KT and Chen, G},
title = {Association between periodontitis and the risk of inadequate disease control in patients with rheumatoid arthritis under biological treatment.},
journal = {Journal of clinical periodontology},
volume = {47},
number = {2},
pages = {148-159},
doi = {10.1111/jcpe.13213},
pmid = {31677352},
issn = {1600-051X},
mesh = {Arthritis, Rheumatoid/*complications/*drug therapy/*epidemiology ; Humans ; Periodontitis/*complications/*epidemiology/*therapy ; Prospective Studies ; },
abstract = {AIM: To assess the association between periodontitis (PD) and inadequate disease control (IDC) in patients with rheumatoid arthritis (RA) receiving biological therapy.<br><br>MATERIALS AND METHODS: In total, 111 RA patients receiving biological therapy for at least 3&#xa0;months were assessed for periodontal disease at baseline. RA disease activity was assessed at baseline and at 3&#xa0;months of follow-up. A multivariable logistic regression analysis was used to estimate the association between PD and IDC, adjusting for age, sex, smoking, diabetes, and baseline RA disease activity. An additional exploratory model further controlled for disease characteristics and other medications.<br><br>RESULTS: Among 111 patients, 84 (75.7%) had PD, of whom 37 (44.0%) received periodontal treatment. Thirty-four (40.5%) of PD patients had IDC; 12 (32.4%) of treated PD patients and 22 (46.8%) of untreated patients had IDC, respectively. The ORs (95% CIs) for IDC were 1.45 (0.50-4.23) in PD patients and 1.84 (0.59-5.76) in untreated PD patients. In the exploratory model, the ORs (95% CIs) for IDC were 5.00 (1.19-21.03) in PD patients and 6.26 (1.34-29.34) in untreated PD patients.<br><br>CONCLUSION: This single-centre, prospective study failed to demonstrate a consistently positive correlation between PD and IDC in RA patients receiving biological treatment.},
}
@article {pmid31673038,
year = {2019},
author = {Golberg, A and Sheviryov, J and Solomon, O and Anavy, L and Yakhini, Z},
title = {Molecular harvesting with electroporation for tissue profiling.},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {15750},
pmid = {31673038},
issn = {2045-2322},
mesh = {Animals ; Electroporation/*methods ; Female ; Gene Ontology ; Genomics ; Hep G2 Cells ; Humans ; Kidney/*metabolism/pathology ; Liver/*metabolism/pathology ; Mice ; Mice, Nude ; Neoplasm Proteins/metabolism ; Neoplasms/genetics/metabolism/pathology ; Proteomics ; RNA, Neoplasm/metabolism ; Transplantation, Heterologous ; },
abstract = {Recent developments in personalized medicine are based on molecular measurement steps that guide personally adjusted medical decisions. A central approach to molecular profiling consists of measuring DNA, RNA, and/or proteins in tissue samples, most notably in and around tumors. This measurement yields molecular biomarkers that are potentially predictive of response and of tumor type. Current methods in cancer therapy mostly use tissue biopsy as the starting point of molecular profiling. Tissue biopsies involve a physical resection of a small tissue sample, leading to localized tissue injury, bleeding, inflammation and stress, as well as to an increased risk of metastasis. Here we developed a technology for harvesting biomolecules from tissues using electroporation. We show that tissue electroporation, achieved using a combination of high-voltage short pulses, 50 pulses 500 V cm[-1], 30 µs, 1 Hz, with low-voltage long pulses 50 pulses 50 V cm[-1], 10 ms, delivered at 1 Hz, allows for tissue-specific extraction of RNA and proteins. We specifically tested RNA and protein extraction from excised kidney and liver samples and from excised HepG2 tumors in mice. Further in vivo development of extraction methods based on electroporation can drive novel approaches to the molecular profiling of tumors and of tumor environment and to related diagnosis practices.},
}
@article {pmid31672492,
year = {2020},
author = {Kim, JE and Kim, BG and Jang, Y and Kang, S and Lee, JH and Cho, NH},
title = {The stromal loss of miR-4516 promotes the FOSL1-dependent proliferation and malignancy of triple negative breast cancer.},
journal = {Cancer letters},
volume = {469},
number = {},
pages = {256-265},
doi = {10.1016/j.canlet.2019.10.039},
pmid = {31672492},
issn = {1872-7980},
mesh = {Antineoplastic Agents/pharmacology ; Cancer-Associated Fibroblasts/metabolism/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/drug effects/genetics ; Disease Progression ; Exosome Multienzyme Ribonuclease Complex/genetics ; Exosomes/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MicroRNAs/*genetics ; Proto-Oncogene Proteins c-fos/*genetics ; Stromal Cells/metabolism/pathology ; Triple Negative Breast Neoplasms/*drug therapy/genetics/pathology ; },
abstract = {Stroma-derived exosomal microRNA (exomiR) contributes to tumor progression, however, which remains poorly understood. In our study, we analyzed exomiRs from the cancer-associated fibroblast (CAF) and normal fibroblast (NF) isolated from an invasive ductal carcinoma (IDC) patient and found that the level of microRNA (miR)-4516 was approximately 5-fold lower in CAF-derived exosomes than NF-derived ones. In gene annotation analysis, miR-4516 target genes were mainly associated with the regulation of proliferation. miR-4516 overexpression or mimic treatment suppressed the proliferation of breast cancer cells, especially triple negative breast cancer (TNBC) cells. Among miR-4516 targets, FOSL1 was overexpressed in TNBC cells compared to non-TNBC cells and promoted tumor proliferation. The expression of miR-4516 and FOSL1 was reversely correlated in breast cancer patient tissues. Particularly, TNBC patients with high FOSL1 expression showed a significant poorer survival than those with low FOSL1 expression. Our results show that the loss of miR-4516 from CAF-derived exosomes is associated with FOSL1-dependent TNBC progression and suggest that miR-4516 can be used as an anti-cancer drug for TNBC.},
}
@article {pmid31666416,
year = {2019},
author = {Autenshlyus, AI and Davletova, KI and Studenikina, AA and Mikhaylova, ES and Varaksin, NA and Zhurakovsky, IP and Proskura, AV and Sidorov, SV and Lyakhovich, VV},
title = {[Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type].},
journal = {Biomeditsinskaia khimiia},
volume = {65},
number = {5},
pages = {424-431},
doi = {10.18097/PBMC20196505424},
pmid = {31666416},
issn = {2310-6972},
mesh = {Breast Neoplasms/*immunology ; Carcinoma, Ductal/*immunology ; Cytokines/*immunology ; *Extracellular Matrix ; Female ; Humans ; Lymphatic Metastasis ; *Tumor Microenvironment ; },
abstract = {The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 was determined by the solid-phase enzyme-linked immunosorbent assay. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1β; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.},
}
@article {pmid31661032,
year = {2019},
author = {Klomek, AB},
title = {Prevention of postpartum suicidality in Israel.},
journal = {Israel journal of health policy research},
volume = {8},
number = {1},
pages = {77},
pmid = {31661032},
issn = {2045-4015},
mesh = {Child ; Female ; Humans ; Israel ; Postpartum Period ; Pregnancy ; Risk Factors ; *Suicide ; USSR ; },
abstract = {Postpartum suicidality in Israel had not been systematically studied until the recent important investigation by Glasser and colleagues. The authors review rates, trends, and characteristics of postpartum women who considered, attempted, or completed suicide in Israel. This commentary argues that, although postpartum suicidality is relatively rare, it is extremely tragic-not just for the women, but for the entire family and community. The main aim of this commentary is to emphasize that preventive efforts should continue and expand, especially among at-risk groups. At-risk groups include the youngest age group, postpartum Arab women, and postpartum former Soviet Union immigrants. Identification of women at risk or suffering from postpartum depression (PPD) is mandated in Israel. Efforts should include broader screening for various types of suicide ideation and behavior. Assessments should specifically include passive suicide ideation, active suicide ideation with method, intent, and plan, as well as various types of suicide attempts and preparatory behaviors. In addition, specific interventions formulated on evidence-based psychotherapies should be provided in family practice, obstetric, and pediatric settings. These settings are less stigmatized in comparison to mental health settings. Potential therapies can be (among others) Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT), which are effective in preventing perinatal depression.},
}
@article {pmid31660917,
year = {2019},
author = {Peng, Z and Klomek, AB and Li, L and Su, X and Sillanmäki, L and Chudal, R and Sourander, A},
title = {Associations between Chinese adolescents subjected to traditional and cyber bullying and suicidal ideation, self-harm and suicide attempts.},
journal = {BMC psychiatry},
volume = {19},
number = {1},
pages = {324},
pmid = {31660917},
issn = {1471-244X},
mesh = {Adolescent ; Adolescent Behavior ; Bullying/*statistics &amp; numerical data ; Child ; China/epidemiology ; Crime Victims/*statistics &amp; numerical data ; Cyberbullying/statistics &amp; numerical data ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; Self-Injurious Behavior/*epidemiology/etiology ; Students/statistics &amp; numerical data ; *Suicidal Ideation ; Suicide, Attempted/*statistics &amp; numerical data ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: The incidence of bullying is high among adolescents. Adolescents who were victims of bullying have a higher risk of self-harm and suicidal behavior than adolescents who were non-victims. However, research on suicide and both traditional and cyber bullying was limited in China. Therefore, this study examined the associations between Chinese adolescents who were the victims of traditional and cyber bullying and the prevalence of suicidal ideation, self-harm and suicide attempts.<br><br>METHODS: This was a population-based study of 2647 students (51.2% girls) with a mean age of 13.6&#x2009;&#xb1;&#x2009;1.1&#x2009;years from 10 junior high schools in Shantou, China. Information on bullying victimization, suicidal ideation, self-harm and suicide attempts were collected using a self-administered questionnaire and the psychopathology of the students was assessed using the Strengths and Difficulties Questionnaire (SDQ). The associations were examined with multinomial logistic regression, adjusted for covariates.<br><br>RESULTS: Traditional bullying victimization was reported by 16.7% of the adolescents, cyber bullying victimization by 9.0% and both by 3.5%. The prevalence of suicidal ideation was 23.5%, self-harm was 6.2% and suicide attempts was 4.2%. Psychopathology symptoms were risk factors for suicide ideation only, ideation plus self-harm, self-harm only and suicide attempts. Victims of both traditional and cyber bullying had the highest risk of suicidal ideation only, ideation plus self-harm and suicide attempts, compared to those reporting one form of bullying. Victims of cyber bullying only had the second highest risk of suicidal ideation only and suicidal ideation plus self-harm compared to non-victims.<br><br>CONCLUSIONS: Adolescents who were victims of both traditional and cyber bullying had greater risks of adverse outcomes of suicidal ideation only, suicidal ideation plus self-harm and suicide attempts. The results of the current study suggest that those exposed to both forms of bullying should be routinely screened for suicidal risk. In addition, school-based anti-bully interventions should also target cyber bullying.},
}
@article {pmid31656498,
year = {2019},
author = {Mohammedi, L and Doula, FD and Mesli, F and Senhadji, R},
title = {Cyclin D1 overexpression in Algerian breast cancer women: correlation with CCND1 amplification and clinicopathological parameters.},
journal = {African health sciences},
volume = {19},
number = {2},
pages = {2140-2146},
pmid = {31656498},
issn = {1729-0503},
mesh = {Adult ; Aged ; Algeria ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cyclin D1/*genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Prognosis ; },
abstract = {BACKGROUND: Cyclin D1 which is associated with cell cycle regulation is solidly established as an oncogene with an important pathogenetic role in breast carcinomas.<br><br>OBJECTIVES: The aim of this study was to relate the Cyclin D1 protein overexpression with the amplification of its gene CCND1 in Estrogen Receptors (ER) positive breast carcinomas, in order to investigate the prognostic effect of their aberrations in relation to ER status, also to correlate the Cyclin D1 overexpression with other prognostic parameters.<br><br>MATERIALS AND METHODS: Chromogenic in situ hybridization (CISH) was used to identify CCND1 amplification on formalin-fixed paraffin-embedded invasive ductal carcinoma, in which immunohistochemistry (IHC) had previously been performed in order to evaluate the pathological relevance of Cyclin D1 overexpression in human breast cancer (n = 138).<br><br>RESULTS: CCND1 amplification was identified in 17/138 (12.3%) tumors and 78/138 (56.5%) tumors have overexpressed Cyclin D1. A significant correlation was identified between CCND1 amplification and Cyclin D1 overexpression (P < 0.001) and both Cyclin D1 and CCND1 were related with ER expression.<br><br>CONCLUSION: Our results show a significant correlation between Cyclin D1 overexpression and CCND1 amplification. Overexpression of Cyclin D1was observed in high proportion of breast cancer which should be considered for routine diagnosis.},
}
@article {pmid31647159,
year = {2020},
author = {Seckin, ZI and Brumble, LM and Libertin, CR},
title = {Serologic screening and infectious disease consultation (IDC): Indicated in heart, lung, liver (HLL) solid organ transplants (SOT) for measles, mumps, rubella, and varicella.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {22},
number = {1},
pages = {e13202},
doi = {10.1111/tid.13202},
pmid = {31647159},
issn = {1399-3062},
mesh = {Adult ; Antibodies, Viral/*blood ; Chickenpox/etiology/immunology/prevention &amp; control ; Communicable Disease Control/*methods ; Communicable Diseases/*etiology/immunology ; Humans ; Measles/etiology/immunology/prevention &amp; control ; Mumps/etiology/immunology/prevention &amp; control ; *Organ Transplantation ; *Referral and Consultation ; Retrospective Studies ; Rubella/etiology/immunology/prevention &amp; control ; *Serologic Tests ; Vaccination ; },
abstract = {BACKGROUND: Solid organ transplant (SOT) recipients are a special group of patients who require comprehensive evaluation for preventable infectious diseases before transplantation. The main aim of our study was to investigate the number of heart, lung, and liver (HLL) transplant recipients who were evaluated for their immune status against measles, mumps, rubella (MMR), and varicella (VZV). As a secondary aim, we investigated whether pre-transplant infectious disease consultation (IDC) improves vaccination rates.<br><br>METHODS: This study was an institution-based retrospective analysis of HLL transplant recipients born in or after 1957 and evaluated at Mayo Clinic, FL Transplant Center between January 1st, 2016 and December 31st, 2017. Data collection was obtained from electronic medical records. The vaccination rates were compared by univariate analysis based on IDC and no ID consultation (NIDC).<br><br>RESULTS: One hundred and eighty-seven (77%) of a total 242 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 187 IDC candidates. Among the 187 IDC patients, mumps, measles, and rubella IgG serologies were performed in 9 (5%), 21 (11%), and 51 (27%), respectively. Among all 242 patients,&#xa0;vaccines given included 2 (0.8%) MMR, 10 (4.1%) varicella and 85 (35.12%) Zostavax. Univariate analysis revealed that Zostavax was given to 76 (40.6%) pre-transplant IDC patients and only in 9 (16.7%) NIDC patients (P&#xa0;<&#xa0;.001).<br><br>CONCLUSIONS: Despite the relatively high IDC rate, patients' screened numbers for MMR IgG levels were low. Results pointed out the need for MMR protocol-driven serologic screening as well as for VZV and IDC prior to transplantation to increase vaccination rates.},
}
@article {pmid31617074,
year = {2020},
author = {Sethy, C and Goutam, K and Nayak, D and Pradhan, R and Molla, S and Chatterjee, S and Rout, N and Wyatt, MD and Narayan, S and Kundu, CN},
title = {Clinical significance of a pvrl 4 encoded gene Nectin-4 in metastasis and angiogenesis for tumor relapse.},
journal = {Journal of cancer research and clinical oncology},
volume = {146},
number = {1},
pages = {245-259},
pmid = {31617074},
issn = {1432-1335},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/*genetics/metabolism ; Carcinoma, Ductal, Breast/*blood supply/*genetics/metabolism ; Cell Adhesion Molecules/biosynthesis/*genetics/metabolism ; Female ; Humans ; Middle Aged ; NF-kappa B/metabolism ; Neovascularization, Pathologic/genetics/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; },
abstract = {PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs).<br><br>METHODS: Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens.<br><br>RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors.<br><br>CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p&#x2009;<&#x2009;0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NF&#x3ba;&#x3b2; pathway.},
}
@article {pmid31612916,
year = {2019},
author = {Shimmura, H and Kuramochi, H and Jibiki, N and Katagiri, S and Nishino, T and Araida, T},
title = {Dramatic response of FOLFIRINOX regimen in a collision pancreatic adenocarcinoma patient with a germline BRCA2 mutation: a case report.},
journal = {Japanese journal of clinical oncology},
volume = {49},
number = {11},
pages = {1049-1054},
doi = {10.1093/jjco/hyz141},
pmid = {31612916},
issn = {1465-3621},
mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; BRCA2 Protein/genetics ; Carcinoma, Ductal, Breast/*drug therapy/genetics ; Carcinoma, Pancreatic Ductal/*drug therapy ; Female ; Fluorouracil/therapeutic use ; Genetic Testing ; Germ Cells ; Germ-Line Mutation ; Humans ; Irinotecan/therapeutic use ; Leucovorin/therapeutic use ; Liver Neoplasms/*drug therapy/secondary ; Lymph Node Excision ; Middle Aged ; Mutation ; Oxaliplatin/therapeutic use ; Pancreatic Neoplasms/*drug therapy ; Pancreaticoduodenectomy ; },
abstract = {Germline BRCA1 and BRCA2 mutations are the most common gene mutations in familial pancreatic adenocarcinoma. Several reports have demonstrated the utility of platinum-based chemotherapy for treating cancer patients who harbour a BRCA mutation. Here we discuss a 47-year-old Japanese female with no relevant past history who presented with epigastralgia and fever in September 2016. A computed tomography scan revealed a low-density, low-enhanced tumour 15 mm in diameter in the head of the pancreas. The pathological diagnosis was a ductal pancreatic carcinoma. A 6 mm low-enhanced metastatic tumour was also detected in segment 4 of the liver. Because she had early onset of the disease and a family history-her mother died of pancreatic adenocarcinoma at age 48-we considered a diagnosis of familial pancreatic adenocarcinoma. She received modified FOLFIRINOX. Two months after starting chemotherapy, she was diagnosed with an invasive ductal carcinoma in the right breast. FOLFIRINOX was continued for 8 cycles (4 months); the primary pancreatic adenocarcinoma shrank and the liver metastatic foci disappeared, but the size of the breast tumour increased. Total right breast excision and sentinel lymph node dissection were performed. FOLFIRINOX was continued and after 12 cycles (6 months), both her pancreatic adenocarcinoma and liver metastasis were no longer visible using imaging. Pancreatoduodenectomy was performed and the primary tumour had shrunk to 2.5 mm. Genetic testing revealed a germline BRCA2 mutation. The FOLFIRINOX regimen showed dramatic effects on the collision pancreatic but not on the breast cancer.},
}
@article {pmid31594782,
year = {2019},
author = {Jakharia-Shah, A and Wheatley, H and Beesley, M},
title = {Reminder of an important clinical lesson: breast cancer metastasis to the parotid gland.},
journal = {BMJ case reports},
volume = {12},
number = {10},
pages = {},
pmid = {31594782},
issn = {1757-790X},
mesh = {Biopsy, Fine-Needle/methods ; Breast Neoplasms/complications/diagnostic imaging/pathology/*secondary ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Parotid Gland/*pathology/surgery ; Parotid Neoplasms/pathology/*secondary/surgery ; Positron Emission Tomography Computed Tomography/methods ; Receptor, ErbB-2/metabolism ; Treatment Outcome ; },
abstract = {A 59-year-old woman presented to an otolaryngology clinic with an 8-week history of a painless lump over her left parotid gland. Her medical history included an invasive ductal carcinoma (33 mm) and a ductal carcinoma in situ (70 mm) of the right breast, for which she had a mastectomy and various adjuvant therapies. The primary tumour presented 8 years prior to the metachronous metastasis. This patient was a non-smoker and had no significant family history. Post-superficial parotidectomy pathology revealed the parotid gland tumour to be oestrogen receptor-positive and HER2 receptor-positive, thus ruling out the initial differential diagnosis of a pleomorphic adenoma. A consequential total parotidectomy with a posterolateral neck dissection was performed with sparing of the facial nerve. The patient recovered well having only encountered a self-resolving salivary fistula. She portrayed no signs of facial nerve palsy and subsequent imaging scans showed no abnormalities.},
}
@article {pmid31584185,
year = {2020},
author = {Xu, Q and Rangaswamy, US and Wang, W and Robbins, SH and Harper, J and Jin, H and Cheng, X},
title = {Evaluation of Newcastle disease virus mediated dendritic cell activation and cross-priming tumor-specific immune responses ex vivo.},
journal = {International journal of cancer},
volume = {146},
number = {2},
pages = {531-541},
doi = {10.1002/ijc.32694},
pmid = {31584185},
issn = {1097-0215},
mesh = {Animals ; Chlorocebus aethiops ; Coculture Techniques ; *Cross-Priming ; Dendritic Cells/*immunology/metabolism ; Female ; HeLa Cells ; Humans ; Immunotherapy/*methods ; Interferon Type I/immunology/metabolism ; Neoplasms/immunology/*therapy ; Newcastle disease virus/genetics/immunology ; Oncolytic Virotherapy/*methods ; Oncolytic Viruses/genetics/immunology ; RNA/administration &amp; dosage/genetics ; RNA, Viral/administration &amp; dosage/genetics ; T-Lymphocytes/immunology ; Vero Cells ; },
abstract = {We have developed an oncolytic Newcastle disease virus (NDV) that has potent in vitro and in vivo anti-tumor activities and attenuated pathogenicity in chickens. In this ex vivo study using the same recombinant NDV backbone with GFP transgene (NDV-GFP, designated as rNDV), we found that rNDV induces maturation of monocyte-derived immature dendritic cells (iDCs) by both direct and indirect mechanisms, which promote development of antigen-specific T cell responses. Addition of rNDV directly to iDCs culture induced DC maturation, as demonstrated by the increased expression of costimulatory and antigen-presenting molecules as well as the production of type I interferons (IFNs). rNDV infection of the HER-2 positive human breast cancer cell line (SKBR3) resulted in apoptotic cell death, release of proinflammatory cytokines, and danger-associated molecular pattern molecules (DAMPs) including high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70). Addition of rNDV-infected SKBR3 cells to iDC culture resulted in greatly enhanced upregulation of the maturation markers and release of type I IFNs by DCs than rNDV-infected DCs only. When co-cultured with autologous T cells, DCs pre-treated with rNDV-infected SKBR3 cells cross-primed T cells in an antigen-specific manner. Altogether, our data strongly support the potential of oncolytic NDV as efficient therapeutic agent for cancer treatment.},
}
@article {pmid31578784,
year = {2020},
author = {Patel, DP and Herrick, JS and Stoffel, JT and Elliott, SP and Lenherr, SM and Presson, AP and Welk, B and Jha, A and Myers, JB and , },
title = {Reasons for cessation of clean intermittent catheterization after spinal cord injury: Results from the Neurogenic Bladder Research Group spinal cord injury registry.},
journal = {Neurourology and urodynamics},
volume = {39},
number = {1},
pages = {211-219},
doi = {10.1002/nau.24172},
pmid = {31578784},
issn = {1520-6777},
mesh = {Adult ; Female ; Health Behavior ; Humans ; Intermittent Urethral Catheterization/*adverse effects ; Male ; Middle Aged ; Patient Compliance ; Patient Satisfaction ; *Quality of Life ; Registries ; Spinal Cord Injuries/*complications ; Urinary Bladder, Neurogenic/*etiology ; Urinary Tract Infections/*etiology ; },
abstract = {INTRODUCTION: Clean intermittent catheterization (CIC) is recommended for bladder management after spinal cord injury (SCI) since it has the lowest complication rate. However, transitions from CIC to other less optimal strategies, such as indwelling catheters (IDCs) are common. In individuals with SCI who stopped CIC, we sought to determine how individual characteristics affect the bladder-related quality of life (QoL) and the reasons for CIC cessation.<br><br>METHODS: The Neurogenic Bladder Research Group registry is an observational study, evaluating neurogenic bladder-related QoL after SCI. From 1479 participants, those using IDC or urinary conduit were asked if they had ever performed CIC, for how long, and why they stopped CIC. Multivariable regression, among participants discontinuing CIC, established associations between demographics, injury characteristics, and SCI complications with bladder-related QoL.<br><br>RESULTS: There were 176 participants who had discontinued CIC; 66 (38%) were paraplegic and 110 (63%) were male. The most common reasons for CIC cessation among all participants were inconvenience, urinary leakage, and too many urine infections. Paraplegic participants who discontinued CIC had higher mean age, better fine motor scores, and lower educational attainment and employment. Multivariable regression revealed years since SCI was associated with worse bladder symptoms (neurogenic bladder symptom score), &#x2265;4 urinary tract infections (UTIs) in a year was associated with worse satisfaction and feelings about bladder symptoms (SCI-QoL difficulties), while tetraplegia was associated better satisfaction and feelings about bladder symptoms (SCI-QoL difficulties).<br><br>CONCLUSIONS: Tetraplegics who have discontinued CIC have an improved QoL compared with paraplegics. SCI individuals who have discontinued CIC and have recurrent UTIs have worse QoL.},
}
@article {pmid31576258,
year = {2019},
author = {Marsili, C and Wilson, CM and Gura, N},
title = {Prospective Surveillance Screenings to Identify Physical Therapy Needs During Breast Cancer Diagnosis and Surviviorship: A Case Report.},
journal = {Cureus},
volume = {11},
number = {7},
pages = {e5265},
pmid = {31576258},
issn = {2168-8184},
abstract = {Breast cancer and its treatments can cause detrimental effects to function and quality of life (QoL). These patients do not conventionally receive physical therapy services until impairments and functional limitations have become extensive. Emerging treatment models advocate for early rehabilitation screenings and proactive interventions, which are termed prospective surveillance. The purpose of this case report was to describe two prospective surveillance screenings at initial diagnosis and survivorship and subsequent physical therapy episodes of care for a patient with breast cancer. A 39-year-old female was diagnosed with invasive ductal carcinoma of the right breast. Approximately three months after the initial diagnosis, the patient had a right nipple-sparing mastectomy and immediate reconstruction with an expander. In addition, one lymph node was removed and underwent a biopsy, which was negative for metastases. The patient was screened by a physical therapist after her initial cancer diagnosis at the breast multidisciplinary clinic. This was after her mastectomy with an expander; the therapist recommended an episode of outpatient physical therapy due to impairments in pain, fatigue, loss of range of motion, weakness, and limitations in performance of her activities of daily living. The patient was seen initially for five visits. She underwent her final reconstructive surgery one month after discharge from physical therapy. Six months after her final reconstructive surgery, she was screened by the same physical therapist in the cancer survivorship clinic. Once again, therapy was recommended due to pain as well as deficits to her range of motion, strength, and functional status. The second episode of care lasted 14 visits and the patient showed improvements in pain, range of motion, shoulder strength and gains in the patient-specific functional scale and upper extremity functional index. This case reflects the importance of prospective surveillance screenings to overall patient outcomes. This patient may not have otherwise received physical therapy and its associated benefits without the prospective screenings by the physical therapist.},
}
@article {pmid31539353,
year = {2019},
author = {Gonzalez, SM and Aguilar-Jimenez, W and Alvarez, N and Rugeles, MT},
title = {Cholecalciferol modulates the phenotype of differentiated monocyte-derived dendritic cells without altering HIV-1 transfer to CD4+ T cells.},
journal = {Hormone molecular biology and clinical investigation},
volume = {40},
number = {1},
pages = {},
doi = {10.1515/hmbci-2019-0003},
pmid = {31539353},
issn = {1868-1891},
mesh = {CD4-Positive T-Lymphocytes/*drug effects/immunology/virology ; Cells, Cultured ; Cholecalciferol/*pharmacology ; Dendritic Cells/*drug effects/immunology/virology ; HIV Infections/*immunology/prevention &amp; control/transmission/virology ; HIV-1/*drug effects/immunology/physiology ; Humans ; Immunologic Factors/pharmacology ; Monocytes/drug effects/immunology/virology ; Virus Internalization/drug effects ; Vitamins/*pharmacology ; },
abstract = {Background Dendritic cells (DCs) play a crucial role during HIV-1 transmission due to their ability to transfer virions to susceptible CD4+ T cells, particularly in the lymph nodes during antigen presentation which favors the establishment of systemic infection. As mature dendritic cells (mDCs) exhibit a greater ability to transfer virions, compared to immature DCs (iDCs), maintenance of an iDC phenotype could decrease viral transmission. The immunomodulatory vitamin D (VitD) has been shown to reduce activation and maturation of DCs; hence, we hypothesized that it would reduce viral transference by DCs. Materials and methods We evaluated the effect of in vitro treatment with a precursor of VitD, cholecalciferol, on the activation/maturation phenotype of differentiated monocyte-derived DCs and their ability to transfer HIV-1 to autologous CD4+ T cells. Results Our findings show that although cholecalciferol decreases the activation of iDCs, it did not impact the maturation phenotype after LPS treatment nor iDCs' ability to transfer viral particles to target cells. Conclusion These findings suggest that despite cholecalciferol potentially modulates the phenotype of mucosal iDCs in vivo, such modulation might not impact the ability of these cells to transfer HIV-1 to target CD4+ T cells.},
}
@article {pmid31538688,
year = {2020},
author = {Haynes, HR and Rose, DSC},
title = {Synchronous small lymphocytic lymphoma and metastatic breast carcinoma in axillary lymph nodes: Preservation of follicular architecture only in the portions of affected lymph nodes involved by metastatic carcinoma.},
journal = {The breast journal},
volume = {26},
number = {2},
pages = {245-246},
doi = {10.1111/tbj.13538},
pmid = {31538688},
issn = {1524-4741},
mesh = {Aged ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/*pathology ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Neoplasms, Multiple Primary/*pathology ; },
abstract = {We present a case of metastatic ductal carcinoma of breast with the incidental discovery of small lymphocytic lymphoma (SLL) in regional axillary nodes. The co-occurence of metastatic carcinoma and low-grade lymphoma in lymph nodes is rare but well recognized. However, in this case, in the lymph nodes in which sizeable metastatic carcinoma deposits were present, the follicular structures between the sinusoidal carcinomatous infiltrates were preserved, whereas the uninvolved portions of the nodes were overrun by SLL. This is the first description of this phenomenon. We suggest that further cases displaying this previously unpublished pattern are collated in order that we may begin to investigate the underlying etiological mediators.},
}
@article {pmid31529566,
year = {2019},
author = {van Kooten, XF and Petrini, LFT and Kashyap, A and Voith von Voithenberg, L and Bercovici, M and Kaigala, GV},
title = {Spatially Resolved Genetic Analysis of Tissue Sections Enabled by Microscale Flow Confinement Retrieval and Isotachophoretic Purification.},
journal = {Angewandte Chemie (International ed. in English)},
volume = {58},
number = {43},
pages = {15259-15262},
doi = {10.1002/anie.201907150},
pmid = {31529566},
issn = {1521-3773},
support = {607322//FP7 People: Marie-Curie Actions/International ; 727761//H2020 European Research Council/International ; },
mesh = {Breast Neoplasms/*genetics/pathology ; DNA, Neoplasm/analysis/metabolism ; Female ; Formaldehyde/chemistry ; Genotype ; Humans ; MCF-7 Cells ; Microscopy, Confocal ; Paraffin Embedding ; Point Mutation ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Proto-Oncogene Proteins p21(ras)/*genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; },
abstract = {We have developed a method for spatially resolved genetic analysis of formalin-fixed paraffin-embedded (FFPE) cell block and tissue sections. This method involves local sampling using hydrodynamic flow confinement of a lysis buffer, followed by electrokinetic purification of nucleic acids from the sampled lysate. We characterized the method by locally sampling an array of points with a circa 200 μm diameter footprint, enabling the detection of single KRAS and BRAF point mutations in small populations of RKO and MCF-7 FFPE cell blocks. To illustrate the utility of this approach for genetic analysis, we demonstrate spatially resolved genotyping of FFPE sections of human breast invasive ductal carcinoma.},
}
@article {pmid31512354,
year = {2020},
author = {Ali Mlees, M},
title = {Diagnosis and surgical treatment of pathologic nipple discharge using ultrasound-guided wire localization of focal ductal dilatation.},
journal = {The breast journal},
volume = {26},
number = {2},
pages = {139-143},
doi = {10.1111/tbj.13493},
pmid = {31512354},
issn = {1524-4741},
mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/pathology ; Dilatation, Pathologic/*diagnosis/pathology ; Feasibility Studies ; Female ; Humans ; Image-Guided Biopsy ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Papilloma/*diagnosis/pathology ; Ultrasonography, Interventional ; },
abstract = {Nipple discharge is the third breast complaint after pain and lumps. The modern high-resolution ultrasound techniques are becoming more sensitive for the visualization of intraductal changes especially focal ductal dilatation (FDD), hypothesized as a radiographic manifestation of the lesion itself and that ultrasound-guided wire localization of this finding would enable identification and excision of the causative lesion. The aim of this study was to evaluate the safety, feasibility, efficiency and outcome of ultrasound-guided wire localization of FDD as possible cause of pathological nipple discharge (PND). The present study was conducted on 56 patients with PND presented to Surgical Oncology Unit at General Surgery Department, Tanta University Hospital from January 2018 to January 2019. The patients subjected to ultrasound-guided wire localization of FDD on the day of surgery, the involved duct was cannulated with a lacrimal duct probe, the targeted tissue was excised, and the specimen was sent for histopathological examination. The patients' age ranged between 26 and 71 years with a mean age of 48 years. The bloody nipple discharge was the commonest presenting symptom in 44 out of 56 patients (78.5%). The duct dilatation on study ultrasound ranged from 2.1 to 3.7 mm with a mean of 2.6 mm. Preoperative ultrasound-guided wire localization of the site of FDD was successfully performed in all cases. Papilloma alone founded in 40 out of 56 patients (71.4%), papilloma + ductal carcinoma in situ (DCIS) in six patients (10.7%), papilloma + invasive ductal carcinoma in six patients (10.7%), DCIS in two patients (3.6%) and duct ectasia in two patients (3.6%). Ultrasound-guided wire localization of FDD is an easy and safe technique for evaluation, precise localization, and targeted excision of the underlying lesions of PND.},
}
@article {pmid31508769,
year = {2019},
author = {Couto, MSA and Firme, VAC and Guerra, MR and Bustamante-Teixeira, MT},
title = {The effect of redistribution of ill-defined causes of death on the mortality rate of breast cancer in Brazil.},
journal = {Ciencia &amp; saude coletiva},
volume = {24},
number = {9},
pages = {3517-3528},
doi = {10.1590/1413-81232018249.31402017},
pmid = {31508769},
issn = {1678-4561},
mesh = {Brazil/epidemiology ; Breast Neoplasms/*mortality ; Cause of Death/*trends ; Cities/statistics &amp; numerical data ; Female ; Humans ; Mortality/*trends ; },
abstract = {The relevance of breast cancer for women has driven research about mortality of this disease. However, these studies are affected by problems generated by deaths due to ill-defined causes (IDC). To highlight distortions caused by IDC in studies that evaluate mortality, we calculated the age-standardized mortality rates of breast cancer, with and without adjustment for IDC for the years 1990, 2000, and 2010. Then, panel data regression models were estimated and enabled us to identify that the adjustment for IDC: has elevated breast cancer mortality rate of Brazilian municipalities by 9% in the period considered; has drawn mortality rates of the South, Southeast, Northeast and North regions closer; has reduced the increasing trend of mortality by almost 60%, mainly in the Southeast and South regions; has increased, more sharply, the mortality in cities with less than 5 thousand inhabitants; has curbed the significance of most factors associated with breast cancer; has revealed that the effect of longevity and the public health expenditure may be overestimated. These results highlight the importance of adjustment for IDC in producing reliable mortality indicators.},
}
@article {pmid31488082,
year = {2019},
author = {McQuerry, JA and Jenkins, DF and Yost, SE and Zhang, Y and Schmolze, D and Johnson, WE and Yuan, Y and Bild, AH},
title = {Pathway activity profiling of growth factor receptor network and stemness pathways differentiates metaplastic breast cancer histological subtypes.},
journal = {BMC cancer},
volume = {19},
number = {1},
pages = {881},
pmid = {31488082},
issn = {1471-2407},
support = {P30 CA033572/CA/NCI NIH HHS/United States ; U01 CA220413/CA/NCI NIH HHS/United States ; U54 CA209978/CA/NCI NIH HHS/United States ; U54CA209978/NH/NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Bcl-2-Like Protein 11/metabolism ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cohort Studies ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Osteonectin/genetics ; Phenotype ; Prognosis ; RNA-Seq/methods ; Receptors, Growth Factor/*metabolism ; Signal Transduction/*genetics ; Snail Family Transcription Factors/metabolism ; Transcriptome/*genetics ; Triple Negative Breast Neoplasms/*genetics/pathology ; },
abstract = {BACKGROUND: Gene expression profiling of rare cancers has proven challenging due to limited access to patient materials and requirement of intact, non-degraded RNA for next-generation sequencing. We customized a gene expression panel compatible with degraded RNA from formalin-fixed, paraffin-embedded (FFPE) patient cancer samples and investigated its utility in pathway activity profiling in patients with metaplastic breast cancer (MpBC).<br><br>METHODS: Activity of various biological pathways was profiled in samples from nineteen patients with MpBC and 8 patients with invasive ductal carcinoma with triple negative breast cancer (TNBC) phenotype using a custom gene expression-based assay of 345 genes.<br><br>RESULTS: MpBC samples of mesenchymal (chondroid and/or osteoid) histology demonstrated increased SNAI1 and BCL2L11 pathway activity compared to samples with non-mesenchymal histology. Additionally, late cornified envelope and keratinization genes were downregulated in MpBC compared to TNBC, and epithelial-to-mesenchymal transition (EMT) and collagen genes were upregulated in MpBC. Patients with high activity of an invasiveness gene expression signature, as well as high expression of the mesenchymal marker and extracellular matrix glycoprotein gene SPARC, experienced worse outcomes than those with low invasiveness activity and low SPARC expression.<br><br>CONCLUSIONS: This study demonstrates the utility of gene expression profiling of metaplastic breast cancer FFPE samples with a custom counts-based assay. Gene expression patterns identified by this assay suggest that, although often histologically triple negative, patients with MpBC have distinct pathway activation compared to patients with invasive ductal TNBC. Incorporation of targeted therapies may lead to improved outcome for MpBC patients, especially in those patients expressing increased activity of invasiveness pathways.},
}
@article {pmid31486035,
year = {2020},
author = {Delaunay, T and Achard, C and Grégoire, M and Tangy, F and Boisgerault, N and Fonteneau, JF},
title = {A Functional Assay to Determine the Capacity of Oncolytic Viruses to Induce Immunogenic Tumor Cell Death.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2058},
number = {},
pages = {127-132},
doi = {10.1007/978-1-4939-9794-7_8},
pmid = {31486035},
issn = {1940-6029},
mesh = {Animals ; Antigen-Presenting Cells/immunology/metabolism ; Cell Death/immunology ; Dendritic Cells/immunology/metabolism ; Genetic Therapy/methods ; Genetic Vectors/*genetics ; Humans ; *Immunomodulation ; Immunophenotyping ; Monocytes/immunology/metabolism ; Neoplasms/*immunology/metabolism/pathology/therapy ; Oncolytic Virotherapy ; Oncolytic Viruses/*genetics/immunology ; },
abstract = {Oncolytic immunotherapy efficacy relies partially on the induction of immunogenic tumor cell death following infection with oncolytic viruses (OV) to induce an antitumor immune response. Here, we describe a method to determine if an OV is able to induce such an immunogenic tumor cell death. This method consists in testing whether tumor cells lysed by an OV are able to induce the maturation of human monocyte-derived immature dendritic cells (Mo-iDC).},
}
@article {pmid31467444,
year = {2020},
author = {Sarhan, MS and Mourad, EF and Nemr, RA and Abdelfadeel, MR and Daanaa, HA and Youssef, HH and Goda, HA and Hamza, MA and Fayez, M and Eichler-Löbermann, B and Ruppel, S and Hegazi, NA},
title = {An inoculum-dependent culturing strategy (IDC) for the cultivation of environmental microbiomes and the isolation of novel endophytic Actinobacteria.},
journal = {The Journal of antibiotics},
volume = {73},
number = {1},
pages = {66-71},
pmid = {31467444},
issn = {1881-1469},
mesh = {Actinobacteria/*chemistry ; Bacteriological Techniques ; Colony Count, Microbial ; Culture Media ; Endophytes/*chemistry ; *Microbiota ; Plant Roots/microbiology ; Plant Shoots/microbiology ; Plants/microbiology ; },
abstract = {The recent introduction of plant-only-based culture media enabled cultivation of not-yet-cultured bacteria that exceed 90% of the plant microbiota communities. Here, we further prove the competence and challenge of such culture media, and further introduce "the inoculum-dependent culturing strategy, IDC". The strategy depends on direct inoculating plant serial dilutions onto plain water agar plates, allowing bacteria to grow only on the expense of natural nutrients contained in the administered inoculum. Developed colonies are successively transferred/subcultured onto plant-only-based culture media, which contains natural nutrients very much alike to those found in the prepared plant inocula. Because of its simplicity, the method is recommended as a powerful tool in screening programs that require microbial isolation from a large number of diverse plants. Here, the method comfortably and successfully recovered several isolates of endophytic Actinobacteria represented by the six genera of Curtobacterium spp., Plantibacter spp., Agreia spp., Herbiconiux spp., Rhodococcus spp., and Nocardioides spp. Furthermore, two of the isolates are most likely novel species belonging to Agreia spp. and Herbiconiux spp.},
}
@article {pmid31452673,
year = {2019},
author = {Dobbels, AA and Lorenz, AJ},
title = {Soybean iron deficiency chlorosis high throughput phenotyping using an unmanned aircraft system.},
journal = {Plant methods},
volume = {15},
number = {},
pages = {97},
pmid = {31452673},
issn = {1746-4811},
abstract = {BACKGROUND: Iron deficiency chlorosis (IDC) is an abiotic stress in soybean [Glycine max (L.) Merr.] that causes significant yield reductions. Symptoms of IDC include interveinal chlorosis and stunting of the plant. While there are management practices that can overcome these drastic yield losses, the preferred way to manage IDC is growing tolerant soybean varieties. To develop varieties tolerant to IDC, breeders may easily phenotype up to thousands of candidate soybean lines every year for severity of symptoms related to IDC, a task traditionally done with a 1-5 visual rating scale. The visual rating scale is subjective and, because it is time consuming and laborious, can typically only be accomplished once or twice during a growing season.<br><br>RESULTS: The goal of this study was to use an unmanned aircraft system (UAS) to improve field screening for tolerance to soybean IDC. During the summer of 2017, 3386 plots were visually scored for IDC stress on two different dates. In addition, images were captured with a DJI Inspire 1 platform equipped with a modified dual camera system which simultaneously captures digital red, green, blue images as well as red, green, near infrared (NIR) images. A pipeline was created for image capture, orthomosaic generation, processing, and analysis. Plant and soil classification was achieved using unsupervised classification resulting in 95% overall classification accuracy. Within the plant classified canopy, the green, yellow, and brown plant pixels were classified and used as features for random forest and neural network models. Overall, the random forest and neural network models achieved similar misclassification rates and classification accuracy, which ranged from 68 to 77% across rating dates. All 36 trials in the field were analyzed using a linear model for both visual score and UAS predicted values on both dates. In 32 of the 36 tests on date 1 and 33 of 36 trials on date 2, the LSD associated with UAS image-based IDC scores was lower than the LSD associated with visual scores, indicating the image-based scores provided more precise measurements of IDC severity.<br><br>CONCLUSIONS: Overall, the UAS was able to capture differences in IDC stress and may be used for evaluations of candidate breeding lines in a soybean breeding program. This system was both more efficient and precise than traditional scoring methods.},
}
@article {pmid31440248,
year = {2019},
author = {Escoter-Torres, L and Caratti, G and Mechtidou, A and Tuckermann, J and Uhlenhaut, NH and Vettorazzi, S},
title = {Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor.},
journal = {Frontiers in immunology},
volume = {10},
number = {},
pages = {1859},
pmid = {31440248},
issn = {1664-3224},
mesh = {Animals ; Gene Expression Regulation/*drug effects/*immunology ; Glucocorticoids/*immunology/pharmacology ; Humans ; Immunosuppressive Agents/*immunology/pharmacology ; Receptors, Glucocorticoid/*immunology ; },
abstract = {For many decades, glucocorticoids have been widely used as the gold standard treatment for inflammatory conditions. Unfortunately, their clinical use is limited by severe adverse effects such as insulin resistance, cardiometabolic diseases, muscle and skin atrophies, osteoporosis, and depression. Glucocorticoids exert their effects by binding to the Glucocorticoid Receptor (GR), a ligand-activated transcription factor which both positively, and negatively regulates gene expression. Extensive research during the past several years has uncovered novel mechanisms by which the GR activates and represses its target genes. Genome-wide studies and mouse models have provided valuable insight into the molecular mechanisms of inflammatory gene regulation by GR. This review focusses on newly identified target genes and GR co-regulators that are important for its anti-inflammatory effects in innate immune cells, as well as mutations within the GR itself that shed light on its transcriptional activity. This research progress will hopefully serve as the basis for the development of safer immune suppressants with reduced side effect profiles.},
}
@article {pmid31437176,
year = {2019},
author = {Santos Junior, OR and da Costa Rocha, MO and Rodrigues de Almeida, F and Sales da Cunha, PF and Souza, SCS and Saad, GP and Santos, TADQ and Ferreira, AM and Tan, TC and Nunes, MCP},
title = {Speckle tracking echocardiographic deformation indices in Chagas and idiopathic dilated cardiomyopathy: Incremental prognostic value of longitudinal strain.},
journal = {PloS one},
volume = {14},
number = {8},
pages = {e0221028},
pmid = {31437176},
issn = {1932-6203},
mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/complications/*diagnostic imaging/mortality/physiopathology ; Chagas Cardiomyopathy/complications/*diagnostic imaging/mortality/physiopathology ; Female ; Follow-Up Studies ; Heart Failure/*diagnostic imaging/etiology/mortality/physiopathology ; Heart Transplantation/statistics &amp; numerical data ; Hospitalization/statistics &amp; numerical data ; Humans ; Male ; Middle Aged ; Prognosis ; Stroke Volume/physiology ; Survival Analysis ; Ventricular Function, Left/physiology ; },
abstract = {BACKGROUND: Chagas cardiomyopathy (CDC) is associated with a poor prognosis compared to other cardiomyopathies. Speckle tracking echocardiography (STE), which provides direct assessment of myocardial fiber deformation, may be useful in predicting prognosis.<br><br>OBJECTIVE: This study assessed STE in CDC and compared with idiopathic cardiomyopathy (IDC), and also examined the incremental prognostic information of STE over left ventricular ejection fraction (LVEF) in these patients.<br><br>METHODS: We enrolled 112 patients, age of 56.7 &#xb1; 11.8 years, 81 with CDC and 31 with IDC. STE indices were obtained at baseline in all patients. The endpoint was a composite of death, hospitalization for heart failure, or need for heart transplantation.<br><br>RESULTS: Patients with IDC had worse LV systolic function compared to CDC, with LVEF of 34.5% vs 41.3%, p = 0.004, respectively. After adjustment for LVEF, there were no differences in STE values between CDC and IDC. During a median follow-up of 18.2 months (range, 11 to 22), 26 patients met the composite end point (24%). LV longitudinal strain was a strong predictor of adverse events, incremental to LVEF and E/e' ratio (HR 1.463, 95% CI 1.130-1.894; p = 0.004). The risk of cardiac events increased significantly in patients with GLS > - 12% (log-rank p = 0.035).<br><br>CONCLUSIONS: STE indices were abnormal in patients with dilated cardiomyopathy, without differences between CDC and IDC. LV longitudinal strain was a powerful predictor of outcome, adding prognostic information beyond that provided by LVEF and E/e' ratio.},
}
@article {pmid31427562,
year = {2019},
author = {Sun, Y and Lei, B and Huang, Q},
title = {SOX18 Affects Cell Viability, Migration, Invasiveness, and Apoptosis in Hepatocellular Carcinoma (HCC) Cells by Participating in Epithelial-to-Mesenchymal Transition (EMT) Progression and Adenosine Monophosphate Activated Protein Kinase (AMPK)/Mammalian Target of Rapamycin (mTOR).},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {25},
number = {},
pages = {6244-6254},
pmid = {31427562},
issn = {1643-3750},
mesh = {Adenylate Kinase/*metabolism ; Apoptosis/physiology ; Carcinoma, Hepatocellular/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Cell Survival/physiology ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms/genetics/*metabolism/*pathology ; Neoplasm Invasiveness ; SOXF Transcription Factors/*metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism ; },
abstract = {BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. It has been verified that the expression of SOX18 is correlated to poor clinical prognosis in patients with ovarian cancer, non-small cell lung cancer, or breast invasive ductal carcinoma. However, the expression pattern and biological function of SOX18 in HCC tissues remains unclear. In this study, we set out to investigate the associated biological function and potential molecular mechanism of the SOX18 gene in HCC cells. MATERIAL AND METHODS The mRNA and protein expression levels of experimental related genes were detected by real-time polymerase chain reaction and western blotting assay, respectively. The MTT method was used to assess cell viability, and cell apoptosis analysis was performed by means of FACScan flow cytometry. Wound-healing assay and Transwell analysis were performed to evaluate the ability of cell migration and invasiveness, respectively. RESULTS SOX18 was highly expressed in various HCC cell lines. In addition, SOX18 promoted cell viability, migration, and invasion and simultaneously induce cell apoptosis. SOX18 promoted epithelial-to-mesenchymal transition (EMT) progression, and SOX18 downregulation activated the autophagy signaling pathway AMPK/mTOR in HCC cells. CONCLUSIONS SOX18 downregulation in HCC cells suppressed cell viability and metastasis, induced cell apoptosis and hindered the occurrence and progression of tumor cells by participating in the EMT process and regulating the autophagy signaling pathway AMPK/mTOR.},
}
@article {pmid31424026,
year = {2020},
author = {Chen, JR and Zhao, JG and Zhu, S and Zhang, MN and Chen, N and Liu, JD and Sun, GX and Shen, PF and Zeng, H},
title = {Clinical and oncologic findings of extraprostatic extension on needle biopsy in de novo metastatic prostate cancer.},
journal = {Asian journal of andrology},
volume = {22},
number = {4},
pages = {427-431},
pmid = {31424026},
issn = {1745-7262},
mesh = {Abiraterone Acetate/therapeutic use ; Adenocarcinoma/metabolism/*secondary/therapy ; Aged ; Androgen Antagonists/therapeutic use ; Antineoplastic Agents/therapeutic use ; Biopsy, Large-Core Needle ; Bone Neoplasms/metabolism/*secondary/therapy ; Docetaxel/therapeutic use ; Functional Status ; Humans ; Kaplan-Meier Estimate ; Male ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Neuroendocrine Tumors ; Orchiectomy ; Prognosis ; Progression-Free Survival ; Proportional Hazards Models ; Prostate-Specific Antigen/metabolism ; Prostatectomy ; Prostatic Neoplasms/metabolism/*pathology/therapy ; Prostatic Neoplasms, Castration-Resistant/metabolism/pathology/therapy ; Retrospective Studies ; Survival Rate ; },
abstract = {This study aimed to explore the clinical and oncologic findings in patients with de novo metastatic prostate cancer (mPCa) and extraprostatic extension (EPE) on biopsy. We retrospectively evaluated data on 630 patients with de novo mPCa between January 2009 and December 2017 in the West China Hospital (Chengdu, China), including evaluating the relationships between EPE and other variables and the association of EPE with survival outcomes by the Chi-square test, Kaplan-Meier curves, and the Cox proportional-hazards model. EPE was found in 70/630 patients, making a prevalence of 11.1%. The presence of EPE on biopsy was associated with higher Gleason scores and higher incidence of neuroendocrine differentiation (NED), intraductal carcinoma of the prostate (IDC-P), and perineural invasion (PNI). Compared with those without EPE, patients with EPE had shorter castration-resistant prostate cancer-free survival (CFS; median: 14.1 vs 17.1 months, P = 0.015) and overall survival (OS; median: 43.7 vs 68.3 months, P = 0.032). According to multivariate analysis, EPE was not an independent predictor for survival. Subgroup analyses demonstrated that patients with favorable characteristics, including negative NED or IDC-P status, Eastern Cooperative Oncology Group (ECOG) score <2, and prostate-specific antigen (PSA) <50 ng ml[-1], had worse prognoses if EPE was detected. In patients with PSA <50 ng ml[-1], EPE was a negative independent predictor for OS (hazard ratio [HR]: 4.239, 95% confidence interval [CI]: 1.218-14.756, P = 0.023). EPE was strongly associated with other aggressive clinicopathological features and poorer CFS and OS. These data suggest that EPE may be an indicator of poor prognosis, particularly in patients, otherwise considered likely to have favorable survival outcomes.},
}
@article {pmid31391072,
year = {2019},
author = {Tan, X and Li, Z and Ren, S and Rezaei, K and Pan, Q and Goldstein, AT and Macri, CJ and Cao, D and Brem, RF and Fu, SW},
title = {Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer.},
journal = {Breast cancer research : BCR},
volume = {21},
number = {1},
pages = {89},
pmid = {31391072},
issn = {1465-542X},
mesh = {3' Untranslated Regions ; Breast Neoplasms/*genetics/*pathology/therapy ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*genetics ; DNA Damage ; Disease Progression ; Drug Resistance, Neoplasm/*genetics ; Epithelial-Mesenchymal Transition/genetics ; Female ; Forkhead Box Protein M1/genetics ; *Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Humans ; MicroRNAs/*genetics ; Models, Biological ; RNA Interference ; Radiation Tolerance/*genetics ; },
abstract = {BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment.<br><br>METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed.<br><br>RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability.<br><br>CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management.},
}
@article {pmid31390230,
year = {2019},
author = {Ortega, A and Olea-Herrero, N and Arenas, MI and Vélez-Vélez, E and Moreno-Gómez-Toledano, R and Muñoz-Moreno, C and Lázaro, A and Esbrit, P and Tejedor, A and Bosch, RJ},
title = {Urinary excretion of parathyroid hormone-related protein correlates with renal function in control rats and rats with cisplatin nephrotoxicity.},
journal = {American journal of physiology. Renal physiology},
volume = {317},
number = {4},
pages = {F874-F880},
doi = {10.1152/ajprenal.00091.2019},
pmid = {31390230},
issn = {1522-1466},
mesh = {Acute Kidney Injury/*chemically induced/pathology/*urine ; Animals ; Antineoplastic Agents/*toxicity ; Biomarkers/urine ; Cisplatin/*toxicity ; Creatinine/urine ; Kidney/pathology ; Kidney Function Tests ; Male ; Parathyroid Hormone-Related Protein/*urine ; Rats ; Rats, Wistar ; },
abstract = {Parathyroid hormone-related protein (PTHrP) and its receptor are abundantly expressed throughout the renal parenchyma, where PTHrP exerts a modulatory action on renal function. PTHrP upregulation is a common event associated with the mechanism of renal injury and repair. However, no study has yet explored the putative excretion of PTHrP in urine, including its potential relationship with renal function. In the present study, we tested this hypothesis by studying the well-known rat model of acute renal injury induced by the chemotherapeutic agent cisplatin. Using Western blot analysis, we could detect a single protein band, corresponding to intact PTHrP, in the urine of both control and cisplatin-injected rats, whose levels were significantly higher in the latter group. PTHrP was detected in rat urine by dot blot, and its quantification with two specific ELISA kits showed that, compared with control rats, those treated with cisplatin displayed a significant increase in urinary PTHrP (expressed as the PTHrP-to-creatinine ratio or 24-h excretion). In addition, a positive correlation between urinary PTHrP excretion and serum creatinine was found in these animals. In conclusion, our data demonstrate that PTHrP is excreted in rat urine and that this excretion is higher with the decrease of renal function. This suggests that urinary PTHrP levels might be a renal function marker.},
}
@article {pmid31388122,
year = {2020},
author = {Goodes, LM and King, GK and Rea, A and Murray, K and Boan, P and Watts, A and Bardsley, J and Hartshorn, C and Thavaseelan, J and Rawlins, M and Brock, JA and Dunlop, SA},
title = {Early urinary tract infection after spinal cord injury: a retrospective inpatient cohort study.},
journal = {Spinal cord},
volume = {58},
number = {1},
pages = {25-34},
pmid = {31388122},
issn = {1476-5624},
mesh = {Adult ; Catheters, Indwelling/statistics &amp; numerical data ; Humans ; Incidence ; Inpatients/statistics &amp; numerical data ; Length of Stay/*statistics &amp; numerical data ; Middle Aged ; Retrospective Studies ; Spinal Cord Injuries/complications/*epidemiology ; Time Factors ; Urinary Catheterization/adverse effects/*statistics &amp; numerical data ; Urinary Tract Infections/*epidemiology/etiology ; Western Australia/epidemiology ; },
abstract = {STUDY DESIGN: Retrospective audit.<br><br>OBJECTIVES: Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI).<br><br>SETTING: Western Australian Hospitals managing SCI patients.<br><br>METHODS: Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts.<br><br>RESULTS: Across the cohort (n&#x2009;=&#x2009;70) UTI rate was 1.1 starts/100 days; UTI by multi-resistant organisms 0.1/100 days. Having &#x2265;1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values&#x2009;<&#x2009;0.001). For patients with &#x2265;1 UTIs (n&#x2009;=&#x2009;43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1&#x2009;SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n&#x2009;=&#x2009;38/70), protocols were followed (85.7%&#x2009;&#x2264;&#x2009;6&#x2009;h apart, 96.1%&#x2009;<&#x2009;8&#x2009;h), but 26% of IC volumes exceeded 500&#x2009;mL; occasional volumes&#x2009;>&#x2009;800&#x2009;mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009; and 3.9, 95%CI 2.6-5.9, p-value&#x2009;<&#x2009;0.001 respectively).<br><br>CONCLUSIONS: Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS.<br><br>SPONSORSHIP: None.},
}
@article {pmid31357083,
year = {2019},
author = {Arabpour, M and Rasolmali, R and Talei, AR and Mehdipour, F and Ghaderi, A},
title = {Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes.},
journal = {Molecular immunology},
volume = {114},
number = {},
pages = {172-178},
doi = {10.1016/j.molimm.2019.07.019},
pmid = {31357083},
issn = {1872-9142},
mesh = {Adult ; Aged ; B-Lymphocytes/*immunology ; Breast Neoplasms/*immunology ; CD40 Ligand/immunology ; Carcinoma, Ductal/immunology ; Female ; Granzymes/*immunology ; Humans ; Interleukins/immunology ; Lymph Nodes/*immunology ; Lymphocyte Activation/*immunology ; Middle Aged ; Perforin/immunology ; Interleukin-21 ; },
abstract = {B lymphocytes with regulatory or effector functions synthesize granzyme B (GZMB). We investigated the frequency and phenotype of GZMB-producing B cells in breast tumor-draining lymph nodes (TDLNs). Mononuclear cells were isolated from 48 axillary lymph nodes and were stimulated with anti-BCR (B cell receptor), recombinant interleukin (IL)-21 and CD40 L alone or in combination. Flow cytometry was used to evaluate the expression of GZMB in B cells, and in 4 samples the phenotype of GZMB[+] B cells was determined. B cells produced GZMB only when stimulated with a combination of IL-21 and anti-BCR for at least 16 h. Adding CD40 L to IL-21 and anti-BCR stimuli resulted in lower GZMB production in B cells. A small fraction of B cells was able to produce perforin in all stimulation conditions, and the majority of GZMB[+] B cells were perforin-negative. Both naïve (CD24[low]CD27[-]) and active/memory (CD24[hi]CD27[+]) B cells expressed GZMB. In patients with invasive ductal carcinoma, the frequency of GZMB[+] B cells was significantly lower in metastatic compared to non-metastatic lymph nodes. The frequency of GZMB[+] B cells did not significantly correlate with prognostic factors such as stage, tumor size or Her2 expression. In summary, a subpopulation of both naïve and memory B cells expressed GZMB in breast TDLNs. Our findings underscore the need to investigate the function of GZMB[+] B cells in breast tumor immunity.},
}
@article {pmid31354196,
year = {2019},
author = {Ogunleye, AJ and Olanrewaju, AJ and Arowosegbe, M and Omotuyi, OI},
title = {Molecular docking based screening analysis of GSK3B.},
journal = {Bioinformation},
volume = {15},
number = {3},
pages = {201-208},
pmid = {31354196},
issn = {0973-2063},
abstract = {GSK3B has been an interesting drug target in the pharmaceutical industry. Its dysfunctional expression has prognostic significance in the top 3 cause of death associated with non-communicable diseases (cancer, Alzheimer's disease and type 2 diabetes). Previous studies have shown clearly that inhibiting GSK3B has proven therapeutic significance in Alzheimer's disease, but its contribution to various cancers has not been clearly resolved. In this study we report the contribution and prognostic significance of GSK3B to two breast cancer subtypes; ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC) using the Oncomine platform. We performed high throughput screening using molecular docking. We identified BT-000775, a compound that was subjected to further computational hit optimization protocols. Through computational predictions, BT-000775 is a highly selective GSK3B inhibitor, with superior binding affinity and robust ADME profiles suitable for the patho-physiological presentations.},
}
@article {pmid31352554,
year = {2019},
author = {Zacharioudakis, K and Kontoulis, T and Vella, JX and Zhao, J and Ramakrishnan, R and Cunningham, DA and Mufti, RA and Leff, DR and Thiruchelvam, P and Hogben, K and Hadjiminas, DJ},
title = {Can we see what is invisible? The role of MRI in the evaluation and management of patients with pathological nipple discharge.},
journal = {Breast cancer research and treatment},
volume = {178},
number = {1},
pages = {115-120},
pmid = {31352554},
issn = {1573-7217},
mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Preoperative Period ; Retrospective Studies ; Sensitivity and Specificity ; },
abstract = {INTRODUCTION: The aim of this study was to determine the ability of MRI to identify and assess the extent of disease in patients with pathological nipple discharge (PND) with an occult malignancy not evident on standard pre-operative evaluation with mammography and ultrasound.<br><br>METHODS: Patients presenting to the breast unit of Imperial College Healthcare NHS Trust between December 2009 and December 2018 with PND and normal imaging were enrolled in the study. Pre-operative bilateral breast MRI was performed in all patients as part of our protocol and all patients were offered diagnostic microdochectomy.<br><br>RESULTS: A total of 82 patients fulfilled our selection criteria and were enrolled in our study. The presence of an intraductal papilloma (IDP) was identified as the cause of PND in 38 patients (46.3%), 14 patients had duct ectasia (DE-17%) and 5 patients had both an IDP and DE. Other benign causes were identified in 11 patients (13.4%). Despite normal mammography and ultrasound a malignancy was identified in 14 patients (17%). Eleven patients had DCIS (13.4%), two had invasive lobular carcinoma and one patient had an invasive ductal carcinoma. The sensitivity of MRI in detecting an occult malignancy was 85.71% and the specificity was 98.53%. The positive predictive value was 92.31% and the negative predictive value was 97.1%.<br><br>CONCLUSIONS: Although a negative MRI does not exclude the presence of an occult malignancy the high sensitivity and specificity of this diagnostic modality can guide the surgeon and alter the management of patients&#xa0;with PND.},
}
@article {pmid31351155,
year = {2019},
author = {Ding, Q and Chen, H and Lim, B and Damodaran, S and Chen, W and Tripathy, D and Piha-Paul, S and Luthra, R and Meric-Bernstam, F and Sahin, AA},
title = {HER2 somatic mutation analysis in breast cancer: correlation with clinicopathological features.},
journal = {Human pathology},
volume = {92},
number = {},
pages = {32-38},
doi = {10.1016/j.humpath.2019.07.006},
pmid = {31351155},
issn = {1532-8392},
mesh = {Breast/*pathology ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; DNA Mutational Analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Receptor, ErbB-2/*genetics/metabolism ; Retrospective Studies ; },
abstract = {HER2 mutations have been reported in approximately 2% of breast cancers. Regardless of HER2 overexpression or amplification status, breast cancer with HER2 mutations may respond to HER2-targeted therapy. As HER2 mutation is rare, the clinical and pathological features of HER2-mutated breast cancers, such as hormonal status, histological grade, and metastasis, remain poorly defined. Therefore, the identification of HER2-mutated breast cancer has clinical significance. We retrospectively screened patients with metastatic breast cancer in whom molecular profiling had been performed using next-generation sequencing from 2012 to 2015; we identified 18 patients with HER2 mutation. Mutations were found on next-generation sequencing-based panels, including Ion AmpliSeq Cancer Hotspot, Oncomine, FoundationOne, and Guardant360. HER2 mutations were identified in both the tyrosine kinase (n = 14) and extracellular (n = 4) domains. Of the 14 cases with tyrosine kinase domain mutations, 13 were estrogen receptor positive; the 4 cases with extracellular domain mutations were exclusively estrogen receptor negative. In addition, 11 of 14 patients with tyrosine kinase domain mutations had bone metastasis, whereas no patients with HER2 extracellular domain mutations had bone metastasis. Histologically, 13 patients had invasive ductal carcinoma, 1 had metaplastic carcinoma, and 4 had invasive lobular carcinoma (ILC). All 4 ILCs were high grade and pleomorphic, and not only had an HER2 mutation in the kinase domain but also had an HER2 mutation involving the L755 site. Specific mutation sites may be involved in the pathogenesis of nonclassic ILC.},
}
@article {pmid31350286,
year = {2019},
author = {Lourenco, C and Kalkat, M and Houlahan, KE and De Melo, J and Longo, J and Done, SJ and Boutros, PC and Penn, LZ},
title = {Modelling the MYC-driven normal-to-tumour switch in breast cancer.},
journal = {Disease models &amp; mechanisms},
volume = {12},
number = {7},
pages = {},
pmid = {31350286},
issn = {1754-8411},
support = {//CIHR/Canada ; },
mesh = {Breast/*metabolism/pathology ; Breast Neoplasms/metabolism/*pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Female ; Gene Expression Regulation, Neoplastic ; *Genes, myc ; Humans ; *Models, Biological ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction ; },
abstract = {The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated an in vivo model that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the phosphoinositide 3 kinase pathway (PIK3CA[H1047R]) led to the development of organised acinar structures in mice. Expressing both PIK3CA[H1047R] and deregulated MYC led to the development of invasive ductal carcinoma. Therefore, the deregulation of MYC expression in this setting creates a MYC-dependent normal-to-tumour switch that can be measured in vivo These MYC-driven tumours exhibit classic hallmarks of human breast cancer at both the pathological and molecular level. Moreover, tumour growth is dependent upon sustained deregulated MYC expression, further demonstrating addiction to this potent oncogene and regulator of gene transcription. We therefore provide a MYC-dependent model of breast cancer, which can be used to assay invivo tumour signalling pathways, proliferation and transformation from normal breast acini to invasive breast carcinoma. We anticipate that this novel MYC-driven transformation model will be a useful research tool to better understand the oncogenic function of MYC and for the identification of therapeutic vulnerabilities.},
}
@article {pmid31338037,
year = {2019},
author = {Rodriguez, J and Schulz, S and Giraldo, BF and Voss, A},
title = {Risk Stratification in Idiopathic Dilated Cardiomyopathy Patients Using Cardiovascular Coupling Analysis.},
journal = {Frontiers in physiology},
volume = {10},
number = {},
pages = {841},
pmid = {31338037},
issn = {1664-042X},
abstract = {Cardiovascular diseases are one of the most common causes of death; however, the early detection of patients at high risk of sudden cardiac death (SCD) remains an issue. The aim of this study was to analyze the cardio-vascular couplings based on heart rate variability (HRV) and blood pressure variability (BPV) analyses in order to introduce new indices for noninvasive risk stratification in idiopathic dilated cardiomyopathy patients (IDC). High-resolution electrocardiogram (ECG) and continuous noninvasive blood pressure (BP) signals were recorded in 91 IDC patients and 49 healthy subjects (CON). The patients were stratified by their SCD risk as high risk (IDCHR) when after two years the subject either died or suffered life-threatening complications, and as low risk (IDCLR) when the subject remained stable during this period. Values were extracted from ECG and BP signals, the beat-to-beat interval, and systolic and diastolic blood pressure, and analyzed using the segmented Poincaré plot analysis (SPPA), the high-resolution joint symbolic dynamics (HRJSD) and the normalized short time partial directed coherence methods. Support vector machine (SVM) models were built to classify these patients according to SCD risk. IDCHR patients presented lowered HRV and increased BPV compared to both IDCLR patients and the control subjects, suggesting a decrease in their vagal activity and a compensation of sympathetic activity. Both, the cardio -systolic and -diastolic coupling strength was stronger in high-risk patients when comparing with low-risk patients. The cardio-systolic coupling analysis revealed that the systolic influence on heart rate gets weaker as the risk increases. The SVM IDCLR vs. IDCHR model achieved 98.9% accuracy with an area under the curve (AUC) of 0.96. The IDC and the CON groups obtained 93.6% and 0.94 accuracy and AUC, respectively. To simulate a circumstance in which the original status of the subject is unknown, a cascade model was built fusing the aforementioned models, and achieved 94.4% accuracy. In conclusion, this study introduced a novel method for SCD risk stratification for IDC patients based on new indices from coupling analysis and non-linear HRV and BPV. We have uncovered some of the complex interactions within the autonomic regulation in this type of patient.},
}
@article {pmid31331321,
year = {2019},
author = {Nkinda, L and Patel, K and Njuguna, B and Ngangali, JP and Memiah, P and Bwire, GM and Majigo, MV and Mizinduko, M and Pastakia, SD and Lyamuya, E},
title = {C - reactive protein and interleukin - 6 levels among human immunodeficiency virus -infected patients with dysglycemia in Tanzania.},
journal = {BMC endocrine disorders},
volume = {19},
number = {1},
pages = {77},
pmid = {31331321},
issn = {1472-6823},
support = {-//Intra-ACP academic mobility scholarship/ ; },
mesh = {Biomarkers/*blood ; Blood Glucose/*analysis ; C-Reactive Protein/*analysis ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Glucose Intolerance/*blood/epidemiology/virology ; HIV/*isolation &amp; purification ; HIV Infections/*complications/virology ; Humans ; Incidence ; Interleukin-6/*blood ; Male ; Middle Aged ; Prognosis ; Tanzania/epidemiology ; },
abstract = {BACKGROUND: Chronic inflammation has been associated with dysglycemia among people living with HIV (PLHIV). There is however, limited data regarding this phenomenon in sub-Sahara Africa (SSA). Therefore we assessed the levels of C-reactive protein (CRP) and Interleukin 6 (IL-6) on a cohort of PLHIV and its associations with dysglycemia in Tanzania.<br><br>METHODS: We conducted a cross-sectional study at the Infectious Disease Clinic (IDC) in Tanzania from March to May 2018. Purposive sampling was used to identify participants who had an undetectable viral load, were on 1st line anti-retroviral therapy (ART) and had an overnight fast. The WHO stepwise approach for non-communicable disease (NCD) surveillance was used to collect data. Fasting blood glucose and blood glucose after 75&#x2009;g oral glucose load was measured, and Enzyme-linked immunosorbent assay (ELISA) was used to test for inflammatory markers (IL-6 and CRP). Associations were explored using the Chi square test and binary logistic regression was performed to estimate the odds ratios. A p-value less than 0.05 was considered statistically significant.<br><br>RESULTS: A total of 240 participants were enrolled. Forty two percent were overweight/obese (>&#x2009;25&#x2009;kg/m[2]), 89% had a high waist to height ratio. The median ART duration was 8(5-10) years. The prevalence of dysglycemia among our cohort of PLHIV was 32%. High CRP was associated with a 2.05 increased odds of having dysglycemia OR 2.05 (1.15-3.65) (p&#x2009;=&#x2009;0.01). Taking stavudine was associated with a 1.99 odds of having dysglycemia OR 1.99 (1.04-3.82) (p&#x2009;=&#x2009;0.03).We did not find a significant association between IL-6 and dysglycemia.<br><br>CONCLUSION: High CRP and taking stavudine were significantly associated with dysglycemia among PLHIV with undetectable viral load.},
}
@article {pmid31319513,
year = {2019},
author = {Fang, A and Dong, J and Zhang, R},
title = {Simulation of Heavy Metals Migration in Soil-Wheat System of Mining Area.},
journal = {International journal of environmental research and public health},
volume = {16},
number = {14},
pages = {},
pmid = {31319513},
issn = {1660-4601},
mesh = {China ; Edible Grain/chemistry ; Environmental Monitoring ; Metals, Heavy/analysis/*metabolism ; Mining ; Regression Analysis ; Soil ; Soil Pollutants/analysis/*metabolism ; Triticum/*metabolism ; },
abstract = {Heavy metals in the soil of mining areas have become a primary source of pollution, which could cause deleterious health effects in people exposed through soil-plant systems via multi-pathways. A long-term field experiment under natural conditions was carried out to explore the distribution characteristic and migration law of heavy metals in a soil-wheat system of a mining area in Xuzhou. According to the second level standard of environmental quality standards for soils of China (GB 15618-1995), 30.8 g of CrCl3·6H2O, 8.3 g of Pb(CH3COO)2·3H2O, and 16.5 g of ZnSO4·7H2O were added into the soil of three experimental sites, respectively. The other experimental site with no additional compounds was used as the control site. The Cr, Pb, and Zn concentrations in the soil-wheat system were counted and their corresponding migration models were constructed. From 2014 to 2017, the mean concentrations of Cr (49.09 mg·kg[-1]), Pb (20.08 mg·kg[-1]), and Zn (39.11 mg·kg[-1]) in the soil of the addition sites were higher than that of the control site. The mean concentrations of Cr, Pb, and Zn in wheat of the addition sites were greater than that of the control site with the values of 3.29, 0.06, and 29 mg·kg[-1]. In comparison, the Cr, Pb, and Zn concentrations in the soil of all experimental sites were lower than the second level standard of environmental quality standards for soils of China (GB 15618-1995), whereas the Cr concentration exceeded its corresponding soil background value of Xuzhou in 2017. The Pb concentration in soil of the addition site was greater than its corresponding background value from 2014 to 2016. The Pb and Zn concentrations in wheat of all experimental sites were lower than the national hygienic standard for grains of China (GB2715-2005) and the national guidelines for cereals of China (NY 861-2004), but the Cr concentration significantly exceeded the national guidelines for cereals of China (NY 861-2004). By constructing the Identical-Discrepant-Contrary (IDC) gray connection models, the result showed that there was a non-linear relationship of Cr, Pb, and Zn concentrations in the soil-wheat system, and the absolute values of most correlation coefficients r were lower than 0.5 and the values of greyness f G (r) were more than 0.5. The curvilinear regression models could not reflect the relationship of Cr, Pb, and Zn concentrations in the soil-wheat system with the regression coefficient r 2 values far less than 1. Due to the values of regression coefficient r 2 being close to 1, this study suggested that the allocation estimation models could be used for simulating the Cr, Pb, and Zn migration in the soil-wheat system of a mining area in Xuzhou.},
}
@article {pmid31312338,
year = {2019},
author = {Traoré, B and Koulibaly, M and Diallo, A and Bah, M},
title = {Molecular profile of breast cancers in Guinean oncological settings.},
journal = {The Pan African medical journal},
volume = {33},
number = {},
pages = {22},
pmid = {31312338},
issn = {1937-8688},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/genetics/*pathology ; Breast Neoplasms, Male/epidemiology/genetics/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Female ; Guinea/epidemiology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/epidemiology/*pathology ; },
abstract = {Breast cancer is a complex disease characterized by the accumulation of multiple molecular alterations giving each tumor phenotype and an own evolutionary potential. This study aimed to describe the distribution of the profile and molecular subtypes of breast cancers followed at Surgical Oncology Unit of Donka National Hospital. This was retrospective and descriptive study on cases of breast cancer in which the hormone receptor status and expression of the Her2 oncogene have been performed from 2007 to 2016. We recorded 58 cases including 56 (96.6%) women and 2 (3.4%) men. The average age was 48.2 ± 10.9. Invasive ductal carcinoma accounted for 50 (86.2%) cases. The SBR grade was II in 31(53.4%) cases, III in 21 (36.2%) cases and I in 6 (10.3%) cases. The tumor was classified as T4 in 36 (62.1%) cases; it was metastatic in 11(19.0%) cases. Estrogen receptors were positive in 29 (50.0%) cases, progesterone receptors positive in 25 (43.1%) cases, the Her2 oncogene was positive in 22 (39.3%) cases. The distribution of molecular sub-types was: 20 (34.5%) luminal A, 15 (25.9%) triple negative, 13 (22.4%) Her2 overexpressed, 8 (13.8%) luminal B and 2 (3.2%) undetermined. This preliminary study showed the poor accessibility of immunohistochemistry for the molecular diagnosis of breast cancer in our country. Luminal A subtypes and triple negatives were more common. The determination of molecular subtypes is a rational basis for hormone therapy and targeted therapy, thus personalizing the treatment of breast cancer.},
}
@article {pmid31308566,
year = {2019},
author = {Malik, SS and Baig, M and Khan, MB and Masood, N},
title = {Survival analysis of breast cancer patients with different treatments: a multicentric clinicopathological study.},
journal = {JPMA. The Journal of the Pakistan Medical Association},
volume = {69},
number = {7},
pages = {976-980},
pmid = {31308566},
issn = {0030-9982},
mesh = {Adult ; Age Factors ; Antineoplastic Agents/*therapeutic use ; Body Mass Index ; Breast Neoplasms/epidemiology/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/epidemiology/mortality/pathology/*therapy ; Cohort Studies ; Combined Modality Therapy ; Consanguinity ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy/*methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Obesity/epidemiology ; Overweight/epidemiology ; Pakistan/epidemiology ; Prospective Studies ; Radiotherapy/*methods ; Risk Factors ; Survival Analysis ; Survival Rate ; },
abstract = {OBJECTIVE: To explore and better understand clinic pathological details of breast cancer patients and analyse their survival rate among different treatment groups.<br><br>METHODS: The prospective cohort, multi-centric study was conducted from September, 2014, to February, 2018, at five hospitals in Rawalpindi and Islamabad, Pakistan, and comprised histo-pathologically confirmed breast cancer cases. Patient characteristics and medical history were collected using a detailed questionnaire. All the subjects were followed up, and information regarding their current health and treatment status was collected. Data was analysed using SPSS 24.<br><br>RESULTS: There were 347 subjects with a mean age of 44.3&#xb1;12.2 years and body mass index of 27.9&#xb1;4.0 kg/m2. Younger age, increased body mass index, consanguinity and family history were major contributing factors in breast cancer development (p<0.05). Overall, 267(77%) had invasive ductal carcinoma and Grade II tumour 234(67%) was more frequent. A total of 221(64%) cases had positive lymph nodes and 97(28%) had metastasis to different body organs. Overall survival analysis showed statistically significant role (p<0.0001) of all treatment options.<br><br>CONCLUSIONS: Combination of different treatments can provide more promising health outcomes in breast cancer cases.},
}
@article {pmid31299411,
year = {2019},
author = {Molina, J and Noguer, M and Lepe, JA and Pérez-Moreno, MA and Aguilar-Guisado, M and Lasso de la Vega, R and Peñalva, G and Crespo-Rivas, JC and Gil-Navarro, MV and Salvador, J and Cisneros, JM},
title = {Clinical impact of an educational antimicrobial stewardship program associated with infectious diseases consultation targeting patients with cancer: Results of a 9-year quasi-experimental study with an interrupted time-series analysis.},
journal = {The Journal of infection},
volume = {79},
number = {3},
pages = {206-211},
doi = {10.1016/j.jinf.2019.07.002},
pmid = {31299411},
issn = {1532-2742},
mesh = {*Anti-Bacterial Agents/therapeutic use ; *Antimicrobial Stewardship ; Communicable Diseases/drug therapy/*epidemiology/etiology ; Drug Utilization/statistics &amp; numerical data ; Female ; Health Plan Implementation ; Humans ; Male ; Neoplasms/complications/*epidemiology ; *Referral and Consultation ; Time Factors ; },
abstract = {OBJECTIVES: Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. However, their effectiveness or safety in immunocompromised hosts needs to be proved.<br><br>METHODS: An ecologic quasi-experimental study was performed from January 2009 to June 2017 in the Oncology department of a tertiary-care hospital. A stable program of Infectious Diseases consultation (IDC) already existed at this unit, and an educational ASP was added in 2011. Its main intervention consisted of face-to-face educational interviews. Antibiotic consumption was assessed through quarterly Defined Daily Doses (DDD) per 100 occupied bed-days. Mortality was evaluated in patients with bloodstream infections through the quarterly incidence density per 1000 admissions, and the annual mortality rates at 7 and 30-days. Time-trends were analysed through segmented-regression analysis, and the impact of the ASP was assessed through before-after interrupted time-series analysis.<br><br>RESULTS: Mortality significantly decreased throughout the study period (-13.3% annual reduction for 7-day mortality rate, p&#xa0;<&#xa0;0.01; -8.1% annual reduction for 30-day mortality, p&#x202f;=&#x202f;0.03), parallel to a reduction in antibiotic consumption (quarterly reduction -0.4%, p&#x202f;=&#x202f;0.01), especially for broader-spectrum antibiotics. The before-after study settled a significant inflexion point on the ASP implementation for the reduction of antibiotic consumption (change in level 0.95 DDD, p&#x202f;=&#x202f;0.71; change in slope -1.98 DDD per quarter, p&#xa0;<&#xa0;0.01). The decreasing trend for mortality before the ASP also continued after its implementation.<br><br>CONCLUSIONS: The combination of an ASP with IDC improved antibiotic use among patients with cancer, and was accompanied by a reduction of mortality of bacteraemic infections. Implementation of the ASP was necessary to effectively change antibiotic use.},
}
@article {pmid31291711,
year = {2020},
author = {Xu, Q and Shao, Y and Zhang, J and Zhang, H and Zhao, Y and Liu, X and Guo, Z and Chong, W and Gu, F and Ma, Y},
title = {Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response.},
journal = {Cancer research and treatment},
volume = {52},
number = {1},
pages = {218-245},
pmid = {31291711},
issn = {2005-9256},
support = {81572851//National Scientific Foundation of China/ ; 81672636//National Scientific Foundation of China/ ; },
mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*drug therapy/*etiology/mortality ; Carrier Proteins/*genetics ; Cell Transformation, Neoplastic/*genetics ; *Disease Susceptibility ; Female ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Proteins/*genetics ; Prognosis ; Recurrence ; Treatment Outcome ; Tumor Burden ; },
abstract = {PURPOSE: Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression.<br><br>MATERIALS AND METHODS: AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3's correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3's impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected.<br><br>RESULTS: AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines.<br><br>CONCLUSION: AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.},
}
@article {pmid31288210,
year = {2019},
author = {Shelef, L and Klomek, AB and Fruchter, E and Kedem, R and Mann, JJ and Zalsman, G},
title = {Suicide ideation severity is associated with severe suicide attempts in a military setting.},
journal = {European psychiatry : the journal of the Association of European Psychiatrists},
volume = {61},
number = {},
pages = {49-55},
doi = {10.1016/j.eurpsy.2019.06.005},
pmid = {31288210},
issn = {1778-3585},
mesh = {Adult ; Female ; Humans ; Intention ; Male ; Middle Aged ; Military Personnel/*psychology ; Risk Factors ; Self Report ; Self-Control/*psychology ; *Severity of Illness Index ; *Suicidal Ideation ; Suicide, Attempted/psychology ; Veterans/*psychology ; Young Adult ; },
abstract = {BACKGROUND: There is an ongoing debate on the effectiveness of suicidal behavior prevention measures in the military. The association of three widely used tools with severe suicide attempts was assessed in this setting.<br><br>METHODS: Thirty-nine Israeli soldiers (59% males), mean age 19 yrs., who attempted suicide during military service were divided into two groups: severe (n&#x2009;=&#x2009;14; 35.9%) and moderate suicide attempts, and were assessed using the Scale for Suicide Ideation (SSI), Suicide Intent Scale (SIS) and the Columbia Suicide Severity Rating Scale (C-SSRS).<br><br>RESULTS: Seven items from the SSI (p&#x2009;=&#x2009;0.008), two items from SIS and one item from C-SSRS were associated with severe suicide attempts. Kendall's tau-b correlation with bootstrap demonstrated stability of these correlations.<br><br>CONCLUSION: Greater severity of suicidal ideation was associated with more severe suicide attempts. The combination of male gender, available firearms and current severe suicide ideation is high-risk danger sign in a military setting, even when reported intent to die is low.},
}
@article {pmid31284267,
year = {2019},
author = {Liu, S and Wei, H and Li, Y and Diao, L and Lian, R and Zhang, X and Zeng, Y},
title = {Characterization of dendritic cell (DC)-10 in recurrent miscarriage and recurrent implantation failure.},
journal = {Reproduction (Cambridge, England)},
volume = {158},
number = {3},
pages = {247-255},
doi = {10.1530/REP-19-0172},
pmid = {31284267},
issn = {1741-7899},
mesh = {Abortion, Habitual/*immunology/metabolism ; Adult ; Cell Differentiation ; Dendritic Cells/immunology/*metabolism ; Embryo Implantation/*immunology ; Female ; Humans ; Interleukin-10/*metabolism ; Interleukin-6/metabolism ; Pregnancy ; Tumor Necrosis Factor-alpha/metabolism ; },
abstract = {During pregnancy, the maternal immune system must tolerate the persistence of semi-allogeneic fetus in the maternal tissue. Inadequate recognition of fetal antigens may lead to pregnancy complications, such as recurrent miscarriage (RM) and recurrent implantation failure (RIF). Dendritic cells (DCs) are key regulators of protective immune responses and the development and maintenance of tolerance. Regarding that DCs are important in the establishment of immune tolerance in human pregnancy, it would be important to study the microenvironment in which DCs reside or are activated may affect their functions toward tolerance rather than active immune response. IL-10 plays a critical role in the maintenance of normal pregnancy, and the increased production of IL-10 is associated with successful pregnancy. In this study, we provide an in-depth comparison of the phenotype and cytokine production by DC-10 and other DC subsets, such as iDC and mDC. CD14+ monocyte-derived DCs were differentiated in the presence of IL-10 (DC-10) in vitro from ten normal fertile controls, six RM women and seven RIF women, and characterized for relevant markers. DC-10 was characterized by relatively low expression of costimulatory molecule CD86, as well as MHC class II molecule HLA-DR, high expression of tolerance molecules HLA-G, ILT2, ILT4 and immunosuppressive cytokine IL-10, but produced little or no proinflammatory cytokines, such as TNF-α, IL-6 and IL-12p70. Our study provides a better understanding of the phenotypical properties of DC-10, which may participate in the complex orchestration that leads to maternal immune tolerance and homeostatic environment in human pregnancy.},
}
@article {pmid31275451,
year = {2019},
author = {Simeunovic, D and Odanovic, N and Pljesa-Ercegovac, M and Radic, T and Radovanovic, S and Coric, V and Milinkovic, I and Matic, M and Djukic, T and Ristic, A and Risimic, D and Seferovic, P and Simic, T and Simic, D and Savic-Radojevic, A},
title = {Glutathione Transferase P1 Polymorphism Might Be a Risk Determinant in Heart Failure.},
journal = {Disease markers},
volume = {2019},
number = {},
pages = {6984845},
pmid = {31275451},
issn = {1875-8630},
mesh = {Aged ; Cardiomyopathy, Dilated/complications/*genetics ; Coronary Artery Disease/complications/*genetics ; Female ; Glutathione S-Transferase pi/*genetics ; Heart Failure/etiology/*genetics ; Humans ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; },
abstract = {Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0.031), which was higher when combined with the variant GSTA1∗B allele (OR = 2.2, p = 0.034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 "risk-associated" genotype (OR = 2.8, p = 0.033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2.1, p = 0.056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗AA/GSTP1∗IleIle carriers (p = 0.021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0.041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0.041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF.},
}
@article {pmid31256281,
year = {2019},
author = {D'Iorio, A and Maggi, G and Vitale, C and Amboni, M and Di Meglio, D and Trojano, L and Santangelo, G},
title = {Prospective memory in Parkinson's disease: the role of the motor subtypes.},
journal = {Journal of neurology},
volume = {266},
number = {10},
pages = {2505-2511},
pmid = {31256281},
issn = {1432-1459},
mesh = {Aged ; Cognitive Dysfunction/etiology/*physiopathology ; Executive Function/physiology ; Female ; Humans ; Hypokinesia/etiology/*physiopathology ; Male ; *Memory, Episodic ; Middle Aged ; Muscle Rigidity/etiology/*physiopathology ; Parkinson Disease/classification/complications/*physiopathology ; Tremor/etiology/*physiopathology ; },
abstract = {BACKGROUND: Prospective memory (PM) is defined as memory for future intentions and it is typically divided into time-based and event-based PM. Deficit of PM has been reported in patients with Parkinson's disease (PD) but no study has yet explored the association between motor subtypes (tremor dominant and rigidity/bradykinesia dominant) and performance on PM tasks. The aim of the study was to explore the role of motor subtypes in the defect of PM.<br><br>METHODS: Consecutive outpatients with tremor dominant (TD-PD) or rigidity/bradykinesia dominant (PIGD-PD) PD and healthy subjects (HCs) were enrolled and underwent a neuropsychological battery assessing PM, verbal memory and executive functions and questionnaires assessing apathy, functional autonomy, and perceived memory disturbances.<br><br>RESULTS: We enrolled 28 patients with TD-PD, 28 patients with PIGD-PD and 50 HCs. The three groups did not differ on demographic and cognitive variables. Patients with TD-PD performed worse on time-based PM tasks than patients with PIGD-PD and HCs; no significant difference was found among the three groups on event-based PM tasks. Executive dysfunctions contributed to reduced time-based PM scores in TD-PD. Moreover, severe deficit of time-based and more frequency of perceived failures of PM contributed to reduced functional autonomy in TD-PD.<br><br>CONCLUSION: The finding of a poorer performance of patients with TD-PD than ones with PIGD-PD and HCs suggests a selective deficit of time-based PM abilities in TD-PD group; therefore, deficit of time-based PM might be considered as a distinctive non-motor symptom of TD-PD and it might affect the functional autonomy in this subtype of PD.},
}
@article {pmid31244288,
year = {2019},
author = {Ghaderi, F and Mehdipour, F and Hosseini, A and Talei, A and Ghaderi, A},
title = {Establishment and Characterization of a New Triple Negative Breast Cancer Cell Line from an Iranian Breast Cancer Tissue.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {20},
number = {6},
pages = {1683-1689},
pmid = {31244288},
issn = {2476-762X},
mesh = {Adult ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Culture Techniques ; Cell Line, Tumor ; *Cell Movement ; *Cell Proliferation ; *Chromosome Aberrations ; Female ; Humans ; Karyotyping ; Triple Negative Breast Neoplasms/metabolism/*pathology ; },
abstract = {Breast cancer is the most common malignancy and the leading cause of cancer-related death among women worldwide. The underlying mechanisms for breast cancer development, especially in young women, are not completely understood. Although there are several experimental models to understand the biology of breast cancer such as immortalized cell lines, many of these cell lines have been in culture for decades and most of them have been derived from Caucasians or African-Americans. So, it is required to establish a new cell line derived from primary tumors and Asian women. In this study Pari-Institute for Cancer Research (Pari-ICR) was derived from the primary breast tumor of a 36-years old patient with invasive ductal carcinoma. We characterized the cell line by examining morphology, expression of different markers, and functional profile. Immunocytochemistry showed that this cell line does not express estrogen and progesterone receptors as well as human epidermal growth factor receptor 2 (HER2). Pari-ICR cell line expresses high levels of Vimentin, Ezrin, and S100 but does not express EpCAM, Cytokeratin19, Pan-cytokeratin, Nestin, and Desmin. Its doubling time of Pari-ICR was about 22h and was able to grow as colonies in soft agar. It displayed a higher ability of migration and invasion in comparison with MCF-7 cell line. This breast cancer cell line can serve as a model for understanding the molecular mechanisms of breast carcinogenesis. Moreover, it can be used as an appropriate resource to find novel biomarkers or assess new drugs.},
}
@article {pmid31243309,
year = {2019},
author = {Zwarts, I and van Zutphen, T and Kruit, JK and Liu, W and Oosterveer, MH and Verkade, HJ and Uhlenhaut, NH and Jonker, JW},
title = {Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR.},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {9299},
pmid = {31243309},
issn = {2045-2322},
mesh = {Adipose Tissue/metabolism ; Animals ; Diet ; Duodenum/metabolism ; Fructose/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Glucose Transporter Type 5/*metabolism ; HEK293 Cells ; Haplorhini ; Humans ; Hydrocarbons, Fluorinated/pharmacology ; Ligands ; Liver X Receptors/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Response Elements ; Sulfonamides/pharmacology ; Transcription, Genetic ; },
abstract = {Fructose has become a major constituent of our modern diet and is implicated as an underlying cause in the development of metabolic diseases. The fructose transporter GLUT5 (SLC2A5) is required for intestinal fructose absorption. GLUT5 expression is induced in the intestine and skeletal muscle of type 2 diabetes (T2D) patients and in certain cancers that are dependent on fructose metabolism, indicating that modulation of GLUT5 levels could have potential in the treatment of these diseases. Using an unbiased screen for transcriptional control of the human GLUT5 promoter we identified a strong and specific regulation by liver X receptor α (LXRα, NR1H3). Using promoter truncations and site-directed mutagenesis we identified a functional LXR response element (LXRE) in the human GLUT5 promoter, located at -385 bp relative to the transcriptional start site (TSS). Finally, mice treated with LXR agonist T0901317 showed an increase in Glut5 mRNA and protein levels in duodenum and adipose tissue, underscoring the in vivo relevance of its regulation by LXR. Together, our findings show that LXRα regulates GLUT5 in mice and humans. As a ligand-activated transcription factor, LXRα might provide novel pharmacologic strategies for the selective modulation of GLUT5 activity in the treatment of metabolic disease as well as cancer.},
}
@article {pmid31240968,
year = {2021},
author = {Shenkman, G and Pardo Aviv, L and Hain, D and Goren, O and Shapira, S and Nakash, O and Brunstein Klomek, A and Berant, E},
title = {The moderation of attachment in the association between depressive symptoms and self-harm among a clinical sample.},
journal = {Journal of mental health (Abingdon, England)},
volume = {30},
number = {1},
pages = {58-65},
doi = {10.1080/09638237.2019.1630723},
pmid = {31240968},
issn = {1360-0567},
mesh = {Anxiety/epidemiology ; Anxiety Disorders ; *Depression/epidemiology ; Humans ; Object Attachment ; *Self-Injurious Behavior/epidemiology ; },
abstract = {BACKGROUND: Self-harm is a severe health problem worldwide and in particular in clinical settings. The association of depression and self-harm has been extensively studied alongside various variables that have been examined as moderating this association. However, no previous study has examined the moderating role of attachment in this association.<br><br>AIM: We explored the role of attachment orientation in moderating the association between depressive symptoms and self-harm among a sample of patients in a community mental health clinic.<br><br>METHOD: This study was a de-identified archival study of patients' medical charts, and used a convenience sample of 199 patients, which completed self-report measures following the initial intake appointment as part of clinic procedures.<br><br>RESULTS: Findings showed that both attachment anxiety and avoidance moderated the association between depressive symptoms and self-harm, such that depressive symptoms were positively associated with self-harm only when attachment anxiety scores were high, and attachment avoidance scores were high or average.<br><br>CONCLUSIONS: Attachment anxiety and avoidance should be assessed in the initial intake of patients as it has a contribution to understanding self-harm vulnerability among new patients. Future studies should explore this moderation longitudinally so causality could be inferred.},
}
@article {pmid31238731,
year = {2019},
author = {Farsang, A and Bódi, I and Fölker, O and Minkó, K and Benyeda, Z and Bálint, &#xc1; and Oláh, I},
title = {Avian coronavirus infection induces mannose-binding lectin production in dendritic cell precursors of chicken lymphoid organs.},
journal = {Acta veterinaria Hungarica},
volume = {67},
number = {2},
pages = {183-196},
doi = {10.1556/004.2019.020},
pmid = {31238731},
issn = {0236-6290},
mesh = {Animals ; Avian Proteins/metabolism ; Cecum/*immunology ; *Chickens ; Coronavirus Infections/metabolism/*veterinary ; Dendritic Cells/*metabolism ; Gammacoronavirus/physiology ; Mannose-Binding Lectins/*metabolism ; Poultry Diseases/*metabolism ; Specific Pathogen-Free Organisms ; Spleen/*immunology ; },
abstract = {The aim of this immunocytochemical study was to compare mannose-binding lectin (MBL) production induced by avian coronavirus in the spleen and caecal tonsil (CT). One-day-old specific-pathogen-free (SPF) chickens were experimentally infected with six QX field isolates and the H120 vaccine strain. In the negative control birds, the spleen was MBL negative, while the CT showed scattered MBL-positive cells in close proximity and within the surface epithelium and germinal centre (GC)-like cell clusters. MBL was detectable in the ellipsoid-associated cells (EACs) and cell clusters in the periarterial lymphoid sheath (PALS) by 7 days post infection (dpi). In both organs, the MBL-positive cells occupy antigen-exposed areas, indicating that GC formation depends on resident precursors of dendritic cells. The majority of MBL-positive EACs express the CD83 antigen, providing evidence that coronavirus infection facilitated the maturation of dendritic cell precursors. Surprisingly, co-localisation of MBL and CD83 was not detectable in the CT. In the spleen (associated with circulation), the EACs producing MBL and expressing CD83 are a common precursor of both follicular (FDC) and interdigitating dendritic cells (IDC). In the CT (gut-associated lymphoid tissue, GALT) the precursors of FDC and IDC are MBL-producing cells and CD83-positive cells, respectively. In the CT the two separate precursors of lymphoid dendritic cells provide some 'autonomy' for the GALT.},
}
@article {pmid31229512,
year = {2019},
author = {Cao, L and Basudan, A and Sikora, MJ and Bahreini, A and Tasdemir, N and Levine, KM and Jankowitz, RC and McAuliffe, PF and Dabbs, D and Haupt, S and Haupt, Y and Lucas, PC and Lee, AV and Oesterreich, S and Atkinson, JM},
title = {Frequent amplifications of ESR1, ERBB2 and MDM4 in primary invasive lobular breast carcinoma.},
journal = {Cancer letters},
volume = {461},
number = {},
pages = {21-30},
pmid = {31229512},
issn = {1872-7980},
support = {F30 CA203154/CA/NCI NIH HHS/United States ; K99 CA193734/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; },
mesh = {Apoptosis ; Biomarkers, Tumor ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Cell Cycle Checkpoints ; Cell Cycle Proteins/*genetics/metabolism ; Cell Proliferation ; DNA Copy Number Variations ; Estrogen Receptor alpha/*genetics ; Female ; Follow-Up Studies ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/genetics/metabolism/*pathology ; Prognosis ; Proto-Oncogene Proteins/*genetics/metabolism ; Receptor, ErbB-2/*genetics ; Retrospective Studies ; Survival Rate ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics/metabolism ; },
abstract = {Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). To identify potential genetic drivers of ILC progression, we used NanoString nCounter technology to investigate the DNA copy number (CN) in 70 well-curated primary ILC samples. We confirmed prior observations of frequent amplification of CCND1 (33%), and MYC (17%) in ILC, but additionally identified a substantial subset of ILCs with ESR1 and ERBB2 (19%) amplifications. Of interest, tumors with ESR1 CN gains (14%) and amplification (10%) were more likely to recur compared to those with normal CN. Finally, we observed that MDM4 (MDMX) was amplified in 17% of ILC samples. MDM4 knockdown in TP53 wild-type ILC cell lines caused increased apoptosis, decreased proliferation associated with cell cycle arrest, and concomitant activation of TP53 target genes. Similar effects were seen in TP53 mutant cells, indicting a TP53-independent role for MDM4 in ILC. To conclude, amplification of ESR1 and MDM4 are potential genetic drivers of ILC. These amplifications may represent actionable, targetable tumor dependencies, and thus have potential clinical implications and warrant further study.},
}
@article {pmid31222554,
year = {2019},
author = {Arya, BK and Bhattacharya, SD and Harigovind, G and Das, RS and Khan, T and Ganaie, F and Niyogi, SK and Ravikumar, KL and Manoharan, A and Bhattacharyya, S and Panda, S and Mandal, S and Acharya, B},
title = {Streptococcus pneumoniae Acquisition and Carriage in Vaccine Naïve Indian Children with HIV and their Parents: A Longitudinal Household Study.},
journal = {Indian journal of pediatrics},
volume = {86},
number = {11},
pages = {1002-1010},
pmid = {31222554},
issn = {0973-7693},
support = {Fulbright-Nehru Doctoral Research Award 2014-15//United States Department of State's Bureau of Educational and Cultural Affairs, and USIEF, New Delhi/International ; 5/7/463/2010-RHN//Indian Council of Medical Research/International ; },
mesh = {Carrier State/*microbiology ; Child ; Child, Preschool ; Female ; HIV Infections/*complications/epidemiology/microbiology ; Humans ; India ; Longitudinal Studies ; Male ; Microbial Sensitivity Tests ; Nasopharynx/microbiology ; Parents ; Pneumococcal Infections/epidemiology/*microbiology/transmission/virology ; Pneumococcal Vaccines/*administration &amp; dosage ; Prevalence ; Prospective Studies ; Serogroup ; Serotyping ; Streptococcus pneumoniae/immunology/*pathogenicity ; Vaccination ; },
abstract = {OBJECTIVES: To investigate the difference in pneumococcal carriage, acquisition, antibiotic resistance profiles and serotype distribution, in human immunodeficiency virus (HIV) affected and unaffected families.<br><br>METHODS: A prospective cohort study was conducted in children with and without HIV in West Bengal from March 2012 through August 2014, prior to 13-valent pneumococcal conjugate vaccine (PCV-13) immunization. One thousand four hundred forty one nasopharyngeal swabs were collected and cultured at five-time points from children and their parents for pneumococcal culture, and serotyping by Quellung method.<br><br>RESULTS: One hundred twenty five HIV infected children and their parents, and 47 HIV uninfected children and their parents participated. Two hundred forty pneumococcal isolates were found. In children under 6 y, the point prevalence of colonization was 31% in children living with HIV (CLH) and 32% in HIV uninfected children (HUC), p&#x2009;=&#x2009;0.6. The most common vaccine type (VT) serotypes were 6A, 6B and 19A. All isolates from parents and 71% from children in the HIV uninfected cohort were PCV-13 representative, compared to 33% of isolates from CLH and their parents. Acquisition rate in children was 1.77 times that of parents (OR&#x2009;=&#x2009;1.77, 95%CI: 1.18-2.65). The HIV status of child or parent did not affect acquisition. Isolates from CLH were more frequently resistant to multiple antibiotics (p&#x2009;=&#x2009;0.02).<br><br>CONCLUSIONS: While the rate of pneumococcal carriage and acquisition did not differ between CLH and HUC, HIV affected families had exposure to a wider range of serotypes including non-vaccine type serotypes and antibiotic resistant serotypes, than HIV unaffected families.},
}
@article {pmid31217350,
year = {2019},
author = {Lodd, E and Wiggenhauser, LM and Morgenstern, J and Fleming, TH and Poschet, G and Büttner, M and Tabler, CT and Wohlfart, DP and Nawroth, PP and Kroll, J},
title = {The combination of loss of glyoxalase1 and obesity results in hyperglycemia.},
journal = {JCI insight},
volume = {4},
number = {12},
pages = {},
pmid = {31217350},
issn = {2379-3708},
mesh = {Animals ; CRISPR-Cas Systems ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2/genetics ; Diet ; Disease Models, Animal ; Gene Knockout Techniques ; Genetic Predisposition to Disease ; Glucose/metabolism ; Hyperglycemia/*etiology/genetics ; Insulin Resistance ; Lactoylglutathione Lyase/genetics/*physiology ; Liver/metabolism ; Male ; Obesity/*complications ; Pyruvaldehyde/metabolism ; Retina/pathology ; Zebrafish/growth &amp; development ; },
abstract = {The increased formation of methylglyoxal (MG) under hyperglycemia is associated with the development of microvascular complications in patients with diabetes mellitus; however, the effects of elevated MG levels in vivo are poorly understood. In zebrafish, a transient knockdown of glyoxalase 1, the main MG detoxifying system, led to the elevation of endogenous MG levels and blood vessel alterations. To evaluate effects of a permanent knockout of glyoxalase 1 in vivo, glo1-/- zebrafish mutants were generated using CRISPR/Cas9. In addition, a diet-induced-obesity zebrafish model was used to analyze glo1-/- zebrafish under high nutrient intake. Glo1-/- zebrafish survived until adulthood without growth deficit and showed increased tissue MG concentrations. Impaired glucose tolerance developed in adult glo1-/- zebrafish and was indicated by increased postprandial blood glucose levels and postprandial S6 kinase activation. Challenged by an overfeeding period, fasting blood glucose levels in glo1-/- zebrafish were increased which translated into retinal blood vessel alterations. Thus, the data have identified a defective MG detoxification as a metabolic prerequisite and glyoxalase 1 alterations as a genetic susceptibility to the development of type 2 diabetes mellitus under high nutrition intake.},
}
@article {pmid31203172,
year = {2019},
author = {Raetz, AG and David, SS},
title = {When you're strange: Unusual features of the MUTYH glycosylase and implications in cancer.},
journal = {DNA repair},
volume = {80},
number = {},
pages = {16-25},
pmid = {31203172},
issn = {1568-7856},
support = {R01 CA067985/CA/NCI NIH HHS/United States ; R29 CA067985/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; DNA/metabolism ; *DNA Damage ; DNA Glycosylases/*metabolism ; *DNA Repair ; Guanine/analogs &amp; derivatives/metabolism ; Humans ; Neoplasms/genetics/*metabolism ; *Signal Transduction ; },
abstract = {MUTYH is a base-excision repair glycosylase that removes adenine opposite 8-oxoguanine (OG). Variants of MUTYH defective in functional activity lead to MUTYH-associated polyposis (MAP), which progresses to cancer with very high penetrance. Whole genome and whole exome sequencing studies have found MUTYH deficiencies in an increasing number of cancer types. While the canonical OG:A repair activity of MUTYH is well characterized and similar to bacterial MutY, here we review more recent evidence that MUTYH has activities independent of OG:A repair and appear centered on the interdomain connector (IDC) region of MUTYH. We summarize evidence that MUTYH is involved in rapid DNA damage response (DDR) signaling, including PARP activation, 9-1-1 and ATR signaling, and SIRT6 activity. MUTYH alters survival and DDR to a wide variety of DNA damaging agents in a time course that is not consistent with the formation of OG:A mispairs. Studies that suggest MUTYH inhibits the repair of alkyl-DNA damage and cyclopyrimidine dimers (CPDs) is reviewed, and evidence of a synthetic lethal interaction with mismatch repair (MMR) is summarized. Based on these studies we suggest that MUTYH has evolved from an OG:A mispair glycosylase to a multifunctional scaffold for DNA damage response signaling.},
}
@article {pmid31200836,
year = {2019},
author = {Jeyapala, R and Savio, AJ and Olkhov-Mitsel, E and Kamdar, S and Zhao, F and Cuizon, C and Liu, RSC and Zlotta, A and Fleshner, N and van der Kwast, T and Bapat, B},
title = {GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.},
journal = {European urology oncology},
volume = {2},
number = {3},
pages = {231-238},
doi = {10.1016/j.euo.2018.08.003},
pmid = {31200836},
issn = {2588-9311},
mesh = {Biomarkers, Tumor/genetics ; Carcinoma, Intraductal, Noninfiltrating/blood/genetics/mortality/pathology ; Cell Line, Tumor ; DNA Methylation ; DNA-Binding Proteins/genetics ; Dioxygenases ; Epigenesis, Genetic ; Homeodomain Proteins/*genetics ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*genetics/metabolism/*pathology/surgery ; Proto-Oncogene Proteins/genetics ; Recurrence ; Survival Analysis ; },
abstract = {BACKGROUND: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required.<br><br>OBJECTIVE: To investigate tumor-specific methylation of the transcription factor GBX2 as a novel prognosticator and predictor of BCR in PCa patients stratified by histopathologic features including IDC/C.<br><br>Using genome-wide methylome profiling, we identified higher GBX2 methylation in grade group (GG) 4 tumors compared to GG1 (discovery cohort). The prognostic nature of GBX2 methylation was validated in silico using The Cancer Genome Atlas data (n=478) and a quantitative methylation assay for radical prostatectomy samples (n=254). Regulation of GBX2 methylation was investigated in prostate cells using methyl-CpG-binding domain sequencing and methylation analysis in functional knockouts of TET2, a key epigenetic player in prostate carcinogenesis.<br><br>The association of GBX2 methylation with Gleason score (GS), pathologic stage (pT), IDC/C, and BCR was analyzed using Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression analyses were used to predict BCR.<br><br>RESULTS: GBX2 methylation was associated with GS (p<0.05), pT (p<0.01), and BCR (p<0.05). GBX2 methylation (p=0.004), GS (p<0.001), pT (p=0.012), and prostate-specific antigen (p=0.005) were independent predictors of BCR. Among IDC/C-negative patients, GBX2 methylation improved prediction of BCR (p=0.002). Loss of TET2 in prostate cells resulted in greater GBX2 methylation.<br><br>CONCLUSIONS: We identified GBX2 methylation as a novel prognostic factor in PCa and an independent predictor of BCR. We demonstrated the additive value of GBX2 methylation in predicting BCR among IDC/C-negative patients and elucidated a novel TET2-mediated upstream epigenetic regulatory mechanism of GBX2.<br><br>PATIENT SUMMARY: We identified GBX2 methylation as a promising prognostic biomarker that could improve the identification of prostate cancer patients at higher risk of biochemical recurrence.},
}
@article {pmid31192864,
year = {2019},
author = {Horimoto, Y and Terao, T and Tsutsumi, Y and Tanabe, M and Mogushi, K and Hlaing, MT and Sasaki, R and Saeki, H and Okazaki, M and Sonoue, H and Arakawa, A and Saito, M},
title = {Estrogen Receptor-positive Ductal Carcinoma In Situ Frequently Overexpresses HER2 Protein Without Gene Amplification.},
journal = {The American journal of surgical pathology},
volume = {43},
number = {9},
pages = {1221-1228},
doi = {10.1097/PAS.0000000000001300},
pmid = {31192864},
issn = {1532-0979},
mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Female ; Gene Amplification ; Genes, erbB-2 ; Humans ; Middle Aged ; Receptor, ErbB-2/*biosynthesis ; Receptors, Estrogen/metabolism ; },
abstract = {Overexpression of human epidermal growth factor receptor 2 (HER2) protein is well known to be more frequent in ductal carcinoma in situ (DCIS) than in invasive ductal carcinoma (IDC). However, the reasons for this difference are poorly understood. On the basis of the high frequency of estrogen receptor-positive (ER+) and HER2-positive (HER2+) DCIS, we hypothesized that this tumor type overexpresses HER2 protein without gene amplification and retrospectively investigated the HER2/neu gene status of 71 ER(+)HER2(+) DCIS, surgically removed during the 2007 to 2017 period, employing fluorescence in situ hybridization (FISH). To compare HER2 protein expressions between in situ and invasive components of individual tumors, 86 pT1mi/1a IDC with predominantly in situ disease were also examined. Furthermore, for comparison of FISH status between in situ and coexisting invasive components, another patient cohort, 78 FISH-positive IDC cases, were employed. To elucidate biological differences among DCIS with various combinations of ER and HER2 protein expressions, we also analyzed public microarray data of mRNA. HER2 gene amplification was observed in 35% of ER(+) and HER2 protein-overexpressing specimens, significantly lower than the 94% in ER-negative (ER-) and HER2 protein-overexpressing specimens (P<0.001). HER2 protein expression was decreased in the invasive component as compared with coexisting in situ portions in 40% of individual tumors, whereas the FISH status of these 2 components was well preserved. Moreover, ER(+) and HER2 protein-overexpressing DCIS showed significantly higher hypoxia-inducible factor-1α protein expression than the ER(+) and HER2 protein-nonoverexpressing tumors (P=0.016). We revealed that ER(+) and HER2 protein-overexpressing DCIS, especially ER-high tumors, frequently overexpress HER2 protein without gene amplification. Our data may provide novel insights for understanding the biology of DCIS.},
}
@article {pmid31192530,
year = {2019},
author = {Zhang, J and Zhao, B and Jin, F},
title = {The assessment of 8th edition AJCC prognostic staging system and a simplified staging system for breast cancer: The analytic results from the SEER database.},
journal = {The breast journal},
volume = {25},
number = {5},
pages = {838-847},
doi = {10.1111/tbj.13347},
pmid = {31192530},
issn = {1524-4741},
mesh = {Breast Neoplasms/*classification/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/genetics ; Female ; Humans ; Middle Aged ; Neoplasm Staging/*standards/statistics &amp; numerical data ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; SEER Program ; United States ; },
abstract = {The prognostic value of the prognostic staging system that incorporated estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (Her-2), and histological grade has been validated in breast cancer (BC) patients, but the staging system seems to be somewhat complex. Recently, an updated bioscore system based on these tumor biological factors was proposed. The purpose of this study was to compare the prognostic stratification between prognostic staging system of American Joint Commission on Cancer (AJCC) and a simplified staging system based on the bioscore system and anatomic TNM staging for BC patients. A total of 44 593 patients with invasive ductal carcinoma who underwent radical resection between 2010 and 2011 were reviewed using the SEER database. The patients were reclassified into different groups according to the anatomic staging system, prognostic staging system, risk bioscore system, and simplified staging system, respectively. The prognostic differences between different groups were compared and clinicopathologic features were analyzed. The anatomic TNM staging failed to clearly distinguish the prognostic difference between stage IIIB and stage IIIC. Therefore, we proposed an adjusted anatomic staging, in which T1N3 and T2N3 were downstaged from stage IIIC to stage IIIB, and T4N2 was upstaged from stage IIIB to stage IIIC. Histological grade III, ER(-), PR(-), and Her-2(-) were identified as independent prognostic factors in the multivariate analysis, and these factors were separately marked as 1 point. There were significant survival differences among different risk points except for the comparison between 0 and 1 point. The higher the risk points, the poorer the prognosis of BC patients. In addition, the curve distance between stage IIA and stage IIB was not significantly broaden according to the prognostic staging system. However, the prognostic stratification for BC patients could be significantly improved by the simplified staging system incorporated the bioscore system and adjusted anatomic staging. Several drawbacks may still exist in the prognostic staging system of AJCC. A simplified staging system that incorporated risk score system and the anatomic staging could provide more accurate prognostic information for BC patients.},
}
@article {pmid31182966,
year = {2019},
author = {Bao, Y and Wang, L and Shi, L and Yun, F and Liu, X and Chen, Y and Chen, C and Ren, Y and Jia, Y},
title = {Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.},
journal = {Cellular &amp; molecular biology letters},
volume = {24},
number = {},
pages = {38},
pmid = {31182966},
issn = {1689-1392},
mesh = {Breast Neoplasms/*genetics ; Down-Regulation/genetics ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics/metabolism ; Receptors, Cell Surface/*metabolism ; Reproducibility of Results ; Sequence Analysis, RNA ; Signal Transduction/*genetics ; Transcriptome/genetics ; Up-Regulation/genetics ; },
abstract = {BACKGROUND: Exploration of the genes with abnormal expression during the development of breast cancer is essential to provide a deeper understanding of the mechanisms involved. Transcriptome sequencing and bioinformatics analysis of invasive ductal carcinoma and paracancerous tissues from the same patient were performed to identify the key genes and signaling pathways related to breast cancer development.<br><br>METHODS: Samples of breast tumor tissue and paracancerous breast tissue were obtained from 6 patients. Sequencing used the Illumina HiSeq platform. All. Only perfectly matched clean reads were mapped to the reference genome database, further analyzed and annotated based on the reference genome information. Differentially expressed genes (DEGs) were identified using the DESeq R package (1.10.1) and DEGSeq R package (1.12.0). Using KOBAS software to execute the KEGG bioinformatics analyses, enriched signaling pathways of DEGs involved in the occurrence of breast cancer were determined. Subsequently, quantitative real time PCR was used to verify the accuracy of the expression profile of key DEGs from the RNA-seq result and to explore the expression patterns of novel cancer-related genes on 8 different clinical individuals.<br><br>RESULTS: The transcriptomic sequencing results showed 937 DEGs, including 487 upregulated and 450 downregulated genes in the breast cancer specimens. Further quantitative gene expression analysis was performed and captured 252 DEGs (201 downregulated and 51 upregulated) that showed the same differential expression pattern in all libraries. Finally, 6 upregulated DEGs (CST2, DRP2, CLEC5A, SCD, KIAA1211, DTL) and 6 downregulated DEGs (STAC2, BTNL9, CA4, CD300LG, GPIHBP1 and PIGR), were confirmed in a quantitative real time PCR comparison of breast cancer and paracancerous breast tissues from 8 clinical specimens. KEGG analysis revealed various pathway changes, including 20 upregulated and 21 downregulated gene enrichment pathways. The extracellular matrix-receptor (ECM-receptor) interaction pathway was the most enriched pathway: all genes in this pathway were DEGs, including the THBS family, collagen and fibronectin. These DEGs and the ECM-receptor interaction pathway may perform important roles in breast cancer.<br><br>CONCLUSION: Several potential breast cancer-related genes and pathways were captured, including 7 novel upregulated genes and 76 novel downregulated genes that were not found in other studies. These genes are related to cell proliferation, movement and adhesion. They may be important for research into breast cancer mechanisms, particularly CST2 and CA4. A key signaling pathway, the ECM-receptor interaction signal pathway, was also identified as possibly involved in the development of breast cancer.},
}
@article {pmid31182685,
year = {2019},
author = {Arabpour, M and Ghods, A and Shariat, M and Talei, AR and Mehdipour, F and Ghaderi, A},
title = {Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer.},
journal = {Iranian journal of immunology : IJI},
volume = {16},
number = {2},
pages = {108-116},
doi = {10.22034/IJI.2019.80254},
pmid = {31182685},
issn = {1735-367X},
mesh = {4-1BB Ligand/*metabolism ; Adult ; B-Lymphocytes/*immunology ; Breast Neoplasms/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Female ; Flow Cytometry ; Humans ; Lymphocyte Activation ; Middle Aged ; Neoplasm Staging ; Receptors, Estrogen/metabolism ; Sentinel Lymph Node/*metabolism ; },
abstract = {BACKGROUND: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity.<br><br>OBJECTIVE: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters.<br><br>METHODS: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti&#x2012;CD19 and anti&#x2012;4-1BBL antibodies and subjected to flow cytometry.<br><br>RESULTS: 4-1BBL expression was detected on 2.8 &#xb1; 1.7% of unstimulated B cells, while 27.4 &#xb1; 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER&#x2012; or PR&#x2012; patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage.<br><br>CONCLUSIONS: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.},
}
@article {pmid31177561,
year = {2019},
author = {Downes, MR and Xu, B and van der Kwast, TH},
title = {Gleason grade patterns in nodal metastasis and corresponding prostatectomy specimens: impact on patient outcome.},
journal = {Histopathology},
volume = {75},
number = {5},
pages = {715-722},
doi = {10.1111/his.13938},
pmid = {31177561},
issn = {1365-2559},
mesh = {Aged ; Aged, 80 and over ; Humans ; Lymphatic Metastasis/*pathology ; Male ; Middle Aged ; *Neoplasm Grading ; Pelvic Neoplasms/*pathology/secondary ; Prognosis ; Prostate/pathology ; Prostatectomy ; Prostatic Neoplasms/*pathology ; Retrospective Studies ; },
abstract = {AIMS: Lymph node metastases at the time of prostatectomy are an infrequent finding. The correlation of the pattern of nodal metastases with patient outcome has yet to be explored.<br><br>METHODS AND RESULTS: Lymph node-positive prostatectomies were retrospectively reviewed. The presence of cribriform carcinoma (CC), intraductal carcinoma (IDC) and ISUP grade (G) were documented. The largest nodal metastasis was assessed for the morphological patterns present. G was assigned to the metastasis based on percentage morphological patterns present. Statistical analysis used spss to assess disease-specific survival (DSS), disease-free survival (DFS) and distant metastasis-free survival (DMFS). One hundred and ten cases were identified: G5 (n&#xa0;=&#xa0;52), G4 (n&#xa0;=&#xa0;8), G3 (n&#xa0;=&#xa0;34), G2 (n&#xa0;=&#xa0;10) and no G (n&#xa0;=&#xa0;6; treatment effect). IDC or CC was present in 103 (94%) specimens. More than one positive node correlated with worse DFS [P&#xa0;=&#xa0;0.012, hazard ratio (HR)&#xa0;=&#xa0;1.951, 95% confidence interval (CI)&#xa0;=&#xa0;1.142-3.331] and DMFS (P&#xa0;=&#xa0;0.009, HR&#xa0;=&#xa0;2.647, 95% CI&#xa0;=&#xa0;1.239-5.651). G in the prostate and nodal metastasis were poorly correlated (kappa&#xa0;=&#xa0;0.073, P&#xa0;=&#xa0;0.195). The presence of pattern 5 was seen in 33 nodes (30%) and correlated with DFS (P&#xa0;=&#xa0;0.020, HR&#xa0;=&#xa0;1.903, 95% CI&#xa0;=&#xa0;1.091-3.320), DSS (P&#xa0;=&#xa0;0.021, HR&#xa0;=&#xa0;5.937, 95% CI&#xa0;=&#xa0;1.084-32.533) and DMFS (P&#xa0;=&#xa0;0.007, HR&#xa0;=&#xa0;2.695, 95% CI&#xa0;=&#xa0;1.269-5.726). Nodal cribriform pattern showed no prognostic correlation and pattern 3 metastasis showed a significant trend towards better outcome (DMFS P&#xa0;=&#xa0;0.033, HR&#xa0;=&#xa0;0.431, 95% CI&#xa0;=&#xa0;0.194-0.958).<br><br>CONCLUSIONS: IDC or CC is identified in 94% of node-positive prostate cancers. Although G in the largest nodal metastasis has prognostic significance, its G does not reflect that of the primary prostatic adenocarcinoma.},
}
@article {pmid31172621,
year = {2019},
author = {Hamzah, JL and Ong, KW and Tan, BY},
title = {Isolated invasive ductal carcinoma of the nipple-areolar complex: A rare occurrence yet to be reported in current literature.},
journal = {The breast journal},
volume = {25},
number = {4},
pages = {706-708},
doi = {10.1111/tbj.13308},
pmid = {31172621},
issn = {1524-4741},
mesh = {Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; Nipples/*pathology ; Paget's Disease, Mammary/pathology ; Ultrasonography, Mammary ; },
abstract = {Invasive ductal carcinoma of the nipple-areolar complex is exceedingly rare. Patients who present with bloody nipple discharge with or without the presence of Paget's disease constitute one-third of all symptomatic in situ patients. Only rarely does an invasive cancer cause nipple discharge in the absence of a clinical mass. Even more obscure is the case of the invasive cancer involving solely the nipple-areolar complex. Sir James Paget first described 'an eczematous change in the skin of the nipple preceding an underlying mammary cancer' in 1874, which is now known as Paget's disease, considered to be ductal carcinoma in situ of the nipple-areolar region. There are two competing theories as to the pathogenesis of Paget's disease of the breast-one suggests that Pagetoid cells are keratinocytes that have undergone malignant transformation. According to this theory, Paget's disease of the breast represents an in situ carcinoma of the skin-and that overlying skin changes and underlying malignancy are discontinuous. The second theory suggests that cells migrate along basement membranes and enter the epidermis and dermis of the nipple-areola complex. Pagetoid cells and underlying carcinomas demonstrate similar immunohistochemical staining patterns.},
}
@article {pmid31171819,
year = {2019},
author = {Chavez, DE and Gronau, I and Hains, T and Kliver, S and Koepfli, KP and Wayne, RK},
title = {Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus).},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {8329},
pmid = {31171819},
issn = {2045-2322},
mesh = {*Adaptation, Physiological ; Animals ; Animals, Wild/genetics ; *Biological Evolution ; Body Patterning ; Canidae/*genetics ; Computational Biology ; DNA/analysis ; Diet ; Female ; *Genomics ; Genotype ; Hedgehog Proteins/genetics ; Molar ; Monte Carlo Method ; Pigmentation ; Predatory Behavior ; },
abstract = {Within the Canidae, the African wild dog (Lycaon pictus) is the most specialized with regards to cursorial adaptations (specialized for running), having only four digits on their forefeet. In addition, this species is one of the few canids considered to be an obligate meat-eater, possessing a robust dentition for taking down large prey, and displays one of the most variable coat colorations amongst mammals. Here, we used comparative genomic analysis to investigate the evolutionary history and genetic basis for adaptations associated with cursoriality, hypercanivory, and coat color variation in African wild dogs. Genome-wide scans revealed unique amino acid deletions that suggest a mode of evolutionary digit loss through expanded apoptosis in the developing first digit. African wild dog-specific signals of positive selection also uncovered a putative mechanism of molar cusp modification through changes in genes associated with the sonic hedgehog (SHH) signaling pathway, required for spatial patterning of teeth, and three genes associated with pigmentation. Divergence time analyses suggest the suite of genomic changes we identified evolved ~1.7 Mya, coinciding with the diversification of large-bodied ungulates. Our results show that comparative genomics is a powerful tool for identifying the genetic basis of evolutionary changes in Canidae.},
}
@article {pmid31171772,
year = {2019},
author = {Haythorne, E and Rohm, M and van de Bunt, M and Brereton, MF and Tarasov, AI and Blacker, TS and Sachse, G and Silva Dos Santos, M and Terron Exposito, R and Davis, S and Baba, O and Fischer, R and Duchen, MR and Rorsman, P and MacRae, JI and Ashcroft, FM},
title = {Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells.},
journal = {Nature communications},
volume = {10},
number = {1},
pages = {2474},
pmid = {31171772},
issn = {2041-1723},
support = {FC001999/WT_/Wellcome Trust/United Kingdom ; G0900747/MRC_/Medical Research Council/United Kingdom ; MR/T002107/1/MRC_/Medical Research Council/United Kingdom ; 095531/WT_/Wellcome Trust/United Kingdom ; 095531/Z/11/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Adenosine Triphosphate/metabolism ; Animals ; Diabetes Mellitus, Experimental/*genetics/metabolism ; Diabetes Mellitus, Type 2/*genetics/metabolism ; Gene Expression Profiling ; Gluconeogenesis ; Glucose/*metabolism ; Glycolysis ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism ; Metabolomics ; Mice ; Mice, Transgenic ; Mitochondria/*metabolism ; NAD/metabolism ; Oxidative Phosphorylation ; Oxygen Consumption ; Potassium Channels, Inwardly Rectifying/genetics ; Proteomics ; },
abstract = {Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.},
}
@article {pmid31171763,
year = {2019},
author = {Kim, SJ and Kim, JY},
title = {An Unusual Cutaneous Recurrence of Carcinoma in the Mastectomy Bed and Its Imaging Features: A Case Report.},
journal = {The American journal of case reports},
volume = {20},
number = {},
pages = {800-805},
pmid = {31171763},
issn = {1941-5923},
mesh = {Adult ; Biopsy, Needle ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/methods ; Mastectomy/*methods ; Neoplasm Recurrence, Local/*diagnostic imaging/surgery ; Rare Diseases ; Risk Assessment ; Skin Neoplasms/*secondary/surgery ; Ultrasonography, Doppler, Color/methods ; },
abstract = {BACKGROUND Chest wall recurrences of carcinoma after mastectomy usually involve subcutaneous tissue or the deep muscular layer. Recurrences arising in the skin are rare, and there are few reports of the associated radiologic features. This report presents an unusual case of cutaneous recurrence in the mastectomy bed and demonstrates its radiologic features using sonography and magnetic resonance imaging (MRI). CASE REPORT A 44-year-old woman presented with a palpable lump in the inferomedial area of the right chest wall. Six years ago, she had undergone total mastectomy for ductal carcinoma in situ in her right breast. Sonography showed an indistinct, oval, heterogeneous echoic mass measuring 0.9 cm, confined within the skin layer, corresponding to the palpable lump. A color Doppler sonogram showed minimal, spotted vascularity in and around the mass. Sonography-guided fine-needle aspiration biopsy was performed, revealing multiple clusters of atypical cells, suggestive of ductal carcinoma. On subsequent breast MRI, the mass, measuring 1.3 cm, was again localized to the skin; dynamic contrast-enhanced scans showed a circumscribed margin, oval shape, and rim enhancement (morphology) and slow initial enhancement and persistent delayed enhancement (kinetics). The mass was surgically excised and the pathological examination confirmed the diagnosis as recurrent invasive ductal carcinoma in the dermis. CONCLUSIONS Cutaneous recurrence in the mastectomy bed can manifest as a mass with suspicious radiologic features: indistinct margin on the sonogram and rim enhancement on the MRI. Awareness of such radiologic features may aid in differentiating between the various cutaneous manifestations encountered after mastectomy.},
}
@article {pmid31169985,
year = {2019},
author = {Yamashita, H and Kurita, A and Azuma, S and Kudo, Y and Matsuzaki, N and Yazumi, S},
title = {Usefulness of immunohistochemical staining for MUC5AC in differentiating primary pancreatic cancer from pancreatic metastasis of breast cancer.},
journal = {Diagnostic cytopathology},
volume = {47},
number = {10},
pages = {1037-1041},
doi = {10.1002/dc.24249},
pmid = {31169985},
issn = {1097-0339},
mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Diagnosis, Differential ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Middle Aged ; Mucin 5AC/genetics/*metabolism ; Pancreatic Neoplasms/metabolism/*pathology/secondary ; },
abstract = {Diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its differentiation from metastases to the pancreas from other organs remains challenging. We report a case in which immunohistochemical staining for MUC5AC was useful in distinguishing primary pancreatic cancer from breast cancer metastasis. A 51-year-old Japanese woman who underwent curative resection of her breast cancer was referred to our hospital with a pancreatic head tumor. Although we surmised her pancreatic tumor to be metastatic breast cancer based on her past history and imaging studies, she was subsequently diagnosed with PDAC on the basis of immunohistochemical staining for MUC5AC using specimens obtained by endoscopic ultrasound-fine-needle aspiration. Thus, MUC5AC may be a useful diagnostic marker for discriminating PDAC from a secondary malignancy.},
}
@article {pmid31146042,
year = {2019},
author = {Zhu, J and Sun, K and Xu, X and Sun, J and Kong, Q and Wang, S and Shi, J},
title = {A Preliminary Attempt of Nonintervention in the Treatment of Patients with Intervertebral Disc Calcification Combined with Ossification of the Posterior Longitudinal Ligament.},
journal = {World neurosurgery},
volume = {129},
number = {},
pages = {181-185},
doi = {10.1016/j.wneu.2019.05.169},
pmid = {31146042},
issn = {1878-8769},
mesh = {Child ; Female ; Humans ; Intervertebral Disc/*pathology ; Ossification of Posterior Longitudinal Ligament/*complications/pathology ; Ossification, Heterotopic/*complications/pathology ; Remission, Spontaneous ; *Watchful Waiting ; },
abstract = {BACKGROUND: Calcification of intervertebral disc is a common impairment, which has been considered as the degenerative condition of the spine. In clinical practice, we note that the onset of intervertebral disc calcification (IDC) and ossification of the posterior longitudinal ligament (OPLL) can exist simultaneously in some cases, especially in younger children. However, only 8 cases have been reported in detail previously. In addition, controversy remains in terms of the best way to treat this condition.<br><br>CASE DESCRIPTION: An 8-year-old female child was referred to our department in March 2018 complaining of severe back pain and neck pain with a sign of neurologic dysfunction. Computed tomography and magnetic resonance imaging revealed the calcified intervertebral disc and OPLL at the C5-C6 level and spinal cord compression. We performed a noninterventional strategy for the patient. The patient's symptom recovered significantly in approximately 1 month. At 6 months of follow-up, the patient felt no discomfort, and computed tomography revealed the complete resorption of ossified lesion. Magnetic resonance imaging also showed no sign of compression on the spinal cord and nerve root at the involved segment.<br><br>CONCLUSIONS: Pediatric IDC accompanied with OPLL is much less frequent, but we must be aware of this disease. Since the distribution of this disease is age-specific and sex-specific, further research is necessary. Treatment for IDC combined with OPLL needs to follow the treatment principles as described in the text.},
}
@article {pmid31142066,
year = {2019},
author = {Zhao, JG and Nie, L and Chen, XQ and Chen, N and Zeng, H},
title = {[The subgroup analysis of the prognostic value of the intraductal carcinoma of the prostate in patients with metastatic prostate cancer].},
journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]},
volume = {57},
number = {6},
pages = {422-427},
doi = {10.3760/cma.j.issn.0529-5815.2019.06.006},
pmid = {31142066},
issn = {0529-5815},
support = {81402110, 81672547//National Natural Science Foundation of China/ ; },
mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/mortality/*pathology/secondary ; Retrospective Studies ; },
abstract = {Objective: To determine the prognostic value of the intraductal carcinoma of the prostate IDC-P in metastatic prostate cancer (mPCa) patients of different subgroups. Methods: Data of 582 de novo mPCa patients between January 2011 and December 2017 diagnosed at Departments of Urology, West China Hospital, Sichuan University were retrospectively analyzed. The age was (70±8) years (range: 45 to 89 years). IDC-P was identified from 12-core prostate biopsy. The prognostic role of IDC-P was assessed by Kaplan-Meier curves and Cox regression. Subgroup analysis was conducted by the forest plot. The endpoints were castration-resistant prostate cancer free survival (CFS) and overall survival (OS). Results: In total, 177/582 (30.4%) patients harbored IDC-P. Patients with IDC-P had poorer CFS and OS than those without IDC-P (mCFS: 12.1 months vs. 16.9 months, P=0.000; mOS: 39.7 months vs. not reached, P=0.000). Multivariate Cox regression analysis indicated that, the existence of IDC-P was an independent prognosticator of both CFS (HR=1.40, 95% CI: 1.10 to 1.79, P=0.006) and OS (HR=1.51, 95% CI: 1.02 to 2.25, P=0.041). Subanalysis indicated that, in most subgroups, IDC-P was an adverse prognosticator of both CFS and OS. Even in subgroups with adverse clinicopathological features, e.g. Gleason score 9 to 10 (CFS: HR=1.467, P=0.007; OS: HR=1.807, P=0.013), baseline prostate specific antigen≥50 μg/L (CFS: HR=1.616, P=0.000; OS: HR=1.749, P=0.006), anemia (CFS: HR=1.653, P=0.036; OS: HR=2.100, P=0.038), alkaline phosphatase≥160 U/L (CFS: HR=1.326, P=0.038; OS: HR=1.725, P=0.010) or abnormal lactate dehydrogenase level (CFS: HR=1.614, P=0.001; OS: HR=1.900, P=0.003), IDC-P was still closely associated with shorter CFS and OS. Conclusions: The presence of IDC-P was closely related to poor survival outcomes for patients with mPCa. IDC-P was an adverse prognosticator in most subgroup patients. The description of IDC-P in the pathological report of prostate biopsy would help clinicians to evaluate the prognosis of mPCa patients more accurately and make better treatment choices.},
}
@article {pmid31134761,
year = {2019},
author = {Chen, S and Chen, H and Yi, Y and Jiang, X and Lei, H and Luo, X and Chen, Y and Liu, S and Yuan, D and Jia, X and Li, J},
title = {Comparative study of breast cancer with or without concomitant Paget disease: An analysis of the SEER database.},
journal = {Cancer medicine},
volume = {8},
number = {8},
pages = {4043-4054},
pmid = {31134761},
issn = {2045-7634},
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/etiology/mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Paget's Disease, Mammary/*epidemiology/etiology/mortality/pathology ; Population Surveillance ; Prognosis ; SEER Program ; },
abstract = {BACKGROUND: Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone.<br><br>METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, 2000-2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD-IDC) and 1489 women who had PD with ductal carcinoma in situ (PD-DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD.<br><br>RESULTS: PD-IDC and PD-DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P&#xa0;=&#xa0;0.182 in PD-IDC and P&#xa0;=&#xa0;0.371 in PD-DCIS), HER2 status (P&#xa0;=&#xa0;0.788 in PD-IDC and P&#xa0;=&#xa0;0.643 in PD-DCIS), and combined molecular subtype (P&#xa0;=&#xa0;0.196 in PD-IDC and P&#xa0;=&#xa0;0.853 in PD-DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD-IDC as well as PD-DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD-DCIS (ICD-O-3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I-III cancer) and was associated with worse survival outcomes than the other type of PD-DCIS.<br><br>CONCLUSIONS: Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD-DCIS cases were invasive breast cancer cases that required special treatment.},
}
@article {pmid31120568,
year = {2019},
author = {Henry, NL and Cannon-Albright, LA},
title = {Breast cancer histologic subtypes show excess familial clustering.},
journal = {Cancer},
volume = {125},
number = {18},
pages = {3131-3138},
pmid = {31120568},
issn = {1097-0142},
support = {NU58DP0063200-01/CC/CDC HHS/United States ; //University of Utah/ ; P30 CA42014//Huntsman Cancer Institute/ ; HHSN261201800016C/CA/NCI NIH HHS/United States ; //Utah Cancer Registry/ ; HHSN261201800016I/CA/NCI NIH HHS/United States ; //Huntsman Cancer Foundation/ ; P30 CA042014/CA/NCI NIH HHS/United States ; },
mesh = {Adenocarcinoma, Mucinous/epidemiology/*genetics/pathology ; Breast Neoplasms/epidemiology/*genetics/pathology ; Carcinoma, Lobular/epidemiology/*genetics/pathology ; Family ; Female ; Genetic Predisposition to Disease ; Humans ; Inflammatory Breast Neoplasms/epidemiology/*genetics/pathology ; Middle Aged ; Pedigree ; SEER Program ; Utah/epidemiology ; },
abstract = {BACKGROUND: The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype.<br><br>METHODS: By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives.<br><br>RESULTS: The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n&#xa0;=&#xa0;178], lobular [n&#xa0;=&#xa0;1688], and mucinous [n&#xa0;=&#xa0;542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P&#xa0;=&#xa0;.011) as well as for inflammatory breast cancers (P&#xa0;=&#xa0;.024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P&#xa0;=&#xa0;.03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P&#xa0;<&#xa0;.001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P&#xa0;=&#xa0;.00021) subtypes.<br><br>CONCLUSIONS: These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.},
}
@article {pmid31111513,
year = {2019},
author = {Shah, RB and Shore, KT and Yoon, J and Mendrinos, S and McKenney, JK and Tian, W},
title = {PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma).},
journal = {The Prostate},
volume = {79},
number = {11},
pages = {1267-1273},
doi = {10.1002/pros.23831},
pmid = {31111513},
issn = {1097-0045},
mesh = {Adenocarcinoma/*genetics/metabolism/pathology ; Alleles ; Biomarkers, Tumor ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Humans ; Male ; Mutation ; Neoplasm Grading ; PTEN Phosphohydrolase/*genetics/metabolism ; Prostatic Neoplasms/*genetics/metabolism/pathology ; },
abstract = {BACKGROUND: The loss of PTEN tumor suppressor gene is one of the most common somatic genetic aberrations in prostate cancer (PCa) and is frequently associated with high-risk disease. Deletion or mutation of at least one PTEN allele has been reported to occur in 20% to 40% of localized PCa and up to 60% of metastases. The goal of this study was to determine if somatic alteration detected by PTEN immunohistochemical loss of expression is associated with specific histologic features.<br><br>METHODS: Two hundred sixty prostate core needle biopsies with PCa were assessed for PTEN loss using an analytically validated immunohistochemical assay. Blinded to PTEN status, each tumor was assessed for the Grade Group (GG) and the presence or absence of nine epithelial features. Presence of stromogenic PCa was also assessed and defined as grade 3 reactive tumor stroma as previously described: the presence of carcinoma associated stromal response with epithelial to stroma ratio of greater than 50% reactive stroma.<br><br>RESULTS: Eight-eight (34%) cases exhibited PTEN loss while 172 (66%) had intact PTEN. PTEN loss was significantly (P&#x2009;<&#x2009;0.05) associated with increasing GG, poorly formed glands (74% of total cases with loss vs 49% of intact), and three well-validated unfavorable pathological features: intraductal carcinoma of the prostate (IDC-P) (69% of total cases with loss vs 12% of intact), cribriform Gleason pattern 4 (38% of total cases with loss vs 10% of intact) and stromogenic PCa (23% of total cases with loss vs 6% of intact). IDC-P had the highest relative risk (4.993, 95% confidence interval, 3.451-7.223, P&#x2009;<&#x2009;0.001) for PTEN loss. At least one of these three unfavorable pathological features were present in 67% of PCa exhibiting PTEN loss, while only 11% of PCa exhibited PTEN loss when none of these three unfavorable pathological features were present.<br><br>CONCLUSIONS: PCa with PTEN loss demonstrates a strong correlation with known unfavorable histologic features, particularly IDC-P. This is the first study showing the association of PTEN loss with stromogenic PCa.},
}
@article {pmid31109373,
year = {2019},
author = {Tan, W and Tao, L and Zhou, Z and Yin, W and Chen, Y},
title = {Tumor-to-tumor metastasis: a rare case of breast carcinoma metastasizing to a pheochromocytoma, and a literature review.},
journal = {Diagnostic pathology},
volume = {14},
number = {1},
pages = {46},
pmid = {31109373},
issn = {1746-1596},
support = {NO. JCYJ201710//the Science and Research Foundation of Peking University, Shenzhen Hospital/ ; NO. SZSM201812088//the "San-ming" Project of Medicine in Shenzhen/ ; },
mesh = {Adrenal Gland Neoplasms/*diagnostic imaging/secondary ; Adrenal Glands/diagnostic imaging/pathology ; Adult ; Breast/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Pheochromocytoma/*diagnostic imaging/secondary ; Tomography, X-Ray Computed ; },
abstract = {BACKGROUND: Tumor-to-tumor metastasis is a well-recognized but uncommon entity. Breast carcinoma is one of the most common metastatic donors. Breast carcinoma metastasizes commonly to adrenal glands. However, the co-existence of a metastatic lesion with an existing adrenal tumor is a rare finding.<br><br>CASE PRESENTATION: A 35-year-old woman was diagnosed with pheochromocytoma using computed tomography and ultrasound examinations. The tumor was surgically removed. Histological and immunohistochemical staining suggested that there were two components in the tumor: pheochromocytoma and metastatic cancer.<br><br>CONCLUSION: This is the second published case of pheochromocytoma with tumor-to-tumor metastasis from an invasive ductal carcinoma of the breast. Furthermore, we highlight the importance of awareness of tumor-to-tumor metastasis in pathological diagnosis.},
}
@article {pmid31107526,
year = {2019},
author = {Nasir, A and Lehrke, HD and Mounajjed, T and Said, S and Zhang, L and Yasir, S and Shah, SS and Chandan, VS and Smyrk, TC and Moreira, RK and Boland Froemming, JM and Herrera Hernandez, LP and Wu, TT and Graham, RP},
title = {Albumin In Situ Hybridization Can Be Positive in Adenocarcinomas and Other Tumors From Diverse Sites.},
journal = {American journal of clinical pathology},
volume = {152},
number = {2},
pages = {190-199},
doi = {10.1093/ajcp/aqz032},
pmid = {31107526},
issn = {1943-7722},
mesh = {Adenocarcinoma/genetics/*metabolism/pathology ; Albumins/genetics/*metabolism ; Bile Duct Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Hepatocellular/genetics/*metabolism/pathology ; Cholangiocarcinoma/genetics/*metabolism/pathology ; Gallbladder Neoplasms/genetics/*metabolism/pathology ; Humans ; In Situ Hybridization ; Liver Neoplasms/genetics/*metabolism/pathology ; Retrospective Studies ; },
abstract = {OBJECTIVES: Albumin messenger RNA (mRNA) expression is a marker of hepatocellular differentiation. Most published data are from review of tissue microarrays, and albumin in situ hybridization (ISH) expression across several tumor types is incompletely characterized.<br><br>METHODS: Sections from 221 tumors were evaluated for albumin mRNA. Immunohistochemistry was used to confirm diagnoses. Albumin ISH was performed according to manufacturer-provided instructions. Fifty-nine cases were evaluated with both commercial ISH assays.<br><br>RESULTS: Albumin mRNA was detected in all hepatocellular carcinomas (HCCs) and 81% of intrahepatic cholangiocarcinomas. Lung (20%), gallbladder (39%), hepatoid pancreatic (n = 1 of 1) adenocarcinoma, breast invasive ductal carcinoma (18%), yolk sac tumor (25%), and acinar cell carcinoma (29%) showed expression. Both assays were concordant in 93% of cases.<br><br>CONCLUSIONS: Albumin ISH was expressed in all HCCs studied. It was also positive in intrahepatic cholangiocarcinoma and patchy positive in gallbladder adenocarcinoma and a subset of other neoplasms, which can be a potential pitfall.},
}
@article {pmid31100224,
year = {2018},
author = {Montironi, R and Zhou, M and Magi-Galluzzi, C and Epstein, JI},
title = {Features and Prognostic Significance of Intraductal Carcinoma of the Prostate.},
journal = {European urology oncology},
volume = {1},
number = {1},
pages = {21-28},
doi = {10.1016/j.euo.2018.03.013},
pmid = {31100224},
issn = {2588-9311},
mesh = {Biopsy ; Carcinoma, Ductal/*diagnosis/genetics ; Diagnosis, Differential ; Disease Management ; *Genomic Instability ; Humans ; Male ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/*diagnosis/genetics ; Tumor Burden ; },
abstract = {CONTEXT: Intraductal carcinoma of the prostate (IDC-P) is an intraglandular/ductal neoplastic growth of glandular epithelial cells characterized by marked abnormality of the glandular architecture and/or cytological atypia that exceeds what is typically seen in high-grade prostatic intraepithelial neoplasia (HPGIN). It has been shown that IDC-P is a strong independent indicator of poor prognosis for prostate carcinoma (PCa).<br><br>OBJECTIVE: To review the pathological and genetic features, diagnostic criteria and differential diagnosis, and clinical significance of IDC-P.<br><br>EVIDENCE ACQUISITION: PubMed was searched using keywords including prostate carcinoma, intraductal carcinoma, IDC, histology, diagnostic criteria, and prognosis. The references in relevant articles were also reviewed.<br><br>EVIDENCE SYNTHESIS: IDC-P is a distinct entity with characteristic morphological and genetic features. It is strongly associated with aggressive PCa with high Gleason score/grade groups and large tumor volume, and portends unfavorable clinical outcomes. Morphological diagnostic criteria have been established to distinguish it from other lesions with similar histological features. IDC-P is an uncommon finding in prostate biopsies, and is even rarer as an isolated finding without concomitant PCa. However, patients with isolated IDC-P in biopsy specimens are recommended to have either definitive treatment or immediate repeat biopsy.<br><br>CONCLUSIONS: It is critical to recognize and report IDC-P, especially in prostate biopsies, where the clinical impact of such a diagnosis is greatest.<br><br>PATIENT SUMMARY: Intraductal carcinoma is a unique form of aggressive prostate cancer. In this report, we review its pathological and genetic features and poor prognostic significance. It is critical for pathologists to recognize and report this lesion in prostate specimens, especially in prostate biopsies for patient management.},
}
@article {pmid31092426,
year = {2019},
author = {Rusak, A and Jablonska, K and Piotrowska, A and Grzegrzolka, J and Wojnar, A and Dziegiel, P},
title = {Correlation of Expression of CHI3L1 and Nogo-A and their Role in Angiogenesis in Invasive Ductal Breast Carcinoma.},
journal = {Anticancer research},
volume = {39},
number = {5},
pages = {2341-2350},
doi = {10.21873/anticanres.13351},
pmid = {31092426},
issn = {1791-7530},
mesh = {Aged ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/genetics ; Chitinase-3-Like Protein 1/*genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Middle Aged ; Neovascularization, Pathologic/*genetics ; Nogo Proteins/*genetics ; Receptors, Cell Surface/genetics ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor C/*genetics ; Vascular Endothelial Growth Factor D/genetics ; },
abstract = {BACKGROUND/AIM: Chitinase 3 like 1 (CHI3L1) is a secretion glycoprotein. Elevated levels of this protein are observed in cancer diseases. The biological role of CHI3L1 is not yet fully known, but the connection between CHI3L1 and angiogenesis has been shown. Recent reports also describe the association of Nogo isoforms and Nogo-B receptor (NgBR) with a proliferative potential, cancer cell invasiveness, and angiogenesis. The aim of this study was to evaluate the levels of CHI3L1, Nogo-A, Nogo-A/B, and NgBR and correlate them with clinical-pathological data, to study their role in angiogenesis in invasive ductal breast carcinoma (IDC).<br><br>MATERIALS AND METHODS: A total of 77 IDC cases were used in the study. Immunohistochemistry was used to determine the level of expression of CHI3L1, Nogo-A, Nogo-A/B, NgBR and vascular endothelial growth factors (VEGFA, VEGFC and VEGFD). The obtained results were subjected to statistical analysis including clinicalpathological data.<br><br>RESULTS: A statistically significant positive correlation of CHI3L1 and Nogo-A expression (r=0.474, p>0.0001) and a positive correlation of Nogo-A and VEGFC expression (r=0.280, p=0.013) were found.<br><br>CONCLUSION: CHI3L1 and Nogo-A are important in angiogenesis in IDC.},
}
@article {pmid31087408,
year = {2019},
author = {Baydoun, S and Gonzalez, P and Whitman, GJ and Dryden, M and Xi, Y and Dogan, B},
title = {Is Ductography Still Warranted in the 21st century?.},
journal = {The breast journal},
volume = {25},
number = {4},
pages = {654-662},
doi = {10.1111/tbj.13302},
pmid = {31087408},
issn = {1524-4741},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Diseases/diagnostic imaging/*pathology ; Breast Neoplasms/diagnostic imaging/pathology ; Contrast Media ; Female ; Humans ; Image-Guided Biopsy ; Magnetic Resonance Imaging/methods ; Mammography/*methods/statistics &amp; numerical data ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography, Mammary ; Young Adult ; },
abstract = {OBJECTIVE: To determine the utility of ductography in conjunction with mammography and ultrasound in patients with pathologic nipple discharge, and the incremental role of MRI after triple-modality evaluation.<br><br>MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who had presented with pathologic nipple discharge and had undergone mammography and/or ultrasound and ductography between January 1, 2005, and October 31, 2010. We tested the diagnostic sensitivity, specificity and accuracy of combined triple-modality evaluation as well as of MRI performed in addition to these imaging techniques. We used the gold standard of image-guided biopsies, surgical excision, or long-term clinical and imaging follow-up.<br><br>RESULTS: Among 94 study patients, benign papillomas were identified in 42 (44.7%), abscess in one (1%), duct ectasia in four (4.3%), and malignancy (invasive ductal carcinoma or ductal carcinoma in situ) or high-risk lesion (atypical ductal hyperplasia) in 10 (10.6%). Forty-six patients (49%) underwent surgical excision; 89.1% of which had presurgical planning with ductography. In 35 (37.2%) with negative imaging, resolution of nipple discharge was confirmed on median clinical and imaging follow-up of 36&#xa0;months. Two patients with negative imaging were lost to follow-up. Sensitivity, specificity, PPV, and NPV for accurately demonstrating the etiology of pathologic nipple discharge were 13%, 97%, 89%, and 37% respectively for mammography; 73%, 97%, 98%, and 64% respectively for ultrasound; 76%, 72%, 84%, and 61% respectively for ductography; 86%, 70%, 85%, and 72% respectively for combined ultrasound and ductography; and 75%, 100%, 100% and 67% respectively for DCE-MRI.<br><br>CONCLUSION: The combination of mammography, ultrasound and ductography is highly accurate for identifying the etiology of pathologic nipple discharge. DCE-MRI can be used as an alternate to ductography if necessary.},
}
@article {pmid31063527,
year = {2019},
author = {Ciurea, AI and Boca, I and Rogojan, L and Ciule, LD and Ciortea, CA},
title = {Pectoralis muscle metastases from breast cancer in a young patient detected by automated breast ultrasound.},
journal = {Medical ultrasonography},
volume = {21},
number = {2},
pages = {200-203},
doi = {10.11152/mu-1769},
pmid = {31063527},
issn = {2066-8643},
mesh = {Adult ; Breast Neoplasms/*pathology/therapy ; Fatal Outcome ; Female ; Humans ; Muscle Neoplasms/*diagnostic imaging/*secondary ; Neoplasm Recurrence, Local/*diagnostic imaging ; Pectoralis Muscles/*diagnostic imaging ; Ultrasonography, Mammary/*methods ; },
abstract = {Metastases to the skeletal muscle from breast cancer represent an unusual and rare condition. We present the case of a 27-year-old female with left breast cancer (IDC NST G3) who underwent neoadjuvant chemotherapy followed by conservativesurgery (sectorectomy and lymphadenectomy) and radiation therapy. Two months after the end of radiotherapy she presented with a 2 mm skin lesion and she was referred for a screening ultrasound. The screening automated breast ultrasound (ABUS) revealed local recurrence and pectoralis metastases, lesions evaluated also by magnetic resonance imaging. The diagnosis was confirmed by the ultrasound-guided biopsy.},
}
@article {pmid31060593,
year = {2019},
author = {Petridis, C and Arora, I and Shah, V and Megalios, A and Moss, C and Mera, A and Clifford, A and Gillett, C and Pinder, SE and Tomlinson, I and Roylance, R and Simpson, MA and Sawyer, EJ},
title = {Frequency of pathogenic germline variants in BRCA1, BRCA2, PALB2, CHEK2 and TP53 in ductal carcinoma in situ diagnosed in women under the age of 50 years.},
journal = {Breast cancer research : BCR},
volume = {21},
number = {1},
pages = {58},
pmid = {31060593},
issn = {1465-542X},
support = {MC_PC_14105/MRC_/Medical Research Council/United Kingdom ; 8873/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Adult ; Age Factors ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/epidemiology/*genetics ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/*genetics ; Case-Control Studies ; Checkpoint Kinase 2/genetics ; Computational Biology ; DNA Copy Number Variations ; Female ; *Gene Frequency ; Genotype ; *Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Neoplasm Grading ; Tumor Suppressor Protein p53/genetics ; },
abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal breast cancer, and approximately 20% of screen-detected tumours are pure DCIS. Most risk factors for breast cancer have similar associations with DCIS and IDC; however, there is limited data on the prevalence of the known high and moderate penetrance breast cancer predisposition genes in DCIS and which women with DCIS should be referred for genetic screening. The aim of this study was to assess the frequency of germline variants in BRCA2, BRCA1, CHEK2, PALB2 and TP53 in DCIS in women aged less than 50 years of age.<br><br>METHODS: After DNA extraction from the peripheral blood, Access Array technology (Fluidigm) was used to amplify all exons of these five known breast cancer predisposition genes using a custom made targeted sequencing panel in 655 cases of pure DCIS presenting in women under the age of 50&#x2009;years together with 1611 controls.<br><br>RESULTS: Case-control analysis revealed an excess of pathogenic variants in BRCA2 (OR&#x2009;=&#x2009;27.96, 95%CI 6.56-119.26, P&#x2009;=&#x2009;2.0&#x2009;&#xd7;&#x2009;10[-10]) and CHEK2 (OR&#x2009;=&#x2009;8.04, 95%CI 2.93-22.05, P&#x2009;=&#x2009;9.0&#x2009;&#xd7;&#x2009;10[-6]), with weaker associations with PALB2 (P&#x2009;=&#x2009;0.003), BRCA1 (P&#x2009;=&#x2009;0.007) and TP53 (P&#x2009;=&#x2009;0.02). For oestrogen receptor (ER)-positive DCIS the frequency of pathogenic variants was 9% under the age of 50 (14% with a family history of breast cancer) and 29% under the age of 40 (42% with a family history of breast cancer). For ER-negative DCIS, the frequency was 9% (16% with a family history of breast cancer) and 8% (11% with a family history of breast cancer) under the ages of 50 and 40, respectively.<br><br>CONCLUSIONS: This study has shown that breast tumourigenesis in women with pathogenic variants in BRCA2, CHEK2, PALB2, BRCA1 and TP53 can involve a DCIS precursor stage and that the focus of genetic testing in DCIS should be on women under the age of 40 with ER-positive DCIS.},
}
@article {pmid31057361,
year = {2019},
author = {Aplin, FP and Fridman, GY},
title = {Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy.},
journal = {Frontiers in neuroscience},
volume = {13},
number = {},
pages = {379},
pmid = {31057361},
issn = {1662-4548},
support = {R01 DC009255/DC/NIDCD NIH HHS/United States ; R01 NS092726/NS/NINDS NIH HHS/United States ; R21 NS081425/NS/NINDS NIH HHS/United States ; },
abstract = {Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.},
}
@article {pmid31049740,
year = {2019},
author = {Sanderink, WBG and Laarhuis, BI and Strobbe, LJA and Sechopoulos, I and Bult, P and Karssemeijer, N and Mann, RM},
title = {A systematic review on the use of the breast lesion excision system in breast disease.},
journal = {Insights into imaging},
volume = {10},
number = {1},
pages = {49},
pmid = {31049740},
issn = {1869-4101},
abstract = {PURPOSE: To outline the current status of and provide insight into possible future research on the breast lesion excision system (BLES) as a diagnostic and therapeutic device.<br><br>METHODS: A systematic search of the literature was performed using PubMed, Embase, and the Cochrane databases to identify relevant studies published between January 2002 and April 2018. Studies were considered eligible for inclusion if they evaluated the diagnostic or therapeutic accuracy or safety of BLES.<br><br>RESULTS: Ultimately, 17 articles were included. The reported underestimation rates of atypical ductal hyperplasia and ductal carcinoma in situ (DCIS) ranged from 0 to 14.3% and from 0 to 22.2%, respectively. Complete excision rates for invasive ductal carcinoma and DCIS ranged from 5.3 to 76.3%. Bleeding was the most frequently reported complication (0-11.8%). Device-related complications may arise, with an empty basket being the most common (0.6-3.6%). Thermal damage of the specimen, caused by the use of a radiofrequency cutting wire, was reported in eight of the included studies. Most thermal artifacts were reported as superficial and small (0.1-1.9&#x2009;mm).<br><br>CONCLUSIONS: The BLES, an automated, image-guided, single-pass biopsy system for breast lesions using radiofrequency is designed to excise and retrieve an intact tissue specimen. It is an efficient and safe breast biopsy method with acceptable complication rates, which may be used as an alternative to vacuum-assisted biopsies. The variable rate of complete excision raises questions about the possibility to use BLES as a therapeutic device for the excision of small lesions. Further research should focus on this aspect of BLES.},
}
@article {pmid31046734,
year = {2019},
author = {Aras, S and Maroun, MC and Song, Y and Bandyopadhyay, S and Stark, A and Yang, ZQ and Long, MP and Grossman, LI and Fernández-Madrid, F},
title = {Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.},
journal = {BMC cancer},
volume = {19},
number = {1},
pages = {411},
pmid = {31046734},
issn = {1471-2407},
support = {R01 CA122277/CA/NCI NIH HHS/United States ; R01 CA122277//National Institutes of Health/ ; W81XWH-16-1-0516//U.S. Department of Defense/ ; },
mesh = {Autoantigens/metabolism ; Autoimmunity ; Breast Neoplasms/*diagnosis/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/*genetics/*metabolism ; Neoplasm Invasiveness ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Prospective Studies ; Protein Array Analysis ; Rapamycin-Insensitive Companion of mTOR Protein/genetics ; Transcription Factors/*genetics/*metabolism ; Up-Regulation ; },
abstract = {BACKGROUND: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V.<br><br>METHODS: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1&#x3b1;. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype.<br><br>RESULTS: We identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis.<br><br>CONCLUSIONS: MNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis.},
}
@article {pmid31045815,
year = {2019},
author = {Li, JP and Zhang, XM and Zhang, Z and Zheng, LH and Jindal, S and Liu, YJ},
title = {Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma.},
journal = {Medicine},
volume = {98},
number = {18},
pages = {e15449},
pmid = {31045815},
issn = {1536-5964},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Carcinoma, Ductal/*mortality/*pathology ; Disease-Free Survival ; Female ; Genes, p53/*physiology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Triple Negative Breast Neoplasms/*mortality/*pathology ; Tumor Suppressor Protein p53/genetics ; },
abstract = {TP53 gene is mutated in approximately 80% of triple-negative breast cancer (TNBC). However, the prognostic significance of immunohistochemical (IHC)-detected p53 protein expression remains controversial in TNBC. In this study, we retrospectively analyzed the association between IHC-detected p53 expression and the prognosis in a cohort of 278 patients with stage I-III triple-negative breast invasive ductal carcinoma (IDC), who received surgery at the department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12. We found a positive expression ratio of IHC-detected p53 in triple-negative breast IDC of 58.6% (163/278). Furthermore, levels of expression were significantly associated with vessel tumor emboli and higher histologic grade (P = .038, P = .043, respectively), with the highest expression level observed in G3 breast cancer (64.7%). Additionally, Kaplan-Meier analysis showed that p53 expression indicated worse overall survival (OS) in the whole cohort (79.6% vs 89.6%, Log-rank test P = .025) as well as in stratified prognostic stage II patients (90.8% vs 100%, Log-rank test P = .027). The mortality risk of p53 expression patients was 2.22 times higher than that of p53 negative patients (HR: 2.222; 95%CI: 1.147-4.308). In addition, p53 expression was also associated with poor disease-free survival (DFS) (76.7% vs 86.8%, P = .020). Cox proportional hazard ratio model showed p53 expression was an independent risk factor for OS (P = .018) and DFS (P = .018) after controlling for tumor size, lymph node status, and vessel tumor emboli. Altogether, our data showed that IHC-detected p53 expression is a promising prognostic candidate for poor survival in triple-negative breast IDC patients. However, more studies are needed to determine if p53 may be applied to clinical practice as a biomarker and/or novel therapeutic target for TNBC.},
}
@article {pmid31040709,
year = {2019},
author = {Hinnen, D and Kruger, DF},
title = {Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials.},
journal = {Diabetes, metabolic syndrome and obesity : targets and therapy},
volume = {12},
number = {},
pages = {447-455},
pmid = {31040709},
issn = {1178-7007},
abstract = {BACKGROUND: Patients with type 2 diabetes (T2D) are at increased cardiovascular (CV) risk compared to subjects without diabetes, with some data estimating that CV disease (CVD) risk is doubled in these individuals. Additionally, CVD remains the leading cause of death in patients with T2D, so it is paramount to determine the relationship between these two diseases.<br><br>PURPOSE: Older diabetes treatments have limited CV safety data. In 2008, the US Food and Drug Administration published guidance for manufacturers on antihyperglycemic agents, requiring studies to ensure CV safety of new therapies. Since then, manufacturers of many newer agents have conducted and published results from CV outcomes trials (CVOTs), with more trials due to publish soon. This review discusses the relationship between CVD and T2D and explores findings from the latest CVOTs of glucose-lowering agents to guide nurse practitioners in their prescribing patterns for patients with T2D.<br><br>CONCLUSION: Patients with T2D are at high risk of CVD, so CV risk should be carefully considered when managing these patients, and CV risks and benefits of antidiabetic drugs should be included in prescribing decisions.},
}
@article {pmid31023035,
year = {2019},
author = {Albayrak, M and Senol, O and Demirkaya-Miloglu, F and Calik, M and Kadioglu, Y},
title = {Novel chemometrics‑assisted spectroscopic methods for diagnosis and monitoring of invasive ductal carcinoma in breast tissue.},
journal = {Bratislavske lekarske listy},
volume = {120},
number = {3},
pages = {184-187},
doi = {10.4149/BLL_2019_031},
pmid = {31023035},
issn = {0006-9248},
mesh = {Adult ; *Breast Neoplasms/diagnosis ; *Carcinoma, Ductal, Breast/diagnosis ; Female ; Humans ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; },
abstract = {OBJECTIVES: Early diagnosis of breast cancer is extremely important because it is the most common female cancer and a leading cause of cancer death in adult women. In this study, it is aimed to create Raman mapping with developed chemometrics‑assisted Raman and FT-IR spectroscopy methods for the diagnosis of invasive ductal carcinoma (IDC) in breast tissue samples.<br><br>METHODS: Samples were deparaffinized and 20&#x2011;micron layers of each tissue were located on a coverslip. Mapping of both healthy and cancerous tissues were performed by exposing them to Raman laser at 532 and 758 nm while excitation was recorded at wavenumbers in range of 100-4,000 cm-1. Orthogonal partial least square (OPLS) algorithm was applied to evaluate obtained Raman spectra. Latent variable was selected to explain the whole model.<br><br>RESULTS: Healthy and IDC tissues were accurately and precisely clustered with Raman mapping and obtained results were compared to those obtained by means of histopathology and FT-IR methods. It is claimed that the proposed method has a great potential in clustering and separating IDC tissues from the healthy ones.<br><br>CONCLUSION: This novel, rapid, precise, easy and objective diagnosis method may be an alternative to conventional diagnostic methods for IDC in breast tissue (Fig. 5, Ref. 22).},
}
@article {pmid31022251,
year = {2019},
author = {Ishikane, M and Hayakawa, K and Kutsuna, S and Takeshita, N and Ohmagari, N},
title = {The impact of infectious disease consultation in candidemia in a tertiary care hospital in Japan over 12 years.},
journal = {PloS one},
volume = {14},
number = {4},
pages = {e0215996},
pmid = {31022251},
issn = {1932-6203},
mesh = {Aged ; Candidemia/*epidemiology/mortality ; Communicable Diseases/*epidemiology ; Female ; Humans ; Japan/epidemiology ; Kaplan-Meier Estimate ; Male ; *Referral and Consultation ; *Tertiary Care Centers ; },
abstract = {BACKGROUND: Candidemia is one of the major causes of morbidity and mortality as a hospital acquired infection. Infectious diseases consultation (IDC) might be beneficial to improve candidemia outcomes; however, only limited data from short periods of time are available thus far.<br><br>METHODS: An observational study of all candidemia patients at a large tertiary care hospital between 2002 and 2013 was conducted. A candidemia episode was defined as &#x2265; 1 positive result for Candida spp. in blood culture. Patients who died or transferred to another hospital within two days after their first positive blood culture were excluded. Independent risk factors for 30-day mortality were determined.<br><br>RESULTS: Among 275 patients with 283 episodes of candidemia, 194 (68.6%) were male, and the mean age was 70.0 &#xb1; 15.8 years. Central line-associated bloodstream infections, peripheral line-associated bloodstream infections, intra-abdominal infection, and unknown source comprised 220 (77.7%), 35 (12.4%), 13 (4.7%), and 15 (5.3%) episodes, respectively. A total of 126 patients (44.5%) received IDC. Factors independently associated with 30-day mortality in patients with candidemia were urinary catheters use (adjusted hazard ratio [HR] = 2.94; 95% confidence interval [CI] = 1.48-5.87; P = 0.002) and severe sepsis/septic shock (adjusted HR = 2.10; 95% CI = 1.20-3.65; P = 0.009). IDC was associated with a 46% reduction in 30-day mortality (adjusted HR = 0.54; 95% CI = 0.32-0.90; P = 0.017).<br><br>CONCLUSION: IDC was independently associated with a reduction in 30-day mortality. Only 44.5% of patients with candidemia in this cohort received IDC. Routine IDC should be actively considered for patients with candidemia.},
}
@article {pmid31016756,
year = {2019},
author = {Zenan, H and Zixiong, L and Zhicheng, Y and Mei, H and Xiongbin, Y and Tiantian, W and Min, D and Renbin, L and Changchang, J},
title = {Clinical prognostic evaluation of immunocytes in different molecular subtypes of breast cancer.},
journal = {Journal of cellular physiology},
volume = {234},
number = {11},
pages = {20584-20602},
doi = {10.1002/jcp.28662},
pmid = {31016756},
issn = {1097-4652},
mesh = {Aging ; Biomarkers, Tumor ; Blood Platelets/classification/physiology ; Breast Neoplasms/*classification/*genetics/pathology ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Leukocytes/*classification/*physiology ; Logistic Models ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics/*metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/*pathology ; },
abstract = {To retrospectively analyze the relationship between preoperative blood parameters and postoperative clinical outcomes in patients with different molecular subtypes of breast cancer (BC), a cohort of 601 patients with BC in the Third Affiliated Hospital, Sun Yat-sen University, was retrospectively reviewed. They were categorized into four subtypes according to the expression of ER, PR, HER-2, and KI-67%. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts, the neutrophil-to-lymphocyte ratio (NLR), the neutrophil-to-monocyte ratio (NMR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR) were recorded. Univariate and multivariate analyses were performed to identify the relationship between parameters and ratios and disease-free survival (DFS) and overall survival (OS). Luminal subtypes of BC had smaller tumor volume, better differentiation degree of invasive ductal carcinoma, less lymph node metastasis, and better clinical outcome than the HER-2 overexpression and triple-negative BC (TNBC) subtypes. In multivariate analysis, age and LMR were the independent prognostic factors of DFS in patients with luminal A (age, p = 0.005; LMR, P = 0.026); PLR in patients with luminal B (DFS; p = 0.032; OS, p= 0.012); LMR in patients with HER-2 overexpression (DFS; p = 0.008; OS, p = 0.017); and NLR for DFS (p = 0.014); and WBC for OS (p = 0.008) in patients with TNBC. LMR was the benign predictor of luminal A and HER-2 overexpression. PLR was the adverse predictor of luminal B. WBC and NLR were the adverse predictors of TNBC. Therefore, these peripheral blood parameters can play an important role in the diagnosis and treatment of patients with different molecular subtypes of BC.},
}
@article {pmid31004170,
year = {2019},
author = {Harbertson, J and Scott, PT and Lemus, H and Michael, NL and Hale, BR},
title = {Cross-Sectional Study of Sexual Behavior, Alcohol Use, and Mental Health Conditions Associated With Sexually Transmitted Infections Among Deploying Shipboard US Military Personnel.},
journal = {Military medicine},
volume = {184},
number = {11-12},
pages = {e693-e700},
doi = {10.1093/milmed/usz070},
pmid = {31004170},
issn = {1930-613X},
mesh = {Adult ; Alcohol Drinking/adverse effects/epidemiology/*psychology ; Cross-Sectional Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Mental Disorders/*diagnosis/epidemiology/psychology ; Middle Aged ; Military Personnel/psychology/*statistics &amp; numerical data ; Risk Factors ; Risk-Taking ; Sexual Behavior/*psychology ; Sexually Transmitted Diseases/*diagnosis/epidemiology/psychology ; Ships/statistics &amp; numerical data ; United States/epidemiology ; },
abstract = {INTRODUCTION: Limited comprehensive data exist on risk behavior associated with sexually transmitted infections (STI) among ship-assigned US military personnel during the predeployment time period (PDT). This study examined whether sexual risk behaviors, alcohol use, involuntary drug consumption (IDC), posttraumatic stress disorder (PTSD), and depression during the 12 months prior to deployment were associated with provider-diagnosed STIs in this population.<br><br>MATERIALS AND METHODS: Using cross-sectional data collected during 2012-2014 among sexually active personnel, multivariable regression assessed factors associated with STIs among all men (n = 1,831). Stratified analyses were conducted among men who have sex with women (MSW, n = 1,530), men who have sex with men or men and women (MSM, n = 83), and excluded those not reporting sexual partner gender (n = 218).<br><br>RESULTS: Among MSW, transactional sex (AOR 3.8, 95% CI 1.5-9.4) meeting sexual partners at work (AOR 4.3, 95% CI 2.0-9.2), IDC (AOR 6.6, 95% CI 3.0-14.5), and incomplete mental health assessments (AOR 4.4, 95% CI 1.6-12.0) were significantly associated with STIs after adjustment. Among all men, those who identified as MSM (AOR 4.6, 95% CI 1.9-11.2) and drug screen positive (AOR 3.3, 95% CI 1.3-8.6) were significantly more likely to report an STI.<br><br>CONCLUSIONS: Previously unreported factors significantly associated with STIs at the PDT among MSW in the adjusted analysis were meeting sexual partners at work and IDC. IDC during the PDT warrants further exploration. These results can inform tailored STI reduction interventions among shipboard personnel and similarly aged civilians undergoing similar transition/travel experiences.},
}
@article {pmid30995855,
year = {2019},
author = {Mikudova, V and Rejlekova, K and Gyarfas, J and Oravcova, I and Chovanec, M and Mardiak, J and Mego, M},
title = {Leptomeningeal Metastasis in a Breast Cancer Treated with Two Lines of Intrathecal Chemotherapy - a Case Report.},
journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti},
volume = {32},
number = {2},
pages = {139-142},
doi = {10.14735/amko2018139},
pmid = {30995855},
issn = {1802-5307},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*adverse effects ; Breast Neoplasms/*drug therapy/pathology ; Female ; Humans ; Injections, Spinal ; Meningeal Neoplasms/*drug therapy/secondary ; Prognosis ; },
abstract = {BACKGROUND: Leptomeningeal metastasis (LM) in breast cancer is associated with a poor prognosis. Although no randomised trial has demonstrated that intrathecal chemotherapy actually prolongs survival, this treatment is considered standard of care in this setting. The prognosis of patients with LM is poor, with a median overall survival time of less than 6 months.<br><br>METHODS: Herein, we report a case of a young woman with breast cancer who presented with LM at the time of relapse and was subsequently treated with two lines of intrathecal chemotherapy that prolonged survival.<br><br>RESULTS: A 28-year old woman without a significant past medical history was diagnosed with triple-negative invasive ductal carcinoma. Eight months after adjuvant treatment she developed multiple brain metastases and LM developed subsequently 1 month after finishing whole brain irradiation. Initially, she was treated with a combination of methotrexate, cytarabine and dexamethasone intrathecally but after 3 months she presented with a worsening clinical status and increased numbers of cancer cells in cerebrospinal fluid. Subsequently, she received a combination of thiotepa and methotrexate intrathecally, which resulted in a prolonged response lasting 10 months. The patient died 32 months after initial diagnosis and 18 months from LM infiltration due to disease progression in the liver and lungs as well as LM.<br><br>CONCLUSION: The prognosis of patients with LM remains poor because of the limited effectiveness of currently available therapies; however, intrathecal chemotherapy could substantially prolong survival in selected patients.},
}
@article {pmid30993692,
year = {2019},
author = {Khani, F and Wobker, SE and Hicks, JL and Robinson, BD and Barbieri, CE and De Marzo, AM and Epstein, JI and Pritchard, CC and Lotan, TL},
title = {Intraductal carcinoma of the prostate in the absence of high-grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations.},
journal = {The Journal of pathology},
volume = {249},
number = {1},
pages = {79-89},
doi = {10.1002/path.5283},
pmid = {30993692},
issn = {1096-9896},
mesh = {Aged ; Biomarkers, Tumor/*genetics ; Carcinoma in Situ/classification/*genetics/pathology ; Carcinoma, Ductal/classification/*genetics/pathology ; DNA Copy Number Variations ; Gene Dosage ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Mitogen-Activated Protein Kinases/genetics ; *Mutation ; Neoplasm Grading ; Neoplasm Invasiveness ; *Oncogenes ; PTEN Phosphohydrolase/genetics ; Phenotype ; Phosphatidylinositol 3-Kinase/genetics ; Prostatic Neoplasms/classification/*genetics/pathology ; Transcriptional Regulator ERG/genetics ; Transcriptome ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) most often appears associated with high-grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC-P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low-grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC-P (iIDC-P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC-P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC-P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC-P alterations were similar to those previously described in high-grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC-P (BRCA2, CHEK2, CDK12) and other known PCa-associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC-P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC-P and the low-grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC-P in four. Despite a CNA profile similar to conventional PCa, iIDC-P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC-P is not likely a precursor to the associated low-grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.},
}
@article {pmid30989460,
year = {2019},
author = {Lee, J and Kim, HE and Song, YS and Cho, EY and Lee, A},
title = {miR-106b-5p and miR-17-5p could predict recurrence and progression in breast ductal carcinoma in situ based on the transforming growth factor-beta pathway.},
journal = {Breast cancer research and treatment},
volume = {176},
number = {1},
pages = {119-130},
pmid = {30989460},
issn = {1573-7217},
support = {NRF-2017R1D1A1B03034165//National Research Foundation of Korea/ ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Recurrence, Local ; RNA Interference ; Signal Transduction ; Transcriptome ; Transforming Growth Factor beta/*metabolism ; },
abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to identify potential markers predicting recurrence.<br><br>METHODS: Forty archival tissues diagnosed as primary or recurrent DCIS and DCIS adjacent to IDC were analyzed. MiRNA hierarchical clustering showed up-regulation of miR-17-5p and miR-106b-5p in recurrent DCIS and DCIS adjacent to IDC. Target genes were predicted based on pre-formed miRNA databases and PanCancer Pathway panel. MiRNAs were transfected into MCF-10A and MCF-7 cells; western blot analysis was performed with MCF-7 cell line to evaluate the effects on TGF-&#x3b2; downstream pathway.<br><br>RESULTS: miRNA hierarchical clustering showed 17 dysregulated miRNAs, including miR-17-5p and miR-106b-5p. Based on miRNA database and nCounter Pancancer pathway analysis, TGF&#x3b2;RII was selected as target of miR-106b-5p and miR-17-5p. MiR-106b-5p- and miR-17-5p-transfected MCF-7 cells showed decreased expression of TGF&#x3b2;RII, especially in cells transfected with both miRNAs.<br><br>CONCLUSION: miR-106b-5p and miR-17-5p might have a role in breast cancer recurrence and progression by suppressing TGF-&#x3b2; activity, leading to early breast cancer carcinogenesis.},
}
@article {pmid30985953,
year = {2019},
author = {Erro, R and Picillo, M and Amboni, M and Savastano, R and Scannapieco, S and Cuoco, S and Santangelo, G and Vitale, C and Pellecchia, MT and Barone, P},
title = {Comparing postural instability and gait disorder and akinetic-rigid subtyping of Parkinson disease and their stability over time.},
journal = {European journal of neurology},
volume = {26},
number = {9},
pages = {1212-1218},
doi = {10.1111/ene.13968},
pmid = {30985953},
issn = {1468-1331},
mesh = {Aged ; Female ; Gait Disorders, Neurologic/etiology/*physiopathology ; Humans ; Hypokinesia/etiology/*physiopathology ; Longitudinal Studies ; Male ; Middle Aged ; Parkinson Disease/classification/complications/*physiopathology ; Postural Balance/*physiology ; Tremor/etiology/*physiopathology ; },
abstract = {BACKGROUND AND PURPOSE: Parkinson disease (PD) patients are classically classified according to two alternative motor subtyping methods: (i) tremor-dominant versus postural instability and gait disorder; (ii) tremor-dominant versus akinetic-rigid. The degree of overlap between the two classification systems at diagnosis of PD and their temporal stability, as well as the correspondence between the two systems, were examined over a follow-up period of 4 years.<br><br>METHODS: Newly diagnosed, untreated PD patients were classified as tremor-dominant versus postural instability and gait disorder and tremor-dominant versus akinetic-rigid at baseline and after 2 and 4&#xa0;years.<br><br>RESULTS: There was a poor overlap between the two classification systems at any time point and baseline subtype status could not predict 4-year subtype membership. In fact, about half of our cohort shifted category during the first 2&#xa0;years, regardless of the classification scheme adopted. A lower rate of shift was observed from 2- to 4-year follow-up.<br><br>CONCLUSIONS: The two classical motor subtyping methods of PD poorly overlap, which implies that a patient can be categorized as tremor-dominant in one classification system but not in the other. Moreover, their temporal instability undermines their prognostic value in the early stage of PD.},
}
@article {pmid30982780,
year = {2019},
author = {Ren, W and Guan, W and Zhang, J and Wang, F and Xu, G},
title = {Pyridoxine 5'-phosphate oxidase is correlated with human breast invasive ductal carcinoma development.},
journal = {Aging},
volume = {11},
number = {7},
pages = {2151-2176},
pmid = {30982780},
issn = {1945-4589},
mesh = {Adult ; Aged ; Binding, Competitive ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; MCF-7 Cells ; MicroRNAs/genetics/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Pyridoxaminephosphate Oxidase/antagonists &amp; inhibitors/genetics/*metabolism ; RNA, Long Noncoding/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Tumor Stem Cell Assay ; },
abstract = {Pyridoxine 5'-phosphate oxidase (PNPO) is a converting enzyme for an active form of vitamin B6. This study aims to evaluate the biological function and the regulatory mechanism of PNPO in human breast invasive ductal carcinoma (IDC). We unveiled for the first time that PNPO was upregulated in patients with IDC and was correlated with the overall survival of patients with metastasis at the later stages. Suppression of PNPO inhibited breast cancer cell proliferation, migration, invasion and colony formation, arrested cell cycle at the G2/M phase and induced cell apoptosis. PNPO was positively correlated with lncRNA MALAT1 which was negatively correlated with miR-216b-5p. PNPO was down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells. A microRNA response element was found in both PNPO and MALAT1 transcripts for miR-216b-5p and the dual-luciferase reporter assay confirmed the binding of these transcripts. Knockdown of MALAT1 resulted in an increase of miR-216b-5p and a decrease of PNPO mRNA, indicating a regulatory mechanism of competing endogenous RNAs. Taken together, these results reveal the biological function and a regulatory mechanism of PNPO, in which the MALAT1/miR-216b-5p/PNPO axis may be important in IDC development. Targeting this axis may have therapeutic potential for breast cancer.},
}
@article {pmid30959550,
year = {2019},
author = {Deva Magendhra Rao, AK and Patel, K and Korivi Jyothiraj, S and Meenakumari, B and Sundersingh, S and Sridevi, V and Rajkumar, T and Pandey, A and Chatterjee, A and Gowda, H and Mani, S},
title = {Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications.},
journal = {Molecular oncology},
volume = {13},
number = {6},
pages = {1342-1355},
pmid = {30959550},
issn = {1878-0261},
mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Gene Regulatory Networks/genetics ; Humans ; Prognosis ; RNA, Long Noncoding/genetics/*metabolism ; Sequence Analysis, RNA ; },
abstract = {Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated with early-stage breast cancer. RNA sequencing was performed on six invasive ductal carcinoma (IDC) tissues along with paired normal tissue samples, seven ductal carcinoma in situ tissues, and five apparently normal breast tissues. We identified 375 differentially expressed lncRNAs (DElncRNAs) in IDC tissues compared to paired normal tissues. Antisense transcripts (~ 58%) were the largest subtype among DElncRNAs. About 20% of the 375 DElncRNAs were supported by typical split readings leveraging their detection confidence. Validation was performed in n = 52 IDC and paired normal tissue by qRT-PCR for the identified targets (ADAMTS9-AS2, EPB41L4A-AS1, WDFY3-AS2, RP11-295M3.4, RP11-161M6.2, RP11-490M8.1, CTB-92J24.3, and FAM83H-AS1). We evaluated the prognostic significance of DElncRNAs based on TCGA datasets and report that overexpression of FAM83H-AS1 was associated with patient poor survival. We confirmed that the downregulation of ADAMTS9-AS2 in breast cancer was due to promoter hypermethylation through in vitro silencing experiments and pyrosequencing.},
}
@article {pmid30943919,
year = {2019},
author = {Campbell, EJ and Dachs, GU and Morrin, HR and Davey, VC and Robinson, BA and Vissers, MCM},
title = {Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels.},
journal = {BMC cancer},
volume = {19},
number = {1},
pages = {307},
pmid = {30943919},
issn = {1471-2407},
support = {R1512//Canterbury Medical Research Foundation/ ; R1512//New Zealand Breast Cancer Foundation/ ; },
mesh = {Antigens, Neoplasm/genetics/*metabolism ; Ascorbic Acid/*metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carbonic Anhydrase IX/genetics/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins/genetics/*metabolism ; Retrospective Studies ; Survival Analysis ; Up-Regulation ; Vascular Endothelial Growth Factor A/genetics/*metabolism ; },
abstract = {BACKGROUND: The transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer.<br><br>METHODS: In a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1&#x3b1;, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters.<br><br>RESULTS: HIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with decreased disease-free and disease-specific survival. Grade 1 tumors had higher ascorbate levels than did grade 2 or 3 tumors. Higher ascorbate levels were associated with less tumor necrosis, with lower HIF-1 pathway activity and with increased disease-free and disease-specific survival.<br><br>CONCLUSIONS: Our findings indicate that there is a direct correlation between intracellular ascorbate levels, activation of the HIF-1 pathway and patient survival in breast cancer. This is consistent with the known capacity of ascorbate to stimulate the activity of the regulatory HIF hydroxylases and suggests that optimisation of tumor ascorbate could have clinical benefit via modulation of the hypoxic response.},
}
@article {pmid30916846,
year = {2019},
author = {Leshem, R and van Lieshout, PHHM and Ben-David, S and Ben-David, BM},
title = {Does emotion matter? The role of alexithymia in violent recidivism: A systematic literature review.},
journal = {Criminal behaviour and mental health : CBMH},
volume = {29},
number = {2},
pages = {94-110},
doi = {10.1002/cbm.2110},
pmid = {30916846},
issn = {1471-2857},
mesh = {*Affective Symptoms ; Aggression/psychology ; Crime/*statistics &amp; numerical data ; Criminals/*psychology ; *Emotions ; Humans ; Male ; *Recidivism ; Recurrence ; Risk Assessment ; Risk Factors ; Violence/*psychology/statistics &amp; numerical data ; },
abstract = {BACKGROUND: Several variables have been evidenced for their association with violent reoffending. Resultant interventions have been suggested, yet the rate of recidivism remains high. Alexithymia, characterised by deficits in emotion processing and verbal expression, might interact with these other risk factors to affect outcomes.<br><br>AIM: Our goal was to examine the role of alexithymia as a possible moderator of risk factors for violent offender recidivism. Our hypothesis was that, albeit with other risk factors, alexithymia increases the risk of violent reoffending.<br><br>METHOD: We conducted a systematic literature review, using terms for alexithymia and violent offending and their intersection.<br><br>RESULTS: (a) No study that directly tests the role of alexithymia in conjunction with other potential risk factors for recidivism and actual violent recidivism was uncovered. (b) Primarily alexithymia researchers and primarily researchers into violence have separately found several clinical features in common between aspects of alexithymia and violence, such as impulsivity (total n&#xa0;=&#xa0;24 studies). (c) Other researchers have established a relationship between alexithymia and both dynamic and static risk factors for violent recidivism (n&#xa0;=&#xa0;16 studies).<br><br>CONCLUSION: Alexithymia may be a possible moderator of risk of violent offence recidivism. Supplementing offenders' rehabilitation efforts with assessments of alexithymia may assist in designing individually tailored interventions to promote desistance among violent offenders.},
}
@article {pmid30914612,
year = {2019},
author = {Oki, T and Sugimoto, T and Ogawa, M and Dabanaka, K and Hanazaki, K},
title = {[A Case of Early-Onset Breast Cancer for Which the Operative Indication for Breast Conservation Was Based on BRCA Genetic Testing].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {46},
number = {3},
pages = {555-557},
pmid = {30914612},
issn = {0385-0684},
mesh = {Adult ; *Breast Neoplasms/genetics/surgery ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Testing ; Humans ; Mastectomy, Segmental ; Neoadjuvant Therapy ; *Neoplasm Recurrence, Local ; },
abstract = {We report a case of a patient with early-onset breast cancer who decided to undergo adaptation for breast-conserving surgery based on the results of genetic testing. A 25-year-old woman became aware of a lump in her left breast and visited a nearby hospital, where she was diagnosed with breast cancer. She has no personal history. Her paternal grandfather was diagnosed with rectal cancer at age 60. Ultrasonography revealed an irregularly-shaped hypoechoic mass measuring 3.8 cm in the C area of her left breast and an enlarged lymph node 2.0 cm in diameter in the left axillary area. The breast tumor was pathologically diagnosed as invasive ductal carcinoma by core needle biopsy and was immunohistochemically characterized as ER(-), PgR(-), and HER2(-), s o-called triple negative. Moreover, lymph node metastasis was confirmed by fine needle aspiration cytology. She underwent neoadjuvant chemotherapy and achieved a clinical complete response. A woman with early-onset triple negative breast cancer has a high probability of hereditary breast and ovarian cancer, with a high risk of ipsilateral second breast cancer after conserving surgery. Thus, BRCA genetic testing may be necessary before surgery. As no pathogenic mutation wasfound in BRCA 1/2 in this case, the patient underwent breast-conserving surgery followed by radiation therapy for the conserved breast. The patient remained healthy and without any recurrence 4 years and 2 months after surgery.},
}
@article {pmid30914564,
year = {2019},
author = {Takizawa, K and Sakata, J and Ando, T and Yuza, K and Toge, K and Hirose, Y and Nakano, T and Ishikawa, H and Katada, T and Miura, K and Nagahashi, M and Shimada, Y and Kameyama, H and Kobayashi, T and Wakai, T},
title = {[A Case of Peritoneal Recurrence of Invasive Ductal Carcinoma Derived from Intraductal Papillary Mucinous Neoplasm after Surgery Treated with Palliative Radiation Therapy and Chemotherapy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {46},
number = {2},
pages = {372-374},
pmid = {30914564},
issn = {0385-0684},
mesh = {*Adenocarcinoma, Mucinous ; Aged, 80 and over ; *Carcinoma, Pancreatic Ductal/pathology/therapy ; Combined Modality Therapy ; Humans ; Male ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/pathology/therapy ; *Peritoneal Neoplasms/secondary/therapy ; },
abstract = {An 82-year-old man with a diagnosis ofintraductal papillary mucinous carcinoma(IPMC)underwent pancreaticoduodenectomy followed by adjuvant chemotherapy with S-1. Six months after surgery, he had upper abdominal pain, and CT demonstrated a recurrent intraabdominal tumor located at the surgical incision scar. It was diagnosed as a solitary peritoneal recurrence, and palliative radiation therapy at a dose of 30 Gy was performed for the relief of abdominal pain after administration ofoxycodone. He was free ofpain without pharmacological therapy and received subsequent chemotherapy with nabpaclitaxel plus gemcitabine(GnP). He remains free ofpain and alive without progression ofthe disease 24 months after recurrence. Hypofractionated-accelerated radiotherapy is feasible and results in pain relief for local recurrence of IPMC.},
}
@article {pmid30914555,
year = {2019},
author = {Monden, K and Sakurai, K and Fujisaki, S and Kubota, H and Suzuki, Y and Adachi, K and Suzuki, S and Tomita, R},
title = {[The Diagnostic Problem of Automated Breast Volume Scanner(ABUS)for a Breast Cancer Patient with Dementia-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {46},
number = {2},
pages = {345-347},
pmid = {30914555},
issn = {0385-0684},
mesh = {Aged, 80 and over ; *Breast Neoplasms/complications/diagnosis ; *Dementia/complications ; Female ; Humans ; Mammography ; Mastectomy ; *Sentinel Lymph Node Biopsy ; },
abstract = {The patient was an 84-year-old woman.She had presented with a mass on her right breast.Mammography revealed an illdefined mass.Handheld ultrasonography(HHUS)revealed a low echoic mass, 25mm in diameter, on the AC area of her right breast.An automated breast volume scanner(ABUS)was not useful for detecting the lesion because the patient had dementia and restless body movements.A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma, which was positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.We examined her whole body and made a diagnosis of T2N0M0, StageⅡA.She underwent a muscle-preserving mastectomy plus sentinel lymph node biopsy.The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma, positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.The surgical margins were negative for malignancy, and no metastasis was observed in the sentinel lymph node.She was given endocrine as adjuvant therapies.Three years after the surgery, she was well without metastases.Patients with dementia could not use ABUS.HHUS will be useful for these patients.},
}
@article {pmid30913871,
year = {2019},
author = {Chen, WR and Deng, JP and Wang, J and Sun, JY and He, ZY and Wu, SG},
title = {Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases.},
journal = {Cancer research and treatment},
volume = {51},
number = {4},
pages = {1437-1448},
pmid = {30913871},
issn = {2005-9256},
support = {81872459//National Natural Science Foundation of China/ ; 81803050//National Natural Science Foundation of China/ ; 2016J01635//Natural Science Foundation of Fujian Province/ ; 2018A030313666//Guangdong Academy of Sciences/ ; },
mesh = {Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Chemotherapy, Adjuvant ; Clinical Decision-Making/*methods ; Female ; Gene Expression Profiling/methods ; Humans ; Multivariate Analysis ; Neoplasm Micrometastasis/drug therapy/*genetics ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics ; SEER Program ; Treatment Outcome ; },
abstract = {PURPOSE: The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). Methods Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed.<br><br>RESULTS: We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs.<br><br>CONCLUSION: The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.},
}
@article {pmid30912402,
year = {2019},
author = {Asiaf, A and Ahmad, ST and Malik, AA and Aziz, SA and Zargar, MA},
title = {Association of Protein Expression and Methylation of DAPK1 with Clinicopathological Features in Invasive Ductal Carcinoma Patients from Kashmir.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {20},
number = {3},
pages = {839-848},
pmid = {30912402},
issn = {2476-762X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; *DNA Methylation ; Death-Associated Protein Kinases/*genetics/*metabolism ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Promoter Regions, Genetic ; },
abstract = {Aims: Death-associated protein kinase-1 (DAPK1) is a pro-apoptotic Ser/Thr kinase that participates in cell apoptosis and tumor suppression. DAPK1 is frequently lost in many different tumor types including breast cancer. The aim of this study was to evaluate the promoter methylation status of DAPK1 and a possible correlation with the expression of DAPK1 and standard clinicopathological features in invasive ductal breast carcinoma patients (IDC). Methods: Methylation Specific PCR (MSP) was carried out to investigate the promoter methylation status of DAPK1 from 128 breast cancer patients. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry (n=128) and western blotting (n=56). Results: We found significant difference in DAPK1 promoter methylation frequency among breast tumors when compared with the corresponding normal tissues. Hypermethylation of DAPK1 is significantly correlated with the loss of DAPK1 protein expression (P < .001, rs= -0.361). The loss of DAPK1 protein was significantly associated with estrogen receptor (ER) negativity (p= 0.003), triple negative breast cancer (TNB) (p= 0.024) and advanced tumor stages (P = 0.001). Moreover, age at diagnosis (p= 0.041), tumor stage (p= 0.034), ER negativity (p= 0.004) and TNB cancers (p=0.003) correlated significantly with the hypermethylation of the DAPK1 promoter. Coclusion: This study indicates that DAPK1 is methylated in IDC and promoter hypermethylation could be attributed to silencing of DAPK1 gene expression in breast cancer. Thus, we consider DAPK1 inactivation by promoter hypermethylation likely plays a role in the development and progression of breast cancer.},
}
@article {pmid30905927,
year = {2019},
author = {Koc-Günel, S and Tekeli, N and Smaczny, C and Vogl, T and Rohde, G},
title = {A Case of Lymphangioleiomyomatosis (LAM) of the Lung in a Patient with a History of Breast Cancer.},
journal = {The American journal of case reports},
volume = {20},
number = {},
pages = {390-393},
pmid = {30905927},
issn = {1941-5923},
mesh = {Breast Neoplasms/*complications ; Female ; Humans ; Lung Neoplasms/*complications/*diagnosis ; Lymphangioleiomyomatosis/*complications/*diagnosis ; Middle Aged ; Tomography, X-Ray Computed ; },
abstract = {BACKGROUND Lymphangioleiomyomatosis (LAM) is a rare progressive cystic and nodular disease of the lung characterized by smooth muscle cell proliferation. LAM predominantly affects young premenopausal women. This report is of a case of LAM presenting in a 47-year-old woman with a past history of breast cancer and discusses the possibility of an association between the two conditions. CASE REPORT A 47-year-old woman presented as an emergency with an exacerbation of a four-month history of shortness of breath and dry cough. Her symptoms began following the start of anti-hormonal treatment with letrozole and goserelin acetate for a moderately differentiated (grade 2) invasive ductal carcinoma of the breast (pT2, pN0, M0) which was positive for expression of estrogen receptor (ER+), progesterone receptor (PR+), and human epidermal growth factor receptor 2 (HER2+). Until the previous four months, she had breast-conserving treatment with radiotherapy and tamoxifen therapy. Following hospital admission, she was found to be in type I respiratory failure. Chest X-ray, lung computed tomography (CT), and positron-emission tomography (PET) showed diffuse cystic and nodular lung lesions, consistent with a diagnosis of LAM, and antihormonal therapy was discontinued. She developed pericarditis that was treated with the anti-inflammatory agent, colchicine. Treatment with letrozole and sirolimus improved her respiratory symptoms. CONCLUSIONS A rare case of LAM is presented in a woman with a recent history of breast cancer. Because both tumors were hormone-dependent, this may support common underlying gene associations and signaling pathways between the two types of tumor.},
}
@article {pmid30900303,
year = {2019},
author = {Nie, L and Pan, X and Zhang, M and Yin, X and Gong, J and Chen, X and Xu, M and Zhou, Q and Chen, N},
title = {The expression profile and heterogeneity analysis of ERG in 633 consecutive prostate cancers from a single center.},
journal = {The Prostate},
volume = {79},
number = {8},
pages = {819-825},
doi = {10.1002/pros.23785},
pmid = {30900303},
issn = {1097-0045},
mesh = {Biopsy, Large-Core Needle/methods ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Cohort Studies ; Gene Expression ; Gene Rearrangement ; Genetic Heterogeneity ; Humans ; Image-Guided Biopsy/methods ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Prostatic Neoplasms, Castration-Resistant/genetics/*metabolism/pathology ; Serine Endopeptidases/genetics/metabolism ; Transcriptional Regulator ERG/biosynthesis/genetics ; Tumor Burden ; },
abstract = {BACKGROUND: Overexpression of ERG protein resulting from TMPRSS2:ERG rearrangement is highly specific for prostate cancer (PCa). However, the biological function of this fusion protein and its relationship with clinicopathological features still remain controversial.<br><br>METHOD: In this study, we evaluated ERG protein expression/gene rearrangement and heterogeneity by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in a cohort of 633 consecutive PCa initially diagnosed by core-needle biopsy in the West China Hospital.<br><br>RESULT: Overall, ERG protein expression was detected in 16.7% (106 of 633) cases, and frequently observed in PCa patients less than 60 years of age (31.9% vs 15.5%, P&#x2009;=&#x2009;0.004) and in PCa with Gleason score less than 8 (20.0% vs 13.4%, P&#x2009;=&#x2009;0.027), but infrequently observed in cases with intraductal carcinoma of the prostate (IDC-P) (10.0% vs 18.6%, P&#x2009;=&#x2009;0.012). Follow-up analysis found that patients who progressed to castration-resistant prostate cancer (CRPC) have a lower frequency of ERG protein expression at initial biopsies compared to androgen deprivation therapy (ADT)-sensitive cases (14.1% vs 23.5%, P&#x2009;=&#x2009;0.042), but Kaplan-Meier curve showed that ERG protein expression was not an independent prognostic marker. Of all the 106 ERG-positive cases, eight cases (7.5%) exhibited heterogeneous expression of ERG protein, in which ERG was only positive in tumors with Gleason pattern 3, but negative in Gleason pattern 4. The FISH analysis was consistent with IHC in six of these cases. In the other two cases, ERG rearrangement was detected in tumors with both Gleason pattern 3 and 4 by FISH, despite the negative protein expression in Gleason pattern 4. In case 1, a repeated biopsy was performed when the disease progressed to CRPC, and no ERG-positive cells were identified neither by IHC nor FISH.<br><br>CONCLUSION: This was by far the largest series of ERG expression and heterogeneity analysis in Chinese PCa. The ERG rearrangement seemed to be frequently expressed in patients with relatively younger age and lower Gleason score and infrequently expressed in PCa with the IDC-P. PCa with positive ERG were less frequently to progress to CRPC, but there was no prognostic significance of ERG expression. In heterogeneous cases, ERG protein was detectable only in tumors with Gleason pattern 3 but not in pattern 4. Tumor cells with positive ERG expression/rearrangement seemed easily response to ADT.},
}
@article {pmid30897334,
year = {2019},
author = {Wang, YF and Han, J},
title = {OTOR in breast carcinoma as a potent prognostic predictor correlates with cell proliferation, migration, and invasiveness.},
journal = {Biochemistry and cell biology = Biochimie et biologie cellulaire},
volume = {97},
number = {6},
pages = {750-757},
doi = {10.1139/bcb-2018-0305},
pmid = {30897334},
issn = {1208-6002},
mesh = {Biomarkers, Tumor/antagonists &amp; inhibitors/*genetics/metabolism ; Breast Neoplasms/diagnosis/*genetics/metabolism/*pathology ; *Cell Movement ; Cell Proliferation ; Cells, Cultured ; Cohort Studies ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Prognosis ; Proteins/antagonists &amp; inhibitors/*genetics/metabolism ; RNA, Small Interfering/pharmacology ; },
abstract = {Otoraplin (OTOR), recognized as an important cochlear gene, has a predicted secretory signal peptide sequence and harbors a high degree of cross-species conservation. However, its role in tumor progression is relatively unclear, especially in breast carcinoma (BC). This study investigated the clinicopathological significance of OTOR in breast infiltrating ductal carcinoma (IDC) with high metastasis to uncover its biological function in BC. OTOR was highly overexpressed in BC tissues and cells compared with normal samples. OTOR overexpression was associated with certain clinicopathological characteristics and poorer prognosis (overall survival; OS) of patients with breast IDC. As determined using CCK-8, colony formation, wound-healing, and Transwell assays, silencing OTOR using siRNA impeded BC-cell proliferation, migration, and invasiveness, which may have resulted from inactivating the mitogen-activated protein kinase - extracellular-signal-regulated kinase pathway. These results indicate that OTOR plays a crucial role in the progression of and prognosis for BC, which could help to identify future therapeutic targets for treating BC patients.},
}
@article {pmid30890538,
year = {2019},
author = {Rohm, M and Zeigerer, A and Machado, J and Herzig, S},
title = {Energy metabolism in cachexia.},
journal = {EMBO reports},
volume = {20},
number = {4},
pages = {},
pmid = {30890538},
issn = {1469-3178},
mesh = {Adipose Tissue/metabolism ; Animals ; Cachexia/etiology/*metabolism ; *Energy Metabolism ; Gastrointestinal Absorption ; Humans ; Liver/metabolism ; Muscle, Skeletal/metabolism ; Neoplasms/complications/metabolism ; Organ Specificity ; },
abstract = {Cachexia is a wasting disorder that accompanies many chronic diseases including cancer and results from an imbalance of energy requirements and energy uptake. In cancer cachexia, tumor-secreted factors and/or tumor-host interactions cause this imbalance, leading to loss of adipose tissue and skeletal and cardiac muscle, which weakens the body. In this review, we discuss how energy enters the body and is utilized by the different organs, including the gut, liver, adipose tissue, and muscle, and how these organs contribute to the energy wasting observed in cachexia. We also discuss futile cycles both between the organs and within the cells, which are often used to fine-tune energy supply under physiologic conditions. Ultimately, understanding the complex interplay of pathologic energy-wasting circuits in cachexia can bring us closer to identifying effective treatment strategies for this devastating wasting disease.},
}
@article {pmid30890151,
year = {2019},
author = {Tewari, SG and Rajaram, K and Schyman, P and Swift, R and Reifman, J and Prigge, ST and Wallqvist, A},
title = {Short-term metabolic adjustments in Plasmodium falciparum counter hypoxanthine deprivation at the expense of long-term viability.},
journal = {Malaria journal},
volume = {18},
number = {1},
pages = {86},
pmid = {30890151},
issn = {1475-2875},
support = {R01 AI125534/AI/NIAID NIH HHS/United States ; AI125534//National Institute of Allergy and Infectious Diseases/ ; W81XWH-15-C-0061//Medical Research and Materiel Command/ ; },
mesh = {*Adaptation, Physiological ; Animals ; Gene Expression Profiling ; Hypoxanthine/*metabolism ; Metabolic Networks and Pathways ; Metabolomics ; Plasmodium falciparum/growth &amp; development/metabolism/*physiology ; Survival ; Time Factors ; },
abstract = {BACKGROUND: The malarial parasite Plasmodium falciparum is an auxotroph for purines, which are required for nucleic acid synthesis during the intra-erythrocytic developmental cycle (IDC) of the parasite. The capabilities of the parasite and extent to which it can use compensatory mechanisms to adapt to purine deprivation were studied by examining changes in its metabolism under sub-optimal concentrations of hypoxanthine, the primary precursor utilized by the parasite for purine-based nucleic acid synthesis.<br><br>METHODS: The concentration of hypoxanthine that caused a moderate growth defect over the course of one IDC was determined. At this concentration of hypoxanthine (0.5&#xa0;&#x3bc;M), transcriptomic and metabolomic data were collected during one IDC at multiple time points. These data were integrated with a metabolic network model of the parasite embedded in a red blood cell (RBC) to interpret the metabolic adaptation of P. falciparum to hypoxanthine deprivation.<br><br>RESULTS: At a hypoxanthine concentration of 0.5&#xa0;&#x3bc;M, vacuole-like structures in the cytosol of many P. falciparum parasites were observed after the 24-h midpoint of the IDC. Parasites grown under these conditions experienced a slowdown in the progression of the IDC. After 72&#xa0;h of deprivation, the parasite growth could not be recovered despite supplementation with 90&#xa0;&#xb5;M hypoxanthine. Simulations of P. falciparum metabolism suggested that alterations in ubiquinone, isoprenoid, shikimate, and mitochondrial metabolism occurred before the appearance of these vacuole-like structures. Alterations were found in metabolic reactions associated with fatty acid synthesis, the pentose phosphate pathway, methionine metabolism, and coenzyme A synthesis in the latter half of the IDC. Furthermore, gene set enrichment analysis revealed that P. falciparum activated genes associated with rosette formation, Maurer's cleft and protein export under two different nutrient-deprivation conditions (hypoxanthine and isoleucine).<br><br>CONCLUSIONS: The metabolic network analysis presented here suggests that P. falciparum invokes specific purine-recycling pathways to compensate for hypoxanthine deprivation and maintains a hypoxanthine pool for purine-based nucleic acid synthesis. However, this compensatory mechanism is not sufficient to maintain long-term viability of the parasite. Although P. falciparum can complete a full IDC in low hypoxanthine conditions, subsequent cycles are disrupted.},
}
@article {pmid30888194,
year = {2019},
author = {Yang, M and Xu, Z and Zhang, QZ and Wang, K and Ji, XY and Xu, J and Zhang, JY and Niu, G},
title = {A breast one-patient panel of heterogeneous genomes reveals genetic alterations driving DCIS into invasive lesions.},
journal = {Future oncology (London, England)},
volume = {15},
number = {14},
pages = {1565-1576},
doi = {10.2217/fon-2018-0555},
pmid = {30888194},
issn = {1744-8301},
mesh = {Actinin/genetics ; Adult ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics/metabolism/mortality ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/metabolism ; DNA Copy Number Variations ; Female ; *Genetic Heterogeneity ; *Genetic Variation ; *Genomics/methods ; Humans ; Mammography/methods ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Precision Medicine ; Prognosis ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism ; Exome Sequencing ; },
abstract = {Aim: Utilize breast cancer samples in the same patient to indicate breast cancer development. Patients &amp; methods: We performed whole-exome analysis of spatially independent ductal carcinoma in situ (DCIS) and invasive ductal carcinoma samples from the same breast. Results: In VEGF pathway, we observed two genes disrupted in DCIS, while another four (including ACTN2) mutated in invasive ductal carcinoma. When looked up TCGA database, we identified seven breast cancer patients with ACTN2 somatic mutations and observed a dramatic decrease in the overall survival time in ACTN2 mutant patients (p = 0.0182). A further finding in the TCGA database shows that breast cancer patients with ≥2 mutated genes in VEGF pathways showed worse prognosis (p = 0.0013). Conclusion: TCGA database and special case could inform each other to reveal DCIS developmental rules.},
}
@article {pmid30879795,
year = {2019},
author = {Sheaffer, WW and Gray, RJ and Wasif, N and Stucky, CC and Cronin, PA and Kosiorek, HE and Basu, A and Pizzitola, VJ and Patel, B and Giurescu, ME and Lorans, R and McCullough, AE and Ocal, IT and Pockaj, BA},
title = {Predictive factors of upstaging DCIS to invasive carcinoma in BCT vs mastectomy.},
journal = {American journal of surgery},
volume = {217},
number = {6},
pages = {1025-1029},
doi = {10.1016/j.amjsurg.2018.12.069},
pmid = {30879795},
issn = {1879-1883},
mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*pathology/surgery ; Female ; Humans ; *Mastectomy, Radical ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node Biopsy ; },
abstract = {BACKGROUND: Upstaging from DCIS to invasive ductal carcinoma varies widely from 0 to 59%. We aim to identify risk factors associated with upstaging in all DCIS patients and based on specific surgical intervention.<br><br>METHODS: Patients with a pre-operative diagnosis of DCIS undergoing BCT or mastectomy were reviewed. Multivariable analysis was performed to identify risk factors for upstaging.<br><br>RESULTS: In total, 623 patients had a preoperative diagnosis of DCIS. Upstaging occurred in 74 patients (12%) overall. There was no difference in upstaging rates between mastectomy and BCT (11% v 14% p&#x202f;=&#x202f;0.27). Sentinel lymph node biopsy was positive in 4/212 patients (1%). Multivariable analysis revealed suspicion of microinvasion (OR 5.7 95%CI2.2-14.9), surgeon suspicion of invasive disease (OR 2.7, 95% CI 1.2-6.4) and larger size/multicentric/extensive tumor (OR 1.9 95% CI 1.1-3.4) increase risk of upstaging.<br><br>CONCLUSIONS: Suspicion of microinvasion, surgeon suspicion, and tumor size can be used to help guide the use of sentinel lymph node biopsy. For patients without these high risk characteristics, it is hard to justify the use of concurrent SLN biopsy for patients who undergo BCT.},
}
@article {pmid30872758,
year = {2019},
author = {Roth, JD and Pariser, JJ and Stoffel, JT and Lenherr, SM and Myers, JB and Welk, B and Elliott, SP},
title = {Patient subjective assessment of urinary tract infection frequency and severity is associated with bladder management method in spinal cord injury.},
journal = {Spinal cord},
volume = {57},
number = {8},
pages = {700-707},
pmid = {30872758},
issn = {1476-5624},
support = {CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; },
mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Catheters, Indwelling/adverse effects/trends ; Cross-Sectional Studies ; *Diagnostic Self Evaluation ; *Intermittent Urethral Catheterization/adverse effects/trends ; Prospective Studies ; Registries ; Severity of Illness Index ; *Spinal Cord Injuries/complications/diagnosis/therapy ; *Urinary Tract Infections/diagnosis/etiology ; },
abstract = {STUDY DESIGN: The Neurogenic Bladder Research Group (NBRG) registry is a multicenter prospective observational study. This manuscript is retrospective based on a cross-sectional survey.<br><br>OBJECTIVES: To assess patient subjective assessment of urinary tract infection (UTI) frequency and severity are associated with the degree of use of catheters or incontinence products.<br><br>SETTING: Multiple hospitals across the United States.<br><br>METHODS: Eligibility included: age&#x2009;>&#x2009;18 years and acquired SCI. Over 1.5 years, 1479 eligible participants were enrolled. We excluded those with surgical reconstruction or diversion of the bladder. In total, 1282 participants were grouped by bladder management: (1) indwelling catheter (IDC), (2) clean intermittent catheterization (CIC), (3) external devices (pads/condom), and (4) volitional voiding (Void). UTI frequency was classified as 0, 1-3, 4-6, or&#x2009;>&#x2009;6 over the prior year. UTI severity was determined by hospitalization for UTI in the prior year. Multivariate regression compared these factors across groups.<br><br>RESULTS: UTIs were least frequent in Void followed by pads/condom, CIC, and IDC (all p&#x2009;&#x2264;&#x2009;0.001). UTI severity followed a similar pattern. Controlling for covariates, the adjusted odds of UTI frequency (Void&#x2009;=&#x2009;reference) were 2.28 (1.38-3.76) for pads/condom, 3.42 (2.25-5.18) for CIC, and 4.3 (2.59-6.70) for IDC (all p&#x2009;&#x2264;&#x2009;0.001).<br><br>CONCLUSIONS: Patient subjective assessment of UTI frequency is highest with IDC, followed by CIC, pads/condom, and lowest with spontaneous voiding. The odds of hospitalization for UTI were three times higher for IDC than spontaneous voiding. UTI risk should be considered when counseling patients about bladder management options. These associations do not imply causation but warrant further investigation in a prospective manner.<br><br>SPONSORSHIP: Patient-Centered Outcomes Research Institute (PCORI) Award (CER14092138).},
}
@article {pmid30872384,
year = {2019},
author = {Li, Y and Zhang, N and Zhang, H and Yang, Q},
title = {Comparative prognostic analysis for triple-negative breast cancer with metaplastic and invasive ductal carcinoma.},
journal = {Journal of clinical pathology},
volume = {72},
number = {6},
pages = {418-424},
doi = {10.1136/jclinpath-2018-205544},
pmid = {30872384},
issn = {1472-4146},
mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/ethnology/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/ethnology/mortality/*pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Metaplasia ; Middle Aged ; Neoplasm Invasiveness ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/ethnology/mortality/*pathology/therapy ; United States/epidemiology ; Young Adult ; },
abstract = {AIMS: Triple-negative breast cancer comprises different histological subtypes, including metaplastic breast cancer (MBC) and ductal carcinomas (IDCs). The purpose of this study was to compare triple-negative MBC (TN-MBC) with triple-negative IDC (TN-IDC) in terms of survival and predictive factors.<br><br>METHODS: With access to the Surveillance, Epidemiology and End Result (SEER) database, a total of 19&#x2009;383 patients met the eligibility criteria. Clinicopathological characteristics were compared between groups using the &#x3c7;[2] test. Univariate and multivariate analyses were applied to evaluate the disease-specific survival (DSS) and overall survival (OS). Subgroup analyses summarised the hazard ratios of TN-MBC versus TN-IDC using a forest plot.<br><br>RESULTS: A total of 586 patients with TN-MBC and 18&#x2009;797 with TN-IDC were included in this study. Patients with TN-MBC were older and presented with larger tumour sizes, relatively rare lymph node positive disease, and had received more chemotherapy. Compared with TN-IDC, the TN-MBC group showed a significantly poorer prognosis before and after the 1:3 matched case-control analysis. Further subgroup analysis indicated that patients with TN-MBC were older, were from specific races, and those with distant metastasis and not receiving radiotherapy had worse prognosis than patients with TN-IDC in terms of DFS and OS.<br><br>CONCLUSION: Our results showed that patients with TN-MBC had unique clinicopathological characteristics and poorer prognostic subtype compared with TN-IDC. This improves our understanding of the clinicopathological and prognostic features of this rare entity but also provides more convincing therapeutic guidelines for TN-MBC in patients with breast cancer.},
}
@article {pmid30864836,
year = {2019},
author = {Dong, Y and Zhang, WW and Wang, J and Sun, JY and He, ZY and Wu, SG},
title = {The 21-gene recurrence score and effects of adjuvant radiotherapy after breast conserving surgery in early-stage breast cancer.},
journal = {Future oncology (London, England)},
volume = {15},
number = {14},
pages = {1629-1639},
doi = {10.2217/fon-2018-0967},
pmid = {30864836},
issn = {1744-8301},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/*genetics/mortality/*therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Postoperative Care ; Prognosis ; Radiotherapy, Adjuvant ; Recurrence ; SEER Program ; },
abstract = {Aim: To investigate the associations with the 21-gene recurrence score (RS) and effect of adjuvant radiotherapy (RT) for early-stage breast cancer after breast conserving surgery. Methods: We included 13,246 patients in the SEER database. Results: Patients with a higher RS were independently related to nonreceipt of RT (p < 0.001). In both the traditional and Trial Assigning Individualized Options for Treatment (TAILORx) RS cut-offs, the receipt of RT was not related to better breast cancer-specific survival in low- and high-risk RS groups, but was independently related to better breast cancer-specific survival in intermediate-risk RS group before (p = 0.029) and after (p = 0.001) propensity score matching. Conclusion: The 21-gene-RS may impact the decision-making of adjuvant RT in early-stage breast cancer after breast conserving surgery. The survival benefit of adjuvant RT may be limited to patients with intermediate-risk RS.},
}
@article {pmid30843776,
year = {2018},
author = {Menichetti, F and Bertolino, G and Sozio, E and Carmignani, C and Rosselli Del Turco, E and Tagliaferri, E and Sbrana, F and Ripoli, A and Barnini, S and Desideri, I and Dal Canto, L and Tascini, C and , },
title = {Impact of infectious diseases consultation as a part of an antifungal stewardship programme on candidemia outcome in an Italian tertiary-care, University hospital.},
journal = {Journal of chemotherapy (Florence, Italy)},
volume = {30},
number = {5},
pages = {304-309},
doi = {10.1080/1120009X.2018.1507086},
pmid = {30843776},
issn = {1973-9478},
mesh = {Aged ; Antifungal Agents/*therapeutic use ; Antimicrobial Stewardship/methods ; Candida/drug effects ; Candidemia/*drug therapy ; Communicable Diseases/*drug therapy ; Female ; Fluconazole/therapeutic use ; Hospitals, University ; Humans ; Italy ; Male ; Referral and Consultation ; Retrospective Studies ; },
abstract = {Candidemia is a major cause of in-hospital mortality. Antifungal stewardship programme (AFSP) providing infectious diseases consultation (IDC) might improve the outcome. We evaluate the impact on candidemia mortality of IDC as part of AFSP restricting the use of all antifungals with exception of fluconazole. We retrospectively reviewed the charts of patients with documented candidemia in our hospital during the period 2012-2014 evaluating the impact of several variables on 30-days in-hospital mortality. We reviewed data on 276 patients with documented candidemia: 200 (72%) were treated without IDC and 76 (28%) with IDC. In the group without IDC, 52 patients (26%) received no antifungal therapy. Antifungals used for treating candidemia were (no IDC/IDC): azoles (74%/42%); echinocandins (0%/46%); liposomal and lipidic complex amphotericin B (0%/12%). The 30-day in-hospital mortality was respectively (no IDC/IDC) 37% vs. 20% (p = 0.011). The multivariate analysis confirmed IDC as independent factor protecting from death (OR 0.511, 95% CI 0.251-0.994; p = 0.046), together with fungemia due to non-albicans Candida (OR 0.565, 95% CI 0.327-0.977; p = 0.042). Age >65 years was associated with a higher risk of death (OR 1.989, 95% CI 1.055-3.895; p = 0.038). The additional cost for the use of echinocandins driven by IDC in the study period was €207,000. IDC, as a part of a restrictive front-end antimicrobial stewardship programme (ASP), providing a timely right choice of antifungal therapy, increases the cost of antifungal drugs but might be a contributing protective factor from mortality due to candidemia. Efforts to increase the number of IDC in patients with candidemia seems to be warranted.},
}
@article {pmid30843116,
year = {2019},
author = {Goodfellow, J and Gorrie, G and Leach, V and Patel, S and Mackay, G},
title = {Cancer and motor neuron disease-causal or coincidental? Two contrasting cases.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {40},
number = {7},
pages = {1461-1463},
pmid = {30843116},
issn = {1590-3478},
mesh = {Breast Neoplasms/*complications/immunology/pathology ; Carcinoma, Ductal, Breast/*complications/immunology/pathology ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*complications/immunology/pathology/therapy ; Middle Aged ; Motor Neuron Disease/*complications/etiology/immunology ; *Paraneoplastic Syndromes, Nervous System/immunology ; Small Cell Lung Carcinoma/*complications/immunology/pathology/therapy ; },
abstract = {INTRODUCTION: Motor neuron disease (MND) can occur in patients with cancer, but there is minimal evidence that this is more than by chance. We contrast two cases of motor neuronopathies occurring in the context of systemic malignancy and argue that in one case the cause was most likely paraneoplastic, while in the other it was not. CASE 1: A 61-year-old woman developed progressive walking difficulties over 9 months with weakness and stiffness in her legs. EMG showed fibrillations and positive sharp waves in multiple lower limb muscles bilaterally, with neurogenic units and a reduced recruitment pattern. An invasive ductal carcinoma of the breast was identified and she continued to deteriorate neurologically with worsening mobility, upper limb spasticity and fasciculations. She died approximately 26 months after symptom onset. CASE 2: A 57-year-old woman developed weight loss and weakness of her right arm without any sensory symptoms. At presentation, she had wasting and fasciculations in her right upper limb muscles, with normal reflexes, normal left upper limb and lower limb examination. Over the following week, she developed left upper limb weakness and fasciculations, brisk knee reflexes, and flexor plantar responses. Her EMG showed upper and lower limb denervation. She was found to have anti-Hu and anti-CV2 antibodies present in serum. A PET-CT showed active uptake in lymph nodes in the right hilum. Biopsy confirmed a small cell lung cancer. She had chemoradiation therapy and the tumour went into remission. She has remained well on follow-up 24 months later, regaining weight and strength after her chemotherapy. She continues to be monitored for cancer recurrence, but thus far appears to be in remission.<br><br>CONCLUSION: In cases with rapidly progressive MND, particularly of upper limb onset, consideration should be given to testing anti-neuronal antibodies and searching for an occult tumour.},
}
@article {pmid30842485,
year = {2019},
author = {Rossi, A and Dupaty, L and Aillot, L and Zhang, L and Gallien, C and Hallek, M and Odenthal, M and Adriouch, S and Salvetti, A and Büning, H},
title = {Vector uncoating limits adeno-associated viral vector-mediated transduction of human dendritic cells and vector immunogenicity.},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {3631},
pmid = {30842485},
issn = {2045-2322},
mesh = {Animals ; CD8-Positive T-Lymphocytes/immunology/virology ; Capsid/*immunology ; Capsid Proteins/*immunology ; Dendritic Cells/*immunology/virology ; Dependovirus/genetics/*immunology ; Genetic Vectors/*administration &amp; dosage/*immunology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; *Transduction, Genetic ; },
abstract = {AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV's low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model. iDC internalized AAV vectors of various serotypes, but even the most efficient serotype failed to transduce iDC above background. Since AAV vectors reached the cell nucleus, we hypothesized that AAV's intracellular processing occurs suboptimal. On this basis, we screened an AAV peptide display library for capsid variants more suitable for DC transduction and identified the I/VSS family which transduced DC with efficiencies of up to 38%. This property correlated with an improved vector uncoating. To determine the consequence of this novel feature for AAV's in vivo performance, we engineered one of the lead candidates to express a cytoplasmic form of ovalbumin, a highly immunogenic model antigen, and assayed transduction efficiency as well as immunogenicity. The capsid variant clearly outperformed the parental serotype in muscle transduction and in inducing antigen-specific humoral and T cell responses as well as anti-capsid CD8[+] T cells. Hence, vector uncoating represents a major barrier hampering AAV vector-mediated transduction of DC and impacts on its use as vaccine platform.},
}
@article {pmid30825809,
year = {2019},
author = {Owen, WA and Brazeal, HA and Shaw, HL and Lee, MV and Appleton, CM and Holley, SO},
title = {Focal breast pain: imaging evaluation and outcomes.},
journal = {Clinical imaging},
volume = {55},
number = {},
pages = {148-155},
doi = {10.1016/j.clinimag.2019.02.008},
pmid = {30825809},
issn = {1873-4499},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Cancer Pain/diagnostic imaging/etiology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Female ; Follow-Up Studies ; Humans ; Incidental Findings ; Mammography/methods ; Mastodynia/*diagnostic imaging/etiology ; Middle Aged ; Prognosis ; Retrospective Studies ; Ultrasonography, Mammary ; Young Adult ; },
abstract = {OBJECTIVES: To determine the number and characteristics of cancers detected and the optimal imaging evaluation in women presenting with focal breast pain (FBP).<br><br>MATERIALS AND METHODS: We performed a retrospective review of 4720 women who underwent imaging for FBP from 2001 to 2013. Women 18 and over with one or two foci of breast pain and no concurrent breast symptoms were included. 944 patients met criteria. We recorded the imaging work-up, presence and type of finding at the site of pain, BI-RADS&#xae; assessment, and pathological outcomes. Subsequent imaging and clinical follow up was recorded.<br><br>RESULTS: Imaging evaluation consisted of sonogram alone in 286 women, mammogram alone in 231 women, and both in 427 women. 113 women had an imaging finding at the site of pain; 103 were designated benign or probably benign. 12 biopsies of corresponding findings were performed: 9 benign, 1 invasive lobular carcinoma, 1 invasive ductal carcinoma, 1 ductal carcinoma in situ. All three malignancies were seen mammographically; 2 had an ultrasound correlate. At initial evaluation, 4 incidental breast cancers were diagnosed remote from the site of FBP. All were seen on mammogram and 2 of 4 had an ultrasound correlate. On follow up evaluation, 9 cancers were diagnosed at the site of pain and 13 incidental cancers were diagnosed.<br><br>CONCLUSION: FBP is rarely associated with malignancy. Targeted ultrasound may be deferred in women 40 and older with FBP, no other clinical findings, and a negative mammogram.},
}
@article {pmid30820924,
year = {2019},
author = {Murakami, W and Tozaki, M and Nakamura, S and Ide, Y and Inuzuka, M and Hirota, Y and Murakami, K and Takahama, N and Ohgiya, Y and Gokan, T},
title = {The clinical impact of MRI screening for BRCA mutation carriers: the first report in Japan.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {26},
number = {5},
pages = {552-561},
pmid = {30820924},
issn = {1880-4233},
mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*diagnostic imaging/*genetics/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics/pathology ; Female ; Follow-Up Studies ; *Genes, BRCA1 ; *Genes, BRCA2 ; Humans ; Japan ; *Magnetic Resonance Imaging ; Mammography ; Mass Screening/methods ; Middle Aged ; *Mutation ; Public Health Surveillance/methods ; Retrospective Studies ; Young Adult ; },
abstract = {BACKGROUND: There is no consensus on the appropriate surveillance for high-risk women with breast cancer in Japan. We investigated their imaging features and pathological characteristics to build a proper surveillance system for asymptomatic high-risk individuals in the future.<br><br>METHODS: We retrospectively reviewed 93 female (median age 43&#xa0;years) BRCA1 and BRCA2 mutation carriers from our institutional clinical database from 2011 to 2017. The study population was composed of 112 breast cancers. Mammography and MRI were reviewed by examiners blinded to patients' clinical history. Final surgical or biopsy histopathology served as the reference standard in all the patients.<br><br>RESULTS: Fifty-nine breast cancers met selection criteria; of these, 30 were BRCA1-associated tumors, and 29 were BRCA2-associated tumors. Invasive ductal carcinoma was the most prevalent type in both BRCA1 and BRCA2. There were statistically significant differences in phenotype, nuclear grade, and Ki-67 labeling index between BRCA1 and BRCA2 mutation carriers. Additionally, imaging findings on mammography and MRI were statistically different. Tumors in BRCA2 carriers demonstrated mammographic calcifications more frequently, while those in BRCA1 carriers demonstrated a mass or architectural distortion (P&#x2009;<&#x2009;0.001). Enhancement pattern on MRI also significantly differed between the two subgroups (P&#x2009;=&#x2009;0.006). The size of MRI-detected lesions was statistically smaller than the size of those detected by other modalities (P&#x2009;=&#x2009;0.004).<br><br>CONCLUSIONS: The imaging and histological characteristics of BRCA1/2 mutation carriers were consistent with other countries' studies. MRI-detected lesions were significantly smaller than lesions detected by non-MRI modality. All lesions in BRCA1 mutation carriers could be detected by MRI.},
}
@article {pmid30813596,
year = {2019},
author = {Myers, MB and McKim, KL and Banda, M and George, NI and Parsons, BL},
title = {Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology.},
journal = {International journal of molecular sciences},
volume = {20},
number = {5},
pages = {},
pmid = {30813596},
issn = {1422-0067},
mesh = {Alleles ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Female ; Fluorescein/metabolism ; Humans ; Middle Aged ; Mutation/genetics ; *Mutation Rate ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/genetics ; Polymerase Chain Reaction ; *Precision Medicine ; Proto-Oncogene Proteins B-raf/genetics ; Receptor, ErbB-2/genetics/metabolism ; },
abstract = {Information regarding the role of low-frequency hotspot cancer-driver mutations (CDMs) in breast carcinogenesis and therapeutic response is limited. Using the sensitive and quantitative Allele-specific Competitor Blocker PCR (ACB-PCR) approach, mutant fractions (MFs) of six CDMs (PIK3CA H1047R and E545K, KRAS G12D and G12V, HRAS G12D, and BRAF V600E) were quantified in invasive ductal carcinomas (IDCs; including ~20 samples per subtype). Measurable levels (i.e., ≥ 1 × 10[-5], the lowest ACB-PCR standard employed) of the PIK3CA H1047R, PIK3CA E545K, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E mutations were observed in 34/81 (42%), 29/81 (36%), 51/81 (63%), 9/81 (11%), 70/81 (86%), and 48/81 (59%) of IDCs, respectively. Correlation analysis using available clinicopathological information revealed that PIK3CA H1047R and BRAF V600E MFs correlate positively with maximum tumor dimension. Analysis of IDC subtypes revealed minor mutant subpopulations of critical genes in the MAP kinase pathway (KRAS, HRAS, and BRAF) were prevalent across IDC subtypes. Few triple-negative breast cancers (TNBCs) had appreciable levels of PIK3CA mutation, suggesting that individuals with TNBC may be less responsive to inhibitors of the PI3K/AKT/mTOR pathway. These results suggest that low-frequency hotspot CDMs contribute significantly to the intertumoral and intratumoral genetic heterogeneity of IDCs, which has the potential to impact precision oncology approaches.},
}
@article {pmid30807826,
year = {2019},
author = {Griggs, RB and Santos, DF and Laird, DE and Doolen, S and Donahue, RR and Wessel, CR and Fu, W and Sinha, GP and Wang, P and Zhou, J and Brings, S and Fleming, T and Nawroth, PP and Susuki, K and Taylor, BK},
title = {Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes.},
journal = {Neurobiology of disease},
volume = {127},
number = {},
pages = {76-86},
pmid = {30807826},
issn = {1095-953X},
support = {R01 DA037621/DA/NIDA NIH HHS/United States ; F31 NS083292/NS/NINDS NIH HHS/United States ; R56 NS107398/NS/NINDS NIH HHS/United States ; R01 NS062306/NS/NINDS NIH HHS/United States ; R01 NS045954/NS/NINDS NIH HHS/United States ; T32 NS077889/NS/NINDS NIH HHS/United States ; },
mesh = {Adenylyl Cyclases/*metabolism ; Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/drug effects/physiology ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Diabetes Mellitus, Type 2/complications/*metabolism ; Diabetic Neuropathies/*metabolism ; Guanine Nucleotide Exchange Factors/*metabolism ; Male ; Mice ; Pain Measurement ; Posterior Horn Cells/drug effects/metabolism ; Pyruvaldehyde/*metabolism/pharmacology ; Signal Transduction/drug effects/physiology ; TRPA1 Cation Channel/*metabolism ; },
abstract = {Painful diabetic neuropathy (PDN) is a devastating neurological complication of diabetes. Methylglyoxal (MG) is a reactive metabolite whose elevation in the plasma corresponds to PDN in patients and pain-like behavior in rodent models of type 1 and type 2 diabetes. Here, we addressed the MG-related spinal mechanisms of PDN in type 2 diabetes using db/db mice, an established model of type 2 diabetes, and intrathecal injection of MG in conventional C57BL/6J mice. Administration of either a MG scavenger (GERP10) or a vector overexpressing glyoxalase 1, the catabolic enzyme for MG, attenuated heat hypersensitivity in db/db mice. In C57BL/6J mice, intrathecal administration of MG produced signs of both evoked (heat and mechanical hypersensitivity) and affective (conditioned place avoidance) pain. MG-induced Ca[2+] mobilization in lamina II dorsal horn neurons of C57BL/6J mice was exacerbated in db/db, suggestive of MG-evoked central sensitization. Pharmacological and/or genetic inhibition of transient receptor potential ankyrin subtype 1 (TRPA1), adenylyl cyclase type 1 (AC1), protein kinase A (PKA), or exchange protein directly activated by cyclic adenosine monophosphate (Epac) blocked MG-evoked hypersensitivity in C57BL/6J mice. Similarly, intrathecal administration of GERP10, or inhibitors of TRPA1 (HC030031), AC1 (NB001), or Epac (HJC-0197) attenuated hypersensitivity in db/db mice. We conclude that MG and sensitization of a spinal TRPA1-AC1-Epac signaling cascade facilitate PDN in db/db mice. Our results warrant clinical investigation of MG scavengers, glyoxalase inducers, and spinally-directed pharmacological inhibitors of a MG-TRPA1-AC1-Epac pathway for the treatment of PDN in type 2 diabetes.},
}
@article {pmid30798329,
year = {2019},
author = {Sawai, H and Kurimoto, M and Koide, S and Kiriyama, Y and Haba, S and Matsuo, Y and Morimoto, M and Koide, H and Kamiya, A and Yamao, K},
title = {Invasive Ductal Carcinoma Arising in Mucinous Cystic Neoplasm of Pancreas: A Case Report.},
journal = {The American journal of case reports},
volume = {20},
number = {},
pages = {242-247},
pmid = {30798329},
issn = {1941-5923},
mesh = {Adult ; Carcinoma, Pancreatic Ductal/*pathology ; Cystadenoma, Mucinous/*pathology ; Female ; Humans ; Mutation ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*pathology ; Pancreatic Neoplasms/*pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; },
abstract = {BACKGROUND Mucinous cystic neoplasm (MCN) of the pancreas is a rare mucin-producing cystic neoplasm that has a characteristic histological feature referred to as ovarian-type stroma (OS) underlying the epithelium. Pancreatic ductal carcinoma arises from MCN as a precursor lesion, but data on progression pathways are limited. CASE REPORT A 40-year-old female was referred to our hospital for further investigation of a pancreatic cyst. Further examination showed a 7.0 cm multilocular cyst in the pancreatic tail and a solid mass in the thick septum of the cystic tumor. Distal pancreatectomy and splenectomy were performed. Histological examination revealed a moderately differentiated invasive ductal carcinoma (IDC) with a diameter of 0.5 cm in the thick septum of the cystic lesion and a cyst wall composed of epithelium with low-grade to severe dysplasia. The epithelium covered an OS. Pathological diagnosis was IDC arising in MCN of the pancreas. Immunohistochemical examination showed that MUC1 expression was negative in MCN but positive in IDC. KRAS mutation was observed in both MCN and IDC regions. CONCLUSIONS We present a rare case of moderately differentiated pancreatic IDC arising in MCN. To elucidate the underlying progression pathway, we explored the correlation between KRAS mutation and MUC expression as a clinicopathological parameter.},
}
@article {pmid30789657,
year = {2019},
author = {Nguyen, B and Veys, I and Leduc, S and Bareche, Y and Majjaj, S and Brown, DN and Boeckx, B and Lambrechts, D and Sotiriou, C and Larsimont, D and Desmedt, C},
title = {Genomic, Transcriptomic, Epigenetic, and Immune Profiling of Mucinous Breast Cancer.},
journal = {Journal of the National Cancer Institute},
volume = {111},
number = {7},
pages = {742-746},
doi = {10.1093/jnci/djz023},
pmid = {30789657},
issn = {1460-2105},
mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; DNA Methylation/genetics ; Epigenomics/methods ; Female ; Genomic Instability/genetics ; Genomics/methods ; Humans ; Lymphatic Metastasis ; Mucin-2/*genetics ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Transcriptome/genetics ; },
abstract = {Although invasive ductal breast cancer (IDC) represents the most common histological type of breast cancer, minor subtypes exist such as mucinous breast cancer (MuBC). MuBC are distinguished by tumor cells floating in extracellular mucin. MuBC patients are generally older and associated with a favorable prognosis. To unravel the molecular architecture of MuBC, we applied low-pass whole-genome sequencing and microscopic evaluation of stromal tumor infiltrating lymphocytes to 30 MuBC from a retrospective institutional cohort. We further analyzed two independent datasets from the International Cancer Genomics Consortium and The Cancer Genome Atlas. Genomic data (n = 26 MuBC, n = 535 estrogen receptor [ER] positive/HER2-negative IDC), methylation data (n = 28 MuBC, n = 529 ER-positive/HER2-negative IDC), and transcriptomic data (n = 27 MuBC, n = 467 ER-positive/HER2-negative IDC) were analyzed. MuBC was characterized by low tumor infiltrating lymphocyte levels (median = 0.0%, average = 3.4%, 95% confidence interval = 1.9% to 4.9%). Compared with IDC, MuBC had a lower genomic instability (P = .01, two-sided Mann-Whitney U test) and a decreased prevalence of PIK3CA mutations (39.7% in IDC vs 6.7% in MuBC, P = .01 in the International Cancer Genomics Consortium; and 34.8% vs 0.0%, P = .02 in The Cancer Genome Atlas, two-sided Fisher's exact test). Finally, our report identifies aberrant DNA methylation of MUC2 as a possible cause of extracellular production of mucin in MuBC.},
}
@article {pmid30786684,
year = {2018},
author = {Hybiak, J and Domagala, P and Domagala, W},
title = {BRCA1 and PARP1 mRNA expression during progression from normal breast to ductal carcinoma in situ and invasive breast cancer: a laser microdissection study.},
journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists},
volume = {69},
number = {4},
pages = {347-355},
doi = {10.5114/pjp.2018.81694},
pmid = {30786684},
issn = {1233-9687},
mesh = {BRCA1 Protein/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Humans ; Laser Capture Microdissection ; Poly (ADP-Ribose) Polymerase-1/*genetics ; RNA, Messenger ; },
abstract = {The contribution of DNA damage repair mechanisms to the progression of normal breast to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma is largely unknown. The purpose of this report was to assess the mRNA expression levels of two important genes associated with DNA repair, BRCA1 and PARP1, in normal breast tissue, DCIS G1, G2 and G3, and co-existing adjacent invasive ductal carcinoma. BRCA1 and PARP1 mRNA expression was assessed in 32 ductal carcinomas in situ of the breast using a laser microdissection and pressure catapulting system and quantitative real-time PCR. The relative expression of BRCA1 mRNA was significantly increased in DCIS G2 and DCIS G3 relative to normal breast tissue (p = 0.02, p = 0.001, respectively). Significant differences in BRCA1 expression were observed between DCIS G1 and G2 (p = 0.02) and between DCIS G1 and G3 (p = 0.0007). No significant differences in BRCA1 expression were observed between normal breast tissue and DCIS G1 and between DCIS component and adjacent invasive ductal carcinoma. No significant differences in the relative expression of PARP1 mRNA were observed between groups. Increased BRCA1 mRNA expression (but not PARP1 mRNA) occurs early in the development of breast cancer, i.e. at the noninvasive (DCIS) stage, suggesting a demand for increased activity of a DNA double-strand break repair by homologous recombination. DCIS G1 and normal breast tissue share highly similar BRCA1 and PARP1 expression level. This finding supports the idea that DCIS G1 belongs to a separate family of precursor lesions with low malignant potential.},
}
@article {pmid30772465,
year = {2019},
author = {Ducommun, S and Deak, M and Zeigerer, A and Göransson, O and Seitz, S and Collodet, C and Madsen, AB and Jensen, TE and Viollet, B and Foretz, M and Gut, P and Sumpton, D and Sakamoto, K},
title = {Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates.},
journal = {Cellular signalling},
volume = {57},
number = {},
pages = {45-57},
doi = {10.1016/j.cellsig.2019.02.001},
pmid = {30772465},
issn = {1873-3913},
mesh = {AMP-Activated Protein Kinases/*metabolism ; Animals ; Guanine Nucleotide Exchange Factors/*metabolism ; Hepatocytes/metabolism ; Homeostasis/genetics/physiology ; Lipid Metabolism/genetics ; Liver/*metabolism ; Mass Spectrometry/methods ; Membrane Proteins/*metabolism ; Mice, Knockout ; Muscle Proteins/*metabolism ; Phosphorylation ; Substrate Specificity ; },
abstract = {AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis, acting as a sensor of energy and nutrient status. As such, AMPK is considered a promising drug target for treatment of medical conditions particularly associated with metabolic dysfunctions. To better understand the downstream effectors and physiological consequences of AMPK activation, we have employed a chemical genetic screen in mouse primary hepatocytes in an attempt to identify novel AMPK targets. Treatment of hepatocytes with a potent and specific AMPK activator 991 resulted in identification of 65 proteins phosphorylated upon AMPK activation, which are involved in a variety of cellular processes such as lipid/glycogen metabolism, vesicle trafficking, and cytoskeleton organisation. Further characterisation and validation using mass spectrometry followed by immunoblotting analysis with phosphorylation site-specific antibodies identified AMPK-dependent phosphorylation of Gapex-5 (also known as GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1)) on Ser902 in hepatocytes and starch-binding domain 1 (STBD1) on Ser175 in multiple cells/tissues. As new promising roles of AMPK as a key metabolic regulator continue to emerge, the substrates we identified could provide new mechanistic and therapeutic insights into AMPK-activating drugs in the liver.},
}
@article {pmid30771577,
year = {2019},
author = {Liao, W and Li, C and Tang, Y and Huang, F and Kuang, H and Liang, S and Yang, Y},
title = {Aquaporin-4 antibody positive short transverse myelitis associated with breast cancer.},
journal = {Multiple sclerosis and related disorders},
volume = {30},
number = {},
pages = {119-122},
doi = {10.1016/j.msard.2019.02.011},
pmid = {30771577},
issn = {2211-0356},
mesh = {Adult ; Antibodies/*cerebrospinal fluid ; Aquaporin 4/*immunology ; Breast Neoplasms/*cerebrospinal fluid/complications/diagnostic imaging ; Carcinoma/*cerebrospinal fluid/complications/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Myelitis, Transverse/*blood/complications/diagnostic imaging ; Spinal Cord/diagnostic imaging ; },
abstract = {Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). A typical finding on spinal magnetic resonance imaging (MRI) of NMOSD is longitudinally extensive transverse myelitis (LETM). However, patients with NMOSD presenting with short-segment transverse myelitis (STM) during myelitis attacks associated with breast cancer are uncommon. We report a case of a 35-year-old woman with STM and left eye optic neuritis. The patient was positive for serum aquaporin-4 antibodies (AQP4-IgG), and a biopsy of the left breast showed invasive ductal carcinoma. The patient was diagnosed with NMOSD and breast malignancy. This is the first report of a patient with NMOSD whose spinal MRI showed STM and serum test showed that the patient's AQP4-IgG was positive and complicated by breast cancer. This case improves our understanding of the association between NMOSD and cancer and raises the question of whether it was a coincidental occurrence. It is important to search for extensive malignancies in patients presenting with atypical MRI or no reaction to traditional therapies.},
}
@article {pmid30771195,
year = {2019},
author = {Miyake, M and Yamada, A and Miyake, K and Endo, I},
title = {Esophageal metastasis of breast cancer during endocrine therapy for pleural dissemination 21 years after breast surgery: a case report.},
journal = {Surgical case reports},
volume = {5},
number = {1},
pages = {22},
pmid = {30771195},
issn = {2198-7793},
abstract = {BACKGROUND: The esophageal metastasis of breast cancer is rare. Moreover, it is extremely unusual for patients to experience the symptoms of esophageal metastasis during their lifetimes. We present a case of dysphagia caused by esophageal metastasis after a long interval following a primary mastectomy.<br><br>CASE PRESENTATION: A 77-year-old woman with a history of heterochronous bilateral breast cancer and under treatment for pleural dissemination recurrence originating from right breast cancer complained of dysphagia. At the age of 56, she had undergone a right radical mastectomy for right breast cancer. The histopathological findings revealed invasive ductal carcinoma, pT3N1M0, which was estrogen receptor (ER)- and progesterone receptor (PgR)-positive. At the age of 73, she underwent a second operation, a left modified radical mastectomy. The histopathological examination revealed invasive ductal carcinoma, pT1N0M0, which was negative for ER, PgR, and human epidermal growth factor receptor 2 (HER2). Four years after completion of adjuvant therapy for the left breast cancer, pleural effusion on her left side was observed and histopathological examination of a sample revealed pleural dissemination resulting from the right breast cancer. After initiation of therapy for recurrence, she developed dysphagia and, therefore, underwent an upper gastrointestinal tract endoscopic examination. The examination revealed whole circumferential stenosis and a band unstained by Lugol's solution located 30&#x2009;cm from her incisors. Examination of a biopsy specimen revealed a subepithelial luminal structure and dysplastic cells. Immunostaining was positive for CK7 and negative for CK20; furthermore, the sample was ER and PgR-positive. Considering the pathological findings, the patient was diagnosed with esophageal metastasis of her right breast cancer.<br><br>CONCLUSIONS: Metastatic lesions in the esophagus are often located in the submucosa; therefore, they may not be definitively diagnosed by histopathological examination of mucosal biopsy specimens. Esophageal metastasis originating from breast cancer often occurs as a part of multiple organ metastases; however, esophageal metastasis is usually not considered a prognostic factor for patients. Therefore, treatment should be determined according to the severity of the other metastatic sites and the degree of esophageal stenosis.},
}
@article {pmid30770989,
year = {2019},
author = {Yan, Z and Ohuchida, K and Zheng, B and Okumura, T and Takesue, S and Nakayama, H and Iwamoto, C and Shindo, K and Moriyama, T and Nakata, K and Miyasaka, Y and Ohtsuka, T and Mizumoto, K and Oda, Y and Hashizume, M and Nakamura, M},
title = {CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis.},
journal = {Journal of cancer research and clinical oncology},
volume = {145},
number = {5},
pages = {1147-1164},
pmid = {30770989},
issn = {1432-1335},
mesh = {Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor ; Carcinoma, Pancreatic Ductal/genetics/metabolism/mortality/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Survival ; Disease Models, Animal ; Disease Progression ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/secondary ; Male ; Mice ; Middle Aged ; Pancreatic Neoplasms/genetics/*metabolism/mortality/*pathology ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism ; RNA Interference ; RNA, Small Interfering/genetics ; Receptors, Thrombopoietin/genetics/*metabolism ; Signal Transduction ; Xenograft Model Antitumor Assays ; },
abstract = {PURPOSE: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer.<br><br>METHODS: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model.<br><br>RESULTS: CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model.<br><br>CONCLUSIONS: CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.},
}
@article {pmid30769363,
year = {2019},
author = {Guillamat-Prats, R and Rami, M and Herzig, S and Steffens, S},
title = {Endocannabinoid Signalling in Atherosclerosis and Related Metabolic Complications.},
journal = {Thrombosis and haemostasis},
volume = {119},
number = {4},
pages = {567-575},
doi = {10.1055/s-0039-1678738},
pmid = {30769363},
issn = {2567-689X},
mesh = {Adipose Tissue/metabolism ; Animals ; Arachidonic Acid/chemistry ; Atherosclerosis/*metabolism ; Bile Acids and Salts/chemistry ; Blood Glucose/metabolism ; Cardiovascular System/metabolism ; Cytokines/metabolism ; Endocannabinoids/*metabolism ; Humans ; Inflammation ; Insulin Resistance ; Ligands ; Lipid Metabolism ; Lipids/chemistry ; Liver/metabolism ; Mice ; Mice, Knockout ; Obesity, Abdominal/metabolism ; Pancreas/metabolism ; Receptor, Cannabinoid, CB2/*metabolism ; Receptors, Cannabinoid/metabolism ; Receptors, G-Protein-Coupled/*metabolism ; Risk Factors ; *Signal Transduction ; },
abstract = {Endocannabinoids are a group of arachidonic acid-derived lipid mediators binding to cannabinoid receptors CB1 and CB2. An overactivity of the endocannabinoid system plays a pathophysiological role in the development of visceral obesity and insulin resistance. Moreover, elevated circulating endocannabinoid levels are also prevalent in atherosclerosis. The pathophysiological increase of endocannabinoid levels is due to an altered expression of endocannabinoid synthesizing and degrading enzymes induced by inflammatory mediators such as cytokines or lipids. Emerging experimental evidence suggests that enhanced endocannabinoid signalling affects atherosclerosis via multiple effects, including a modulation of vascular inflammation, leukocyte recruitment, macrophage cholesterol metabolism and consequently atherosclerotic plaque stability. In addition, recent findings in various metabolic disease models highlight the relevance of peripheral CB1 cannabinoid receptors in adipose tissue, liver and pancreas, which crucially regulate lipid and glucose metabolism as well as macrophage properties in these organs. This suggests that targeting the endocannabinoid system in the vasculature and peripheral organs might have a therapeutic potential for atherosclerosis by inhibiting vascular inflammation and improving metabolic risk factors. This review will provide a brief update on the effects of endocannabinoid signalling in atherosclerosis and related metabolic complications.},
}
@article {pmid30762822,
year = {2019},
author = {Louarn, N and Dauta, A and Lechapt-Zalcman, E and Kauv, P and Itti, E},
title = {Meningeal Metastasis Relapse With Focal Involvement of Cranial Bone Flap: A Case Resolved by 18F-DOPA PET/MRI.},
journal = {Clinical nuclear medicine},
volume = {44},
number = {4},
pages = {e315-e317},
doi = {10.1097/RLU.0000000000002492},
pmid = {30762822},
issn = {1536-0229},
mesh = {Breast Neoplasms/pathology ; *Dihydroxyphenylalanine ; Female ; *Fluorine Radioisotopes ; Humans ; *Magnetic Resonance Imaging ; Meningeal Neoplasms/*diagnostic imaging/*secondary ; Middle Aged ; *Multimodal Imaging ; *Positron-Emission Tomography ; Recurrence ; Skull/diagnostic imaging/metabolism ; },
abstract = {A 63-year-old woman was referred to our PET/MRI platform to evaluate the possible relapse of a meningeal metastasis, complicating an invasive ductal carcinoma of the left breast. This metastasis was diagnosed on a left hemiparesis and treated by surgery and radiation therapy. One year later, the same symptoms led to another brain MRI examination that found a contrast-enhanced lesion in the operating site. We decided to perform a F-DOPA PET/MRI to document this lesion, which confirmed the diagnosis of a probable relapse and revealed a focal uptake on the bone flap.},
}
@article {pmid30761666,
year = {2019},
author = {Yilmaz, R and Akpinar, Y and Ozyavuz, I and Önder, S and Tukenmez, M and Dursun, M},
title = {Synchronous metastatic leiomyosarcoma and primer invasive ductal carcinoma tumors in the same breast: Mammography, ultrasonography, and magnetic resonance imaging findings.},
journal = {The breast journal},
volume = {25},
number = {2},
pages = {310-311},
doi = {10.1111/tbj.13211},
pmid = {30761666},
issn = {1524-4741},
mesh = {Adult ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Leiomyosarcoma/*diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Mammography ; Ultrasonography, Mammary ; Unilateral Breast Neoplasms/*diagnostic imaging/pathology/secondary ; },
}
@article {pmid30760857,
year = {2019},
author = {Alsaleem, M and Toss, MS and Joseph, C and Aleskandarany, M and Kurozumi, S and Alshankyty, I and Ogden, A and Rida, PCG and Ellis, IO and Aneja, R and Green, AR and Mongan, NP and Rakha, EA},
title = {The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {32},
number = {7},
pages = {967-976},
doi = {10.1038/s41379-019-0209-9},
pmid = {30760857},
issn = {1530-0285},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Genomic Instability/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Middle Aged ; Tissue Array Analysis ; Young Adult ; },
abstract = {E-cadherin is a tumor suppressor gene in invasive lobular breast cancer. However, a proportion of high-grade ductal carcinoma shows reduced/loss of E-cadherin. In this study, we assessed the underlying mechanisms and molecular implications of E-cadherin loss in invasive ductal carcinoma. This study used large, well-characterized cohorts of early-stage breast cancer-evaluated E-cadherin expression via various platforms including immunohistochemistry, microarray analysis using Illumina HT-12 v3, copy number analysis using Affymetrix SNP 6.0 arrays, and next-generation sequencing for differential gene expression. Our results showed 27% of high-grade invasive ductal carcinoma showed reduced/loss of E-cadherin membranous expression. CDH1 copy number loss was in 21% of invasive ductal carcinoma, which also showed low CDH1 mRNA expression (p = 0.003). CDH1 copy number was associated with copy number loss of TP53, ATM, BRCA1, and BRCA2 (p < 0.001). Seventy-nine percent of invasive ductal carcinoma with reduced CDH1 mRNA expression showed elevated expression of E-cadherin transcription suppressors TWIST2, ZEB2, NFKB1, LLGL2, CTNNB1 (p < 0.01). Reduced/loss E-cadherin expression was associated with differential expression of 2143 genes including those regulating Wnt (FZD2, GNG5, HLTF, WNT2, and CER1) and PIK3-AKT (FGFR2, GNF5, GNGT1, IFNA17, and IGF1) signaling pathways. Interestingly, key genes differentially expressed between invasive lobular carcinoma and invasive ductal tumors did not show association with E-cadherin loss in invasive ductal carcinoma. We conclude that E-cadherin loss in invasive ductal carcinoma is likely a consequence of genomic instability occurring during carcinogenesis. Potential novel regulators controlling E-cadherin expression in invasive ductal carcinoma warrant further investigation.},
}
@article {pmid30728399,
year = {2019},
author = {Kaur, P and Porras, TB and Ring, A and Carpten, JD and Lang, JE},
title = {Comparison of TCGA and GENIE genomic datasets for the detection of clinically actionable alterations in breast cancer.},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {1482},
pmid = {30728399},
issn = {2045-2322},
support = {P30 CA014089/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*genetics/pathology ; Computer Simulation ; DNA Copy Number Variations/genetics ; Databases, Genetic/*standards/*trends ; Exome/genetics ; Female ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Mutation/genetics ; Precision Medicine/methods ; },
abstract = {Whole exome sequencing (WES), targeted gene panel sequencing and single nucleotide polymorphism (SNP) arrays are increasingly used for the identification of actionable alterations that are critical to cancer care. Here, we compared The Cancer Genome Atlas (TCGA) and the Genomics Evidence Neoplasia Information Exchange (GENIE) breast cancer genomic datasets (array and next generation sequencing (NGS) data) in detecting genomic alterations in clinically relevant genes. We performed an in silico analysis to determine the concordance in the frequencies of actionable mutations and copy number alterations/aberrations (CNAs) in the two most common breast cancer histologies, invasive lobular and invasive ductal carcinoma. We found that targeted sequencing identified a larger number of mutational hotspots and clinically significant amplifications that would have been missed by WES and SNP arrays in many actionable genes such as PIK3CA, EGFR, AKT3, FGFR1, ERBB2, ERBB3 and ESR1. The striking differences between the number of mutational hotspots and CNAs generated from these platforms highlight a number of factors that should be considered in the interpretation of array and NGS-based genomic data for precision medicine. Targeted panel sequencing was preferable to WES to define the full spectrum of somatic mutations present in a tumor.},
}
@article {pmid30725231,
year = {2019},
author = {Liu, Y and Pandey, PR and Sharma, S and Xing, F and Wu, K and Chittiboyina, A and Wu, SY and Tyagi, A and Watabe, K},
title = {ID2 and GJB2 promote early-stage breast cancer progression by regulating cancer stemness.},
journal = {Breast cancer research and treatment},
volume = {175},
number = {1},
pages = {77-90},
pmid = {30725231},
issn = {1573-7217},
support = {R01CA205067//National Cancer Institute (US)/ ; F31 CA200286/CA/NCI NIH HHS/United States ; F31CA200286//National Cancer Institute/ ; R01CA173499//National Cancer Institute/ ; R01 CA173499/CA/NCI NIH HHS/United States ; P30 CA012197/CA/NCI NIH HHS/United States ; R01CA185650//National Cancer Institute/ ; R01 CA205067/CA/NCI NIH HHS/United States ; R01 CA185650/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; *Biomarkers, Tumor ; Breast Neoplasms/drug therapy/*genetics/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Proliferation ; Chalcone/analogs &amp; derivatives/chemistry/pharmacology ; Connexin 26 ; Connexins/*genetics ; Disease Models, Animal ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Inhibitor of Differentiation Protein 2/*genetics ; Mice ; Neoplasm Staging ; Neoplastic Stem Cells/*metabolism ; Prognosis ; *Promoter Regions, Genetic ; },
abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer which could progress to or recur as invasive breast cancer. The underlying molecular mechanism of DCIS progression is yet poorly understood, and appropriate biomarkers to distinguish benign form of DCIS from potentially invasive tumor are urgently needed.<br><br>METHODS: To identify the key regulators of DCIS progression, we performed gene-expression analysis of syngeneic breast cancer cell lines MCF10A, DCIS.com, and MCF10CA and cross-referenced the targets with patient cohort data.<br><br>RESULTS: We identified ID2 as a critical gene for DCIS initiation and found that ID2 promoted DCIS formation by enhancing cancer stemness of pre-malignant cells. ID2 also plays a pivotal role in survival of the aggressive cancer cells. In addition, we identified INHBA and GJB2 as key regulators for the transition of benign DCIS to aggressive phenotype. These two genes regulate migration, colonization, and stemness of invasive cancer cells. Upregulation of ID2 and GJB2 predicts poor prognosis after breast-conserving surgery. Finally, we found a natural compound Helichrysetin as ID2 inhibitor which suppresses DCIS formation in vitro and in vivo.<br><br>CONCLUSION: Our results indicate that ID2 is a key driver of DCIS formation and therefore is considered to be a potential target for prevention of DCIS, while INHBA and GJB2 play vital roles in progression of DCIS to IDC and they may serve as potential prognosis markers.},
}
@article {pmid30719718,
year = {2019},
author = {Dianatinasab, M and Fararouei, M and Daneshi, N and Rezaian, S and Mohammadianpanah, M and Chaman, R and Ghiasvand, R},
title = {Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case-control study.},
journal = {International journal of cancer},
volume = {145},
number = {11},
pages = {2917-2925},
doi = {10.1002/ijc.32182},
pmid = {30719718},
issn = {1097-0215},
mesh = {Abortion, Spontaneous/epidemiology ; Adult ; Breast Feeding/statistics &amp; numerical data ; Breast Neoplasms/*epidemiology/etiology ; Carcinoma, Ductal, Breast/*epidemiology/etiology ; Carcinoma, Lobular/*epidemiology/etiology ; Case-Control Studies ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Humans ; Iran ; Middle Aged ; Risk Factors ; },
abstract = {Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast are the most common histological subtypes of breast cancer. However, the associations and heterogeneity between histological subtypes and their risk factors are not well established. This study aimed to investigate risk factors for IDC and ILC. This case-control study included 1,009 incident breast cancer cases and 1,009 hospital controls, frequency-matched by age. Data were obtained from the patients' medical files and an interview administered via a questionnaire. Multinomial logistic regression was used and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The heterogeneity of the associations was assessed using the Wald test. Family history of breast cancer was associated with IDC (OR 2.64, 95% CI: 1.97-3.55) but not ILC (OR 0.81, 95% CI: 0.42-1.57; p for heterogeneity <0.001). Conversely, a history of miscarriage was associated with ILC (OR 1.71, 95% CI: 1.17-2.51) but not IDC (OR 1.18, 95% CI: 0.95-1.46; p for heterogeneity = 0.04). Similarly, type 2 diabetes was associated with ILC but not IDC (p for heterogeneity = 0.02). Age at first delivery and breastfeeding were significantly associated with IDC but not ILC, though p values for heterogeneity did not reach the significance level. Deliberate weight loss and age at menarche were significantly associated with ILC but not IDC (p for heterogeneity ≥0.27). Smoking, history of benign breast disease and BMI were associated with both subtypes. The present study supports the hypothesis that IDC and ILC are etiologically distinct tumours.},
}
@article {pmid30712460,
year = {2020},
author = {Song, G and He, L and Yang, X and Yang, Y and Cai, X and Liu, K and Feng, G},
title = {Identification of aberrant gene expression during breast ductal carcinoma in situ progression to invasive ductal carcinoma.},
journal = {The Journal of international medical research},
volume = {48},
number = {1},
pages = {300060518815364},
pmid = {30712460},
issn = {1473-2300},
mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cluster Analysis ; Databases, Genetic ; *Disease Progression ; Down-Regulation/genetics ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics/metabolism ; Reproducibility of Results ; Signal Transduction/genetics ; Up-Regulation/genetics ; },
abstract = {OBJECTIVE: It has been reported that 80% of all breast carcinoma cases are invasive ductal carcinoma (IDC), and 45% to 78% of invasive breast carcinoma cases are associated with ductal carcinoma in situ (DCIS). Therefore, it is important to gain insights into transcriptome changes that occur during DCIS progression to IDC.<br><br>METHODS: We downloaded Gene Expression Omnibus databases GSE21422 and GSE3893, and performed differentially expressed gene (DEG) analysis and cluster analysis, followed by pathway enrichment analysis and Oncomine analysis.<br><br>RESULTS: Twenty-six conserved DEGs were identified in both GSE21422 and GSE3893. These genes are mainly enriched in intermediate filament-based processes, immune responses, Staphylococcus aureus infection response, and phagosomes. Among them, FCGR2A, HLA-DRA, C3AR1, and FYB were reported to be involved in DCIS progression to IDC. High expression of HLA-DRA, C3AR1, and FYB in different types of breast cancer was validated using different Oncomine datasets. Moreover, elevated HLA-DRA and FYB levels were associated with breast cancer recurrence. Importantly, the overexpression of FYB was correlated with breast cancer metastasis.<br><br>CONCLUSIONS: This study revealed the molecular characteristics associated with progression from DCIS to IDC. It also identified potential biomarkers for DCIS progression to IDC, which will aid breast cancer diagnosis and prevention.},
}
@article {pmid30692436,
year = {2018},
author = {Kodera, A and Inoue, H and Ogura, K and Sakaguchi, S and Yukawa, H and Matsuoka, A and Tanaka, N and Kinoshita, J and Yoshimatsu, K and Naritaka, Y and Hirano, A},
title = {[Bevacizumab plus Paclitaxel Therapy Was Effective for Metastatic Breast Cancer with Dysphagia Due to Mediastinal Lymph Node Metastasis-A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {45},
number = {13},
pages = {2276-2278},
pmid = {30692436},
issn = {0385-0684},
mesh = {Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration &amp; dosage ; *Breast Neoplasms/complications/drug therapy ; *Deglutition Disorders/drug therapy/etiology ; Female ; Humans ; Lymph Nodes ; Paclitaxel/administration &amp; dosage ; Quality of Life ; },
abstract = {A 69-year-old woman noticed a tumor of the right breast, and presented to our hospital with dysphagia. A tumor of size 10 cm exposed to the skin and swollen axillary lymph node were observed. She was diagnosed with invasive ductal carcinoma, luminal-B by core-needle biopsy. CT scan revealed primary breast cancer with lung, bone, and lymph node metastasis. Endoscopic and fluoroscopic findings of the esophagus showed severe stenosis by extrinsic compression. In order to improve the quality of life(QOL)immediately, bevacizumab plus paclitaxel therapy was initiated. After the first course, the dysphagia improved, and she was able to take normal meals after 2 courses of treatment. Primary tumor and metastatic lesions had remarkably shrunk on CT scan. After 4 courses of treatment, we changed to endocrine therapy and continued outcome treatment. Bevacizumab was effective for immediate improvement of QOL in such as an oncologic emergent case of metastatic breast cancer.},
}
@article {pmid30689164,
year = {2019},
author = {da Silva Filho, AF and Vieira-de-Mello, GS and Dos Santos, PB and de Melo Rêgo, MJB and Ribeiro-Silva, A and Beltrão, EIC},
title = {N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast.},
journal = {Pathology oncology research : POR},
volume = {25},
number = {2},
pages = {759-768},
pmid = {30689164},
issn = {1532-2807},
mesh = {Adult ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/enzymology/*pathology ; Carcinoma, Ductal, Breast/enzymology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/enzymology/*pathology ; Female ; Humans ; Middle Aged ; N-Acetylglucosaminyltransferases/analysis/*metabolism ; },
abstract = {Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6), -T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.},
}
@article {pmid30675210,
year = {2019},
author = {Smalley, T and Islam, SMA and Apostolatos, C and Apostolatos, A and Acevedo-Duncan, M},
title = {Analysis of PKC-ζ protein levels in normal and malignant breast tissue subtypes.},
journal = {Oncology letters},
volume = {17},
number = {2},
pages = {1537-1546},
pmid = {30675210},
issn = {1792-1074},
abstract = {It is estimated that breast cancer will be the second leading cause of cancer-associated mortality in women in 2018. Previous research has demonstrated that the atypical protein kinase C-ζ (PKC-ζ) is a component of numerous dysregulated pathways in breast cancer, including cellular proliferation, survival, and cell cycle upregulation. The present study investigated the PKC-ζ protein in breast tissue to evaluate its potential as a biomarker for breast cancer invasion, and demonstrated that an overexpression of PKC-ζ protein can be indicative of carcinogenesis. The present study analyzed the expression of PKC-ζ in individuals with no tumor complications and malignant female human breast tissue samples (lobular carcinoma in situ, invasive lobular carcinoma, ductal carcinoma in situ and invasive ductal carcinoma) with the use of western blot analysis, immunohistochemistry and statistical analysis (83 samples). The present study also evaluated the invasive behavior of MDA-MB-231 breast cancer cells following the knockdown of PKC-ζ with a Transwell invasion assay and an immunofluorescent probe for filamentous actin (F-actin) organization. The data demonstrated that PKC-ζ expression was identified to be higher in invading tissues when compared with non-invading tissues. The results also suggest that PKC-ζ is more abundant in ductal tissues when compared with lobular tissues. In addition, the protein studies also suggest that PKC-ζ is a component for invasive behavior through the Ras-related C3 botulinum toxin substrate 1 (Rac1) and Ras homolog gene family member A (RhoA) pathway, and PKC-ζ is required for the F-actin reorganization in invasive cells. Therefore, PKC-ζ should be considered to be a biomarker in the development of breast cancer as well as an indicator of invading tumor cells.},
}
@article {pmid30659137,
year = {2019},
author = {Traylor, M and Tozer, DJ and Croall, ID and Lisiecka-Ford, DM and Olorunda, AO and Boncoraglio, G and Dichgans, M and Lemmens, R and Rosand, J and Rost, NS and Rothwell, PM and Sudlow, CLM and Thijs, V and Rutten-Jacobs, L and Markus, HS and , },
title = {Genetic variation in PLEKHG1 is associated with white matter hyperintensities (n = 11,226).},
journal = {Neurology},
volume = {92},
number = {8},
pages = {e749-e757},
pmid = {30659137},
issn = {1526-632X},
support = {FS/15/61/31626/BHF_/British Heart Foundation/United Kingdom ; MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; RG/16/4/32218/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Adult ; Aged ; Brain Ischemia/diagnostic imaging/*genetics ; Cerebral Small Vessel Diseases/diagnostic imaging/*genetics ; Female ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Rho Guanine Nucleotide Exchange Factors/*genetics ; Stroke/diagnostic imaging/*genetics ; Stroke, Lacunar/diagnostic imaging/genetics ; White Matter/*diagnostic imaging ; },
abstract = {OBJECTIVE: To identify novel genetic associations with white matter hyperintensities (WMH).<br><br>METHODS: We performed a genome-wide association meta-analysis of WMH volumes in 11,226 individuals, including 8,429 population-based individuals from UK Biobank and 2,797 stroke patients. Replication of novel loci was performed in an independent dataset of 1,202 individuals. In all studies, WMH were quantified using validated automated or semi-automated methods. Imputation was to either the Haplotype Reference Consortium or 1,000 Genomes Phase 3 panels.<br><br>RESULTS: We identified a locus at genome-wide significance in an intron of PLEKHG1 (rs275350, &#x3b2; [SE] = 0.071 [0.013]; p = 1.6 &#xd7; 10[-8]), a Rho guanine nucleotide exchange factor that is involved in reorientation of cells in the vascular endothelium. This association was validated in an independent sample (overall p value, 2.4 &#xd7; 10[-9]). The same single nucleotide polymorphism was associated with all ischemic stroke (odds ratio [OR] [95% confidence interval (CI)] 1.07 [1.03-1.12], p = 0.00051), most strongly with the small vessel subtype (OR [95% CI] 1.09 [1.00-1.19], p = 0.044). Previous associations at 17q25 and 2p16 reached genome-wide significance in this analysis (rs3744020; &#x3b2; [SE] = 0.106 [0.016]; p = 1.2 &#xd7; 10[-11] and rs7596872; &#x3b2; [SE] = 0.143 [0.021]; p = 3.4 &#xd7; 10[-12]). All identified associations with WMH to date explained 1.16% of the trait variance in UK Biobank, equivalent to 6.4% of the narrow-sense heritability.<br><br>CONCLUSIONS: Genetic variation in PLEKHG1 is associated with WMH and ischemic stroke, most strongly with the small vessel subtype, suggesting it acts by promoting small vessel arteriopathy.},
}
@article {pmid30659022,
year = {2019},
author = {Guo, Q and Li, VZ and Nichol, JN and Huang, F and Yang, W and Preston, SEJ and Talat, Z and Lefrère, H and Yu, H and Zhang, G and Basik, M and Gonçalves, C and Zhan, Y and Plourde, D and Su, J and Torres, J and Marques, M and Habyan, SA and Bijian, K and Amant, F and Witcher, M and Behbod, F and McCaffrey, L and Alaoui-Jamali, M and Giannakopoulos, NV and Brackstone, M and Postovit, LM and Del Rincón, SV and Miller, WH},
title = {MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma In Situ.},
journal = {Cancer research},
volume = {79},
number = {7},
pages = {1646-1657},
pmid = {30659022},
issn = {1538-7445},
support = {R01 CA207445/CA/NCI NIH HHS/United States ; R21 CA226567/CA/NCI NIH HHS/United States ; PJT-156269//CIHR/Canada ; MOP-142281//CIHR/Canada ; },
mesh = {Animals ; Breast Carcinoma In Situ/metabolism/*pathology ; Breast Neoplasms/metabolism/*pathology ; CRISPR-Cas Systems ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Heterografts ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mice ; Mice, Nude ; Nodal Protein/*metabolism ; Protein Serine-Threonine Kinases/genetics/*metabolism ; *Signal Transduction ; },
abstract = {The mechanisms by which breast cancers progress from relatively indolent ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion. NODAL, a morphogen essential for embryogenic patterning, is often reexpressed in breast cancer. Here we describe a MNK1/NODAL signaling axis that promotes DCIS progression to IDC. We generated MNK1 knockout (KO) or constitutively active MNK1 (caMNK1)-expressing human MCF-10A-derived DCIS cell lines, which were orthotopically injected into the mammary glands of mice. Loss of MNK1 repressed NODAL expression, inhibited DCIS to IDC conversion, and decreased tumor relapse and metastasis. Conversely, caMNK1 induced NODAL expression and promoted IDC. The MNK1/NODAL axis promoted cancer stem cell properties and invasion in vitro. The MNK1/2 inhibitor SEL201 blocked DCIS progression to invasive disease in vivo. In clinical samples, IDC and DCIS with microinvasion expressed higher levels of phospho-MNK1 and NODAL versus low-grade (invasion-free) DCIS. Cumulatively, our data support further development of MNK1 inhibitors as therapeutics for preventing invasive disease. SIGNIFICANCE: These findings provide new mechanistic insight into progression of ductal carcinoma and support clinical application of MNK1 inhibitors to delay progression of indolent ductal carcinoma in situ to invasive ductal carcinoma.},
}
@article {pmid30652428,
year = {2019},
author = {Liu, Y and Ide, Y and Inuzuka, M and Tazawa, S and Kanada, Y and Matsunaga, Y and Kuwayama, T and Sawada, T and Akashi-Tanaka, S and Nakamura, S},
title = {BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ.},
journal = {Molecular genetics &amp; genomic medicine},
volume = {7},
number = {3},
pages = {e493},
pmid = {30652428},
issn = {2324-9269},
mesh = {Adult ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/*genetics ; Female ; Genetic Testing/standards ; Humans ; Incidence ; Japan ; *Mutation ; },
abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations.<br><br>METHODS: A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR).<br><br>RESULTS: (a) Of 325 patients (with or without invasive cancer), 19.1% (62/325) tested positive for BRCA1/BRCA2 mutations. And 18.4% (9/49) was positive for BRCA1/BRCA2 mutations in DCIS, compared with 19.2% (53/276) in IDC (p&#xa0;=&#xa0;1.000). Among BRCA mutations, 14.5% (9/62) had DCIS compared with nonmutations (15.2%, 40/263). Incidence of DCIS was 3.0% (1/33) of BRCA1 mutations and 27.5% (8/29) of BRCA2 mutation (p&#xa0;=&#xa0;0.009). (b) Median age of diagnosis in BRCA mutation carriers was 39&#xa0;years, compared with 46&#xa0;years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between BRCA mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX&#xa0;&#x2265;&#xa0;2 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266-20.763; p&#xa0;=&#xa0;0.022), age at diagnosis &#x2264;35&#xa0;years (OR 0.149, 95% CI 0.023-0.954, p&#xa0;=&#xa0;0.045) and ER+/HER2+ status (OR 5.034, 95% CI 1.092-23.210, p&#xa0;=&#xa0;0.038) remained as independent significant predictors for BRCA mutation. Ki67 index (cut off by 14% or 30%) did not differ between BRCA mutation carriers and noncarriers (p&#xa0;=&#xa0;0.459 and p&#xa0;=&#xa0;0.651). (c) There was a significant difference in ER-positive tumors among BRCA2 carriers and noncarriers (p&#xa0;=&#xa0;0.042). Subgroup analysis showed BRCA2 carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+/PR+ (p&#xa0;=&#xa0;0.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) BRCA mutation was not associated with an increased risk of IBTR and CBTR.<br><br>CONCLUSION: DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX &#x2265;2, age at diagnosis &#x2264;35&#xa0;years and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing.},
}
@article {pmid30621656,
year = {2019},
author = {Framarino-Dei-Malatesta, M and Chiarito, A and Bianciardi, F and Fiorelli, M and Ligato, A and Naso, G and Pecorella, I},
title = {Metastases to extraocular muscles from breast cancer: case report and up-to-date review of the literature.},
journal = {BMC cancer},
volume = {19},
number = {1},
pages = {36},
pmid = {30621656},
issn = {1471-2407},
mesh = {Adult ; Breast Neoplasms/*diagnosis/diagnostic imaging/drug therapy/pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Muscle Neoplasms/*diagnosis/diagnostic imaging/pathology/secondary ; Neoplasm Metastasis ; Piperazines/therapeutic use ; Pyridines/therapeutic use ; },
abstract = {BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer.<br><br>CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3&#x2009;years and letrozole in the following 3&#x2009;years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20&#x2009;months.<br><br>CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20&#x2009;months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.},
}
@article {pmid30608397,
year = {2019},
author = {Bertozzi, S and Cedolini, C and Londero, AP and Baita, B and Giacomuzzi, F and Capobianco, D and Tortelli, M and Uzzau, A and Mariuzzi, L and Risaliti, A},
title = {Sentinel lymph node biopsy in patients affected by breast ductal carcinoma in situ with and without microinvasion: Retrospective observational study.},
journal = {Medicine},
volume = {98},
number = {1},
pages = {e13831},
pmid = {30608397},
issn = {1536-5964},
mesh = {Aged ; Breast/pathology ; Breast Carcinoma In Situ/mortality/pathology/*surgery ; Breast Neoplasms/mortality/pathology/*surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*surgery ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Micrometastasis ; Neoplasm Recurrence, Local/pathology ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node/pathology ; Sentinel Lymph Node Biopsy/*mortality ; },
abstract = {With the introduction of an organized mammographic screening, the incidence of ductal carcinoma in situ (DCIS) has experienced an important increase. Our experience with sentinel lymph node biopsy (SLNB) among patients with DCIS is reviewed.We collected retrospective data on patients operated on their breasts for DCIS (pTis), DCIS with microinvasion (DCISM) (pT1mi) and invasive ductal carcinoma (IDC) sized ≤2 cm (pT1) between January 2002 and June 2016, focusing on the result of SLNB.543 DCIS, 84 DCISM, and 2111 IDC were included. In cases of DCIS and DCISM, SLNB resulted micrometastatic respectively in 1.7% and 6.0% of cases and macrometastatic respectively in 0.9% and 3.6% of cases. 5-year disease-free survival and overall survival in DCISM and IDC were similar, while significantly longer in DCIS. 5-year local recurrence rate of DCIS and DCISM were respectively 2.5% and 7.9%, and their 5-year distant recurrence rate respectively 0% and 4%. IDC, tumor grading ≥2 and lymph node (LN) macrometastasis were significant predictors for decreased overall survival. Significant predictors for distant metastases were DCISM, IDC, macroscopic nodal metastasis, and tumor grading ≥2. Predictors for the microinvasive component in DCIS were tumor multifocality/multicentricity, grading ≥2, ITCs and micrometastases.Our study suggests that despite its rarity, sentinel node metastasis may also occur in case of DCIS, which in most cases are micrometastases. Even in the absence of an evident invasive component, microinvasion should always be suspected in these cases, and their management should be the same as for IDC.},
}
@article {pmid30607556,
year = {2019},
author = {Wang, G and Zhou, C and Conklin, C and Hayes, MM and Villamil, CF and Ostry, A and Jones, EC},
title = {Metastatic breast carcinoma to the urinary bladder-a report of 11 cases including a tumor to tumor metastasis.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {474},
number = {3},
pages = {333-339},
pmid = {30607556},
issn = {1432-2307},
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary/therapy ; Carcinoma, Lobular/chemistry/mortality/*secondary/therapy ; Carcinoma, Squamous Cell/chemistry/mortality/*pathology/therapy ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Time Factors ; Urinary Bladder Neoplasms/chemistry/mortality/*secondary/therapy ; },
abstract = {Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.},
}
@article {pmid30594914,
year = {2019},
author = {Khorshidi, H and Azari, I and Oskooei, VK and Taheri, M and Ghafouri-Fard, S},
title = {DSCAM-AS1 up-regulation in invasive ductal carcinoma of breast and assessment of its potential as a diagnostic biomarker.},
journal = {Breast disease},
volume = {38},
number = {1},
pages = {25-30},
doi = {10.3233/BD-180351},
pmid = {30594914},
issn = {1558-1551},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Carcinoma, Ductal, Breast/*diagnosis/*genetics ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Association Studies ; Humans ; Middle Aged ; RNA, Long Noncoding/*genetics ; Real-Time Polymerase Chain Reaction ; Tamoxifen/therapeutic use ; Up-Regulation ; },
abstract = {BACKGROUND: The long non-coding RNA (lncRNA) DSCAM-AS1 has been demonstrated to participate in the pathogenesis of breast cancer and tamoxifen resistance.<br><br>OBJECTIVE: To evaluate expression profile of DSCAM-AS1&#xa0;in invasive ductal carcinoma of breast and its suitability as a biomarker for diagnosis of breast cancer.<br><br>METHODS: We evaluated expression of DSCAM-AS1&#xa0;in 108 breast tissues including tumoral and adjacent non-cancerous tissues (ANCTs) by means of quantitative real time PCR.<br><br>RESULTS: DSCAM-AS1&#xa0;was up-regulated in tumoral tissues compared with ANCTs (Fold change = 2.86, P =&#xa0;0.011). Its expression was significantly higher in patients aged less than 55 compared with older patients (P =&#xa0;0.02). However, its expression levels had not a good performance as a diagnostic biomarker for breast cancer.<br><br>CONCLUSIONS: The significant up-regulation of DSCAM-AS1&#xa0;in tumoral tissues compared with ANCTs provides further evidences for participation of this lncRNA in the pathogenesis of breast cancer.},
}
@article {pmid30587740,
year = {2018},
author = {Yano, Y and Kuga, T and Harada, T and Sano, F and Inokuchi, T and Fujii, Y},
title = {[A Case of Suspected Therapy-Related Leukemia after Chemotherapy for Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {45},
number = {12},
pages = {1775-1777},
pmid = {30587740},
issn = {0385-0684},
mesh = {*Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; Female ; Humans ; *Leukemia/chemically induced ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasms, Second Primary ; Sentinel Lymph Node Biopsy ; },
abstract = {Therapy-related leukemia(TRL)is a distinctive clinical syndrome that occurs after exposure to chemotherapy or radiotherapy. We report a case of suspected TRLafter chemotherapy in a patient with breast cancer. A 61-year-old woman underwent total mastectomy and sentinel lymph node biopsy(negative)for her breast cancer. Histopathologic analysis showed invasive ductal carcinoma, pStage I. Her subtype histology was Luminal B-type, and postoperative adjuvant chemotherapy and endocrine therapy were administered. Four years after chemotherapy, a blood examination showed pancytopenia. Bone marrow examination showed acute promyelocytic leukemia. She was treated with chemotherapy and achieved complete remission. Breast cancer provides long-term survival after treatment. Attention should be paid to the occurrence of TRLin breast cancer surveillance.},
}
@article {pmid30582225,
year = {2019},
author = {Bertagnolo, V and Grassilli, S and Volinia, S and Al-Qassab, Y and Brugnoli, F and Vezzali, F and Lambertini, E and Palomba, M and Piubello, Q and Orvieto, E and Natali, C and Piva, R and Croce, CM and Capitani, S},
title = {Ectopic expression of PLC-β2 in non-invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR-146a.},
journal = {Molecular carcinogenesis},
volume = {58},
number = {5},
pages = {708-721},
pmid = {30582225},
issn = {1098-2744},
support = {FIRB RBAP10Z7FS_002//Italian MIUR/International ; IG 170631//Associazione Italiana per la Ricerca sul Cancro/International ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Proliferation ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplastic Stem Cells/metabolism/*pathology ; Phospholipase C beta/genetics/*metabolism ; Prognosis ; Tumor Cells, Cultured ; },
abstract = {Cells in non-invasive breast lesions are widely believed to possess molecular alterations that render them either susceptible or refractory to the acquisition of invasive capability. One such alteration could be the ectopic expression of the β2 isoform of phosphoinositide-dependent phospholipase C (PLC-β2), known to counteract the effects of hypoxia in low-invasive breast tumor-derived cells. Here, we studied the correlation between PLC-β2 levels and the propensity of non-invasive breast tumor cells to acquire malignant features. Using archival FFPE samples and DCIS-derived cells, we demonstrate that PLC-β2 is up-regulated in DCIS and that its forced down-modulation induces an epithelial-to-mesenchymal shift, expression of the cancer stem cell marker CD133, and the acquisition of invasive properties. The ectopic expression of PLC-β2 in non-transformed and DCIS-derived cells is, to some extent, dependent on the de-regulation of miR-146a, a tumor suppressor miRNA in invasive breast cancer. Interestingly, an inverse relationship between the two molecules, indicative of a role of miR-146a in targeting PLC-β2, was not detected in primary DCIS from patients who developed a second invasive breast neoplasia. This suggests that alterations of the PLC-β2/miR-146a relationship in DCIS may constitute a molecular risk factor for the appearance of new breast lesions. Since neither traditional classification systems nor molecular characterizations are able to predict the malignant potential of DCIS, as is possible for invasive ductal carcinoma (IDC), we propose that the assessment of the PLC-β2/miR-146a levels at diagnosis could be beneficial for identifying whether DCIS patients may have either a low or high propensity for invasive recurrence.},
}
@article {pmid30577784,
year = {2018},
author = {Ssemmanda, S and Katagirya, E and Bukirwa, P and Alele, D and Lukande, R and Kalungi, S},
title = {Breast diseases histologically diagnosed at a tertiary facility in Uganda (2005-2014).},
journal = {BMC cancer},
volume = {18},
number = {1},
pages = {1285},
pmid = {30577784},
issn = {1471-2407},
mesh = {Adult ; Breast Diseases/diagnosis/*epidemiology/pathology ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Female ; Fibroadenoma/diagnosis/*epidemiology/pathology ; Humans ; Male ; Risk Factors ; Uganda/epidemiology ; },
abstract = {BACKGROUND: The prevalence and distribution of histologically diagnosed breast disease are not well documented in low income countries, Uganda inclusive. Although the greater majority of breast lesions globally are benign, breast cancer is the most frequently diagnosed cancer all over the world. We aimed at documenting the prevalence of different breast diseases histologically diagnosed at the histopathology laboratory of the Department of Pathology of the Makerere University College of Health Sciences (MakCHS Lab) over a decade (2005-2014). We also describe the demographic characteristics of the patients in Uganda diagnosed with breast disease at the MakCHS Lab during the same period.<br><br>METHODS: This was a 10&#x2009;year retrospective study of histologically diagnosed breast disease between 2005 and 2014 inclusive at the MakCHS Lab. We extracted information from hard copies of all 2510 histopathology reports retrieved from archives of the Department of Pathology at the MakCHS Lab. 640 records that were either damaged beyond recognition of key details, were duplicated, were implausible or had no conclusive diagnosis made were excluded. Information to be analyzed was then entered into Epidata (version 3.1) on a password protected laptop. Data analysis was done using SPSS software (v16 for Windows &#xd7;&#x2009;64).<br><br>RESULTS: From the 1870 patients' records eventually analyzed, breast disease was most diagnosed in female patients (97.1%). The overall mean age for breast disease diagnosis was 33&#x2009;years (S.D&#x2009;&#xb1;&#x2009;16.46) and median age 26&#x2009;years (IQR: 20-43). Fibroadenoma (40.1%) was the most diagnosed breast disease overall. We noticed steadily increasing frequency of diagnosis of cancerous breast diseases over the last half of the study period. Invasive ductal carcinoma was the most diagnosed breast cancer (326 cases, 55.6%). A high female to male breast cancer ratio of 48:1 was observed. The highest regional breast cancer proportion was from the Western region of the Country.<br><br>CONCLUSIONS: There is need for more research into the picture of breast disease in the country, covering various demographic characteristics of the country's population for all regions and informing about its incidence rates and prevalence and also the breast cancer risk estimate for benign breast disease.},
}
@article {pmid30570854,
year = {2018},
author = {Sunar, V and T Dogan, H and Sarici, F and Ates, O and Akin, S and Baspinar, B and Aksoy, S and Altundag, K},
title = {Association between androgen receptor status and prognosis in triple negative breast cancer.},
journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology},
volume = {23},
number = {5},
pages = {1325-1330},
pmid = {30570854},
issn = {1107-0625},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Ductal, Breast/metabolism/*secondary/therapy ; Carcinoma, Lobular/metabolism/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptors, Androgen/*metabolism ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/metabolism/*pathology/therapy ; },
abstract = {PURPOSE: Triple negative breast cancer (TNBC) is a heterogeneous disease group with a higher recurrence risk and poorer prognosis. In this study, we aimed to investigate the frequency and prognostic value of androgen receptor (AR) expression in tissues of TNBC patients.<br><br>METHODS: A total of 84 TNBC patients treated between 2000 - 2015 in Hacettepe University Cancer Institute were included and their medical records were analyzed retrospectively. The available paraffin blocks were assessed immunohistochemically to determine AR expression. Tumors with &#x2265;1% nuclear staining were considered AR-positive, while the ones with <1% staining were considered AR-negative. We analyzed the association between AR expression, and clinical-pathologic characteristics and prognosis in TNBC.<br><br>RESULTS: Of the 84 TNBC patients, 25 (29.8%) were AR-positive. The frequency of grade 3 tumors was lower among AR-positive TNBC tumors compared to AR-negative tumors (40 vs 86.4%, p<0.001). In the AR-positive group, invasive ductal carcinoma (IDC) was less prevalent compared to AR-negative group (56 vs 86.4%, p<0.002). However, there were not statistically significant differences between AR positive and negative groups in terms of overall survival (OS) and disease free survival (DFS) (p=0.449, p=0.733, respectively). We found that grade 3 tumors were less frequent in AR-positive TNBC in our study. Nonetheless, we did not detect statistically significant difference in terms of overall survival and disease free survival between AR positive and negative TNBC.<br><br>CONCLUSION: Routine evaluation of AR could contribute to further studies that may enlighten the role of AR targeting therapies in TNBC.},
}
@article {pmid30562218,
year = {2019},
author = {Alkhasawneh, A and Nassri, A and John, I},
title = {Dedifferentiated Melanoma With Expression of Cytokeratin and GATA3 in a Patient With History of Breast Carcinoma.},
journal = {The American Journal of dermatopathology},
volume = {41},
number = {7},
pages = {502-504},
doi = {10.1097/DAD.0000000000001322},
pmid = {30562218},
issn = {1533-0311},
mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Dedifferentiation ; Female ; GATA3 Transcription Factor/metabolism ; Humans ; Keratins/metabolism ; Lymphatic Metastasis ; Melanoma/metabolism/*secondary ; Middle Aged ; Neoplasms, Second Primary/metabolism/*pathology ; Skin Neoplasms/metabolism/*pathology/secondary ; },
abstract = {Melanoma is one of the great mimickers in pathology because it has diverse morphologies and can be mistaken for carcinoma or sarcoma. In most cases, immunochemistry is helpful in supporting the diagnosis and excluding other differentials. However, metastatic melanoma may lose immunohistochemical melanocytic markers and express nonmelanocytic lineage markers, which often poses a diagnostic dilemma and may be misdiagnosed as a poorly differentiated carcinoma or sarcoma. We report the case of a 52-year-old woman who had a history of recurrent melanoma on her right shoulder with axillary lymph node metastasis (BRAF V600K-mutated melanoma) and right-side breast-invasive ductal carcinoma (stage pT1b N0sn). One year later, she presented with a left-sided chest wall mass and enlarging left axillary lymph nodes. Needle core biopsies were obtained from both lesions, and histologic examination showed a poorly differentiated tumor with pleomorphic/anaplastic morphology and necrosis. The tumor cells were strongly immunoreactive for GATA-3 without expression of melanocytic markers (S100, Melan A, HMB45, SOX10, MITF, and tyrosinase). The history of melanoma prompted molecular analysis, and the lesion was found to harbor the BRAF V600K mutation, consistent with metastatic dedifferentiated melanoma. Recognition of metastatic dedifferentiated melanoma is important to avoid misdiagnosis of carcinoma, especially in patients with a previous history of carcinoma.},
}
@article {pmid30558571,
year = {2018},
author = {Semango, GP and Charles, RM and Swai, CI and Mremi, A and Amsi, P and Sonda, T and Shao, ER and Mavura, DR and Joosten, LAB and Sauli, E and Nyindo, M},
title = {Prevalence and associated risk factors for Kaposi's sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study.},
journal = {BMC cancer},
volume = {18},
number = {1},
pages = {1258},
pmid = {30558571},
issn = {1471-2407},
support = {001//Tanzania Commission for Science and Technology/ ; },
mesh = {Adolescent ; Adult ; Age Factors ; CD4 Lymphocyte Count ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; HIV Infections/*complications/immunology ; Humans ; Infant ; Infant, Newborn ; Male ; Prevalence ; Referral and Consultation ; Retrospective Studies ; Risk Factors ; Sarcoma, Kaposi/*epidemiology ; Sex Factors ; Tanzania ; Young Adult ; },
abstract = {BACKGROUND: Kaposi's sarcoma (KS) is a multifocal angioproliferative tumor involving blood and lymphatic vessels, caused by Human Herpes Virus-8 (HHV-8). KS is an important AIDS-defining tumor with high prevalence in Sub-Saharan Africa, including Tanzania which has high HIV and HHV-8 sero-prevalence. It is critically important to monitor the prevalence of AIDS-defining tumors, such as KS, in the age of HIV/AIDS. We studied the prevalence of KS and associated risk factors among HIV-positive patients at Kilimanjaro Christian Medical Centre (KCMC), a referral hospital in northern Tanzania, over the period from January 2012 to December 2015.<br><br>METHODS: This was a retrospective hospital-based cross-sectional study to determine the prevalence of KS among HIV/AIDS patients between 2012 and 2015. The study included 1100 HIV patients' data which were collected at the Infectious Disease Clinic (IDC) from patients' files. Stata version 13 (StataCorp LP, Texas 77,845 USA) was used for all statistical analyses. The prevalence of KS was calculated across levels of a number of categorical variables. Logistic regression was performed to determine relative risk of KS for all characteristics. We included all variables with p-values &#x2264;10% in the multivariate analysis, including ART use, as this is considered to have an influence on KS. In the multivariate analysis, statistical significance was established based on a two-tailed p-value &#x2264;5%. All patients' notes were kept confidential as per the Helsinki declaration.<br><br>RESULTS: Our results revealed a 4.6% prevalence of KS at KCMC hospital, between January 2012 and December 2015, 51(4.6%) patients were diagnosed with KS out of 1100 HIV-positive patients. The study further revealed that KS in HIV patients was most associated with low CD4 cell count (less than or equal to 200 cells/&#x3bc;l). Moreover, women were more likely than men to diagnosed with KS, with higher odds significantly associated with KS (OR 0.42, p&#x2009;<&#x2009;0.009). Increased age, above 35&#x2009;years, among the HIV seropositive patients was significantly associated with KS (OR 25.67, p&#x2009;<&#x2009;0.007). HIV patients who were none smokers were more likely to suffer from KS compared to HIV smokers (OR 0.41, p&#x2009;<&#x2009;0.010).<br><br>CONCLUSION: KS remains a common malignant vascular tumor commonly associated with HIV/AIDS in Tanzania. Our study highlights the need for continued efforts to combat HIV, as well as associated diseases such as KS. Continued availability of ART (Anti-Retroviral Therapy) to HIV/AIDS patients, and test reagents for CD4 cell count and viral load determination are important measures to alleviate the suffering of these patients. Furthermore, studies to gather more evidence on ART resistance are highly needed to guide treatment choices.},
}
@article {pmid30557036,
year = {2019},
author = {Dabarian, AL and Mady, C and Barbosa-Ferreira, JM and Ianni, BM and Hotta, VT and Ramires, FJA and Lopes, HF and Buck, PC and Pessoa, FG and Fonseca, KCB and Nogueira, AR and Fernandes, F},
title = {Dysregulation of insulin levels in Chagas heart disease is associated with altered adipocytokine levels.},
journal = {Canadian journal of physiology and pharmacology},
volume = {97},
number = {2},
pages = {140-145},
doi = {10.1139/cjpp-2018-0349},
pmid = {30557036},
issn = {1205-7541},
mesh = {Adipokines/*blood/metabolism ; Adult ; Autonomic Nervous System/physiopathology ; Cardiomyopathy, Dilated/blood/diagnosis/*metabolism/physiopathology ; Chagas Cardiomyopathy/blood/diagnosis/*metabolism/physiopathology ; Echocardiography, Doppler ; Electrocardiography ; Female ; Heart ; Heart Rate/physiology ; Humans ; Insulin/*blood/metabolism ; Male ; Middle Aged ; },
abstract = {Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 μU/mL) when compared with control (8.0 ± 4.9 μU/mL) and IDC (9.9 ± 5.0 μU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 μg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.},
}
@article {pmid30544169,
year = {2019},
author = {Martínez Nicolás, I and Lê Cook, B and Flores, M and Del Olmo Rodriguez, M and Hernández Rodríguez, C and Llamas Sillero, P and Baca-Garcia, E},
title = {The impact of a comprehensive electronic patient portal on the health service use: an interrupted time-series analysis.},
journal = {European journal of public health},
volume = {29},
number = {3},
pages = {413-418},
doi = {10.1093/eurpub/cky257},
pmid = {30544169},
issn = {1464-360X},
mesh = {Ambulatory Care/statistics &amp; numerical data ; Chronic Disease ; Emergency Service, Hospital/statistics &amp; numerical data ; Health Services Research ; Hospitalization/statistics &amp; numerical data ; Humans ; Interrupted Time Series Analysis ; *Patient Portals ; Patient Readmission/statistics &amp; numerical data ; Spain ; *Utilization Review ; },
abstract = {BACKGROUND: There is little empirical research on the potential benefit that electronic patient portals (EPP) can have on the care quality and health outcomes of diverse multi-ethnic international populations. The purpose of this study is to determine the extent to which an EPP was associated with improvements in health service use.<br><br>METHODS: Using a quasi-experimental interrupted time-series approach, we assessed health service use before (April 2012-September 2015) and after (October 2015-December 2016) the implementation of a comprehensive EPP at four hospitals in Madrid, Spain. Primary outcomes were number of outpatient visits, any hospital admission, any 30-day all-cause readmission and any emergency department visit.<br><br>RESULTS: Implementation of the EPP was associated with a significant decline in readmissions. Among patients with chronic heart failure, EPP implementation was associated with a significant decline for all outcome measures, and among patients with COPD, a decline in all outcomes except readmissions. Among patients diagnosed with malignant hematological diseases, no significant changes were identified.<br><br>CONCLUSIONS: EPPs hold promise for reducing hospital readmissions. Certain patient populations with chronic conditions may differentially benefit from portal use depending on their needs for communication with their providers.},
}
@article {pmid30542725,
year = {2018},
author = {Shettar, A and Damineni, S and Mukherjee, G and Kondaiah, P},
title = {Gap junction β‑2 expression is negatively associated with the estrogen receptor status in breast cancer tissues and is a regulator of breast tumorigenesis.},
journal = {Oncology reports},
volume = {40},
number = {6},
pages = {3645-3653},
doi = {10.3892/or.2018.6764},
pmid = {30542725},
issn = {1791-2431},
mesh = {Animals ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinogenesis/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Connexin 26 ; Connexins/genetics/*metabolism ; Female ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, Nude ; Receptors, Estrogen/*metabolism ; Up-Regulation ; },
abstract = {Gap junction β‑2 gene (GJB2, also known as connexin 26) is a member of the connexin family which forms gap junction channels. Many connexin genes have been considered to be tumor suppressor genes. However, the overexpression of GJB2 has been found to be associated with a poor prognosis in several human cancers. In our previous microarray study, we revealed the overexpression of GJB2 in breast cancer tissues. Hence, in this study, we investigated the expression of GJB2 in human breast cancer and its role in breast cancer cell proliferation and migration. The RT‑qPCR results revealed the upregulation of the GJB2 gene in invasive ductal carcinoma (P<0.001) of the breast. Immunohistochemical analysis revealed an intense cytoplasmic and membrane staining. We observed that the staining for GJB2 was more intense in the majority of the estrogen receptor (ER)‑negative breast cancer tissues compared to the normal breast tissues (P<0.0001). By contrast, the majority of the ER‑positive breast cancer samples exhibited weak to moderate staining; however, this difference was not statistically significant compared to the normal tisues. The knockdown of GJB2 in human breast cancer cell lines using shRNA led to a significant decrease in the proliferative ability and an increase in the migratory ability of breast cancer cells. In addition, the knockdown of GJB‑2 led to a significant reduction in tumor volume and proliferation (as demonstrated by MIB‑1 staining) in orthotopic xenografts in immunocompromised mice. On the whole, the findings of this study indicate that GJB2 may be an important regulator of breast tumorigenesis.},
}
@article {pmid30524164,
year = {2018},
author = {Pusina, S},
title = {Correlation of Serum Levels of Urokinase Activation Plasminogen (uPA) and Its Inhibitor (PAI-1) with Hormonal and HER-2 Status in the Early Invasive Breast Cancer.},
journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)},
volume = {72},
number = {5},
pages = {335-340},
pmid = {30524164},
issn = {1986-5961},
mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*blood/genetics/pathology ; Carcinoma, Ductal, Breast/*blood/genetics/pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Plasminogen Activator Inhibitor 1/*blood ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*physiology ; Urokinase-Type Plasminogen Activator/*blood ; Young Adult ; },
abstract = {INTRODUCTION: Breast cancer is the most common malignant tumor in women. On the list of causes of death immediately after lung cancer. It is a heterogeneous disease, considering the differences in morphological, cytogenetic, molecular, clinical and therapeutic aspects, so that the prognosis in a patient with the same histological grade and pathological status may vary.<br><br>AIM: In this paper we wanted to identify the correlation between the assay of the serum values of uPA-PAI-1 complexes and individual prognostic-predictive parameters, primarily with the status of estrogenic (Er), progesterogenic (PgR) and Her-2 receptors ("human epidermal growth factor).<br><br>MATERIAL AND METHODS: The study was conducted at the Clinic for General and Abdominal Surgery, University Clinical Center of Sarajevo (CCUS), from September 2016 to April 2017. The study included 66 patients, ages 18 to 75, in whom by the needle biopsy preoperatively was pathohistologically verified primary invasive breast cancer.<br><br>RESULTS: Two thirds of the sample were classified as invasive ductal carcinoma, similar to the percentage (68.2%) of pT2 size, and almost half in the grade G3. Lymph node status was negative in 54.5% of respondents, and positive in 31.8% of respondents. Most patients had positive estrogenic (83.3%) and progesterone receptors (62.1%). Almost 80% was Her-2 negative. The blood vessel invasion was present in 56.1%, while the neural invasion was present in less than a third of the sample (30.3%). Median values of uPA-PAI-1 complexes were 1.4 (interquartile range 0.9); almost 70% of the sample was negative for the status analysis of uPA-PAI-1 complex (<1).<br><br>DISCUSSION: A statistically significant difference was determined in the mean values of uPA-PAI-1 complexes in subgroups according to menopausal status, tumor size, histological grade, histological type (invasive ductal carcinoma vs. invasive lobular cancer versus invasive ductal carcinoma vs. invasive lobular cancer), status axillary lymph nodes, Ki67 status (as binary variables), invasion of the blood vessels and neural invasion, as well as subgroups according to the status of expression of hormonal (estrogen and progesterone) receptors.<br><br>CONCLUSION: There is a statistically significant difference in the mean values of the uPA-PAI-1 complex and Her-2 receptor expression. Generally, in perspective, this would be the role played by the uPA/PAI-1 complex in breast cancer, which is that the elevated complex values have a negative prognosis and effect on survival, similar to the negative Her-2 receptor status. Complex uPA/PAI-1 is not a specific serum protein in breast cancer patients and cannot be taken as an individual prognostic-predictive marker for mass pre- or post treatment screening and prediction. Unfortunately, none of the biomarkers are able to independently and fully identify patients of the unknown stage of the disease with better or worse prognosis or to identify cases of more aggressive tumor behavior of the same stage for timely inclusion of adjuvant therapy and reduction of the risk of metastatic disease. The decision on treatment and prognosis should be the result of a combination of all diagnostic, therapeutic, pathohistological and molecular-genetic variables.},
}
@article {pmid30531838,
year = {2019},
author = {Pearson, SJ and Roy Sarkar, T and McQueen, CM and Elswood, J and Schmitt, EE and Wall, SW and Scribner, KC and Wyatt, G and Barhoumi, R and Behbod, F and Rijnkels, M and Porter, WW},
title = {ATM-dependent activation of SIM2s regulates homologous recombination and epithelial-mesenchymal transition.},
journal = {Oncogene},
volume = {38},
number = {14},
pages = {2611-2626},
pmid = {30531838},
issn = {1476-5594},
support = {R01 CA207445/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; S10 RR022532/RR/NCRR NIH HHS/United States ; T32 ES026568/ES/NIEHS NIH HHS/United States ; R01 HD083952/HD/NICHD NIH HHS/United States ; R21 CA185460/CA/NCI NIH HHS/United States ; R01 ES025209/ES/NIEHS NIH HHS/United States ; R21 CA190941/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Ataxia Telangiectasia Mutated Proteins/*genetics ; BRCA1 Protein/genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cadherins/genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics ; Cell Line, Tumor ; DNA Damage/genetics ; DNA Repair/genetics ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Genomic Instability/genetics ; Homologous Recombination/*genetics ; Humans ; MCF-7 Cells ; Mice ; Mice, Nude ; Phosphorylation/genetics ; Rad51 Recombinase/genetics ; },
abstract = {There is increasing evidence that genomic instability is a prerequisite for cancer progression. Here we show that SIM2s, a member of the bHLH/PAS family of transcription factors, regulates DNA damage repair through enhancement of homologous recombination (HR), and prevents epithelial-mesenchymal transitions (EMT) in an Ataxia-telangiectasia mutated (ATM)-dependent manner. Mechanistically, we found that SIM2s interacts with ATM and is stabilized through ATM-dependent phosphorylation in response to IR. Once stabilized, SIM2s interacts with BRCA1 and supports RAD51 recruitment to the site of DNA damage. Loss of SIM2s through the introduction of shSIM2 or the mutation of SIM2s at one of the predicted ATM phosphorylation sites (S115) reduces HR efficiency through disruption of RAD51 recruitment, resulting in genomic instability and induction of EMT. The EMT induced by the mutation of S115 is characterized by a decrease in E-cadherin and an induction of the basal marker, K14, resulting in increased invasion and metastasis. Together, these results identify a novel player in the DNA damage repair pathway and provides a link in ductal carcinoma in situ progression to invasive ductal carcinoma through loss of SIM2s, increased genomic instability, EMT, and metastasis.},
}
@article {pmid30519573,
year = {2018},
author = {Son, K and Yu, S and Shin, W and Han, K and Kang, K},
title = {A Simple Guideline to Assess the Characteristics of RNA-Seq Data.},
journal = {BioMed research international},
volume = {2018},
number = {},
pages = {2906292},
pmid = {30519573},
issn = {2314-6141},
mesh = {Gene Expression ; High-Throughput Nucleotide Sequencing/*statistics &amp; numerical data ; Humans ; *Principal Component Analysis ; RNA/*genetics ; Sequence Analysis, RNA ; Transcriptome/*genetics ; },
abstract = {Next-generation sequencing (NGS) techniques have been used to generate various molecular maps including genomes, epigenomes, and transcriptomes. Transcriptomes from a given cell population can be profiled via RNA-seq. However, there is no simple way to assess the characteristics of RNA-seq data systematically. In this study, we provide a simple method that can intuitively evaluate RNA-seq data using two different principal component analysis (PCA) plots. The gene expression PCA plot provides insights into the association between samples, while the transcript integrity number (TIN) score plot provides a quality map of given RNA-seq data. With this approach, we found that RNA-seq datasets deposited in public repositories often contain a few low-quality RNA-seq data that can lead to misinterpretations. The effect of sampling errors for differentially expressed gene (DEG) analysis was evaluated with ten RNA-seq data from invasive ductal carcinoma tissues and three RNA-seq data from adjacent normal tissues taken from a Korean breast cancer patient. The evaluation demonstrated that sampling errors, which select samples that do not represent a given population, can lead to different interpretations when conducting the DEG analysis. Therefore, the proposed approach can be used to avoid sampling errors prior to RNA-seq data analysis.},
}
@article {pmid30499665,
year = {2018},
author = {Okada, K and Moon, HJ and Finney, J and Meier, A and Mure, M},
title = {Extracellular Processing of Lysyl Oxidase-like 2 and Its Effect on Amine Oxidase Activity.},
journal = {Biochemistry},
volume = {57},
number = {51},
pages = {6973-6983},
pmid = {30499665},
issn = {1520-4995},
support = {P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM110761/GM/NIGMS NIH HHS/United States ; R01 GM113101/GM/NIGMS NIH HHS/United States ; },
mesh = {Amino Acid Oxidoreductases/chemistry/genetics/*metabolism ; Amino Acid Sequence ; Amino Acid Substitution ; Binding Sites ; Breast Neoplasms/enzymology ; Cell Line ; Collagen Type IV/metabolism ; Female ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Mutagenesis, Site-Directed ; Proprotein Convertases/antagonists &amp; inhibitors/genetics/metabolism ; Protein Domains ; Protein Processing, Post-Translational ; Protein-Lysine 6-Oxidase/chemistry/genetics/metabolism ; RNA, Small Interfering/genetics ; Serine Endopeptidases/genetics/metabolism ; },
abstract = {Overexpression of lysyl oxidase-like 2 (LOXL2) is associated with several hepatic and vascular fibrotic diseases and tumor progression in some aggressive cancers. Secreted LOXL2 promotes extracellular matrix cross-linking by catalyzing the oxidative deamination of peptidyl lysine. A great deal remains to be learned about the post-translational modifications of LOXL2, including whether such modifications modulate enzymatic and disease-promoting activities; such knowledge would inform the development of potential therapies. We discovered that upon secretion in cell culture, LOXL2 undergoes proteolytic processing of the first two of four scavenger receptor cysteine-rich domains at the N-terminus. A similar pattern of processing was also evident in tissue extracts from an invasive ductal carcinoma patient. Processing occurred at [314]Arg-[315]Phe-[316]Arg-[317]Lys↓-[318]Ala-, implicating proprotein convertases. siRNA-mediated knockdown of proprotein convertases (furin, PACE4, and PC5/6), as well as incubation with their recombinant forms, showed that PACE4 is the major protease that acts on extracellular LOXL2. Unlike LOX, which requires cleavage of its propeptide for catalytic activation, cleavage of LOXL2 was not essential for tropoelastin oxidation or for cross-linking of collagen type IV in vitro. However, in the latter case, processing enhanced the extent of collagen cross-linking ∼2-fold at ≤10 nM LOXL2. These results demonstrate an important difference in the regulatory mechanisms for LOX and LOXL2 catalytic activity. Moreover, they pave the way for further studies of potential differential functions of LOXL2 isoforms in fibrosis and tumor progression.},
}
@article {pmid30470306,
year = {2018},
author = {Schmidt, SF and Rohm, M and Herzig, S and Berriel Diaz, M},
title = {Cancer Cachexia: More Than Skeletal Muscle Wasting.},
journal = {Trends in cancer},
volume = {4},
number = {12},
pages = {849-860},
doi = {10.1016/j.trecan.2018.10.001},
pmid = {30470306},
issn = {2405-8025},
mesh = {Antineoplastic Agents/pharmacology/*therapeutic use ; Cachexia/etiology/mortality/*physiopathology/prevention &amp; control ; Combined Modality Therapy/methods ; Humans ; Muscle, Skeletal/physiopathology ; Neoplasms/*complications/drug therapy/mortality/physiopathology ; Nutritional Support/*methods ; Paraneoplastic Syndromes/etiology/mortality/*physiopathology/prevention &amp; control ; Quality of Life ; Treatment Outcome ; },
abstract = {Cancer cachexia is a multifactorial condition characterized by body weight loss that negatively affects quality of life and survival of patients with cancer. Despite the clinical relevance, there is currently no defined standard of care to effectively counteract cancer-associated progressive tissue wasting. Skeletal muscle atrophy represents the main manifestation of cancer cachexia. However, cancer cachexia is increasingly seen as a systemic phenomenon affecting and/or influenced by various organs. Here, we describe recent developments elucidating the roles of different tissues as well as tissue crosstalk in this wasting syndrome, including potential links to other cancer-associated morbidities. A more comprehensive understanding of cancer cachexia etiology and heterogeneity may enable the development of intervention strategies to prevent or reverse this devastating condition.},
}
@article {pmid30423024,
year = {2019},
author = {Sokol, ES and Feng, YX and Jin, DX and Basudan, A and Lee, AV and Atkinson, JM and Chen, J and Stephens, PJ and Frampton, GM and Gupta, PB and Ross, JS and Chung, JH and Oesterreich, S and Ali, SM and Hartmaier, RJ},
title = {Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {30},
number = {1},
pages = {115-123},
pmid = {30423024},
issn = {1569-8041},
mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*secondary ; Carcinoma, Lobular/drug therapy/genetics/*secondary ; Drug Resistance, Neoplasm/*genetics ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neurofibromin 1/*genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed.<br><br>PATIENTS AND METHODS: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes.<br><br>RESULTS: Whereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P&#x2009;<&#x2009;0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P&#x2009;<&#x2009;0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%).<br><br>CONCLUSIONS: This study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.},
}
@article {pmid30412075,
year = {2018},
author = {Lee, SJ and Chung, MS and Shin, SJ and Choi, YY},
title = {Correlation of tumor uptake on breast-specific gamma imaging and fluorodeoxyglucose PET/CT with molecular subtypes of breast cancer.},
journal = {Medicine},
volume = {97},
number = {43},
pages = {e12840},
pmid = {30412075},
issn = {1536-5964},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*secondary ; Female ; Fluorodeoxyglucose F18/*pharmacology ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; *Multimodal Imaging ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography/*methods ; Prognosis ; Radiopharmaceuticals/pharmacology ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; },
abstract = {Mechanisms of technetium-99m sesta-methoxyisobutylisonitrile (sestamibi) and F-fluorodeoxyglucose (FDG) uptake by tumor are different. The purpose of this study was to investigate the association between the tumor uptake of these 2 tracers in invasive ductal carcinoma and to examine thecorrelation of uptake of each tracer with prognostic factors and tumor molecular subtypes.A total of 96 patients with invasive ductal carcinoma who underwent preoperative breast-specific gamma imaging and FDG positron-emission tomography/computed tomography were retrospectively enrolled. Tumor-to-background ratio (TBR) of sestamibi and maximum standardized uptake value (SUVmax) of FDG were correlated with each other. Each of them was then compared with prognostic factors and molecular subtypes.In all tumors, there was a moderate positive correlation between TBR and SUVmax (r = 0.520, P < .001). Both TBR and SUVmax were significantly correlated with tumor size, incidence of axillary lymph node metastasis, histologic grade, estrogen receptor, progesterone receptor status, and Ki-67.There is a moderate degree of association between TBR of sestamibi and SUVmax of FDG in the invasive breast cancer. Two imaging indexes showed the similar tendency related with prognostic factors and molecular subtypes. While both TBR and SUVmax were significantly different between luminal A and nonluminal A tumors, neither of them had high enough sensitivity or specificity to obviate pathologic and molecular diagnosis.},
}
@article {pmid30409703,
year = {2019},
author = {Wolff, G and Taranko, AE and Meln, I and Weinmann, J and Sijmonsma, T and Lerch, S and Heide, D and Billeter, AT and Tews, D and Krunic, D and Fischer-Posovszky, P and Müller-Stich, BP and Herzig, S and Grimm, D and Heikenwälder, M and Kao, WW and Vegiopoulos, A},
title = {Diet-dependent function of the extracellular matrix proteoglycan Lumican in obesity and glucose homeostasis.},
journal = {Molecular metabolism},
volume = {19},
number = {},
pages = {97-106},
pmid = {30409703},
issn = {2212-8778},
mesh = {Adipocytes/metabolism ; Adipose Tissue/metabolism ; Adipose Tissue, White/metabolism ; Adiposity/drug effects ; Adult ; Animals ; Diet, High-Fat ; Extracellular Matrix/metabolism ; Female ; Glucose/*metabolism ; Homeostasis ; Humans ; Insulin Resistance ; Intra-Abdominal Fat/metabolism ; Liver/metabolism ; Lumican/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/*metabolism ; Proteoglycans/metabolism ; },
abstract = {OBJECTIVE: Extracellular matrix remodeling is required for adipose expansion under increased caloric intake. In turn, inhibited expandability due to aberrant collagen deposition promotes insulin resistance and progression towards the metabolic syndrome. An emerging role for the small leucine-rich proteoglycan Lumican in metabolically driven nonalcoholic fatty liver disease sparks an interest in further understanding its role in diet-induced obesity and metabolic complications.<br><br>METHODS: Whole body ablation of Lumican (Lum[-/-]) gene and adeno-associated virus-mediated over-expression were used in combination with control or high fat diet to assess energy balance, glucose homeostasis as well as adipose tissue health and remodeling.<br><br>RESULTS: Lumican was found to be particularly enriched in the stromal cells isolated from murine gonadal white adipose tissue. Likewise murine and human visceral fat showed a robust increase in Lumican as compared to fat from the subcutaneous depot. Lumican null female mice exhibited moderately increased fat mass, decreased insulin sensitivity and increased liver triglycerides in a diet-dependent manner. These changes coincided with inflammation in adipose tissue and no overt effects in adipose expandability, i.e. adipocyte formation and hypertrophy. Lumican over-expression in visceral fat and liver resulted in improved insulin sensitivity and glucose clearance.<br><br>CONCLUSIONS: These data indicate that Lumican may represent a functional link between the extracellular matrix, glucose homeostasis, and features of the metabolic syndrome.},
}
@article {pmid30409127,
year = {2018},
author = {Ye, FG and Xia, C and Ma, D and Lin, PY and Hu, X and Shao, ZM},
title = {Nomogram for predicting preoperative lymph node involvement in patients with invasive micropapillary carcinoma of breast: a SEER population-based study.},
journal = {BMC cancer},
volume = {18},
number = {1},
pages = {1085},
pmid = {30409127},
issn = {1471-2407},
support = {MOST2016YFC0900300//Ministry of Science and Technology of the People's Republic of China/ ; 81672601//National Natural Science Foundation of China (CN)/ ; 15410724000//Shanghai Committee of Science and Technology Funds/ ; },
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Axilla/pathology ; *Breast Neoplasms/epidemiology/pathology ; *Carcinoma, Papillary/epidemiology/pathology ; Follow-Up Studies ; *Lymph Nodes/pathology ; Lymphatic Metastasis ; Nomograms ; Odds Ratio ; Population Surveillance ; Preoperative Period ; Reproducibility of Results ; Risk Factors ; ROC Curve ; SEER Program ; Breast Neoplasms, Male/epidemiology/pathology ; },
abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. This study was to identify risk factors accounting for IMPC of the breast and to develop a nomogram to preoperatively predict the probability of lymph node involvement.<br><br>METHODS: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation sets. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. A logistic regression model was used to construct the nomogram in the training set and then varified in the validation set. Nomogram performance was quantified with respect to discrimination and calibration using R 3.4.1 software.<br><br>RESULTS: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. Logistic regression analysis indicated larger lesions, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95% confidential interval (CI) 0.692 to 0.777), demonstrating a good prediction performance. Calibration curve for the nomogram was plotted and the slope was close to 1, which demonstrated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, with AUC of 0.748 (95% CI 0.701 to 0.767).<br><br>CONCLUSIONS: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinicalpathologic parameters was established, which could accurately preoperatively predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients.},
}
@article {pmid30407355,
year = {2018},
author = {Liu, A and Feng, Y and Chen, B and Li, L and Wu, D and Qian, J and Yang, A},
title = {A case report of metastatic breast cancer initially presenting with esophageal dysphagia.},
journal = {Medicine},
volume = {97},
number = {45},
pages = {e13184},
pmid = {30407355},
issn = {1536-5964},
mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Deglutition Disorders/*etiology ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Esophageal Neoplasms/*secondary/therapy ; Esophagectomy/methods ; Esophagus/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Tomography, X-Ray Computed ; },
abstract = {RATIONALE: Breast cancer metastasis to the esophagus is uncommon. To our knowledge, the present case is the first report of breast cancer with dysphagia as the initial symptom.<br><br>PATIENT CONCERNS: A 62-year-old woman was admitted to our hospital for progressive dysphagia.<br><br>DIAGNOSES: Endoscopic ultrasound-guided fine needle biopsy of the esophageal lesion found poorly differentiated carcinoma, and surgical resection of the breast nodule revealed invasive ductal carcinoma.<br><br>INTERVENTIONS: The patient underwent an esophagectomy, and the immunohistochemistry of surgical specimen was identified as metastatic breast cancer. Then patient was treated with chemotherapy and hormone therapy.<br><br>OUTCOMES: The patient remained symptom-free during 5 months of follow-up examinations.<br><br>LESSONS: This case indicates that metastatic breast cancer to the esophagus should be considered as a cause of esophageal stricture in older women.},
}
@article {pmid30406220,
year = {2017},
author = {Cheng, C and Thakur, R and Nair, AR and Sterrett, S and Fridman, G},
title = {Miniature Elastomeric Valve Design for Safe Direct Current Stimulator.},
journal = {IEEE Biomedical Circuits and Systems Conference : healthcare technology : [proceedings]. IEEE Biomedical Circuits and Systems Conference},
volume = {2017},
number = {},
pages = {1-4},
pmid = {30406220},
support = {R01 NS092726/NS/NINDS NIH HHS/United States ; R21 NS081425/NS/NINDS NIH HHS/United States ; },
abstract = {For safety reasons, commercial neural implants use charge-balanced biphasic pulses to interact with target neurons using metal electrodes. Short biphasic pulses are used to avoid irreversible electrochemical reactions at the electrode-tissue interfaces. Biphasic pulses are effective at exciting neurons, but quite limited in inhibiting their activity. In contrast, direct current can both excite and inhibit neurons, however delivered to metal electrodes, it causes toxic electrochemical reactions. We recently introduced Safe Direct Current Stimulator (SDCS) technology, which can excite or inhibit neurons without violating the safety criteria. Instead of direct current, SDCS generates an ionic direct current (iDC) from a biphasic input signal using a network of fluidic channels and mechanical valves. A key enabler towards transforming SDCS concept from a benchtop design to an implantable neural prosthesis is the design of a miniature valve. In this work, we present poly-dimethylsiloxane (PDMS) based elastomeric valves, squeeze valve (SV) and plunger valve (PV) capable of being actuated using a shape memory alloy wire.},
}
@article {pmid30388104,
year = {2018},
author = {Golan, Y and Alhadeff, R and Glaser, F and Ganoth, A and Warshel, A and Assaraf, YG},
title = {Demonstrating aspects of multiscale modeling by studying the permeation pathway of the human ZnT2 zinc transporter.},
journal = {PLoS computational biology},
volume = {14},
number = {11},
pages = {e1006503},
pmid = {30388104},
issn = {1553-7358},
support = {R35 GM122472/GM/NIGMS NIH HHS/United States ; R01 AI055926/AI/NIAID NIH HHS/United States ; },
mesh = {Cation Transport Proteins/genetics/*metabolism ; Computational Biology/methods ; Deficiency Diseases/metabolism/therapy ; Homeostasis ; Humans ; *Models, Theoretical ; Monte Carlo Method ; Mutagenesis, Site-Directed ; Permeability ; Zinc/deficiency/*metabolism ; },
abstract = {Multiscale modeling provides a very powerful means of studying complex biological systems. An important component of this strategy involves coarse-grained (CG) simplifications of regions of the system, which allow effective exploration of complex systems. Here we studied aspects of CG modeling of the human zinc transporter ZnT2. Zinc is an essential trace element with 10% of the proteins in the human proteome capable of zinc binding. Thus, zinc deficiency or impairment of zinc homeostasis disrupt key cellular functions. Mammalian zinc transport proceeds via two transporter families: ZnT and ZIP; however, little is known about the zinc permeation pathway through these transporters. As a step towards this end, we herein undertook comprehensive computational analyses employing multiscale techniques, focusing on the human zinc transporter ZnT2 and its bacterial homologue, YiiP. Energy calculations revealed a favorable pathway for zinc translocation via alternating access. We then identified key residues presumably involved in the passage of zinc ions through ZnT2 and YiiP, and functionally validated their role in zinc transport using site-directed mutagenesis of ZnT2 residues. Finally, we use a CG Monte Carlo simulation approach to sample the transition between the inward-facing and the outward-facing states. We present our structural models of the inward- and outward-facing conformations of ZnT2 as a blueprint prototype of the transporter conformations, including the putative permeation pathway and participating residues. The insights gained from this study may facilitate the delineation of the pathways of other zinc transporters, laying the foundations for the molecular basis underlying ion permeation. This may possibly facilitate the development of therapeutic interventions in pathological states associated with zinc deficiency and other disorders based on loss-of-function mutations in solute carriers.},
}
@article {pmid30385093,
year = {2019},
author = {Shee, K and Muller, KE and Marotti, J and Miller, TW and Wells, WA and Tsongalis, GJ},
title = {Ductal Carcinoma in Situ Biomarkers in a Precision Medicine Era: Current and Future Molecular-Based Testing.},
journal = {The American journal of pathology},
volume = {189},
number = {5},
pages = {956-965},
pmid = {30385093},
issn = {1525-2191},
support = {F30 CA216966/CA/NCI NIH HHS/United States ; R01 CA200994/CA/NCI NIH HHS/United States ; R01 CA211869/CA/NCI NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Disease Progression ; Female ; Humans ; Neoplasm Invasiveness ; *Precision Medicine ; Prognosis ; },
abstract = {Historically, ductal carcinoma in situ (DCIS) of the breast has been managed aggressively with surgery and radiotherapy because of a risk of progression to invasive ductal carcinoma. However, this treatment paradigm has been challenged by overtreatment concerns and evidence that suggests that DCIS can be stratified according to risk of recurrence or risk of progression to invasive disease. Traditional methods of risk stratification include histologic grade and hormone receptor status. Recent technological advancements have enabled an era of precision medicine, where DCIS can be molecularly analyzed by tools, such as next-generation DNA and RNA sequencing, to identify molecular biomarkers for risk stratification. These findings have led to the development of tools such as the Oncotype DX Breast DCIS Score, a gene expression-based assay with the potential to prevent overtreatment in low-risk disease.},
}
@article {pmid30375263,
year = {2018},
author = {Talei, A and Tahmasebi, S and Akrami, M and Zangouri, V and Rezaianzadeh, A and Arasteh, P and Eghbali, T and Hosseini, S},
title = {The Shiraz Breast Cancer Registry (SBCR): study design and primary reports.},
journal = {Personalized medicine},
volume = {15},
number = {6},
pages = {471-479},
doi = {10.2217/pme-2018-0047},
pmid = {30375263},
issn = {1744-828X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Breast Neoplasms/epidemiology/genetics ; Carcinoma, Ductal, Breast/epidemiology ; Iran/epidemiology ; Neoplasm Staging ; Preliminary Data ; Prognosis ; Registries ; Research Design ; *Breast Neoplasms, Male/epidemiology/genetics ; },
abstract = {AIM: This is a description of the largest breast cancer (BC) registry in Iran, termed the Shiraz Breast Cancer Registry (SBCR).<br><br>METHODS: Data on baseline and clinical characteristics, socioeconomic status, imaging, physical examination, histopathology, treatment and prognosis have been recorded for each individual.<br><br>RESULTS: Overall, 5937 were included in the report. Mean age of first presentation was 49.05&#xa0;&#xb1;&#xa0;11.69&#xa0;years. Mean tumor size was 2.78&#xa0;&#xb1;&#xa0;1.76&#xa0;cm. Most patients had stage 2 (46.9%) and 3 (25.5%) BCs, respectively. Most common type of BC was invasive ductal carcinoma (83.3%), followed by medullary carcinoma (3.8%). Overall, 12.9% were triple negative (HER2-, ER- and PR-).<br><br>CONCLUSION: The study provides an overview on the status of BC's in Iran and a wide opportunity for future studies.},
}
@article {pmid30372658,
year = {2019},
author = {Steger, M and Bermejo-Jambrina, M and Yordanov, T and Wagener, J and Brakhage, AA and Pittl, V and Huber, LA and Haas, H and Lass-Flörl, C and Posch, W and Wilflingseder, D},
title = {β-1,3-glucan-lacking Aspergillus fumigatus mediates an efficient antifungal immune response by activating complement and dendritic cells.},
journal = {Virulence},
volume = {10},
number = {1},
pages = {957-969},
pmid = {30372658},
issn = {2150-5608},
mesh = {Aspergillosis/microbiology ; Aspergillus fumigatus/*chemistry/genetics/*immunology ; *Complement Activation ; Cytokines/immunology ; Dendritic Cells/*immunology ; Echinocandins/therapeutic use ; Humans ; Immunity, Innate ; Mutation ; Spores, Fungal/immunology ; THP-1 Cells ; *beta-Glucans ; },
abstract = {Complement system and dendritic cells (DCs) form - beside neutrophils and macrophages - the first line of defense to combat fungal infections. Therefore, we here studied interactions of these first immune elements with Aspergillus fumigatus lacking ß-1,3-glucans (fks1tetOn[rep] under repressed conditions) to mechanistically explain the mode of action of echinocandins in more detail. Echinocandins are cell wall active agents blocking β-glucan synthase, making the A. fumigatus fks1tetOn mutant a good model to study immune-modulatory actions of these drugs. We now demonstrate herein, that complement was activated to significantly higher levels by the fks1-deficient strain compared to its respective wild type. This enhanced covalent linking of complement fragments to the A. fumigatus fks1tetOn[rep] mutant further resulted in enhanced DC binding and internalization of the fungus. Additionally, we found that fks1tetOn[rep] induced a Th1-/Th17-polarizing cytokine profile program in DCs. The effect was essentially dependent on massive galactomannan shedding, since blocking of DC-SIGN significantly reduced the fks1tetOn[rep]-mediated induction of an inflammatory cytokine profile.Our data demonstrate that lack of ß-1,3-glucan, also found under echinocandin therapy, results in improved recognition of Aspergillus fumigatus by complement and DCs and therefore not only directly affects the fungus by its fungistatic actions, but also is likely to exert indirect antifungal mechanisms by strengthening innate host immune mechanisms.Abbreviations: C: complement; CR:complement receptor; DC: dendritic cell; iDC: immature dendritic cell; DC-SIGN: Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; ERK: extracellular signal-regulated kinases; JNK : c-Jun N-terminal kinases; MAPK: mitogen-activated protein kinase; NHS: normal human serum; PRR: pattern recognition receptor; Th :T helper; TLR :Toll-like receptor; WT: wild type.},
}
@article {pmid30371651,
year = {2018},
author = {Drucis, K and Brzeziński, M and Gniadek, K},
title = {[Synchronous gastrointestinal stromal tumor of stomach and invasive ductal carcinoma of both breasts].},
journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego},
volume = {45},
number = {268},
pages = {161-163},
pmid = {30371651},
issn = {1426-9686},
mesh = {Breast Neoplasms/*complications/diagnostic imaging/surgery ; Carcinoma, Ductal/*complications/diagnostic imaging/surgery ; Female ; Gastrointestinal Stromal Tumors/*complications/diagnostic imaging/surgery ; Humans ; Mastectomy ; Middle Aged ; Stomach/diagnostic imaging/surgery ; Stomach Neoplasms/*complications/diagnostic imaging/surgery ; },
abstract = {UNLABELLED: Gastrointestinal stromal tumor (GIST), despite the fact that it accounts for less than 5% of all sarcomas, is the most common mesenchymal tumor of the alimentary canal. Synchronous and metachronous stromal tumors are very rare findings. Only a few such cases can be found in the literature, and yet most of them is connected with Von Recklinghausen's disease or Carney's triad in which it is proved a much higher frequency of occurrence of this kind of tumors.<br><br>CASE REPORT: We present a case of 64 years old women, who was diagnosed with invasive ductal carcinoma of both breast due to screening mammography. Patent was qualified to bilateral mastectomy. Perioperative computer tomography scan revealed an additional pathological abnormality situated beyond stomach light, which after resection and immunohistochemistry was found to be a gastrointestinal stromal tumor. This case emphasize the problem of synchronous stromal tumors, the detection of which is often difficult due to nonspecific symptoms. Despite the fact that the most common localization of coexisting tumors is the digestive tract, one should remember about the possibility of occurrence in less frequent locations such as the breast.},
}
@article {pmid30362328,
year = {2018},
author = {Abood, RA},
title = {Breast Cancer in Basra Oncology Center: A Clinico- Epidemiological Analysis.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {19},
number = {10},
pages = {2943-2946},
pmid = {30362328},
issn = {2476-762X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Iraq/epidemiology ; Middle Aged ; Neoplasm Staging/methods ; Retrospective Studies ; Young Adult ; },
abstract = {Background: Breast cancer is the most common cancer affecting women, and the leading cause of cancer-related deaths. Objective: This study was performed to evaluate clinico-epidemiological features of breast cancer from Iraq during a five-year period. Methodology: This is a retrospective descriptive study. Medical notes and histopathological reports of patients with confirmed diagnosis of breast cancer between January 2011 and December 2015 were reviewed for age, gender, site, laterality, histopathological type, grade of differentiation and TNM stage at diagnosis. Results: A total of 1,000 patients were included in the study. Mean age at diagnosis was 50 years (range 22-85 years), and females constituted 99.2% of cases. Most cases (98.7%) were unilateral and most common (85.5%) histological subtype was invasive ductal carcinoma. Majority of the cases (58%) were moderately differentiated (grade II), wherein 45% belonged to stage II in TNM system, and nearly half (49%) of patients had locally advanced or metastatic cancer. Conclusion: Breast cancer presents at least a decade earlier and at a more advanced stage in Iraqi women when compared to the Western World. Steps for early detection are essential for initiation of prompt therapy and reduction of mortality.},
}
@article {pmid30350269,
year = {2019},
author = {Jerevall, PL and Brock, J and Palazzo, J and Wieczorek, T and Misialek, M and Guidi, AJ and Wu, Y and Erlander, MG and Zhang, Y and Schnabel, CA and Goss, PE and Horick, N and Sgroi, DC},
title = {Discrepancy in risk assessment of hormone receptor positive early-stage breast cancer patients using breast cancer index and recurrence score.},
journal = {Breast cancer research and treatment},
volume = {173},
number = {2},
pages = {375-383},
doi = {10.1007/s10549-018-5013-6},
pmid = {30350269},
issn = {1573-7217},
mesh = {Adult ; Age Factors ; Aged ; Breast/pathology ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnosis/epidemiology ; Prognosis ; Prospective Studies ; Risk Assessment/methods ; Risk Factors ; Tumor Burden ; },
abstract = {PURPOSE: A recent comparison of the prognostic accuracy of Breast Cancer Index (BCI) and the Recurrence Score (RS) showed that BCI was more precise than RS. BCI identified a subset of RS low and intermediate risk patients with clinically relevant elevated rates of distant recurrences (DR). The current study analyzed the correlation of BCI and RS risk classification to clinical and pathological parameters and further examined the re-categorization between the two risk group indices in a multi-institutional cohort of hormone receptor positive (HR+) breast cancer patients.<br><br>METHODS: 560 women with HR+, lymph node-negative breast cancer who underwent testing with RS as part of their routine clinical care were included in the final analysis. Individual risk was assessed using predefined categories of RS and BCI (Low, Intermediate and High, respectively). Correlations between BCI, RS, and standard clinical-pathological prognostic factors were examined, and re-categorization of risk groups between BCI and RS was analyzed.<br><br>RESULTS: An overall significant association between histological tumor grade and RS or BCI was observed with high-grade tumors more prevalent among RS and BCI high-risk patients. The invasive ductal carcinoma histologic subtype was associated with 98% and 93% of high-risk RS and BCI cases, respectively. The invasive lobular subtype accounted for 0% and 6% of high-risk RS and BCI cases, respectively. A poor agreement between the two biomarker risk group indices was demonstrated with more than 51% of the total cohort stratified differently between BCI and RS. As compared with RS, BCI stratified fewer patients into the intermediate-risk group (29% vs. 39%, BCI and RS, respectively) and more patients into the high-risk group (19% vs. 7%, BCI and RS, respectively). Subsets of both RS low- and intermediate-risk patients were identified by BCI as high risk.<br><br>CONCLUSIONS: In this clinical series, BCI and RS risk groups demonstrated a significant association with histological tumor grade. BCI showed a modest correlation with tumor size and no correlation with age, while RS showed no correlation with tumor size or age. Compared with RS, BCI classifies fewer intermediate risk patients, identifies subsets of low and intermediate RS risk patients as high-risk, and provides distinct individualized risk assessment for patients with early-stage breast cancer.},
}
@article {pmid30339213,
year = {2019},
author = {Jacob, T and Bracha, J},
title = {Identification of Signs and Symptoms of Axillary Web Syndrome and Breast Seroma During a Course of Physical Therapy 7 Months After Lumpectomy: A Case Report.},
journal = {Physical therapy},
volume = {99},
number = {2},
pages = {229-239},
doi = {10.1093/ptj/pzy110},
pmid = {30339213},
issn = {1538-6724},
mesh = {Aged ; Axilla/*physiopathology ; Female ; Humans ; Lymphatic Diseases/etiology/*therapy ; Lymphedema/*therapy ; Mastectomy/*adverse effects ; *Physical Therapy Modalities ; Postoperative Complications/etiology ; Seroma/etiology/*therapy ; Syndrome ; },
abstract = {BACKGROUND AND PURPOSE: Axillary web syndrome (AWS) and seroma are common and function-limiting side effects following treatments for breast cancer. Studies of AWS and seroma are rare, and there are no guidelines for physical therapy in these cases.<br><br>CASE DESCRIPTION: After left breast lumpectomy due to invasive ductal carcinoma, a 65-year-old female patient underwent intraoperative radiation therapy and whole breast radiation. Seven months later, during treatment for breast swelling, AWS and breast seroma were identified by a physical therapist certified in lymphedema treatment. Treatment goals were to reduce breast swelling and pain and to improve shoulder movements. Interventions included manual lymph drainage, left arm stretching, and instruction about self-lymphatic-drainage and stretching exercise. Also, a compression bra was ordered, and continued daily activities and physical activity were recommended.<br><br>OUTCOMES: Improvement in shoulder movement, breast swelling, and pain.<br><br>DISCUSSION: Because evidence for treatment guidelines following treatments for breast cancer is lacking, close follow-up for treatment-related complications is recommended. Management should be chosen according to signs and symptoms. Realistic expectations can reduce patient frustration and improve coping strategies and compliance with self-treatment demands. Clinical studies to support these conclusions are required.},
}
@article {pmid30332671,
year = {2019},
author = {Kitamura, M and Nakayama, T and Mukaisho, KI and Mori, T and Umeda, T and Moritani, S and Kushima, R and Tani, M and Sugihara, H},
title = {Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling.},
journal = {Pathobiology : journal of immunopathology, molecular and cellular biology},
volume = {86},
number = {2-3},
pages = {92-101},
doi = {10.1159/000492833},
pmid = {30332671},
issn = {1423-0291},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Comparative Genomic Hybridization ; *DNA Copy Number Variations ; *Disease Progression ; Female ; GATA3 Transcription Factor/genetics ; Humans ; Middle Aged ; Paraffin Embedding ; Tumor Suppressor Protein p53/genetics ; },
abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors.<br><br>METHODS: We used surgically resected, formalin-fixed, paraffin-embedded tissues of 22 DCIS and 30 IDC lesions. We performed immunohistochemical intrinsic subtyping, array-based comparative genomic hybridization, and unsupervised clustering.<br><br>RESULTS: The samples were divided into 2 major clusters, A and B. Cluster A showed a greater number of gene and chromosome copy number alterations, a larger IDC/DCIS ratio, a higher frequency of nonluminal subtype, a lower frequency of luminal subtype, and a higher nuclear grade, when compared with cluster B. However, there was no difference in the frequencies of lymph node metastasis between clusters A and B. We identified 9 breast-cancer-related genes, including TP53 and GATA3, that highly contributed to the discrimination of A and B clusters.<br><br>CONCLUSION: Classification of breast tumors into rapidly progressive cluster A and the other (cluster B) may contribute to select the treatment appropriate for their progression risk.},
}
@article {pmid30325954,
year = {2018},
author = {Dhage, S and Ernlund, A and Ruggles, K and Axelrod, D and Berman, R and Roses, D and Schneider, RJ},
title = {A genomic ruler to assess oncogenic transition between breast tumor and stroma.},
journal = {PloS one},
volume = {13},
number = {10},
pages = {e0205602},
pmid = {30325954},
issn = {1932-6203},
support = {T32 CA009161/CA/NCI NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast/*metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology/surgery ; Cell Transformation, Neoplastic/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genomics ; Humans ; Mastectomy ; Microarray Analysis ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Staging ; RNA, Messenger/metabolism ; Stromal Cells/*metabolism/pathology ; },
abstract = {BACKGROUND: Cancers induce gene expression alterations in stroma surrounding tumors that supports cancer progression. However, it is actually not at all known the extent of altered stromal gene expression enacted by tumors nor the extent to which altered stromal gene expression penetrates the stromal tissue. Presently, post-surgical "tumor-free" stromal tissue is determined to be cancer-free based on solely on morphological normality-a criteria that has not changed in more than 100 years despite the existence of sophisticated gene expression data to the contrary. We therefore investigated the extent to which breast tumors alter stromal gene expression in three dimensions in women undergoing mastectomy with the intent of providing a genomic determination for development of future risk of recurrence criteria, and to inform the need for adjuvant full-breast irradiation.<br><br>METHODS AND FINDINGS: Genome-wide gene expression changes were determined in histopathologically normal breast tissue in 33 women undergoing mastectomy for stage II and III primary invasive ductal carcinoma at serial distances in three dimensions from the tumor. Gene expression was determined by genome-wide mRNA analysis and subjected to metagene mRNA characterization. Tumor-like gene expression signatures in stroma were identified that surprisingly transitioned to a plastic, normalizing homeostatic signature with distance from tumor. Stroma closest to tumor displayed a pronounced tumor-like signature enriched in cancer-promoting pathways involved in disruption of basement membrane, cell migration and invasion, WNT signaling and angiogenesis. By 2 cm from tumor in all dimensions, stromal tissues were in transition, displaying homeostatic and tumor suppressing gene activity, while also expressing cancer supporting pathways.<br><br>CONCLUSIONS: The dynamics of gene expression in the post-tumor breast stroma likely co-determines disease outcome: reversion to normality or transition to transformation in morphologically normal tissue. Our stromal genomic signature may be important for personalizing surgical and adjuvant therapeutic decisions and risk of recurrence.},
}
@article {pmid30306389,
year = {2018},
author = {DeVaux, RS and Herschkowitz, JI},
title = {Beyond DNA: the Role of Epigenetics in the Premalignant Progression of Breast Cancer.},
journal = {Journal of mammary gland biology and neoplasia},
volume = {23},
number = {4},
pages = {223-235},
pmid = {30306389},
issn = {1573-7039},
mesh = {Animals ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; DNA/*genetics ; Disease Progression ; Epigenesis, Genetic/*genetics ; Female ; Humans ; },
abstract = {Ductal Carcinoma in Situ (DCIS) is an early breast cancer lesion that is considered a nonobligate precursor to development of invasive ductal carcinoma (IDC). Although only a small subset of DCIS lesions are predicted to progress into a breast cancer, distinguishing innocuous from minacious DCIS lesions remains a clinical challenge. Thus, patients diagnosed with DCIS will undergo surgery with the potential for radiation and hormone therapy. This has led to a current state of overdiagnosis and overtreatment. Interrogating the transcriptome alone has yet to define clear functional determinants of progression from DCIS to IDC. Epigenetic changes, critical for imprinting and tissue specific development, in the incorrect context can lead to global signaling rewiring driving pathological phenotypes. Epigenetic signaling pathways, and the molecular players that interpret and sustain their signals, are critical to understanding the underlying pathology of breast cancer progression. The types of epigenetic changes, as well as the molecular players, are expanding. In addition to DNA methylation, histone modifications, and chromatin remodeling, we must also consider enhancers as well as the growing field of noncoding RNAs. Herein we will review the epigenetic interactions that have been uncovered in early stage lesions that impact breast cancer progression, and how these players may be utilized as biomarkers to mitigate overdiagnosis and overtreatment.},
}
@article {pmid30303137,
year = {2018},
author = {Jafarian, AH and Tasbandi, A and Gilan, H and Sheikhi, M and Roshan, NM},
title = {Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {61},
number = {4},
pages = {500-504},
doi = {10.4103/IJPM.IJPM_67_18},
pmid = {30303137},
issn = {0974-5130},
mesh = {Adult ; Aged ; CD4 Antigens/*analysis ; CD8 Antigens/*analysis ; Carcinoma, Ductal, Breast/*immunology/mortality/pathology ; Cross-Sectional Studies ; Female ; Humans ; Immunohistochemistry ; Ki-1 Antigen/*analysis ; Middle Aged ; Prognosis ; Triple Negative Breast Neoplasms/*immunology/mortality/pathology ; },
abstract = {BACKGROUND: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors.<br><br>MATERIALS AND METHODS: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels.<br><br>RESULTS: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes.<br><br>CONCLUSION: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.},
}
@article {pmid30290054,
year = {2018},
author = {Gaowa, S and Futamura, M and Tsuneki, M and Kamino, H and Tajima, JY and Mori, R and Arakawa, H and Yoshida, K},
title = {Possible role of p53/Mieap-regulated mitochondrial quality control as a tumor suppressor in human breast cancer.},
journal = {Cancer science},
volume = {109},
number = {12},
pages = {3910-3920},
pmid = {30290054},
issn = {1349-7006},
support = {15ck0106006&#xa0;h0002 (to HA)//AMED/ ; H26-practical-general-001 (to HA)//Ministry of Health, Labour and Welfare for the Practical Research for Innovative Cancer/ ; 23659178 (to HA)//KAKENIHI/ ; 24240117 (to HA)//KAKENIHI/ ; 17K10542 (to MF)//KAKENIHI/ ; 25670169 (to HA)//KAKENIHI/ ; 29-E-1 (to HA), 30-A-3 (to HA)//The National Cancer Center Research and Development Fund/ ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Caspases/metabolism ; Cell Line, Tumor ; Cytoplasm/metabolism ; DNA Methylation ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Mitochondria/metabolism ; Mitochondrial Proteins/*genetics/*metabolism ; Mutation ; Promoter Regions, Genetic ; Tumor Suppressor Protein p53/*genetics/*metabolism ; },
abstract = {Mitochondria-eating protein (Mieap), encoded by a p53-target gene, plays an important role in mitochondrial quality control (MQC). Mieap has been reported to have a critical role in tumor suppression in colorectal cancer. Here, we investigated its role as a tumor suppressor in breast cancer. The enforced expression of exogenous Mieap in breast cancer cells induced caspase-dependent apoptosis, with activation of both caspase-3/7 and caspase-9. Immunohistochemistry revealed endogenous Mieap in the cytoplasm in 24/75 (32%) invasive ductal carcinomas (IDC), 15/27 (55.6%) cases of ductal carcinoma in situ (DCIS) and 16/18 (88.9%) fibroadenomas (FA) (IDC vs DCIS; P = 0.0389, DCIS vs FA; P = 0.0234, IDC vs FA; P < 0.0001). In IDC, the Mieap promoter was methylated in 6/46 (13%) cases, whereas p53 was mutated in 6/46 (13%) cases. Therefore, the p53/Mieap-regulated MQC pathway was inactivated in 12/46 IDC (26.1%). Interestingly, all tumors derived from the 12 patients with Mieap promoter methylation or p53 mutations pathologically exhibited more aggressive and malignant breast cancer phenotypes. Impairment of p53/Mieap-regulated MQC pathway resulted in significantly shorter disease-free survival (DFS) (P = 0.021), although p53 status is more prognostic in DFS than Mieap promoter methylation. These results indicate that p53/Mieap-regulated MQC has a critical role in tumor suppression in breast cancer, possibly in part through mitochondrial apoptotic pathway.},
}
@article {pmid30287681,
year = {2018},
author = {Ng, CS and Sinha, A and Aniweh, Y and Nah, Q and Babu, IR and Gu, C and Chionh, YH and Dedon, PC and Preiser, PR},
title = {tRNA epitranscriptomics and biased codon are linked to proteome expression in Plasmodium falciparum.},
journal = {Molecular systems biology},
volume = {14},
number = {10},
pages = {e8009},
pmid = {30287681},
issn = {1744-4292},
mesh = {Codon ; Epigenesis, Genetic ; Erythrocytes ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Humans ; Plasmodium falciparum/genetics/*physiology ; Protein Biosynthesis ; Protein Processing, Post-Translational ; Proteomics/methods ; Protozoan Proteins/*genetics/*metabolism ; RNA, Transfer/*metabolism ; },
abstract = {Among components of the translational machinery, ribonucleoside modifications on tRNAs are emerging as critical regulators of cell physiology and stress response. Here, we demonstrate highly coordinated behavior of the repertoire of tRNA modifications of Plasmodium falciparum throughout the intra-erythrocytic developmental cycle (IDC). We observed both a synchronized increase in 22 of 28 modifications from ring to trophozoite stage, consistent with tRNA maturation during translational up-regulation, and asynchronous changes in six modifications. Quantitative analysis of ~2,100 proteins across the IDC revealed that up- and down-regulated proteins in late but not early stages have a marked codon bias that directly correlates with parallel changes in tRNA modifications and enhanced translational efficiency. We thus propose a model in which tRNA modifications modulate the abundance of stage-specific proteins by enhancing translation efficiency of codon-biased transcripts for critical genes. These findings reveal novel epitranscriptomic and translational control mechanisms in the development and pathogenesis of Plasmodium parasites.},
}
@article {pmid30287091,
year = {2018},
author = {Schumacher, D and Morgenstern, J and Oguchi, Y and Volk, N and Kopf, S and Groener, JB and Nawroth, PP and Fleming, T and Freichel, M},
title = {Compensatory mechanisms for methylglyoxal detoxification in experimental &amp; clinical diabetes.},
journal = {Molecular metabolism},
volume = {18},
number = {},
pages = {143-152},
pmid = {30287091},
issn = {2212-8778},
mesh = {Aged ; Aldo-Keto Reductases/metabolism ; Animals ; Diabetes Mellitus, Experimental/*metabolism ; Diabetes Mellitus, Type 2/*metabolism ; Female ; Glycation End Products, Advanced/metabolism ; Humans ; Kidney/metabolism ; Lactoylglutathione Lyase/genetics/metabolism ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Pyruvaldehyde/*metabolism ; },
abstract = {OBJECTIVES: The deficit of Glyoxalase I (Glo1) and the subsequent increase in methylglyoxal (MG) has been reported to be one the five mechanisms by which hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have been shown to metabolize MG; however, the relative contribution of this superfamily to the detoxification of MG in vivo, particularly within the diabetic state, remains unknown.<br><br>METHODS: CRISPR/Cas9-mediated genome editing was used to generate a Glo1 knock-out (Glo1[-/-]) mouse line. Streptozotocin was then applied to investigate metabolic changes under hyperglycemic conditions.<br><br>RESULTS: Glo1[-/-] mice were viable and showed no elevated MG or MG-H1 levels under hyperglycemic conditions. It was subsequently found that the enzymatic efficiency of various oxidoreductases in the liver and kidney towards MG were increased in the Glo1[-/-] mice. The functional relevance of this was supported by the altered distribution of alternative detoxification products. Furthermore, it was shown that MG-dependent AKR activity is a potentially clinical relevant pathway in human patients suffering from diabetes.<br><br>CONCLUSIONS: These data suggest that in the absence of GLO1, AKR can effectively compensate to prevent the accumulation of MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may provide a better means of identifying patients who are at risk for the development of late complications caused by elevated levels of MG.},
}
@article {pmid30276443,
year = {2019},
author = {Fortis, SP and Vaxevanis, CK and Mahaira, LG and Sofopoulos, M and Sotiriadou, NN and Dinou, A and Arnogiannaki, N and Stavropoulos-Giokas, C and Thanos, D and Baxevanis, CN and Perez, SA},
title = {Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics.},
journal = {Cancer immunology, immunotherapy : CII},
volume = {68},
number = {1},
pages = {57-70},
pmid = {30276443},
issn = {1432-0851},
support = {Grant GER_1968 (ISPEBREAST)//GSTR/ ; Donation//Haegeman-Goossens family/ ; },
mesh = {Biomarkers, Tumor/blood/*genetics ; Breast Neoplasms/classification/*genetics/immunology ; Cytokines/blood ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Leukocytes, Mononuclear/metabolism ; MicroRNAs/blood/*genetics ; Prognosis ; },
abstract = {Breast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23α, miR-146α, miR-155 and miR-181α), in operable BCa patients, with non-metastatic, invasive ductal carcinoma, not receiving neoadjuvant chemotherapy. These miRNAs, known to be involved in both tumor cell progression and immune pathways regulation, were analyzed in relation to circulating cytokines, tumor immune-cell infiltration and established prognostic clinicopathological characteristics. We have identified three different clusters, with overall low (C1), moderate (C2) or high (C3) expression levels of these six circulating miRNAs, which define three distinct groups of non-metastatic BCa patients characterized by different clinicopathological and immune-related characteristics, with possibly different clinical outcomes. Our data provide the proof-of-principle to support the notion that, up- or down-regulation of the same circulating miRNA may reflect different prognosis in BCa. Nonetheless, the prognostic and/or predictive potential of these three "signatures" needs to be further evaluated in larger cohorts of BCa patients with an, at least, 5-year clinical follow-up.},
}
@article {pmid30273605,
year = {2019},
author = {Hannafon, BN and Ding, WQ},
title = {Functional Role of miRNAs in the Progression of Breast Ductal Carcinoma in Situ.},
journal = {The American journal of pathology},
volume = {189},
number = {5},
pages = {966-974},
pmid = {30273605},
issn = {1525-2191},
support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Disease Progression ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Neoplasm Invasiveness ; Prognosis ; },
abstract = {miRNAs are small RNAs that influence gene expression by targeting mRNAs. Depending on the function of their target genes, miRNAs may regulate the expression of oncogenes and tumor suppressors, thereby contributing to the promotion or inhibition of tumor progression. Ductal carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a potential precursor to invasive ductal carcinoma. Many of the genetic events required for the invasive progression of DCIS occur at the preinvasive stage, and these events include changes in the expression of miRNAs. Aberrant expression of miRNAs can influence specific oncogenic or tumor-suppressive pathways required for breast cancer progression. miRNAs in DCIS have been shown to influence hormone signaling, cell-cell adhesion, epithelial-to-mesenchymal transition, transforming growth factor β signaling, maintenance of cancer stem cells, and modulation of the extracellular matrix. Additionally, extracellular DCIS miRNAs, such as those found in exosomes, may promote invasive progression by modifying the tumor microenvironment. Here, we review the miRNAs that have been identified in DCIS and how they may contribute to the progression to invasive disease. We also touch on the current state of miRNA therapy development, including the current challenges, and discuss the key future perspectives for research into miRNA function for the purpose of miRNA therapy development for DCIS.},
}
@article {pmid30261528,
year = {2018},
author = {Kopf, S and Nawroth, PP},
title = {Diabetic Pulmopathy: A New Clinical Challenge for Diabetology.},
journal = {Experimental and clinical endocrinology &amp; diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association},
volume = {126},
number = {9},
pages = {590-591},
doi = {10.1055/a-0715-2743},
pmid = {30261528},
issn = {1439-3646},
mesh = {*Diabetes Complications/therapy ; Diabetes Mellitus, Type 2/*complications ; Exercise Therapy ; Humans ; Pulmonary Fibrosis/diagnosis/*etiology/therapy ; },
}
@article {pmid30253811,
year = {2018},
author = {Abu-Sbeih, H and Ali, FS and Luo, W and Qiao, W and Raju, GS and Wang, Y},
title = {Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis.},
journal = {Journal for immunotherapy of cancer},
volume = {6},
number = {1},
pages = {95},
pmid = {30253811},
issn = {2051-1426},
mesh = {Adult ; Aged ; Antineoplastic Agents, Immunological/*adverse effects/therapeutic use ; Biomarkers ; Biopsy ; Colitis/*diagnosis/*etiology ; Comorbidity ; Disease Management ; *Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*complications/drug therapy/immunology ; Odds Ratio ; Retrospective Studies ; Severity of Illness Index ; },
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICPI) are efficacious treatments for advanced malignancies but can result in immune mediated diarrhea and colitis (IDC). Currently, the guidelines for the treatment of IDC depend only on clinical symptoms. Endoscopic and histologic features of such adverse events are not well studied in a manner that can help to gauge treatment plans. We aimed to characterize endoscopic and histologic features of IDC and to assess their association with clinical outcomes.<br><br>METHODS: Our study included patients who had undergone endoscopy for IDC (1/2010 to 3/2018). Patients with GI infection at time of onset were excluded. High-risk endoscopic features were ulcers deeper than 2&#xa0;mm, larger than 1&#xa0;cm, and extensive colonic involvement. Univariate and multivariate logistic regression were performed to assess the association of endoscopic and histological features with clinical outcomes.<br><br>RESULTS: A total of 182 patients was included; most were white (92%), males (65%) with a mean age of 60&#xa0;years. Median time from ICPI initiation to IDC was 7&#xa0;weeks. Fifty-three percent had grade 3-4 diarrhea, and 32% grade 3-4 colitis. Forty-nine patients had mucosal ulcerations, 66 non-ulcerative inflammation and 67 normal endoscopy. Calprotectin was higher in patients with ulceration (P&#x2009;=&#x2009;0.04). The sensitivity of lactoferrin to detect histologic and endoscopic inflammation was 90% and 70% respectively. Patients who underwent endoscopy earlier than 7&#xa0;days after IDC onset had shorter duration of IDC symptoms and duration of steroid treatment than those who underwent endoscopy after 7&#xa0;days of IDC onset (P&#x2009;=&#x2009;0.026 and P&#x2009;=&#x2009;0.053, respectively). Patients who underwent endoscopy >&#x2009;30&#xa0;days of symptom onset required longer duration of steroids (P&#x2009;=&#x2009;0.02), had more recurrent symptoms (P&#x2009;< 0.01) and received later infliximab/vedolizumab add-on therapy than did those who underwent endoscopy &#x2264;30&#xa0;days (P&#x2009;=&#x2009;0.03). High-risk features were associated with more frequent (P&#x2009;=&#x2009;0.03) and longer duration (P&#x2009;=&#x2009;0.02) hospitalization and infliximab/vedolizumab requirement (P&#x2009;< 0.01). Patients with active histological inflammation had more recurrence (P&#x2009;< 0.01) and repeat endoscopy (P&#x2009;< 0.01). Repeat endoscopy was required in 47 patients. A multivariate logistic regression revealed that longer ICPI treatment was associated with more frequent hospitalizations (OR 1.00; 95%CI 1.00-1.01; P&#x2009;< 0.01) and high-risk endoscopic features were associated with the requirement of infliximab/vedolizumab (OR 3.89; 95%CI 1.68-9.01; P&#x2009;< 0.01).<br><br>CONCLUSION: High risk endoscopic features and active histologic inflammation represent important markers of disease severity with clinical implications and should be used in a timely manner to devise IDC-focused treatment algorithms.},
}
@article {pmid30247211,
year = {2018},
author = {Cai, M and Feng, G and Zhang, G},
title = {A Case of Radioactivity Concentrated in Orbital Implant in 99mTc-MDP Bone Scan and SPECT/CT.},
journal = {Clinical nuclear medicine},
volume = {43},
number = {12},
pages = {e453-e454},
doi = {10.1097/RLU.0000000000002277},
pmid = {30247211},
issn = {1536-0229},
mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Orbital Implants/*adverse effects ; Orbital Neoplasms/*diagnostic imaging/secondary ; Radiopharmaceuticals ; *Single Photon Emission Computed Tomography Computed Tomography ; Technetium Tc 99m Medronate ; },
abstract = {A 27-year-old woman, who has received a hydroxyapatite orbital implant in the right eye due to a trauma 6 years ago, was newly diagnosis with left breast invasive ductal carcinoma. Tc-MDP bone scan showed an increased radiotracer accumulation in the right orbit and SPECT/CT confirmed the focal accumulation at the site of the implant, without any sign of local malignant lesions or orbital infection. Radionuclide imaging could provide certain useful information in diagnosing or differential diagnosing orbital disease.},
}
@article {pmid30236106,
year = {2018},
author = {Schultz, S and Bartsch, H and Sotlar, K and Petat-Dutter, K and Bonin, M and Kahlert, S and Harbeck, N and Vogel, U and Seeger, H and Fehm, T and Neubauer, HJ},
title = {Progression-specific genes identified in microdissected formalin-fixed and paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive ductal breast cancers.},
journal = {BMC medical genomics},
volume = {11},
number = {1},
pages = {80},
pmid = {30236106},
issn = {1755-8794},
mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Formaldehyde/chemistry ; *Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Paraffin Embedding ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; },
abstract = {BACKGROUND: The transition from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) is an important step during breast carcinogenesis. Understanding its molecular changes may help to identify high-risk DCIS that progress to IBC. Here, we describe a transcriptomic profiling analysis of matched formalin-fixed and paraffin-embedded (FFPE) DCIS and IBC components of individual breast tumours, containing both tumour compartments. The study was performed to validate progression-associated transcripts detected in an earlier gene profiling project using fresh frozen breast cancer tissue. In addition, FFPE tissues from patients with pure DCIS (pDCIS) were analysed to identify candidate transcripts characterizing DCIS with a high or low risk of progressing to IBC.<br><br>METHODS: Fifteen laser microdissected pairs of DCIS and IBC were profiled by Illumina DASL technology and used for expression validation by qPCR. Differential expression was independently validated using further 25 laser microdissected DCIS/IBC sample pairs. Additionally, laser microdissected epithelial cells from 31 pDCIS were investigated for expression of candidate transcripts using qPCR.<br><br>RESULTS: Multiple statistical calculation methods revealed 1784 mRNAs which are differentially expressed between DCIS and IBC (P&#x2009;<&#x2009;0.05), of which 124 have also been identified in the gene profiling project using fresh frozen breast cancer tissue. Nine mRNAs that had been selected from the gene list obtained using fresh frozen tissues by applying pathway and network analysis (MMP11, GREM1, PLEKHC1, SULF1, THBS2, CSPG2, COL10A1, COL11A1, KRT14) were investigated in tissues from the same 15 microdissected specimens and the 25 independent tissue samples by qPCR. All selected transcripts were also detected in tumour cells from pDCIS. Expression of MMP11 and COL10A1 increased significantly from pDCIS to DCIS of DCIS/IBC mixed tumours.<br><br>CONCLUSION: We confirm differential expression of progression-associated transcripts in FFPE breast cancer samples which might mediate the transition from DCIS to IBC. MMP11 and COL10A1 may characterize pure DCIS with a high risk developing IDC.},
}
@article {pmid30227836,
year = {2018},
author = {Jouali, F and Marchoudi, N and Talbi, S and Bilal, B and El Khasmi, M and Rhaissi, H and Fekkak, J},
title = {Detection of PIK3/AKT pathway in Moroccan population with triple negative breast cancer.},
journal = {BMC cancer},
volume = {18},
number = {1},
pages = {900},
pmid = {30227836},
issn = {1471-2407},
mesh = {Adult ; Aged ; Class I Phosphatidylinositol 3-Kinases/*genetics ; Exons/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Middle Aged ; Morocco/epidemiology ; Oncogene Protein v-akt/*genetics ; PTEN Phosphohydrolase/*genetics ; Retrospective Studies ; Signal Transduction/genetics ; Triple Negative Breast Neoplasms/epidemiology/*genetics/pathology ; },
abstract = {BACKGROUND: Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10-20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes. Due to the absence of molecular markers for TNBC his treatment options remains limited, without proven targeted therapies, which emphasize the need for discovering molecular markers that could be targeted for patient treatment, An important number of TNBC cases harbor aberrations in the phosphoinositide 3-kinase (PI3K) pathway, leading to constitutive activation of the downstream signaling pathway. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~ 30%) observed, along with protein loss of PTEN and AKT activation by phosphorylation (pAkt). Therefore, we propose to analyze clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in Moroccan triple negative breast cancer patients.<br><br>METHODS: We conducted a retrospective study of 39 patients diagnosed with triple negative breast cancer between early 2013 and 2016. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of TNBC subtype from Moroccan patients and to correlate the results with clinical-pathologic data.<br><br>RESULTS: All patients were female with a median age of 46&#xa0;years from (34-65). Most patients have had invasive ductal carcinoma (84.6%) and 69.2% of them were grade III SBR. Among the 39, 9 were right sided tumor patients and the remaining 30 were left-sided. Mutational analysis of PIK3CA gene was achieved in all TNBC patients. PIK3CA hotspot mutations were detected in 5/39 of TNBC (13%), in detail, among these 5 TNBC patients, one harbored mutation in exons 9 and four in exon 20.<br><br>CONCLUSION: The PI3KCA gene is highly activated and plays a crucial role in the pathogenesis of TNBC more, therefore, may be a potential therapeutic target to improve outcomes in patients.},
}
@article {pmid30208271,
year = {2018},
author = {Nuñez, NN and Khuu, C and Babu, CS and Bertolani, SJ and Rajavel, AN and Spear, JE and Armas, JA and Wright, JD and Siegel, JB and Lim, C and David, SS},
title = {The Zinc Linchpin Motif in the DNA Repair Glycosylase MUTYH: Identifying the Zn[2+] Ligands and Roles in Damage Recognition and Repair.},
journal = {Journal of the American Chemical Society},
volume = {140},
number = {41},
pages = {13260-13271},
pmid = {30208271},
issn = {1520-5126},
support = {R01 CA067985/CA/NCI NIH HHS/United States ; R29 CA067985/CA/NCI NIH HHS/United States ; T32 ES007059/ES/NIEHS NIH HHS/United States ; },
mesh = {Amino Acid Motifs ; Animals ; Base Sequence ; Binding Sites ; Cysteine/chemistry ; DNA Glycosylases/chemistry/genetics/*metabolism ; Geobacillus stearothermophilus/enzymology ; Humans ; Ligands ; Mice ; Mutation ; Protein Binding ; Sequence Alignment ; Zinc/*metabolism ; },
abstract = {The DNA base excision repair (BER) glycosylase MUTYH prevents DNA mutations by catalyzing adenine (A) excision from inappropriately formed 8-oxoguanine (8-oxoG):A mismatches. The importance of this mutation suppression activity in tumor suppressor genes is underscored by the association of inherited variants of MUTYH with colorectal polyposis in a hereditary colorectal cancer syndrome known as MUTYH-associated polyposis, or MAP. Many of the MAP variants encompass amino acid changes that occur at positions surrounding the two-metal cofactor-binding sites of MUTYH. One of these cofactors, found in nearly all MUTYH orthologs, is a [4Fe-4S][2+] cluster coordinated by four Cys residues located in the N-terminal catalytic domain. We recently uncovered a second functionally relevant metal cofactor site present only in higher eukaryotic MUTYH orthologs: a Zn[2+] ion coordinated by three Cys residues located within the extended interdomain connector (IDC) region of MUTYH that connects the N-terminal adenine excision and C-terminal 8-oxoG recognition domains. In this work, we identified a candidate for the fourth Zn[2+] coordinating ligand using a combination of bioinformatics and computational modeling. In addition, using in vitro enzyme activity assays, fluorescence polarization DNA binding assays, circular dichroism spectroscopy, and cell-based rifampicin resistance assays, the functional impact of reduced Zn[2+] chelation was evaluated. Taken together, these results illustrate the critical role that the "Zn[2+] linchpin motif" plays in MUTYH repair activity by providing for proper engagement of the functional domains on the 8-oxoG:A mismatch required for base excision catalysis. The functional importance of the Zn[2+] linchpin also suggests that adjacent MAP variants or exposure to environmental chemicals may compromise Zn[2+] coordination, and ability of MUTYH to prevent disease.},
}
@article {pmid30185420,
year = {2019},
author = {Lee, JY and Schizas, M and Geyer, FC and Selenica, P and Piscuoglio, S and Sakr, RA and Ng, CKY and Carniello, JVS and Towers, R and Giri, DD and de Andrade, VP and Papanastasiou, AD and Viale, A and Harris, RS and Solit, DB and Weigelt, B and Reis-Filho, JS and King, TA},
title = {Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {25},
number = {2},
pages = {674-686},
pmid = {30185420},
issn = {1557-3265},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {Breast Carcinoma In Situ/*genetics/*pathology ; Carcinoma, Lobular/*genetics/*pathology ; Clonal Evolution/*genetics ; Disease Progression ; *Genetic Heterogeneity ; *Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Neoplasm Metastasis ; Neoplasm Staging ; Tumor Burden ; Exome Sequencing ; },
abstract = {PURPOSE: Lobular carcinoma in situ (LCIS) is a preinvasive lesion of the breast. We sought to define its genomic landscape, whether intralesion genetic heterogeneity is present in LCIS, and the clonal relatedness between LCIS and invasive breast cancers.Experimental Design: We reanalyzed whole-exome sequencing (WES) data and performed a targeted amplicon sequencing validation of mutations identified in 43 LCIS and 27 synchronous more clinically advanced lesions from 24 patients [9 ductal carcinomas in situ (DCIS), 13 invasive lobular carcinomas (ILC), and 5 invasive ductal carcinomas (IDC)]. Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic trees were defined using validated computational methods.<br><br>RESULTS: WES of 43 LCIS lesions revealed a genomic profile similar to that previously reported for ILCs, with CDH1 mutations present in 81% of the lesions. Forty-two percent (18/43) of LCIS were found to be clonally related to synchronous DCIS and/or ILCs, with clonal evolutionary patterns indicative of clonal selection and/or parallel/branched progression. Intralesion genetic heterogeneity was higher among LCIS clonally related to DCIS/ILC than in those nonclonally related to DCIS/ILC. A shift from aging to APOBEC-related mutational processes was observed in the progression from LCIS to DCIS and/or ILC in a subset of cases.<br><br>CONCLUSIONS: Our findings support the contention that LCIS has a repertoire of somatic genetic alterations similar to that of ILCs, and likely constitutes a nonobligate precursor of breast cancer. Intralesion genetic heterogeneity is observed in LCIS and should be considered in studies aiming to develop biomarkers of progression from LCIS to more advanced lesions.},
}
@article {pmid30185184,
year = {2018},
author = {Du, JJ and Chen, YF and Peng, Y and Li, XJ and Ma, W},
title = {Calcification of the intervertebral disc and ossification of posterior longitudinal ligament in children.},
journal = {BMC musculoskeletal disorders},
volume = {19},
number = {1},
pages = {316},
pmid = {30185184},
issn = {1471-2474},
support = {81501929//National Natural Science Foundation of China/ ; No. Z161100000116057//Beijing Municipal Science and Technology Commission/ ; },
mesh = {Adolescent ; Calcinosis/*complications/*diagnostic imaging/therapy ; Cervical Vertebrae/*diagnostic imaging ; Child ; Conservative Treatment ; Humans ; Male ; Neck Pain/diagnostic imaging/etiology/therapy ; Ossification of Posterior Longitudinal Ligament/*complications/*diagnostic imaging/therapy ; },
abstract = {BACKGROUND: IDC in children, first reported by Baron in 1924, is very rare. OPLL of the cervical spine mainly affect people ages 50-70 years. The coexistence of IDC and OPLL in children is very rare, only six cases with 3 to 24 months' follow-up were reported to date.<br><br>CASE PRESENTATION: A 6-year-old boy presented with complains of neck pain at July 2007. The boy was treated by conservative treatment and observed up for 9&#xa0;years. Neck pain greatly improved after a one-month conservative treatment and never recur. Laboratory tests revealed elevated ESR and CRP at admission and found nothing abnormal at 19-month and 9-year follow-up. Computed tomography and magnetic resonance imaging revealed IDC at C2/3, C3/4 and OPLL at C3/4 at admission and found minor calcification at C2/3 remained but calcification at C3/4 and OPLL at C3/4 completely disappeared at 19-month and 9-year follow-up. Nineteen months after initial diagnosis, restoration of T2-weighted signal intensity of C2/3 and C3/4 discs was observed through MRI. Loss of T2-weighted signal intensity of C2/3 disc and decrease of T2-weighted signal intensity of C3/4 disc was observed at 9-year follow-up.<br><br>CONCLUSIONS: IDC with OPLL in children is very rare. Conservative treatments are recommended with affirmative short-term and long-term clinical effects. More intensive observation with long-term follow-ups may be needed to warrant the clinical effects.},
}
@article {pmid30183588,
year = {2018},
author = {Abdalla, AS and Lazarevska, A and Omer, MM and Tan, E and Asaad, A and Sathananthan, S},
title = {Metastatic Breast Cancer to the Cervix Presenting with Abnormal Vaginal Bleeding During Chemotherapy: A Case Report and Literature Review.},
journal = {Chirurgia (Bucharest, Romania : 1990)},
volume = {113},
number = {4},
pages = {564-570},
doi = {10.21614/chirurgia.113.4.564},
pmid = {30183588},
issn = {1221-9118},
mesh = {Antineoplastic Agents/*adverse effects ; Breast Neoplasms/complications/drug therapy/*secondary ; Female ; Humans ; Uterine Cervical Neoplasms/complications/*secondary ; Uterine Hemorrhage/chemically induced/*etiology ; },
abstract = {The most common sites of invasive breast cancer metastasis are the lungs, liver, bones and brain. Less frequent sites include the gastrointestinal tract, pancreas, spleen, thyroid, adrenals, kidneys, heart and female genital tract. The uterus is reported as a rare site for metastasis, and even more so for an isolated metastasis. Other sites of extra-genital sources for uterine metastases include the colon, stomach, pancreas, gallbladder, lung, cutaneous melanoma, urinary bladder and thyroid. The rarity of breast cancer metastasis to the uterine cervix could be explained by the fact that the cervix has a small blood supply and an afferent lymph drainage system alone. It is rare to diagnose a cervical metastasis prior to eliciting the primary breast disease. Invasive lobular carcinoma metastasises to the female reproductive system more frequently than invasive ductal carcinoma. This paper presents a case of breast cancer metastasis to the cervix.},
}
@article {pmid30171046,
year = {2019},
author = {Hess, J and Unger, K and Maihoefer, C and Schüttrumpf, L and Wintergerst, L and Heider, T and Weber, P and Marschner, S and Braselmann, H and Samaga, D and Kuger, S and Pflugradt, U and Baumeister, P and Walch, A and Woischke, C and Kirchner, T and Werner, M and Werner, K and Baumann, M and Budach, V and Combs, SE and Debus, J and Grosu, AL and Krause, M and Linge, A and Rödel, C and Stuschke, M and Zips, D and Zitzelsberger, H and Ganswindt, U and Henke, M and Belka, C},
title = {A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {25},
number = {5},
pages = {1505-1516},
doi = {10.1158/1078-0432.CCR-18-0776},
pmid = {30171046},
issn = {1557-3265},
mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; *Biomarkers, Tumor ; Female ; Head and Neck Neoplasms/*etiology/*mortality/pathology/therapy ; Humans ; Kaplan-Meier Estimate ; Male ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Papillomaviridae ; Papillomavirus Infections/complications ; Prognosis ; Proportional Hazards Models ; *Transcriptome ; Treatment Outcome ; },
abstract = {PURPOSE: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined.<br><br>EXPERIMENTAL DESIGN: We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; n = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; n = 77). A prognostic miRNA signature was developed for freedom from recurrence and tested for other endpoints. Recursive-partitioning analysis was performed on the miRNA signature, tumor and nodal stage, and extracapsular nodal spread. Technical validation used qRT-PCR. An miRNA-mRNA target network was generated and analyzed.<br><br>RESULTS: For DKTK-ROG and LMU-KKG patients, the median follow-up was 5.1 and 5.3 years, and the 5-year freedom from recurrence rate was 63.5% and 75.3%, respectively. A five-miRNA signature (hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p) predicted freedom from recurrence in DKTK-ROG [hazard ratio (HR) 4.42; 95% confidence interval (CI), 1.98-9.88, P < 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40-12.81, P = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50-6.12, P = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65-6.04, P < 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88-13.92, P < 0.001), all confirmed in LMU-KKG data. Adjustment for relevant covariates maintained the miRNA signature predicting all endpoints. Recursive-partitioning analysis of both samples combined classified patients into low (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P < 0.001).<br><br>CONCLUSIONS: The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.See related commentary by Clump et al., p. 1441.},
}
@article {pmid30149270,
year = {2018},
author = {Yirmiya, K and Djalovski, A and Motsan, S and Zagoory-Sharon, O and Feldman, R},
title = {Stress and immune biomarkers interact with parenting behavior to shape anxiety symptoms in trauma-exposed youth.},
journal = {Psychoneuroendocrinology},
volume = {98},
number = {},
pages = {153-160},
doi = {10.1016/j.psyneuen.2018.08.016},
pmid = {30149270},
issn = {1873-3360},
mesh = {Adolescent ; Adult ; Adverse Childhood Experiences ; Anxiety/*etiology/metabolism/psychology ; Biomarkers/blood ; Child ; Female ; Humans ; Hydrocortisone/analysis ; Hypothalamo-Hypophyseal System ; Immunity, Innate/physiology ; Immunoglobulin A, Secretory ; Male ; Mother-Child Relations/*psychology ; Mothers ; Parenting/*psychology ; Pituitary-Adrenal System ; Saliva/chemistry ; Social Behavior ; Stress Disorders, Post-Traumatic/metabolism ; Stress, Psychological/metabolism ; },
abstract = {The relations between stress, HPA-axis, and the immune system have been extensively studied; however, no study to date addressed the joint contribution of immune and HPA biomarkers to the development of anxiety in youth exposed to chronic trauma as mediated by mother-child interaction patterns. A unique cohort of war-exposed children and their mothers, compared to matched controls, were followed from infancy and the current study reports findings from early adolescence (mean age = 11.66, SD = 1.23; N = 111; exposed = 58 control = 53). Youth and mothers' salivary cortisol (CT) and secretory immunoglobulin (s-IgA) levels were measured three times during a 4-hour lab visit, mother-child interaction patterns were quantified from a joint task, and children's anxiety symptoms diagnosed. Trauma-exposed children had higher levels of CT and s-IgA, exhibited more anxiety symptoms, and showed lower social collaboration with mother during the joint task. Trauma-exposed mothers had higher CT and s-IgA levels and showed less supportive parenting during mother-child interaction. Structural equation modeling defined three bio-behavioral paths by which trauma increases anxiety in youth. While the first path charted a behavioral link from exposure to child anxiety via diminished maternal support, the other two paths described mediated biological paths, one through HPA-axis functioning, the other via the immune system. Paths via the child's HPA and immune system were mediated by the parallel maternal variable. Findings are the first to describe the complex bio-behavioral interplay of stress and immune biomarkers and parenting behavior in shaping to the development of risk and resilience trajectories in youth growing up amidst chronic trauma.},
}
@article {pmid30144784,
year = {2018},
author = {Shah, S and Brock, EJ and Jackson, RM and Ji, K and Boerner, JL and Sloane, BF and Mattingly, RR},
title = {Downregulation of Rap1Gap: A Switch from DCIS to Invasive Breast Carcinoma via ERK/MAPK Activation.},
journal = {Neoplasia (New York, N.Y.)},
volume = {20},
number = {9},
pages = {951-963},
pmid = {30144784},
issn = {1476-5586},
support = {U54 CA193489/CA/NCI NIH HHS/United States ; F31 CA213807/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R25 GM058905/GM/NIGMS NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; R21 CA175931/CA/NCI NIH HHS/United States ; },
mesh = {Biomarkers ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Cell Line, Tumor ; Cytoskeleton/metabolism ; Down-Regulation ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; GTPase-Activating Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Immunohistochemistry ; Mitogen-Activated Protein Kinases/metabolism ; Neoplasm Invasiveness ; RNA Interference ; },
abstract = {Diagnosis of breast ductal carcinoma in situ (DCIS) presents a challenge since we cannot yet distinguish those cases that would remain indolent and not require aggressive treatment from cases that may progress to invasive ductal cancer (IDC). The purpose of this study is to determine the role of Rap1Gap, a GTPase activating protein, in the progression from DCIS to IDC. Immunohistochemistry (IHC) analysis of samples from breast cancer patients shows an increase in Rap1Gap expression in DCIS compared to normal breast tissue and IDCs. In order to study the mechanisms of malignant progression, we employed an in vitro three-dimensional (3D) model that more accurately recapitulates both structural and functional cues of breast tissue. Immunoblotting results show that Rap1Gap levels in MCF10.Ca1D cells (a model of invasive carcinoma) are reduced compared to those in MCF10.DCIS (a model of DCIS). Retroviral silencing of Rap1Gap in MCF10.DCIS cells activated extracellular regulated kinase (ERK) mitogen-activated protein kinase (MAPK), induced extensive cytoskeletal reorganization and acquisition of mesenchymal phenotype, and enhanced invasion. Enforced reexpression of Rap1Gap in MCF10.DCIS-Rap1GapshRNA cells reduced Rap1 activity and reversed the mesenchymal phenotype. Similarly, introduction of dominant negative Rap1A mutant (Rap1A-N17) in DCIS-Rap1Gap shRNA cells caused a reversion to nonmalignant phenotype. Conversely, expression of constitutively active Rap1A mutant (Rap1A-V12) in noninvasive MCF10.DCIS cells led to phenotypic changes that were reminiscent of Rap1Gap knockdown. Thus, reduction of Rap1Gap in DCIS is a potential switch for progression to an invasive phenotype. The Graphical Abstract summarizes these findings.},
}
@article {pmid30124442,
year = {2018},
author = {Clement, Z and McLeay, W and Hoffmann, C and Shin, P and Kiu, A and Eaton, M},
title = {Role of radiotherapy in women over the age of 65 after breast conserving surgery for breast cancer: A 5-year retrospective study.},
journal = {Breast disease},
volume = {37},
number = {4},
pages = {197-205},
doi = {10.3233/BD-180340},
pmid = {30124442},
issn = {1558-1551},
mesh = {Aged ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Female ; Humans ; Mammography ; Mastectomy, Segmental/*statistics &amp; numerical data ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Radiotherapy, Adjuvant ; Retrospective Studies ; Risk Factors ; },
abstract = {BACKGROUND/OBJECTIVE: This study aimed to analyse the local recurrence (LR) and breast cancer related mortality (BCRM) in older women who underwent breast-conserving surgery (BCS) with and without adjuvant radiotherapy (XRT).<br><br>METHODS: This retrospective study included a total of 299 women who underwent BCS for early breast carcinoma, between the years of 2007 and 2011. Predictive risk factors, local recurrence (LR) and breast cancer related mortality (BCRM) were assessed with a mean follow-up period of 84 months.<br><br>RESULTS: Women over the age of 65 in the XRT and No-XRT groups showed similar incidence of LR (5.8% vs 5%, p =&#xa0;0.838). Women over 65 years old with XRT had a higher rate of BCRM (5.8% vs 0%, p =&#xa0;0.05). Resection margins >5&#xa0;mm had a lower rate of BCRM (HR 0.395, p =&#xa0;0.05). Women under the age of 65, invasive ductal carcinoma, grade-3 tumours, HER-2 positive, triple negative, lympho-vascular invasion, axillary lymph node positivity, high breast density on mammography were associated with increased risk of LR and BCRM.<br><br>CONCLUSIONS: XRT in women over the age of 65 did not decrease the risk of LR. Adjuvant XRT in older women should be offered to selective patients with high risk patient and tumour factors.},
}
@article {pmid30110913,
year = {2018},
author = {Liu, S and Cruz, ID and Ramos, CC and Taleon, P and Ramasamy, R and Shah, J},
title = {Pilot Study of Immunoblots with Recombinant Borrelia burgdorferi Antigens for Laboratory Diagnosis of Lyme Disease.},
journal = {Healthcare (Basel, Switzerland)},
volume = {6},
number = {3},
pages = {},
pmid = {30110913},
issn = {2227-9032},
abstract = {Accurate laboratory diagnosis of Lyme disease (Lyme borreliosis), caused by the spirochete Borrelia burgdorferi (BB), is difficult and yet important to prevent serious disease. The US Centers for Disease Control and Prevention (CDC) presently recommends a screening test for serum antibodies followed by confirmation with a more specific Western blot (WB) test to detect IgG and IgM antibodies against antigens in whole cell lysates of BB. Borrelia species related to BB cause tick-borne relapsing fever (TBRF). TBRF is increasingly recognized as a health problem in the US and occurs in areas where Lyme disease is prevalent. The two groups of Borrelia share related antigens. We have developed a modified WB procedure termed the Lyme immunoblots (IBs) using recombinant antigens from common strains and species of the BB sensu lato complex for serological diagnosis of Lyme disease. A reference collection of 178 sera from 26 with and 152 patients without Lyme disease were assessed by WB and IB in a blinded manner using either criteria for positive antibody reactions recommended by the CDC or criteria developed in-house. The sensitivity, specificity, positive and negative predictive values obtained with the reference sera suggest that the Lyme IB is superior to the Lyme WB for detection of specific antibodies in Lyme disease. The Lyme IB showed no significant reaction with rabbit antisera produced against two Borrelia species causing TBRF in the US, suggesting that the Lyme IB may be also useful for excluding TBRF.},
}
@article {pmid30110018,
year = {2018},
author = {Yildirim, N and Bahceci, A},
title = {Use of pertuzumab and trastuzumab during pregnancy.},
journal = {Anti-cancer drugs},
volume = {29},
number = {8},
pages = {810-813},
doi = {10.1097/CAD.0000000000000658},
pmid = {30110018},
issn = {1473-5741},
mesh = {Adult ; Antibodies, Monoclonal, Humanized/administration &amp; dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/*therapeutic use ; Breast Neoplasms/*drug therapy ; Docetaxel/administration &amp; dosage/adverse effects ; Female ; Fetus/*drug effects ; Humans ; Oligohydramnios/*chemically induced ; Pregnancy ; Pregnancy Complications, Neoplastic/*drug therapy ; Trastuzumab/administration &amp; dosage/adverse effects ; Young Adult ; },
abstract = {Trastuzumab and pertuzumab are monoclonal antibodies used for the treatment of breast cancer. Until now, there have been no reports on the use of pertuzumab during pregnancy and on its potential effects on the fetus. Herein, we present a breast cancer patient who received trastuzumab and pertuzumab treatment during the first 20 weeks of pregnancy. This 22-year-old patient initially diagnosed with invasive ductal carcinoma of the breast was found to be negative for estrogen receptor and progesterone receptor and positive for human epidermal growth factor receptor in the immunohistochemical examination. At the time of diagnosis, she had metastatic lesions and a protocol of docetaxel, trastuzumab, pertuzumab, q21, and zolendronic acid 4 mg every month was started. Following six courses of therapy, she had near-complete response, and, after administration of the same course of treatment for two additional cycles, treatment with pertuzumab plus trastuzumab was continued. While she was being followed-up with remission, a 20-week pregnancy was detected. A fetal ultrasound examination showed oligohydramnios and right renal agenesis. Treatment was stopped, and the fetus was monitored. After 7 weeks of follow-up, fetal growth retardation and anhydramnios were detected. The pregnancy was terminated. Fetal autopsy showed no urinary system pathology, but macroscopic and microscopic hyperplasia of the right adrenal gland was identified. Concomitant use of pertuzumab and trastuzumab during pregnancy may be associated with an unresolved oligohydramnios and/or anhydramnios risk. Extreme caution should be used when these monoclonal antibodies are administered during pregnancy.},
}
@article {pmid30101014,
year = {2018},
author = {Yan, L and Dong, X and Xu, H and Huang, J and Wang, W and Huang, L and Wan, Q and Gong, J},
title = {Paraneoplastic cerebellar degeneration associated with breast cancer: A case report and review of the literature.},
journal = {Molecular and clinical oncology},
volume = {9},
number = {2},
pages = {163-167},
pmid = {30101014},
issn = {2049-9450},
abstract = {Paraneoplastic cerebellar degeneration (PCD) is a rare neurological complication of cancer characterized by rapid development of cerebellar ataxia. We herein present a case of a 67-year-old female patient with PCD caused by breast cancer. The patient presented with progressively worsening cerebellar deficits that had been misdiagnosed for several months prior to the identification of the anti-Yo autoantibodies in the serum. A whole-body positron emission tomography/computed tomography scan revealed a lesion in the lower outer quadrant of the left breast with slightly increased metabolism. On mammography, a lobulated high-density mass was identified in the left breast. The patient underwent left breast lumpectomy and the histological examination confirmed the presence of an invasive ductal carcinoma. After breast surgery, the patient exhibited marked neurological improvement at the 12-month follow-up. Therefore, it is crucial that clinicians include paraneoplastic neurological syndromes in the differential diagnosis of neurological disorders. The detection of characterized onconeural antibodies in the serum or cerebrospinal fluid may provide guidance in the search for an underlying tumor.},
}
@article {pmid30096623,
year = {2018},
author = {Lahav-Kadmiel, Z and Brunstein-Klomek, A},
title = {Bullying victimization and depressive symptoms in adolescence: The moderating role of parent-child conflicts among boys and girls.},
journal = {Journal of adolescence},
volume = {68},
number = {},
pages = {152-158},
doi = {10.1016/j.adolescence.2018.07.014},
pmid = {30096623},
issn = {1095-9254},
mesh = {Adolescent ; Bullying/*psychology ; Child ; Crime Victims/*psychology ; Depression/*etiology ; Family Conflict/*psychology ; Female ; Humans ; Israel ; Male ; *Parent-Child Relations ; Self Report ; Sex Factors ; },
abstract = {INTRODUCTION: The association between bullying victimization and depressive symptoms has been studied extensively over the years. Among the variables studied as having an impact on this association were different characteristics of the parent-child relationship. The current study was the first to specifically examine parent-child conflicts as a moderator in the association between victimization and depressive symptoms among adolescents. In addition, it was the first to examine the roles of the child and parent's gender in this moderation.<br><br>METHODS: 505 7th-9th graders from two schools in two different cities across Israel (mean age&#x202f;=&#x202f;12.736, SD&#x202f;=&#x202f;0.8154) participated in this study. 223 (44.2%) of the participants were male. The participants filled out a battery of self-report questionnaires assessing the different study's variables.<br><br>RESULTS: Significant gender differences were found: among girls, the association between bullying victimization and depressive symptoms was stronger when the level of parent-child conflicts was high, while among boys, it was stronger when the level of conflicts was low.<br><br>CONCLUSIONS: Our results indicate that the psychological outcomes for victims depend on their relationship with their parents. Bullying intervention programs should include the victims' parents. Furthermore, intervention programs should be designed to fit the different needs of girls and boys.},
}
@article {pmid30096287,
year = {2018},
author = {Ngara, M and Palmkvist, M and Sagasser, S and Hjelmqvist, D and Björklund, &#xc5;K and Wahlgren, M and Ankarklev, J and Sandberg, R},
title = {Exploring parasite heterogeneity using single-cell RNA-seq reveals a gene signature among sexual stage Plasmodium falciparum parasites.},
journal = {Experimental cell research},
volume = {371},
number = {1},
pages = {130-138},
doi = {10.1016/j.yexcr.2018.08.003},
pmid = {30096287},
issn = {1090-2422},
mesh = {Erythrocytes/*parasitology/pathology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Ontology ; Genetic Heterogeneity ; Humans ; Life Cycle Stages/*genetics ; Molecular Sequence Annotation ; Plasmodium falciparum/*genetics/growth &amp; development/metabolism ; Protozoan Proteins/*genetics/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis ; *Transcriptome ; },
abstract = {The malaria parasite has a complex lifecycle, including several events of differentiation and stage progression, while actively evading immunity in both its mosquito and human hosts. Important parasite gene expression and regulation during these events remain hidden in rare populations of cells. Here, we combine a capillary-based platform for cell isolation with single-cell RNA-sequencing to transcriptionally profile 165 single infected red blood cells (iRBCs) during the intra-erythrocytic developmental cycle (IDC). Unbiased analyses of single-cell data grouped the cells into eight transcriptional states during IDC. Interestingly, we uncovered a gene signature from the single iRBC analyses that can successfully discriminate between developing asexual and sexual stage parasites at cellular resolution, and we verify five, previously undefined, gametocyte stage specific genes. Moreover, we show the capacity of detecting expressed genes from the variable gene families in single parasites, despite the sparse nature of data. In total, the single parasite transcriptomics holds promise for molecular dissection of rare parasite phenotypes throughout the malaria lifecycle.},
}
@article {pmid30094720,
year = {2018},
author = {Hashemi-Sadraei, N and Müller-Greven, GM and Abdul-Karim, FW and Ulasov, I and Downs-Kelly, E and Burgett, ME and Lauko, A and Qadan, MA and Weil, RJ and Ahluwalia, MS and Du, L and Prayson, RA and Chao, ST and Budd, TG and Barnholtz-Sloan, J and Nowacki, AS and Keri, RA and Gladson, CL},
title = {Expression of LC3B and FIP200/Atg17 in brain metastases of breast cancer.},
journal = {Journal of neuro-oncology},
volume = {140},
number = {2},
pages = {237-248},
pmid = {30094720},
issn = {1573-7373},
support = {R01 CA175120/CA/NCI NIH HHS/United States ; R01-CA152883//National Institutes of Health/ ; R01-CA175120//National Institutes of Health/ ; RPC 2010-1070-R1//Cleveland Clinic Foundation/ ; },
mesh = {Adult ; Aged ; Autophagy-Related Proteins ; Biomarkers, Tumor/metabolism ; Brain/metabolism/pathology ; Brain Neoplasms/*metabolism/mortality/*secondary/therapy ; Breast Neoplasms/metabolism/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology/therapy ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Meta-Analysis as Topic ; Microtubule-Associated Proteins/*metabolism ; Middle Aged ; Protein-Tyrosine Kinases/*metabolism ; RNA, Messenger/metabolism ; Retrospective Studies ; },
abstract = {BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer.<br><br>METHODS: In this retrospective study, specimens from 44 patients with brain metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining.<br><br>RESULTS: LC3-puncta[+] tumor cells and FIP200/Atg17 expression were detected in greater than 90% of brain metastases but there were considerable intra- and inter-tumor differences in expression levels. High numbers of LC3-puncta[+] tumor cells in brain metastases correlated with a significantly shorter survival time in triple-negative breast cancer. FIP200/Atg17 protein levels were significantly higher in metastases that subsequently recurred following therapy. The percentages of LC3 puncta[+] tumor cells and FIP200/Atg17 protein expression levels, but not mRNA levels, were significantly higher in metastases than primary-BC. Meta-analysis of gene expression datasets revealed a significant correlation between higher FIP200(RB1CC1)/Atg17 mRNA levels in primary-BC tumors and shorter disease-free survival.<br><br>CONCLUSIONS: These results support assessments of precision medicine-guided targeting of autophagy in treatment of brain metastases in breast cancer patients.},
}
@article {pmid30094484,
year = {2018},
author = {Tadros, AB and Wen, HY and Morrow, M},
title = {Breast Cancers of Special Histologic Subtypes Are Biologically Diverse.},
journal = {Annals of surgical oncology},
volume = {25},
number = {11},
pages = {3158-3164},
pmid = {30094484},
issn = {1534-4681},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA008748//NIH/NCI Cancer Center Support Grant/ ; },
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology/surgery ; Carcinoma, Lobular/genetics/metabolism/*pathology/surgery ; Female ; Follow-Up Studies ; Gene Expression Profiling/*methods ; Genomics ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; },
abstract = {BACKGROUND/OBJECTIVE: Cancers classified as "special histologic subtypes" are felt to have a good prognosis. We used the 21-gene Oncotype DX Breast Recurrence Score[®] multigene assay to examine prognostic variation within special histologic subtypes. We also examined the Recurrence Score[®] (RS) distribution among the more common ductal (IDC) and lobular (ILC) cancers.<br><br>METHODS: 610,350 tumor specimens examined in the Genomic Health clinical laboratory from 2/2004 to 8/2017 were included. Specimen histology was classified centrally using a single H&amp;E slide and World Health Organization criteria. RS distribution (low&#x2009;<&#x2009;18, intermediate 18-30, and high&#x2009;&#x2265;&#x2009;31) was compared among histologic subtypes.<br><br>RESULTS: Median patient age was 60&#xa0;years (IQR 51-67); 80% were node negative. Most patients had low RS results (59.2%); only 9.5% had high results. The lowest mean RS was seen in the papillary subtype (11); the highest in the IDC group (18.4). Mean RS for all special subtypes was lower than that of IDC patients. When the high RS threshold was decreased from 31 to 25, as used in the TAILORx and RxPONDER trials, the number of high RS-result patients increased from 9.5% to 16.8%. Patients with ILC had a lower mean RS result than patients with IDC, 16.5 versus 18.4.<br><br>CONCLUSION: There is substantial diversity in predicted prognosis among patients with cancers classified as special histologic subtypes, with 12-25% having intermediate RS results and 0.5-9% having high RS results. Pending further definition of the role of chemotherapy for patients with intermediate RS results by TAILORx and RxPONDER, the RS result may help to inform systemic therapy decisions in these patients.},
}
@article {pmid30087348,
year = {2018},
author = {Senyilmaz-Tiebe, D and Pfaff, DH and Virtue, S and Schwarz, KV and Fleming, T and Altamura, S and Muckenthaler, MU and Okun, JG and Vidal-Puig, A and Nawroth, P and Teleman, AA},
title = {Dietary stearic acid regulates mitochondria in vivo in humans.},
journal = {Nature communications},
volume = {9},
number = {1},
pages = {3129},
pmid = {30087348},
issn = {2041-1723},
support = {MC_G0802535/MRC_/Medical Research Council/United Kingdom ; SFB1036//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; MC_UU_12012/2/MRC_/Medical Research Council/United Kingdom ; MC_UU_00014/5/MRC_/Medical Research Council/United Kingdom ; MC_UU_00014/2/MRC_/Medical Research Council/United Kingdom ; BB/H002731/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; SFB1118//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; 724286//EC | European Research Council (ERC)/International ; G0600717/MRC_/Medical Research Council/United Kingdom ; MRC_MC_UU_12012/2//Medical Research Council (MRC)/International ; RG/12/13/29853//BHF Centre of Research Excellence, Oxford (BHF Centre of Research Excellence in Oxford)/International ; G0802051/MRC_/Medical Research Council/United Kingdom ; MC_UU_12012/5/MRC_/Medical Research Council/United Kingdom ; G0400192/MRC_/Medical Research Council/United Kingdom ; RG/12/13/29853/BHF_/British Heart Foundation/United Kingdom ; RG/18/7/33636/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Adult ; Beverages ; Carnitine/analogs &amp; derivatives/blood ; Case-Control Studies ; Cross-Over Studies ; Diabetes Mellitus/*metabolism ; Diet ; Fatty Acids/metabolism ; Female ; Humans ; Male ; Middle Aged ; Mitochondria/*metabolism ; Mitochondrial Dynamics ; Musa ; Oxygen/chemistry ; Stearic Acids/*metabolism ; },
abstract = {Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. We previously showed that the fatty acid stearic acid (C18:0) signals via a dedicated pathway to regulate mitofusin activity and thereby mitochondrial morphology and function in cell culture. Whether this pathway is poised to sense changes in dietary intake of C18:0 in humans is not known. We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.},
}
@article {pmid30085937,
year = {2018},
author = {Zhou, T and Xu, D and Tang, B and Ren, Y and Han, Y and Liang, G and Wang, J and Wang, L},
title = {Expression of programmed death ligand-1 and programmed death-1 in samples of invasive ductal carcinoma of the breast and its correlation with prognosis.},
journal = {Anti-cancer drugs},
volume = {29},
number = {9},
pages = {904-910},
pmid = {30085937},
issn = {1473-5741},
mesh = {Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/*genetics ; Carcinoma, Ductal, Breast/genetics/*pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/*drug effects ; Risk Factors ; Triple Negative Breast Neoplasms/genetics/*pathology ; },
abstract = {The aim of the current study is to investigate programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) expressions and to analyze the relationship between the expression of PD-L1 and PD-1 proteins and the molecular type, clinicopathological factors, and prognosis of invasive ductal carcinoma. We enrolled 136 patients with invasive ductal carcinoma of the breast. The expression of PD-L1 in tumor cells and that of PD-1 on paratumor-infiltrating immune cells was detected by immunohistochemistry, and the data were analyzed using SPSS software. The positive expression rates of PD-L1 and PD-1 in triple-negative breast cancer (TNBC) were 47.8 and 43.5%, which were higher than those of other subtypes (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 (P<0.05). The expression of PD-1 in the tumor-infiltrating immune cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 and the histological grade (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of PD-1 in paratumor-infiltrating immune cells (P<0.001). The expression of PD-L1 in tumor cells was found to be an independent prognostic risk factor with the progression-free survival rate for breast invasive ductal carcinoma (P=0.003). These results indicate that PD-L1 and PD-1 were highly expressed in TNBC which suggests that patients with TNBC may benefit from targeted immune therapies to a greater degree than patients with other subtypes. PD-L1 expression is an independent risk factor for breast invasive ductal carcinoma and expression of PD-L1 is expected to be a prognostic factor for breast cancer.},
}
@article {pmid30078647,
year = {2018},
author = {Deipolyi, AR and Riedl, CC and Bromberg, J and Chandarlapaty, S and Klebanoff, CA and Sofocleous, CT and Yarmohammadi, H and Brody, LA and Boas, FE and Ziv, E},
title = {Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study.},
journal = {Journal of vascular and interventional radiology : JVIR},
volume = {29},
number = {9},
pages = {1226-1235},
pmid = {30078647},
issn = {1535-7732},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/genetics/pathology ; Clinical Decision-Making ; DNA Mutational Analysis ; Embolization, Therapeutic/adverse effects/*methods ; Female ; Gene Expression Profiling ; Humans ; Liver Neoplasms/*diagnostic imaging/genetics/secondary/*surgery ; Middle Aged ; *Mutation ; New York City ; Patient Selection ; Phosphatidylinositol 3-Kinases/*genetics ; Pilot Projects ; *Positron Emission Tomography Computed Tomography ; Precision Medicine ; Predictive Value of Tests ; Preliminary Data ; Radiopharmaceuticals/*administration &amp; dosage/adverse effects ; Retrospective Studies ; Risk Factors ; Signal Transduction/genetics ; Time Factors ; Treatment Outcome ; },
abstract = {PURPOSE: To describe imaging response and survival after radioembolization for metastatic breast cancer and to delineate genetic predictors of imaging responses and outcomes.<br><br>MATERIALS AND METHODS: This retrospective study included 31 women (average age, 52 y) with liver metastasis from invasive ductal carcinoma who underwent resin and glass radioembolization (average cumulative dose, 2.0 GBq &#xb1; 1.8) between January 2011 and September 2017 after receiving &#x2265; 3 lines of chemotherapy. Twenty-four underwent genetic profiling with MSK-IMPACT or Sequenom; 26 had positron-emission tomography (PET)/CT imaging before and after treatment. Survival after the first radioembolization and 2-4-month PET/CT imaging response were assessed. Laboratory and imaging features were assessed to determine variables predictive of outcomes. Unpaired Student t tests and Fisher exact tests were used to compare responders and nonresponders categorized by changes in fluorodeoxyglucose avidity. Kaplan-Meier survival analysis was used to determine the impact of predictors on survival after radioembolization.<br><br>RESULTS: Median survival after radioembolization was 11 months (range, 1-49 mo). Most patients (18 of 26; 69%) had complete or partial response based on changes in fluorodeoxyglucose avidity. Imaging response was associated with longer survival (P&#xa0;= .005). Whereas 100% of patients with PI3K pathway mutations showed an imaging response, only 45% of wild-type patients showed a&#xa0;response (P&#xa0;= .01). Median survival did not differ between PI3K pathway wild-type (10.9 mo) and mutant (undefined) patients (P&#xa0;=&#xa0;.50).<br><br>CONCLUSIONS: These preliminary data suggest that genomic profiling may predict which patients with metastatic breast cancer benefit most from radioembolization. PI3K pathway mutations are associated with improved imaging response, which is associated with longer survival.},
}
@article {pmid30071094,
year = {2018},
author = {Hong, JH and Ko, YH and Kang, K},
title = {RNA variant identification discrepancy among splice-aware alignment algorithms.},
journal = {PloS one},
volume = {13},
number = {8},
pages = {e0201822},
pmid = {30071094},
issn = {1932-6203},
mesh = {*Algorithms ; Breast/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Computational Biology/*methods ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; RNA/metabolism ; *RNA Splicing ; Sequence Alignment/*methods ; Sequence Analysis, RNA/*methods ; },
abstract = {Next-generation sequencing (NGS) techniques have been generating various molecular maps, including transcriptomes via RNA-seq. Although the primary purpose of RNA-seq is to quantify the expression level of known genes, RNA variants are also identifiable. However, care must be taken to account for RNA's dynamic nature. In this study, we evaluated the following popular splice-aware alignment algorithms in the context of RNA variant-calling analysis: HISAT2, STAR, STAR (two-pass mode), Subread, and Subjunc. For this, we performed RNA-seq with ten pieces of invasive ductal carcinoma from breast tissue and three pieces of adjacent normal tissue from a single patient. These RNA-seq data were used to evaluate the performance of splice-aware aligners. Surprisingly, the number of common potential RNA editing sites (pRESs) identified by all alignment algorithms was less than 2% of the total. The main cause of this difference was the mapped reads on the splice junctions. In addition, the RNA quality significantly affected the outcome. Therefore, researchers must consider these experimental and bioinformatic features during RNA variant analysis. Further investigations of common pRESs discovered that BDH1, CCDC137, and TBC1D10A transcripts contained a single non-synonymous RNA variant that was unique to breast cancer tissue compared to adjacent normal tissue; thus, further clinical validation is required.},
}
@article {pmid30066839,
year = {2018},
author = {Zhu, X and Zeng, Z and Qiu, D and Chen, J},
title = {Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c‑Fos and ATP6V0D2.},
journal = {International journal of molecular medicine},
volume = {42},
number = {4},
pages = {2071-2079},
pmid = {30066839},
issn = {1791-244X},
mesh = {Cell Transdifferentiation/*immunology ; Dendritic Cells/*immunology/pathology ; Humans ; Osteoclasts/*immunology/pathology ; Proto-Oncogene Proteins c-fos/*immunology ; Receptor Activator of Nuclear Factor-kappa B/*immunology ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Signal Transduction/*immunology ; T-Lymphocytes/*immunology/pathology ; Vacuolar Proton-Translocating ATPases/*immunology ; },
abstract = {Osteoimmunological studies have revealed that T cells exert a powerful impact on the formation and activity of osteoclasts and bone remodeling. Evidence demonstrates that immature dendritic cells (iDCs) are more efficient transdifferentiating into osteoclasts (OCs) than monocytes. However, whether Vγ9Vδ2 T (γδ T) cells stimulate or inhibit iDC transdifferentiation into OCs has never been reported. The aim of the present study was to investigate the effects of γδ T cells on this transdifferentiation process. γδ T cells and iDCs were isolated from the peripheral blood of healthy volunteers separately and were co‑cultured with Transwelll inserts, with γδ T cells in the upper chamber and iDCs in the lower chamber. IDCs were treated with macrophage‑colony stimulating factor and receptor activator of nuclear factor‑κB (RANK) ligand. Tartrate resistant acid phosphatase (TRAP) assay and dentine resorption assay were performed to detect OC formation and their resorption capacity, respectively. The mRNA expression of OCs was examined using a microarray and real time‑quantitative polymerase chain reaction to trace the changes during iDC transdifferentiation into OCs. The results demonstrated that γδ T cells significantly inhibited the generation of the TRAP‑positive OCs from iDCs and their resorption capacity. The microarray analysis identified decreased expression level of Fos proto‑oncogene AP‑1 transcription factor subunit (c‑Fos), ATPase H+ transporting V0 subunit d (ATP6V0D2) and cathepsin K when iDCs were co‑cultured with γδ T cells. These genes are associated with OC differentiation, indicating that γδ T cells suppressed iDCs osteoclastogenesis by downregulation of the RANK/c‑Fos/ATP6V0D2 signaling pathway. The present findings provide novel insights into the interactions between human γδ T cells and iDCs, and demonstrate that γδ T cells are capable of inhibiting OC formation and their activity via downregulation of genes associated with OC differentiation.},
}
@article {pmid30066480,
year = {2018},
author = {Dodson, A and Parry, S and Ibrahim, M and Bartlett, JM and Pinder, S and Dowsett, M and Miller, K},
title = {Breast cancer biomarkers in clinical testing: analysis of a UK national external quality assessment scheme for immunocytochemistry and in situ hybridisation database containing results from 199 300 patients.},
journal = {The journal of pathology. Clinical research},
volume = {4},
number = {4},
pages = {262-273},
pmid = {30066480},
issn = {2056-4538},
support = {16591/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*diagnosis/genetics/metabolism/pathology ; Databases, Factual ; Estrogen Receptor alpha/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Ireland ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; United Kingdom ; },
abstract = {We describe a collated data set of results from clinical testing of breast cancers carried out between 2009 and 2016 in the United Kingdom and Republic of Ireland. More than 199 000 patient biomarker data sets, together with clinicopathological parameters were collected. Our analyses focused on human epidermal growth factor receptor-2 (HER2), oestrogen receptor (ER) and progesterone receptor (PR), with the aim of the study being to provide robust confirmatory evidence on known associations in these biomarkers and to uncover new data on previously undescribed or unconfirmed associations, thus strengthening the evidence-base in clinical breast cancer testing. Overall, 13.1% of tumours were HER2-positive; 10.6% in ER-positive tumours, and 25.5% in ER-negative tumours. Higher rates of HER2 positivity were significantly associated with patient age <56 years versus age ≥56 years, symptomatic versus screen-detected tumours, testing of involved axillary node versus primary breast cancer, invasive ductal carcinoma (not otherwise specified) versus other histological types, higher histological grade, increasing tumour size, increasing nodal involvement, ER-negative versus ER-positive tumour status, PR-negative versus PR-positive tumour status. Where ER status was known, 82.7% of tumours were ER-positive; 80.9% in women age <56 years, and 83.6% in those age ≥56 years (ER-positive cut-off ≥1.0% positive tumour cells or equivalent). Where PR status was known, 64.9% of tumours were PR-positive; 65.8% in women age <56 years, and 64.4% in women age ≥56 years (PR-positive cut off ≥10.0% or equivalent). These analyses of clinical test results provide contemporary benchmarking data for HER2, ER and PR positive rates.},
}
@article {pmid30063890,
year = {2018},
author = {Papadopoulos, EI and Papachristopoulou, G and Ardavanis, A and Scorilas, A},
title = {A comprehensive clinicopathological evaluation of the differential expression of microRNA-331 in breast tumors and its diagnostic significance.},
journal = {Clinical biochemistry},
volume = {60},
number = {},
pages = {24-32},
doi = {10.1016/j.clinbiochem.2018.07.008},
pmid = {30063890},
issn = {1873-2933},
mesh = {Adenofibroma/diagnosis/*genetics/pathology ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/genetics/pathology ; Carcinoma, Lobular/diagnosis/genetics/pathology ; Diagnosis, Differential ; Female ; Humans ; MicroRNAs/*genetics ; Prognosis ; Real-Time Polymerase Chain Reaction ; },
abstract = {OBJECTIVE: MicroRNA-331 (miR-331) has shown regulatory activity against several genes whose expression has been claimed to be deregulated in breast tumors, including that of epidermal growth factor receptor 2 (HER2). Herein, the clinical value of miR-331 expression was investigated by analyzing its levels in breast benign and malignant tumors.<br><br>METHODS: The expression levels of miR-331 were quantified via real-time PCR in 130 malignant and 66 benign breast tissue specimens collected after surgical resection of primary tumors. The generated data were analyzed by applying several statistical tests in order to examine the relationship of miR-331 expression with various established clinicopathological features and survival data of patients.<br><br>RESULTS: Our data showed that miR-331 was overexpressed in malignant breast tumors compared to their benign counterparts both overall (P&#x202f;=&#x202f;0.026) and individually when the subgroups of fibroadenoma and invasive ductal carcinoma were analyzed with each other (P&#x202f;=&#x202f;0.001). ROC curve analysis confirmed the diagnostic value of these variations, providing an AUC value equal to 0.597 (P&#x202f;=&#x202f;0.026) and 0.663 (P&#x202f;=&#x202f;0.001), respectively. Furthermore, miR-331 levels were elevated (P&#x202f;=&#x202f;0.026) in ductal cancerous specimens compared to the lobular ones but failed to correlate with other clinicopathological features or survival data of the breast cancer patients.<br><br>CONCLUSIONS: Our results provide evidence that miR-331 levels might provide valuable information regarding the differential diagnosis of benign and malignant breast tumors but present no prognostic value for breast cancer.},
}
@article {pmid30060783,
year = {2018},
author = {Lateef, F and Jamal, S and Nasir, S},
title = {Her-2/neu Oncogene Amplification by Fluorescence In Situ Hybridization and Protein Overexpression on Immunohistochemistry in Breast Cancer.},
journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP},
volume = {28},
number = {8},
pages = {581-585},
doi = {10.29271/jcpsp.2018.08.581},
pmid = {30060783},
issn = {1681-7168},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/*pathology ; Carcinoma, Lobular/*genetics/metabolism/*pathology ; Cross-Sectional Studies ; DNA, Neoplasm/analysis ; Female ; *Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence/*methods ; Middle Aged ; Receptor, ErbB-2/*genetics/metabolism ; },
abstract = {OBJECTIVE: To investigate the concordance and discordance between the test results of Her-2/neu by immunohisto-chemistry (IHC) and flourescence In Situ hybridization (FISH) in breast cancer cases.<br><br>STUDY DESIGN: Descriptive cross-sectional study.<br><br>PLACE AND DURATION OF STUDY: Department of Histopathology, Dr. Ziauddin Hospital, Karachi, from 2011 to 2016.<br><br>METHODOLOGY: Forty-three specimens of invasive ductal carcinoma of breast were evaluated for grade and Her-2/neu status using IHC and FISH methods. Concordance and discordance between their results was determined.<br><br>RESULTS: There is 100% concordance between FISH and IHC in cases scoring 0, 1+ (negative) and 3+ (positive) immunostaining. Tumour cases scoring 2+ immunostaining showed amplification in 69.2% cases. All grade-I tumours were non-amplified on FISH, while most of the grade-III tumours showed Her-2/neu amplification on FISH. There is significant association of Her-2/neu IHC with tumour grade and FISH (p<0.05). A fairly high proportion i.e. 69.7% of cases showed Her-2/neu gene amplification. There was high concordance between Her-2/neu testing on IHC and FISH, (Kappa co-efficient 0.466, p <0.001).<br><br>CONCLUSION: Her-2/neu amplification increases with increasing grade of breast cancer. A high proportion of Her-2/neu gene amplified cases indicates aggressive disease in that area and need for FISH testing on large scale, which is the gold standard for equivocal cases on immunohistochemistry.},
}
@article {pmid30051683,
year = {2018},
author = {Solanki, R and Agrawal, N and Ansari, M and Jain, S and Jindal, A},
title = {COX-2 Expression in Breast Carcinoma with Correlation to Clinicopathological Parameters.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {19},
number = {7},
pages = {1971-1975},
pmid = {30051683},
issn = {2476-762X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Cyclooxygenase 2/*metabolism ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Prognosis ; },
abstract = {Objective: Breast carcinoma is the most common malignant tumor and the leading cause of carcinoma deaths in women. Its etiology is multifactorial, implicating reproductive factors, hormonal imbalances and genetic predispositions. Studies have shown that Cycloxygenase-2 (COX-2) plays an important role in the carcinogenesis and increased expression has been regarded as a poor prognostic factor. The objective of our study is 1. To study COX-2 expression in normal breast tissue, DCIS and invasive breast cancer. 2. To determine COX-2 expression with clinicopathological prognostic parameters. Methods: Radical mastectomy specimens were studied for COX-2 expression by immunohistochemistry in 50 patients diagnosed as breast carcinoma. COX-2 expression is quantified as IHS Score and separately calculated for normal breast epithelium near the tumor, DCIS and invasive areas. Relationship between COX-2 expression with various clinicopathological parameters was evaluated. Result: The results of our study suggest an association of the expression of COX-2 to the factors associated with poor prognosis in breast cancer, such as larger tumor size, positive lymph node status, higher T stage and N stage and lymphovascular invasion. There was a higher COX-2 expression in the DCIS component as compared to the invasive ductal carcinoma component and the adjoining breast epithelium. Conclusion: Our study established the role of COX-2 in carcinogenesis and its association with adverse prognostic factors.},
}
@article {pmid30050552,
year = {2018},
author = {Bai, G and Jenkins, S and Yuan, W and Graef, GL and Ge, Y},
title = {Field-Based Scoring of Soybean Iron Deficiency Chlorosis Using RGB Imaging and Statistical Learning.},
journal = {Frontiers in plant science},
volume = {9},
number = {},
pages = {1002},
pmid = {30050552},
issn = {1664-462X},
abstract = {Iron deficiency chlorosis (IDC) is an abiotic stress in soybean that can cause significant biomass and yield reduction. IDC is characterized by stunted growth and yellowing and interveinal chlorosis of early trifoliate leaves. Scoring IDC severity in the field is conventionally done by visual assessment. The goal of this study was to investigate the usefulness of Red Green Blue (RGB) images of soybean plots captured under the field condition for IDC scoring. A total of 64 soybean lines with four replicates were planted in 6 fields over 2 years. Visual scoring (referred to as Field Score, or FS) was conducted at V3-V4 growth stage; and concurrently RGB images of the field plots were recorded with a high-throughput field phenotyping platform. A second set of IDC scores was done on the plot images (displayed on a computer screen) consistently by one person in the office (referred to as Office Score, or OS). Plot images were then processed to remove weeds and extract six color features, which were used to train computer-based IDC scoring models (referred to as Computer Score, or CS) using linear discriminant analysis (LDA) and support vector machine (SVM). The results showed that, in the fields where severe IDC symptoms were present, FS and OS were strongly positively correlated with each other, and both of them were strongly negatively correlated with yield. CS could satisfactorily predict IDC scores when evaluated using FS and OS as the reference (overall classification accuracy > 81%). SVM models appeared to outperform LDA models; and the SVM model trained to predict IDC OS gave the highest prediction accuracy. It was anticipated that coupling RGB imaging from the high-throughput field phenotyping platform with real-time image processing and IDC CS models would lead to a more rapid, cost-effective, and objective scoring pipeline for soybean IDC field screening and breeding.},
}
@article {pmid30033677,
year = {2018},
author = {Damin, AP and Pozzer, CL and Farret, TF and Reginatto, AG and Trindade, EN},
title = {Gigantic invasive ductal carcinoma of the breast.},
journal = {The breast journal},
volume = {24},
number = {6},
pages = {1082},
doi = {10.1111/tbj.13087},
pmid = {30033677},
issn = {1524-4741},
mesh = {Breast Neoplasms/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/drug therapy/*pathology/surgery ; Female ; Humans ; Lung Neoplasms/drug therapy/secondary ; Middle Aged ; },
}
@article {pmid30028473,
year = {2018},
author = {Gabanti, E and Lilleri, D and Scaramuzzi, L and Zelini, P and Rampino, T and Gerna, G},
title = {Comparison of the T-cell response to human cytomegalovirus (HCMV) as detected by cytokine flow cytometry and QuantiFERON-CMV assay in HCMV-seropositive kidney transplant recipients.},
journal = {The new microbiologica},
volume = {41},
number = {3},
pages = {195-202},
pmid = {30028473},
issn = {1121-7138},
mesh = {Adolescent ; Adult ; Aged ; Cytokines/*physiology ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/blood/*immunology ; Female ; Flow Cytometry ; Humans ; Immunity, Cellular ; Immunoassay/methods ; *Kidney Transplantation ; Male ; Middle Aged ; Sensitivity and Specificity ; T-Lymphocytes/*physiology ; *Transplant Recipients ; Young Adult ; },
abstract = {Human cytomegalovirus (HCMV)-specific T-cell response in kidney transplant recipients (KTR) helps to identify patients at risk for severe infection. To assess the T-cell response, this study compared our in-house developed reference test, based on T-cell (both CD4+ and CD8+) stimulation by autologous HCMV-infected dendritic cells (iDC) and subsequent detection by cytokine flow cytometry (CFC-iDC), with the Quanti-FERON-CMV (QF-CMV) assay. Fifty-three HCMV-seropositive KTR were enrolled. At the DNAemia peak, 33 (62%) had low viral load (LVL, <3x105 DNA copies/mL) self-resolving infection, 19 (36%) high viral load (HVL, >3x105 DNA copies/mL) infection treated with antivirals, and one LVL patient (2%) tissue-invasive disease alone. Both assays showed a delayed recovery of HCMV-specific T-cell immunity in HVL vs LVL patients. Immune reconstitution kinetics did not significantly differ between the two assays in HVL patients. QF-CMV and CFC-iDC showed comparable sensitivities, but QF-CMV had a lower (although not significantly) specificity. Indeed, 7/19 HVL patients (37%) were erroneously considered protected from severe infection by QF-CMV, whereas CFC-iDC misidentified only 3/19 (16%) patients as protected. Although our reference test takes longer to complete, it appears slightly better at predicting patients at risk for severe HCMV infection. Moreover, QF-CMV may provide false negative results with some HLA types.},
}
@article {pmid30026605,
year = {2018},
author = {Sen, U and Saxena, H and Khurana, J and Nayak, A and Gupta, A},
title = {Plasmodium falciparum RUVBL3 protein: a novel DNA modifying enzyme and an interacting partner of essential HAT protein MYST.},
journal = {Scientific reports},
volume = {8},
number = {1},
pages = {10917},
pmid = {30026605},
issn = {2045-2322},
support = {SB/YS/LS-297/2013//Department of Science and Technology, Ministry of Science and Technology (DST)/International ; BT/08/IYBA/2014-4//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; },
mesh = {ATPases Associated with Diverse Cellular Activities/chemistry ; Adenosine Triphosphatases/chemistry/genetics/*metabolism ; Carrier Proteins/chemistry ; Chromatin Assembly and Disassembly ; DNA/*metabolism ; DNA Helicases/chemistry ; Fungal Proteins/chemistry ; Gene Expression Regulation, Developmental ; Histone Acetyltransferases/*metabolism ; Histones/metabolism ; Models, Molecular ; Plasmodium falciparum/chemistry/genetics/*metabolism ; Protein Domains ; Protozoan Proteins/chemistry/genetics/metabolism ; Sequence Homology, Nucleic Acid ; Yeasts/chemistry/metabolism ; },
abstract = {RUVBLs constitute a conserved group of ATPase proteins that play significant role in a variety of cellular processes including transcriptional regulation, cell cycle and DNA damage repair. Three RUVBL homologues, namely, PfRUVBL1, PfRUVBL2 and PfRUVBL3 have been identified in P. falciparum, unlike its eukaryotic counterparts, which have two RUVBL proteins (RUVBL1 &amp; RUVBL2). The present study expands our understanding of PfRUVBL3 protein and thereby basic biology of Plasmodium in general. Here, we have shown that parasite PfRUVBL3 is a true homolog of human/yeast RUVBL2 protein. Our result show that PfRUVBL3 constitutively expresses throughout the stages of intra-erythrocytic cycle (IDC) with varied localization. In addition to ATPase and oligomerization activity, we have for the first time shown that PfRUVBL3 possess DNA cleavage activity which interestingly is dependent on its insertion domain. Furthermore, we have also identified RUVBL3 to be an interacting partner of an essential chromatin remodeling protein PfMYST and together they colocalize with H3K9me1 histone in parasitophorous vacuole during the ring stage of IDC suggesting their potential involvement in chromatin remodeling and gene transcription.},
}
@article {pmid30024024,
year = {2019},
author = {Brunstein Klomek, A and Barzilay, S and Apter, A and Carli, V and Hoven, CW and Sarchiapone, M and Hadlaczky, G and Balazs, J and Kereszteny, A and Brunner, R and Kaess, M and Bobes, J and Saiz, PA and Cosman, D and Haring, C and Banzer, R and McMahon, E and Keeley, H and Kahn, JP and Postuvan, V and Podlogar, T and Sisask, M and Varnik, A and Wasserman, D},
title = {Bi-directional longitudinal associations between different types of bullying victimization, suicide ideation/attempts, and depression among a large sample of European adolescents.},
journal = {Journal of child psychology and psychiatry, and allied disciplines},
volume = {60},
number = {2},
pages = {209-215},
doi = {10.1111/jcpp.12951},
pmid = {30024024},
issn = {1469-7610},
mesh = {Adolescent ; Bullying/*statistics &amp; numerical data ; Crime Victims/*statistics &amp; numerical data ; Depression/*epidemiology ; Europe ; Female ; Humans ; Longitudinal Studies ; Male ; *Suicidal Ideation ; Suicide, Attempted/*statistics &amp; numerical data ; },
abstract = {BACKGROUND: The association between bullying victimization and depression, suicide ideation and suicide attempts has been studied mainly in cross-sectional studies. This study aims to test the bidirectional effect and the chronicity versus sporadic effect of physical, verbal, and relational bullying victimization on suicidal ideation/attempts and depression.<br><br>METHODS: Longitudinal assessments with an interval of 3- and 12-months were performed within a sample of 2,933 adolescents (56.1% females; mean age 14.78, SD&#xa0;=&#xa0;.89) from 10 European countries, participating in the Saving and Empowering Young Lives in Europe (SEYLE) school-based multicenter control sample. Multilevel Structural Equation Models were used, controlling for sociodemographic variables. Victimization was considered chronic when a student was victimized in the first two time points and sporadic when it was reported only at one point but not in another.<br><br>RESULTS: Bidirectional prospective association between all types of victimization and depression were found. Among participants, who reported victimization once (but not twice), physical victimization, but not verbal and relational, was associated with later suicidal ideation and attempts. Chronic victimization of any type increased likelihood for later depression compared with sporadic and no-victimization. Chronic relational victimization increased the likelihood of later suicidal ideation, and chronic physical victimization increased the likelihood for suicidal attempts.<br><br>CONCLUSIONS: The results support the bidirectional effect of victimization and depression and indicate that there are complex longitudinal associations between victimization and suicidal ideation/attempts. Physical victimization may especially carry effect on suicidal risk over time. Interventions should focus on victimization as a cause of distress but also aim to prevent vulnerable adolescents from becoming targets of victimization.},
}
@article {pmid30009102,
year = {2018},
author = {Katz, H and Jafri, H and Saad, R and Limjoco, T and Tirona, MT},
title = {Colonic Obstruction from an Unusual Cause: A Rare Case of Metastatic Invasive Ductal Carcinoma to the Colon.},
journal = {Cureus},
volume = {10},
number = {5},
pages = {e2588},
pmid = {30009102},
issn = {2168-8184},
abstract = {Colon metastasis from breast cancer is rare. Gastrointestinal (GI) metastasis is more frequently seen in patients with invasive lobular carcinoma of the breast compared to invasive ductal carcinoma; however, the most common sites of metastasis still remain the lymph nodes, lungs, liver, and bones. We describe a 68-year-old female with a remote history of invasive ductal carcinoma of the breast who presented with abdominal pain and a palpable mass. On imaging, she was found to have a colonic obstruction and underwent a right hemicolectomy that proved to be metastatic invasive ductal carcinoma of the breast.},
}
@article {pmid29985403,
year = {2018},
author = {Painter, HJ and Chung, NC and Sebastian, A and Albert, I and Storey, JD and Llinás, M},
title = {Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development.},
journal = {Nature communications},
volume = {9},
number = {1},
pages = {2656},
pmid = {29985403},
issn = {2041-1723},
support = {R21 AI133379/AI/NIAID NIH HHS/United States ; },
mesh = {Erythrocytes/parasitology ; Gene Expression Profiling ; Gene Ontology ; Genes, Protozoan/*genetics ; Genome, Protozoan/*genetics ; Humans ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/*genetics/physiology ; RNA, Messenger/genetics/metabolism ; RNA, Protozoan/genetics/metabolism ; *Transcription, Genetic ; },
abstract = {Genome-wide analysis of transcription in the malaria parasite Plasmodium falciparum has revealed robust variation in steady-state mRNA abundance throughout the 48-h intraerythrocytic developmental cycle (IDC), suggesting that this process is highly dynamic and tightly regulated. Here, we utilize rapid 4-thiouracil (4-TU) incorporation via pyrimidine salvage to specifically label, capture, and quantify newly-synthesized RNA transcripts at every hour throughout the IDC. This high-resolution global analysis of the transcriptome captures the timing and rate of transcription for each newly synthesized mRNA in vivo, revealing active transcription throughout all IDC stages. Using a statistical model to predict the mRNA dynamics contributing to the total mRNA abundance at each timepoint, we find varying degrees of transcription and stabilization for each mRNA corresponding to developmental transitions. Finally, our results provide new insight into co-regulation of mRNAs throughout the IDC through regulatory DNA sequence motifs, thereby expanding our understanding of P. falciparum mRNA dynamics.},
}
@article {pmid29983888,
year = {2018},
author = {Kaymak, A and Sayols, S and Papadopoulou, T and Richly, H},
title = {Role for the transcriptional activator ZRF1 in early metastatic events in breast cancer progression and endocrine resistance.},
journal = {Oncotarget},
volume = {9},
number = {47},
pages = {28666-28690},
pmid = {29983888},
issn = {1949-2553},
abstract = {Breast cancer is one of the most common malignancies among women which is often treated with hormone therapy and chemotherapy. Despite the improvements in detection and treatment of breast cancer, the vast majority of breast cancer patients are diagnosed with metastatic disease either at the beginning of the disease or later during treatment. Still, the molecular mechanisms causing a therapy resistant metastatic breast cancer are still elusive. In the present study we addressed the function of the transcriptional activator ZRF1 during breast cancer progression. We provide evidence that ZRF1 plays an essential role for the early metastatic events in vitro and acts like a tumor suppressor protein during the progression of breast invasive ductal carcinoma into a more advanced stage. Hence, depletion of ZRF1 results in the acquisition of metastatic behavior by facilitating the initiation of the metastatic cascade, notably for cell adhesion, migration and invasion. Furthermore absence of ZRF1 provokes endocrine resistance via misregulation of cell death and cell survival related pathways. Taken together, we have identified ZRF1 as an important regulator of breast cancer progression that holds the potential to be explored for new treatment strategies in the future.},
}
@article {pmid29981615,
year = {2018},
author = {Du, R and Zhang, H and Shu, W and Chen, B and Li, Y and Zhang, X and Wu, X and Wang, Z},
title = {Correlation between Ki-67 Expression and Hemodynamics of Contrast-Enhanced Ultrasound in Patients with Breast Infiltrative Ductal Carcinoma.},
journal = {The American surgeon},
volume = {84},
number = {6},
pages = {856-861},
pmid = {29981615},
issn = {1555-9823},
mesh = {Adolescent ; Adult ; Breast Neoplasms/*diagnostic imaging/*metabolism/physiopathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*metabolism/physiopathology ; Cohort Studies ; Contrast Media ; Female ; Hemodynamics ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Regional Blood Flow ; Ultrasonography, Mammary ; Young Adult ; },
abstract = {Breast cancer causes great threats to public health worldwide. The aim of this study was to investigate the correlation between Ki-67 expression and the hemodynamics of contrast-enhanced ultrasound (CEUS) in patients with infiltrative ductal carcinoma (IDC). CEUS was performed on 109 masses in 85 IDC cases before resection. Based on the immunohistochemical staining on the antigen Ki-67, the masses were divided into negative group, weakly positive group, positive group, and strong-positive group. Significant statistical differences were noticed in time to peak, arrive intensity, and peak intensity in the positive groups compared with the negative group. Compared with the positive groups, the negative group showed significant statistical differences in arrive intensity and peak intensity. The antigen Ki-67 was positively correlated with arrived intensity, intensity changes, and rising curve's slope. In contrast, it was negatively correlated with arrived time, time to peak, and continuous time. The hemodynamic parameters of CEUS were correlated with the expression of antigen Ki-67. On this basis, Ki-67 is an effective supplement to the diagnosis of IDC.},
}
@article {pmid29973382,
year = {2018},
author = {Bayindir-Buchhalter, I and Wolff, G and Lerch, S and Sijmonsma, T and Schuster, M and Gronych, J and Billeter, AT and Babaei, R and Krunic, D and Ketscher, L and Spielmann, N and Hrabe de Angelis, M and Ruas, JL and Müller-Stich, BP and Heikenwalder, M and Lichter, P and Herzig, S and Vegiopoulos, A},
title = {Cited4 is a sex-biased mediator of the antidiabetic glitazone response in adipocyte progenitors.},
journal = {EMBO molecular medicine},
volume = {10},
number = {8},
pages = {},
pmid = {29973382},
issn = {1757-4684},
mesh = {Adipocytes/*drug effects/metabolism ; Animals ; Diabetes Mellitus, Type 2/*drug therapy/metabolism ; Female ; Humans ; Hypoglycemic Agents/*therapeutic use ; Male ; Mice ; Molecular Targeted Therapy ; PPAR gamma/metabolism ; Rosiglitazone/*therapeutic use ; Sex Factors ; Stem Cells/drug effects/metabolism ; Thermogenesis ; Transcription Factors/biosynthesis/*metabolism ; Transcription, Genetic/drug effects ; Uncoupling Protein 1/biosynthesis ; },
abstract = {Most antidiabetic drugs treat disease symptoms rather than adipose tissue dysfunction as a key pathogenic cause in the metabolic syndrome and type 2 diabetes. Pharmacological targeting of adipose tissue through the nuclear receptor PPARg, as exemplified by glitazone treatments, mediates efficacious insulin sensitization. However, a better understanding of the context-specific PPARg responses is required for the development of novel approaches with reduced side effects. Here, we identified the transcriptional cofactor Cited4 as a target and mediator of rosiglitazone in human and murine adipocyte progenitor cells, where it promoted specific sets of the rosiglitazone-dependent transcriptional program. In mice, Cited4 was required for the proper induction of thermogenic expression by Rosi specifically in subcutaneous fat. This phenotype had high penetrance in females only and was not evident in beta-adrenergically stimulated browning. Intriguingly, this specific defect was associated with reduced capacity for systemic thermogenesis and compromised insulin sensitization upon therapeutic rosiglitazone treatment in female but not male mice. Our findings on Cited4 function reveal novel unexpected aspects of the pharmacological targeting of PPARg.},
}
@article {pmid29973218,
year = {2018},
author = {Zubeldia-Plazaola, A and Recalde-Percaz, L and Moragas, N and Alcaraz, M and Chen, X and Mancino, M and Fernández-Nogueira, P and Prats de Puig, M and Guzman, F and Noguera-Castells, A and López-Plana, A and Enreig, E and Carbó, N and Almendro, V and Gascón, P and Bragado, P and Fuster, G},
title = {Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis.},
journal = {Breast cancer research : BCR},
volume = {20},
number = {1},
pages = {65},
pmid = {29973218},
issn = {1465-542X},
mesh = {Animals ; Apoptosis/genetics ; Biomarkers, Tumor/*blood/genetics ; Carcinoma, Ductal, Breast/*blood/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*blood/genetics/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Glucocorticoids/*blood ; Heterografts ; Humans ; Laminin/genetics ; Mice ; Myoepithelioma/blood/genetics/pathology ; Tumor Microenvironment/genetics ; },
abstract = {BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocorticoids in ductal carcinoma in situ (DCIS) in breast cancer, focusing specially on myoepithelial cells.<br><br>METHODS: To clarify the role of glucocorticoids at breast cancer onset, we evaluated the effects of cortisol and corticosterone on epithelial and myoepithelial cells using 2D and 3D in vitro and in vivo approaches and human samples.<br><br>RESULTS: Glucocorticoids induce a reduction in laminin levels and favour the disruption of the basement membrane by promotion of myoepithelial cell apoptosis in vitro. In an in vivo stress murine model, increased corticosterone levels fostered the transition from DCIS to invasive ductal carcinoma (IDC) via myoepithelial cell apoptosis and disappearance of the basement membrane. RU486 is able to partially block the effects of cortisol in vitro and in vivo. We found that myoepithelial cell apoptosis is more frequent in patients with DCIS+IDC than in patients with DCIS.<br><br>CONCLUSIONS: Our findings show that physiological stress, through increased glucocorticoid blood levels, promotes the transition from DCIS to IDC, particularly by inducing myoepithelial cell apoptosis. Since this would be a prerequisite for invasive features in patients with DCIS breast cancer, its clinical management could help to prevent breast cancer progression to IDC.},
}
@article {pmid29959495,
year = {2018},
author = {Eck, DL and Nguyen, DC and Barnes, LL and Jansen, DA},
title = {Treatment of Breast Animation Deformity in Implant-Based Reconstruction with Selective Nerve Ablation.},
journal = {Aesthetic plastic surgery},
volume = {42},
number = {6},
pages = {1472-1475},
doi = {10.1007/s00266-018-1184-0},
pmid = {29959495},
issn = {1432-5241},
mesh = {Adult ; Breast Implantation/*adverse effects/methods ; *Breast Implants ; Breast Neoplasms/pathology/*surgery ; Denervation/methods ; Esthetics ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/adverse effects/methods ; Mastectomy/methods ; Pectoralis Muscles/*innervation/*surgery ; Peripheral Nerves/*surgery ; Prosthesis Failure ; Reoperation/methods ; Treatment Outcome ; },
abstract = {Breast animation deformity is a known complication of subpectoral implant placement that is usually corrected by repositioning the implant to the prepectoral position. Other less common treatment options include performing the muscle splitting biplanar technique, triple plane technique, neuromodulator injections, and secondary neurotomies via transection of the pectoral muscle. We report a patient with animation deformity successfully treated with direct identification and ablation of the medial and lateral pectoral nerves using selective bipolar electrocautery. The patient is a woman with a history of invasive ductal carcinoma who underwent bilateral mastectomy and breast reconstruction with subpectoral implant placement and autologous fat grafting. Within 1 year of her breast reconstruction, she developed hyperactive pectoralis muscle contraction with resulting distortion of both breasts. Given the disadvantages of repositioning the implant to the prepectoral position and transecting the pectoralis muscles via secondary neurotomy, we chose to directly identify and selectively ablate distal branches of the medial and lateral pectoral nerves. This offers a novel technique for correcting breast animation deformity without transecting the pectoralis muscles, causing muscle atrophy, and preserving the subpectoral implant position.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .},
}
@article {pmid29956094,
year = {2018},
author = {Graff-Baker, AN and Orozco, JIJ and Marzese, DM and Salomon, MP and Hoon, DSB and Goldfarb, M},
title = {Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers.},
journal = {Annals of surgical oncology},
volume = {25},
number = {10},
pages = {3082-3087},
doi = {10.1245/s10434-018-6582-7},
pmid = {29956094},
issn = {1534-4681},
mesh = {Aged ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal, Breast/genetics/pathology/surgery ; Carcinoma, Lobular/genetics/pathology/surgery ; DNA Methylation ; *Epigenomics ; Female ; Follow-Up Studies ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genome, Human ; Humans ; Middle Aged ; Neoplasms, Second Primary/*genetics/pathology/surgery ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Transcriptome ; },
abstract = {BACKGROUND: Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy.<br><br>METHODS: RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n&#x2009;=&#x2009;36) and invasive lobular (ILC, n&#x2009;=&#x2009;40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs.<br><br>RESULTS: Differentially expressed genes were identified in IDC SBCs (n&#x2009;=&#x2009;727) and in ILC SBCs (n&#x2009;=&#x2009;261; Wilcoxon's test; P&#x2009;<&#x2009;0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes.<br><br>CONCLUSIONS: Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations.},
}
@article {pmid29954760,
year = {2018},
author = {Kase, AM and Menke, D and Tan, W},
title = {Breast cancer metastasis to the bladder: a literature review.},
journal = {BMJ case reports},
volume = {2018},
number = {},
pages = {},
pmid = {29954760},
issn = {1757-790X},
mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/drug therapy/*pathology ; *Cancer Survivors ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Cystoscopy ; Estradiol/*analogs &amp; derivatives/therapeutic use ; Fatal Outcome ; Female ; Fulvestrant ; Humans ; Middle Aged ; Receptor, ErbB-2 ; Urinary Bladder Neoplasms/complications/diagnosis/drug therapy/*secondary ; Urinary Bladder, Overactive/*etiology ; },
abstract = {Given the prevalence of breast cancer and the mortality associated with metastatic disease, it is imperative for physicians to not only be aware of common sites but also of rare metastatic destinations such as the bladder. A postmenopausal woman with a medical history of stage 2 invasive ductal carcinoma, oestrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative, in remission for 9 years, presented to her primary care physician with concerns of increased urinary urgency, frequency and incontinence. The patient underwent cystoscopy with biopsy of an area of granulation tissue. Biopsy revealed adenocarcinoma consistent with breast primary. The common sites of metastases from breast cancer are lung, bone and liver. This case is unique where breast cancer was found to metastasise to the bladder. It is important for physicians to consider further investigation when a breast cancer survivor develops urinary symptoms even without haematuria.},
}
@article {pmid29951883,
year = {2018},
author = {Finet, JE and Wiggers, GA},
title = {Pharmacologic Management of Cancer Therapeutics-Induced Cardiomyopathy in Adult Cancer Survivors.},
journal = {Current heart failure reports},
volume = {15},
number = {4},
pages = {270-279},
pmid = {29951883},
issn = {1546-9549},
mesh = {Adult ; *Cancer Survivors ; *Cardiomyopathies/chemically induced/drug therapy/epidemiology ; Cardiovascular Agents/*therapeutic use ; Comorbidity ; Global Health ; Heart Failure/*drug therapy/epidemiology ; Humans ; Neoplasms/*drug therapy/epidemiology ; },
abstract = {PURPOSE OF REVIEW: The number of cancer survivors is exponentially increasing worldwide, due to both advances in cancer detection and treatment strategies, as well as the aging and growth of the population. This decrease in cancer mortality has brought forth a concurrent increase of non-ischemic (toxic) dilated cardiomyopathy in the survivor population, also known as cancer therapeutics-induced cardiomyopathy (CTIC). The optimal pharmacological management for this condition is still elusive, and hence, the focus of this work.<br><br>RECENT FINDINGS: Our review of the literature did not identify any prospective randomized clinical trial of CTIC in adult cancer survivors, neither published nor in progress. However, available data seem to suggest that, when managed with standard guideline-derived medical therapy, the outcomes of CTIC are comparable to that of idiopathic dilated cardiomyopathy (IDC). Nonetheless, the evidence behind this strategy is inadequate. Until new information becomes available, pharmacological management of CTIC must parallel that of IDC. However, implementation of such may be hindered by other cancer therapeutics-induced comorbidities and conditioned by the particular effects of heart failure pharmacotherapy on cancer outcomes. This work succinctly reviews these three areas, in the context of adult cancer survivors.},
}
@article {pmid29946183,
year = {2018},
author = {Krings, G and Chen, YY},
title = {Genomic profiling of metaplastic breast carcinomas reveals genetic heterogeneity and relationship to ductal carcinoma.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {31},
number = {11},
pages = {1661-1674},
doi = {10.1038/s41379-018-0081-z},
pmid = {29946183},
issn = {1530-0285},
mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/*genetics/pathology ; Female ; Gene Expression Profiling ; *Genetic Heterogeneity ; Humans ; Metaplasia ; Middle Aged ; Transcriptome ; Triple Negative Breast Neoplasms/*genetics/pathology ; },
abstract = {Metaplastic breast carcinomas comprise a histologically heterogenous group of tumors. Although most are triple (estrogen/progesterone receptor, HER2) negative, these rare tumors are clinicopathologically distinct from other triple negative carcinomas and may be aggressive with worse chemotherapy responses. On the other hand, metaplastic carcinomas are histologically diverse, which is reflected in gene expression differences among subtypes. Whether metaplastic carcinomas are genetically distinct from other triple negative cancers and whether genetic differences underlie histologic subtypes remains poorly understood. We sequenced 408 cancer-related genes in 28 metaplastic carcinomas, including chondroid matrix-producing carcinomas (n = 10), spindle cell carcinomas (n = 5), and carcinomas with squamous (n = 5), mixed spindle/squamous (n = 5), and mixed metaplastic (n = 3) differentiation. Metaplastic carcinomas were highly enriched for PIK3CA/PIK3R1 (61%) and Ras-Map kinase (25%) pathway aberrations compared to other triple negative carcinomas (TCGA dataset 14%, p < 0.001 and 7%, p = 0.005, respectively) and harbored a high frequency of TP53 (64%) and TERT promoter (25%) mutations, but this varied among subtypes. Chondroid-matrix producing carcinomas lacked PI-3 kinase and Ras-Map kinase aberrations and TERT promoter mutations, compared to 100%, 39%, and 39% of non-matrix-producing tumors, respectively. TERT promoter mutations were enriched (47%) in spindle cell carcinomas and tumors with squamous or spindle/squamous differentiation. Spindle cell carcinomas lacked TP53 mutations, in contrast to other subtypes (78%, p = 0.003). Separate analysis of paired ductal carcinoma in situ and metaplastic carcinoma revealed shared clonality in all cases (n = 8). Activating PI-3 kinase and Ras pathway mutations were early events, and inactivating mutations in tumor suppressors including RB1, CDKN2A, and TP53 were associated with invasion in individual cases. Metaplastic components of two tumors showed genetic progression from separately sequenced paired invasive ductal carcinoma. The findings suggest that metaplastic carcinomas are genetically distinct from other triple negative breast cancers and highlight genetic heterogeneity that broadly correlates with histologic subtype. Heterologous elements progress from associated ductal carcinoma.},
}
@article {pmid29943843,
year = {2018},
author = {Esmaeili, SA and Mahmoudi, M and Rezaieyazdi, Z and Sahebari, M and Tabasi, N and Sahebkar, A and Rastin, M},
title = {Generation of tolerogenic dendritic cells using Lactobacillus rhamnosus and Lactobacillus delbrueckii as tolerogenic probiotics.},
journal = {Journal of cellular biochemistry},
volume = {119},
number = {9},
pages = {7865-7872},
doi = {10.1002/jcb.27203},
pmid = {29943843},
issn = {1097-4644},
mesh = {Adult ; Case-Control Studies ; Cell Culture Techniques ; Cells, Cultured ; Cytokines/genetics/metabolism ; Dendritic Cells/*cytology/immunology/microbiology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/metabolism ; Interleukin-4/pharmacology ; Lactobacillus delbrueckii/immunology/*physiology ; Lacticaseibacillus rhamnosus/immunology/*physiology ; Lupus Erythematosus, Systemic/immunology/*microbiology ; Male ; Monocytes/*cytology/drug effects/immunology/microbiology ; Probiotics ; },
abstract = {Systemic lupus erythematosus (SLE) concurs with excessive uncontrolled inflammatory immune responses that lead to the loss of immune tolerance. Dendritic cells (DCs) are important and determinant immune cells that regulate immune responses. Tolerogenic DCs with regulatory markers and cytokines could induce regulatory immune cells and responses. Tolerogenic probiotics are capable of producing regulatory DCs from monocytes in in vitro conditions. The purpose of this study was to evaluate the effect of Lactobacillus delbrueckii and Lactobacillus rhamnosus on the production of DCs in an in vitro condition. Peripheral blood mononuclear cells were isolated from the healthy and SLE donors. Monocytes were cultured with optimized concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to produce immature DCs (IDCs). An IDC uptake assay was performed, and IDCs of healthy and SLE donors were divided into three subgroups following 48 hours of treatment with GM-CSF and IL-4, along with L. delbrueckii, L. rhamnosus, and mixed probiotics for the production of tolerogenic DCs. The surface expression of Human Leukocyte Antigen-antigen D Related (HLA-DR), CD86, CD80, CD83, CD1a, and CD14 was analyzed using flow cytometry, and the gene expression levels of indoleamine 2,3-dioxygenase (IDO), IL-10, and IL-12 were measured using real-time polymerase chain reaction. We observed significantly reduced expression of costimulatory molecules and other surface markers in the probiotic-induced mature DCs (MDCs) in both healthy and SLE donor groups in comparison with lipopolysaccharide (LPS)-induced MDCs. In addition, the expression of IDO and IL-10 increased, whereas IL-12 decreased significantly in probiotic-induced MDCs compared with LPS-induced MDCs. IDCs and especially mature tolerogenic DC of SLE patients highly expressed IDO. The results of the current study suggested that live probiotics could modify properties of DCs to modulatory cells, which might contribute to the induction of tolerance and renovation of immune hemostasis.},
}
@article {pmid29941485,
year = {2018},
author = {Nagle, AM and Levine, KM and Tasdemir, N and Scott, JA and Burlbaugh, K and Kehm, J and Katz, TA and Boone, DN and Jacobsen, BM and Atkinson, JM and Oesterreich, S and Lee, AV},
title = {Loss of E-cadherin Enhances IGF1-IGF1R Pathway Activation and Sensitizes Breast Cancers to Anti-IGF1R/InsR Inhibitors.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {24},
number = {20},
pages = {5165-5177},
pmid = {29941485},
issn = {1557-3265},
support = {F30 CA203154/CA/NCI NIH HHS/United States ; F31 CA224567/CA/NCI NIH HHS/United States ; R01 CA094118/CA/NCI NIH HHS/United States ; T32 GM008424/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Breast Neoplasms/drug therapy/metabolism/pathology ; Cadherins/genetics/*metabolism ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; *Drug Resistance, Neoplasm ; Drug Synergism ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor I/antagonists &amp; inhibitors/*metabolism ; Mice ; RNA, Small Interfering/genetics ; Receptor, IGF Type 1 ; Receptors, Somatomedin/antagonists &amp; inhibitors/*metabolism ; Signal Transduction/*drug effects ; Xenograft Model Antitumor Assays ; },
abstract = {Purpose: Insulin-like growth factor 1 (IGF1) signaling regulates breast cancer initiation and progression and associated cancer phenotypes. We previously identified E-cadherin (CDH1) as a repressor of IGF1 signaling and in this study examined how loss of E-cadherin affects IGF1R signaling and response to anti-IGF1R/insulin receptor (InsR) therapies in breast cancer.Experimental Design: Breast cancer cell lines were used to assess how altered E-cadherin levels regulate IGF1R signaling and response to two anti-IGF1R/InsR therapies. In situ proximity ligation assay (PLA) was used to define interaction between IGF1R and E-cadherin. TCGA RNA-seq and RPPA data were used to compare IGF1R/InsR activation in estrogen receptor-positive (ER+) invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) tumors. ER+ ILC cell lines and xenograft tumor explant cultures were used to evaluate efficacy to IGF1R pathway inhibition in combination with endocrine therapy.Results: Diminished functional E-cadherin increased both activation of IGF1R signaling and efficacy to anti-IGF1R/InsR therapies. PLA demonstrated a direct endogenous interaction between IGF1R and E-cadherin at points of cell-cell contact. Increased expression of IGF1 ligand and levels of IGF1R/InsR phosphorylation were observed in E-cadherin-deficient ER+ ILC compared with IDC tumors. IGF1R pathway inhibitors were effective in inhibiting growth in ER+ ILC cell lines and synergized with endocrine therapy and similarly IGF1R/InsR inhibition reduced proliferation in ILC tumor explant culture.Conclusions: We provide evidence that loss of E-cadherin hyperactivates the IGF1R pathway and increases sensitivity to IGF1R/InsR targeted therapy, thus identifying the IGF1R pathway as a potential novel target in E-cadherin-deficient breast cancers. Clin Cancer Res; 24(20); 5165-77. ©2018 AACR.},
}
@article {pmid29916548,
year = {2018},
author = {Lan, VTT and Son, HV and Trang, VL and Trang, NT and Phuong, NT and Toan, NL and Duong, PAT},
title = {Methylation profiles of miR34 gene family in Vietnamese patients suffering from breast and lung cancers.},
journal = {Molecular medicine reports},
volume = {18},
number = {2},
pages = {2476-2484},
doi = {10.3892/mmr.2018.9182},
pmid = {29916548},
issn = {1791-3004},
mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics/pathology ; DNA Methylation/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/epidemiology/*genetics/pathology ; MicroRNAs/*genetics ; Middle Aged ; Promoter Regions, Genetic ; Vietnam/epidemiology ; },
abstract = {The three genes encoding small non‑coding microRNA (miR)34a, MIR34b and MIR34c act as tumor‑suppressor genes. Their aberrant expressions regulated by DNA methylation have been frequently found in various types of cancer. In the present study, the DNA promoter methylation profiles of the MIR34 gene family were analyzed using the methylation specific polymerase chain reaction in order to clarify their association with breast and lung cancer, non‑cancerous or normal adjacent tissues. The methylation frequency of MIR34a was significantly higher in breast cancer (49.37%) compared with normal adjacent tissues (30.38%). The methylation frequency of MIR34b/c was 59.49 and 62.03% in breast cancer and normal adjacent tissues, respectively. MIR34a methylation showed a significant concordance with that of MIR34b/c only in breast cancer tissue. MIR34a methylation was significantly associated with cancer and the invasive ductal carcinoma type of breast cancer (P=0.015 and P=0.02, respectively). Methylation frequency of MIR34a and MIR34b/c was 48.42 and 56.84% in lung cancer, and 47.22 and 51.39% in pulmonary diseases, respectively. No significant association was observed between the methylation status of MIR34a and MIR34b/c, and the clinicopathological features of lung cancer or with those of non‑cancerous pulmonary diseases. Promoter methylation of MIR34a and MIR34b/c occurs frequently and concomitantly in breast and lung cancer, as well as in pulmonary diseases tissues, but not in breast normal tissues adjacent to tumor. These results of the present study emphasize the involvement of MIR34 methylation in human diseases, including cancer. Furthermore, MIR34a methylation may be a promising marker for a subtype of breast cancer.},
}
@article {pmid29915849,
year = {2018},
author = {Linjawi, S and AlGaithy, Z and Sindi, S and Hamdi, N and Linjawi, A and Alharbi, M},
title = {Regulation of Lipocalin-2 oncogene and its impact on gene polymorphisms on breast cancer patients in Jeddah, Saudi Arabia.},
journal = {Saudi medical journal},
volume = {39},
number = {6},
pages = {558-563},
pmid = {29915849},
issn = {1658-3175},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Breast Neoplasms/blood/*genetics ; Carcinoma, Ductal, Breast/blood/*genetics ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Genotype ; Humans ; Lipocalin-2/blood/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Saudi Arabia ; Young Adult ; },
abstract = {OBJECTIVES: To identify the impact of Lipocalin-2 (LCN2) gene polymorphisms on breast cancer patients in western Saudi Arabia.<br><br>METHODS: It is a case control study in which blood samples of participants from Medical Reference Clinics and King Abdulaziz University Hospital in Jeddah, Saudi Arabia have been taken between 2014 and 2016. This study recruited 128 participants (50% control, 50% patients) and used Tetra-Primer amplification-refractory mutation system-polymerase chain reaction method for the detection of missense SNP (rs11556770). The study measured LCN2 plasma protein expression by enzyme-linked immunosorbent assay technique.&#xa0;Results: The results have shown that 100% of the genotypes were normal allele (G/G). In contrast, the&#xa0;plasma level of LCN2 was considerably elevated among patients as compared to control (p=0.001), and higher in invasive ductal carcinoma patients (p=0.001). The LCN2 protein expression in plasma level was significantly elevated among patients, particularly who demonstrated invasive ductal carcinoma.&#xa0;Conclusion: There is no significant relationship between breast cancer patients and LCN2 gene polymorphisms &#xa0; (rs11556770).},
}
@article {pmid29906691,
year = {2018},
author = {Sakamoto, S and Tsuruga, Y and Fujii, Y and Shomura, H and Hattori, A and Kazui, K},
title = {Intraductal tubulopapillary neoplasm of the pancreas presenting as recurrent acute pancreatitis: A case report.},
journal = {International journal of surgery case reports},
volume = {48},
number = {},
pages = {122-125},
pmid = {29906691},
issn = {2210-2612},
abstract = {INTRODUCTION: The 2010 World Health Organization classification of intraductal neoplasms of the pancreas includes intraductal tubulopapillary neoplasms (ITPNs) and intraductal papillary mucinous neoplasms, the latter being a rare and new concept. ITPN sometimes cause acute pancreatitis; therefore, distinguishing ITPN from idiopathic acute pancreatitis is important but challenging.<br><br>PRESENTATION OF CASE: We present the case of a 72-year-old male who had recurrent pancreatitis for the past 2 years, his diagnosis was idiopathic acute pancreatitis. He was admitted to our hospital with severe acute pancreatitis and cholangitis due to intrapancreatic bile duct stenosis. After the treatment of cholangitis, contrast-enhanced computed tomography revealed a tumor at the pancreatic head. Endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis of the main pancreatic duct and distal bile duct, and adenocarcinoma was detected using brush cytology of the bile duct stricture and pancreatic juice. The patient was diagnosed with invasive ductal carcinoma and pancreaticoduodenectomy was performed. Histopathological findings revealed dilation of the pancreatic duct, and proliferation of columnar cells and cuboid epithelial cells in the main pancreatic duct of the pancreatic head. Mucus production was poor, and immunostaining results revealed ITPN. The patient is alive and do not exhibit signs of recurrence for 12 months.<br><br>DISCUSSION: ITPNs can cause acute pancreatitis, which can be challenging to preoperatively diagnose. ITPNs presenting as acute pancreatitis are rare, with reported only 5 cases.<br><br>CONCLUSION: It is important to be keep in mind that there is a possibility of ITPN after diagnosis of idiopathic acute pancreatitis.},
}
@article {pmid29904947,
year = {2018},
author = {Dong, C and Liu, Y and Jiang, K and Wang, H and Qu, W and Zhang, C and Liang, R and Gao, Z and Zhao, B and Miao, Q and Shao, S and Wang, L},
title = {The Nogo-B receptor promotes human hepatocellular carcinoma cell growth via the Akt signal pathway.},
journal = {Journal of cellular biochemistry},
volume = {119},
number = {9},
pages = {7738-7746},
pmid = {29904947},
issn = {1097-4644},
support = {R01 HL108938/HL/NHLBI NIH HHS/United States ; },
mesh = {Animals ; Carcinoma, Hepatocellular/genetics/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Gene Knockdown Techniques ; Hep G2 Cells ; Humans ; Liver Neoplasms/genetics/metabolism/*pathology ; Male ; Mice ; Neoplasm Transplantation ; Phosphorylation ; Proto-Oncogene Proteins c-akt/*metabolism ; Receptors, Cell Surface/*genetics/*metabolism ; Signal Transduction ; },
abstract = {Nogo-B receptor (NgBR) is a type I receptor with a single transmembrane domain and specifically binds to ligand Nogo-B. A previous study demonstrated that NgBR was highly expressed in human breast invasive ductal carcinoma and promoted epithelial-mesenchymal transition in breast tumor cells. Our recent work found that NgBR expression was associated with a poor prognosis in human patients with hepatocellular carcinoma (HCC). Here, we elucidate that the increased expression of NgBR contributes toward the increased cell growth of human HCC cells both in vitro and in vivo. Cell viability and clonogenic survival analysis results demonstrated that knockdown of NgBR inhibits the cell growth in human HCC cells, which correlates with a reduction in the phosphorylation of Akt levels. Furthermore, overexpression of NgBR by the cotransfected pIRES-NgBR plasmid together with NgBR siRNA in human HCC cells can rescue impaired phosphorylation of Akt levels in NgBR knockdown human HCC cells. In addition, cell viability analyses showed that NgBR overexpression can rescue the cell growth inhibition presented in human HCC NgBR knockdown cells. Taken together, our results suggest that NgBR potentially acts as an oncogene in HCC by increasing Akt activity. Thus, NgBR may represent a new potential diagnostic and therapeutic target for the treatment of HCC.},
}
@article {pmid29889862,
year = {2018},
author = {Awungafac, G and Amin, ET and Fualefac, A and Takah, NF and Agyingi, LA and Nwobegahay, J and Ondoa, P and Njukeng, PA},
title = {Viral load testing and the use of test results for clinical decision making for HIV treatment in Cameroon: An insight into the clinic-laboratory interface.},
journal = {PloS one},
volume = {13},
number = {6},
pages = {e0198686},
pmid = {29889862},
issn = {1932-6203},
mesh = {Adult ; Aged ; Anti-Retroviral Agents/pharmacology/*therapeutic use ; Cameroon ; Decision Making ; HIV/drug effects ; HIV Infections/*drug therapy/virology ; Humans ; Middle Aged ; Retrospective Studies ; Treatment Failure ; *Viral Load/drug effects ; Young Adult ; },
abstract = {BACKGROUND: The viral load (VL) in patients receiving antiretroviral therapy (ART) is the best predictor of treatment outcome. The anticipated benefits of VL monitoring depend on the actual uptake of VL test results for clinical decisions. The objective of this study was to assess the uptake and utilization of VL test results for clinical decisions on HIV treatment in Cameroon, from 2013 to 2017.<br><br>METHODS: This was a retrospective cohort analysis of data from files of patients receiving ART at Buea, Limbe, Bamenda and Bafoussam regional hospital HIV treatment centers. A simple random pick of six file blocks was performed in each shelf that corresponded to a year of initiation, and the contents of all selected files were reviewed and the information needed for the study entered a structured questionnaire. The data collected was recorded in Epi Info (version 7.1.5.2), and analyzed using SATA (version 12.1; StataCorp LP).<br><br>RESULTS: Eight hundred and thirty files were reviewed. The mean duration on ART was 39.4&#xb1;12 months. Viral load testing uptake was 24.33% and only one VL test had been done by all patients. Approximately 65% of the patients did the first VL after more than 24 months on ART. The median turnaround (TAT) time for VL testing was 6 days (Interquartile range (IQR) 3-7days). Among 201 patients who did a VL test, 94.55% had VL suppression (&#x2264;1000copies/mm3). Approximately 54% of the patients with virologic failure were switched to a second-line regimen.<br><br>CONCLUSIONS: The uptake of viral load testing is low in North West, South West and West Regions of Cameroon. The current TAT for VL testing is plausible. The rate of switch to second line regimen is low. It is time to strengthen the scale up of VL testing and improve the rate of switch to second-line regimen in Cameroon.},
}
@article {pmid29886591,
year = {2018},
author = {Liu, JY and Zou, LP and Wu, HJ and Zhao, ZH and Zhang, ZG},
title = {[Effects of ubiquitin-specific proteases 2-69 on proliferation of breast cancer cells].},
journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology},
volume = {47},
number = {6},
pages = {455-460},
doi = {10.3760/cma.j.issn.0529-5807.2018.06.013},
pmid = {29886591},
issn = {0529-5807},
mesh = {Blotting, Western ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; *Cell Proliferation ; Cyclin D1/metabolism ; Endopeptidases/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; Neoplasm Proteins/genetics/*metabolism ; RNA, Messenger/metabolism ; Transfection ; Tumor Cells, Cultured ; Ubiquitin Thiolesterase ; },
abstract = {Objective: To investigate the expression and significance of ubiquitin-specific proteases 2-69(USP2-69) in invasive ductal carcinoma of breast. Methods: Twenty-four cases of human breast tissue with invasive ductal carcinoma diagnosed at Huanshan Hospital, Fudan University from 2013 to 2015 were collected, and the expression of USP2-69 mRNA and protein was detected by molecular hybridization, Western blot and immunohistochemistry. USP2-69 was over-expressed in cultured human breast cancer cell line MCF-7 by USP2-69 plasmid transfection. The cellular proliferative activity was investigated in vitro. Results: The USP2-69 mRNA and protein were highly expressed in breast invasive ductal carcinoma, compared to adjacent normal tissues (P<0.01). Ki-67 protein expression was also increased in cases with high USP2-69 protein level. Western blot showed significantly higher USP2-69 protein level in cancer tissue compared to the adjacent normal tissue. In the cultured tumor cells, there was increased S phase fraction, cellular proliferation rate, flat positive clones, cyclin D1 expression and decreased p27 expression in USP2-69-transfected MCF-7 cells. Conclusions: USP2-69 is over-expressed in breast invasive ductal carcinoma, and is closely related to proliferation promoting effects. The data provide an important experimental basis for further study on the molecular mechanism of breast cancer cell proliferation.},
}
@article {pmid29884570,
year = {2019},
author = {Campo-Sánchez, SM and Camargo-Trillos, J and Calle-Ramírez, JA and Gómez-Wolff, LR and Sánchez-Patiño, LA and García-García, HI},
title = {Colorectal cancer survival at an oncologic center in Colombia. A historic cohort study.},
journal = {Revista de gastroenterologia de Mexico (English)},
volume = {84},
number = {2},
pages = {174-184},
doi = {10.1016/j.rgmx.2018.04.002},
pmid = {29884570},
issn = {2255-534X},
mesh = {Adenocarcinoma/mortality/therapy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Colombia/epidemiology ; Colorectal Neoplasms/*mortality/therapy ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; *Oncology Service, Hospital ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Analysis ; Young Adult ; },
abstract = {INTRODUCTION AND AIMS: In Colombia, cancer of the colon is the third most frequent cancer in relation to incidence and mortality. Five-year survival depends on stage at diagnosis, albeit that rate is not known for the country. The aim of the present study was to characterize the overall survival and disease-free survival rates in an adult population with colorectal cancer treated at an oncology center in Medellín, Colombia.<br><br>MATERIALS AND METHODS: A retrospective cohort study was conducted. The case records of patients with a histologic diagnosis of colorectal cancer, seen within the time frame of 2011 and 2015, were reviewed. The overall survival and disease-free survival curves were calculated using the Kaplan-Meier method.<br><br>RESULTS: A total of 824 (54.9%) patients with cancer of the colon and 676 (45.1%) with cancer of the rectum were treated. Mean patient age was 63.3 years, female sex predominated (56.3%), and 98.1% of the tumors were adenocarcinomas. The majority of the lesions were stage iii (31.9% in the colon and 35.5% in the rectum) at the time of diagnosis. Surgery was the most frequent treatment in the colon (85.2%) and radiotherapy was the most frequent in the rectum (75.4%). Overall survival at the median follow-up (27.3 months) was 66.7% for cancer of the colon and 63.9% for cancer of the rectum. Disease-free survival at the median follow-up (18.6 months in colon and 14.9 in rectum) was 72.5 and 68.9%, respectively.<br><br>CONCLUSIONS: The clinical characteristics and treatment of patients were similar to those found in other studies. Two-year survival was higher than in other Colombian reports and 5-year survival was lower than that observed in developed countries.},
}
@article {pmid29879758,
year = {2019},
author = {Choi, CW and Jeong, MH and Park, YS and Son, CH and Lee, HR and Koh, EK},
title = {Combination Treatment of Stereotactic Body Radiation Therapy and Immature Dendritic Cell Vaccination for Augmentation of Local and Systemic Effects.},
journal = {Cancer research and treatment},
volume = {51},
number = {2},
pages = {464-473},
pmid = {29879758},
issn = {2005-9256},
support = {50601-2017//Ministry of Science and Technology/ ; 50595-2018//Ministry of Science and Technology/ ; },
mesh = {Animals ; Antigen Presentation/immunology ; Antigen-Presenting Cells/immunology/metabolism ; Cancer Vaccines/*administration &amp; dosage/*immunology ; Cell Line, Tumor ; Combined Modality Therapy ; Cytokines/metabolism ; Dendritic Cells/*immunology/metabolism ; Disease Models, Animal ; Humans ; Immunotherapy ; Kaplan-Meier Estimate ; Mice ; Neoplasms/*immunology/mortality/pathology/*therapy ; *Radiosurgery/methods ; Tumor Burden ; },
abstract = {PURPOSE: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs).<br><br>METHODS AND MATERIALS: CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system.<br><br>RESULTS: Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group.<br><br>CONCLUSION: The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.},
}
@article {pmid29879027,
year = {2018},
author = {Yin, L and Li, J and Wei, Y and Ma, D and Sun, Y and Sun, Y},
title = {Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient receiving tamoxifen: A case report and literature review.},
journal = {Medicine},
volume = {97},
number = {23},
pages = {e10900},
pmid = {29879027},
issn = {1536-5964},
mesh = {Antineoplastic Agents, Hormonal/*adverse effects/therapeutic use ; Breast/pathology ; Breast Neoplasms/drug therapy/*pathology ; Endometrial Neoplasms/*pathology ; Endometrium/pathology ; Fatal Outcome ; Female ; Humans ; Laparotomy/methods ; Mastectomy/methods ; Middle Aged ; Ovarian Neoplasms/chemically induced/*pathology ; Ovary/pathology ; Small Cell Lung Carcinoma/chemically induced/*pathology ; Tamoxifen/*adverse effects/therapeutic use ; Tomography, X-Ray Computed ; },
abstract = {RATIONALE: Small cell carcinoma of the ovary (SCCO) is a rare and aggressive extra-pulmonary variant of small cell tumors of uncertain histogenesis. The pathogenesis and optimal treatment of SCCO is unclear. We present a very rare case of a synchronous primary ovarian small cell carcinoma and endometrioid adenocarcinoma of the uterus in a patient after 2 years of tamoxifen treatment for breast cancer. This is the first such report in the English literature.<br><br>PATIENT CONCERNS: A 46-year-old woman had a history of left breast cancer that was treated with a simple mastectomy and sentinel lymph node biopsy in 2013. The post-operative pathology was invasive ductal carcinoma of the left breast. she had been taking tamoxifen for 2 years. The patient underwent an exploratory laparotomy to reduce the tumor burden, improve bowel compression symptoms, and promote defecation in 2015. The post-operative pathology revealed a rare, simultaneous occurrence of two tumors (endometrial adenocarcinoma and SCCO [pulmonary type]).<br><br>DIAGNOSES: Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient.<br><br>INTERVENTIONS: The patient received 3 courses of chemotherapy after operation. The effect was not apparent and the general health status was poor.<br><br>OUTCOMES: The patient died of progressive disease 7 months post-operatively.<br><br>LESSONS: The present case suggests that tamoxifen use might be among many etiologic factors in SCCO development. Despite its rarity, SCCO requires a high degree of attention in clinical work because it is an aggressive tumor that has a poor prognosis.},
}
@article {pmid29875947,
year = {2018},
author = {Kharmoum, S and Soughi, M},
title = {[Toxidermy mimicking acute chemotherapy-induced lupus erythematosus].},
journal = {The Pan African medical journal},
volume = {29},
number = {},
pages = {66},
doi = {10.11604/pamj.2018.29.66.6083},
pmid = {29875947},
issn = {1937-8688},
mesh = {Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*adverse effects ; Breast Neoplasms/drug therapy ; Capecitabine/administration &amp; dosage ; Carcinoma, Ductal, Breast/drug therapy ; Docetaxel ; Female ; Humans ; Lichenoid Eruptions/*diagnosis/immunology ; Lupus Erythematosus, Cutaneous/chemically induced/*diagnosis ; Middle Aged ; Skin Diseases/*diagnosis/immunology ; Taxoids/administration &amp; dosage ; },
abstract = {Acute chemotherapy-induced lupus erythematosus (ALE) is rare. A few cases have been reported in the literature criminalizing capecitabine, paclitaxel and docetaxel. We report the case of a 64-year old female patient without a history of autoimmune diseases or of drug allergy followed up for invasive ductal carcinoma in the right breast immediately metastatized to the liver and to the lymph nodes. After AC60 first line chemotherapy regimen (a total of 6 cycles), she was treated with docetaxel at a dose of 100 mg/m[2]. After 5 cycles, she had diffuse erythematous lesions on both hands, forearms, cheeks and on the peribuccal area. She underwent corticosteroid therapy with sun protection and could continue the same chemotherapy until the eighth cycle. Patient's evolution was marked by the progression of the disease. She was treated with capecitabine at a dose of 1250 mg/m[2] twice a day. After six cycles she had erythematosquamous and itchy patches on the face resembling the wings of a butterfly (Panel A, Panel B) with oral ulceration and digital pulpitis (Panel C). This initially suggested acute chemotherapy-induced cutaneous lupus erythematosus. Biopsy suggested lichenoid toxidermia. Immunological assessment was performed to exclude chemotherapy-induced cutaneous lupus erythematosus, which showed anti-native DNA antibodies and negative anti-histone antibodies. Anti-nuclear antibody test is positive at 320; this test may be positive in 50-70% of patients with breast cancer, ENT or lymphoma. In the light of these results the diagnosis of toxidermia was the more likely.},
}
@article {pmid29874679,
year = {2018},
author = {Kopf, S and Groener, JB and Kender, Z and Fleming, T and Brune, M and Riedinger, C and Volk, N and Herpel, E and Pesta, D and Szendrödi, J and Wielpütz, MO and Kauczor, HU and Katus, HA and Kreuter, M and Nawroth, PP},
title = {Breathlessness and Restrictive Lung Disease: An Important Diabetes-Related Feature in Patients with Type 2 Diabetes.},
journal = {Respiration; international review of thoracic diseases},
volume = {96},
number = {1},
pages = {29-40},
doi = {10.1159/000488909},
pmid = {29874679},
issn = {1423-0356},
mesh = {Adult ; Aged ; Diabetes Complications/epidemiology ; Diabetes Mellitus, Type 2/*complications ; Dyspnea/epidemiology/*etiology ; Female ; Humans ; Incidence ; Lung Diseases, Interstitial/diagnosis/*etiology ; Male ; Middle Aged ; Prediabetic State/complications ; Respiratory Function Tests ; Tomography, X-Ray Computed ; Walk Test ; },
abstract = {BACKGROUND: Diabetes mellitus is a significant comorbidity of interstitial lung disease (ILD).<br><br>OBJECTIVES: The aim of this study was to investigate the incidence of restrictive lung disease (RLD) and ILD in patients with prediabetes and type 2 diabetes (T2D).<br><br>METHODS: Forty-eight nondiabetics, 68 patients with prediabetes, 29 newly diagnosed T2D, and 110 patients with long-term T2D were examined for metabolic control, diabetes-related complications, breathlessness, and lung function. Five participants with T2D, breathlessness, and RLD underwent multidetector computed tomography (MDCT) and a Six-Minute Walk Test (6MWT). Lung tissue from 4 patients without diabetes and from 3 patients with T2D was histologically examined for presence of pulmonary fibrosis.<br><br>RESULTS: Breathlessness in combination with RLD was significantly increased in patients with prediabetes and T2D (p < 0.01). RLD was found in 9% of patients with prediabetes, in 20% of patients with newly diagnosed T2D, and in 27% of patients with long-term T2D. Thus, patients with long-term T2D had an increased risk of RLD (OR 5.82 [95% CI 1.71-20.5], p < 0.01). RLD was significantly associated with glucose metabolism and albuminuria (p < 0.01); furthermore, presence of nephropathy increased the risk of RLD (OR 8.57 [95% CI 3.4-21.9], p < 0.01) compared to nondiabetics. MDCT revealed ILD in 4 patients, the 6MWT correlated with the extent of ILD, and histological analysis showed fibrosing ILD in patients with T2D.<br><br>CONCLUSIONS: This study demonstrates increased breathlessness and a high prevalence of RLD in patients with T2D, indicating an association between diabetes and fibrosing ILD.},
}
@article {pmid29870876,
year = {2018},
author = {Mills, MN and Yang, GQ and Oliver, DE and Liveringhouse, CL and Ahmed, KA and Orman, AG and Laronga, C and Hoover, SJ and Khakpour, N and Costa, RLB and Diaz, R},
title = {Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {98},
number = {},
pages = {48-58},
doi = {10.1016/j.ejca.2018.04.011},
pmid = {29870876},
issn = {1879-0852},
mesh = {Adult ; Aged ; Carcinoma, Adenoid Cystic/*pathology/therapy ; Carcinoma, Ductal, Breast/*parasitology/therapy ; Carcinoma, Lobular/*pathology/therapy ; Databases, Factual/statistics &amp; numerical data ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; Prognosis ; Triple Negative Breast Neoplasms/*pathology/therapy ; United States ; },
abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC.<br><br>METHODS: A total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC)&#xa0;or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan-Meier analysis, log-rank testing&#xa0;and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome.<br><br>RESULTS: MBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%)&#xa0;and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p&#xa0;<&#xa0;0.001). TNBC predicted an inferior OS in IDC (p&#xa0;<&#xa0;0.001) and ILC (p&#xa0;<&#xa0;0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%)&#xa0;and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p&#xa0;<&#xa0;0.001). TNBC patients with MBC (HR 1.39, p&#xa0;<&#xa0;0.001), MedBC (HR 0.42, p&#xa0;<&#xa0;0.001)&#xa0;and ACC (HR 0.32, p&#xa0;=&#xa0;0.003) differed significantly in OS when compared to IDC.<br><br>CONCLUSION(S): Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes&#xa0;and thus, has the potential to aid in the development of optimum personalised treatments.},
}
@article {pmid29867980,
year = {2018},
author = {Alamri, A and Rahman, R and Zhang, M and Alamri, A and Gounni, AS and Kung, SKP},
title = {Semaphorin-3E Produced by Immature Dendritic Cells Regulates Activated Natural Killer Cells Migration.},
journal = {Frontiers in immunology},
volume = {9},
number = {},
pages = {1005},
pmid = {29867980},
issn = {1664-3224},
mesh = {Animals ; Cell Communication/immunology ; Cells, Cultured ; Cytoskeletal Proteins ; Dendritic Cells/*immunology ; Gene Expression Regulation ; Glycoproteins/*genetics/immunology ; Immunity, Innate ; Killer Cells, Natural/*cytology ; *Lymphocyte Activation ; Membrane Proteins/*genetics/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Semaphorins ; Signal Transduction/immunology ; },
abstract = {Natural killer (NK) cells and dendritic cells (DCs) are two innate immune cells that are critical in regulating innate and adaptive immunity. Cellular functions and migratory responses of NK or DC can be further regulated in NK-DC crosstalk that involves multiple cytokine signals and/or direct cell-cell contacts. Semaphorin-3E (Sema-3E) is a member of a large family of Semaphorin proteins that play diverse regulatory functions in different biological systems upon its binding to the cognate receptors. However, possible role(s) of Sema-3E on the regulation of NK-cell functions has not been elucidated. Here, we first demonstrated that DC and NK cells expressed Sema-3E and its receptors, respectively. To formally address the importance of DC-derived Sema-3E in regulating NK-cell migration, we compared in vitro migratory responses of activated NK cells (aNKs) toward different conditioned media of DCs (immature, lipopolysaccharide- or Poly I:C-stimulated) derived from Sema-3E[+/+] or Sema-3E[-/-] mice. We observed that aNKs exhibited enhanced migrations toward the conditioned medium of the immature Sema-3E[-/-] DC, when compared with that of the immature Sema-3E[+/+] DC. Addition of exogenous recombinant Sema-3E to the conditioned medium of the Sema-3E[-/-] immature DC (iDC) abrogated such enhanced NK-cell migration. Our current work revealed a novel role of Sema-3E in limiting NK-cell migrations toward iDC in NK-DC crosstalk.},
}
@article {pmid29860265,
year = {2018},
author = {Guo, X and Li, J and Zhang, H and Liu, H and Liu, Z and Wei, X},
title = {Relationship Between ADAMTS8, ADAMTS18, and ADAMTS20 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) Expressions and Tumor Molecular Classification, Clinical Pathological Parameters, and Prognosis in Breast Invasive Ductal Carcinoma.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {24},
number = {},
pages = {3726-3735},
pmid = {29860265},
issn = {1643-3750},
mesh = {ADAMTS Proteins/*biosynthesis/genetics ; Adult ; Aged ; Breast Neoplasms/classification/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/classification/genetics/*metabolism/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptors, Estrogen/metabolism ; Transcriptome ; },
abstract = {BACKGROUND The aim of this study was to investigate the correlations between ADAMTSs expression and breast invasive ductal carcinoma (IDC), and to offer a theoretical basis for novel treatment methods for IDC patients. MATERIAL AND METHODS Non-proliferative catheter of breast fibroadenoma (FA) and IDC were used as the normal control and experimental group, respectively. Immunohistochemical (IHC) staining and Western blot (WB) analysis was used to assess protein expression levels of ADAMTS8, ADAMTS18, and ADAMTS20 in both FA and IDC tissues. The results of IHC, the relationship between the protein expression and the tumor molecular classification, and clinical pathological parameters were all evaluated. RESULTS IHC and WB results showed that the expression of ADAMTS8/18 in IDC samples was higher than in FA samples, while the expression of ADAMTS20 in IDC samples was lower than that in FA samples. According to the results of WB, the level of ADAMTS8 was higher in the HER2+ group than in the HER2- group and FA group. The expression of ADAMTS18 in the HR+ (including ER+ and PR+) group was significantly higher than in the HR- group and FA group. The expression of ADAMTS18 protein was also higher in the Ki67+ group than in the Ki67- group. ADAMTS20 was higher in HER2+ IDC compared with the basal subtype of IDC. CONCLUSIONS ADAMTS8/18/20 levels were not significantly correlated to the molecular subtype of IDC. ADAMTS18/20 was significantly associated with histological grade of IDC. ADAMTS8 may predict poor prognosis results of IDC patients.},
}
@article {pmid29848684,
year = {2018},
author = {Rusak, A and Jablonska, K and Piotrowska, A and Grzegrzolka, J and Nowak, A and Wojnar, A and Dziegiel, P},
title = {The Role of CHI3L1 Expression in Angiogenesis in Invasive Ductal Breast Carcinoma.},
journal = {Anticancer research},
volume = {38},
number = {6},
pages = {3357-3366},
doi = {10.21873/anticanres.12602},
pmid = {29848684},
issn = {1791-7530},
mesh = {Antigens, CD34/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Chitinase-3-Like Protein 1/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic/genetics/*metabolism/pathology ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor C/metabolism ; Vascular Endothelial Growth Factor D/metabolism ; },
abstract = {BACKGROUND/AIM: An increased level of chitinase 3 like 1 protein (CHI3L1) expression is observed in patients with cancer and may have potential prognostic value. The aim of this study was to evaluate the role of CHI3L1 in angiogenesis in invasive ductal breast carcinoma (IDC) (n=110).<br><br>MATERIALS AND METHODS: Immunohistochemistry was used to assess the expression of CHI3L1, CD31, CD34, vascular endothelial growth factor (VEGFA, VEGFC and VEGFD). Real-time polymerase chain reaction and western blot were used to determine the level of CHI3L1 mRNA and protein.<br><br>RESULTS: Immunohistochemistry demonstrated positive correlation between CHI3L1 expression and angiogenesis markers: CD31 (r=0.34, p=0.0003), CD34 (r=0.24, p=0.012), VEGFD (r=0.24, p=0.013). Higher CHI3L1 expression in estrogen receptor-negative (p=0.041) and progesterone receptor-negative (p=0.014) cancer was observed. Higher CHI3L1 expression was reported in cancer tissues in comparison to non-malignant breast lesions.<br><br>CONCLUSION: These results suggest a potential role of CHI3L1 in angiogenesis in IDC and may suggest its involvement in cancer progression.},
}
@article {pmid29804148,
year = {2018},
author = {Santangelo, G and Bisecco, A and Trojano, L and Sacco, R and Siciliano, M and d'Ambrosio, A and Della Corte, M and Lavorgna, L and Bonavita, S and Tedeschi, G and Gallo, A},
title = {Cognitive performance in multiple sclerosis: the contribution of intellectual enrichment and brain MRI measures.},
journal = {Journal of neurology},
volume = {265},
number = {8},
pages = {1772-1779},
pmid = {29804148},
issn = {1432-1459},
mesh = {Adolescent ; Adult ; Atrophy ; Brain/*diagnostic imaging ; Cognition Disorders/diagnostic imaging/etiology ; *Cognitive Reserve ; Cross-Sectional Studies ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/complications/*diagnostic imaging/*psychology ; Organ Size ; Young Adult ; },
abstract = {Cognitive reserve (CR) is a construct that originates from the observation of poor correspondence between brain damage and clinical symptoms. The aim of the study was to investigate the association between cognitive reserve (CR), brain reserve (BR) and cognitive functions and to evaluate whether CR might attenuate/moderate the negative impact of brain atrophy and lesion load on cognitive functions in multiple sclerosis (MS). To achieve these aims, ninety-eight relapsing-remitting MS patients underwent the brief repeatable battery of neuropsychological tests and Stroop test (ST). CR was assessed by vocabulary-based estimate of lifetime intellectual enrichment. All patients underwent a 3T MRI to assess T2-lesion load and atrophy measures, including normalized gray matter and white matter (nWMV) volumes. The BR was evaluated by maximal lifetime brain volume expressed by intracranial volume (ICV). Hierarchical regressions were used to investigate whether higher BR and/or CR is related to better cognitive performances after controlling for potentially confounding factors. The ICV was not associated with any cognitive tests. Intellectual enrichment was positively associated with performance on tests assessing memory, attention and information processing speed, verbal fluency and inhibitory control. Significant relationship between nWMV and ST was moderated by intellectual enrichment. In conclusion, the findings suggested that CR seems to mitigate cognitive dysfunction in MS patients and can reduce the negative impact of brain atrophy on inhibitory control, relevant for integrity of instrumental activities of daily living.},
}
@article {pmid29804074,
year = {2018},
author = {Schellenberg, AE and Wood, ML and Baniak, N and Hayes, P},
title = {Metastatic ductal carcinoma of the breast to colonic mucosa.},
journal = {BMJ case reports},
volume = {2018},
number = {},
pages = {},
pmid = {29804074},
issn = {1757-790X},
mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*secondary ; Colonic Neoplasms/diagnosis/*secondary ; Colonoscopy ; Female ; Humans ; Incidental Findings ; Intestinal Mucosa/pathology ; Rectal Neoplasms/diagnosis/*secondary ; },
abstract = {Breast cancer is the most common malignancy among women, while invasive ductal carcinoma is the most common type of invasive breast cancer. Metastatic spread to the colon and rectum in breast cancer is rare. This report describes a case of a 69-year-old woman with metastatic ductal breast cancer to the rectosigmoid, presenting as an incidental finding on screening colonoscopy. The breast carcinoma was first diagnosed 2 years prior. Colonic biopsies from colonoscopy confirmed metastatic adenocarcinoma consistent with a breast primary. Ultimately her clinical condition worsened as she developed malignant ascites, a small bowel obstruction, and new bone metastases, and the patient succumbed to her illness. Cases of metastatic breast cancer to the gastrointestinal tract have predominantly been lobular breast carcinoma. Increased awareness of colonic metastasis may lead to more accurate diagnosis and earlier systemic treatment.},
}
@article {pmid29802469,
year = {2018},
author = {Di Oto, E and Biserni, GB and Varga, Z and Morandi, L and Cucchi, MC and Masetti, R and Foschini, MP},
title = {X chromosome gain is related to increased androgen receptor expression in male breast cancer.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {473},
number = {2},
pages = {155-163},
pmid = {29802469},
issn = {1432-2307},
support = {Fundamentally Oriented Funds for Research - RFO//Universit&#xe0; di Bologna/ ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Chromosomes, Human, X/genetics ; Gene Amplification ; Genes, X-Linked/*genetics ; Humans ; Male ; Middle Aged ; Receptors, Androgen/biosynthesis/*genetics ; *Sex Chromosome Aberrations ; },
abstract = {X chromosome gain has been previously described in male breast cancer (MBC). Androgen receptor (AR) gene is located on X chromosome. The aim of this study was to investigate the role of the X chromosome gain in the development of MBC and its relation with AR gene copy number and expression.The X chromosome status was assessed in 66 cases of male invasive and in situ duct breast carcinoma, in 34 cases of gynecomastia associated with cancer, and in 11 cases of tumor-free gynecomastia. Cases were tested by fluorescence in situ hybridization (FISH) to assess the X chromosome status and AR amplification. AR expression was studied by immunohistochemistry (IHC). In addition, AR methylation status was assessed.X chromosome gain was observed in 74.7% of invasive duct carcinoma, in 20.6% of in situ duct carcinoma, and in 14.6% of gynecomastia when associated with cancer, while all cases of tumor-free gynecomastia showed wild X chromosome asset. AR gene copy number when increased paralleled the number of X chromosomes. AR IHC expression was observed in 100% of MBC tested. AR gene methylation status revealed low level or absence of methylation.These data suggest that X chromosome can play a role in the neoplastic transformation of male breast epithelium. X chromosome gain is paralleled by AR gene polysomy. Polysomic AR genes show low methylation levels and high AR protein expression on IHC. These data should be taken into consideration for MBC treatment planning.},
}
@article {pmid29772102,
year = {2018},
author = {Zhao, J and Sun, G and Liao, B and Zhang, X and Armstrong, CM and Yin, X and Liu, J and Chen, J and Yang, Y and Zhao, P and Tang, Q and Wang, Z and Chen, Z and Li, X and Wei, Q and Li, X and Chen, N and Gao, AC and Shen, P and Zeng, H},
title = {Novel nomograms for castration-resistant prostate cancer and survival outcome in patients with de novo bone metastatic prostate cancer.},
journal = {BJU international},
volume = {122},
number = {6},
pages = {994-1002},
doi = {10.1111/bju.14398},
pmid = {29772102},
issn = {1464-410X},
mesh = {Aged ; Bone Neoplasms/drug therapy/metabolism/*secondary ; Humans ; Male ; Models, Statistical ; *Nomograms ; Prostate-Specific Antigen/analysis ; Prostatic Neoplasms, Castration-Resistant/metabolism/mortality/*pathology ; Survival Analysis ; },
abstract = {OBJECTIVES: To develop nomograms predicting the incidence of castration-resistant prostate cancer (CRPC) and overall survival (OS) for de novo metastatic prostate cancer (PCa).<br><br>PATIENTS AND METHODS: Data from 449 patients with de novo metastatic PCa were retrospectively analysed. Patients were randomly divided into a training (n = 314, 70%) and a validation cohort (n = 135, 30%). Predictive factors were selected using a Cox proportional hazards model and were further used for building predictive models. The outcomes were incidence of CRPC and OS.<br><br>RESULTS: Predictive factors included: Gleason score (GS), intraductal carcinoma of the prostate (IDC-P), Eastern Cooperative Oncology Group status, and alkaline phosphatase, haemoglobin and prostate-specific antigen levels. IDC-P and GS were the strongest prognosticators for both the incidence of CRPC and OS. Nomograms for predicting CRPC and OS had an internal validated concordance index of 0.762 and 0.723, respectively. Based on the &#x3b2; coefficients of the final model, risk classification systems were constructed. For those with favourable, intermediate and poor prognosis, the median time to CRPC was 62.6, 28.0 and 13.0&#xa0;months (P < 0.001), respectively; and the median OS was not reached, 55.0 and 33.0&#xa0;months, respectively (P < 0.001).<br><br>CONCLUSIONS: We developed two novel nomograms to predict the incidence of CRPC and OS for patients with de novo metastatic PCa. These tools may assist in physician decision-making and the designing of clinical trials.},
}
@article {pmid29760696,
year = {2018},
author = {Cougoule, C and Lastrucci, C and Guiet, R and Mascarau, R and Meunier, E and Lugo-Villarino, G and Neyrolles, O and Poincloux, R and Maridonneau-Parini, I},
title = {Podosomes, But Not the Maturation Status, Determine the Protease-Dependent 3D Migration in Human Dendritic Cells.},
journal = {Frontiers in immunology},
volume = {9},
number = {},
pages = {846},
pmid = {29760696},
issn = {1664-3224},
mesh = {Cell Differentiation ; *Cell Movement ; Cells, Cultured ; Chemokines/immunology ; Dendrites/immunology ; Dendritic Cells/*cytology/enzymology ; Endopeptidases/*metabolism ; Humans ; Macrophages/immunology ; Podosomes/*immunology ; Toll-Like Receptors/immunology ; rho-Associated Kinases/immunology ; },
abstract = {Dendritic cells (DC) are professional Antigen-Presenting Cells scattered throughout antigen-exposed tissues and draining lymph nodes, and survey the body for pathogens. Their ability to migrate through tissues, a 3D environment, is essential for an effective immune response. Upon infection, recognition of Pathogen-Associated Molecular Patterns (PAMP) by Toll-like receptors (TLR) triggers DC maturation. Mature DC (mDC) essentially use the protease-independent, ROCK-dependent amoeboid mode in vivo, or in collagen matrices in vitro. However, the mechanisms of 3D migration used by human immature DC (iDC) are still poorly characterized. Here, we reveal that human monocyte-derived DC are able to use two migration modes in 3D. In porous matrices of fibrillar collagen I, iDC adopted the amoeboid migration mode. In dense matrices of gelled collagen I or Matrigel, iDC used the protease-dependent, ROCK-independent mesenchymal migration mode. Upon TLR4 activation by LPS, mDC-LPS lose the capacity to form podosomes and degrade the matrix along with impaired mesenchymal migration. TLR2 activation by Pam3CSK4 resulted in DC maturation, podosome maintenance, and efficient mesenchymal migration. Under all these conditions, when DC used the mesenchymal mode in dense matrices, they formed 3D podosomes at the tip of cell protrusions. Using PGE2, known to disrupt podosomes in DC, we observed that the cells remained in an immature status and the mesenchymal migration mode was abolished. We also observed that, while CCL5 (attractant of iDC) enhanced both amoeboid and mesenchymal migration of iDC, CCL19 and CCL21 (attractants of mDC) only enhanced mDC-LPS amoeboid migration without triggering mesenchymal migration. Finally, we examined the migration of iDC in tumor cell spheroids, a tissue-like 3D environment. We observed that iDC infiltrated spheroids of tumor cells using both migration modes. Altogether, these results demonstrate that human DC adopt the mesenchymal mode to migrate in 3D dense environments, which relies on their capacity to form podosomes independent of their maturation status, paving the way of further investigations on in vivo DC migration in dense tissues and its regulation during infections.},
}
@article {pmid29759595,
year = {2018},
author = {Da Ros, L and Moretti, A and Querzoli, P and Pedriali, M and Lupini, L and Bassi, C and Carcoforo, P and Negrini, M and Frassoldati, A},
title = {HER2-Positive Lobular Versus Ductal Carcinoma of the Breast: Pattern of First Recurrence and Molecular Insights.},
journal = {Clinical breast cancer},
volume = {18},
number = {5},
pages = {e1133-e1139},
doi = {10.1016/j.clbc.2018.04.006},
pmid = {29759595},
issn = {1938-0666},
mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Immunological/therapeutic use ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Carcinoma, Lobular/drug therapy/genetics/*pathology ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local/epidemiology ; Receptor, ErbB-2 ; Retrospective Studies ; Trastuzumab/therapeutic use ; },
abstract = {BACKGROUND: Infiltrating lobular carcinoma (ILC) represents about 10% of breast cancer and rarely shows overexpression of human epidermal growth factor receptor 2 (HER2). We compared biological and clinical characteristics of HER2-positive ILC versus HER2-positive infiltrating ductal carcinoma (IDC).<br><br>PATIENTS AND METHODS: We retrospectively analyzed the data of 328 patients with HER2-positive pure ductal or lobular breast carcinoma, comparing clinical and biological data at diagnosis as well as outcome between the 2 histologies. A gene-mutation analysis was performed in a subset of patients.<br><br>RESULTS: Two hundred ninety-one patients (88.7%) had IDC and 37 patients (11.3%) ILC. ILC resulted more frequently in multicenter (24.3% vs. 6.5%, P&#xa0;< .0001) and node-positive (54.1% vs. 45%, P&#xa0;=&#xa0;.013) disease of lower proliferative activity (Mib1&#xa0;< 20%: 51.4% vs. 22.3%, P&#xa0;< .0001) and lower histologic grade (grade 3: 32.4% vs. 57.4%, P&#xa0;= .038). Disease recurred in 57 patients (17.4%) and involved the bone in 40% of ILC patients (vs. 17% of IDC patients) and the viscera in 30% of ILC patients (vs. 59.6% of IDC patients). No difference in the recurrence rate between the 2 histologies was observed in patients treated with adjuvant trastuzumab (12.5% of ILC patients and 8.3% of IDC patients). Exploratory molecular analysis revealed a higher frequency of mutations in ILC, with more cases of multiple mutations.<br><br>CONCLUSION: HER2-positive ILC shows different biological behavior than IDC, with a possible higher mutation load. Despite lower proliferation activity and estrogen receptor expression in ILC breast cancer, trastuzumab is clearly an effective therapy for this histologic subtype.},
}
@article {pmid29751292,
year = {2018},
author = {Maida, A and Zota, A and Vegiopoulos, A and Appak-Baskoy, S and Augustin, HG and Heikenwalder, M and Herzig, S and Rose, AJ},
title = {Dietary protein dilution limits dyslipidemia in obesity through FGF21-driven fatty acid clearance.},
journal = {The Journal of nutritional biochemistry},
volume = {57},
number = {},
pages = {189-196},
doi = {10.1016/j.jnutbio.2018.03.027},
pmid = {29751292},
issn = {1873-4847},
support = {//CIHR/Canada ; },
mesh = {Animals ; CD36 Antigens/genetics ; Dietary Proteins/*pharmacology ; Dyslipidemias/*diet therapy/etiology/metabolism ; Fatty Acids/*metabolism ; Fibroblast Growth Factors/*metabolism ; Hypertriglyceridemia/diet therapy/etiology ; Lipid Metabolism/drug effects ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Obese ; Non-alcoholic Fatty Liver Disease/diet therapy/etiology ; Obesity/*complications/metabolism ; },
abstract = {Recent studies have demonstrated that dietary protein dilution (PD) can promote metabolic inefficiency and improve glucose metabolism. However, whether PD can promote other aspects of metabolic health, such as improve systemic lipid metabolism, and mechanisms therein remains unknown. Mouse models of obesity, such as high-fat-diet-fed C57Bl/6 N mice, and New Zealand Obese mice were fed normal (i.e., 20%P) and protein-dilute (i.e., 5%EP) diets. FGF21-/- and Cd36-/- and corresponding littermate +/+ controls were also studied to examine gene-diet interactions. Here, we show that chronic PD retards the development of hypertrigylceridemia and fatty liver in obesity and that this relies on the induction of the hepatokine fibroblast growth factor 21 (FGF21). Furthermore, PD greatly enhances systemic lipid homeostasis, the mechanisms by which include FGF21-stimulated, and cluster of differentiation 36 (CD36) mediated, fatty acid clearance by oxidative tissues, such as heart and brown adipose tissue. Taken together, our preclinical studies demonstrate a novel nutritional strategy, as well as highlight a role for FGF21-stimulated systemic lipid metabolism, in combating obesity-related dyslipidemia.},
}
@article {pmid29748110,
year = {2018},
author = {Santangelo, G and Vitale, C and Baiano, C and D'Iorio, A and Longo, K and Barone, P and Amboni, M and Conson, M},
title = {Interoceptive processing deficit: A behavioral marker for subtyping Parkinson's disease.},
journal = {Parkinsonism &amp; related disorders},
volume = {53},
number = {},
pages = {64-69},
doi = {10.1016/j.parkreldis.2018.05.001},
pmid = {29748110},
issn = {1873-5126},
mesh = {Aged ; Female ; Gait Disorders, Neurologic/etiology/*physiopathology ; Humans ; Interoception/*physiology ; Male ; Middle Aged ; Parkinson Disease/*classification/complications/*physiopathology ; Postural Balance/*physiology ; Tremor/etiology/*physiopathology ; },
abstract = {BACKGROUND: Non-motor symptoms in Parkinson's disease (PD), such as cognitive, emotional, autonomic and somatosensory alterations, are not ubiquitous but vary between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes of the syndrome. Non-motor phenomena (e.g., anxiety, depression and apathy) have been related to representation of autonomic and somatosensory sensations (interoception), and recent findings suggest interoceptive deficits in PD.<br><br>OBJECTIVES: To test whether interoceptive processing is differently affected in TD and PIGD phenotypes, by assessing both interoceptive accuracy and sensibility in PD patients with TD and PIGD subtypes, and in healthy controls.<br><br>METHODS: Interoceptive accuracy was measured by the heartbeat perception task requiring participants to count their own heartbeats in a given time interval. A time-estimation, control task was also administered asking participants to count the seconds in a set period of time. Interoceptive sensibility was assessed by a questionnaire of subjective interoception. Finally, the patients underwent measures of anxiety, depression, apathy and anhedonia, and impulsive-compulsive disturbances.<br><br>RESULTS: The main results showed reduced interoceptive accuracy and sensibility in TD patients relative to both PIGD patients and healthy controls. Reduced interoceptive accuracy of TD group was a reliable result since their performance on the time estimation control task was comparable to that of both PIGD patients and healthy controls.<br><br>CONCLUSIONS: These findings demonstrate that the behavioural assessment of different aspects of interoceptive processing can provide with a further marker for subtyping patients with PD.},
}
@article {pmid29745077,
year = {2018},
author = {Marusa Borgonio-Cuadra, V and Miranda-Duarte, A and Rojas-Toledo, X and Garcia-Hernandez, N and Alfredo Sierra-Ramirez, J and Cardenas-Garcia, M and Elena Hernandez-Caballero, M},
title = {Association between promoter hypermethylation of the DACT2 gene and tumor stages in breast cancer.},
journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology},
volume = {23},
number = {2},
pages = {361-365},
pmid = {29745077},
issn = {1107-0625},
mesh = {Adaptor Proteins, Signal Transducing ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carrier Proteins/*genetics ; Cell Line, Tumor ; CpG Islands/genetics ; DNA Methylation/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Genetic Association Studies ; Humans ; Middle Aged ; Neoplasm Proteins/*genetics ; Neoplasm Staging ; Promoter Regions, Genetic ; },
abstract = {PURPOSE: Aberrant methylation of CpG islands in the promoter is a hallmark of cancer, leading to transcriptional silencing of tumor suppressor genes. The aim of this work was to evaluate the promoter methylation status of the DACT2 gene in breast cancer (BC) tissue and to analyze its possible effect on tumor type or grade.<br><br>METHODS: CpG island from the DACT2 promoter in region -240 to -14 from transcriptional start site (TSS) were obtained. Through the use of sodium bisulfite DNA conversion analysis, followed by detection with MSP (methylation specific PCR), we analyzed 79 BC and 15 adjacent healthy samples.<br><br>RESULTS: T he c ases a nalyzed w ere i n s tage I (2.5%), I I (38%), or III (59.5%). The most frequent tumor type was invasive ductal carcinoma (71.4%). Methylation analysis comparing tumor tissues with adjacent non-cancerous tissues showed statistical significance. Methylation was observed in 32.9% (26/79) of the samples; no methylation was found in adjacent healthy tissue. DACT2 methylation was associated with tumor stage I-II (p=0.03) and stage III (p=0.004).<br><br>CONCLUSION: An association was found of DACT2 promoter methylation with advanced tumor stages. This gene has been suggested as a potential biomarker, however, more investigation is required to validate this function.},
}
@article {pmid29739984,
year = {2018},
author = {Du, T and Zhu, L and Levine, KM and Tasdemir, N and Lee, AV and Vignali, DAA and Houten, BV and Tseng, GC and Oesterreich, S},
title = {Invasive lobular and ductal breast carcinoma differ in immune response, protein translation efficiency and metabolism.},
journal = {Scientific reports},
volume = {8},
number = {1},
pages = {7205},
pmid = {29739984},
issn = {2045-2322},
support = {F30 CA203154/CA/NCI NIH HHS/United States ; },
mesh = {Aged ; Atlases as Topic ; Breast Neoplasms/diagnosis/genetics/*immunology/metabolism ; Carcinoma, Ductal, Breast/diagnosis/genetics/*immunology/metabolism ; Carcinoma, Lobular/diagnosis/genetics/*immunology/metabolism ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genome, Human ; Humans ; Immune System/immunology/metabolism/pathology ; Immunotherapy/methods ; Lymphatic Metastasis ; Metabolic Networks and Pathways/genetics/*immunology ; Middle Aged ; Neoplasm Proteins/classification/genetics/*immunology/metabolism ; Neoplasm Recurrence, Local/diagnosis/genetics/*immunology/metabolism ; Protein Biosynthesis ; Tumor Escape/genetics ; },
abstract = {Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). ILC differs from IDC in a number of histological and clinical features, such as single strand growth, difficulty in detection, and frequent late recurrences. To understand the molecular pathways involved in the clinical characteristics of ILC, we compared the gene expression profiles of luminal A ILC and luminal A IDC using data from TCGA and utilized samples from METABRIC as a validation data set. Top pathways that were significantly enriched in ILC were related to immune response. ILC exhibited a higher activity of almost all types of immune cells based on cell type-specific signatures compared to IDC. Conversely, pathways that were less enriched in ILC were related to protein translation and metabolism, which we functionally validated in cell lines. The higher immune activity uncovered in our study highlights the currently unexplored potential of a response to immunotherapy in a subset of patients with ILC. Furthermore, the lower rates of protein translation and metabolism - known features of tumor dormancy - may play a role in the late recurrences of ILC and lower detection rate in mammography and PET scanning.},
}
@article {pmid29733543,
year = {2018},
author = {Nahleh, Z and Otoukesh, S and Mirshahidi, HR and Nguyen, AL and Nagaraj, G and Botrus, G and Badri, N and Diab, N and Alvarado, A and Sanchez, LA and Dwivedi, AK},
title = {Disparities in breast cancer: a multi-institutional comparative analysis focusing on American Hispanics.},
journal = {Cancer medicine},
volume = {7},
number = {6},
pages = {2710-2717},
pmid = {29733543},
issn = {2045-7634},
mesh = {Black or African American ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/metabolism/pathology/therapy ; Disease Management ; Ethnicity ; Female ; *Healthcare Disparities ; *Hispanic or Latino ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; },
abstract = {UNLABELLED: Breast cancer (BC) is the leading cause of cancer death in Hispanic/Latino women nationwide. Hispanic women are more likely to be presented with advanced disease and adverse prognosis subtypes. The aim of this study is to describe the clinico- pathological characteristics and disparities in breast cancer in this group at two tertiary care University-based medical centers. After IRB approval, Cancer registry was used to analyze the variables of 3441 patients with breast cancer diagnosed and treated consecutively at two large tertiary University based medical and cancer center database centers in El Paso, TX and Loma Linda, CA between 2005 and 2015. Association between race/ethnicity and cancer type, stage, hormone receptor status and treatment option were investigated. Overall 45.5% of the patients were Hispanic (n: 1566) and those were more likely to be diagnosed at a younger age (57 years) similar to African Americans, more likely to have invasive ductal carcinoma type (82.7%) &amp; triple negative disease (17.1%, 95%CI: 15% to 19%). 58.8% of Hispanics (95%CI: 56% to 61%) have hormone receptor (HR)+ &amp; HER2- as opposed to 71% in non-Hispanic White people. In addition, Hispanic individuals presented with advanced stages of BC (25.3%, 95% CI: 23% to 28%) similar to African American (25.4%), and had a lower proportion of lumpectomy (50%) similar to African American (50%). When compared to African American patients, Hispanic patients had a higher prevalence of triple negative BC (17.11% in Hispanics Versus 13.86% in African American).<br><br>CONCLUSION: Hispanics had significantly higher relative risk of advanced stages at presentation (Relative Risk Ratio (RRR)&#xa0;=&#xa0;2.05, P&#xa0;<&#xa0;0.001), triple negative tumors (RRR&#xa0;=&#xa0;2.64, P&#xa0;<&#xa0;0.0001), HER2&#xa0;+&#xa0;/HR - disease (RRR&#xa0;=&#xa0;1.77, P&#xa0;<&#xa0;0.0001), and less HR+ /HER2- BC (RRR&#xa0;=&#xa0;0.69, P&#xa0;<&#xa0;0.0001). Hispanics and African Americans are diagnosed with breast cancer at a younger age, have a higher prevalence of Triple negative breast cancer, and are diagnosed at more advanced stages of disease. Increasing awareness and targeting minority populations for health promotion interventions, screening and early detection continue to be of paramount importance to reduce the burden of health disparities.},
}
@article {pmid29703057,
year = {2018},
author = {Xie, L and Lin, C and Zhang, H and Bao, X},
title = {Second malignancy in young early-stage breast cancer patients with modern radiotherapy: A long-term population-based study (A STROBE-compliant study).},
journal = {Medicine},
volume = {97},
number = {17},
pages = {e0593},
pmid = {29703057},
issn = {1536-5964},
mesh = {Adult ; Age Factors ; Axilla ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Cancer Survivors/*statistics &amp; numerical data ; Carcinoma, Ductal, Breast/*radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lymph Node Excision ; Lymph Nodes/pathology/surgery ; Mastectomy, Segmental ; Neoplasm Staging ; Neoplasms, Second Primary/*epidemiology/etiology ; Radiotherapy, Adjuvant/adverse effects/methods ; Risk Factors ; SEER Program ; Time Factors ; Young Adult ; },
abstract = {Second cancer is a leading cause of death in long-term survivors of younger early-stage breast cancer patients. To date, relationship of age, receipt of radiotherapy (RT), and estimated doses received by target organs have not yet been well elucidated. Using Surveillance, Epidemiology, and End Results database, patients aged 20 to 44, diagnosed with a first primary staging I-IIIA ipsilateral breast invasive ductal carcinoma, underwent surgery during 1988 to 2009 were identified, and those with a second malignancy at ≥1-year follow-up were analyzed to calculate cumulative incidences (CIs) of second malignancy in whole group and each subgroup. Subgroups were dichotomized by surgery type, axillary dissection, and axillary lymph node status. With a median follow-up of 11.8 years, 22,628 women including 1495 patients (6.6%) developing second malignancies (3.7% contralateral breast cancer, 2.9% non-breast second malignancies, and 0.7% high-dose site second malignancies) were identified. Three-dimensional coordinate systems with age at primary diagnosis, time after primary breast cancer diagnosis, and CI of second malignancy as 3 axes, for endpoints including all second malignancy, second primary contralateral breast cancer, and non-breast second malignancy were presented, along with the risk in RT and non-RT groups in overall group and subgroups. Five-, 10-, 15-, and 20-year all second malignancy-free survivals in RT and non-RT groups were 89.5% versus 85.4%, 80.1% versus 75.0%, 72.9% versus 67.9%, and 65.6% versus 61.8% (P < .0001). From the large national dataset, a broad visualized overview of second malignancy risk, including second contralateral breast cancer and non-breast second cancer, suggests generally beneficial therapeutic ratio for radiotherapy in young women with early-stage breast cancer.},
}
@article {pmid29700276,
year = {2018},
author = {Rahmani, M and Nili, F and Tabibian, E},
title = {Endometrial Metastasis from Ductal Breast Carcinoma: A Case Report with Literature Review.},
journal = {The American journal of case reports},
volume = {19},
number = {},
pages = {494-499},
pmid = {29700276},
issn = {1941-5923},
mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Endometrial Neoplasms/*secondary ; Female ; Humans ; Menorrhagia/etiology ; Middle Aged ; Uterine Hemorrhage/etiology ; },
abstract = {BACKGROUND There are few reports of breast cancer cases with uterine metastases; among them, myometrium is more frequently involved than endometrium. The majority of breast cancer metastases to endometrium are lobular type, and there have been only 5 reported cases of ductal type since 1984. Here, we describe a new case of invasive ductal carcinoma with metastases to endometrium and isolated presentation of abnormal uterine bleeding, in addition to reviewing the existing literature on other similar cases. CASE REPORT The patient was a 51-year-old Persian woman with no remarkable past medical or family history of cancer, who presented with a 6-month complaint of menorrhagia to our gynecology clinic. Diagnostic studies including trans-vaginal ultrasonography, pathological examination of endometrial curettage specimen, immunohistochemistry findings, and X-plane and magnetic resonance mammography, and breast core-needle biopsy revealed invasive ductal breast carcinoma as the origin of the endometrial metastasis. CONCLUSIONS Abnormal uterine bleeding in a premenopausal patient should alert clinicians to the possibility of secondary as well as primary neoplasms. It is necessary to differentiate a metastatic tumor from a primary one, since the treatment and prognosis are completely different.},
}
@article {pmid29695771,
year = {2018},
author = {Bharti, R and Dey, G and Das, AK and Mandal, M},
title = {Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.},
journal = {British journal of cancer},
volume = {118},
number = {11},
pages = {1442-1452},
pmid = {29695771},
issn = {1532-1827},
mesh = {Animals ; Antigens, CD/metabolism ; Azacitidine/pharmacology ; Breast Neoplasms/blood supply/*metabolism ; Cadherins/metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Chick Embryo ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Human Umbilical Vein Endothelial Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Interleukin-6/*metabolism ; Models, Biological ; Monoamine Oxidase/*metabolism ; Neoplasm Invasiveness ; Receptors, Interleukin-6/*metabolism ; Vascular Endothelial Growth Factor A/*metabolism ; },
abstract = {BACKGROUND: Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis.<br><br>METHODS: We employed various in-vitro and in-vivo techniques and clinical samples.<br><br>RESULTS: We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1&#x3b1; was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen.<br><br>CONCLUSIONS: Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.},
}
@article {pmid29694313,
year = {2018},
author = {Vergine, M and Musella, A and Gulotta, E and Frusone, F and De Luca, A and Maceli, F and Libia, A and Benedetti Panici, P and Monti, M},
title = {Paget's disease of the male breast: case report and a point of view from actual literature.},
journal = {Il Giornale di chirurgia},
volume = {39},
number = {2},
pages = {114-117},
pmid = {29694313},
issn = {0391-9005},
mesh = {Aged ; Alzheimer Disease/complications ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms, Male/complications/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Combined Modality Therapy ; *Estrogens ; Humans ; Male ; Mastectomy ; Neoplasms, Hormone-Dependent/complications/drug therapy/*pathology/surgery ; Neoplasms, Multiple Primary/*pathology/surgery ; Nipples/*pathology ; Paget's Disease, Mammary/complications/etiology/*pathology/surgery ; *Progesterone ; Skin Ulcer/etiology ; Tamoxifen/therapeutic use ; },
abstract = {INTRODUCTION: Paget disease of the nipple in man is a very rare breast cancer, and there are not standard procedures or guidelines. In any cases, a Paget's disease could hide an invasive ductal breast cancer.<br><br>CASE DESCRIPTION: We report the case of a 77-years old man affected by Alzheimer's disease, who presented to our attention because of an ulcerated palpable mass in the right nipple. A biopsy of the lesion showed "intra-epidermic proliferation of epitelioid cells, associated with linfo-plasmacellular infiltration of superficial dermis, compatible with Paget's disease (pTis)". We discussed the case in the multidisciplinary meeting and decided to subject the patient to surgery, so a right mastectomy plus sentinel lymph node biopsy (SLNB) were performed. Histo-pathological examination revealed "invasive ductal carcinoma of the breast, associated with a small component of in situ ductal carcinoma and Paget's disease of the nipple with superficial ulceration". Resection margins were free. Sentinel lymph node was negative. Biological features were as follows: ER 95%, PR 60%, Her-2/neu 1+, Ki-67 35%. The patient was discharged in the third post-operative day in good conditions. In the following weeks the patient's healing process was good and free of complications.<br><br>CONCLUSIONS: Clinical recognition of Paget's disease is very important also in man, because it can be the alarm bell for an underlying invasive ductal breast cancer, often more aggressive than in woman.},
}
@article {pmid29692363,
year = {2018},
author = {Babaei, R and Schuster, M and Meln, I and Lerch, S and Ghandour, RA and Pisani, DF and Bayindir-Buchhalter, I and Marx, J and Wu, S and Schoiswohl, G and Billeter, AT and Krunic, D and Mauer, J and Lee, YH and Granneman, JG and Fischer, L and Müller-Stich, BP and Amri, EZ and Kershaw, EE and Heikenwälder, M and Herzig, S and Vegiopoulos, A},
title = {Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis.},
journal = {Science signaling},
volume = {11},
number = {527},
pages = {},
doi = {10.1126/scisignal.aai7838},
pmid = {29692363},
issn = {1937-9145},
support = {R01 DK090166/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; },
mesh = {Adipocytes, Beige/*metabolism/pathology ; Adipogenesis/genetics ; Adipose Tissue/*metabolism/pathology ; Animals ; Cell Differentiation/genetics ; Cells, Cultured ; Female ; Gene Expression Profiling ; Humans ; Inflammation/*genetics/metabolism ; Janus Kinases/*genetics/metabolism ; Lipase/genetics/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; STAT3 Transcription Factor/genetics/metabolism ; Signal Transduction/genetics ; Transforming Growth Factor beta/*genetics/metabolism ; },
abstract = {The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as β3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGFβ signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors. Jak/Stat3 inhibited TGFβ signaling to the transcription factors Srf and Smad3 by repressing local Tgfb3 and Tgfb1 expression before the core transcriptional adipogenic cascade was activated. This pathway cross-talk was triggered in stromal cells by ATGL-dependent adipocyte lipolysis and a transient wave of IL-6 family cytokines at the onset of adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Our results provide insight into the activation of adipocyte progenitors and are relevant for the therapeutic targeting of adipose tissue inflammatory pathways.},
}
@article {pmid29686118,
year = {2018},
author = {Sheehan, J and Tate, J and Mott, R and Geer, C and Wolfe, R and Strowd, RE and Guzik, A},
title = {Pearls &amp; Oy-sters: The critical role of histopathology in diagnosing cancer-associated necrotizing CNS vasculitis.},
journal = {Neurology},
volume = {90},
number = {17},
pages = {808-811},
doi = {10.1212/WNL.0000000000005350},
pmid = {29686118},
issn = {1526-632X},
mesh = {Aged ; Breast Neoplasms/pathology ; Carcinoma, Squamous Cell/*complications/diagnostic imaging/secondary ; Electroencephalography ; Female ; Humans ; Magnetic Resonance Imaging ; Vasculitis, Central Nervous System/*complications/diagnostic imaging ; },
abstract = {OBJECTIVE: To highlight the importance of a broad differential and histopathologic confirmation in patients with newly diagnosed cancer with brain lesions atypical for CNS metastasis.<br><br>METHODS: We report 2 cases of biopsy-proven CNS vasculitis in patients undergoing treatment for a newly diagnosed nonmetastatic cancer. Comprehensive medical record review was performed to identify the clinical presentation, representative neuroimaging, histopathologic features, and response to treatment.<br><br>RESULTS: Patient 1 presented 1 month into induction therapy of malignant vaginal squamous cell carcinoma (stage 3, T2N1M0) with acute episodic left-sided hemiparesis due to seizure activity progressing to severe encephalopathy. Imaging revealed a right frontoparietal lesion while systemic workup was unrevealing. Biopsy demonstrated necrotizing vasculitis. Patient 2 presented 6 months after diagnosis of right breast invasive ductal carcinoma (stage IIa, T2N0M0, estrogen receptor-positive, progesterone receptor-positive, human epidermal growth factor receptor-2 positive) with subacute bifrontal headaches with associated phonophobia. Imaging showed hyperintense lesions involving the right temporoparietal region and systemic workup was unrevealing. Brain biopsy showed a necrotizing vasculitis. Patient 1 was treated with methyprednisolone and plasmapheresis and patient 2 was treated with prednisone. Both patients showed complete resolution of symptoms shortly after treatment and improvement on imaging.<br><br>CONCLUSIONS: These cases highlight the importance of comprehensive evaluation of new brain lesions in patients with nonmetastatic solid tumors. Characteristics of new brain lesions in patients with cancer that should raise suspicion of diagnoses other than brain metastasis include (1) primary malignancy without regional or distant metastasis, (2) imaging without discrete mass-like enhancement, and (3) cortically based location of lesions not at the gray-white matter junction.},
}
@article {pmid29679553,
year = {2018},
author = {Swellam, M and El Magdoub, HM and Hassan, NM and Hefny, MM and Sobeih, ME},
title = {Potential diagnostic role of circulating MiRNAs in breast cancer: Implications on clinicopathological characters.},
journal = {Clinical biochemistry},
volume = {56},
number = {},
pages = {47-54},
doi = {10.1016/j.clinbiochem.2018.04.013},
pmid = {29679553},
issn = {1873-2933},
mesh = {Adult ; Aged ; Biomarkers, Tumor/blood/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*blood/diagnosis/metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/metabolism/pathology/secondary ; Diagnosis, Differential ; Early Diagnosis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis/diagnosis/pathology ; MicroRNAs/*blood/metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; RNA, Neoplasm/*blood/metabolism ; *Up-Regulation ; Young Adult ; },
abstract = {BACKGROUND: Circulating miRNAs are stable in body fluids and resembles their levels in cancer tissue/cells. They have been expressed in many cancers among them is breast cancer. Authors aimed to investigate the expression levels of three circulating oncomiRNAs (miRNA-21, miRNA-222 and miRNA-373) in serum samples as a minimally non-invasive method for early detection of breast cancer, and study their relation with clinicopathological characters.<br><br>METHODS: MiRNAs expression levels were determined using quantitative real-time polymerase chain reaction (qPCR) in serum samples from three groups: primary breast cancer patients (n&#x202f;=&#x202f;137), benign breast lesion patients (n&#x202f;=&#x202f;60), and healthy individuals as control group (n&#x202f;=&#x202f;38). Statistical analyses were carried out using SPSS.<br><br>RESULTS: Significant differences were observed between the expression levels of the studied miRNAs in the investigated groups, as their median levels were increased in breast cancer patients followed by benign group patients then the healthy individuals. MiRNA-373 reported the highest diagnostic efficacy as compared to miRNA-21 and miRNA-222 with high area under the curve (AUC equals 0.987). The relation between tested miRNAs and clinicopathological factors revealed significant difference with clinical stages and histological grades. Level of miRNA-21 and miRNA-373 were statistically significantly higher in invasive duct carcinoma (IDC) as compared to non-IDC. Similarly, their levels were increased in lymph node metastasis (P&#x202f;<&#x202f;0.01). MiRNA-222 and miRNA-373 were significantly increased in positive PgR and positive Her-2/neu status, respectively.<br><br>CONCLUSION: Assessment of miRNAs in serum samples can be applied as minimally non-invasive markers for early detection of breast cancer, and as discriminator between different clinicopathological characters.},
}
@article {pmid29676352,
year = {2018},
author = {Guleria, P and Srinivas, V and Basannar, D and Dutta, V},
title = {Comparison of lymphangiogenesis, lymphatic invasion, and axillary lymph node metastasis in breast carcinoma.},
journal = {Indian journal of pathology &amp; microbiology},
volume = {61},
number = {2},
pages = {176-180},
doi = {10.4103/IJPM.IJPM_774_16},
pmid = {29676352},
issn = {0974-5130},
mesh = {Aged ; Antibodies, Monoclonal, Murine-Derived/*immunology ; Axilla/pathology ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphangiogenesis/*physiology ; Lymphatic Metastasis/*pathology ; Lymphatic Vessels/pathology ; Mastectomy, Modified Radical ; Middle Aged ; },
abstract = {CONTEXT: Lymphangiogenesis correlates with poor prognosis in Invasive Ductal Carcinoma (IDC) breast. D2-40 antibody, a specific marker for lymphatic endothelium, differentiates lymphatic from vascular endothelium. Therefore, the aims of this study were to estimate lymphangiogenesis using D2-40 antibody and correlate with lymphatic invasion (LI) and axillary lymph node (LN) status and compare lymphatic mean vessel density (LMVD) with Tumor (T) and Node (N) stages and grade of tumor.<br><br>METHODS AND MATERIAL: The study was conducted on fifty consecutive cases of IDC breast who underwent modified radical mastectomy (MRM) from Jan 2009 to March 2011. Hematoxylin-eosin sections and Immunohistochemistry (IHC) slides were studied along with their LN status. LMVD was counted after D2-40 immunostaining (100x magnification) in three hot spots in peritumoral areas and averaged. LI as opposed to vascular invasion (BVI), and LN status for all cases were assessed.<br><br>STATISTICAL ANALYSIS: Statistical analysis was done using SPSS software (version 14.0 for Windows). Pearson's correlations, &#x3c7;[2] tests and Mann-Whitney U test were used.<br><br>RESULTS: Lymphangiogenesis varied from 0 to 58 with mean LMVD of 11. Of 50 cases, five showed no lymphatic vessels in peritumoral areas; of these five, three had positive LNs. 21/50 cases had LI. No statistical significant association was seen between lymphangiogenesis and LI. 34/50 cases had positive LNs. Mean LMVD was higher in patients with N2/N3 stage as compared to N0/N1 stage and was statistically significant (P = 0.013).<br><br>CONCLUSIONS: D2-40 is specific marker for lymphatic endothelium. LI and lymphangiogenesis, as opposed to BVI, are better prognostic indicators in IDC breast.},
}
@article {pmid29672601,
year = {2018},
author = {Kassardjian, A and Shintaku, PI and Moatamed, NA},
title = {Expression of immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-L1), in female breast carcinomas.},
journal = {PloS one},
volume = {13},
number = {4},
pages = {e0195958},
pmid = {29672601},
issn = {1932-6203},
mesh = {Adult ; B7-H1 Antigen/*genetics/metabolism ; *Biomarkers, Tumor ; Breast Neoplasms/*genetics/immunology/metabolism/pathology ; CTLA-4 Antigen/*genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/immunology/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Female ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; T-Lymphocyte Subsets/immunology/*metabolism ; Tissue Array Analysis ; },
abstract = {BACKGROUND: Immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) have emerged as promising new targets for cancer therapeutics. While tumor expression of PD-L1 has been shown to have objective responses to anti-PD-L1 immunotherapies, the clinical implications of CTLA-4 expression in tumor cells or immune cells in the tumor microenvironment is still controversial. We investigated the expression of CTLA-4 and PD-L1 in human breast tumors and provided a scoring system for the systematic evaluation of CTLA-4 staining.<br><br>METHODS: Immunohistochemical staining for PD-L1 and CTLA-4 expression was performed on a tissue microarray of 102 cores, which included normal and neoplastic breast tissues. Neoplastic cores were divided into four groups: Ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) and invasive tubular carcinoma (ITC). PD-L1 and CTLA-4 expressions were scored based on a system which accounted for the percentage and intensity of positivity and results provided in conjunction with available clinical and demographic data.<br><br>RESULTS: Overall, CTLA-4 was over-expressed in 49 of 93 (52.7%) breast tumors. Subcategorically, CTLA-4 was positive in 3 of 8 (37.5%) ductal carcinoma in situ, 40 of 73 (55%) of invasive ductal carcinomas, 4 of 10 (40%) of invasive lobular carcinomas and 2 of 2 (100%) of invasive tubular carcinomas. All 6 normal breast tissues were interpreted as negative for CTLA-4 staining. Only 4.1% of the invasive ductal carcinomas were positive for PD-L1 reactivity and the remaining carcinomas stained negative.<br><br>CONCLUSIONS: This study shows a significant overexpression of CTLA-4 in >50% of breast carcinomas with no such overexpression of CTLA-4 in benign breast tissues. PDL-1 staining is seen in only a small number of invasive ductal carcinomas (4.1%). These findings suggest the need for further investigation of anti-CTLA-4 and anti-PD-L1 immunotherapies and their efficacy in the treatment of breast carcinomas with overexpression of these immune modulators. In addition, the proposed scoring system will facilitate a more systematic correlation between tumor reactivity and clinical outcome which can be applied to all intracytoplasmic tumor markers.},
}
@article {pmid29669935,
year = {2018},
author = {Zhu, S and Ward, BM and Yu, J and Matthew-Onabanjo, AN and Janusis, J and Hsieh, CC and Tomaszewicz, K and Hutchinson, L and Zhu, LJ and Kandil, D and Shaw, LM},
title = {IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma.},
journal = {JCI insight},
volume = {3},
number = {8},
pages = {},
pmid = {29669935},
issn = {2379-3708},
support = {F31 CA206378/CA/NCI NIH HHS/United States ; R01 CA142782/CA/NCI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; Humans ; Insulin Receptor Substrate Proteins/*genetics ; Lymph Nodes/pathology ; Middle Aged ; Mutation, Missense/genetics ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Receptor, IGF Type 1 ; Receptors, Somatomedin/*genetics ; Exome Sequencing/methods ; },
abstract = {Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC. IRS2 mutations identified in PILC enhance invasion, revealing a role for this signaling adaptor in the aggressive nature of PILC.},
}
@article {pmid29661250,
year = {2018},
author = {Liu, WS and Chan, SH and Chang, HT and Li, GC and Tu, YT and Tseng, HH and Fu, TY and Chang, HY and Liou, HH and Ger, LP and Tsai, KW},
title = {Isocitrate dehydrogenase 1-snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability.},
journal = {Breast cancer research : BCR},
volume = {20},
number = {1},
pages = {25},
pmid = {29661250},
issn = {1465-542X},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Cell Proliferation/genetics ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Isocitrate Dehydrogenase/*genetics ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Signal Transduction/genetics ; Snail Family Transcription Factors/*genetics ; },
abstract = {BACKGROUND: The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown.<br><br>METHODS: In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion.<br><br>RESULTS: The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08-2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIF&#x3b1; (hypoxia-inducible factor-1 alpha) and NF&#x3ba;B (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32-4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39-4.50; p = 0.002) in patients with breast cancer.<br><br>CONCLUSION: Our findings revealed that a IDH1[low]/Snail[high] molecular signature could serve as an independent biomarker for poor prognosis in breast cancer.},
}
@article {pmid29655534,
year = {2018},
author = {Kariminezhad, E and Elektorowicz, M},
title = {Comparison of constant, pulsed, incremental and decremental direct current applications on solid-liquid phase separation in oil sediments.},
journal = {Journal of hazardous materials},
volume = {358},
number = {},
pages = {475-483},
doi = {10.1016/j.jhazmat.2018.04.002},
pmid = {29655534},
issn = {1873-3336},
abstract = {Phase separation of oil wastes can mitigate the effects on the environment, by decreasing the volume of hazardous materials and regenerate energy. This study focused on the advanced electrokinetic method as a treatment technology to treat oil sediments from oil refineries and separate them into their individual phase components. The effects of four types of electrical field on the phase separation of oil sediments from an oil refinery were investigated namely constant direct current (CDC), pulsed direct current (PDC), incremental direct current (IDC) and decremental direct current (DDC). The results showed that the extent and quality of phase separation differed based on the type of electrical current applied, and indicated that different mechanisms such as electroosmosis, electrophoresis, electro-demulsification, and electro-sedimentation might have been involved in the separation process depending on the type of electrical supply. The application of DDC and IDC was found to cause a significant separation of solids by electrophoresis with the movement of almost 70% of solids to the anode of the reactors. The DDC and IDC regimes resulted in the most efficient phase separation of the oil sediments, and even incurred a highly resolved separation of light hydrocarbons at the top anode.},
}
@article {pmid29650905,
year = {2018},
author = {Fujimoto, Y and Yamaguchi, K and Ueno, A and Sakurai, R and Nagahisa, Y and Imai, S and Kawamoto, K},
title = {[A Case of HER2-Positive Breast Cancer with Liver Metastases Showing Three Years of Complete Response to Combination Therapy with Trastuzumabplus Pertuzumab].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {45},
number = {3},
pages = {459-461},
pmid = {29650905},
issn = {0385-0684},
mesh = {Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Middle Aged ; Receptor, ErbB-2/analysis ; Recurrence ; Trastuzumab/administration &amp; dosage ; },
abstract = {A 48-year-old woman with severe interstitial pneumonitis was diagnosed with right breast cancer(invasive ductal carcinoma, T1aN1M0, ER+, PgR-, HER2 3+)and underwent modified radical mastectomy.The patient was administered tamoxifen as adjuvant therapy.However, 1 year after the mastectomy, multiple liver metastases were found and the patient received 2 anti-HER2 agents, trastuzumab and pertuzumab.A complete response(CR)was observed with the disappearance of the liver metastases in 7 months.CR was maintained for 2 years after the initiation of treatment, and then, we started trastuzumab monotherapy, which has resulted in long-term disease control.},
}
@article {pmid29621999,
year = {2018},
author = {Balekouzou, A and Yin, P and Bekolo, CE and Pamatika, CM and Djeintote, M and Nambei, SW and Ba-Mpoutou, B and Mandjiza, DR and Shu, C and Yin, M and Qing, T and Koffi, B},
title = {Histo-epidemiological profile of breast cancers among women in the Central African Republic: about 174 cases.},
journal = {BMC cancer},
volume = {18},
number = {1},
pages = {387},
pmid = {29621999},
issn = {1471-2407},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology/therapy ; Central African Republic/epidemiology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Public Health Surveillance ; Retrospective Studies ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer in women worldwide and leading cause of cancer deaths indeveloping countries. There is very limited data on BC in the Central African Republic. The purpose of this study was to describe the epidemiological and histopathological characteristics of BC in Bangui.<br><br>METHODS: This retrospective study reviewed cancer data registries and medical records from the Pathology Unit of the National Laboratory in Bangui and the General Surgery and Gyneacology service from 2003 to 2015. A questionnaire was designed to collect information and data was analysed using descriptive and inferential statistical methods.<br><br>RESULTS: In total, 174 cases of BC were recorded, with an average annual frequency of13.4 cases per year. The age of the women at diagnosis varied from 16 to 90&#xa0;years with a median of 45.5&#xa0;years and InterQuartile range (IQR) 18&#xa0;years. The age group of 45-54&#xa0;years represented the majority of the study population (n&#xa0;=&#x2009;51, 29.3%).About 25.9%ofthe patients were non-educated and 85.6% lived in cities. Over 48 % of the women were housewives with a moderate economic status (n&#xa0;=&#x2009;99, 56.9%). Sixty nine percent of the specimens received at the pathology unit were pieces of breast tumour. Invasive ductal carcinoma (n&#xa0;=&#x2009;113, 64.9%) was the main histological form and most of the tumours were of Grade III (n&#xa0;=&#x2009;14, 46.7%). The only imaging assessment was ultrasound performed in (n&#xa0;=&#x2009;53, 30.4%) women. Surgery was performed in (n&#xa0;=&#x2009;166, 95.4%) patients, while (n&#xa0;=&#x2009;159, 91.4%) received complementary chemotherapy. At the end of the study, 84.5%of the cases had died, 12.1% were alive and 3.4% were considered "lost to follow-up".<br><br>CONCLUSION: BC is an important public health problem and affected most of the younger Central African women. Epidemiological and histological characteristics are more or less common to those described other developing countries. It is imperative to improve the awareness of health care institutions and women on the burden of BC, to carry out early screening of BC, and to strengthen the capacity of women's health care system.},
}
@article {pmid29621845,
year = {2018},
author = {Gilbert, B and Naidoo, TL and Redwig, F},
title = {Ins and outs of urinary catheters.},
journal = {Australian journal of general practice},
volume = {47},
number = {3},
pages = {132-136},
doi = {10.31128/AFP-10-17-4362},
pmid = {29621845},
issn = {2208-7958},
mesh = {Catheter-Related Infections/nursing/prevention &amp; control ; Clinical Competence/standards ; Humans ; Urinary Catheterization/*adverse effects/*standards/trends ; Urinary Catheters/adverse effects/standards/trends ; },
abstract = {BACKGROUND: Inserting an indwelling catheter (IDC) is a common medical procedure that is often performed poorly and inappropriately, and can lead to significant morbidity. Although most catheterisations are performed by nursing staff, medical personnel need to be aware of the procedure, products and common IDC complications.<br><br>OBJECTIVE: Current guidelines and literature were reviewed to outline catheterisation indications, catheter types and provide a general understanding of complications associated with IDCs for&amp;nbsp;the general practitioner (GP).<br><br>DISCUSSION: There is evidence that IDCs are often used when not indicated and improperly managed when inserted. IDCs can cause significant morbidity, prolong hospital stay and increase healthcare costs. Infection and traumatic insertion are common complications; advances in catheter design have helped to limit these complications. Most complications are avoidable, do not require specialist input and can be managed by community nurses or GPs. Reviewing indications, adopting proper technique for insertion and defining management strategies can limit complications.},
}
@article {pmid29621776,
year = {2018},
author = {Weigand, T and Singler, B and Fleming, T and Nawroth, P and Klika, KD and Thiel, C and Baelde, H and Garbade, SF and Wagner, AH and Hecker, M and Yard, BA and Amberger, A and Zschocke, J and Schmitt, CP and Peters, V},
title = {Carnosine Catalyzes the Formation of the Oligo/Polymeric Products of Methylglyoxal.},
journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology},
volume = {46},
number = {2},
pages = {713-726},
doi = {10.1159/000488727},
pmid = {29621776},
issn = {1421-9778},
mesh = {Animals ; Anserine/analysis/chemistry/metabolism ; Carnosine/analysis/*chemistry/*metabolism ; Cell Line ; Cell Survival/drug effects ; Chromatography, High Pressure Liquid ; Glutathione/analysis ; Glutathione Peroxidase/genetics/metabolism ; Glycation End Products, Advanced/chemistry/metabolism ; Humans ; Membrane Glycoproteins/metabolism ; Membrane Transport Proteins/metabolism ; Mice ; Oxidative Stress/drug effects ; Peptide Transporter 1/genetics/metabolism ; Podocytes/cytology/drug effects/metabolism ; Polymers/*chemistry/metabolism ; Pyruvaldehyde/*chemistry/toxicity ; Serum Albumin/chemistry ; Superoxide Dismutase/genetics/metabolism ; Symporters/genetics/metabolism ; },
abstract = {BACKGROUND/AIMS: Reactive dicarbonyl compounds, such as methylglyoxal (MG), contribute to diabetic complications. MG-scavenging capacities of carnosine and anserine, which have been shown to mitigate diabetic nephropathy, were evaluated in vitro and in vivo.<br><br>METHODS: MG-induced cell toxicity was characterized by MTT and MG-H1-formation, scavenging abilities by Western Blot and NMR spectroscopies, cellular carnosine transport by qPCR and microplate luminescence and carnosine concentration by HPLC.<br><br>RESULTS: In vitro, carnosine and anserine dose-dependently reduced N-carboxyethyl lysine (CEL) and advanced glycation end products (AGEs) formation. NMR studies revealed the formation of oligo/polymeric products of MG catalyzed by carnosine or anserine. MG toxicity (0.3-1 mM) was dose-dependent for podocytes, tubular and mesangial cells whereas low MG levels (0.2 mM) resulted in increased cell viability in podocytes (143&#xb1;13%, p<0.001) and tubular cells (129&#xb1;3%, p<0.001). Incubation with carnosine/anserine did not reduce MG-induced toxicity, independent of incubation times and across large ranges of MG to carnosine/anserine ratios. Cellular carnosine uptake was low (<0.1% in 20 hours) and cellular carnosine concentrations remained unaffected. The putative carnosine transporter PHT1 along with the taurine transporter (TauT) was expressed in all cell types while PEPT1, PEPT2 and PHT2, also belonging to the proton-coupled oligopeptide transporter (POT) family, were only expressed in tubular cells.<br><br>CONCLUSION: While carnosine and anserine catalyze the formation of MG oligo/polymers, the molar ratios required for protection from MG-induced cellular toxicity are not achievable in renal cells. The effect of carnosine in vivo, to mitigate diabetic nephropathy may therefore be independent upon its ability to scavenge MG and/or carnosine is mainly acting extracellularly.},
}
@article {pmid29602724,
year = {2019},
author = {Grimm, LJ and Saha, A and Ghate, SV and Kim, C and Soo, MS and Yoon, SC and Mazurowski, MA},
title = {Relationship between Background Parenchymal Enhancement on High-risk Screening MRI and Future Breast Cancer Risk.},
journal = {Academic radiology},
volume = {26},
number = {1},
pages = {69-75},
doi = {10.1016/j.acra.2018.03.013},
pmid = {29602724},
issn = {1878-4046},
mesh = {Adult ; Aged ; Breast/*diagnostic imaging ; Breast Neoplasms/diagnostic imaging/*epidemiology ; Carcinoma, Ductal, Breast/*epidemiology ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology ; Carcinoma, Lobular/*epidemiology ; Cohort Studies ; Early Detection of Cancer ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; North Carolina/epidemiology ; Parenchymal Tissue/*diagnostic imaging ; Retrospective Studies ; Risk Factors ; Young Adult ; },
abstract = {RATIONALE AND OBJECTIVES: To determine if background parenchymal enhancement (BPE) on screening breast magnetic resonance imaging (MRI) in high-risk women correlates with future cancer.<br><br>MATERIALS AND METHODS: All screening breast MRIs (n&#x2009;=&#x2009;1039) in high-risk women at our institution from August 1, 2004, to July 30, 2013, were identified. Sixty-one patients who subsequently developed breast cancer were matched 1:2 by age and high-risk indication with patients who did not develop breast cancer (n&#x2009;=&#x2009;122). Five fellowship-trained breast radiologists independently recorded the BPE. The median reader BPE for each case was calculated and compared between the cancer and control cohorts.<br><br>RESULTS: Cancer cohort patients were high-risk because of a history of radiation therapy (10%, 6 of 61), high-risk lesion (18%, 11 of 61), or breast cancer (30%, 18 of 61); BRCA mutation (18%, 11 of 61); or family history (25%, 15 of 61). Subsequent malignancies were invasive ductal carcinoma (64%, 39 of 61), ductal carcinoma in situ (30%, 18 of 61) and invasive lobular carcinoma (7%, 4of 61). BPE was significantly higher in the cancer cohort than in the control cohort (P&#x2009;=&#x2009;0.01). Women with mild, moderate, or marked BPE were 2.5 times more likely to develop breast cancer than women with minimal BPE (odds ratio&#x2009;=&#x2009;2.5, 95% confidence interval: 1.3-4.8, P&#x2009;=&#x2009;.005). There was fair interreader agreement (&#x3ba;&#x2009;=&#x2009;0.39).<br><br>CONCLUSIONS: High-risk women with greater than minimal BPE at screening MRI have increased risk of future breast cancer.},
}
@article {pmid29599319,
year = {2018},
author = {Litwin, M and Szczepańska-Buda, A and Michałowska, D and Grzegrzółka, J and Piotrowska, A and Gomułkiewicz, A and Wojnar, A and Dzięgiel, P and Witkiewicz, W},
title = {Aberrant Expression of PIWIL1 and PIWIL2 and Their Clinical Significance in Ductal Breast Carcinoma.},
journal = {Anticancer research},
volume = {38},
number = {4},
pages = {2021-2030},
doi = {10.21873/anticanres.12441},
pmid = {29599319},
issn = {1791-7530},
mesh = {Adult ; Aged ; Aged, 80 and over ; Argonaute Proteins/*biosynthesis/genetics ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cohort Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; RNA, Messenger/biosynthesis/genetics ; Real-Time Polymerase Chain Reaction ; },
abstract = {BACKGROUND/AIM: P-Element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) are involved in epigenetic regulation of gene expression in germline cells. Aberrant expression of piRNA and PIWI proteins have been identified in various types of tumour cells. The aim of this study was to evaluate the expression profiles of PIWI-like protein-1, -2 (PIWIL1 and PIWIL2), their immunohistochemical (IHC) characteristics in ductal breast cancer, and determine their correlation with clinicopathological parameters of this type of cancer.<br><br>MATERIALS AND METHODS: Material for IHC studies comprised of 101 invasive ductal carcinoma (IDC) cases and 31 mastopathy tissues. Frozen fragments of paired tissue specimens (tumour and adjacent non-malignant breast tissue) taken from 55 patients with IDC and 18 samples of mastopathy were used for molecular studies using real-time polymerase chain reaction (RT-PCR).<br><br>RESULTS: A statistically significantly higher level of PIWIL1 and PIWIL2 was found in IDC compared to mastopathy samples (p&#x2264;0.0001). Increased expression of PIWIL1 was correlated with increased PIWIL2 expression in breast cancer tissue. Surprisingly, PIWIL1 mRNA was detected only in cancer and mastopathy, but was not found in most normal breast tissues, although it is noteworthy that the PIWIL2 mRNA level was statistically significantly lower in mastopathy and IDC samples compared to normal breast tissues.<br><br>CONCLUSION: Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development.},
}
@article {pmid29579338,
year = {2018},
author = {Uemura, MI and French, JT and Hess, KR and Liu, D and Raghav, K and Hortobagyi, GN and Arun, BK and Valero, V and Ueno, NT and Alvarez, RH and Woodward, WA and Debeb, BG and Moulder, SL and Lim, B and Tripathy, D and Ibrahim, NK},
title = {Development of CNS metastases and survival in patients with inflammatory breast cancer.},
journal = {Cancer},
volume = {124},
number = {11},
pages = {2299-2305},
doi = {10.1002/cncr.31336},
pmid = {29579338},
issn = {1097-0142},
mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Breast/pathology/surgery ; Central Nervous System Neoplasms/*epidemiology/prevention &amp; control/secondary ; Chemotherapy, Adjuvant/methods ; Female ; Follow-Up Studies ; Humans ; Incidence ; Inflammatory Breast Neoplasms/mortality/*pathology/therapy ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/methods ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Taxoids/therapeutic use ; Treatment Outcome ; Young Adult ; },
abstract = {BACKGROUND: Inflammatory breast cancer (IBC) is associated with a poor prognosis and high risk of central nervous system (CNS) metastases.<br><br>METHODS: We retrospectively reviewed stage III-IBC patients compared with noninflammatory invasive ductal carcinoma (NI-IDC) patients treated between January 1, 1984, and December 31, 2011, who began primary treatment within 1 year of diagnosis and had been followed up for at least 1 year before the development of CNS metastasis or death. Cumulative CNS metastasis incidence and post-CNS metastasis overall survival (OS) estimates were computed. Multivariable Cox proportional hazard models explored factors for post-CNS metastasis survival.<br><br>RESULTS: A total of 2323 patients were identified (589-IBC/1734-NI-IDC). Eighty-one IBC patients developed CNS metastasis, versus 154 NI-IDC patients. The 2-, 5-, and 10-year cumulative CNS metastasis incidence rates in IBC and NI-IDC were 9.8%, 15.8%, 17.4% and 6.5%, 10.1%, and 12.7%, respectively. This was significantly different between IBC and NI-IDC patients (P = .0037). Multicovariate competing risk regression models in IBC and NI-IDC patients showed no statistically significant associations with the risk of developing CNS metastasis, except neoadjuvant taxane use in NI-IDC patients (hazard ratio, 0.45; 95% confidence interval, 0.24-0.83; P = .011). The median follow-up was 7.2 years, and the median post-CNS metastasis OS was not significantly different between IBC (7.6 months) and NI-IDC (5.6 months) patients. One hundred ninety patients with CNS metastasis died. HER2-positive patients had better OS, with a median 14.1 versus 4.3 months (P < .0001). Age >50 years (P = .012) but not IBC status was a significant predictor of post-CNS metastasis survival.<br><br>CONCLUSION: IBC patients demonstrated higher CNS metastasis incidence rates but OS following CNS metastases is similar in both groups. HER2 status and age may play prognostic roles. Cancer 2018;124:2299-305. &#xa9; 2018 American Cancer Society.},
}
@article {pmid29551677,
year = {2018},
author = {Luo, J and Feng, J and Wen, Q and Qoyawayma, C and Wang, W and Chen, L and Lu, J and Zhan, Y and Xu, L and Zang, H and Fan, S and Chu, S},
title = {Elevated expression of IRS-1 associates with phosphorylated Akt expression and predicts poor prognosis of breast invasive ductal carcinoma.},
journal = {Human pathology},
volume = {79},
number = {},
pages = {9-17},
doi = {10.1016/j.humpath.2018.03.003},
pmid = {29551677},
issn = {1532-8392},
mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*enzymology/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*enzymology/mortality/pathology/therapy ; Female ; Humans ; Immunohistochemistry ; Insulin Receptor Substrate Proteins/*analysis ; Middle Aged ; Neoplasm Invasiveness ; Phosphorylation ; Prognosis ; Proto-Oncogene Proteins c-akt/*analysis ; Risk Factors ; Time Factors ; Tissue Array Analysis ; Up-Regulation ; },
abstract = {Overexpression of insulin receptor substrate 1 (IRS-1) has been reported to promote cell growth, atypical hyperplasia, and carcinogenesis, and phosphorylated Akt (p-Akt) is certified to be involved in many types of cancers such as breast invasive ductal carcinoma (BIDC). However, the relationship between IRS-1 and Akt, as well as the role of expression of IRS-1 in BIDC, has never been reported. The purpose of this research is to investigate the association between expression of IRS-1 and p-Akt proteins and clinicopathological features of BIDC by immunohistochemistry, as well as the survival status. The results showed that the percentage of either elevated expression of IRS-1 or positive p-Akt expression in BIDC was significantly higher than that in control breast tissue from noncancer patients (P < .001 and P = .001, respectively). Overexpression of IRS-1 was evidently associated with positive expression of p-Akt (r = 0.337, P < .001). Also, positive percentage of p-Akt expression was statistically different among different molecular subtypes of BIDC (highest in luminal B BIDC, P = .009). Furthermore, significantly worse overall survival was found in BIDC patients with high expression of IRS-1 and p-Akt than in patients with low expression (P = .006 and P = .004, respectively). The multivariate Cox proportional hazard regression analysis showed that high expression of IRS-1 and positive expression of p-Akt protein were independent poor prognostic factors for patients with BIDC (P = .022 and P = .046, respectively). In conclusion, we report for the first time that overexpression of IRS-1 protein is associated with expression of p-Akt, and overexpression of IRS-1 and positive expression of p-Akt might be independent biomarkers for poor prognosis in BIDC.},
}
@article {pmid29551588,
year = {2018},
author = {Moraru, A and Wiederstein, J and Pfaff, D and Fleming, T and Miller, AK and Nawroth, P and Teleman, AA},
title = {Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes.},
journal = {Cell metabolism},
volume = {27},
number = {4},
pages = {926-934.e8},
doi = {10.1016/j.cmet.2018.02.003},
pmid = {29551588},
issn = {1932-7420},
mesh = {Animals ; Cells, Cultured ; Diabetes Mellitus, Type 2/*metabolism ; Drosophila melanogaster ; Hyperglycemia/metabolism ; Insulin Resistance ; Lactoylglutathione Lyase/genetics ; Obesity/metabolism ; Pyruvaldehyde/*metabolism ; },
abstract = {The molecular causes of type 2 diabetes (T2D) are not well understood. Both type 1 diabetes (T1D) and T2D are characterized by impaired insulin signaling and hyperglycemia. From analogy to T1D, insulin resistance and hyperglycemia are thought to also play causal roles in T2D. Recent clinical studies, however, found that T2D patients treated to maintain glycemia below the diabetes definition threshold (HbA1c < 6.5%) still develop diabetic complications. This suggests additional insulin- and glucose-independent mechanisms could be involved in T2D progression and/or initiation. T2D patients have elevated levels of the metabolite methylglyoxal (MG). We show here, using Drosophila glyoxalase 1 knockouts, that animals with elevated methylglyoxal recapitulate several core aspects of T2D: insulin resistance, obesity, and hyperglycemia. Thus elevated MG could constitute one root cause of T2D, suggesting that the molecular causes of elevated MG warrant further study.},
}
@article {pmid29546577,
year = {2018},
author = {Mendler, M and Kopf, S and Groener, JB and Riedinger, C and Fleming, TH and Nawroth, PP and Okun, JG},
title = {Urine levels of 5-aminoimidazole-4-carboxamide riboside (AICAR) in patients with type 2 diabetes.},
journal = {Acta diabetologica},
volume = {55},
number = {6},
pages = {585-592},
doi = {10.1007/s00592-018-1130-2},
pmid = {29546577},
issn = {1432-5233},
support = {CRC1118//Deutsche Forschungsgemeinschaft/ ; CRC1118//Deutsche Forschungsgemeinschaft/ ; CRC1118//Deutsche Forschungsgemeinschaft/ ; CRC1118//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Adenylate Kinase/metabolism ; Adult ; Aged ; Aminoimidazole Carboxamide/*analogs &amp; derivatives/urine ; Animals ; Case-Control Studies ; Cohort Studies ; Diabetes Complications/metabolism/prevention &amp; control/urine ; Diabetes Mellitus, Type 2/complications/metabolism/prevention &amp; control/*urine ; Female ; Humans ; Male ; Middle Aged ; Prediabetic State/pathology/therapy/urine ; Ribonucleotides/*urine ; Risk Factors ; Risk Reduction Behavior ; Signal Transduction/physiology ; },
abstract = {AIMS: 5-Aminoimidazole-4-carboxamide riboside (AICAR) is an endogenous activator of AMPK, a central regulator of energy homeostasis. Loss and/or reduction of AMPK signaling plays an important role in the development of insulin resistance in type 2 diabetes. The loss of AMPK in diabetes could be due to a loss of AICAR. The aim of this study was to characterize urine levels of AICAR in diabetes and determine whether an association exists with respect to late complications, e.g., retinopathy, nephropathy and neuropathy.<br><br>METHODS: Urine AICAR was measured by liquid chromatography tandem mass spectrometry in 223 patients consisting of 5 healthy controls, 63 patients with pre-diabetes, 29 patients with newly diagnosed type 2 diabetes and 126 patients with long-standing type 2 diabetes. For statistical analyses, nonparametric Kruskal-Wallis test, one-way ANOVA and multivariate regression analysis were performed to investigate the associations of urinary AICAR excretion within different groups and different clinical parameters.<br><br>RESULTS: The mean urine AICAR for all 223 patients was 694.7&#x2009;&#xb1;&#x2009;641.1&#xa0;ng/ml. There was no significant difference in urine AICAR between the control and patients with diabetes (592.3&#x2009;&#xb1;&#x2009;345.1 vs. 697.1&#x2009;&#xb1;&#x2009;646.5&#xa0;ng/ml). No association between any of the biochemical and/or clinical parameters measured and urine AICAR was found, with the exception of age of patient (R&#x2009;=&#x2009;-&#xa0;0.34; p&#x2009;<&#x2009;0.01) and estimated glomerular filtration rate (R&#x2009;=&#x2009;0.19; p&#x2009;=&#x2009;0.039). These results were confirmed additionally by linear regression analysis.<br><br>CONCLUSIONS: Clinical diabetes is not associated with a change in endogenous AICAR levels. Loss of AICAR may therefore not be a mechanism by which AMPK signaling is reduced in diabetes.},
}
@article {pmid29538201,
year = {2018},
author = {Hsu, CC and Li, WY and Chu, PY},
title = {Salivary duct carcinoma of the supraglottis with a distinct presentation: A case report and literature review.},
journal = {Medicine},
volume = {97},
number = {11},
pages = {e0095},
pmid = {29538201},
issn = {1536-5964},
mesh = {Airway Obstruction/etiology/surgery ; *Carcinoma/pathology/physiopathology/therapy ; Chemoradiotherapy/*methods ; *Cytoreduction Surgical Procedures/instrumentation/methods ; Humans ; *Larynx/pathology/physiopathology/surgery ; Lasers, Gas/therapeutic use ; Lymphatic Metastasis/pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Salivary Ducts/*pathology ; *Salivary Gland Neoplasms/pathology/physiopathology/therapy ; Salivary Glands, Minor/*pathology ; Treatment Outcome ; },
abstract = {RATIONALE: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. We present the first case of advanced SDC of the minor salivary gland arising from the supraglottis and review the literature on the clinicopathologic characteristics and prognosis of SDC.<br><br>PATIENT CONCERNS: A 59-year-old male patient with progressive difficulty in swallowing and a muffled voice for 2 months.<br><br>DIAGNOSES: The patient was diagnosed with SDC arising from the supraglottis with extensive tumor invasion into the subsites of the larynx and pharynx.<br><br>INTERVENTIONS: Due to impending airway obstruction, the patient underwent CO2 laser debulking surgery. In addition to local disease, lymph node and distant metastases were also noted at diagnosis and concurrent chemoradiation therapy was arranged.<br><br>OUTCOMES: Laryngeal function was preserved and tracheostomy was avoided. The patient has survived for >1 year after the initial diagnosis.<br><br>LESSONS: SDC is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. Here we presented the first case of advanced SDC of the minor salivary gland arising from the supraglottis that was treated with CO2 laser debulking surgery followed by concurrent chemoradiation therapy. Due to their rarity, further studies are required to establish the most effective treatment protocol for advanced SDC.},
}
@article {pmid29528718,
year = {2018},
author = {Kizy, S and Huang, JL and Marmor, S and Blaes, A and Yuan, J and Beckwith, H and Tuttle, TM and Hui, JYC},
title = {Distribution of 21-Gene Recurrence Scores Among Breast Cancer Histologic Subtypes.},
journal = {Archives of pathology &amp; laboratory medicine},
volume = {142},
number = {6},
pages = {735-741},
doi = {10.5858/arpa.2017-0169-OA},
pmid = {29528718},
issn = {1543-2165},
mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/classification/epidemiology/*genetics/pathology ; Epidemiological Monitoring ; Female ; Humans ; Logistic Models ; Middle Aged ; Receptor, ErbB-2/*genetics ; Risk Factors ; United States/epidemiology ; Young Adult ; },
abstract = {CONTEXT: - The 21-gene recurrence score (RS) provides a probability of distant recurrence for estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. The utility of RS for rarer histologic subtypes of breast cancer is uncertain.<br><br>OBJECTIVE: - To determine the distribution of RS among various histologic subtypes using a population database.<br><br>DESIGN: - Women between the ages of 18 and 75 with estrogen receptor-positive, HER2-negative breast cancer and known RS results were identified using the Surveillance, Epidemiology, and End Results database. Recurrence scores were categorized into risk groups using both traditional and Trial Assigning Individualized Options for Treatment cutoffs. Multivariable logistic regression was used to determine factors associated with high-risk RS.<br><br>RESULTS: - We identified 45&#x2009;618 patients with stage I to III, estrogen receptor-positive, HER2-negative breast cancer who had RS available. Overall, 3087 (7%) and 6337 (14%) of cancers were classified as high risk based on traditional and Trial Assigning Individualized Options for Treatment RS cutoffs, respectively. The proportion of high-risk RS ranged from 1% (tubular, 2 of 225) to 68% (medullary, 13 of 19) and 4% (tubular, 10 of 225) to 79% (medullary, 15 of 19) for traditional and Trial Assigning Individualized Options for Treatment cutoffs, respectively. Based on multivariable logistic regression (excluding medullary), subtypes other than invasive ductal carcinoma and papillary carcinoma were significantly associated with lower RS. The strongest predictors of a high-risk RS were higher tumor grade and negative progesterone receptor status.<br><br>CONCLUSIONS: - We identified distinct distributions of RS among different histologic subtypes of breast cancer. Excluding medullary carcinoma, histologic subtypes other than invasive ductal carcinoma and papillary carcinoma all predict lower RS.},
}
@article {pmid29522808,
year = {2018},
author = {Levy, DA and Mika, R and Radzyminski, C and Ben-Zvi, S and Tibon, R},
title = {Behavioral reconsolidation interference with episodic memory within-subjects is elusive.},
journal = {Neurobiology of learning and memory},
volume = {150},
number = {},
pages = {75-83},
pmid = {29522808},
issn = {1095-9564},
support = {MC_UU_00005/8/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Adult ; Cues ; Female ; Humans ; Male ; Memory Consolidation/*physiology ; *Memory, Episodic ; Mental Recall/*physiology ; Photic Stimulation ; Young Adult ; },
abstract = {In studies of behavioral reconsolidation interference, reactivation of a consolidated memory using some form of reminder is followed by the presentation of new information that can cause interference with that memory. Under these conditions, the interference not only impairs retrieval by indirect processes such as cue interference, but supposedly disrupts the original memory trace directly. Almost all studies of behavioral reconsolidation interference in episodic memory in humans have employed between-subjects paradigms, and deduced reminder effects from intrusion errors. Such studies might introduce confounds arising, for example, from differences in retrieval strategies engendered by the pre-test treatments. We therefore set out to examine whether behavioral reconsolidation interference in episodic memory might be demonstrated within-subjects and by direct memory strength rather than intrusion errors. In three separate experiments, we attempted to disrupt reconsolidation of episodic object-picture memory using a reminder + retroactive interference manipulation. We applied the manipulation over three consecutive days, using a forced-choice recognition test without intrusions from interfering learning, keeping all other study and test parameters constant. No effects of reminder-potentiated interference were observed for measures of accuracy, response times, subjective expressions of recollection, or levels of confidence, as substantiated by Bayesian analyses. These results highlight the difficulty of observing clear behavioral reconsolidation interference effects within-subjects in human episodic memory, and provide some indications of what might be boundary conditions for its demonstration.},
}
@article {pmid29516978,
year = {2018},
author = {Li, F and Ren, Y and Wang, Z},
title = {Programmed death 1 Ligand 1 expression in breast cancer and its association with patients' clinical parameters.},
journal = {Journal of cancer research and therapeutics},
volume = {14},
number = {1},
pages = {150-154},
doi = {10.4103/jcrt.JCRT_602_17},
pmid = {29516978},
issn = {1998-4138},
mesh = {Adult ; Aged ; B7-H1 Antigen/*genetics/metabolism ; *Biomarkers, Tumor ; Breast Neoplasms/drug therapy/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/pathology ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; },
abstract = {OBJECTIVE: To evaluate the expression of programmed death 1 ligand 1 (PD-L1) in the cancer tissues and tumor-adjacent normal tissues of patients with invasive ductal carcinoma of the breast and to analyze the relationship between the expression of PD-L1 and the clinicopathological features of patients.<br><br>MATERIALS AND METHODS: This study included 112 cases of patients with invasive ductal carcinoma of breast who received surgical treatment from March 2012 to February 2016 in Xuzhou Cancer Hospital. The clinical materials of included patients were retrospectively analyzed. The immunohistochemical assay and real-time polymerase chain reaction (PCR) assay were applied to examine the expression of mRNA and protein of PD-L1 in breast cancer specimens of 112 cases and paired tumor-adjacent tissue specimens of 57 cases. The relationship between PD-L1 protein expression and clinicopathological features of patients was analyzed.<br><br>RESULTS: PD-L1 protein was mainly expressed in the cytoplasm. The positive rate of PD-L1 expression in invasive ductal carcinoma was 19.6% (22/112), and the positive rate of PD-L1 expression of tumor-adjacent normal tissues was 3.5% (2/57), indicating that the positive rate of PD-L1 expression of cancerous tissues was significantly higher than that of in tumor-adjacent normal tissues (P < 0.05); the positive expression of PD-L1 was not related with the patients' age, menopause history, family history of breast cancer, tumor size, and location of the tumor (P > 0.05) while it was related with lymph node metastasis, the clinic staging, and histopathological grading (P < 0.05). Real-time PCR was applied to detect the mRNA expression of PD-L1 in breast-invasive ductal carcinoma with the mean &#x394;Ct value of 7.79 &#xb1; 2.25. However, the mRNA expression of PD-L1 in normal tumor-adjacent tissues was of low expression with the mean &#x394;Ct value of 12.37 &#xb1; 3.33. The difference was statistically significant (P< 0.05).<br><br>CONCLUSION: The expression of PD-L1 in breast-invasive ductal carcinoma was significantly increased, and it was related to histological grading, clinical staging, and lymph node metastasis of breast cancer. PD-L1 may be a significant marker for the prognosis of breast cancer patients.},
}
@article {pmid29513137,
year = {2018},
author = {Ein-Dor, T and Verbeke, WJMI and Mokry, M and Vrtička, P},
title = {Epigenetic modification of the oxytocin and glucocorticoid receptor genes is linked to attachment avoidance in young adults.},
journal = {Attachment &amp; human development},
volume = {20},
number = {4},
pages = {439-454},
doi = {10.1080/14616734.2018.1446451},
pmid = {29513137},
issn = {1469-2988},
mesh = {Adult ; *Avoidance Learning ; DNA Methylation/genetics ; *Epigenesis, Genetic ; Female ; Humans ; Interpersonal Relations ; Male ; *Object Attachment ; Receptors, Glucocorticoid/*genetics ; Receptors, Oxytocin/*genetics ; Self Report ; Stress, Psychological ; Young Adult ; },
abstract = {Attachment in the context of intimate pair bonds is most frequently studied in terms of the universal strategy to draw near, or away, from significant others at moments of personal distress. However, important interindividual differences in the quality of attachment exist, usually captured through secure versus insecure - anxious and/or avoidant - attachment orientations. Since Bowlby's pioneering writings on the theory of attachment, it has been assumed that attachment orientations are influenced by both genetic and social factors - what we would today describe and measure as gene by environment interaction mediated by epigenetic DNA modification - but research in humans on this topic remains extremely limited. We for the first time examined relations between intra-individual differences in attachment and epigenetic modification of the oxytocin receptor (OXTR) and glucocorticoid receptor (NR3C1) gene promoter in 109 young adult human participants. Our results revealed that attachment avoidance was significantly and specifically associated with increased OXTR and NR3C1 promoter methylation. These findings offer first tentative clues on the possible etiology of attachment avoidance in humans by showing epigenetic modification in genes related to both social stress regulation and HPA axis functioning.},
}
@article {pmid29505681,
year = {2018},
author = {Schmitt, FCF and Salgado, E and Friebe, J and Schmoch, T and Uhle, F and Fleming, T and Zemva, J and Kihm, L and Nusshag, C and Morath, C and Zeier, M and Bruckner, T and Mehrabi, A and Nawroth, PP and Weigand, MA and Hofer, S and Brenner, T},
title = {Cell cycle arrest and cell death correlate with the extent of ischaemia and reperfusion injury in patients following kidney transplantation - results of an observational pilot study.},
journal = {Transplant international : official journal of the European Society for Organ Transplantation},
volume = {31},
number = {7},
pages = {751-760},
doi = {10.1111/tri.13148},
pmid = {29505681},
issn = {1432-2277},
mesh = {Biomarkers/blood/urine ; C-Reactive Protein/metabolism ; *Cell Cycle Checkpoints ; *Cell Death ; Cold Ischemia/*adverse effects ; Delayed Graft Function ; Humans ; Keratin-18/blood/urine ; Kidney Transplantation/*adverse effects ; Middle Aged ; Pilot Projects ; Receptor for Advanced Glycation End Products/blood ; Reperfusion Injury/*etiology ; Transplantation Immunology ; },
abstract = {A prolonged cold ischaemia time (CIT) is suspected to be associated with an increased ischaemia and reperfusion injury (IRI) resulting in an increased damage to the graft. In total, 91 patients were evaluated for a delayed graft function within 7 days after kidney transplantation (48 deceased, 43 living donors). Blood and urine samples were collected before, immediately after the operation, and 1, 3, 5, 7 and 10 days later. Plasma and/or urine levels of total keratin 18 (total K18), caspase-cleaved keratin 18 (cc K18), the soluble receptor for advanced glycation end products (sRAGE), tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP7) were measured. As a result of prolonged CIT and increased IRI, deceased donor transplantations were shown to suffer from a more distinct cell cycle arrest and necrotic cell death. Plasmatic total K18 and urinary TIMP-2 and IGFBP7 were therefore demonstrated to be of value for the detection of a delayed graft function (DGF), as they improved the diagnostic performance of a routinely used clinical scoring system. Plasmatic total K18 and urinary TIMP-2 and IGFBP7 measurements are potentially suitable for early identification of patients at high risk for a DGF following kidney transplantation from deceased or living donors.},
}
@article {pmid29495422,
year = {2018},
author = {Xu, H and Dorn, GW and Shetty, A and Parihar, A and Dave, T and Robinson, SW and Gottlieb, SS and Donahue, MP and Tomaselli, GF and Kraus, WE and Mitchell, BD and Liggett, SB},
title = {A Genome-Wide Association Study of Idiopathic Dilated Cardiomyopathy in African Americans.},
journal = {Journal of personalized medicine},
volume = {8},
number = {1},
pages = {},
pmid = {29495422},
issn = {2075-4426},
support = {P30 DK072488/DK/NIDDK NIH HHS/United States ; P50 HL077107/HL/NHLBI NIH HHS/United States ; R35 HL135736/HL/NHLBI NIH HHS/United States ; },
abstract = {Idiopathic dilated cardiomyopathy (IDC) is the most common form of non-ischemic chronic heart failure. Despite the higher prevalence of IDC in African Americans, the genetics of IDC have been relatively understudied in this ethnic group. We performed a genome-wide association study to identify susceptibility genes for IDC in African Americans recruited from five sites in the U.S. (662 unrelated cases and 1167 controls). The heritability of IDC was calculated to be 33% (95% confidence interval: 19-47%; p = 6.4 × 10[-7]). We detected association of a variant in a novel intronic locus in the CACNB4 gene meeting genome-wide levels of significance (p = 4.1 × 10[-8]). The CACNB4 gene encodes a calcium channel subunit expressed in the heart that is important for cardiac muscle contraction. This variant has not previously been associated with IDC in any racial group. Pathway analysis, based on the 1000 genes most strongly associated with IDC, showed an enrichment for genes related to calcium signaling, growth factor signaling, neuronal/neuromuscular signaling, and various types of cellular level signaling, including gap junction and cAMP signaling. Our results suggest a novel locus for IDC in African Americans and provide additional insights into the genetic architecture and etiology.},
}
@article {pmid29483434,
year = {2018},
author = {Ishizuka, M and Tsubota, Y and Ueda, A and Sueoka, N and Yoshikawa, K and Yamamoto, D},
title = {[Local Control by Mastectomy in Advanced Breast Cancer with Liver Metastasis after Chemotherapy, Radiotherapy, and Hyperthermia - A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {45},
number = {2},
pages = {321-323},
pmid = {29483434},
issn = {0385-0684},
mesh = {Biopsy, Needle ; Breast Neoplasms/pathology/*therapy ; Chemoradiotherapy ; Female ; Fever ; Humans ; Liver Neoplasms/secondary/*therapy ; Mastectomy ; Middle Aged ; },
abstract = {Advanced breast cancer has a poor prognosis compared to early breast cancer; however, quality of life and radical operation can be improved in some case by using multidisciplinary treatment. A 54-year-old woman was examined at the hospital because of an enlarging tumor in the left breast. She was aware of a lump for 3 years. Results of the initial examination indicated invasive ductal carcinoma with liver metastasis. She first received chemotherapy(AC followed by weekly paclitaxel). After 4 courses of weekly paclitaxel, computed tomography revealed axillary lymph nodes involved in the axillary vein. Operation was difficult and conversion therapy was administered. The patient underwent radiotherapy, hyperthermia, and hormone therapy. After 1 year from the start of hormone therapy, the metastasis had disappeared and the patient underwent operation in our unit. Eight months after operation, no recurrence was observed.},
}
@article {pmid29480844,
year = {2018},
author = {Wang, X and Jin, M and Ye, Q and Wang, M and Hu, Y and Yang, Y and Yang, J and Cai, J},
title = {Solitary duodenum metastasis from breast cancer with 8 years' latency: A case report.},
journal = {Medicine},
volume = {97},
number = {2},
pages = {e9550},
pmid = {29480844},
issn = {1536-5964},
mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Diagnosis, Differential ; Duodenal Neoplasms/drug therapy/pathology/*secondary/surgery ; Female ; Humans ; Middle Aged ; },
abstract = {RATIONALE: Advanced breast cancer frequently metastasizes to the lungs, liver, and bones. Metastatic involvement of the duodenal bulb is extremely rare and difficult to detect by endoscopy.<br><br>PATIENT CONCERNS: A 51-year-old menopausal woman presented with abdominal fullness and obstructive symptoms, and was diagnosed with adenocarcinoma in the duodenal bulb. The patient had undergone modified radical mastectomy of the left breast for infiltrating ductal carcinoma (IDC) 8 years previously.<br><br>DIAGNOSIS: Metastatic infiltration of the duodenal bulb originating from IDC was proven histologically and immunohistochemically.<br><br>INTERVENTIONS: She received chemotherapy with docetaxel and capecitabine followed by hormone maintenance therapy with letrozole after operation.<br><br>OUTCOMES: After treatment, the patient recovered well. She is currently being followed up.<br><br>LESSONS: Patients with known breast cancer history with the IDC histological type and presenting with nonspecific abdominal symptoms or signs, such as abdominal fullness, nausea, and vomiting, should undergo endoscopy with histopathological examination in order to detect possible gastrointestinal metastasis of the primary breast tumor. This report intends to alert people to heed this type of breast cancer metastasis and not treat it as a primary gastrointestinal tumor.},
}
@article {pmid29475895,
year = {2018},
author = {Rhone, P and Ruszkowska-Ciastek, B and Bielawski, K and Brkic, A and Zarychta, E and Góralczyk, B and Roszkowski, K and Rość, D},
title = {Comprehensive analysis of haemostatic profile depending on clinicopathological determinants in breast cancer patients.},
journal = {Bioscience reports},
volume = {38},
number = {2},
pages = {},
pmid = {29475895},
issn = {1573-4935},
mesh = {Aged ; Breast Neoplasms/*blood/pathology ; Female ; Humans ; Lipoproteins/blood ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/*blood ; Plasminogen Activator Inhibitor 1/blood ; Thromboplastin/metabolism ; Tissue Plasminogen Activator/blood ; },
abstract = {Thrombosis is one of the leading causes of mortality in cancer patients. The aim of the study was to evaluate the concentrations and activities of selected haemostatic parameters in the plasma of patients diagnosed with breast cancer (BrCa) and to make an attempt at finding associations with their levels and selected clinicopathological factors; clinical classification, histological grading, and molecular subtype of BrCa. The study involved 145 Caucasian ethnicity women. Eighty-five women aged 45-66 with primary BrCa without distant metastases (M0). Inclusion criteria were as follows: histopathological examination confirming the diagnosis of primary BrCa, without previous radiotherapy and chemotherapy. The control group consisted of 60, post-menopausal women, aged 45-68. Haemostatic profile expressed by concentrations and activities of tissue factor (TF) and its inhibitor (TFPI) as well as concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured applying immunoassay techniques. A significantly higher concentration of PAI-1 was noted in patients with BrCa localized in the left breast. We observed significantly lower activity of TFPI and significantly higher concentration of PAI-1 in the group of patients with invasive ductal carcinoma as compared with invasive lobular carcinoma. A significantly higher concentration of t-PA in patients with pT2 BrCa in relation to pT1 cases was noted. Based on comprehensive analysis of haemostatic profile depending on clinicopathological features, we suggest that haemostatic parameters play crucial roles in invasion and metastases of malignant tumours.},
}
@article {pmid29471435,
year = {2018},
author = {Desmedt, C and Salgado, R and Fornili, M and Pruneri, G and Van den Eynden, G and Zoppoli, G and Rothé, F and Buisseret, L and Garaud, S and Willard-Gallo, K and Brown, D and Bareche, Y and Rouas, G and Galant, C and Bertucci, F and Loi, S and Viale, G and Di Leo, A and Green, AR and Ellis, IO and Rakha, EA and Larsimont, D and Biganzoli, E and Sotiriou, C},
title = {Immune Infiltration in Invasive Lobular Breast Cancer.},
journal = {Journal of the National Cancer Institute},
volume = {110},
number = {7},
pages = {768-776},
pmid = {29471435},
issn = {1460-2105},
mesh = {Breast Neoplasms/diagnosis/*immunology/metabolism/*pathology ; Carcinoma, Lobular/diagnosis/*immunology/metabolism/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Lymphocyte Count ; Lymphocytes, Tumor-Infiltrating/metabolism/*pathology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; },
abstract = {BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC.<br><br>METHODS: We considered two patient series with TIL data: a multicentric retrospective series (n&#x2009;=&#x2009;614) and the BIG 02-98 study (n&#x2009;=&#x2009;149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n&#x2009;=&#x2009;159) and IDC (n&#x2009;=&#x2009;468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n&#x2009;=&#x2009;98) and IDC (n&#x2009;=&#x2009;388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided.<br><br>RESULTS: TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P < .001). In ILC, high TIL levels were associated with young age, lymph node involvement, and high proliferative tumors. In the univariate analysis, high TIL levels were associated with worse prognosis in the retrospective and BIG 02-98 lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition.<br><br>CONCLUSIONS: This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.},
}
@article {pmid29470686,
year = {2018},
author = {Fukuda, J and Tanaka, S and Ishida, N and Ioka, T and Ikezawa, K and Takakura, R and Nakao, M and Ohkawa, K and Katayama, K and Nagata, S},
title = {A case of stage IA pancreatic ductal adenocarcinoma accompanied with focal pancreatitis demonstrated by contrast-enhanced ultrasonography.},
journal = {Journal of medical ultrasonics (2001)},
volume = {45},
number = {4},
pages = {617-622},
pmid = {29470686},
issn = {1613-2254},
mesh = {Carcinoma, Pancreatic Ductal/complications/*diagnostic imaging/pathology/surgery ; *Contrast Media ; Early Diagnosis ; Female ; Humans ; *Microbubbles ; Middle Aged ; Neoplasm Staging ; Pancreas/diagnostic imaging/pathology ; Pancreatic Neoplasms/complications/*diagnostic imaging/pathology/surgery ; Pancreatitis/complications/*diagnostic imaging/pathology ; Tomography, X-Ray Computed ; *Ultrasonography ; },
abstract = {A patient with slight dilatation of the main pancreatic duct was followed-up with ultrasonography every 6 months as a high-risk case of pancreatic cancer. Twelve years later, a faint hypoechoic area 13 mm in diameter was first detected on the body of the pancreas. Contrast-enhanced ultrasonography revealed a well-demarcated hypoenhanced area 8 mm in diameter and a hyperenhanced area with an unclear margin. The former was suspected to be a small pancreatic cancer lesion, and the latter to be focal pancreatitis accompanying cancer. However, contrast-enhanced dynamic CT did not suggest any tumor, diagnosis of adenocarcinoma was confirmed with pancreatic juice cytology through endoscopic retrograde pancreatography. Surgical resection was performed, and the lesion was pathologically diagnosed as invasive ductal carcinoma as follows: pTS1 (1.0 cm), infiltrative type (pT1), stage IA. When comparing the images from contrast-enhanced ultrasonography with the pathological findings, the hypoenhanced area corresponded to ductal adenocarcinoma, and the hyperenhanced area to focal pancreatitis. Contrast-enhanced ultrasonography was able to reveal detailed information on the focal lesion in the pancreas, and it was effective for the early diagnosis of pancreatic cancer.},
}
@article {pmid29461494,
year = {2018},
author = {Seimon, RV and Wild-Taylor, AL and Gibson, AA and Harper, C and McClintock, S and Fernando, HA and Hsu, MSH and Luz, FQD and Keating, SE and Johnson, NA and Grieve, SM and Markovic, TP and Caterson, ID and Byrne, NM and Sainsbury, A},
title = {Less Waste on Waist Measurements: Determination of Optimal Waist Circumference Measurement Site to Predict Visceral Adipose Tissue in Postmenopausal Women with Obesity.},
journal = {Nutrients},
volume = {10},
number = {2},
pages = {},
pmid = {29461494},
issn = {2072-6643},
mesh = {*Adiposity ; Aged ; Anthropometry/*methods ; Female ; Humans ; Intra-Abdominal Fat/*diagnostic imaging/physiopathology ; *Magnetic Resonance Imaging ; Middle Aged ; Obesity/*diagnosis/diagnostic imaging/physiopathology ; *Postmenopause ; Predictive Value of Tests ; Reproducibility of Results ; *Waist Circumference ; },
abstract = {With obesity being a leading cause of preventable death, it is vital to understand how best to identify individuals with greater risk of metabolic disease, especially those with high visceral adipose tissue (VAT). This study aimed to determine whether three commonly used waist circumference (WC) measurement sites could provide accurate estimations of VAT, as determined by magnetic resonance imaging (MRI), which is a gold standard for measuring VAT, in postmenopausal women with obesity. VAT volume was measured by MRI of the total abdomen in 97 women aged 57.7 ± 0.4 years (mean ± SEM), mean body mass index 34.5 ± 0.2 kg/m[2]. WC was measured at the midpoint between the lowest rib and the iliac crest (WCmid), the narrowest point of the torso (WCnarrow), and at the level of the umbilicus (WCumbilicus). WC differed significantly according to measurement site, with WCnarrow (102.1 ± 0.7 cm) < WCmid (108.3 ± 0.7 cm) < WCumbilicus (115.7 ± 0.8 cm) (p < 0.001). WCmid, WCnarrow and WCumbilicus were all significantly correlated with VAT, as measured by MRI (r = 0.581, 0.563 and 0.390, respectively; p < 0.001 for all), but the relationships between WCmid or WCnarrow and VAT determined by MRI were stronger than for WCumbilicus. Measurement of either WCmid or WCnarrow provides valid estimates of VAT in postmenopausal women with obesity, with WCnarrow being favoured in light of its greater ease and speed of measurement in this population.},
}
@article {pmid29436376,
year = {2018},
author = {Yu, BH and Tang, SX and Xu, XL and Cheng, YF and Bi, R and Shui, RH and Tu, XY and Lu, HF and Zhou, XY and Yang, WT},
title = {Breast carcinoma in sclerosing adenosis: a clinicopathological and immunophenotypical analysis on 206 lesions.},
journal = {Journal of clinical pathology},
volume = {71},
number = {6},
pages = {546-553},
doi = {10.1136/jclinpath-2017-204751},
pmid = {29436376},
issn = {1472-4146},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis/genetics ; Biopsy ; Breast Carcinoma In Situ/*chemistry/genetics/pathology/surgery ; Breast Neoplasms/*chemistry/genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/genetics/pathology/surgery ; Carcinoma, Lobular/*chemistry/genetics/pathology/surgery ; Diagnostic Errors ; Female ; Fibrocystic Breast Disease/*chemistry/genetics/pathology/surgery ; Humans ; *Immunohistochemistry ; Immunophenotyping/*methods ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Phenotype ; Predictive Value of Tests ; Reproducibility of Results ; Retrospective Studies ; *Sclerosis ; Tumor Burden ; },
abstract = {AIMS: To fully elucidate the clinicopathological features of breast carcinoma in sclerosing adenosis (SA-BC).<br><br>METHODS: Clinical and histological characteristics of 206 SA-BCs from 180 patients were retrospectively evaluated. Immunohistochemical phenotype was examined. The clinicopathological relevance of the topographical pattern of SA-BCs was analysed.<br><br>RESULTS: Overall, up to 46 patients (25.6%) had contralateral cancer, either SA associated or not. Of 99 cases who underwent core needle biopsy (CNB), 36 were underestimated as adenosis or atypical ductal hyperplasia at CNB, 5 invasive cases were misinterpreted as in situ carcinomas, whereas 4 ductal carcinoma in situ (DCIS) cases were overdiagnosed as invasive carcinoma. Microscopically, 163 tumours were in situ, including 136 DCIS, 19 lobular carcinomas in situ (LCIS) and 8 mixed DCIS/LCIS; of these carcinomas in situ (CIS), 37 had microinvasion. The DCIS group exhibited low, intermediate and high grades in 53.7%, 34.6% and 11.8% of cases, respectively, mostly with solid (43.4%) or cribriform (41.9%) pattern. Forty out of 43 invasive cases were invasive ductal carcinoma (IDC), mostly DCIS predominant. Immunophenotypically, luminal A phenotype was identified in 55.1%, 63.2% and 45.0% of DCIS, LCIS and IDC cases, respectively. Topographical type A group (carcinoma being entirely confined to SA, n=176) was characterised by smaller size, less invasiveness, lower grade and more frequency of luminal A immunophenotype compared with type B group (&#x2265; 50% but not all of the carcinomatous lesion being located in SA, n=30) (all P<0.05).<br><br>CONCLUSIONS: CIS, especially non-high-grade DCIS, represents the most common variant of SA-BC, and luminal A is the most predominant immunophenotype. CNB assessment might be challenging in some SA-BCs. The topographical pattern has great clinicopathological relevance. Careful evaluation of the contralateral breast and long-term follow-up for patients with SA-BC is necessary given its high prevalence of bilaterality.},
}
@article {pmid29422258,
year = {2018},
author = {Papachristopoulou, G and Papadopoulos, EI and Nonni, A and Rassidakis, GZ and Scorilas, A},
title = {Expression Analysis of miR-29b in Malignant and Benign Breast Tumors: A Promising Prognostic Biomarker for Invasive Ductal Carcinoma With a Possible Histotype-Related Expression Status.},
journal = {Clinical breast cancer},
volume = {18},
number = {4},
pages = {305-312.e3},
doi = {10.1016/j.clbc.2017.11.007},
pmid = {29422258},
issn = {1938-0666},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology/therapy ; Carcinoma, Ductal, Breast/genetics/*pathology/therapy ; Carcinoma, Lobular/genetics/pathology/therapy ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Prognosis ; ROC Curve ; Survival Analysis ; },
abstract = {BACKGROUND: Aberrations in microRNA levels seem to provide valuable information regarding breast cancer prognosis and therapy. In this study, we sought to analyze miR-29b expression in breast tumors and thus explore its clinical value.<br><br>MATERIALS AND METHODS: One hundred twenty-one malignant and 56 benign breast tissue specimens were collected and subjected to extraction of total RNA, which was polyadenylated and reverse transcribed to cDNA. Subsequently, a highly sensitive quantitative real-time polymerase chain reaction protocol was developed and miR-29b levels, estimated via the comparative CT method, were finally subjected to comprehensive statistical analysis.<br><br>RESULTS: MiR-29b levels did not differ between the analyzed benign and malignant breast tissue specimens, but were found to be significantly (P&#xa0;= .010) decreased in invasive ductal adenocarcinomas compared with their lobular counterparts, albeit receiver operating characteristics curve analysis did not verify the latter correlation. Additionally, miR-29b expression was elevated in samples with positive estrogen receptor status (P&#xa0;= .021) in the overall population, whereas it was negatively correlated (P&#xa0;= .035) with primary tumor staging in the ductal subset and increased in poorly-differentiated tumors of lobular origin (P&#xa0;= .041). Furthermore, Kaplan-Meier and Cox regression analyses showed that patients with ductal carcinoma and elevated miR-29b levels had a significantly longer disease-free survival (P&#xa0;= .010) and a lower risk to relapse (hazard ratio&#xa0;= 0.35, 95% confidence interval, 0.15-0.81; P&#xa0;= .014).<br><br>CONCLUSION: Our results provide evidence that miR-29b levels constitute a promising biomarker of favorable prognosis for patients with invasive ductal breast carcinoma and imply that its expression status might be affected by the histological origin of breast malignancy.},
}
@article {pmid29416801,
year = {2018},
author = {More, TH and RoyChoudhury, S and Christie, J and Taunk, K and Mane, A and Santra, MK and Chaudhury, K and Rapole, S},
title = {Metabolomic alterations in invasive ductal carcinoma of breast: A comprehensive metabolomic study using tissue and serum samples.},
journal = {Oncotarget},
volume = {9},
number = {2},
pages = {2678-2696},
pmid = {29416801},
issn = {1949-2553},
abstract = {Invasive ductal carcinoma (IDC) is the most common type of breast cancer and the leading cause of breast cancer related mortality. In the present study, metabolomic profiles of 72 tissue samples and 146 serum samples were analysed using targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM/MS) and untargeted gas chromatography mass spectrometry (GC-MS) approaches. Combination of univariate and multivariate statistical treatment identified significant alterations of 42 and 32 metabolites in tissue and serum samples of IDC, respectively when compared to control. Some of the metabolite changes from tissue were also reflected in serum, indicating a bi-directional interaction of metabolites in IDC. Additionally, 8 tissue metabolites and 9 serum metabolites showed progressive change from control to benign to IDC suggesting their possible role in malignant transformation. We have identified a panel of three metabolites viz. tryptophan, tyrosine, and creatine in tissue and serum, which could be useful in screening of IDC subjects from both control and benign. The metabolomic alterations in IDC showed perturbations in purine and pyrimidine metabolism, amino sugar metabolism, amino acid metabolism, fatty acid biosynthesis etc. Comprehensively, this study provides valuable insights into metabolic adaptations of IDC, which can help to identify diagnostic markers as well as potential therapeutic targets.},
}
@article {pmid29403520,
year = {2018},
author = {Waters, BM and Amundsen, K and Graef, G},
title = {Gene Expression Profiling of Iron Deficiency Chlorosis Sensitive and Tolerant Soybean Indicates Key Roles for Phenylpropanoids under Alkalinity Stress.},
journal = {Frontiers in plant science},
volume = {9},
number = {},
pages = {10},
pmid = {29403520},
issn = {1664-462X},
support = {P20 GM103427/GM/NIGMS NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; P30 GM110768/GM/NIGMS NIH HHS/United States ; },
abstract = {Alkaline soils comprise 30% of the earth and have low plant-available iron (Fe) concentration, and can cause iron deficiency chlorosis (IDC). IDC causes soybean yield losses of $260 million annually. However, it is not known whether molecular responses to IDC are equivalent to responses to low iron supply. IDC tolerant and sensitive soybean lines provide a contrast to identify specific factors associated with IDC. We used RNA-seq to compare gene expression under combinations of normal pH (5.7) or alkaline pH (7.7, imposed by 2.5 mM bicarbonate, or pH 8.2 imposed by 5 mM bicarbonate) and normal (25 μM) or low (1 μM) iron conditions from roots of these lines. Thus, we were able to treat pH and Fe supply as separate variables. We also noted differential gene expression between IDC sensitive and tolerant genotypes in each condition. Classical iron uptake genes, including ferric-chelate reductase (FCR) and ferrous transporters, were upregulated by both Fe deficiency and alkaline stress, however, their gene products did not function well at alkaline pH. In addition, genes in the phenylpropanoid synthesis pathway were upregulated in both alkaline and low Fe conditions. These genes lead to the production of fluorescent root exudate (FluRE) compounds, such as coumarins. Fluorescence of nutrient solution increased with alkaline treatment, and was higher in the IDC tolerant line. Some of these genes also localized to previously identified QTL regions associated with IDC. We hypothesize that FluRE become essential at alkaline pH where the classical iron uptake system does not function well. This work could result in new strategies to screen for IDC tolerance, and provide breeding targets to improve crop alkaline stress tolerance.},
}
@article {pmid29394825,
year = {2017},
author = {Goto, W and Kashiwagi, S and Asano, Y and Takada, K and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M},
title = {[A Case of Bladder Metastasis from Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {44},
number = {12},
pages = {1933-1935},
pmid = {29394825},
issn = {0385-0684},
mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal/drug therapy/*secondary ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Urinary Bladder Neoplasms/drug therapy/*secondary ; },
abstract = {A 64-year-old woman visited hospital with a chief complaint of a nodule at the left neck skin. Skin biopsy revealed adenocarcinoma, and the diagnosis was skin metastasis of unknown primary origin. Positron emission tomography and computed tomography showed multiple bone and lymph node metastasis, left breast tumor, bladder tumor, and hydronephrosis. A needle biopsy of breast revealed invasive ductal carcinoma, and transurethral biopsy of bladder revealed adenocarcinoma. The findings were similar to those for the breast and the expression pattern of estrogen-receptor was the same. We diagnosed her with breast cancer and bladder metastasis. We administered systemic chemotherapy, however she died 10 days later. Bladder metastasis of breast cancer is rarely encountered in clinical practice and is often accompanied by life threatening symptoms. Careful histopathological examinations and rapid systemic chemotherapy are significant.},
}
@article {pmid29394824,
year = {2017},
author = {Goto, W and Kashiwagi, S and Asano, Y and Takada, K and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M},
title = {[A Case of Breast Cancer Associated with Dermatitis That Was Difficult to Differentiate from Dermatomyositis].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {44},
number = {12},
pages = {1930-1932},
pmid = {29394824},
issn = {0385-0684},
mesh = {Breast Neoplasms/*complications/pathology ; Dermatitis/*diagnosis/*etiology ; Dermatomyositis/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; },
abstract = {A 46-year-old woman visited our hospital with a chief complaint of a mass in the right breast. Breast ultrasonography revealed a hypoechoic area with an indistinct border on the right breast, and right axillary lymph node swelling. A core needle biopsy revealed invasive ductal carcinoma, and the diagnosis was right breast cancer, cT2N2M0, Stage III A, HER2-enriched type. We administered 4 courses of FEC followed by weekly paclitaxel plus trastuzumab. After the treatment, she had eruption and erythema on the face, precordium and forearm. Though dermatomyositis associated cancer was suspected, a definite diagnosis was not made. However, skin symptoms were improved significantly after mastectomy, suggesting that she had dermatomyositis. For the skin symptom during breast cancer treatment, the examination should be made with the possibility of the adverse effect of chemotherapy and dermatomyositis associated cancer.},
}
@article {pmid29394793,
year = {2017},
author = {Katsumori, T and Ohshima, H and Hamaguchi, H and Yamamoto, S and Tsukamoto, Y and Iwanaga, T and Ohkawara, S},
title = {[A Case of Long-Term Survival of Breast Cancer with Lymph Node and Liver Metastases Treated with Sequential Anti-HER2 Drugs, Chemotherapy, and Endocrine Therapy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {44},
number = {12},
pages = {1838-1840},
pmid = {29394793},
issn = {0385-0684},
mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/therapy ; Chemoradiotherapy ; Endocrine System ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Lymphatic Metastasis ; Middle Aged ; Receptor, ErbB-2/*antagonists &amp; inhibitors ; },
abstract = {A 50s-year-old woman underwent left partial mastectomy with axillary lymphadenectomy for breast cancer. Histological examination indicated invasive ductal carcinoma, pT1c, pN0, Stage I , ly(+), ER(+), PgR(+). She received adjuvant therapy with tamoxifen and 50 Gy of irradiation to the residual breast. Four years after mastectomy, she was found to have left Rotter lymph node metastasis; then, anastrozole was administered instead of tamoxifen. Nine months later, she was found to have liver metastasis. Immunohistostaining revealed that the breast cancer was HER2-positive; she received AC followed by paclitaxel(PTX)with trastuzumab(T), and achieved complete response(CR). Subsequently, abdominal, cervical lymph node, and liver metastases appeared. Letrozole followed by lapatinib with capecitabine, FEC100, PTX with T, eribulin, S-1, docetaxel with pertuzumab and T, everolimus with exemestane, bevacizumab, and PTX were then administered, resulting in long-term disease control. Sixteen years after mastectomy, she receives outpatient chemotherapy in performance status 1 state.},
}
@article {pmid29394713,
year = {2017},
author = {Waraya, M and Hayashi, K and Oshida, S and Yamamoto, K and Hosoya, S and Habiro, T and Inukai, M and Kosaka, Y and Sengoku, N and Watanabe, M},
title = {[A Case Report of Ipsilateral Nipple Skin Recurrence].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {44},
number = {12},
pages = {1595-1597},
pmid = {29394713},
issn = {0385-0684},
mesh = {Aged ; Axilla ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*secondary/*surgery ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy, Segmental ; Nipples/*pathology/surgery ; Recurrence ; },
abstract = {We report our experience with a patient with breast cancer who showed recurrence in the nipple skin 5 years and 10 months after a breast-preserving surgery. The patient was a woman, and was 65-years old at the time of initial surgery. Breast-preserving surgery and axillary lymph-node dissection were performed for left breast cancer. Invasive ductal carcinoma of the breast(pT3N0M0)was triple-negative, and the patient postoperatively received adjuvant chemotherapy. Left breast pain developed 5 years and 6 months after surgery. Computed tomography showed no evidence of recurrence, and the symptoms resolved after treatment with non-steroidal anti-inflammatory drugs(NSAIDs). After 3 months, however, the left nipple had enlarged to about 1.5 cm, and the surrounding skin was red and painful. Treatment with NSAIDs was thus resumed. After 1 week, redness of the nipple skin and pain were improved. However, the nipple had enlarged to twice its normal size. Nipple skin biopsy was subsequently performed, and revealed adenocarcinoma invading the skin. Left axillary lymph-node metastasis was suspected, but there was no evidence of metastasis to other sites or recurrence. Conservative total mastectomy with axillary lymph-node dissection was thus performed. The histopathological diagnosis was the recurrence of invasive ductal carcinoma, arising mainly in the reticular layer of the dermis. Chemotherapy was administered postoperatively. There has been no evidence of recurrence as of 1 year after surgery.},
}
@article {pmid29394534,
year = {2017},
author = {Inoue, T and Shimomura, A and Sugimoto, T and Wakamiya, S and Chou, U and Fujiwara, A and Uchikoshi, F and Watanabe, T and Kitamura, N},
title = {[Local Control of Advanced Breast Cancer with Giant Ulcer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {44},
number = {12},
pages = {1062-1064},
pmid = {29394534},
issn = {0385-0684},
mesh = {Biopsy ; Breast Neoplasms/complications/pathology/*therapy ; Carcinoma, Ductal/complications/*therapy ; Chemoradiotherapy ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Ulcer/*etiology ; },
abstract = {This study reports the treatment and local control of advanced breast cancer with a giant ulcer. A 53-year-old woman presented with a large left breast tumor and an associated giant ulcer, with massive exudates, bleeding, and an offensive odor. Histopathological examination revealed an invasive ductal carcinoma(Luminal B type). Computed tomography(CT) showed multiple metastases to the lymph nodes, lungs, liver and bones. The patient received chemotherapy with a combina- tion of paclitaxel(PTX 90mg/m / 2)and bevacizumab(BEV 10 mg/kg). After 4 courses of chemotherapy, there was a significant reduction in the tumor size, the discharge of exudates and bleeding as well as lumbago and femoral pain. High CEA and CA15-3 levels had been normalized and CT showed a remarkable decrease in metastases. Compared to the tumor itself, the ulcer associated with it had shown a smaller decrease in size, and there was the possibility of perforation in the thin chest wall. Suspecting these outcomes to the adverse events of BEV, its use was discontinued, and starting with course 5 of chemothera- py, we administrated only PTX(90mg/m2). Subsequently, the ulcer showed obvious granulation and was infected. CT of the chest prior to the second course of PTX revealed pleurisy, pneumonia and atelectasis. Following the administration of antibiotics, while infection in the ulcer had subsided, pleurisy and pneumonia continued, with increased right pleural effusion, which finally required drainage. We had to discontinue the administration of PTX. BEV, although effective as first-line therapy, has the adverse effect of slowing wound healing. Therefore, even though the combination therapy of BEV and PTX is markedly effective for systemic therapy, it should be altered for local wound healing as in this case.},
}
@article {pmid29378343,
year = {2018},
author = {Enríquez-Marulanda, A and Beltrán-Osorio, LD and Escobar, LA and Granados, AM and Velásquez-Lasprilla, F and Orozco, JL},
title = {Anti-Yo-Associated Paraneoplastic Cerebellar Degeneration Manifesting as Acute Cerebellitis with Posterior Cranial Fossa Hypertension.},
journal = {World neurosurgery},
volume = {112},
number = {},
pages = {117-122},
doi = {10.1016/j.wneu.2018.01.105},
pmid = {29378343},
issn = {1878-8769},
mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Cranial Fossa, Posterior/*pathology/surgery ; Craniotomy/*methods ; Female ; Humans ; Intracranial Hypertension/*etiology/pathology/surgery ; Middle Aged ; Paraneoplastic Cerebellar Degeneration/*complications/pathology/surgery ; },
abstract = {BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a rare complication of some malignant cancers. It is most commonly described in women with gynecologic or breast malignancies; however, there have been reports in other types of cancers. Symptoms include ataxia, dysarthria, and tremors, which could be the first manifestations of an underlying malignancy.<br><br>CASE DESCRIPTION: A 50-year-old woman had an acute PCD with anti-Yo antibodies from an underlying breast invasive ductal carcinoma. She presented with intracranial hypertension in the posterior cranial fossa that required an emergent decompressive craniectomy.<br><br>CONCLUSIONS: PCD is an uncommon disease that may manifest initially as posterior cranial fossa hypertension and subsequent acute hydrocephalus owing to diffuse cerebellar swelling. To our knowledge, this is the first described case of an anti-Yo PCD that has manifested as acute posterior cranial fossa hypertension owing to diffuse cerebellar edema. Early diagnosis and treatment should be pursued to improve long-term outcomes.},
}
@article {pmid29373327,
year = {2018},
author = {D'heygere, E and Meulemans, J and Vander Poorten, V},
title = {Salivary duct carcinoma.},
journal = {Current opinion in otolaryngology &amp; head and neck surgery},
volume = {26},
number = {2},
pages = {142-151},
doi = {10.1097/MOO.0000000000000436},
pmid = {29373327},
issn = {1531-6998},
mesh = {Disease-Free Survival ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Rare Diseases ; Receptor, ErbB-2/genetics ; Receptors, Androgen/genetics ; Risk Assessment ; Salivary Ducts/*pathology/surgery ; Salivary Gland Neoplasms/*genetics/mortality/pathology/*surgery ; Survival Rate ; },
abstract = {PURPOSE OF REVIEW: The review puts new information on geno- and phenotype of salivary duct carcinoma (SDC) in the perspective of the updated 2017 WHO classification.<br><br>RECENT FINDINGS: The proportion of SDC is increasing. This may be because of a true rise in incidence, but certainly to better diagnostic tests and changed WHO definitions. In this light, a substantial proportion of carcinoma expleomorphic adenoma is now attributed to the category of SDC. 'Low-grade SDC' and 'SDC in-situ' of the former WHO classification, are now named low-grade and high-grade intraductal carcinoma (IDC), respectively. Recent series quantify biologic aggressiveness: perineural growth, vascular invasion, and extracapsular extension in lymph node metastasis are each observed in two out of three patients with SDC. Most patients die within 3 years, but once 5-year disease-free survival is reached, further disease activity is exceptional. The typical molecular biological profile with high human epidermal growth factor receptor 2 and androgen receptor expression is increasingly successfully exploited in clinical trials for advanced SDC.<br><br>SUMMARY: The aggressive SDC is increasingly diagnosed. Despite intensive combined surgery and radiation therapy, many patients recur, for whom new bullets, targeting the molecular biological mechanisms, are the subject of ongoing clinical trials.},
}
@article {pmid29373286,
year = {2018},
author = {Sachdeva, R and Schlotterer, A and Schumacher, D and Matka, C and Mathar, I and Dietrich, N and Medert, R and Kriebs, U and Lin, J and Nawroth, P and Birnbaumer, L and Fleming, T and Hammes, HP and Freichel, M},
title = {TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation.},
journal = {Molecular metabolism},
volume = {9},
number = {},
pages = {156-167},
pmid = {29373286},
issn = {2212-8778},
mesh = {Animals ; Cells, Cultured ; Diabetic Retinopathy/genetics/*metabolism ; Female ; Lactoylglutathione Lyase/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pyruvaldehyde/blood/*metabolism ; Retina/metabolism ; TRPC Cation Channels/*genetics/metabolism ; },
abstract = {OBJECTIVE: Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6[-/-] compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy.<br><br>METHODS: We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types. Chronic hyperglycemia was induced by Streptozotocin (STZ) treatment. To assess the development of diabetic retinopathy, vasoregression, pericyte loss, and thickness of individual retinal layers were analyzed. Plasma and cellular methylglyoxal (MG) levels, as well as Glyoxalase 1 (GLO1) enzyme activity and protein expression, were measured in WT and Trpc1/4/5/6[-/-] cells or tissues. MG-evoked toxicity in cells of both genotypes was compared by MTT assay.<br><br>RESULTS: We find that Trpc1/4/5/6[-/-] mice are protected from hyperglycemia-evoked vasoregression determined by the formation of acellular capillaries and pericyte drop-out. In addition, Trpc1/4/5/6[-/-] mice are resistant to the STZ-induced reduction in retinal layer thickness. The RCS metabolite methylglyoxal, which represents a key mediator for the development of diabetic retinopathy, was significantly reduced in plasma and red blood cells (RBCs) of STZ-treated Trpc1/4/5/6[-/-] mice compared to controls. GLO1 is the major MG detoxifying enzyme, and its activity and protein expression were significantly elevated in Trpc1/4/5/6-deficient cells, which led to significantly increased resistance to MG toxicity. GLO1 activity was also increased in retinal extracts from Trpc1/4/5/6[-/-] mice. The TRPCs investigated here are expressed at different levels in endothelial and glial cells of the retina.<br><br>CONCLUSION: The protective phenotype in diabetic retinopathy observed in Trpc1/4/5/6[-/-] mice is suggestive of a predominant action of TRPCs in M&#xfc;ller cells and microglia because of their central position in the retention of a proper homoeostasis of the neurovascular unit.},
}
@article {pmid29367511,
year = {2017},
author = {Sakamoto, N and Ueda, S and Mizoguchi, H and Kawahara, I and Kobayashi, T and Hamaguchi, M and Yoshikawa, M},
title = {[SIGNIFICANCE OF INTRADUCTAL CARCINOMA OF THE PROSTATE IN POST-OPERATIVE BIOCHEMICAL RECURRENCE].},
journal = {Nihon Hinyokika Gakkai zasshi. The japanese journal of urology},
volume = {108},
number = {1},
pages = {5-11},
doi = {10.5980/jpnjurol.108.5},
pmid = {29367511},
issn = {0021-5287},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*diagnosis/*etiology ; Predictive Value of Tests ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms/pathology/*surgery ; Time Factors ; },
abstract = {(Objective) We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy specimens. (Materials and methods) We evaluated 441 patients treated with radical prostatectomy and analyzed data on IDC-P, lymph node metastases, Gleason score, seminal vesicle invasion, extraprostatic extension, surgical margin, total cancer volume, and zonal origin of dominant cancer focus in radical prostatectomy specimens. The median follow-up was 50 months (range 6-164 months). (Results) We identified IDC-P in 112 cases (25.4%). The five-year biochemical progression-free survival rate in patients with IDC-P was significantly lower than for those without IDC-P (35.8% vs 69.6%; p<0.0001). In a univariate analysis, IDC-P (p<0.0001), lymph node metastases (p=0.0022), Gleason score (p<0.0001), seminal vesicle invasion (p<0.0001), extraprostatic extension (p<0.0001), surgical margin (p<0.0001) and total cancer volume (p<0.0001) were significantly associated with the biochemical progression-free survival. In a multivariate analysis, Gleason score (p<0.0001), IDC-P (p=0.0002), seminal vesicle invasion (p=0.0011), extraprostatic extension (p=0.0012), surgical margin (p=0.0019) and lymph node metastases (p=0.0402) were significantly associated with biochemical progression-free survival. (Conclusions) The presence of IDC-P is an independent factor of biochemical recurrence in prostate cancer patients treated with radical prostatectomy. We therefore recommend that the presence of IDC-P in radical prostatectomy specimens be reported.},
}
@article {pmid29362505,
year = {2018},
author = {Hand, BN and Krause, JS and Simpson, KN},
title = {Polypharmacy and adverse drug events among propensity score matched privately insured persons with and without spinal cord injury.},
journal = {Spinal cord},
volume = {56},
number = {6},
pages = {591-597},
pmid = {29362505},
issn = {1476-5624},
support = {UL1 TR001450/TR/NCATS NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Drug-Related Side Effects and Adverse Reactions/*epidemiology ; Female ; Humans ; Insurance, Health ; Likelihood Functions ; Male ; Middle Aged ; Odds Ratio ; *Polypharmacy ; Propensity Score ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Spinal Cord Injuries/drug therapy/*epidemiology ; United States/epidemiology ; Young Adult ; },
abstract = {STUDY DESIGN: Retrospective quasi-experimental design.<br><br>OBJECTIVES: To compare the incidence of adverse drug events (ADEs) between persons with and without spinal cord injury (SCI), while controlling for all potential and available risk factors.<br><br>SETTING: A commercially available claims dataset consisting of ~170 million patient cases in the United States between 2012 and 2013.<br><br>METHODS: Participants (aged 18-64 years) included 2779 persons with polypharmacy and traumatic or non-traumatic SCI and 2779 propensity score-matched persons with polypharmacy without SCI. The cohorts were matched using demographic variables including number of concomitant prescriptions, comorbidities, hospital admissions, age, gender, and geographic region. Inpatient and outpatient claims records containing 395 distinct IDC-9 codes indicative of ADEs were extracted. Incidence and frequency of ADEs were compared between groups using logistic and Poisson regression, respectively.<br><br>RESULTS: Persons with SCI were significantly more likely to experience an ADE than matched controls (Odds Ratio&#x2009;=&#x2009;1.45, p&#x2009;<&#x2009;0.0001). Among persons with ADEs (n&#x2009;=&#x2009;1552), individuals with SCI experienced fewer ADEs over time than matched controls (Incidence Rate Ratio&#x2009;=&#x2009;0.91, p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSIONS: While persons with SCI and polypharmacy are at a greater risk for experiencing an ADE, their medical care after an ADE may be better managed than that of a matched control population. There may be a need for practice guidelines that facilitate proactive identification of persons with SCI at the highest risk of ADE. Steps may then be taken to mitigate risk, in contrast to current practice trends that appear to take a reactive approach after an ADE has occurred.},
}
@article {pmid29362351,
year = {2018},
author = {Sakagami, M and Hirano, T and Suzuki, S and Adachi, K and Kubota, H and Hara, Y and Enomoto, K and Tomita, R and Fujisaki, S and Sakurai, K},
title = {[A Case of Advanced Breast Cancer with Liver Metastasis Successfully Treated with Multi-Disciplinary].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {45},
number = {1},
pages = {190-192},
pmid = {29362351},
issn = {0385-0684},
mesh = {Adult ; Breast Neoplasms/*drug therapy/*pathology/surgery ; Carcinoma, Ductal/*drug therapy/*secondary/surgery ; Combined Modality Therapy ; Female ; Humans ; Liver Neoplasms/*drug therapy/*secondary ; Neoplasm Staging ; Treatment Outcome ; },
abstract = {We report a case of advanced breast cancer with liver metastasis(T2N1M1, Stage IV)achieving a significant improvement of QOL by multi-disciplinary therapy. The patient was 37-year-old woman who had breast lump and axillary lymph nodes swelling with liver metastasis. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma, negative for estrogen receptor and progesterone receptor, and positive for HER2/neu protein expression. The Ki-67 positive cell index was 40%. She received 16 courses of DOC plus HER plus PER(docetaxel 75mg/m / 2, trastuzumab 6 mg/kg, pertu- zumab 450mg/body, and received 4 courses of EC(epirubicin 90mg/m / 2, cyclophosphamide 600 mg/m2). The breast lesion and liver metastatic lesion disappeared after chemotherapy. We checked up whole body. There was no metastatic lesion. Therefore, we diagnosed a clinical complete response. We performed muscle preserving mastectomy and axillary lymph nodes dissection. The pathological diagnosis from resected specimens were pathological complete response. The surgical margin was negative. She was started the endocrine therapy by tamoxifen(20mg/day). Three years after surgery, she was well without metastases. Multi-disciplinary therapy can improve patient QOL and the clinical outcomes in Stage IV advanced breast cancer.},
}
@article {pmid29360854,
year = {2018},
author = {Dolka, I and Czopowicz, M and Gruk-Jurka, A and Wojtkowska, A and Sapierzyński, R and Jurka, P},
title = {Diagnostic efficacy of smear cytology and Robinson's cytological grading of canine mammary tumors with respect to histopathology, cytomorphometry, metastases and overall survival.},
journal = {PloS one},
volume = {13},
number = {1},
pages = {e0191595},
pmid = {29360854},
issn = {1932-6203},
mesh = {Animals ; Biopsy ; Dog Diseases/*diagnosis/pathology ; Dogs ; Female ; Mammary Neoplasms, Animal/*diagnosis/pathology ; *Neoplasm Metastasis ; Sensitivity and Specificity ; Survival Analysis ; },
abstract = {Cytology is a simple, rapid, and inexpensive method used for pre-operative diagnosis of canine mammary tumors (CMTs) in veterinary practice. Studies related to human breast cancer showed the Robinson's grading system-established for invasive ductal carcinoma, not otherwise specified (IDC, NOS) and used on cytological material-to not only closely correspond to the histopathological grading but also be helpful in assessing prognosis and selecting most suitable treatments before surgery. The objectives of this study were: to evaluate the accuracy of cytological diagnosis and cytological Robinson's grading system compared to the histopathological examination of CMTs; to compare of cytological features and cytomorphometric parameters with tumor behavior, as well as cytological and histological grading; and to determine an association of the Robinson's grading system and cytological background details with metastases, and patients' survival. We report substantial diagnostic accuracy in detecting simple types and high grade tumors. Cytological diagnosis of tumor behavior showed relatively low sensitivity and specificity compared to human studies, and this might be caused by the heterogeneous morphology of CMTs. The presence of mucosecretory material and extracellular matrix was not significantly associated with tumor behavior. We report a positive correlation between both grading systems and cytological features (included in Robinson's grading), the presence of necrotic debris, inflammation, and red blood cells. A negative correlation was determined only for the presence of extracellular matrix. The univariate and multivariate analyses confirmed a significantly higher risk of developing metastasis and shorter overall survival for dogs with tumors of grade 2 or 3 on cytology. In addition, these tumors were the most common cause of CMT-related deaths in dogs. Taken together, our findings suggest that the Robinson's method of cytological grading applied for malignant CMTs evaluated in cytological smears regardless of tumor type can be adapted to veterinary cytology. Additionally, some background features seem to aid malignancy assessment.},
}
@article {pmid29358028,
year = {2018},
author = {Santangelo, G and Garramone, F and Baiano, C and D'Iorio, A and Piscopo, F and Raimo, S and Vitale, C},
title = {Personality and Parkinson's disease: A meta-analysis.},
journal = {Parkinsonism &amp; related disorders},
volume = {49},
number = {},
pages = {67-74},
doi = {10.1016/j.parkreldis.2018.01.013},
pmid = {29358028},
issn = {1873-5126},
mesh = {Adult ; Aged ; Aged, 80 and over ; Avoidance Learning/*physiology ; *Character ; Exploratory Behavior/*physiology ; *Extraversion, Psychological ; Female ; Humans ; Male ; Middle Aged ; Neuroticism/*physiology ; Parkinson Disease/complications/*physiopathology ; Personality Disorders/etiology/*physiopathology ; },
abstract = {INTRODUCTION: Personality changes are considered pre-motor features of Parkinson's disease (PD). Cross-sectional studies revealed that PD patients were more introvert, apprehensive, and cautious than healthy subjects (HS), whereas other studies failed to disclose these behavioural traits. Some studies found mixed results concerning Novelty Seeking (NS) and Harm Avoidance (HA) profiles in PD patients. To better clarify the personality profile in PD we performed a meta-analysis on studies exploring such topic according to both Cloninger's Psychobiological Model (PM) and Big Five Model (BFM) METHODS: The meta-analysis included 17 studies evaluating the personality in PD patients compared with HS. The outcomes were the dimensions of the temperament and character of the PM and personality traits of BFM. Effect sizes from data reported in the primary studies were computed using Hedges'g unbiased approach. Heterogeneity among the studies and publication bias were assessed. Meta-regressions were conducted with age at evaluation, gender, schooling, and type of personality trait tools as moderators.<br><br>RESULTS: As for PM, PD patients scored higher on HA and lower on NS than HS. No difference was found on Reward Dependence, Perseverance/Persistence and on character level. As for BFM, higher levels of Neuroticism, but lower levels of Openness and Extraversion were associated with PD.<br><br>DISCUSSION: The personality profile in PD is characterized by high Neuroticism and HA, and by low Openness, Extraversion and NS. The personality profile delineated in the present study on PD patients seems to reflect the premorbid one and might contribute to development and persistence of affective disorders.},
}
@article {pmid29356019,
year = {2018},
author = {Shalaby, N and Al-Ebraheem, A and Le, D and Cornacchi, S and Fang, Q and Farrell, T and Lovrics, P and Gohla, G and Reid, S and Hodgson, N and Farquharson, M},
title = {Time-resolved fluorescence (TRF) and diffuse reflectance spectroscopy (DRS) for margin analysis in breast cancer.},
journal = {Lasers in surgery and medicine},
volume = {50},
number = {3},
pages = {236-245},
doi = {10.1002/lsm.22795},
pmid = {29356019},
issn = {1096-9101},
mesh = {Breast Neoplasms/*diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/surgery ; Female ; Humans ; *Margins of Excision ; Mastectomy ; Reproducibility of Results ; *Spectrometry, Fluorescence ; },
abstract = {PURPOSE: One of the major problems in breast cancer surgery is defining surgical margins and establishing complete tumor excision within a single surgical procedure. The goal of this work is to establish instrumentation that can differentiate between tumor and normal breast tissue with the potential to be implemented in vivo during a surgical procedure.<br><br>METHODS: A time-resolved fluorescence and reflectance spectroscopy (tr-FRS) system is used to measure fluorescence intensity and lifetime as well as collect diffuse reflectance (DR) of breast tissue, which can subsequently be used to extract optical properties (absorption and reduced scatter coefficient) of the tissue. The tr-FRS data obtained from patients with Invasive Ductal Carcinoma (IDC) whom have undergone lumpectomy and mastectomy surgeries is presented. A preliminary study was conducted to determine the validity of using banked pre-frozen breast tissue samples to study the fluorescence response and optical properties. Once the validity was established, the tr-FRS system was used on a data-set of 40 pre-frozen matched pair cases to differentiate between tumor and normal breast tissue. All measurements have been conducted on excised normal and tumor breast samples post surgery.<br><br>RESULTS: Our results showed the process of freezing and thawing did not cause any significant differences between fresh and pre-frozen normal or tumor breast tissue. The tr-FRS optical data obtained from 40 banked matched pairs showed significant differences between normal and tumor breast tissue.<br><br>CONCLUSION: The work detailed in the main study showed the tr-FRS system has the potential to differentiate malignant from normal breast tissue in women undergoing surgery for known invasive ductal carcinoma. With further work, this successful outcome may result in the development of an accurate intraoperative real-time margin assessment system. Lasers Surg. Med. 50:236-245, 2018. &#xa9; 2018 Wiley Periodicals, Inc.},
}
@article {pmid29353241,
year = {2018},
author = {Jabs, M and Rose, AJ and Lehmann, LH and Taylor, J and Moll, I and Sijmonsma, TP and Herberich, SE and Sauer, SW and Poschet, G and Federico, G and Mogler, C and Weis, EM and Augustin, HG and Yan, M and Gretz, N and Schmid, RM and Adams, RH and Gröne, HJ and Hell, R and Okun, JG and Backs, J and Nawroth, PP and Herzig, S and Fischer, A},
title = {Inhibition of Endothelial Notch Signaling Impairs Fatty Acid Transport and Leads to Metabolic and Vascular Remodeling of the Adult Heart.},
journal = {Circulation},
volume = {137},
number = {24},
pages = {2592-2608},
doi = {10.1161/CIRCULATIONAHA.117.029733},
pmid = {29353241},
issn = {1524-4539},
mesh = {Adaptor Proteins, Signal Transducing ; Angiopoietins/genetics/metabolism ; Animals ; CD36 Antigens/genetics/metabolism ; Calcium-Binding Proteins ; Endothelium, Vascular/cytology/*metabolism ; Fatty Acid-Binding Proteins/genetics/metabolism ; Fatty Acids/genetics/*metabolism ; Glucose/genetics/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; Mice ; Mice, Transgenic ; Myocardium/*metabolism ; Myocytes, Cardiac/metabolism ; Neovascularization, Physiologic ; Receptors, Notch/genetics/*metabolism ; Ribosomal Protein S6 Kinases/genetics/metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases/genetics/metabolism ; *Vascular Remodeling ; },
abstract = {BACKGROUND: Nutrients are transported through endothelial cells before being metabolized in muscle cells. However, little is known about the regulation of endothelial transport processes. Notch signaling is a critical regulator of metabolism and angiogenesis during development. Here, we studied how genetic and pharmacological manipulation of endothelial Notch signaling in adult mice affects endothelial fatty acid transport, cardiac angiogenesis, and heart function.<br><br>METHODS: Endothelial-specific Notch inhibition was achieved by conditional genetic inactivation of Rbp-j&#x3ba; in adult mice to analyze fatty acid metabolism and heart function. Wild-type mice were treated with neutralizing antibodies against the Notch ligand Delta-like 4. Fatty acid transport was studied in cultured endothelial cells and transgenic mice.<br><br>RESULTS: Treatment of wild-type mice with Delta-like 4 neutralizing antibodies for 8 weeks impaired fractional shortening and ejection fraction in the majority of mice. Inhibition of Notch signaling specifically in the endothelium of adult mice by genetic ablation of Rbp-j&#x3ba; caused heart hypertrophy and failure. Impaired heart function was preceded by alterations in fatty acid metabolism and an increase in cardiac blood vessel density. Endothelial Notch signaling controlled the expression of endothelial lipase, Angptl4, CD36, and Fabp4, which are all needed for fatty acid transport across the vessel wall. In endothelial-specific Rbp-j&#x3ba;-mutant mice, lipase activity and transendothelial transport of long-chain fatty acids to muscle cells were impaired. In turn, lipids accumulated in the plasma and liver. The attenuated supply of cardiomyocytes with long-chain fatty acids was accompanied by higher glucose uptake, increased concentration of glycolysis intermediates, and mTOR-S6K signaling. Treatment with the mTOR inhibitor rapamycin or displacing glucose as cardiac substrate by feeding a ketogenic diet prolonged the survival of endothelial-specific Rbp-j&#x3ba;-deficient mice.<br><br>CONCLUSIONS: This study identifies Notch signaling as a novel regulator of fatty acid transport across the endothelium and as an essential repressor of angiogenesis in the adult heart. The data imply that the endothelium controls cardiomyocyte metabolism and function.},
}
@article {pmid29350308,
year = {2018},
author = {Ory, V and Kietzman, WB and Boeckelman, J and Kallakury, BV and Wellstein, A and Furth, PA and Riegel, AT},
title = {The PPARγ agonist efatutazone delays invasive progression and induces differentiation of ductal carcinoma in situ.},
journal = {Breast cancer research and treatment},
volume = {169},
number = {1},
pages = {47-57},
pmid = {29350308},
issn = {1573-7217},
support = {P30CA051008//National Cancer Institute/ ; RO1CA205632//National Institutes of Health/ ; P30 CA051008/CA/NCI NIH HHS/United States ; R01 CA205632/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; CA009686//T32 Training Grant in Tumor Biology/ ; R01 CA112176/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/genetics/pathology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Neoplasm Invasiveness/genetics/pathology ; PPAR gamma/*genetics ; Thiazolidinediones/*administration &amp; dosage ; Xenograft Model Antitumor Assays ; },
abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a pre-invasive lesion of the breast considered a precursor of invasive ductal carcinoma. This study aimed to determine whether activated PPARγ acts as a tumor suppressor in human DCIS progression.<br><br>METHODS: We utilized the high-affinity PPAR&#x3b3; agonist, efatutazone, to activate endogenous PPAR&#x3b3; in a well-defined model for the progression of basal (triple negative) DCIS, MCFDCIS cells, cultured under 2D and 3D conditions. We studied the effects of activated PPAR&#x3b3; on DCIS progression in MCFDCIS xenograft and C3(1)/Tag transgenic mice treated with 30&#xa0;mg/kg of efatutazone.<br><br>RESULTS: In vitro, efatutazone did not alter the MCFDCIS cell proliferation but induced phenotypic and gene expression changes, indicating that activated PPAR&#x3b3; is able to differentiate MCFDCIS cells into more luminal and lactational-like cells. In addition, MCFDCIS tumorsphere formation in 3D was reduced by PPAR&#x3b3; activation. In vivo, efatutazone-treated MCFDCIS tumors exhibited fat deposition along with upregulation of PPAR&#x3b3; responsive genes in both epithelial and stromal compartments, suggesting features of milk-producing mammary epithelial cell differentiation. The efatutazone-treated lesions were less invasive with fewer CD44+/p63+ basal progenitor cells. PPAR&#x3b3; activation downregulated Akt phosphorylation in these tumors, although the ERK pathway remained unchanged. Similar trends in gene expression changes consistent with lactational and luminal cell differentiation were observed in the C3(1)/Tag mouse model after efatutazone treatment.<br><br>CONCLUSIONS: Our data suggest that activation of the PPAR&#x3b3; pathway differentiates DCIS lesions and may be a useful approach to delay DCIS progression.},
}
@article {pmid29349758,
year = {2018},
author = {Feinberg, J and Wetstone, R and Greenstein, D and Borgen, P},
title = {Is DCIS Overrated?.},
journal = {Cancer treatment and research},
volume = {173},
number = {},
pages = {53-72},
doi = {10.1007/978-3-319-70197-4_5},
pmid = {29349758},
issn = {0927-3042},
mesh = {Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/mortality/pathology/*therapy ; Female ; Gene Expression Profiling ; Humans ; Neoplasm Invasiveness ; },
abstract = {Ductal carcinoma in situ (DCIS), the noninvasive form of breast cancer (BC), comprises just over 20% of breast cancer cases diagnosed each year in the USA. Most patients are treated with local excision of the disease followed by whole breast radiation therapy. Total mastectomy is not an uncommon approach, and total mastectomy with a contralateral risk-reducing mastectomy has been on the rise in the past decade. In estrogen receptor-positive disease, patients are often offered endocrine ablative therapy with a selective estrogen receptor modulator or an aromatase inhibitor as both treatment and prevention. Local regional treatment options have no impact upon ultimate overall survival. Long-term survival rates are higher in patients with DCIS than with any other form of the disease. Are these strikingly high success rates a testament to effective treatment strategies or is there a significant subset of DCIS that was unlikely to ever progress to invasive ductal carcinoma? DCIS was not seen in the US prior to the advent of screening mammography. When compared to other countries, the USA has the highest utilization of screening mammography and the incidence rate of DCIS. Other lines of evidence include autopsy series examining the breast tissue of women who died of other causes, missed-diagnosis series and current retrospective reviews of DCIS, all align in support of the concept of DCIS as indolent in the majority of cases [3-14]. The evidence suggests that both patient and physician misconceptions about DCIS have led to overdiagnosis and over-treatment of DCIS. Recently, a gene expression profiling tool (12 gene assay, Oncotype DCIS) has emerged that shows considerable promise in predicting class in DCIS patients.},
}
@article {pmid29345622,
year = {2018},
author = {Valero, A and Navarro, AM and Del Cuvillo, A and Alobid, I and Benito, JR and Colás, C and de Los Santos, G and Fernández Liesa, R and García-Lliberós, A and González-Pérez, R and Izquierdo-Domínguez, A and Jurado-Ramos, A and Lluch-Bernal, MM and Montserrat Gili, JR and Mullol, J and Puiggròs Casas, A and Sánchez-Hernández, MC and Vega, F and Villacampa, JM and Armengot-Carceller, M and Dordal, MT and , },
title = {Position paper on nasal obstruction: evaluation and treatment.},
journal = {Journal of investigational allergology &amp; clinical immunology},
volume = {28},
number = {2},
pages = {67-90},
doi = {10.18176/jiaci.0232},
pmid = {29345622},
issn = {1018-9068},
mesh = {Animals ; Humans ; Nasal Cavity/drug effects ; Nasal Obstruction/*drug therapy ; Quality of Life ; Rhinomanometry/methods ; Rhinometry, Acoustic/methods ; },
abstract = {Nasal obstruction (NO) is defined as the subjective perception of discomfort or difficulty in the passage of air through the nostrils. It is a common reason for consultation in primary and specialized care and may affect up to 30%-40% of the population. It affects quality of life (especially sleep) and lowers work efficiency. The aim of this document is to agree on how to treat NO, establish a methodology for evaluating and diagnosing it, and define an individualized approach to its treatment. NO can be unilateral or bilateral, intermittent or persistent and may be caused by local or systemic factors, which may be anatomical, inflammatory, neurological, hormonal, functional, environmental, or pharmacological in origin. Directed study of the medical history and physical examination are key for diagnosing the specific cause. NO may be evaluated using subjective assessment tools (visual analog scale, symptom score, standardized questionnaires) or by objective estimation (active anterior rhinomanometry, acoustic rhinometry, peak nasal inspiratory flow). Although there is little correlation between the results, they may be considered complementary and not exclusive. Assessing the impact on quality of life through questionnaires standardized according to the underlying disease is also advisable. NO is treated according to its cause. Treatment is fundamentally pharmacological (topical and/or systemic) when the etiology is inflammatory or functional. Surgery may be necessary when medical treatment fails to complement or improve medical treatment or when other therapeutic approaches are not possible. Combinations of surgical techniques and medical treatment may be necessary.},
}
@article {pmid29345290,
year = {2018},
author = {Nowak, A and Grzegrzółka, J and Kmiecik, A and Piotrowska, A and Matkowski, R and Dzięgiel, P},
title = {Role of nestin expression in angiogenesis and breast cancer progression.},
journal = {International journal of oncology},
volume = {52},
number = {2},
pages = {527-535},
doi = {10.3892/ijo.2017.4223},
pmid = {29345290},
issn = {1791-2423},
mesh = {Breast Neoplasms/*blood supply/metabolism/pathology ; Carcinoma, Ductal, Breast/*blood supply/metabolism/pathology ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic ; Nestin/genetics/*metabolism ; SOXF Transcription Factors/metabolism ; Triple Negative Breast Neoplasms/blood supply/metabolism/pathology ; },
abstract = {Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the prognostic value of nestin expression in breast tumour cells and to determine whether this expression influences angiogenesis. Immunohistochemical (IHC) analyses were carried out on 124 cases of invasive ductal carcinoma (IDC) of the breast with a panel of murine monoclonal antibodies against nestin, CD31, CD34, SOX-18 and Ki‑67. We evaluated nestin expression in tumour and endothelial cells, Ki‑67 in tumour cells, and CD31, CD34 and SOX-18 in endothelial cells. Our results demonstrated that nestin expression in tumour cells correlated with the area and number of vessels expressing nestin, CD31, CD34 and SOX-18. We also found a positive correlation between nestin-expressing vessels and SOX-18-expressing vessels. Our results are consistent with those of previous studies, in which nestin expression in endothelial cells was shown to be strongly associated with triple-negative subtype, poorly differentiated G3 tumours, a higher proliferation index and a shorter overall survival. Nestin expression was also examined in human breast cancer cell lines (MCF-7, SK-BR-3, MDA‑MB‑231 and BO2 cells) representing a different level of tumour aggressiveness and reflecting histological grade. A higher nestin protein level was observed in more aggressive MDA‑MB‑231 and BO2 cells than in MCF-7 and SK-BR-3 cells.},
}
@article {pmid29336321,
year = {2018},
author = {Yahia, R and Zaoui, C and Derbale, W and Boudi, H and Chebloune, Y and Sahraoui, T and Elkebir, FZ},
title = {[Epstein Barr virus and invasive mammary carcinomas: EBNA, EBERs and molecular profile in a population of West Algeria].},
journal = {Annales de biologie clinique},
volume = {76},
number = {1},
pages = {75-80},
doi = {10.1684/abc.2017.1312},
pmid = {29336321},
issn = {1950-6112},
mesh = {Adult ; Algeria/epidemiology ; Breast Neoplasms/complications/epidemiology/genetics/*virology ; Carcinoma, Ductal, Breast/complications/epidemiology/genetics/*virology ; Enzyme-Linked Immunosorbent Assay ; Epstein-Barr Virus Infections/*diagnosis/epidemiology ; Epstein-Barr Virus Nuclear Antigens/analysis/*isolation &amp; purification/metabolism ; Female ; Herpesvirus 4, Human/genetics/*isolation &amp; purification/metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Molecular Typing/methods ; RNA, Viral/genetics/*isolation &amp; purification/metabolism ; },
abstract = {Breast cancer is the common malignancy that affects women worldwide, but conventional risk factors account for only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr virus (EBV) is a widely studied candidate virus. The objective of this study is to determine the association of EBV infection with infiltrating ductal carcinomas (IDC). This descriptive study was carried out in the laboratory of developmental biology and differentiation, from 2012 to 2014. Of 39 cases, we determined the clinicopathological characteristics of the population. Of the 23 cases of IDC, we implemented the techniques Elisa, immunohistochemistry and in situ hybridization. To determine the serological profile, overexpression of onco-proteins EBNA-1, HER2, the mitotic index Ki67 and detection of the presence of the viral genome. The mean age is 57.40±4, SBR II predominates with 70%, pN+ (27%), RE+ (58%), RP+ (52%), HER2 (81%), Luminal A (34%), Luminal B (14%), HER2 (24%), and triple negative (28%). The serological profile of IgG VCA + in IgG EBNA-1 (87%), EBNA-1 P79 (82%) with a positive relationship between the IgG EBNA-1 and EBNA-1 P79 serology profile (p=0.001), HER2 (p=0.003) and with the molecular profile (p=0.051), EBNA-1 overexpression in (13%). The viral genome (EBER) is found in the tumors 43% representing an inverse relationship with the overexpression of Ki67 and a positive relationship with the overexpression of HER2. In our study we found an association with the presence of the EBV virus and the IDC studied.},
}
@article {pmid29327767,
year = {2017},
author = {Darouich, S and El Amine El Hadj, O and Betaieb, I and Goucha, A and Dhiab, T and Rahal, K and Gamoudi, A and El May, A},
title = {Triple negative breast cancer: A clinico-epidemiological and histopronostic study of 90 cases.},
journal = {La Tunisie medicale},
volume = {95},
number = {1},
pages = {37-44},
pmid = {29327767},
issn = {0041-4131},
mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology/*pathology/therapy ; Female ; Humans ; Incidence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/pathology/therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/diagnosis/*epidemiology/*pathology/therapy ; Tunisia/epidemiology ; },
abstract = {PURPOSE: The aim of this study was to describe the clinico-epidemiological and histopronostic characteristics of triple negative breast cancer (TNBC) and to evaluate the therapeutic results in tunisian women.<br><br>METHODS: We reported the results of a retrospective study including 90 patients treated for TNBC between Junuary 2008 and December 2009 in the Salah Azaiz Institute of Tunis.<br><br>RESULTS: TNBCoccured in 14% of diagnosed breast cancers. The mean age at diagnosis was 53.67 years. Family history of breast cancer was reported in 10% of cases.The majority of tumors were classified as T2 (41%) and associated with invasive ductal carcinoma histological type (99%) and SBR grade-II (54%). Tumor lymph node metastases were detected in 44% of patients.Among operated patients, 46% of patients underwent conservative surgery and 54% radical surgery. Chemotherapy and postoperative radiotherapy were given in97% and 80%of patients, respectively. After a median follow-up of 33.51 months, 61% of patients remained free of disease, 12% hadloco-regional recurrence, 9% had disease progression during chemotherapy and 21% developed systemic disease.<br><br>CONCLUSION: TNBC diagnosis is often made in the advanced stage and has a tendency to recur after treatment. The variable responseto chemotherapy is due to the molecular tumor heterogeneity. The development of targeted therapies is necessary to improve outcome of chemoresistant TNBC.},
}
@article {pmid29307488,
year = {2018},
author = {Casasent, AK and Schalck, A and Gao, R and Sei, E and Long, A and Pangburn, W and Casasent, T and Meric-Bernstam, F and Edgerton, ME and Navin, NE},
title = {Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing.},
journal = {Cell},
volume = {172},
number = {1-2},
pages = {205-217.e12},
pmid = {29307488},
issn = {1097-4172},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA169244/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Movement ; *Clonal Evolution ; Exome ; Female ; Humans ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Sequence Analysis, DNA ; Single-Cell Analysis ; },
abstract = {Ductal carcinoma in situ (DCIS) is an early-stage breast cancer that infrequently progresses to invasive ductal carcinoma (IDC). Genomic evolution has been difficult to delineate during invasion due to intratumor heterogeneity and the low number of tumor cells in the ducts. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells while preserving their spatial context in tissue sections. We applied TSCS to 1,293 single cells from 10 synchronous patients with both DCIS and IDC regions in addition to exome sequencing. Our data reveal a direct genomic lineage between in situ and invasive tumor subpopulations and further show that most mutations and copy number aberrations evolved within the ducts prior to invasion. These results support a multiclonal invasion model, in which one or more clones escape the ducts and migrate into the adjacent tissues to establish the invasive carcinomas.},
}
@article {pmid29299933,
year = {2018},
author = {Aydin, H and Guner, B and Esen Bostanci, I and Bulut, ZM and Aribas, BK and Dogan, L and Gulcelik, MA},
title = {Is there any relationship between adc values of diffusion-weighted imaging and the histopathological prognostic factors of invasive ductal carcinoma?.},
journal = {The British journal of radiology},
volume = {91},
number = {1084},
pages = {20170705},
pmid = {29299933},
issn = {1748-880X},
mesh = {Breast Neoplasms/*diagnostic imaging/*pathology/therapy ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology/therapy ; Contrast Media ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Gadolinium DTPA ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness/*diagnostic imaging/*pathology ; Neoplasm Staging ; Organometallic Compounds ; Prognosis ; Prospective Studies ; },
abstract = {OBJECTIVE: MRI is being used increasingly as a modality that can provide important information about breast cancer. Diffusion-weighted imaging (DWI) is an imaging technique from which apparent diffusion coefficient (ADC) values can be calculated in addition to obtaining important structural information which cannot be obtained from other imaging studies. We did not find any significant relationships between ADC values and prognostic factors, but did provide some explanations for conflicting results in the literature.<br><br>METHODS: The ADC results of 61&#xa0;females with invasive ductal carcinomas were evaluated. DWI was performed and ADC values were calculated from the area in which restriction of diffusion was the highest in ADC mapping. B value was 500 and region of interest (ROI) was designated between 49&#xa0;and&#xa0;100&#xa0;mm[2]. Calculations were performed automatically by the device. Tissue samples were obtained for prognostic factor evaluation. The relationships between ADC and prognostic factors were investigated. Comparisons between groups were made with one-way ANOVA and Kruskal Wallis test. Pairwise comparisons were made with Dunn's test. Analyses of categorical variables were made with Chi-square test.<br><br>RESULTS: We found a weak negative correlation between ADC and Ki-67 values (r = -0.279; p = 0.029). When we compared ADC values in regard to tumour type, we found no significant differences for tumour grade, Ki-67 positivity, estrogen receptor&#xa0;positivity, progesterone receptor&#xa0;positivity, C-erb B2, lymphovascular invasion and ductal carcinoma in situ or lobular carcinoma in situ&#xa0;component. On a side note, we found that mean ADC values decreased as tumour grade increased; however, this was not statistically significant.<br><br>CONCLUSION: The literature contains studies that report conflicting results which may be caused by differences in B values, ROI area and magnetic field strength. Multicentre studies and systematic reviews of these findings may produce crucial data for the use of DWI in breast cancer. Advances in knowledge: To determine if any significant relationship exists between DWI findings and prognostic factors of breast cancer.},
}
@article {pmid29295717,
year = {2018},
author = {Böttcher, R and Kweldam, CF and Livingstone, J and Lalonde, E and Yamaguchi, TN and Huang, V and Yousif, F and Fraser, M and Bristow, RG and van der Kwast, T and Boutros, PC and Jenster, G and van Leenders, GJLH},
title = {Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations.},
journal = {BMC cancer},
volume = {18},
number = {1},
pages = {8},
pmid = {29295717},
issn = {1471-2407},
support = {03O-402//Center for Translational Molecular Medicine/International ; #RS2014-01//Movember Foundation/International ; New Investigator Award//CIHR/Canada ; New Investigator Award//Terry Fox Research Institute/International ; },
mesh = {Adenocarcinoma/*genetics/pathology ; Aged ; Biomarkers, Tumor/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; *DNA Copy Number Variations ; Follow-Up Studies ; *Genomic Instability ; Genomics/*methods ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/*genetics/pathology ; },
abstract = {BACKGROUND: Invasive cribriform and intraductal carcinoma (CR/IDC) is associated with adverse outcome of prostate cancer patients. The aim of this study was to determine the molecular aberrations associated with CR/IDC in primary prostate cancer, focusing on genomic instability and somatic copy number alterations (CNA).<br><br>METHODS: Whole-slide images of The Cancer Genome Atlas Project (TCGA, N&#xa0;=&#x2009;260) and the Canadian Prostate Cancer Genome Network (CPC-GENE, N&#xa0;=&#x2009;199) radical prostatectomy datasets were reviewed for Gleason score (GS) and presence of CR/IDC. Genomic instability was assessed by calculating the percentage of genome altered (PGA). Somatic copy number alterations (CNA) were determined using Fisher-Boschloo tests and logistic regression. Primary analysis were performed on TCGA (N&#x2009;=&#x2009;260) as discovery and CPC-GENE (N&#x2009;=&#x2009;199) as validation set.<br><br>RESULTS: CR/IDC growth was present in 80/260 (31%) TCGA and 76/199 (38%) CPC-GENE cases. Patients with CR/IDC and &#x2265; GS 7 had significantly higher PGA than men without this pattern in both TCGA (2.2 fold; p&#xa0;=&#x2009;0.0003) and CPC-GENE (1.7 fold; p&#xa0;=&#x2009;0.004) cohorts. CR/IDC growth was associated with deletions of 8p, 16q, 10q23, 13q22, 17p13, 21q22, and amplification of 8q24. CNAs comprised a total of 1299 gene deletions and 369 amplifications in the TCGA dataset, of which 474 and 328 events were independently validated, respectively. Several of the affected genes were known to be associated with aggressive prostate cancer such as loss of PTEN, CDH1, BCAR1 and gain of MYC. Point mutations in TP53, SPOP and FOXA1were also associated with CR/IDC, but occurred less frequently than CNAs.<br><br>CONCLUSIONS: CR/IDC growth is associated with increased genomic instability clustering to genetic regions involved in aggressive prostate cancer. Therefore, CR/IDC is a pathologic substrate for progressive molecular tumour derangement.},
}
@article {pmid29290072,
year = {2018},
author = {Kalisya, LM and Bake, JF and Bigabwa, R and Rothstein, DH and Cairo, SB},
title = {Operations for Suspected Neoplasms in a Resource-Limited Setting: Experience and Challenges in the Eastern Democratic of Congo.},
journal = {World journal of surgery},
volume = {42},
number = {7},
pages = {1913-1918},
pmid = {29290072},
issn = {1432-2323},
mesh = {Adult ; Child ; Democratic Republic of the Congo ; Female ; *Health Resources ; Humans ; Male ; Middle Aged ; Neoplasms/*surgery ; Retrospective Studies ; },
abstract = {INTRODUCTION: Surgery is an essential component of a functional health system, with surgical conditions accounting for nearly 11-15% of world disability. While communicable diseases continue to burden low- and low-middle-income countries, non-communicable diseases, such as cancer, are an important cause of morbidity and mortality worldwide. Preliminary data on malignancies in low- and middle-income countries, specifically in Africa, suggest a higher mortality compared to other regions of the world, a difference partially explained by limited availability of screening and early detection systems as well as poorer access to treatment.<br><br>OBJECTIVE: To evaluate the diagnosed tumor burden in the Eastern Democratic Republic of Congo (DRC) and review literature on existing and suspected barriers to accessing appropriate oncologic care.<br><br>METHODS: This is a retrospective study carried out at Healthcare, Education, community Action, and Leadership development Africa, a 197-bed tertiary referral hospital, in the Province of North Kivu, along the eastern border of the DRC from 2012 to 2015. Patient charts were reviewed for diagnoses of presumed malignancy with biopsy results.<br><br>RESULTS: A total of 252 cases of suspected cancer were reviewed during the study period; 39.7% were men. The average age of patients was 43&#xa0;years. Amongst adult patients, the most common presenting condition involved breast lesions with 5.8% diagnosis of fibrocystic breast changes and 2.9% invasive ductal carcinoma of the breast. 37.3% of female patients had lesions involving the cervix or uterus. The most common diagnosis amongst male adults was prostate disease (16.7% of men). For pediatric patients, the most common diagnoses involved bone and/or cartilage (27.3%) followed by skin and soft tissue lesions (20.0%). All patients underwent surgical resection of lesions; some patients were advised to travel out of country for chemotherapy and radiation for which follow-up data are unavailable.<br><br>CONCLUSION: Adequate and timely treatment of malignancy in the DRC faces a multitude of challenges. Access to surgical services for diagnosis and management as well as chemotherapeutic agents is prohibitively limited. Increased collaboration with local clinicians and remote specialist consultants is needed to deliver subspecialty care in resource-poor settings.},
}
@article {pmid29286468,
year = {2017},
author = {Hidmark, AS and Nawroth, PP and Fleming, T},
title = {Analysis of Immune Cells in Single Sciatic Nerves and Dorsal Root Ganglion from a Single Mouse Using Flow Cytometry.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {130},
pages = {},
pmid = {29286468},
issn = {1940-087X},
mesh = {Animals ; Flow Cytometry/*methods ; Ganglia, Spinal/*cytology/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Regeneration/*physiology ; Sciatic Nerve/*cytology/*immunology ; },
abstract = {Nerve-resident immune cells in the peripheral nervous system (PNS) are essential to maintaining neuronal integrity in a healthy nerve. The immune cells of the PNS are affected by injury and disease, affecting the nerve function and the capacity for regeneration. Neuronal immune cells are commonly analyzed by immunofluorescence (IF). While IF is essential for determining the location of the immune cells in the nerve, IF is only semi-quantitative and the method is limited to the number of markers that can be analyzed simultaneously and the degree of surface expression. In this study, flow cytometry was used for quantitative analysis of leukocyte infiltration into sciatic nerves or dorsal root ganglions (DRGs) of individual mice. Single cell analysis was performed using DAPI and several proteins were analyzed simultaneously for either surface or intracellular expression. Both sciatic nerves from one mouse that were treated according to this protocol generated ≥ 30,000 single nucleated events. The proportion of leukocytes in the sciatic nerves, determined by expression of CD45, was approximately 5% of total cell content in the sciatic nerve and approximately 5-10% in the DRG. Although this protocol focuses primarily on the immune cell population within the PNS, the flexibility of flow cytometry to measure a number of markers simultaneously means that the other cells populations present within the nerve, such as Schwann cells, pericytes, fibroblasts, and endothelial cells, can also be analyzed using this method. This method therefore provides a new means for studying systemic effects on the PNS, such as neurotoxicology and genetic models of neuropathy or in chronic diseases, such as diabetes.},
}
@article {pmid29281999,
year = {2017},
author = {Mercogliano, MF and Inurrigarro, G and De Martino, M and Venturutti, L and Rivas, MA and Cordo-Russo, R and Proietti, CJ and Fernández, EA and Frahm, I and Barchuk, S and Allemand, DH and Figurelli, S and Deza, EG and Ares, S and Gercovich, FG and Cortese, E and Amasino, M and Guzmán, P and Roa, JC and Elizalde, PV and Schillaci, R},
title = {Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer.},
journal = {BMC cancer},
volume = {17},
number = {1},
pages = {895},
pmid = {29281999},
issn = {1471-2407},
support = {IDB/PICT 2012-382//Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/International ; PID 2012-066//Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/International ; IDB/PICT 2012-668//Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/International ; IDB/PICT 2012 1017//Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/International ; #20//Instituto Nacional del C&#xe1;ncer (AR)/International ; 1819/03//Consejo Nacional de Investigaciones Cient&#xed;ficas y T&#xe9;cnicas (AR)/International ; PIP 2012 059//Consejo Nacional de Investigaciones Cient&#xed;ficas y T&#xe9;cnicas/International ; BOD/2016//Universidad Cat&#xf3;lica de C&#xf3;rdoba/International ; },
mesh = {Adult ; Aged ; Antineoplastic Agents, Immunological ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*mortality/pathology ; Carcinoma, Papillary/drug therapy/metabolism/*mortality/pathology ; Case-Control Studies ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Mucin-4/*metabolism ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/antagonists &amp; inhibitors/immunology/*metabolism ; Retrospective Studies ; Survival Rate ; Trastuzumab/*pharmacology ; },
abstract = {BACKGROUND: Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC.<br><br>METHODS: We retrospectively studied 86 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy in the adjuvant setting. We explored the association of the IMPC component with clinicopathological parameters at diagnosis and its prognostic value. We compared MUC4 expression in IMPC with respect to other histological breast cancer subtypes by immunohistochemistry.<br><br>RESULTS: IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2-positive cases. It was positively correlated with estrogen receptor expression and tumor size and inversely correlated with patient's age. Disease-free survival was significantly lower in patients with IMPC (hazard ratio&#x2009;=&#x2009;2.6; 95%, confidence interval 1.1-6.1, P&#x2009;=&#x2009;0.0340). MUC4, a glycoprotein associated with metastasis, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression compared to IDC, lobular and mucinous carcinoma.<br><br>CONCLUSION: In HER2-positive breast cancer, the presence of IMPC should be carefully examined. As it is often not informed, because it is relatively difficult to identify or altogether overlooked, we propose MUC4 expression as a useful biomarker to highlight IMPC presence. Patients with MUC4-positive tumors with IMPC component should be more frequently monitored and/or receive additional therapies.},
}
@article {pmid29281012,
year = {2018},
author = {Perdijk, O and van Neerven, RJJ and Meijer, B and Savelkoul, HFJ and Brugman, S},
title = {Induction of human tolerogenic dendritic cells by 3'-sialyllactose via TLR4 is explained by LPS contamination.},
journal = {Glycobiology},
volume = {28},
number = {3},
pages = {126-130},
pmid = {29281012},
issn = {1460-2423},
mesh = {Animals ; Dendritic Cells/drug effects/*immunology ; Humans ; Immune Tolerance/drug effects/*immunology ; Lipopolysaccharides/*analysis/*immunology ; Milk, Human/chemistry ; NF-kappa B/metabolism ; Oligosaccharides/*immunology/pharmacology ; Toll-Like Receptor 4/immunology/*metabolism ; },
abstract = {The human milk oligosaccharide 3'-sialyllactose (3'SL) has previously been shown to activate murine dendritic cells (DC) in a Toll-like receptor (TLR) 4-mediated manner ex vivo. In this study we aimed to investigate whether 3'SL has similar immunomodulatory properties on human DC. 3'SL was shown to induce NF-κB activation via human TLR4. However, LPS was detected in the commercially obtained 3'SL from different suppliers. After the removal of LPS from 3'SL, we studied its ability to modify DC differentiation in vitro. In contrast to LPS and 3'SL, LPS-free 3'SL did not induce functional and phenotypical changes on immature DC (iDC). iDC that were differentiated in the presence of LPS or 3'SL showed a semi-mature phenotype (i.e., fewer CD83+CD86+ DC), produced IL-10 and abrogated IL-12p70 and tumor necrosis factor-alpha levels upon stimulation with several TLR ligands. Differentiation into these tolerogenic DC was completely abrogated by LPS removal from 3'SL. In contrast to previous reports in mice, we found that LPS-free 3'SL does not activate NF-κB via human TLR4. In conclusion, removing LPS from (oligo)saccharide preparations is necessary to study their potential immunomodulatory function.},
}
@article {pmid29276992,
year = {2018},
author = {Levav, I and Klomek, AB},
title = {A review of epidemiologic studies on suicide before, during, and after the Holocaust.},
journal = {Psychiatry research},
volume = {261},
number = {},
pages = {35-39},
doi = {10.1016/j.psychres.2017.12.042},
pmid = {29276992},
issn = {1872-7123},
mesh = {Austria/epidemiology ; Concentration Camps/trends ; Epidemiologic Studies ; Germany/epidemiology ; Holocaust/*psychology/trends ; Humans ; Israel/epidemiology ; Jews/*psychology ; Suicide/*psychology/trends ; Survivors/psychology ; *World War II ; },
abstract = {The available literature on the risk of suicides related to the Holocaust (1939-1945) and its aftermath differs in its time periods, in the countries investigated, and in the robustness of its sources. Reliable information seems to indicate that the risk of suicide for Jews in Nazi Germany and Austria during the pre-war period (1933-1939) was elevated, while information on suicide during the internment in the concentration camps is fraught with problems. The latter derives from the Nazis' decision to hide the statistics on the inmates' causes of death, and from the prevailing life conditions that impeded separation between self-inflicted death and murder. Reliable studies conducted in Israel among refugees who entered pre-state Israel, 1939-1945, and post-World War II survivors reaching Israel (1948 on), show a mixed picture: suicide rates among the former were higher than comparison groups, while the latter group shows evidence of resilience.},
}
@article {pmid29275106,
year = {2018},
author = {Inoue, Y and Yamashita, N and Kitao, H and Tanaka, K and Saeki, H and Oki, E and Oda, Y and Tokunaga, E and Maehara, Y},
title = {Clinical Significance of the Wild Type p53-Induced Phosphatase 1 Expression in Invasive Breast Cancer.},
journal = {Clinical breast cancer},
volume = {18},
number = {4},
pages = {e643-e650},
doi = {10.1016/j.clbc.2017.11.008},
pmid = {29275106},
issn = {1938-0666},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*pathology/surgery ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Comparative Genomic Hybridization ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Copy Number Variations ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Mutation ; Neoplasm Staging ; Prognosis ; Protein Phosphatase 2C/genetics/*metabolism ; Tumor Suppressor Protein p53/genetics ; },
abstract = {BACKGROUND: Wild type p53-induced phosphatase 1 (Wip1), encoded by the protein phosphatase magnesium dependent 1 delta (PPM1D), inhibits p53. PPM1D amplification has been reported in breast cancer. Breast cancer can sometimes develop without a tumor protein 53 (TP53) mutation. In these cases, the p53 pathway might be disrupted by alternative mechanisms, and Wip1 is reported to be a key molecule involved.<br><br>MATERIALS AND METHODS: Primary invasive ductal carcinoma specimens were obtained from 201 cases, for which archival tissue samples for immunohistochemistry were available. We evaluated Wip1 and p21 protein expression (201 cases), Wip1 mRNA expression (63 cases), PPM1D DNA copy number (71 cases) and TP53 status (36 cases) using available samples among the 201 cases, and analyzed their relationships with clinicopathological factors and prognosis.<br><br>RESULTS: The nuclear expression of Wip1 protein was positive in 21 cases (10.4%). The PPM1D DNA copy number was significantly correlated with Wip1 protein expression. All cases with PPM1D amplification by single-nucleotide polymorphism comparative genomic hybridization array showed positive nuclear Wip1 expression. Wip1 protein expression was positively correlated with p21 expression. The tumors with positive Wip1 and negative p21 expression showed the poorest prognosis among all tumor types.<br><br>CONCLUSION: The protein expression of Wip1 might be regulated by PPM1D amplification, independent of TP53 status. Positive Wip1 and negative p21 expression was associated with the poorest prognosis and suggests the loss of p53 function.},
}
@article {pmid29262562,
year = {2017},
author = {Li, J and Sun, L and Xu, F and Xiao, J and Jiao, W and Qi, H and Shen, C and Shen, A},
title = {Characterization of plasma proteins in children of different Mycobacterium tuberculosis infection status using label-free quantitative proteomics.},
journal = {Oncotarget},
volume = {8},
number = {61},
pages = {103290-103301},
pmid = {29262562},
issn = {1949-2553},
abstract = {Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an infectious disease found worldwide. Children infected with MTB are more likely to progress to active TB (ATB); however, the molecular mechanism behind this process has long been a mystery. We employed the label-free quantitative proteomic technology to identify and characterize differences in plasma proteins between ATB and latent TB infection (LTBI) in children. To detect differences that are indicative of MTB infection, we first selected proteins whose expressions were markedly different between the ATB and LTBI groups and the control groups (inflammatory disease control (IDC) and healthy control (HC) groups). A total of 521 proteins differed (> 1.5-fold or < 0.6-fold) in the LTBI group, and 318 proteins in the ATB group when compared with the control groups. Of these, 49 overlapping proteins were differentially expressed between LTBI and ATB. Gene Ontology (GO) analysis revealed most proteins had a cellular and organelle distribution. The MTB infection status was mainly related to differences in binding, cellular and metabolic processes. XRCC4, PCF11, SEMA4A and ATP11A were selected and further verified by qPCR and western blot. At the mRNA level, the expression of XRCC4, PCF11and SEMA4A presented an increased trend in ATB group compare with LTBI. At the protein level, the expression of all these proteins by western blot in ATB/LTBI was consistent with the trends from proteomic detection. Our results provide important data for future mechanism studies and biomarker selection for MTB infection in children.},
}
@article {pmid29249796,
year = {2017},
author = {Farran, Y and Padilla, O and Chambers, K and Philipovskiy, A and Nahleh, Z},
title = {Atypical Presentation of Radiation-Associated Breast Angiosarcoma: A Case Report and Review of Literature.},
journal = {The American journal of case reports},
volume = {18},
number = {},
pages = {1347-1350},
pmid = {29249796},
issn = {1941-5923},
mesh = {Aged ; Breast Neoplasms/*etiology/pathology/radiotherapy ; Carcinoma, Ductal, Breast/radiotherapy ; Female ; Hemangiosarcoma/*etiology/pathology ; Humans ; *Neoplasms, Radiation-Induced ; Pigmentation Disorders/*etiology/pathology ; Radiotherapy, Adjuvant/*adverse effects ; },
abstract = {BACKGROUND Radiation-associated breast angiosarcoma is a rare clinical entity that is thought to be increasing in incidence. CASE REPORT Here we present the case of a 67-year-old female with a history of left breast invasive ductal carcinoma who received breast conserving surgery and radiation therapy eight years ago. She then presented with a painless mild skin discoloration of the left breast that had been present for over one year. Mammograms and ultrasounds were normal. A punch biopsy and a subsequent excisional biopsy revealed the diagnosis of angiosarcoma. The patient was treated with mastectomy and had no subsequent recurrences. CONCLUSIONS The long-term clinical surveillance for all patients who receive breast conservation surgery is recommended and a high degree of suspicion should be exercised in view of potential atypical presentations of this disease.},
}
@article {pmid29246496,
year = {2018},
author = {Hannafon, BN and Ding, WQ},
title = {miRNAs as Biomarkers for Predicting the Progression of Ductal Carcinoma in Situ.},
journal = {The American journal of pathology},
volume = {188},
number = {3},
pages = {542-549},
pmid = {29246496},
issn = {1525-2191},
support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Humans ; MicroRNAs/genetics/*metabolism ; },
abstract = {Ductal carcinoma in situ (DCIS) is defined as a proliferation of neoplastic cells within the duct of the mammary gland that have not invaded into the surrounding stroma. DCIS is considered a precursor to invasive ductal carcinoma (IDC); however, approximately half of DCIS may progress to IDC, if left untreated. Current research has shown that the genomic and transcriptomic changes are present in DCIS before the emergence of invasive disease, indicating that the malignant nature of the DCIS is defined before invasion. However, important questions remain surrounding the specific changes and processes required for malignant progression and identification of prognostic indicators of aggressiveness. miRNAs are small regulatory RNAs that can modulate gene expression by complementary binding to target mRNAs and inducing translational repression and/or mRNA degradation. In the past decade, research has shown that miRNA expression is dysregulated in IDC and that these changes are already present at the DCIS stage. Therefore, changes in miRNA expression may provide the necessary information to identify a clinical indicator of the aggressiveness of DCIS. Herein, we review the miRNA signatures identified in DCIS, describe how these signatures may be used to predict the aggressiveness of DCIS, and discuss future perspectives for DCIS biomarker discovery.},
}
@article {pmid29230302,
year = {2017},
author = {Gharia, B and Seegobin, K and Maharaj, S and Marji, N and Deutch, A and Zuberi, L},
title = {Letrozole-induced hepatitis with autoimmune features: a rare adverse drug reaction with review of the relevant literature.},
journal = {Oxford medical case reports},
volume = {2017},
number = {11},
pages = {omx074},
pmid = {29230302},
issn = {2053-8855},
abstract = {While aromatase inhibitors (AIs) have been known to cause minor elevations in liver enzymes, severe hepatotoxicity is rare. To the best of our knowledge, this is the first reported case of Letrozole-induced hepatitis with autoimmune features. A 70-year-old female with estrogen positive, invasive ductal carcinoma of the breast, presented with jaundice 3 months after starting letrozole. Hepatic transaminases were markedly elevated and her ANA and anti-smooth muscle antibody was positive. Liver biopsy featured drug-induced hepatitis. After stopping letrozole, liver tests trended back to normal within 3 weeks. She scored 9 for Roussel-Uclaf Causality Assessment Method (RUCAM). Over the last 10 years, there have been reported cases of drug-induced hepatitis secondary to AIs. We anticipate that there will be more widespread use of AIs based on recommendations from the TEXT, SOFT and extended AI trials. Therefore, physicians must be aware of this rare but life-threatening complication.},
}
@article {pmid29227474,
year = {2018},
author = {Lehmann, LH and Jebessa, ZH and Kreusser, MM and Horsch, A and He, T and Kronlage, M and Dewenter, M and Sramek, V and Oehl, U and Krebs-Haupenthal, J and von der Lieth, AH and Schmidt, A and Sun, Q and Ritterhoff, J and Finke, D and Völkers, M and Jungmann, A and Sauer, SW and Thiel, C and Nickel, A and Kohlhaas, M and Schäfer, M and Sticht, C and Maack, C and Gretz, N and Wagner, M and El-Armouche, A and Maier, LS and Londoño, JEC and Meder, B and Freichel, M and Gröne, HJ and Most, P and Müller, OJ and Herzig, S and Furlong, EEM and Katus, HA and Backs, J},
title = {A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway.},
journal = {Nature medicine},
volume = {24},
number = {1},
pages = {62-72},
pmid = {29227474},
issn = {1546-170X},
mesh = {Animals ; Epigenesis, Genetic ; Gene Transfer Techniques ; Heart Failure/genetics/*metabolism ; Hexosamines/*biosynthesis ; Histone Deacetylases/genetics/*metabolism ; Mice ; Mice, Knockout ; *Myocardial Contraction ; Myocardium/enzymology ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/metabolism ; Physical Conditioning, Animal ; Proteolysis ; Stromal Interaction Molecule 1/metabolism ; },
abstract = {The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure.},
}
@article {pmid29217299,
year = {2018},
author = {Zahorchak, AF and Macedo, C and Hamm, DE and Butterfield, LH and Metes, DM and Thomson, AW},
title = {High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.},
journal = {Cellular immunology},
volume = {323},
number = {},
pages = {9-18},
pmid = {29217299},
issn = {1090-2163},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; R34 AI123033/AI/NIAID NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; },
mesh = {B7-2 Antigen/*immunology ; B7-H1 Antigen/*immunology ; Cell Differentiation/immunology ; Dendritic Cells/cytology/*immunology ; Humans ; Interleukin-10/immunology ; Lymphocyte Activation ; Monocytes/immunology ; Organ Transplantation/methods ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Transplantation Immunology ; },
abstract = {Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10, the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naïve and memory allogeneic CD4[+] and CD8[+] T cell proliferation and IFNγ, IL-17A and perforin/granzyme B production in MLR. Their stimulatory function was enhanced however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR) sequencing revealed that, among circulating T cell subsets, memory CD8[+] T cells contained the most alloreactive TCR clonotypes and that, while matDC expanded these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated responses. These findings demonstrate the feasibility of generating highly-purified GMP-grade DCreg for systemic infusion, their influence on the alloreactive T cell response, and a key mechanistic role of the PD1 pathway.},
}
@article {pmid29215790,
year = {2018},
author = {Carrascal, MA and Silva, M and Ramalho, JS and Pen, C and Martins, M and Pascoal, C and Amaral, C and Serrano, I and Oliveira, MJ and Sackstein, R and Videira, PA},
title = {Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation.},
journal = {Molecular oncology},
volume = {12},
number = {5},
pages = {579-593},
pmid = {29215790},
issn = {1878-0261},
support = {P01 HL107146/HL/NHLBI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; E-Selectin/genetics/*metabolism ; Female ; Fucose/analogs &amp; derivatives/pharmacology ; Fucosyltransferases/*antagonists &amp; inhibitors ; Humans ; Ligands ; MAP Kinase Signaling System/drug effects ; Middle Aged ; Neoplasm Invasiveness ; Oligosaccharides/*metabolism ; Primary Cell Culture ; Sialyl Lewis X Antigen ; p38 Mitogen-Activated Protein Kinases/genetics/*metabolism ; },
abstract = {Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLe[X][/A]), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLe[X][/A] , to cell adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer. We first analyzed expression of E-selectin ligands in IDC tissue and established primary cell cultures from the tissue. We observed strong reactivity with E-selectin and anti-sLe[X][/A] antibodies in both IDC tissue and cell lines, and expression of α-1,3/4 FUTs FUT4, FUT5, FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC biology, we immortalized a primary IDC cell line with human telomerase reverse transcriptase to create the 'CF1_T cell line'. Treatment with 2-fluorofucose (2-FF), a fucosylation inhibitor, completely abrogated its sLe[X][/A] expression and dramatically reduced adherence of CF1_T cells to E-selectin under hemodynamic flow conditions. In addition, 2-FF-treated CF1_T cells showed a reduced migratory ability, as well as decreased cell proliferation rate. Notably, 2-FF treatment lowered the growth factor expression of CF1_T cells, prominently for FGF2, vascular endothelial growth factor, and transforming growth factor beta, and negatively affected activation of signal-regulating protein kinases 1 and 2 and p38 mitogen-activated protein kinase signaling pathways. These data indicate that fucosylation licenses several malignant features of IDC, such as cell adhesion, migration, proliferation, and growth factor expression, contributing to tumor progression.},
}
@article {pmid29211399,
year = {2018},
author = {Arribillaga, LC and Ledesma, M and Montedoro, A and Pisano, F and Bengió, RG},
title = {OAB score: a clinical model that predicts the probability of presenting overactive detrusor in the urodynamic study.},
journal = {International braz j urol : official journal of the Brazilian Society of Urology},
volume = {44},
number = {2},
pages = {348-354},
pmid = {29211399},
issn = {1677-6119},
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Urinary Bladder, Overactive/*diagnosis/physiopathology ; Urodynamics/*physiology ; },
abstract = {PURPOSE: To create a predictive model of involuntary detrusor contraction (IDC) to improve the diagnostic accuracy of overactive detrusor (OAD), associating overactive bladder (OAB) symptoms with other clinical parameters in the female population.<br><br>MATERIALS AND METHODS: A total of 727 women were studied retrospectively. In all of them, urodynamic study was conducted for urogynecological causes. Demographics information, personal history, symptoms, physical exam, a 3-day frequency/volume chart and urinary culture, were collected in all patients and they subsequently underwent uroflowmetry and urodynamic studies. A logistic regression model was performed in order to determine independent predictors of presence of IDC. Odd ratio (OR) estimation was used to assign a score to each one of the significant variables (p&#x2264;0.05) in the logistic regression model. We performed a ROC curve in order to determine the predictive ability of the score in relation to the presence of OAD.<br><br>RESULTS: presence of OAD was evident in 210 women (29%). In the logistic regression analysis, independent predictors of OAD were urgency, urgency incontinence, nocturia, absence of SUI symptoms, diabetes mellitus, reduction of vaginal trophism and bladder capacity below 150 mL. The probability of IDC diagnosis increases as the score raises (Score 0: 4% until Score &#x2265;10: 88%). Sensitivity was 71% and specificity 72%. The area under the curve of OAB score was 0.784 (p>0.001).<br><br>CONCLUSIONS: OAB score is a clinical tool that shows higher diagnostic accuracy than OAB symptoms alone to predict overactive detrusor.},
}
@article {pmid29209551,
year = {2017},
author = {Yetkin, G and Celayir, F and Akgun, IE and Ucak, R},
title = {Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma.},
journal = {Case reports in surgery},
volume = {2017},
number = {},
pages = {7048149},
pmid = {29209551},
issn = {2090-6900},
abstract = {A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.},
}
@article {pmid29206714,
year = {2018},
author = {Khanlari, M and Schally, AV and Block, NL and Nadji, M},
title = {Expression of GHRH-R, a Potentially Targetable Biomarker, in Triple-negative Breast Cancer.},
journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM},
volume = {26},
number = {1},
pages = {1-5},
doi = {10.1097/PAI.0000000000000622},
pmid = {29206714},
issn = {1533-4058},
mesh = {Biomarkers, Tumor/*genetics ; *Drug Delivery Systems ; Female ; Humans ; Receptors, Neuropeptide/*genetics/metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/*genetics/metabolism ; Triple Negative Breast Neoplasms/*diagnosis/*genetics ; },
abstract = {PURPOSE: Growth hormone-releasing hormone (GHRH) has been shown to modify the growth behavior of many cancers, including breast. GHRH is produced by tumor cells, acts in an autocrine/paracrine manner, and requires the presence of GHRH receptor (GHRH-R) on the tumor cells to exert its effects. GHRH activity can be effectively blocked by synthetic antagonists of its receptor and hence, the expression of GHRH-R by tumor cells could serve as a predictor of response to GHRH-R antagonist therapy. In this study, we investigated the expression of GHRH-R in triple-negative breast cancers (TNBC). As TNBCs are morphologically and immunophenotypically heterogenous, the staining results were also correlated with the histologic subtypes of these tumors.<br><br>MATERIALS AND METHODS: On the basis of histomorphology and immunophenotype, 134 cases of primary TNBCs were further subdivided into medullary, metaplastic, apocrine, and invasive ductal carcinomas of no special type (IDC-NST). Immunohistochemistry for GHRH-R was performed on paraffin sections and the staining results were assessed semiquantitatively as negative, low expression, moderate, and high expression.<br><br>RESULTS: Of the 134 TNBCs, 85 were classified as IDC-NST, 25 as metaplastic, 16 as medullary, and 8 as apocrine carcinoma. Overall, positive reaction for GHRH-R was seen in 77 (57%) of tumors including 66 (77.6%) of IDC-NST. All medullary carcinomas were negative for GHRH-R and, with the exception of 1 case with low expression, none of the metaplastic carcinomas expressed GHRH-R (P<0.005).<br><br>CONCLUSIONS: A considerable number of TNBCs are positive for GHRH-R as a predictor of potential response to anti-GHRH-R treatment. This expression however, varies considerably between histologic subtypes of triple-negative breast cancers. Although most medullary and metaplastic carcinomas do not express GHRH-R, three fourths of the IDC-NST show a positive reaction. Testing for GHRH-R expression is therefore advisable if anti-GHRH-R therapy is being considered.},
}
@article {pmid29195137,
year = {2018},
author = {Rezende, F and Moll, F and Walter, M and Helfinger, V and Hahner, F and Janetzko, P and Ringel, C and Weigert, A and Fleming, I and Weissmann, N and Kuenne, C and Looso, M and Rieger, MA and Nawroth, P and Fleming, T and Brandes, RP and Schröder, K},
title = {The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice.},
journal = {Redox biology},
volume = {15},
number = {},
pages = {12-21},
pmid = {29195137},
issn = {2213-2317},
mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Aorta/metabolism/pathology ; Diabetes Mellitus, Experimental/*genetics/metabolism/pathology ; Endothelial Cells/metabolism ; Gene Expression ; Humans ; Lymphocytes/metabolism/pathology ; Mice ; Mice, Knockout ; NADP/metabolism ; NADPH Oxidases/*genetics/metabolism ; Protein Binding ; Proteins/*genetics ; Reactive Oxygen Species/metabolism ; },
abstract = {AIM: NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes.<br><br>RESULTS: In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice.<br><br>INNOVATION AND CONCLUSION: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.},
}
@article {pmid29189723,
year = {2017},
author = {Giroud, M and Scheideler, M},
title = {Long Non-Coding RNAs in Metabolic Organs and Energy Homeostasis.},
journal = {International journal of molecular sciences},
volume = {18},
number = {12},
pages = {},
pmid = {29189723},
issn = {1422-0067},
mesh = {Adipose Tissue/metabolism ; Animals ; Energy Metabolism/genetics/physiology ; Gene Expression Regulation ; Homeostasis ; Humans ; Muscle, Skeletal/metabolism ; Pancreas/metabolism ; RNA, Long Noncoding/genetics/*metabolism ; },
abstract = {Single cell organisms can surprisingly exceed the number of human protein-coding genes, which are thus not at the origin of the complexity of an organism. In contrast, the relative amount of non-protein-coding sequences increases consistently with organismal complexity. Moreover, the mammalian transcriptome predominantly comprises non-(protein)-coding RNAs (ncRNA), of which the long ncRNAs (lncRNAs) constitute the most abundant part. lncRNAs are highly species- and tissue-specific with very versatile modes of action in accordance with their binding to a large spectrum of molecules and their diverse localization. lncRNAs are transcriptional regulators adding an additional regulatory layer in biological processes and pathophysiological conditions. Here, we review lncRNAs affecting metabolic organs with a focus on the liver, pancreas, skeletal muscle, cardiac muscle, brain, and adipose organ. In addition, we will discuss the impact of lncRNAs on metabolic diseases such as obesity and diabetes. In contrast to the substantial number of lncRNA loci in the human genome, the functionally characterized lncRNAs are just the tip of the iceberg. So far, our knowledge concerning lncRNAs in energy homeostasis is still in its infancy, meaning that the rest of the iceberg is a treasure chest yet to be discovered.},
}
@article {pmid29174251,
year = {2017},
author = {Dalal, J and Katekhaye, V and Jain, R},
title = {Effect of ferric carboxymaltose on hospitalization and mortality outcomes in chronic heart failure: A meta-analysis.},
journal = {Indian heart journal},
volume = {69},
number = {6},
pages = {736-741},
pmid = {29174251},
issn = {2213-3763},
mesh = {*Anemia, Iron-Deficiency/drug therapy/etiology/mortality ; Ferric Compounds/*administration &amp; dosage ; Global Health ; *Heart Failure/complications/mortality/therapy ; Hospitalization/*trends ; Humans ; Infusions, Intravenous ; Maltose/administration &amp; dosage/*analogs &amp; derivatives ; Prospective Studies ; *Quality of Life ; },
abstract = {INTRODUCTION: Iron administration especially intravenous iron therapy is associated with improvements in exercise capacity and quality of life in patients with chronic heart failure (CHF). Our aim was to assess effect of ferric carboxymaltose (FCM) on hospitalization and mortality outcomes in CHF.<br><br>MATERIALS AND METHODS: A literature search across PUBMED, Google Scholar and trials database www.clinicaltrials.gov was conducted to search for randomized controlled trials (till August 2016) comparing FCM to placebo in CHF with or without anaemia. Published human studies in English language which reported data on mortality and hospitalization rates were included. Primary outcome was rates of HF hospitalizations and secondary outcomes were hospitalization due to any cardiovascular (CV) cause, death due to worsening HF and any CV death.<br><br>RESULTS: From 17 studies identified, two were included in final analysis (n=760; 455 in FCM and 305 in placebo arms). We observed significantly lower rates of hospitalization for worsening HF in FCM arm [Risk Ratio (RR) 0.34, 95% confidence interval (CI) 0.19, 0.59, p=0.0001] as well as for any CV hospitalizations [RR 0.49, 95% CI 0.35, 0.70; p<0.0001] (figure). No heterogeneity in studies was seen for these two outcomes (I[2]=0%, p>0.05). No significant treatment effect with FCM was noted in mortality from worsening HF (RR 0.41, 95% CI 0.02, 7.36; p=0.55) or any CV death (RR 0.80, 95% CI 0.40, 1.57; p=0.51).<br><br>CONCLUSION: FCM reduces hospitalization rates in CHF but may not reduce mortality outcome. This finding needs further evaluation in a large, prospective, randomized controlled trial.},
}
@article {pmid29172216,
year = {2018},
author = {Deprez, PH and Garces Duran, R and Moreels, T and Furneri, G and Demma, F and Verbeke, L and Van der Merwe, SW and Laleman, W},
title = {The economic impact of using single-operator cholangioscopy for the treatment of difficult bile duct stones and diagnosis of indeterminate bile duct strictures.},
journal = {Endoscopy},
volume = {50},
number = {2},
pages = {109-118},
doi = {10.1055/s-0043-121268},
pmid = {29172216},
issn = {1438-8812},
mesh = {Adult ; Aged ; Cholangiopancreatography, Endoscopic Retrograde/*economics/methods ; Cholestasis/diagnosis/etiology/*surgery ; Cost-Benefit Analysis ; Female ; Follow-Up Studies ; Gallstones/complications/diagnosis/*surgery ; Humans ; Male ; Middle Aged ; *Models, Economic ; Retrospective Studies ; Severity of Illness Index ; },
abstract = {BACKGROUND AND STUDY AIM: Conventional endoscopic retrograde cholangiopancreatography (ERCP) combines endoscopy and radiography to diagnose and treat pathological conditions of the bile duct. The aim of the present analysis was to evaluate the clinical and economic impact of the use of single-operator intraductal cholangioscopy (IDC), which allows for direct visualization of the bile duct, as an alternative to ERCP for the treatment of difficult bile duct stones and the diagnosis of bile duct strictures.<br><br>PATIENTS AND METHODS: The clinical and economic consequences of single-operator IDC use were evaluated using two decision-tree models, one for management of difficult-to-remove stones and one for stricture diagnosis. A hospital perspective was adopted. Data to populate the models were derived from two Belgian hospitals that specialize in endoscopic procedures of the bile duct. Overall, the examined population consisted of 62 patients with difficult stones and 49 patients with indeterminate strictures.<br><br>RESULTS: In the model for difficult stone management, the use of IDC determined a decrease in the number of procedures (-&#x200a;27&#x200a;% relative reduction) and costs (-&#x200a;&#x20ac;73&#x2005;000;&#x200a;-&#x200a;11&#x200a;% relative reduction) when compared with ERCP. In the model for stricture diagnosis, the use of IDC determined a decrease in the number of procedures (-&#x200a;31&#x200a;% relative reduction) and costs (-&#x200a;&#x20ac;13&#x2005;000;&#x200a;-&#x200a;5&#x200a;% relative variation) when compared with ERCP.<br><br>CONCLUSIONS: The single-operator IDC system performed better than ERCP for the treatment of difficult bile duct stones and the diagnosis of bile duct strictures, and reduced the overall expenditure in hospitals in Belgium.},
}
@article {pmid29164828,
year = {2019},
author = {Koren, D and Rothschild-Yakar, L and Lacoua, L and Brunstein-Klomek, A and Zelezniak, A and Parnas, J and Shahar, G},
title = {Attenuated psychosis and basic self-disturbance as risk factors for depression and suicidal ideation/behaviour in community-dwelling adolescents.},
journal = {Early intervention in psychiatry},
volume = {13},
number = {3},
pages = {532-538},
doi = {10.1111/eip.12516},
pmid = {29164828},
issn = {1751-7893},
support = {//University of Haifa/International ; //Israel Science Foundation/International ; },
mesh = {Adolescent ; Depressive Disorder/*diagnosis/psychology ; Depressive Disorder, Major/diagnosis/psychology ; *Ego ; Female ; Humans ; Independent Living/psychology ; Male ; Pilot Projects ; Prodromal Symptoms ; Psychotic Disorders/*diagnosis/psychology ; Risk Factors ; Self-Injurious Behavior/diagnosis/psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; Surveys and Questionnaires ; },
abstract = {BACKGROUND AND AIMS: Adolescents at clinical high risk (CHR) for psychosis, as defined by the presence of attenuated psychosis symptoms (APS), exhibit increased levels of suicidal ideation and behaviour. However, no research thus far has examined the link between basic self-disturbances (SDs), an established marker for CHR, and suicidality/self-harm in this population. The goal of this pilot study was to assess the association between SD, depression and suicidal ideation and behaviour among non-help-seeking adolescents from the community.<br><br>METHOD: A total of 100 community-dwelling adolescents (age range: 13-16) were assessed using the Examination of Anomalous Self-experience, Prodromal Questionnaire, Structured Interview for Prodromal Syndromes, Mood and Anxiety Symptom Questionnaire and the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). The K-SADS was used to derive a binary diagnosis of unipolar depression, as well as to measure suicidal ideation and behaviour and self-harm.<br><br>RESULTS: In a multiple regression analysis, SD accounted for variance in depressive symptoms and suicidality/self-harm over and above that accounted for by APS. Moreover, SD accounted for variance in suicidality/self-harm over and above that accounted for by depression symptoms.<br><br>CONCLUSIONS: These pilot results suggest that SD might be a unique dimension of vulnerability to depression and suicidality/self-harm in adolescence. Also, they encourage assessment of SD as part of a suicide risk assessment, particularly in the context of risk for subsequent psychosis.},
}
@article {pmid29155474,
year = {2018},
author = {Gilboa, Y and Frenkel, TI and Schlesinger, Y and Rousseau, S and Hamiel, D and Achiron, R and Perlman, S},
title = {Visual biofeedback using transperineal ultrasound in second stage of labor.},
journal = {Ultrasound in obstetrics &amp; gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology},
volume = {52},
number = {1},
pages = {91-96},
doi = {10.1002/uog.18962},
pmid = {29155474},
issn = {1469-0705},
mesh = {Adult ; *Biofeedback, Psychology ; Delivery, Obstetric/*methods ; Female ; Head/*diagnostic imaging/embryology ; Humans ; Infant, Newborn ; Labor Stage, Second/*physiology ; Perineum/*diagnostic imaging ; Pregnancy ; Pregnancy Outcome ; Prospective Studies ; Self Report ; *Ultrasonography/methods ; },
abstract = {OBJECTIVE: To assess the obstetric and psychological effects of visual biofeedback by transperineal ultrasound (TPU) during the second stage of labor.<br><br>METHODS: This was a prospective, single-center observational study of low-risk nulliparous women with epidural analgesia undergoing vaginal delivery. Visual biofeedback using TPU was provided to 26 women during the second stage of labor. Pushing efficacy was assessed by the change in the angle of progression (AoP) at rest and during pushing efforts, before and after biofeedback. Obstetric outcomes included incidence of perineal tearing, mode of delivery and length of second stage of labor. Psychological outcomes were assessed by self-reported measures obtained during the postnatal hospital stay and included measures of perceived control and maternal satisfaction with childbirth, as well as level of maternal feelings of connectedness with the newborn. Obstetric and psychological results were compared with those of a control group of 69 women who received standard obstetric coaching from midwives.<br><br>RESULTS: Pushing efficacy increased significantly following visual biofeedback by TPU (P&#x2009;=&#x2009;0.01), as indicated by a significantly lower delta AoP before (mean, 22.2&#xb0; (95% CI, 13.9-31.7&#xb0;)) compared with after (mean, 35.2&#xb0; (95% CI, 25.9-45.3&#xb0;)) biofeedback. A significant association was found between visual biofeedback and an intact perineum following delivery (P&#x2009;=&#x2009;0.03). No significant differences were found between the two groups with regard to mode of delivery or length of the second stage. Feelings of maternal connectedness with the newborn were significantly stronger (P&#x2009;=&#x2009;0.003) in women who received visual biofeedback than in those who did not. However, perceived control during childbirth and maternal satisfaction with childbirth did not differ significantly between the biofeedback and control groups.<br><br>CONCLUSIONS: This pilot study suggests that biofeedback using TPU may serve as a complementary tool to coached maternal pushing during the second stage of labor, with obstetric as well as psychological benefits. Further studies are required to confirm our findings and define the optimal duration of the intervention. Copyright &#xa9; 2017 ISUOG. Published by John Wiley &amp; Sons Ltd.},
}
@article {pmid29154888,
year = {2017},
author = {Hou, N and Wen, Y and Yuan, X and Xu, H and Wang, X and Li, F and Ye, B},
title = {Activation of Yap1/Taz signaling in ischemic heart disease and dilated cardiomyopathy.},
journal = {Experimental and molecular pathology},
volume = {103},
number = {3},
pages = {267-275},
pmid = {29154888},
issn = {1096-0945},
support = {R01 HL072166/HL/NHLBI NIH HHS/United States ; R01 HL111480/HL/NHLBI NIH HHS/United States ; R01 HL122793/HL/NHLBI NIH HHS/United States ; },
mesh = {Acyltransferases ; Adaptor Proteins, Signal Transducing/*genetics ; Animals ; Cardiomyopathies/genetics/pathology ; Cardiomyopathy, Dilated/*genetics/pathology ; DNA-Binding Proteins/*genetics ; Humans ; Mice ; Muscular Dystrophies/genetics/pathology ; Myocardial Ischemia/*genetics/pathology ; Nuclear Proteins/*genetics ; Phosphoproteins/*genetics ; Signal Transduction/genetics ; TEA Domain Transcription Factors ; Transcription Factors/*genetics ; YAP-Signaling Proteins ; },
abstract = {Genetic manipulation of key components of the evolutionally conserved Hippo pathway has shown that the precise control of these signaling molecules is critical to cardiac development and response to stresses. However, how this pathway is involved in the progression of cardiac dysfunction in different heart diseases remains unclear. We investigated the expressional levels and subcellular localization of Yap1, Taz, and Tead1 and determined Hippo target gene expression in failing human hearts with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (IDC) and mouse desmin-related cardiomyopathy (DES). Our results demonstrated that Yap1, Taz, and Tead1 were significantly increased in failing human and DES hearts compared with the non-failing controls (NFH) or wild type (WT) mouse hearts at both mRNA and protein levels. Interestingly, adult human and mouse hearts had more Taz than Yap1 by mRNA and protein expression and their increases in diseased hearts were proportional and did not change Yap1/Taz ratio. Yap1, Taz, and Tead1 were accumulated in the nuclear fraction and cardiomyocyte nuclei of diseased hearts. The ratio of Yap1 phosphorylated at serine 127 (human) or serine 112 (mouse) to the total Yap1 (pYap1/Yap1) was significantly lower in the nuclear fraction of diseased hearts than that in normal controls. More importantly, Hippo downstream targets Ankrd1, Ctgf, and Cyr61 were transcriptionally elevated in the diseased hearts. These results suggest that Yap1/Taz signaling is activated in human and mouse dysfunctional hearts. Further investigation with relevant animal models will determine whether this pathway is a potential target for preventing and reversing abnormal remodeling during the progression of different cardiac disorders.},
}
@article {pmid29146271,
year = {2018},
author = {Co, M and Kwong, A and Shek, T},
title = {Factors affecting the under-diagnosis of atypical ductal hyperplasia diagnosed by core needle biopsies - A 10-year retrospective study and review of the literature.},
journal = {International journal of surgery (London, England)},
volume = {49},
number = {},
pages = {27-31},
doi = {10.1016/j.ijsu.2017.11.005},
pmid = {29146271},
issn = {1743-9159},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/methods/*statistics &amp; numerical data ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma in Situ/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Carcinoma, Lobular/pathology ; Diagnostic Errors ; Female ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult ; },
abstract = {INTRODUCTION: Due to the possibility of underestimation, surgical excision is usually offered to patients with atypical ductal hyperplasia (ADH) diagnosed with core needle biopsy (CNB). Here we review the 10-year data of patients with ADH diagnosed by CNB, aiming to identify the factors associated with under-diagnosis.<br><br>METHODS: Retrospective review of database from 1st Jan 2005 to 31st Dec 2014 was performed; patients with ADH diagnosed by CNB were identified. Diagnosis upgrade rate and its risk factors were evaluated.<br><br>RESULTS: 104 patients were found to have ADH on CNB, 101 patients received excisional biopsy while 3 patients refused operation. 34 patients had ductal carcinoma in situ (DCIS) after excision, 6 had invasive ductal carcinoma, 1 had lobular carcinoma in situ and 1 had angiosarcoma. CNB under-diagnosed up to 41.6% of malignant lesions. Breast mass on presentation and suspicious mammograms (BIRADS &#x2265; 4) are associated with diagnosis upgrade (P&#xa0;=&#xa0;0.0005, 0.0001). Literature review of 39 studies between 1997 and 2017 revealed 3125 excision procedures performed for ADH diagnosed by CNB, the pooled median diagnosis upgrade rate was 25% (Range 4-54%).<br><br>CONCLUSION: We recommend excision in all patients with ADH diagnosed by CNB, especially in patients with suspicious mammographic features.},
}
@article {pmid29142588,
year = {2017},
author = {Mwakigonja, AR and Lushina, NE and Mwanga, A},
title = {Characterization of hormonal receptors and human epidermal growth factor receptor-2 in tissues of women with breast cancer at Muhimbili National Hospital, Dar es salaam, Tanzania.},
journal = {Infectious agents and cancer},
volume = {12},
number = {},
pages = {60},
pmid = {29142588},
issn = {1750-9378},
abstract = {BACKGROUND: Breast cancer is a leading cause of morbidity and deaths among women worldwide. In Tanzania there is no published data on human epidermal growth receptor-2 (HER2/neu) expression in breast carcinoma. Hormonal receptors and HER2/neu status reportedly influence post-mastectomy adjuvant therapy and predict treatment outcome and prognosis. Here we evaluate hormonal receptors and HER-2 status in biopsies of women with breast cancer at Muhimbili National Hospital (MNH).<br><br>METHODS: A cross-sectional study of female breast post-modified radical mastectomy (MRM)/incisional biopsies confirmed to be carcinoma at the Histopathology Unit (January-December 2013). Tissue blocks having poor morphology, without tumor, secondary tumors, cases outside the study period and male patients were excluded. Routine staining was done followed by immunohistochemistry for estrogen (ER), and progesterone (PgR) receptors and HER2. Data analyzed using Statistical Package for Social Sciences (SPSS).<br><br>RESULTS: A total of 218 cases were confirmed to be carcinoma including 70 meeting inclusion criteria. Age at diagnosis ranged 18-75&#xa0;years and mean age was 48.36&#xa0;years. Majority (64.3%) were in the 36-55&#xa0;years age-group. Histologically, most (88.6%) women had invasive ductal carcinoma including 43.1% of intermediate grade. A great majority (78%) were stage three. Due to logistical constrains, 75.7% (n&#xa0;=&#xa0;53/70) cases where immunostained for hormones including 43.4% (ER+), 26.4% (PgR+), and 28% (ER+/PgR+). Furthermore, 65.7% (n&#xa0;=&#xa0;46/70) cases were immunostained for HER-2 and 15.2% (n&#xa0;=&#xa0;7/46) were positive, 45.6% were triple negative (ER-,PgR-,HER2-), 23.9% (ER+,PgR+,HER2-) or luminal B, 2.2% (ER+,PgR-,HER2+),13% (ER-,PgR-,HER2+) and 15% (ER+,PgR-,HER2-) with none being triple positive.<br><br>CONCLUSIONS: Hormonal receptors and HER2 expression at MNH appears to be comparable to previous Africans/African Americans reports but not with studies among Caucasians and the current proportion of triple negative breast carcinomas (TNBC) is higher than in a previous Tanzanian report and majority are luminal. HER2 over-expression is relatively common. It is strongly recommended that receptor status assessment be made routine for breast cancer patients at MNH.},
}
@article {pmid29142206,
year = {2017},
author = {Wang, CQ and Li, Y and Huang, BF and Zhao, YM and Yuan, H and Guo, D and Su, CM and Hu, GN and Wang, Q and Long, T and Wang, Y and Tang, CH and Li, X},
title = {EGFR conjunct FSCN1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer.},
journal = {Scientific reports},
volume = {7},
number = {1},
pages = {15654},
pmid = {29142206},
issn = {2045-2322},
mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carrier Proteins/*genetics ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; ErbB Receptors/genetics ; Female ; Gefitinib/administration &amp; dosage ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Microfilament Proteins/*genetics ; Middle Aged ; *Molecular Targeted Therapy ; Neoplasm Recurrence, Local/drug therapy/genetics/pathology ; Progression-Free Survival ; Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology ; },
abstract = {Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.},
}
@article {pmid29131529,
year = {2017},
author = {Yang, LP and Sun, HF and Zhao, Y and Chen, MT and Zhang, N and Jin, W},
title = {Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study.},
journal = {Cancer medicine},
volume = {6},
number = {12},
pages = {2867-2875},
pmid = {29131529},
issn = {2045-7634},
mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Carcinoma, Lobular/mortality/*secondary/therapy ; Chi-Square Distribution ; Disease Progression ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; Young Adult ; },
abstract = {The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease-specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534-0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (P = 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS.},
}
@article {pmid29126758,
year = {2017},
author = {Helal, DS and El-Guindy, DM},
title = {Maspin expression and subcellular localization in invasive ductal carcinoma of the breast: Prognostic significance and relation to microvessel density.},
journal = {Journal of the Egyptian National Cancer Institute},
volume = {29},
number = {4},
pages = {177-183},
doi = {10.1016/j.jnci.2017.09.002},
pmid = {29126758},
issn = {2589-0409},
mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*genetics/*metabolism ; Carcinoma, Ductal, Breast/diagnosis/*genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neovascularization, Pathologic/genetics/metabolism ; Prognosis ; Protein Transport ; Serpins/*genetics/*metabolism ; Tumor Burden ; },
abstract = {Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor. The expression of maspin was evaluated immunohistochemically in 45 IDC cases. The positive rate of maspin expression was 73.3%. Maspin positivity was significantly related to higher tumor grade (p value = 0.041), nodal metastasis (p value = 0.044), perineural invasion (p value = 0.047), and high CD34+MVD (p value = 0.002). Nuclear maspin was detected in 36.6% whereas cytoplasmic maspin was detected in 63.4% of maspin positive cases. A significant inverse relationship was observed between nuclear maspin and high tumor grade (p value = 0.016), and nodal metastasis (p value = 0.047). These results suggest that maspin expression has a prognostic role in breast cancer. Maspin expression is related to increased angiogenesis. Subcellular localization of maspin can strongly affect cancer prognosis. Cytoplasmic maspin relates to poor prognostic parameters whereas nuclear maspin relates to good prognostic ones.},
}
@article {pmid29090670,
year = {2018},
author = {Gurzu, S and Banias, L and Bara, T and Feher, I and Bara, T and Jung, I},
title = {The Epithelial-Mesenchymal Transition Pathway in Two Cases with Gastric Metastasis Originating from Breast Carcinoma, One with a Metachronous Primary Gastric Cancer.},
journal = {Recent patents on anti-cancer drug discovery},
volume = {13},
number = {1},
pages = {118-124},
doi = {10.2174/2212798409666171101121108},
pmid = {29090670},
issn = {2212-3970},
mesh = {Aged ; Breast Neoplasms/diagnosis/*metabolism ; Epithelial-Mesenchymal Transition/*physiology ; Female ; Humans ; Neoplasms, Second Primary/diagnosis/*metabolism/secondary ; Stomach Neoplasms/diagnosis/*metabolism/secondary ; },
abstract = {BACKGROUND: Metastases to the stomach are extremely rare and the metastatic pathway is not well understood.<br><br>OBJECTIVE: To present two unusual gastric metastases and a review of the literature regarding the pathway of Epithelial Mesenchymal Transition (EMT) in the metastatic cells.<br><br>METHOD: The clinicopathological aspects of the two cases were presented in the light of the most recent patents. Data about patents were obtained from the online databases PubMed, World Intellectual Property Organization (WIPO) and Google patents.<br><br>RESULTS: In the first case, in a 73-year-old female, total gastrectomy was performed for a Gastric Cancer (GC) that was proved to be, based on the immunohistochemical features (positivity for mammaglobin and estrogen receptor and negativity for E-cadherin, &#x3b2;-catenin, CD44 and maspin), a metastasis from an invasive lobular carcinoma of the breast, that was later confirmed. In the second case, a 67-year-old female with invasive ductal carcinoma of the breast, which benefited from chemotherapy and mastectomy, presented a metachronous gastric adenocarcinoma with collision-type metastatic breast ductal carcinoma. The aggressiveness of the GC cells was induced through the E-cadherin/maspin pathway, while the CD44-related stem-like properties of the tumor cells induced the aggressiveness of ductal carcinoma.<br><br>CONCLUSION: In females with breast cancer, a possible metastasis in the stomach should be taken into account. Maspin and VSIG1 are not involved in breast cancer histogenesis. The Wnt/&#x3b2;-catenin signaling is not involved in the lobular carcinoma progression. The CD44/HER2 positivity in ductal carcinoma cells might indicate high risk of distant metastasis and low response to chemotherapy.},
}
@article {pmid29084692,
year = {2017},
author = {Chen, K and Wang, CQ and Fan, YQ and Xie, YS and Yin, ZF and Xu, ZJ and Zhang, HL and Cao, JT and Wang, Y and Gao, L},
title = {Model design for screening effective Antihyperlipidemic drugs using zebrafish system.},
journal = {Pakistan journal of pharmaceutical sciences},
volume = {30},
number = {5},
pages = {1697-1707},
pmid = {29084692},
issn = {1011-601X},
mesh = {Animals ; Atorvastatin/pharmacology ; Biomarkers/blood ; Cholesterol/blood ; Diet, High-Fat ; Disease Models, Animal ; Drug Discovery/*methods ; Ezetimibe/pharmacology ; Fenofibrate/pharmacology ; *High-Throughput Screening Assays ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Hyperlipidemias/blood/*drug therapy/etiology ; Hypolipidemic Agents/*pharmacology ; Lipid Metabolism/*drug effects ; Male ; Triglycerides/blood ; Zebrafish/*blood ; },
abstract = {The purpose of this paper was to explore a new method for screening lipid-lowering drugs in zebrafish models. The suitable drug concentrations of atorvastatin (ATV), fenofibrate (FEF) and ezetimibe (EZE) were first determined. Then, the serum cholesterol and triglyceride levels were detected in high-fat diet (HFD)-fed zebrafish. The HFD zebrafish models were constructed and the effects of drugs on them were observed by Oil red O staining and fluorescence labeling. Statistical analyses among groups were conducted using SPSS software. The lowest drug concentration (LDC) and the highest (HDC) of ATV, FEF and EZE were 0.3 μM/37.0μM, 1.2μM/3.5μM, and 6.3 μM/26.4μM, respectively, while, the intermediate (IDC) was, in order, 18.5μM, 1.8μM, 13.2μM. The cholesterol and triglyceride levels in HFD-fed zebrafish were increased after 7 weeks fat feeding (p<0.05). Moreover, the levels of triglyceride were significantly decreased after LDC of ATV and FEF treated (p<0.05), but not that of EZE. While, the cholesterol levels were reduced in three groups (p<0.05). Moreover, the 5 dpf high-fat zebrafish model was established successfully and maintained stably for 24h. ATV produced effects in a concentration-dependent manner, while only IDC and HDC of FEF and EZE made effects on this model. Intravascular cholesterol levels were significantly increased after HCD treatment and decreased after drug treated. The high-fat zebrafish model induced by HFD-fed was available and successful, besides, the Oil red O staining may be an available and rapid method for screening lipid-lowering drugs.},
}
@article {pmid29076877,
year = {2018},
author = {Skálová, A and Stenman, G and Simpson, RHW and Hellquist, H and Slouka, D and Svoboda, T and Bishop, JA and Hunt, JL and Nibu, KI and Rinaldo, A and Vander Poorten, V and Devaney, KO and Steiner, P and Ferlito, A},
title = {The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas.},
journal = {The American journal of surgical pathology},
volume = {42},
number = {2},
pages = {e11-e27},
doi = {10.1097/PAS.0000000000000980},
pmid = {29076877},
issn = {1532-0979},
mesh = {Biomarkers, Tumor/*genetics ; Biopsy ; Carcinoma/*genetics/pathology/therapy ; Diagnosis, Differential ; Gene Fusion ; Genetic Predisposition to Disease ; Humans ; *Molecular Diagnostic Techniques ; Mutation ; Neoplasm Grading ; Phenotype ; Predictive Value of Tests ; Salivary Gland Neoplasms/*genetics/pathology/therapy ; Translocation, Genetic ; },
abstract = {Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.},
}
@article {pmid29072365,
year = {2017},
author = {Chen, H and Wu, K and Wang, M and Wang, F and Zhang, M and Zhang, P},
title = {Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.},
journal = {Cancer medicine},
volume = {6},
number = {12},
pages = {2775-2786},
pmid = {29072365},
issn = {2045-7634},
mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/*mortality/secondary/therapy ; Carcinoma, Papillary/chemistry/*mortality/secondary/therapy ; Chi-Square Distribution ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Propensity Score ; Proportional Hazards Models ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; },
abstract = {There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P < 0.001, 95% CI: 0.293-0.572) and OS (HR = 0.497, P < 0.001, 95% CI: 0.387-0.637). In subgroup analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation.},
}
@article {pmid29069648,
year = {2017},
author = {Huang, R and Han, J and Liang, X and Sun, S and Jiang, Y and Xia, B and Niu, M and Li, D and Zhang, J and Wang, S and Wei, W and Liu, Q and Zheng, W and Zhang, G and Song, Y and Panga, D},
title = {Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit β-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer.},
journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology},
volume = {43},
number = {6},
pages = {2212-2225},
doi = {10.1159/000484300},
pmid = {29069648},
issn = {1421-9778},
mesh = {Androgen Receptor Antagonists/*pharmacology/therapeutic use ; Anilides/*pharmacology/therapeutic use ; Animals ; Apoptosis/drug effects ; Breast Neoplasms/drug therapy/mortality/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Down-Regulation/drug effects ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Nitriles/*pharmacology/therapeutic use ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism ; Receptors, Androgen/chemistry/*genetics/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Signal Transduction/drug effects ; Tosyl Compounds/*pharmacology/therapeutic use ; Transcription, Genetic/*drug effects ; Transplantation, Heterologous ; beta Catenin/genetics/*metabolism ; },
abstract = {BACKGROUND/AIMS: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment.<br><br>METHODS: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer.<br><br>RESULTS: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/&#x3b2;-catenin signaling and inhibited the growth of AR+/ER- breast cancer.<br><br>CONCLUSION: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.},
}
@article {pmid29065116,
year = {2017},
author = {Picillo, M and Pivonello, R and Santangelo, G and Pivonello, C and Savastano, R and Auriemma, R and Amboni, M and Scannapieco, S and Pierro, A and Colao, A and Barone, P and Pellecchia, MT},
title = {Serum IGF-1 is associated with cognitive functions in early, drug-naïve Parkinson's disease.},
journal = {PloS one},
volume = {12},
number = {10},
pages = {e0186508},
pmid = {29065116},
issn = {1932-6203},
mesh = {Adult ; Aged ; Aged, 80 and over ; Cognition Disorders/*blood/complications ; Female ; Humans ; Insulin-Like Growth Factor I/*metabolism ; Male ; Middle Aged ; Parkinson Disease/blood/*complications ; },
abstract = {OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) since the early stages and many patients eventually develop dementia. Yet, occurrence of dementia in PD is unpredictable. Evidence supports the hypothesis that insulin-like growth factor-1 (IGF-1) is involved in cognitive deficits. Our aim was to evaluate the relationship between serum IGF-1 levels and neuropsychological scores in a large cohort of drug-naïve PD patients during the earliest stages of the disease.<br><br>METHODS: Serum IGF-1 levels were determined in 405 early, drug-na&#xef;ve PD patients and 191 healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). The association between serum IGF-1 levels and neuropsychological scores was evaluated with linear regression analysis.<br><br>RESULTS: IGF-1 levels were similar in PD and HC. In PD patients the lowest IGF-1 quartile was a predictor of lower performances at the Semantic Fluency task (&#x3b2; = -3.46, 95%CI: -5.87 to -1.01, p = 0.005), the Symbol Digit Modalities Score (&#x3b2; = -2.09, 95%CI: -4.02 to -0.15, p = 0.034), and Hopkins Verbal Learning Test Retention (&#x3b2; = -0.05, 95%CI: -0.09 to -0.009, p = 0.019).<br><br>CONCLUSIONS: Lower serum IGF-1 levels are associated to poor performances in cognitive tasks assessing executive function, attention and verbal memory in a large cohort of early PD patients. Follow-up studies are warranted to assess if IGF-1 is related to the development of dementia in PD.},
}
@article {pmid29056512,
year = {2017},
author = {Rios Garcia, M and Steinbauer, B and Srivastava, K and Singhal, M and Mattijssen, F and Maida, A and Christian, S and Hess-Stumpp, H and Augustin, HG and Müller-Decker, K and Nawroth, PP and Herzig, S and Berriel Diaz, M},
title = {Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasis and Recurrence.},
journal = {Cell metabolism},
volume = {26},
number = {6},
pages = {842-855.e5},
doi = {10.1016/j.cmet.2017.09.018},
pmid = {29056512},
issn = {1932-7420},
mesh = {Acetyl-CoA Carboxylase/genetics/*metabolism ; Acetylation ; Animals ; Breast Neoplasms/*metabolism/*pathology ; Disease Models, Animal ; Female ; HEK293 Cells ; Humans ; Leptin/metabolism ; Lung Neoplasms/*secondary ; MCF-7 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/metabolism/*pathology ; Tissue Array Analysis ; },
abstract = {Breast tumor recurrence and metastasis represent the main causes of cancer-related death in women, and treatments are still lacking. Here, we define the lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 as a key player in breast cancer metastasis. ACC1 phosphorylation was increased in invading cells both in murine and human breast cancer, serving as a point of convergence for leptin and transforming growth factor (TGF) β signaling. ACC1 phosphorylation was mediated by TGFβ-activated kinase (TAK) 1, and ACC1 inhibition was indispensable for the elevation of cellular acetyl-CoA, the subsequent increase in Smad2 transcription factor acetylation and activation, and ultimately epithelial-mesenchymal transition and metastasis induction. ACC1 deficiency worsened tumor recurrence upon primary tumor resection in mice, and ACC1 phosphorylation levels correlated with metastatic potential in breast and lung cancer patients. Given the demonstrated effectiveness of anti-leptin receptor antibody treatment in halting ACC1-dependent tumor invasiveness, our work defines a "metabolocentric" approach in metastatic breast cancer therapy.},
}
@article {pmid29052527,
year = {2017},
author = {Chen, HR and Wu, YT and Yu, QB and Yang, YY and Wei, YX and Li, HY and Wu, KN and Kong, LQ},
title = {Negative genic switch of HER-2 in the primary tumor instead of the synchronous metastatic nodal lesions after neoadjuvant chemotherapy in a patient with primary HER2-positive breast cancer.},
journal = {World journal of surgical oncology},
volume = {15},
number = {1},
pages = {189},
pmid = {29052527},
issn = {1477-7819},
mesh = {Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Biopsy, Large-Core Needle ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/*genetics/pathology/secondary/therapy ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymph Nodes/*pathology/surgery ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/*methods ; Receptor, ErbB-2/antagonists &amp; inhibitors/*genetics ; Trastuzumab/therapeutic use ; },
abstract = {BACKGROUND: A few retrospective studies have indicated that neoadjuvant chemotherapy (NAC) in breast cancer may change biomarker profiles of the primary tumor. Little is known about the status of HER-2 gene of the synchronous nodal metastases when that of the residual tumor undergoes negative conversion in a neoadjuvant setting.<br><br>CASE PRESENTATION: We describe a female patient with left breast cancer (T2N2M0) who underwent negative conversion of HER-2 in the primary tumor instead of the synchronous nodal lesions after NAC. Core needle biopsy showed invasive ductal carcinoma with HER2 immunohistochemistry (IHC) (2+) and amplified HER-2 gene determined by fluorescence in situ hybridization (FISH). Then, the patient underwent 4&#xa0;cycles of anthracycline- and taxane-based NAC and subsequent left modified radical mastectomy. Postoperative pathology showed invasive ductal carcinoma involving 4 of 12 surgically excised axillary lymph nodes with HER2 IHC (1+) and FISH negative (HER2 gene not amplified) in the residual tumor of the breast specimen. Due to the negative genic switch of HER2 after NAC, the patient rejected to accept trastuzumab. Under the patient's consent, the synchronous nodal lesions were further investigated and showed HER2 IHC(-) but FISH positive (HER-2 gene amplified). Therefore, the patient agreed to accept adjuvant trastuzumab treatment every 3&#xa0;weeks for 1&#xa0;year.<br><br>CONCLUSIONS: We propose further assessment of HER2 gene in the synchronous nodal metastases, especially when negative genic switch of HER-2 occurs in the primary tumor after NAC in order to tailor the systemic regimens for breast cancer patients.},
}
@article {pmid29045292,
year = {2018},
author = {Bennett, JA and Young, RH and Chuang, AY and Lerwill, MF},
title = {Ovarian Metastases of Breast Cancers With Signet Ring Cells: A Report of 17 Cases Including 14 Krukenberg Tumors.},
journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists},
volume = {37},
number = {6},
pages = {507-515},
doi = {10.1097/PGP.0000000000000462},
pmid = {29045292},
issn = {1538-7151},
mesh = {Adenocarcinoma/*secondary ; Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Carcinoma, Signet Ring Cell/*secondary ; Female ; Humans ; Krukenberg Tumor/*secondary ; Middle Aged ; Ovarian Neoplasms/*secondary ; },
abstract = {Krukenberg tumor, defined as metastatic adenocarcinoma to the ovary containing at least 10% signet ring cells, usually arises from the stomach but can also originate from other sites. We reviewed 17 metastatic breast carcinomas to the ovary with signet ring cells to potentially identify features indicative of mammary origin as opposed to other possible primary sites. The patients ranged from 41 to 76 (mean, 53.6) yr. Fourteen had a prior history of invasive breast carcinoma (invasive ductal carcinoma, 4; invasive lobular carcinoma, 3; adenocarcinoma not otherwise specified, 3; carcinoma with ductal and lobular features, 2; and unspecified carcinoma, 2) and metastases were identified 2 to 284 (mean, 79) mo after the original diagnosis. Three patients had no known history of invasive breast carcinoma: 1 was subsequently diagnosed with invasive lobular carcinoma, 1 had suspicious bilateral breast masses identified on imaging, and 1 was lost to follow-up. Bilateral ovarian metastases were present in 87%, and the tumors ranged from 3.8 to 19 (mean, 8) cm. Microscopically the ovarian architecture was effaced in 71% by discrete tumor lobules separated by striking edema. The tumors exhibited a variety of histologic patterns: nests were most common (88%), followed by cords (82%), diffuse sheets (82%), single cells (71%), small clusters (41%), glands (29%), and follicle-like cysts (12%). Signet ring cells comprised 2% to 70% (mean, 33%) of the tumors, with 14 cases meeting the criteria for Krukenberg tumor. Signet ring cells were most frequently observed within diffuse sheets (71%) and cords (65%). Tumor cells arranged in nests, cords, and diffuse sheets are typical of Krukenberg tumor of breast origin, and the patterns recapitulate those seen in primary breast carcinomas. Features characteristic of gastrointestinal origin, such as extracellular mucin, intestinal-type glands, dirty necrosis, microcysts, and goblet cell carcinoid-like foci, were absent. The overall morphologic picture in cases of ovarian spread of breast cancer with signet ring cells is usually strongly suggestive of mammary origin. The diagnosis can be further supported by the clinical history and immunohistochemical evaluation.},
}
@article {pmid29043464,
year = {2018},
author = {Mordang, JJ and Gubern-Mérida, A and Bria, A and Tortorella, F and Mann, RM and Broeders, MJM and den Heeten, GJ and Karssemeijer, N},
title = {The importance of early detection of calcifications associated with breast cancer in screening.},
journal = {Breast cancer research and treatment},
volume = {167},
number = {2},
pages = {451-458},
pmid = {29043464},
issn = {1573-7217},
support = {KUN 2012-5577//KWF Kankerbestrijding/International ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*complications/pathology ; Calcinosis/complications/*diagnosis/pathology ; *Early Diagnosis ; Female ; Humans ; Mammography ; Mass Screening ; Middle Aged ; },
abstract = {PURPOSE: The aim of this study was to assess how often women with undetected calcifications in prior screening mammograms are subsequently diagnosed with invasive cancer.<br><br>METHODS: From a screening cohort of 63,895 women, exams were collected from 59,690 women without any abnormalities, 744 women with a screen-detected cancer and a prior negative exam, 781 women with a false positive exam based on calcifications, and 413 women with an interval cancer. A radiologist identified cancer-related calcifications, selected by a computer-aided detection system, on mammograms taken prior to screen-detected or interval cancer diagnoses. Using this ground truth and the pathology reports, the sensitivity for calcification detection and the proportion of lesions with visible calcifications that developed into invasive cancer were determined.<br><br>RESULTS: The screening sensitivity for calcifications was 45.5%, at a specificity of 99.5%. A total of 68.4% (n&#xa0;=&#xa0;177) of cancer-related calcifications that could have been detected earlier were associated with invasive&#xa0;cancer when diagnosed.<br><br>CONCLUSIONS: Screening sensitivity for detection of malignant calcifications is low. Improving the detection of these early signs of cancer is important, because the majority of lesions with detectable calcifications that are not recalled immediately but detected as interval cancer or in the next screening round are invasive at the time of diagnosis.},
}
@article {pmid29037500,
year = {2017},
author = {Siciliano, M and Trojano, L and De Micco, R and De Mase, A and Garramone, F and Russo, A and Tedeschi, G and Tessitore, A},
title = {Motor, behavioural, and cognitive correlates of fatigue in early, de novo Parkinson disease patients.},
journal = {Parkinsonism &amp; related disorders},
volume = {45},
number = {},
pages = {63-68},
doi = {10.1016/j.parkreldis.2017.10.004},
pmid = {29037500},
issn = {1873-5126},
mesh = {Aged ; Anxiety/epidemiology/etiology ; Apathy ; Cognitive Dysfunction/epidemiology/etiology ; Fatigue/epidemiology/*etiology/*psychology ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications ; Prevalence ; Sleep Wake Disorders/epidemiology/etiology ; },
abstract = {INTRODUCTION: Fatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.<br><br>METHODS: Eighty-one consecutive de novo PD patients (64% men; mean age 65.73&#xa0;&#xb1;&#xa0;8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score&#xa0;&#x2265;&#xa0;8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue.<br><br>RESULTS: Twelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p&#xa0;= 0.04), "episodic anxiety" subscale of PAS (p&#xa0;=&#xa0;0.005), and "cognitive apathy" subscale of AES (p&#xa0;=&#xa0;0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p&#xa0;= 0.745).<br><br>CONCLUSION: In a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.},
}
@article {pmid29026955,
year = {2018},
author = {Watson, L and Dunn, D and Fraser-Kirk, G},
title = {Indolent Rib Osteomyelitis Following Breast Implant Reconstruction: An Unusual Case and Review of the Literature.},
journal = {Aesthetic plastic surgery},
volume = {42},
number = {2},
pages = {447-450},
doi = {10.1007/s00266-017-0975-z},
pmid = {29026955},
issn = {1432-5241},
mesh = {Anti-Bacterial Agents/therapeutic use ; Australia ; Breast Implantation/*adverse effects/methods ; Breast Implants/*adverse effects ; Breast Neoplasms/pathology/*surgery ; Device Removal ; Female ; Follow-Up Studies ; Humans ; Mastectomy/methods ; Middle Aged ; Osteomyelitis/drug therapy/*etiology/physiopathology ; Prosthesis-Related Infections/diagnosis/microbiology/*surgery ; Rare Diseases ; Ribs/*microbiology/pathology ; Risk Assessment ; Treatment Outcome ; },
abstract = {UNLABELLED: Rib osteomyelitis is an infrequently occurring but important complication of breast implant surgery. Although prosthetic or surgical site infection (SSI) and rib osteomyelitis as separate entities are well described in the literature, only five cases of rib or sternal osteomyelitis related to implant placement have been reported globally. Historically patients who experience this complication have not demonstrated an identifiable prevalence of the traditional risk factors associated with SSI or rib osteomyelitis. This report describes the sequence of clinical manifestations of an unusual case of breast implants complicated by rib osteomyelitis. A 56-year-old female underwent mastectomy and insertion of tissue expanders for bilateral invasive ductal carcinoma following which the tissue expanders became infected in the early postoperative period and were subsequently removed. The patient underwent successful expander insertion and subsequent implant exchange surgery several years later and enjoyed an uncomplicated recovery from this. Following nipple reconstruction more than 12 months after successful implant placement, she presented with Staphylococcus epidermidis bacteremia and a left-sided clinical peri-implant infection. Upon removal of her implant, an intraoperative discovery of rib necrosis/osteomyelitis was made for which she was treated. To provide context, the literature was reviewed for other reported cases of rib osteomyelitis following breast implant surgery. This patient, in combination with others reported in the literature, emphasises the diagnostic difficulties posed by this condition as a result of its low incidence and variable or absent clinical features.<br><br>LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .},
}
@article {pmid28993866,
year = {2018},
author = {Stuebs, F and Heidemann, S and Caliebe, A and Mundhenke, C and Arnold, N},
title = {CDH1 mutation screen in a BRCA1/2-negative familial breast-/ovarian cancer cohort.},
journal = {Archives of gynecology and obstetrics},
volume = {297},
number = {1},
pages = {147-152},
doi = {10.1007/s00404-017-4551-1},
pmid = {28993866},
issn = {1432-0711},
mesh = {Adult ; Antigens, CD/*metabolism ; BRCA1 Protein/*metabolism ; BRCA2 Protein/*metabolism ; Breast Neoplasms/*genetics/pathology ; Cadherins/*metabolism ; Cohort Studies ; Early Detection of Cancer ; Female ; Genetic Predisposition to Disease ; Humans ; Mutation ; Ovarian Neoplasms/*genetics/pathology ; },
abstract = {PURPOSE: Mutations in the CDH1 gene are linked both to diffuse gastric cancer and invasive lobular carcinoma (ILC). A high mutation rate is found in families fulfilling the diagnostic criteria for hereditary diffuse gastric cancer. Aim of this study was to clarify whether or not there is a significant contribution of CDH1 mutations in hereditary breast-/ovarian cancer (HBOC).<br><br>METHODS: Ninety-seven unrelated probands fulfilling the diagnostic criteria for HBOC (96 affected, 1 unaffected) but tested negative for pathogenic BRCA1/2 mutations were screened for CDH1 mutations by denaturing high performance liquid chromatography (DHPLC) and subsequent Sanger sequencing of suspicious and positive DHPLC results.<br><br>RESULTS: In total, we found two potentially pathogenic CDH1 alterations, c.1774G&#xa0;>&#xa0;A, pAla592Thr, and c.2512 A&#xa0;>&#xa0;G, p.Ser838Gly, classified as variants of unknown significance according to ClinVar. In addition, we detected a high number of known CDH1 polymorphisms (n&#xa0;=&#xa0;62), some of them more frequent in patients with lobular (55%) than in those with invasive ductal carcinoma (27%).<br><br>CONCLUSION: Although none of the probands studied carried a clearly pathogenic CDH1 mutation, CDH1 could be considered a potential breast cancer gene, esp. for ILC worth including it in the NGS (next generation sequencing) HBOC panel.},
}
@article {pmid28982860,
year = {2017},
author = {Grzegrzolka, J and Wojtyra, P and Biala, M and Piotrowska, A and Gomulkiewicz, A and Rys, J and Podhorska-Okolow, M and Dziegiel, P},
title = {Correlation Between Expression of Twist and Podoplanin in Ductal Breast Carcinoma.},
journal = {Anticancer research},
volume = {37},
number = {10},
pages = {5485-5493},
doi = {10.21873/anticanres.11978},
pmid = {28982860},
issn = {1791-7530},
mesh = {Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/genetics/mortality/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/mortality/surgery ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Membrane Glycoproteins/*analysis/genetics ; Middle Aged ; Nuclear Proteins/*analysis/genetics ; Proportional Hazards Models ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Stromal Cells/chemistry/pathology ; Time Factors ; Treatment Outcome ; Twist-Related Protein 1/*analysis/genetics ; Up-Regulation ; },
abstract = {BACKGROUND/AIM: As a result of activation of transcription factors engaged in epithelial-mesenchymal transition (EMT), such as Twist, inhibition of epithelial markers and an increased expression of mesenchymal markers are observed. One of the specific markers of cancer-associated fibroblasts is podoplanin (PDPN) - a mucin-type membrane glycoprotein. The aim of this work was to study the localisation and intensity of expression of Twist and PDPN on the mRNA and protein level in cases of invasive ductal breast carcinoma (IDC), and its association with patients' clinico-pathological data.<br><br>MATERIALS AND METHODS: The study included archival material in a form of 80 paraffin IDC blocks and 11 IDC fragments frozen in liquid nitrogen. Immunohistochemical expression of Twist and PDPN was evaluated using light microscope and semiquantitative scale for evaluation of nuclear expression or immunoreactive scale (IRS) for evaluation of cytoplasmic expression. Material was isolated from frozen IDC fragments using laser micro-dissection (from cancer and stromal cells, separately) and was used to perform real-time PCR.<br><br>RESULTS: Twist expression was higher in stromal cells in comparison to cancer cells. Analysis of patients' survival rate showed, that higher expression of Twist in cancer cells was associated with shorter overall survival time and shorter event-free survival time. The expression of PDPN was also higher in stromal cells in comparison with cancer cells. In addition, positive correlation was observed between expression of Twist and PDPN in stromal cells of IDC (r=0.267; p<0.05).<br><br>CONCLUSION: The relationship between the higher expression of Twist in both cancer and stromal cells and shorter patients' survival indicates Twist as a potential useful prognostic marker in IDC. Positive correlation of Twist and PDPN expression may indicate the role of PDPN in EMT in IDC.},
}
@article {pmid28977635,
year = {2017},
author = {Kumar, V and Fleming, T and Terjung, S and Gorzelanny, C and Gebhardt, C and Agrawal, R and Mall, MA and Ranzinger, J and Zeier, M and Madhusudhan, T and Ranjan, S and Isermann, B and Liesz, A and Deshpande, D and Häring, HU and Biswas, SK and Reynolds, PR and Hammes, HP and Peperkok, R and Angel, P and Herzig, S and Nawroth, PP},
title = {Homeostatic nuclear RAGE-ATM interaction is essential for efficient DNA repair.},
journal = {Nucleic acids research},
volume = {45},
number = {18},
pages = {10595-10613},
pmid = {28977635},
issn = {1362-4962},
mesh = {Animals ; Ataxia Telangiectasia Mutated Proteins/*metabolism ; Cell Nucleus/enzymology/metabolism ; Cellular Senescence ; DNA/metabolism ; DNA Breaks, Double-Stranded ; *DNA Repair ; DNA Repair Enzymes/metabolism ; DNA-Binding Proteins/metabolism ; Homeostasis ; Lung/physiopathology ; MRE11 Homologue Protein ; Mice, Inbred C57BL ; Mice, Knockout ; Pulmonary Fibrosis/genetics/physiopathology ; Receptor for Advanced Glycation End Products/genetics/*metabolism ; Reperfusion Injury/genetics/metabolism ; Signal Transduction ; },
abstract = {The integrity of genome is a prerequisite for healthy life. Indeed, defects in DNA repair have been associated with several human diseases, including tissue-fibrosis, neurodegeneration and cancer. Despite decades of extensive research, the spatio-mechanical processes of double-strand break (DSB)-repair, especially the auxiliary factor(s) that can stimulate accurate and timely repair, have remained elusive. Here, we report an ATM-kinase dependent, unforeseen function of the nuclear isoform of the Receptor for Advanced Glycation End-products (nRAGE) in DSB-repair. RAGE is phosphorylated at Serine376 and Serine389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response. nRAGE preferentially co-localized with the MRE11 nuclease subunit of the MRN complex and orchestrates its nucleolytic activity to the ATR kinase signaling. This promotes efficient RPA2S4-S8 and CHK1S345 phosphorylation and thereby prevents cellular senescence, IPF and carcinoma formation. Accordingly, loss of RAGE causatively linked to perpetual DSBs signaling, cellular senescence and fibrosis. Importantly, in a mouse model of idiopathic pulmonary fibrosis (RAGE-/-), reconstitution of RAGE efficiently restored DSB-repair and reversed pathological anomalies. Collectively, this study identifies nRAGE as a master regulator of DSB-repair, the absence of which orchestrates persistent DSB signaling to senescence, tissue-fibrosis and oncogenesis.},
}
@article {pmid28974441,
year = {2017},
author = {Kim, YY and Lee, S and Kim, MJ and Kang, BC and Dhakal, H and Choi, YA and Park, PH and Choi, H and Shin, TY and Choi, HG and Kwon, TK and Khang, D and Kim, SH},
title = {Tyrosol attenuates lipopolysaccharide-induced acute lung injury by inhibiting the inflammatory response and maintaining the alveolar capillary barrier.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {109},
number = {Pt 1},
pages = {526-533},
doi = {10.1016/j.fct.2017.09.053},
pmid = {28974441},
issn = {1873-6351},
mesh = {Acute Lung Injury/*drug therapy/etiology/genetics/*immunology ; Animals ; Cyclooxygenase 2/genetics/immunology ; Cytokines/genetics/immunology ; Humans ; Interleukin-6/genetics/immunology ; Lipopolysaccharides/adverse effects ; Lung/immunology/pathology ; Male ; Mice ; Mice, Inbred BALB C ; NF-kappa B/genetics/immunology ; Nitric Oxide Synthase Type II/genetics/immunology ; Phenylethyl Alcohol/administration &amp; dosage/*analogs &amp; derivatives ; Pulmonary Alveoli/drug effects/immunology ; Signal Transduction/drug effects ; },
abstract = {Acute lung injury (ALI) is a life-threatening disease characterized by increased pulmonary vascular permeability because of alveolar capillary barrier dysfunction and increased immune responses. This study determined the anti-inflammatory effect of tyrosol on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms of action. BALB/c mice were orally administered with tyrosol (0.1, 1, and 10 mg/kg) 1 h before an intratracheal injection of LPS (25 μg/50 μL). Oral treatment with tyrosol inhibited lung vascular permeability, histopathological changes, wet/dry lung weight ratio, and pulmonary vascular cell infiltration. The LPS-induced imbalance in the activity of enzymes, such as superoxide dismutase and myeloperoxidase, was regulated by tyrosol. Pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, were reduced by tyrosol in bronchoalveolar lavage fluid and lung tissue. The activation of inflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and phosphorylated-IκBα, was suppressed by the presence of tyrosol in the lung tissue. In addition, tyrosol attenuated the production of NO, the expression of pro-inflammatory cytokines, the expression of iNOS and COX-2, and the nuclear translocation of nuclear factor-κB in LPS-stimulated RAW 264.7 macrophages. These results suggested that tyrosol is a potential therapeutic agent for treating inflammatory lung diseases.},
}
@article {pmid28967088,
year = {2017},
author = {Cavalieri, S and Stathis, A and Fabbri, A and Sonzogni, A and Perrone, F and Tamborini, E and Pelosi, G and de Braud, F and Platania, M},
title = {Uncommon somatic mutations in metastatic NUT midline carcinoma.},
journal = {Tumori},
volume = {103},
number = {Suppl. 1},
pages = {e5-e8},
doi = {10.5301/tj.5000685},
pmid = {28967088},
issn = {2038-2529},
mesh = {Adult ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/secondary ; DCC Receptor/genetics ; DNA-Binding Proteins/genetics ; Fatal Outcome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; *Mutation ; Neoplasm Proteins ; Nuclear Proteins/*genetics ; Oncogene Proteins/*genetics ; Phosphoproteins/genetics ; RNA Splicing Factors/genetics ; },
abstract = {INTRODUCTION:: NUT midline carcinoma (NMC) is a rare and aggressive epithelial cancer arising from median organs. It is driven by chromosomal translocation t(15;19) involving the rearrangement of NUT (nuclear protein in testis) and BRD4 (bromodomain 4) genes leading to fusion oncoprotein BRD4-NUT.<br><br>CASE PRESENTATION:: We report the case of a woman who was previously treated with induction chemotherapy, surgery, radiotherapy and adjuvant trastuzumab for HER-2 positive invasive ductal carcinoma of the breast. After 6 months of follow-up a lung nodule appeared. A biopsy showed an adenocarcinoma fetal type/lung blastoma, so a left inferior lobectomy was performed: NMC harboring BRD4-NUT rearrangement was diagnosed. After 9 months of follow-up, bone and soft tissue metastases occurred, so the patient was given radiotherapy. Next-generation sequencing technology identified somatic mutations in deleted in colorectal cancer (DCC), mixed lineage leukemia protein 3 (MLL3), and splicing factor 3B subunit 1 (SF3B1) genes in NMC cells from both primitive cancer and metastases. The patient was treated with the experimental BRD4 inhibitor for 10 months, until the disease progressed to the lung and bone. After spinal cord compression, the patient was offered palliative radiotherapy to bone and eventually died aged 39 years.<br><br>CONCLUSIONS:: To the best of our knowledge, our case is the first DCC, MLL3, and SF3B1 mutated NUT midline carcinoma reported in the literature. If these mutations were confirmed to play a role in this neoplasm, clinical trials analyzing targeted therapies should be considered, eg. colorectal cancer-like chemotherapies for DCC mutations, hypomethylating agents for MLL3 mutations or SF3B1 inhibitors in case of specific somatic mutations.},
}
@article {pmid28954989,
year = {2017},
author = {Nozoe, T and Nozoe, E and Kono, M and Ohga, T and Ezaki, T},
title = {Further evidence to demonstrate the significance of serum appearance of anti-p53 antibody as a marker for progressive potential in invasive ductal carcinoma of the breast.},
journal = {The journal of medical investigation : JMI},
volume = {64},
number = {3.4},
pages = {241-244},
doi = {10.2152/jmi.64.241},
pmid = {28954989},
issn = {1349-6867},
mesh = {Adult ; Aged ; Antibodies/*blood ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*pathology ; Carcinoma, Ductal, Breast/blood/*pathology ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Tumor Suppressor Protein p53/*immunology ; },
abstract = {BACKGROUND: Serum appearance of anti-p53 antibody (p53Ab) has been reported as an indicator for progressive potential of human tumor tumors including breast cancer. But its significance in breast cancer has not been discussed fully.<br><br>METHODS: Relationship between serum appearance of p53Abs and representative data accounting for progressive potential in breast cancer, nuclear grade (NG), triple negative cancer, and the cumulative score based on these two data (TGS) was investigated among 129 women with invasive ductal carcinoma (IDC) of the breast, who had been treated with surgical resection.<br><br>RESULTS: There was a significant correlation between appearance of p53Abs and recurrence of the tumors (P = 0.035). Significant correlation of serum appearance of p53Abs with negative expression of ER (P = 0.011), the proportion of TNBC (P = 0.013), NG (P = 0.017), and TGS (P = 0.0005).<br><br>CONCLUSIONS: Preoperative serum appearance of p53Abs can be correlated with pathological nuclear grade, incidence of triple negative breast cancer, and TGS. These results might demonstrate more powerful significance of serum appearance of p53Abs as an indicator of progressive potential in IDC of the breast. J. Med. Invest. 64: 241-244, August, 2017.},
}
@article {pmid28942323,
year = {2018},
author = {Nawroth, PP and Bendszus, M and Pham, M and Jende, J and Heiland, S and Ries, S and Schumann, C and Schmelz, M and Schuh-Hofer, S and Treede, RD and Kuner, R and Oikonomou, D and Groener, JB and Kopf, S},
title = {The Quest for more Research on Painful Diabetic Neuropathy.},
journal = {Neuroscience},
volume = {387},
number = {},
pages = {28-37},
doi = {10.1016/j.neuroscience.2017.09.023},
pmid = {28942323},
issn = {1873-7544},
mesh = {Animals ; *Biomedical Research ; Diabetic Neuropathies/*complications/diagnosis/drug therapy ; Disease Progression ; Humans ; Pain/*complications ; },
abstract = {A 62-year-old diabetologist diagnosed himself to have diabetes type-2, with an HbA1c of 9.5. Five months after lifestyle intervention and a multi-drug approach, HbA1c was 6.3, systolic blood pressure was below 135mmHg and BMI reduced to 27. But he suffered from severe painful diabetic neuropathy. Therefore he decided to visit his friend, a famous neuroscientist at an even more famous university. He asked him several plain questions: 1. What is the natural course of painful diabetic neuropathy? 2. Why do I have, despite almost normalizing HbA1c, more problems than before? 3. Are you sure my problems are due to diabetes or should we do a nerve biopsy? 4. Are there imaging techniques helpful for the diagnosis of this diabetic complication, starting in the distal nerve endings of the foot and slowly moving ahead? 5. Can you suggest any drug, specific and effective, for relieving painful diabetic neuropathy? This review will use the experts' answers to the questions of the diabetologist, not only to give a summary of the current knowledge, but even more to highlight areas of research needed for improving the fate of patients with painful diabetic neuropathy. Based on the unknowns, which exceed the knowns in diabetic neuropathy, a quest for more public support of research is made.},
}
@article {pmid28938000,
year = {2017},
author = {Suchanski, J and Tejchman, A and Zacharski, M and Piotrowska, A and Grzegrzolka, J and Chodaczek, G and Nowinska, K and Rys, J and Dziegiel, P and Kieda, C and Ugorski, M},
title = {Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.},
journal = {PloS one},
volume = {12},
number = {9},
pages = {e0184970},
pmid = {28938000},
issn = {1932-6203},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Cancer-Associated Fibroblasts/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cell Line ; Cell Movement/*physiology ; Coculture Techniques ; Disease Progression ; Endothelial Cells/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Glycoproteins/genetics/*metabolism ; Middle Aged ; Neoplasm Invasiveness/physiopathology ; RNA, Messenger/metabolism ; },
abstract = {In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such podoplanin-mediated effects can affect tube formation by endothelial cells and participate in their pathological properties in the tumor context. Our experimental data were supported by clinical studies. First, when IDC and DCIS were analyzed by immunohistochemistry according to the presence of podoplanin-expressing cells, the numbers of cancer-associated fibroblasts with high expression of this glycoprotein were significantly higher in IDC than in DCIS cases. Second, using immunofluorescence, the co-localization of PDPN-positive CAFs with blood vessels stained with antibody directed against CD34 was observed in tumor stroma of IDC samples.},
}
@article {pmid28935545,
year = {2018},
author = {Stires, H and Heckler, MM and Fu, X and Li, Z and Grasso, CS and Quist, MJ and Lewis, JA and Klimach, U and Zwart, A and Mahajan, A and Győrffy, B and Cavalli, LR and Riggins, RB},
title = {Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.},
journal = {Molecular and cellular endocrinology},
volume = {471},
number = {},
pages = {105-117},
pmid = {28935545},
issn = {1872-8057},
support = {P30 CA051008/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; U54 CA149147/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*drug effects/genetics ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic/drug effects ; Glutamic Acid/metabolism ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Mitogen-Activated Protein Kinase Kinases/antagonists &amp; inhibitors/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Mutation/genetics ; Protein Kinase Inhibitors/pharmacology ; Receptors, Estrogen/metabolism ; Receptors, Metabotropic Glutamate/*metabolism ; *Signal Transduction/drug effects ; Tamoxifen/*pharmacology ; Transcriptome/drug effects/genetics ; Exome Sequencing ; },
abstract = {Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.},
}
@article {pmid28934992,
year = {2017},
author = {Plonczak, AM and DiMarco, AN and Dina, R and Gujral, DM and Palazzo, FF},
title = {Breast cancer metastases to the thyroid gland - an uncommon sentinel for diffuse metastatic disease: a case report and review of the literature.},
journal = {Journal of medical case reports},
volume = {11},
number = {1},
pages = {269},
pmid = {28934992},
issn = {1752-1947},
mesh = {Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma/diagnosis/*secondary/surgery ; Carcinoma, Papillary/diagnosis ; Chemotherapy, Adjuvant ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/*pathology ; Mastectomy ; Middle Aged ; Neck Dissection ; Radiotherapy, Adjuvant ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/diagnosis/*secondary/surgery ; Thyroidectomy ; },
abstract = {BACKGROUND: Metastases to the thyroid are rare. The most common primary cancer to metastasize to the thyroid is renal cell carcinoma, followed by malignancies of the gastrointestinal tract, lungs, and skin, with breast cancer metastases to the thyroid being rare. Overall, the outcomes in malignancies that have metastasized to the thyroid are poor. There are no prospective studies addressing the role of surgery in metastatic disease of the thyroid. Isolated thyroidectomy has been proposed as a local disease control option to palliate and prevent the potential morbidity of tumor extension related to the airway. Here, we present a case of a patient with breast cancer metastases to the thyroid gland and discuss the role of thyroidectomy in the context of the current literature.<br><br>CASE PRESENTATION: A 62-year-old Afro-Caribbean woman was diagnosed as having bilateral breast carcinoma in 2004, for which she underwent bilateral mastectomy. The pathology revealed multifocal disease on the right, T2N0(0/20)M0 grade 1 and 2 invasive ductal carcinoma, and on the left side, T3N1(2/18)M0 grade 1 invasive ductal carcinoma. Surgery was followed by adjuvant chemotherapy and regional radiotherapy. The disease was under control on hormonal therapy until 2016, when she developed cervical lymphadenopathy. The fine-needle aspiration cytology of the thyroid was reported as papillary thyroid cancer; and the fine-needle biopsy of the left lateral nodal disease was more suggestive of breast malignancy. She underwent a total thyroidectomy and a clearance of the central compartment lymph nodes and a biopsy of the lateral nodal disease. The histopathological analysis was consistent with metastatic breast cancer in the thyroid and lymph nodes with no evidence of a primary thyroid malignancy.<br><br>CONCLUSIONS: A past history of a malignancy elsewhere should raise the index of suspicion of metastatic disease in patients presenting with thyroid lumps with or without cervical lymphadenopathy. Detection of metastases to the thyroid generally indicates poor prognosis, obviating the need of surgery in an already compromised patient. An empirical thyroidectomy should be considered in select patients for local disease control.},
}
@article {pmid28906374,
year = {2017},
author = {Golmohammadi, R and Namazi, MJ and Going, JJ and Derakhshan, MH},
title = {A single nucleotide polymorphism in codon F31I and V57I of the AURKA gene in invasive ductal breast carcinoma in Middle East.},
journal = {Medicine},
volume = {96},
number = {37},
pages = {e7933},
pmid = {28906374},
issn = {1536-5964},
mesh = {Adult ; Aged ; Aged, 80 and over ; Aurora Kinase A/*genetics ; Breast Neoplasms/*genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*genetics/mortality/*pathology ; Case-Control Studies ; Codon ; Female ; Humans ; Iran ; Middle Aged ; Neoplasm Invasiveness ; *Polymorphism, Single Nucleotide ; Prognosis ; Survival Rate ; Young Adult ; },
abstract = {Although few studies have suggested a carcinogenic role for polymorphism of F31I and V57I codons of AURKA gene in invasive ductal carcinoma, contradictory results from different populations mandates regional investigations. We aimed to determine polymorphisms of F31I and V57I codons of AURKA gene and their association with cancer prognosis in patients compared with controls in an eastern population of Iran.A case-control study was conducted on specimens from 100 patients and 100 age- and gender-matched controls. DNA was extracted and the codons F31I and V57I were amplified. The different genotypes were analyzed by PCR-RFLP and electrophoresis.In codon F31I, the frequency of Phe/Ile was 70% and 82% in patients and healthy controls respectively, whereas (Ile/Ile) was 30% in patients and 18% in healthy (P = .047). Analyzing V57I genotypes showed a higher homozygote Val/Val genotype in patients compared with controls (76% vs 68%), whereas the frequency of heterozygous Val/Ile genotype was lower in patients (17%) than controls (30%), yielding a marginal association between breast cancer and Val/Val genotype (P = .048). No association was observed between SNPs of either F31I or V57I genotypes and histological grades. However, there was a significant association between tumor stages and F31I genotype (P for trend = .003).This is the first report of F31I and V57I polymorphisms in AURKA gene in breast cancer in Iran. Determination of allelic polymorphism of those codons will help to understand background genetic predisposition and could have prognostic value in management of breast cancer in the target population.},
}
@article {pmid28902360,
year = {2017},
author = {Ratajczak-Wielgomas, K and Grzegrzolka, J and Piotrowska, A and Matkowski, R and Wojnar, A and Rys, J and Ugorski, M and Dziegiel, P},
title = {Expression of periostin in breast cancer cells.},
journal = {International journal of oncology},
volume = {51},
number = {4},
pages = {1300-1310},
doi = {10.3892/ijo.2017.4109},
pmid = {28902360},
issn = {1791-2423},
mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Adhesion Molecules/*genetics/*metabolism ; Cell Line, Tumor ; Cytoplasm/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Tumor Burden ; Up-Regulation ; },
abstract = {Periostin (POSTN) is a protein involved in multiple processes important for cancer development, both at the stage of cancer initiation and progression, as well as metastasis. The aim of this study was to determine the expression of POSTN in the cells of non-invasive ductal breast carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to correlate it with clinicopathological data. Immunohistochemical studies (IHC) were conducted on 21 cases of fibrocystic breast change (FC), 44 cases of DCIS and 92 cases of IDC. POSTN expression at mRNA (real-time PCR) and protein level (western blot analysis) was also confirmed in selected breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231 and BO2). Statistically significant higher level of POSTN expression in IDC and DCIS cancer cells compared to FC was noted. Also, the level of POSTN expression in the cytoplasm of IDC cells was shown to increase with the increasing degree of tumour malignancy (G) and significantly higher expression of POSTN was observed in each degree of tumour malignancy (G) relative to FC. Statistically significant higher POSTN expression was observed in tumours with estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) phenotypes in comparison to estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) cases, as well as significant negative correlation between POSTN expression in cancer cells and expression of ER and PR (p<0.05). Additionally, statistically significant differences in POSTN expression were shown between particular breast cancer cell lines, both at mRNA and protein level. Observed POSTN expression was the lowest in the case of MCF-7, and the highest in MDA-MB-231 and BO2 of the most aggressive potential clinically corresponding to G3 tumours. POSTN expression in the cytoplasm of IDC cancer cells may play an important role in cancer transformation mechanism.},
}
@article {pmid28901319,
year = {2017},
author = {Tan, R and Wang, L and Song, J and Li, J and He, T},
title = {Expression and significance of Twist, estrogen receptor, and E-cadherin in human breast cancer cells and tissues.},
journal = {Journal of cancer research and therapeutics},
volume = {13},
number = {4},
pages = {707-714},
doi = {10.4103/jcrt.JCRT_1396_16},
pmid = {28901319},
issn = {1998-4138},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis ; Nuclear Proteins/*genetics ; Receptors, Estrogen/*genetics ; Twist-Related Protein 1/*genetics ; },
abstract = {OBJECTIVES: Breast cancer is one of the most common malignancies in women, and the tumor cells' invasion and metastasis is the main cause of death. Recent reports showed that Twist, a transcription factor, plays multiple roles in breast cancer initiation, progress, and metastasis. However, the underlying mechanisms of Twist in tumor invasion and metastasis of breast cancer still remain unclear. Here, we examined the correlation between Twist, E-cadherin, and estrogen receptor (ER) in promoting invasion and metastasis in breast cancer cells and tissues.<br><br>MATERIALS AND METHODS: The mRNA and protein expression of Twist, E-cadherin, and ER in breast cancer cell lines (MCF-7, MDA-MB-435, MDA-MB-231, and ZR-75-30) and human invasive ductal carcinoma (IDC) tissues from 32 patients were detected by reverse transcription-polymerase chain reaction and immunohistochemistry (IHC), respectively.<br><br>RESULTS: Expression of Twist in cells with high ability of invasion and metastasis was higher than that in MCF-7 cell line which has low ability of invasion and metastasis, while the expression of ER and E-cadherin was much more higher in MCF-7 cell line than in other cells. IHC showed that the expression rate of Twist in IDC tissues and adjacent tissues was 84.38% and 31.25% and the positive expression of E-cadherin and ER was 21.88% and 40.63% in IDC tissues and 81.25% and 84.38% in adjacent tissues, respectively. Interestingly, overexpression of Twist promoted cellular invasion and metastasis and decreased the expression of E-cadherin, ER, AKT, and p-AKT in HEK-293 cells.<br><br>CONCLUSIONS: Taken together, these findings demonstrated that Twist was upregulated in high invasion and metastasis cell lines as well as IDC tissues companioned with downregulated expression of E-cadherin and ER, which provides important clues for the deeper study of breast cancer.},
}
@article {pmid28899737,
year = {2017},
author = {Cao, L and Sun, PL and Yao, M and Jia, M and Gao, H},
title = {Expression of YES-associated protein (YAP) and its clinical significance in breast cancer tissues.},
journal = {Human pathology},
volume = {68},
number = {},
pages = {166-174},
doi = {10.1016/j.humpath.2017.08.032},
pmid = {28899737},
issn = {1532-8392},
mesh = {Adaptor Proteins, Signal Transducing/*analysis ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Carcinoma/*chemistry/mortality/secondary/therapy ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Phosphoproteins/*analysis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Transcription Factors ; YAP-Signaling Proteins ; },
abstract = {The transcriptional co-activator YES-associated protein (YAP) has been reported to act as both an oncogene and tumor suppressor in breast cancers. In this study, we evaluated YAP expression immunohistochemically in 324 breast cancer tissues and correlated the expression with clinicopathological findings and patient survival data. Additionally, we reviewed the literature to clarify the role of YAP in breast cancer. We detected YAP, estrogen receptor, progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) expression and a Ki67 labeling index >20% in 53.4%, 49.0%, 45.0%, 28.3%, and 57.4% of invasive ductal carcinoma tissues, respectively. YAP is mainly localized within the tumor cell nuclei, and its expression was associated with the PR status and luminal A subtype. YAP expression also inversely correlated with the HER2 and Ki67 levels and lymph node metastasis. Kaplan-Meier curves revealed associations of YAP expression with favorable disease-free survival (DFS) and overall survival in patients with luminal A breast cancer and with favorable DFS association among patients with invasive ductal carcinoma, luminal B (HER2-), and luminal B (HER2+) breast cancers. A multivariate Cox analysis revealed that YAP expression and PR status were independent favorable predictors of DFS and overall survival, respectively, among patients with breast cancer, whereas tumor-node-metastasis stage and an old age were independent predictors of a poor DFS. Our results, together with the literature review findings, suggest that YAP could be a prognostic marker in patients with breast cancer.},
}
@article {pmid28891551,
year = {2017},
author = {Olarinoye-Akorede, SA and Silas, BT},
title = {Mondor's disease of the breast in a Nigerian woman previously treated for invasive ductal carcinoma in the contralateral breast: A case report.},
journal = {Nigerian journal of clinical practice},
volume = {20},
number = {8},
pages = {1040-1043},
doi = {10.4103/njcp.njcp_354_16},
pmid = {28891551},
issn = {1119-3077},
mesh = {Breast/diagnostic imaging ; Breast Neoplasms/*complications ; Carcinoma, Ductal, Breast/*complications ; Female ; Humans ; Middle Aged ; Nigeria ; Pain/etiology ; Thrombophlebitis/*complications/*diagnostic imaging ; },
abstract = {Mondor's disease is a self-limiting sclerosing angitis mostly affecting the superficial veins of the breast and chest wall. It is seldom diagnosed, and its etiology and epidemiology are speculative. However, numerous predisposing factors including breast cancer have been postulated. In Nigerian literature, only two cases have been documented to the best of our knowledge. This report is aimed at reminding breast specialists to include it as a diagnostic consideration in patients presenting with a breast lump in the appropriate clinical setting. Its imaging features are also highlighted because it may be incorrectly overlooked as mere ductal dilatation. We present the case of a 60-year-old woman who complained of a painful cordlike lesion in her right breast. Mondor's disease was diagnosed based on the clinical and radiological findings. She had also been previously treated for invasive ductal breast carcinoma in the contralateral breast. Mondor's disease is usually a benign entity, which may resolve spontaneously. On the other hand, it may also be the sole presenting symptom or clue of a breast malignancy; hence, a need for increased awareness.},
}
@article {pmid28869838,
year = {2017},
author = {Turczyk, L and Kitowska, K and Mieszkowska, M and Mieczkowski, K and Czaplinska, D and Piasecka, D and Kordek, R and Skladanowski, AC and Potemski, P and Romanska, HM and Sadej, R},
title = {FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells.},
journal = {Neoplasia (New York, N.Y.)},
volume = {19},
number = {10},
pages = {791-804},
pmid = {28869838},
issn = {1476-5586},
mesh = {Biomarkers, Tumor ; Breast Neoplasms/genetics/metabolism/pathology ; Cell Line, Tumor ; Estrogen Receptor alpha/*metabolism ; Female ; Fibroblast Growth Factors/metabolism ; Fibroblasts/drug effects ; Gene Expression ; Gene Knockout Techniques ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Proteolysis ; Receptor, ErbB-2/metabolism ; Receptor, Fibroblast Growth Factor, Type 2/genetics/*metabolism ; Selective Estrogen Receptor Modulators/*pharmacology ; Signal Transduction/*drug effects ; Tamoxifen/*pharmacology ; },
abstract = {Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.},
}
@article {pmid28865741,
year = {2017},
author = {Greenhouse, I and Babushkin, F and Finn, T and Shimoni, Z and Aliman, M and Ben-Ami, R and Cohen, R},
title = {Long-term outcomes of inappropriate antibiotic therapy for upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a retrospective cohort study.},
journal = {Diagnostic microbiology and infectious disease},
volume = {89},
number = {3},
pages = {222-229},
doi = {10.1016/j.diagmicrobio.2017.07.011},
pmid = {28865741},
issn = {1879-0070},
mesh = {Aged ; Cohort Studies ; Drug Prescriptions/standards ; Drug Resistance, Bacterial ; *Enterobacteriaceae/enzymology ; Enterobacteriaceae Infections/*drug therapy ; Humans ; Retrospective Studies ; Treatment Outcome ; Urinary Tract Infections/drug therapy/*microbiology ; *beta-Lactamases/biosynthesis/metabolism ; },
abstract = {BACKGROUND: To evaluate the short- and long-term outcomes of different antimicrobial treatment options for upper urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.<br><br>METHODS: We retrospectively analyzed patients with a first episode of febrile UTI and positive urine culture with ESBL-producing E. coli or K. pneumoniae during 2012-2015. We compared outcomes among patients who received: (1) definitive treatment with a carbapenem (CP), (2) a microbiologically appropriate intravenous non-carbapenem agent (NCA), (3) a non-appropriate antimicrobial (NAA), and (4) an intravenous NAA followed by an oral NCA (NAA-PO).<br><br>RESULTS: The majority of patients received empirical therapy with NAA (165/178, 93%), and definitive treatment with NCA (n=43), NAA (n=50), and NAA-PO (n=59). The NCA group had significantly higher SIRS score than the NAA-PO group (2.18 versus 1.76, P=0.018), but no differences were found between the NCA and NAA groups (2.18 and 1.92, P=0.15). Clinical cure at discharge from the index hospitalization was high (97-100%) in all 3 groups. The NCA group had longer length of stay as compared with the NAA-PO and NAA groups (8.7days versus 5.39 and 5.24days, P<0.0001) and a lower rate of early (48-72h) improvement (79% versus 96-100%, P=0.0002). Among re-admitted patients, re-admission with ESBL-related bloodstream infection was significantly higher in the NAA group as compared to the NAA-PO and NCA groups (33% versus 4% and 0%, respectively, P=0.02). Death rate within 60days was also higher in the NAA and NCA groups as compared with the NAA-PO group (P=0.048).<br><br>CONCLUSIONS: Inappropriate antimicrobial therapy for febrile non-bacteremic UTI with ESBL-producing enterobacteriaceae is associated with favorable short-term outcomes, but also with a long-term risk of relapsed bacteremic UTI. Definitive treatment with appropriate carbapenem-sparing antimicrobial agents effectively prevents late relapses.},
}
@article {pmid28862125,
year = {2017},
author = {Stroescu, C and Gilca, I and Chirita, D and Poenaru, R and Puşcaşu, A and Pescaru, D and Birceanu, A and Niţipir, C and Copcă, N},
title = {Solitary Adrenal Metastases from Breast Invasive Ductal Carcinoma.},
journal = {Chirurgia (Bucharest, Romania : 1990)},
volume = {112},
number = {4},
pages = {473-476},
doi = {10.21614/chirurgia.112.4.473},
pmid = {28862125},
issn = {1221-9118},
mesh = {Adrenal Gland Neoplasms/*secondary/surgery ; *Adrenalectomy ; Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Neoplasm Invasiveness ; Treatment Outcome ; },
abstract = {The usual neoplastic dissease involving suprarenal glands are adrenal metastaes. The majority of suprarenal metastatic disease arise from lung cancer, followed by the stomach and colon cancer, oesophagus, the liver/bile ducts cancer and renal cell carcinoma. Invasive mammary carcinoma usually spreads to the bones, lungs, lymph nodes, liver and the brain. Adrenal gland metastases from invasive no special type carcinoma represents an extremly low rate number of cases. We discuss about a 66 year old patient who presented with a solitary adrenal metastases from triple negative breast invasive carcinoma. The patient underwent total left adrenalectomy in June 2016. No further adjuvants therapies were performed. At the time of writing the patient is in good condition, without any evidence of recurrence. The role of surgical and adjuvant therapy in treating adrenal metastases after breast cancer in survival rate will be determined in future studies.},
}
@article {pmid28860708,
year = {2017},
author = {Li, A and Li, Y and Ge, L and Li, P and Li, W},
title = {Onychomadesis associated with chemotherapy: case report and mini literature review.},
journal = {Drug design, development and therapy},
volume = {11},
number = {},
pages = {2373-2376},
pmid = {28860708},
issn = {1177-8881},
mesh = {Aged ; Albumins/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/*adverse effects ; Breast Neoplasms/therapy ; Capecitabine/administration &amp; dosage ; Carcinoma, Ductal, Breast/therapy ; Female ; Follow-Up Studies ; Humans ; Nail Diseases/*chemically induced/pathology/therapy ; Paclitaxel/administration &amp; dosage ; },
abstract = {The side effects of chemotherapy drugs have increased in recent years, and some side effects can lead to onychomadesis. A 72-year-old woman who was diagnosed with an invasive ductal carcinoma of the right breast underwent a modified radical mastectomy in April 2015, followed by chemotherapy with capecitabine and nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Subsequently, the patient experienced palmoplantar redness, pain, onycholysis, a transparent serous exudate, and onychomadesis. The chemotherapy was discontinued, and the patient was treated with oral vitamin B6, a polymyxin ointment, and a high-energy red light. The palmoplantar redness and pain were alleviated after 1 month. However, although her fingernails improved, dysesthesia symptoms remained, and all her toenails exhibited defects or deformities at a 24-month follow-up. The symptoms of this disorder should be recognized by dermatologists.},
}
@article {pmid28844697,
year = {2017},
author = {Hamada, Y and Nakayama, Y},
title = {Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.},
journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]},
volume = {17},
number = {6},
pages = {951-955},
doi = {10.1016/j.pan.2017.08.006},
pmid = {28844697},
issn = {1424-3911},
mesh = {Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*pathology ; Female ; Humans ; Liver/pathology ; Liver Neoplasms/*secondary ; Lung Neoplasms ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Pancreatic Neoplasms/*pathology ; },
abstract = {BACKGROUND: Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors.<br><br>METHODS: Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters <2&#xa0;cm. The follow-up period of the 20 patients with smaller tumors was 1-24 years.<br><br>RESULTS: The small-tumor group (n&#xa0;=&#xa0;20) included 11 men and 9 women, aged 51-80 years. Five died of liver metastasis (LM group, n&#xa0;=&#xa0;5) and 15 patients (non-LM group, n&#xa0;=&#xa0;15) were either alive without recurrence (n&#xa0;=&#xa0;11) or died of peritonitis carcinomatosa following local recurrence, subarachnoid hemorrhage, primary lung cancer, or old age (n&#xa0;=&#xa0;1 for each cause of death). The LM and non-LM groups did not significantly differ in numbers of venous invasion by the carcinoma in IDCP and non-IDCP area of the pancreas. However, median numbers of invaded veins in the area of IDCP and percentage of invaded vein/total number of vein in IDCP area were significantly higher in the LM group.<br><br>CONCLUSION: Among patients with small IDCP tumors, the LM group showed more aggressive venous invasion by IDPC. Patients in whom &#x2265;60% of veins were invaded by IDCP should be prepared for LM.},
}
@article {pmid28843709,
year = {2018},
author = {Karnik, T and Kimler, BF and Fan, F and Tawfik, O},
title = {PD-L1 in breast cancer: comparative analysis of 3 different antibodies.},
journal = {Human pathology},
volume = {72},
number = {},
pages = {28-34},
doi = {10.1016/j.humpath.2017.08.010},
pmid = {28843709},
issn = {1532-8392},
mesh = {Antibodies, Monoclonal/immunology/*therapeutic use ; B7-H1 Antigen/*immunology ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*drug therapy/immunology ; Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology ; Immunohistochemistry/methods ; Lung Neoplasms/*drug therapy/immunology/pathology ; Treatment Outcome ; },
abstract = {The interaction of programmed cell death-1 and its ligand-1 (PD-L1) serves as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of 3 different PD-L1 antibodies (Ventana SP263, Dako 22C3, and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic, and 46 distantly metastatic diseases. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor, progesterone receptor, HER2, Ki67, molecular type, and triple-negative status. There was excellent agreement between the 3 antibodies, with highly significant κ values (P≤.001). PD-L1 expression was more likely to be associated with higher tumor grade and estrogen receptor-negative, progesterone receptor-negative, triple-negative, and highly proliferative tumors (P<.001). When we studied PD-L1 expression at 0, 1%-9%, 10%-49%, and ≥50% cutoff points by the 3 antibodies, there were 20 discordant cases between the antibodies. Sixteen were of inconsequential impact as far as low and high PD-L1 expression. The 4 differences between antibodies did exhibit an interesting pattern of expression, where there was a general agreement between the BioCare and Ventana antibodies with consistently higher PD-L1 expression compared with the Dako antibody. Given the high concordance, it is not surprising that all 3 antibodies demonstrated the same associations with all pathologic and clinical parameters studied. Standardization studies to identify reliable biomarkers that help in patient selection for immune therapy to improve the risk-benefit ratio for these drugs are still needed.},
}
@article {pmid28830512,
year = {2017},
author = {Gupta, AP and Zhu, L and Tripathi, J and Kucharski, M and Patra, A and Bozdech, Z},
title = {Histone 4 lysine 8 acetylation regulates proliferation and host-pathogen interaction in Plasmodium falciparum.},
journal = {Epigenetics &amp; chromatin},
volume = {10},
number = {1},
pages = {40},
pmid = {28830512},
issn = {1756-8935},
mesh = {Acetylation ; *Cell Proliferation ; Chromatin/metabolism ; Erythrocytes/parasitology ; Histones/*metabolism ; *Host-Parasite Interactions ; Humans ; Open Reading Frames ; Plasmodium falciparum/*genetics/pathogenicity ; Promoter Regions, Genetic ; *Protein Processing, Post-Translational ; Protozoan Proteins/*metabolism ; },
abstract = {BACKGROUND: The dynamics of histone modifications in Plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. Here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cycle (IDC) of P. falciparum.<br><br>RESULTS: Using a dominant-negative transgenic approach, we showed that acetylations of histone H4 play a direct role in transcription. Specifically, these histone modifications mediate an inverse transcriptional relationship between the factors of cell proliferation and host-parasite interaction. Out of the four H4 acetylations, H4K8ac is likely the rate-limiting, regulatory step, which modulates the overall dynamics of H4 posttranslational modifications. H4K8ac exhibits maximum responsiveness to HDAC inhibitors and has a highly dynamic distribution pattern along the genome of P. falciparum during the IDC. Moreover, H4K8ac functions mainly in the euchromatin where its occupancy shifts from intergenic regions located upstream of 5' end of open reading frame into the protein coding regions. This shift is directly or indirectly associated with transcriptional activities at the corresponding genes. H4K8ac is also active in the heterochromatin where it stimulates expression of the main antigenic gene family (var) by its presence in the promoter region.<br><br>CONCLUSIONS: Overall, we demonstrate that H4K8ac is a potential major regulator of chromatin-linked transcriptional changes during P. falciparum life cycle which is associated not only with euchromatin but also with heterochromatin environment. This is potentially a highly significant finding that suggests a regulatory connection between growth and parasite-host interaction both of which play a major role in malaria parasite virulence.},
}
@article {pmid28826004,
year = {2017},
author = {Zemva, J and Fink, CA and Fleming, TH and Schmidt, L and Loft, A and Herzig, S and Knieß, RA and Mayer, M and Bukau, B and Nawroth, PP and Tyedmers, J},
title = {Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux.},
journal = {Redox biology},
volume = {13},
number = {},
pages = {674-686},
pmid = {28826004},
issn = {2213-2317},
mesh = {Amino Acid Transport Systems/metabolism ; *Energy Metabolism ; Glucose/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; *Hormesis ; Pyruvaldehyde/*metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; },
abstract = {Energy production is inevitably linked to the generation of toxic metabolites, such as reactive oxygen and carbonyl species, known as major contributors to ageing and degenerative diseases. It remains unclear how cells can adapt to elevated energy flux accompanied by accumulating harmful by-products without taking any damage. Therefore, effects of a sudden rise in glucose concentrations were studied in yeast cells. This revealed a feedback mechanism initiated by the reactive dicarbonyl methylglyoxal, which is formed non-enzymatically during glycolysis. Low levels of methylglyoxal activate a multi-layered defence response against toxic metabolites composed of prevention, detoxification and damage remission. The latter is mediated by the protein quality control system and requires inducible Hsp70 and Btn2, the aggregase that sequesters misfolded proteins. This glycohormetic mechanism enables cells to pre-adapt to rising energy flux and directly links metabolic to proteotoxic stress. Further data suggest the existence of a similar response in endothelial cells.},
}
@article {pmid28801774,
year = {2017},
author = {Escórcio-Dourado, CS and Martins, LM and Simplício-Revoredo, CM and Sampaio, FA and Tavares, CB and da Silva-Sampaio, JP and Borges, US and Alves-Ribeiro, FA and Lopes-Costa, PV and Lima-Dourado, JC and da Silva, BB},
title = {Bcl-2 antigen expression in luminal A and triple-negative breast cancer.},
journal = {Medical oncology (Northwood, London, England)},
volume = {34},
number = {9},
pages = {161},
pmid = {28801774},
issn = {1559-131X},
mesh = {Adult ; Antigens/metabolism ; Biomarkers, Tumor/immunology/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/*immunology/metabolism ; Triple Negative Breast Neoplasms/*immunology/*pathology ; },
abstract = {Biomarkers for the prognosis of breast cancer have been routinely used in clinical practice, including the expression of hormone receptors, Ki-67 and HER-2. More recently, Bcl-2 has been recognized as an important prognostic factor in breast cancer, although controversies persist with respect to the significance of its expression. The aim of the present study was to evaluate Bcl-2 antigen expression in luminal A and triple-negative breast cancer. Sixty women with invasive ductal carcinoma were included in the study and divided into two groups: Group A (luminal A) and Group B (triple-negative), with 30 cases in each group. Immunohistochemistry was performed on tissue sections to evaluate Bcl-2 antigen expression. Fisher's exact test was used to compare the proportions of cases with cells expressing Bcl-2 between the two subtype cancer groups, with statistical significance being established at p < 0.05. The number of cases with cells expressing Bcl-2 in Groups A and B was 26 (86.7%) and 12 (40.0%), respectively (p < 0.0003). In the present study, the expression of the anti-apoptotic protein Bcl-2 was greater in luminal A breast cancer tissue samples compared to triple-negative breast cancer.},
}
@article {pmid28797564,
year = {2017},
author = {D'Iorio, A and Vitale, C and Piscopo, F and Baiano, C and Falanga, AP and Longo, K and Amboni, M and Barone, P and Santangelo, G},
title = {Impact of anxiety, apathy and reduced functional autonomy on perceived quality of life in Parkinson's disease.},
journal = {Parkinsonism &amp; related disorders},
volume = {43},
number = {},
pages = {114-117},
doi = {10.1016/j.parkreldis.2017.08.003},
pmid = {28797564},
issn = {1873-5126},
mesh = {*Activities of Daily Living ; Anxiety/diagnosis/*etiology ; Apathy/*physiology ; Cognition Disorders/diagnosis/etiology ; Female ; Humans ; Male ; Neuropsychological Tests ; Parkinson Disease/*complications/*psychology ; Psychiatric Status Rating Scales ; Quality of Life/*psychology ; Severity of Illness Index ; Statistics as Topic ; Surveys and Questionnaires ; },
abstract = {INTRODUCTION: Parkinson's disease (PD) is characterized by a wide spectrum of non-motor symptoms that may impact negatively on the activities of the patient's daily life and reduce Health-related quality of life (HRQoL). The present study explored the impact of specific non-motor symptoms on the HRQoL in PD.<br><br>METHODS: Eighty-four outpatients underwent the Montreal Cognitive Assessment (MoCA) assessing global functioning and several questionnaires to assess depression, apathy, impulse control disorders (ICD), anxiety, anhedonia and functional impact of cognitive impairment. The perceived QoL was assessed by Parkinson's Disease Questionnaire (PDQ-8). The PD sample was divided into patients with high and low HRQoL around the median of PDQ-8 and compared on clinical features, cognitive and neuropsychiatric variables. A linear regression analysis, in which the global functioning, apathy, depression, anxiety, anhedonia, ICD and the functional autonomy scores were entered as independent variables and PDQ-8 score as dependent variable, was applied.<br><br>RESULTS: Patients with lower HRQoL were more depressed, apathetic, anxious and showed more severe reduction of functional autonomy and global functioning than patients with high HRQoL. The regression analysis revealed that higher level of anxiety, executive apathy and more reduced functional autonomy were significantly associated with higher score on PDQ-8.<br><br>CONCLUSIONS: The finding indicated that anxiety, apathy associated with impaired planning, attention and organization (i.e., executive apathy evaluated by the Dimensional Apathy Scale) and reduced functional autonomy contribute significantly to reduce the HRQoL in PD. Therefore, early identification and management of these neuropsychiatric symptoms should be relevant to preserve HRQoL in PD.},
}
@article {pmid28793265,
year = {2017},
author = {Niopek, K and Üstünel, BE and Seitz, S and Sakurai, M and Zota, A and Mattijssen, F and Wang, X and Sijmonsma, T and Feuchter, Y and Gail, AM and Leuchs, B and Niopek, D and Staufer, O and Brune, M and Sticht, C and Gretz, N and Müller-Decker, K and Hammes, HP and Nawroth, P and Fleming, T and Conkright, MD and Blüher, M and Zeigerer, A and Herzig, S and Berriel Diaz, M},
title = {A Hepatic GAbp-AMPK Axis Links Inflammatory Signaling to Systemic Vascular Damage.},
journal = {Cell reports},
volume = {20},
number = {6},
pages = {1422-1434},
doi = {10.1016/j.celrep.2017.07.023},
pmid = {28793265},
issn = {2211-1247},
mesh = {AMP-Activated Protein Kinase Kinases ; Animals ; Atherosclerosis/etiology/*metabolism/pathology ; Cell Line ; Cells, Cultured ; Cholesterol/metabolism ; GA-Binding Protein Transcription Factor/chemistry/*metabolism ; Hepatocytes/*metabolism ; Hypercholesterolemia/complications/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Protein Kinases/*metabolism ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Reactive Oxygen Species/metabolism ; *Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism ; },
abstract = {Increased pro-inflammatory signaling is a hallmark of metabolic dysfunction in obesity and diabetes. Although both inflammatory and energy substrate handling processes represent critical layers of metabolic control, their molecular integration sites remain largely unknown. Here, we identify the heterodimerization interface between the α and β subunits of transcription factor GA-binding protein (GAbp) as a negative target of tumor necrosis factor alpha (TNF-α) signaling. TNF-α prevented GAbpα and β complex formation via reactive oxygen species (ROS), leading to the non-energy-dependent transcriptional inactivation of AMP-activated kinase (AMPK) β1, which was identified as a direct hepatic GAbp target. Impairment of AMPKβ1, in turn, elevated downstream cellular cholesterol biosynthesis, and hepatocyte-specific ablation of GAbpα induced systemic hypercholesterolemia and early macro-vascular lesion formation in mice. As GAbpα and AMPKβ1 levels were also found to correlate in obese human patients, the ROS-GAbp-AMPK pathway may represent a key component of a hepato-vascular axis in diabetic long-term complications.},
}
@article {pmid28791367,
year = {2017},
author = {Zheng, T and Wang, A and Hu, D and Wang, Y},
title = {Molecular mechanisms of breast cancer metastasis by gene expression profile analysis.},
journal = {Molecular medicine reports},
volume = {16},
number = {4},
pages = {4671-4677},
pmid = {28791367},
issn = {1791-3004},
mesh = {Breast Neoplasms/*genetics/immunology/metabolism/*pathology ; Cell Adhesion/genetics ; Computational Biology/methods ; Databases, Genetic ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Molecular Sequence Annotation ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Protein Interaction Mapping ; Protein Interaction Maps ; *Transcriptome ; },
abstract = {Metastasis is the main cause of breast cancer‑related mortalities. The present study aimed to uncover the relevant molecular mechanisms of breast cancer metastasis and to explore potential biomarkers that may be used for prognosis. Expression profile microarray data GSE8977, which contained 22 stroma samples (15 were from normal breast and 7 were from invasive ductal carcinoma tumor samples), were obtained from the Gene Expression Omnibus database. Following data preprocessing, differentially expressed genes (DEGs) were selected based on analyses conducted using the linear models for microarray analysis package from R and Bioconductor software. The resulting data were used in subsequent function and pathway enrichment analyses, as well as protein‑protein interaction (PPI) network and subnetwork analyses. Transcription factors (TFs) and tumor‑associated genes were also identified among the DEGs. A total of 234 DEGs were identified, which were enriched in immune response, cell differentiation and cell adhesion‑related functions and pathways. Downregulated DEGs included TFs, such as the proto‑oncogene SPI1, pre‑B‑cell leukemia homeobox 3 (PBX3) and lymphoid enhancer‑binding factor 1 (LEF1), as well as tumor suppressors (TSs), such as capping actin protein, gelsolin like (CAPG) and tumor protein p53‑inducible nuclear protein 1 (TP53INP1). Upregulated DEGs also included TFs and tumor suppressors, consisting of transcription factor 7‑like 2 (TCF7L2) and pleiomorphic adenoma gene‑like 1 (PLAGL1). DEGs that were identified at the hub nodes in the PPI network and the subnetwork were epidermal growth factor receptor (EGFR) and spleen‑associated tyrosine kinase (SYK), respectively. Several genes crucial in the metastasis of breast cancer were identified, which may serve as potential biomarkers, many of which were associated with cell adhesion, proliferation or immune response, and may influence breast cancer metastasis by regulating these function or pathways.},
}
@article {pmid28778029,
year = {2017},
author = {Watanabe, M and Matsuoka, R and Ichimura, Y and Takagaki, T and Iitsuka, Y},
title = {Papillotubular carcinoma with an invasive micropapillary carcinoma component of the breast, characterized by a rapid increase in size due to intra-tumoral hemorrhage: A case report.},
journal = {International journal of surgery case reports},
volume = {38},
number = {},
pages = {189-191},
pmid = {28778029},
issn = {2210-2612},
abstract = {INTRODUCTION: Rapidly enlarging mammary tumors, including invasive breast tumors, are clinically rare. Invasive micropapillary carcinoma (IMPC) of the breast is known to have aggressive behavior and poor clinical course compared to invasive ductal carcinoma.<br><br>CASE PRESENTATION: An 87-year-old woman presented with a rapidly enlarging tumor of the right breast over the course of 3 weeks. Ultrasonography and computed tomography of the chest revealed a giant tumor located on the right chest wall, with heterogeneous parenchymal components and several cystic lesions. Emergency mastectomy was performed because of rapid tumor enlargement complicated by hemorrhage. Histopathological diagnosis confirmed a papillotubular invasive ductal carcinoma with an IMPC component. Tumor cells were negative for estrogen and progesterone receptors, and the human epidermal growth factor receptor 2 score was 2+.<br><br>DISCUSSION: There has been only one report of breast carcinoma with rapid enlargement caused by spontaneous intratumoral hemorrhage to date. IMPC is associated with a high incidence of axillary lymph node metastases, frequent local recurrence, and a poor clinical outcome. In the present case, the specific breast cancer type can be considered as potential factors responsible for hemorrhage induction within the tumor that further enhanced rapid tumor growth.<br><br>CONCLUSION: IMPC is a rare, clinically aggressive variant of invasive ductal carcinoma. Owing to its aggressive clinical behaviors, surgeons should readily recognize the morphology of IMPC.},
}
@article {pmid28765906,
year = {2017},
author = {Wang, J and Song, L and Yang, S and Zhang, W and Lu, P and Li, S and Li, H and Wang, L},
title = {HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma‑not otherwise specified.},
journal = {Molecular medicine reports},
volume = {16},
number = {4},
pages = {4634-4642},
pmid = {28765906},
issn = {1791-3004},
mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Carcinoma, Ductal, Breast/*genetics/*mortality/pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Protein Serine-Threonine Kinases/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Receptors, Progesterone/metabolism ; Survival Analysis ; },
abstract = {Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which have been associated with the incidence and progression of a variety of gastrointestinal malignant tumors in humans. However, the potential association between HPK1 expression and breast cancer, particularly invasive ductal carcinoma‑not otherwise specified (IDC‑NOS) development, has not yet been examined. To address this gap, the present study aimed to evaluate HPK1 expression in IDC‑NOS samples and to determine a relationship with clinical prognostic indicators, such as the expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as overall survival of the patients with IDC‑NOS. HPK1 mRNA and protein expression in samples from 148 patients with IDC‑NOS were detected using immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. A total of 54 out of 148 (36.5%) samples were HPK1‑positive, and 100 out of 148 (67.6%) were ER‑positive. Of the latter, 28% (28/100) were HPK1‑positive, and a significant negative association of HPK1 expression with ER positivity was observed (P=0.002; r=‑0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of IDC‑NOS tissues were PR‑ or HER2‑positive, respectively; however, neither indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1 expression, axillary lymph node metastasis and tumor‑node‑metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER‑positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048). HPK1 mRNA levels did not differ between IDC‑NOS and normal adjacent breast tissues, whereas HPK1 protein levels were lower in IDC‑NOS (P<0.05). These results suggested that HPK1 protein may be a potentially effective IDC-NOS therapeutic target.},
}
@article {pmid28755148,
year = {2017},
author = {Meng, F and Liu, B and Xie, G and Song, Y and Zheng, X and Qian, X and Li, S and Jia, H and Zhang, X and Zhang, L and Yang, YL and Fu, L},
title = {Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast.},
journal = {Breast cancer research and treatment},
volume = {166},
number = {2},
pages = {383-392},
doi = {10.1007/s10549-017-4407-1},
pmid = {28755148},
issn = {1573-7217},
mesh = {Adult ; Aged ; Antigens, Neoplasm/*genetics/*metabolism ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Papillary/genetics/*metabolism ; Cell Adhesion Molecules/metabolism ; Chromosomes, Human, Pair 8/genetics ; Female ; GPI-Linked Proteins/genetics/metabolism ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Proteins/*genetics/*metabolism ; Prognosis ; Survival Analysis ; *Up-Regulation ; },
abstract = {PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast has distinct histological features and molecular genetic profiles. Gains/amplifications of 8q24 are found associated with IMPC. Although the prostate stem cell antigen (PSCA) gene is located at chromosome 8q24, and found over-expressed in prior studies, its prognostic values and biological significance in IMPC have not been well studied.<br><br>METHODS: Fluorescence in situ hybridization (FISH) was used to assess the frequencies of PSCA copy number gains in IMPC, invasive ductal carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC) samples. The protein expression levels of PSCA were examined in 56 IMPC, 72 IDC-NST, and 56 ILC samples using immunohistochemical analysis.<br><br>RESULTS: PSCA gene amplification was detected in 45.2% (14/31) of the IMPC, 28.1% (9/32) of the IDC-NST, and none (0/25) of the ILC. PSCA protein expression was observed in 58.9% (33/56), 40.3% (29/72), and 3.6% (2/56) of IMPC, IDC-NST, and ILC samples, respectively. The concordant&#xa0;rate&#xa0;of the immunohistochemistry and&#xa0;FISH&#xa0;data was 85.2%. PSCA gene amplification highly correlated with its protein overexpression (rs&#xa0;=&#xa0;0.687, P&#xa0;<&#xa0;0.001), suggesting that gene amplification is an important mechanism involved in PSCA overexpression. Our univariate analysis showed that the patients with PSCA-positive IMPC had a decreased disease-free survival (DFS) compared to PSCA-negative IMPC patients (P&#xa0;=&#xa0;0.003). Our multivariate analysis confirmed the worse DFS in PSCA-positive IMPC patients (P&#xa0;=&#xa0;0.022).<br><br>CONCLUSIONS: Our results indicate that PSCA may be an attractive target in the 8q24 amplicon and that it may serve as a molecular marker of metastasis and recurrence in IMPC. The differential expression of PSCA may be associated with cell adhesion. Detection of PSCA protein and gene amplification may help manage and predict the prognosis of IMPC patients.},
}
@article {pmid28732472,
year = {2017},
author = {Kulkarni, S and Jadhav, S and Khopkar, P and Sane, S and Londhe, R and Chimanpure, V and Dhilpe, V and Ghate, M and Yelagate, R and Panchal, N and Rahane, G and Kadam, D and Gaikwad, N and Rewari, B and Gangakhedkar, R},
title = {GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.},
journal = {BMC infectious diseases},
volume = {17},
number = {1},
pages = {506},
pmid = {28732472},
issn = {1471-2334},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Antiretroviral Therapy, Highly Active ; Case-Control Studies ; HIV Infections/*drug therapy/*virology ; *HIV-1/genetics/pathogenicity ; Humans ; India ; Point-of-Care Systems ; Real-Time Polymerase Chain Reaction/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Viral Load/*methods ; },
abstract = {BACKGROUND: Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings.<br><br>METHODS: A systematic validation of the GeneXpert&#xae; HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (<40 to >5&#xa0;L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure.<br><br>RESULTS: The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r&#xa0;=&#xa0;0.886) was statistically significant (p&#xa0;<&#xa0;0.01), the linear regression showed a moderate fit (R[2]&#xa0;=&#xa0;0.784) and differences were within limits of agreement. Reproducibility showed an average variation of 4.15 and 3.52% while Lower limit of detection (LLD) and Upper limit of detection (ULD) were 42 and 1,740,000 copies/ml respectively. The misclassification rates for three viral load cut offs were not statistically different (p&#xa0;=&#xa0;0.736). All seronegative samples were negative and viral loads of the stored samples showed a good fit (R[2]&#xa0;=&#xa0;0.896 to 0.982).<br><br>CONCLUSION: The viral load results of GeneXpert HIV-1 Quant assay compared well with Abbott HIV-1&#xa0;m2000 Real Time PCR; suggesting its use as a Point of care assay for viral load estimation in resource limited settings. Its ease of performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.},
}
@article {pmid28730339,
year = {2017},
author = {Santiago, L and Adrada, BE and Huang, ML and Wei, W and Candelaria, RP},
title = {Breast cancer neoplastic seeding in the setting of image-guided needle biopsies of the breast.},
journal = {Breast cancer research and treatment},
volume = {166},
number = {1},
pages = {29-39},
doi = {10.1007/s10549-017-4401-7},
pmid = {28730339},
issn = {1573-7217},
mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnostic imaging/metabolism/mortality/*pathology ; Female ; Humans ; Image-Guided Biopsy ; Mammography ; Neoplasm Grading ; Neoplasm Seeding ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Time Factors ; Triple Negative Breast Neoplasms/diagnostic imaging/metabolism/mortality/pathology ; },
abstract = {PURPOSE: To identify clinicopathologic, technical, and imaging features associated with neoplastic seeding (NS) following image-guided needle breast biopsy.<br><br>METHODS: We performed an institutional review board-approved retrospective review of patients presenting with a new diagnosis of breast cancer or suspicious breast findings requiring biopsy with subsequent diagnosis of NS. The time from biopsy to NS diagnosis was calculated. Histology, grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, T category, and N category were recorded. Biopsy guidance method, needle gauge, and number of passes were reviewed in addition to the mammographic and sonographic features of the primary tumors and the NS.<br><br>RESULTS: Eight cases of NS were identified in 4010 patients. The mean time from biopsy to NS diagnosis was 60.8&#xa0;days. The most frequent histology was invasive ductal carcinoma (7/8). Six cases were grade 3 (75.0%). Five primary breast cancers were ER, PR, and HER2 negative (62.5%). Seven patients underwent biopsy with ultrasound guidance. Multiple-insertion, non-coaxial ultrasound-guided core-needle biopsy was done in 6 cases. Mammographic presentation of NS was focal asymmetry (3/7 cases), mass (1/7), calcifications only (1/7), or occult (2/7). Sonographic presentation of NS was most often a mass (7/8) with irregular shape (5/7) and without circumscribed margins (6/7) and was occult in 1 case (1/8). NS distribution was subdermal and intradermal.<br><br>CONCLUSION: High-grade, triple-negative breast cancers and multiple-insertion, non-coaxial biopsies may be risk factors for NS. NS should be suspected on the basis of the superficial and linear pattern of disease progression in these patients.},
}
@article {pmid28726282,
year = {2017},
author = {Horikawa, H and Umegaki-Arao, N and Funakoshi, T and Amagai, M and Tanaka, M},
title = {Dermoscopy of pigmented invasive ductal carcinoma mimicking basal cell carcinoma.},
journal = {The Australasian journal of dermatology},
volume = {58},
number = {4},
pages = {326-327},
doi = {10.1111/ajd.12671},
pmid = {28726282},
issn = {1440-0960},
mesh = {Breast Neoplasms/*pathology ; Carcinoma, Basal Cell/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/secondary ; *Dermoscopy ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Nipples ; Skin Neoplasms/*diagnostic imaging/pathology/secondary ; Skin Pigmentation ; },
}
@article {pmid28719381,
year = {2018},
author = {Oliveira, RV and Souza, VB and Souza, PC and Soares, FA and Vassallo, J and Rocha, RM and Schenka, AA},
title = {Detection of Putative Stem-cell Markers in Invasive Ductal Carcinoma of the Breast by Immunohistochemistry: Does It Improve Prognostic/Predictive Assessments?.},
journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM},
volume = {26},
number = {10},
pages = {760-768},
pmid = {28719381},
issn = {1533-4058},
mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Brazil ; Breast Neoplasms/metabolism/mortality/pathology ; *Carcinoma, Ductal, Breast/metabolism/mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Risk Factors ; Survival Rate ; },
abstract = {INTRODUCTION: Experimental evidences from the last 2 decades supports the existence of a special type of neoplastic cell with stem-like features [cancer stem cell (CSC)] and their role in the pathophysiology and therapeutic resistance of breast cancer. However, their clinical value in human breast cancer has not been fully determined.<br><br>MATERIALS AND METHODS: An immunohistochemistry panel of 10 putative CSC markers (CD34, C-KIT, CD10, SOX-2, OCT 3/4, p63, CD24, CD44, CD133, and ESA/EPCAM) was applied to 74 cases of breast cancer, followed in a Regional Cancer Center of Minas Gerais State, Brazil, from 2004 to 2006. Possible associations between CSC markers and classic variables of clinicopathologic relevance were investigated.<br><br>RESULTS: The most frequently positive CSC markers were CD44, CD24, CD133, and ESA (the others were present in <15% of the cases). Two CSC profiles were defined: CD24/CD44 (CSC-1) and CD133/ESA (CSC-2). CSC-1 was significantly associated to patients older than 40 years, tumors of <2.0 cm in diameter, early clinical stages (P<0.05), and increased death risk of 4 times (P=0.03; 95% confidence interval, 1.09-14.41). CSC-2 was related to increased relapse risk of 3.75 times (P=0.04; 95% confidence interval, 1.02-13.69).<br><br>CONCLUSION: The detection of the most frequently positive CSC markers by immunohistochemistry is of clinicopathologic and prognostic relevance.},
}
@article {pmid28717182,
year = {2017},
author = {Bjørklund, SS and Panda, A and Kumar, S and Seiler, M and Robinson, D and Gheeya, J and Yao, M and Alnæs, GIG and Toppmeyer, D and Riis, M and Naume, B and Børresen-Dale, AL and Kristensen, VN and Ganesan, S and Bhanot, G},
title = {Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma.},
journal = {Scientific reports},
volume = {7},
number = {1},
pages = {5568},
pmid = {28717182},
issn = {2045-2322},
mesh = {*Alternative Splicing ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Cohort Studies ; Databases, Genetic ; Exons ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Sequence Analysis, RNA/methods ; },
abstract = {Cancer cells can have different patterns of exon usage of individual genes when compared to normal tissue, suggesting that alternative splicing may play a role in shaping the tumor phenotype. The discovery and identification of gene variants has increased dramatically with the introduction of RNA-sequencing technology, which enables whole transcriptome analysis of known, as well as novel isoforms. Here we report alternative splicing and transcriptional events among subtypes of invasive ductal carcinoma in The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Alternative exon usage was widespread, and although common events were shared among three subtypes, ER+ HER2-, ER- HER2-, and HER2+, many events on the exon level were subtype specific. Additional RNA-seq analysis was carried out in an independent cohort of 43 ER+ HER2- and ER- HER2- primary breast tumors, confirming many of the exon events identified in the TCGA cohort. Alternative splicing and transcriptional events detected in five genes, MYO6, EPB41L1, TPD52, IQCG, and ACOX2 were validated by qRT-PCR in a third cohort of 40 ER+ HER2- and ER- HER2- patients, showing that these events were truly subtype specific.},
}
@article {pmid28710742,
year = {2018},
author = {Avnon, A and Orkaby, N and Hadas, A and Berger, U and Brunstein Klomek, A and Fennig, S},
title = {Inpatient weight curve trajectory as a prognostic factor among adolescents with anorexia nervosa: a preliminary report.},
journal = {Eating and weight disorders : EWD},
volume = {23},
number = {5},
pages = {645-651},
pmid = {28710742},
issn = {1590-1262},
mesh = {Adolescent ; Anorexia Nervosa/physiopathology/*therapy ; Body Mass Index ; Body Weight/*physiology ; Child ; Female ; Humans ; *Inpatients ; Male ; Patient Discharge ; Prognosis ; Recurrence ; Risk Factors ; Treatment Outcome ; Weight Gain/*physiology ; },
abstract = {OBJECTIVE: To investigate the predictive value of weight restoration trajectories for relapse within the first year after discharge from inpatient treatment among adolescents with AN.<br><br>METHODS: Forty four inpatient adolescents (5 boys, 39 girls) aged 11-18 (M 14.85, SD 1.87) diagnosed with anorexia were assessed at admission and discharge from a general hospital inpatient ward. Re-hospitalizations within 1&#xa0;year of discharge were recorded. Factors assessed included 1/BMI at admission, 2/BMI at discharge, 3/percent from target weight (PFTW) at discharge, 4/length of hospitalization, and 5/a weight restoration trajectory measuring weight drops during inpatient weight restoration (rates of negative cubic variation in body weight (NCV).<br><br>RESULTS: Logistic regression indicated that negative cubic variation rates (NCV) predicted re-hospitalization. PFTW was found only marginally significant.<br><br>CONCLUSION: Variations in weight restoration during inpatient treatment may be used to identify patients at risk for relapse. NCV can alert clinicians to initiate early relapse prevention interventions before discharge. Level of Evidence Level III, cohort study.},
}
@article {pmid28709865,
year = {2017},
author = {Wan, G and Tian, L and Yu, Y and Li, F and Wang, X and Li, C and Deng, S and Yu, X and Cai, X and Zuo, Z and Cao, F},
title = {Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer.},
journal = {Biochemical and biophysical research communications},
volume = {491},
number = {1},
pages = {104-111},
doi = {10.1016/j.bbrc.2017.07.053},
pmid = {28709865},
issn = {1090-2104},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/*mortality/pathology ; China/epidemiology ; Female ; Fucosyltransferases/*metabolism ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prevalence ; Prognosis ; Receptor, Notch1/*metabolism ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Up-Regulation ; },
abstract = {PURPOSE: The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer.<br><br>MATERIAL AND METHODS: Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter.<br><br>RESULTS: Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p&#xa0;<&#xa0;0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p&#xa0;=&#xa0;0.005 for Pofut1, p&#xa0;<&#xa0;0.001 for N1IC, p&#xa0;=&#xa0;0.017 for Slug), advanced stage(p&#xa0;=&#xa0;0.039 for Pofut1, p&#xa0;=&#xa0;0.025 for N1IC) and higher histological grade(p&#xa0;=&#xa0;0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r&#xa0;=&#xa0;0.244, p&#xa0;=&#xa0;0.001; r&#xa0;=&#xa0;0.374, p&#xa0;<&#xa0;0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r&#xa0;=&#xa0;0.496, p&#xa0;<&#xa0;0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome.<br><br>CONCLUSION: Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer.},
}
@article {pmid28702871,
year = {2018},
author = {Hirayama, K and Kono, H and Nakata, Y and Akazawa, Y and Wakana, H and Fukushima, H and Fujii, H},
title = {Expression of podoplanin in stromal fibroblasts plays a pivotal role in the prognosis of patients with pancreatic cancer.},
journal = {Surgery today},
volume = {48},
number = {1},
pages = {110-118},
pmid = {28702871},
issn = {1436-2813},
mesh = {Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*genetics/mortality/*pathology ; Disease-Free Survival ; Female ; Fibroblasts/*metabolism/*pathology ; *Gene Expression ; Humans ; Lymphatic Metastasis ; Male ; Membrane Glycoproteins/*genetics/*metabolism ; Middle Aged ; Pancreatic Neoplasms/*genetics/mortality/*pathology ; Prognosis ; Proportional Hazards Models ; Risk Factors ; },
abstract = {PURPOSE: To investigate the role of podoplanin (PDPN) expression in invasive ductal carcinoma of the pancreas (IDCP) in humans.<br><br>METHODS: Tumor samples were obtained from 95 patients with IDCP. Immunohistochemical staining was done to evaluate the expression of PDPN in cancer tissues.<br><br>RESULTS: PDPN was detected predominantly in stromal fibroblasts, stained with &#x3b1;-smooth muscle actin. The cutoff value of PDPN-positive areas was calculated according to a histogram. There was no significant difference in clinicopathologic factors between patients with high vs. those with low PDPN expression. The high PDPN group showed significantly poorer disease-free and disease-specific survival rates than the low PDPN group. Among patients from the high PDPN group, those with lymph node metastases and those with a tumor larger than 20&#xa0;cm in diameter had significantly poorer prognoses than similar patients from the low PDPN group. Multivariate Cox proportional hazards analysis indicated that a high expression of PDPN was an independent risk factor for disease-specific survival.<br><br>CONCLUSIONS: PDPN expression in cancer-related fibrotic tissues is associated with a poor prognosis, especially in patients with large tumors or lymph node metastases.},
}
@article {pmid28700421,
year = {2018},
author = {Xing, D and Jenson, EG and Zwick, CA and Rodriguez, FJ and Kurman, RJ},
title = {Atypical Proliferative (Borderline) Serous Tumor in the Brain: A Case Report.},
journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists},
volume = {37},
number = {1},
pages = {52-56},
doi = {10.1097/PGP.0000000000000389},
pmid = {28700421},
issn = {1538-7151},
mesh = {Biomarkers, Tumor/metabolism ; Biopsy ; Brain/pathology ; Brain Neoplasms/diagnostic imaging/pathology/*secondary ; Breast Neoplasms/*pathology/surgery ; Cell Proliferation ; Cystadenocarcinoma, Serous/diagnostic imaging/pathology/*secondary/surgery ; Cystadenofibroma/diagnostic imaging/*pathology/surgery ; Diagnosis, Differential ; Encephalomalacia/diagnostic imaging/pathology/surgery ; Epithelial Cells/pathology ; Fallopian Tubes/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Ovarian Neoplasms/*pathology/surgery ; Salpingo-oophorectomy ; },
abstract = {A 59-year-old woman with a remote history of invasive ductal carcinoma of the breast was found on a follow-up computed tomography scan of her brain to have a 1-cm lesion in the right frontal lobe in 2008. In the ensuing years, before her current admission, multiple imaging studies of the brain revealed that the lesion was stable and it was, therefore, interpreted as a small area of encephalomalacia related to a thrombosed cortical vein, a cavernoma, or treated metastatic breast cancer. In 2013, the patient underwent a bilateral salpingo-oophorectomy for ovarian tumors that were diagnosed as bilateral serous cystadenofibromas. A partial omentectomy showed no evidence of implants. In June 2016, the brain lesion was completely excised and diagnosed as an atypical proliferative (borderline) serous tumor. Immunohistochemical staining demonstrated that the tumor cells were immunoreactive for Pax8, WT-1, ER, and CK-7 and negative for Gata-3, PR, TTF-1, CDX-2, Napsin A, and CK-20, which was consistent with that diagnosis. We present a brief review of possible mechanisms to account for this unusual presentation and speculate that the most likely one is exfoliation of fallopian tube epithelial cells into the peritoneal cavity, which then gain access to lymphatics resulting in cells implanting in the brain and subsequently progressing to an atypical proliferative (borderline) serous tumor.},
}
@article {pmid28693516,
year = {2017},
author = {Sun, X and Zuo, K and Huang, D and Yu, B and Cheng, Y and Yang, W},
title = {Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report.},
journal = {Diagnostic pathology},
volume = {12},
number = {1},
pages = {52},
pmid = {28693516},
issn = {1746-1596},
mesh = {Biomarkers, Tumor/metabolism ; Breast/pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Lobular/*secondary ; Female ; Humans ; Immunohistochemistry/methods ; Middle Aged ; Pancreatic Neoplasms/*secondary ; Receptors, Progesterone ; },
abstract = {BACKGROUND: Invasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare.<br><br>CASE PRESENTATION: We report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast.<br><br>CONCLUSIONS: To the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.},
}
@article {pmid28681371,
year = {2017},
author = {Kumaki, N and Okamatsu, C and Tokuda, Y and Nakamura, N},
title = {Breast Cancer in Patients of Rheumatoid Arthritis with Methotrexate Therapy Mimicking Histopathological Changes after Neoadjuvant Chemotherapy.},
journal = {The Tokai journal of experimental and clinical medicine},
volume = {42},
number = {2},
pages = {104-108},
pmid = {28681371},
issn = {2185-2243},
mesh = {Aged ; Antirheumatic Agents/*therapeutic use ; Arthritis, Rheumatoid/complications/*drug therapy ; Breast/*pathology ; Breast Neoplasms/complications/*pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/complications/*pathology/*therapy ; *Chemotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy ; Methotrexate/*therapeutic use ; Middle Aged ; *Neoadjuvant Therapy ; },
abstract = {Two breast cancer patients with a history of treatment for long-term rheumatoid arthritis (RA) had histological findings similar to histological changes seen in resected mammary gland specimens following neoadjuvant chemotherapy (NAC). The first patient was a 64-year-old woman who visited our hospital after feeling a lump in her left breast. The second patient was a 68-year-old woman who visited our hospital for an indentation in her left nipple. They were diagnosed with breast cancer following detailed examinations and underwent mastectomy. Both patients had a history of RA and were being treated with Methotrexate. The histological diagnoses of these patients were invasive ductal carcinoma, but frequent dispersal of cancer cell nests, stromal fibrosis, elastosis, edema and inflammatory cell infiltration were seen. Fibrosis was also found in the dissected lymph node. These histological findings were extremely similar to changes that occur in the mammary gland tissue after NAC; however, these patients had not undergone NAC. Methotrexate, which was being administered as an anti-rheumatic drug to the two patients, might have played a role similar to that of metronomic chemotherapy, which involves the continuous use of low-dose anti-cancer drugs, resulting in histological changes similar to those seen after NAC.},
}
@article {pmid28671041,
year = {2017},
author = {Liu, B and Xiong, J and Liu, G and Wu, J and Wen, L and Zhang, Q and Zhang, C},
title = {High expression of Rac1 is correlated with partial reversed cell polarity and poor prognosis in invasive ductal carcinoma of the breast.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {39},
number = {7},
pages = {1010428317710908},
doi = {10.1177/1010428317710908},
pmid = {28671041},
issn = {1423-0380},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*biosynthesis/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Polarity ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; *Prognosis ; rac1 GTP-Binding Protein/*biosynthesis/genetics ; },
abstract = {The change of cell polarity is usually associated with invasion and metastasis. Partial reverse cell polarity in IDC-NOS may play a role in lymphatic tumor spread. Rac1 is a kind of polarity related protein. It plays an important role in invasion and metastasis in tumors. We here investigated the expression of Rac1 and partial reverse cell polarity status in breast cancer and evaluated their value for prognosis in breast cancer. The association of the expression of Rac1 and MUC-1 with clinicopathological parameters and prognostic significance was evaluated in 162 cases of IDC-NOS paraffin-embedded tissues by immunohistochemical method. The Rac1 messenger RNA expression was measured by real-time polymerase chain reaction in 30 breast cancer patients, which was divided into two groups of partial reverse cell polarity and no partial reverse cell polarity. We found that lymph node metastasis of partial reverse cell polarity patients was higher than no partial reverse cell polarity patients (Z = -4.030, p = 0.000). Rac1 was upregulated in partial reverse cell polarity group than no partial reverse cell polarity group (Z = -3.164, p = 0.002), and there was correlationship between the expression of Rac1 and partial reverse cell polarity status (rs = 0.249, p = 0.001). The level of Rac1 messenger RNA expression in partial reverse cell polarity group was significantly higher compared to no partial reverse cell polarity group (t = -2.527, p = 0.017). Overexpression of Rac1 and partial reverse cell polarity correlates with poor prognosis of IDC-NOS patients (p = 0.011). Partial reverse cell polarity and lymph node metastasis remained as independent predictors for poor disease-free survival of IDC-NOS (p = 0.023, p = 0.046). Our study suggests that partial reverse cell polarity may lead to poor prognosis of breast cancer. Overexpression of Rac1 may lead to polarity change in IDC-NOS of the breast. Therefore, Rac1 could be a therapeutic target for breast cancer.},
}
@article {pmid28661760,
year = {2017},
author = {Curigliano, G and Criscitiello, C},
title = {Maximizing the Clinical Benefit of Anthracyclines in Addition to Taxanes in the Adjuvant Treatment of Early Breast Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {35},
number = {23},
pages = {2600-2603},
doi = {10.1200/JCO.2017.72.5960},
pmid = {28661760},
issn = {1527-7755},
mesh = {Anthracyclines/administration &amp; dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Breast Neoplasms/pathology/*therapy ; Bridged-Ring Compounds/administration &amp; dosage ; Carcinoma, Ductal, Breast/secondary/*therapy ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; *Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Radiotherapy, Adjuvant ; Taxoids/administration &amp; dosage ; },
abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A healthy 56-year-old postmenopausal woman discovered a palpable mass at the one o'clock position of the left breast. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer that measured 3.5 cm. There was extensive lymphovascular invasion. Pathology review indicated a poorly differentiated, grade 3 invasive ductal carcinoma and ductal carcinoma in situ (largest focus, 3.5 cm). The margins were negative. Two of the 11 axillary lymph nodes contained metastatic carcinoma. Immunohistochemical studies previously obtained on the core biopsy indicated that the tumor was positive for estrogen receptor expression (50%), negative for progesterone receptor expression, and had a Ki-67 score of 60%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. Our multidisciplinary tumor board recommended adjuvant chemotherapy, postmastectomy radiation therapy, and endocrine therapy. A 52-year-old postmenopausal woman presented with a palpable mass of the right breast. An initial core biopsy confirmed carcinoma in the breast. She underwent quadrantectomy and axillary node dissection. The final pathology report disclosed a moderately differentiated invasive ductal carcinoma (diameter, 2.5 cm). The margins were negative. None of the three sentinel lymph nodes contained metastatic carcinoma. Immunohistochemical studies showed that the tumor was positive for estrogen receptor expression (90%) and for progesterone receptor expression (40%) and had a Ki-67 score of 20%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. A genomic assay was obtained and suggested an intermediate to high risk of recurrence. Her past medical history was notable for hypertension and moderately overweight status (body mass index, 39 kg/m[2]). Our multidisciplinary tumor board recommended adjuvant chemotherapy, postsurgical radiation therapy, and endocrine therapy.},
}
@article {pmid28658335,
year = {2017},
author = {Aquino, RGF and Vasques, PHD and Cavalcante, DIM and Oliveira, ALS and Oliveira, BMK and Pinheiro, LGP},
title = {Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases.},
journal = {Revista do Colegio Brasileiro de Cirurgioes},
volume = {44},
number = {2},
pages = {163-170},
doi = {10.1590/0100-69912017002010},
pmid = {28658335},
issn = {1809-4546},
mesh = {Adult ; Aged ; Aged, 80 and over ; *Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology/*secondary ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; },
abstract = {OBJECTIVE: to analyze the relation of anatomopathological features and axillary involvement in cases of invasive ductal carcinoma.<br><br>METHODS: this is a cross-sectional study of 220 breast cancer patients submitted to radical mastectomy or quadrantectomy with axilar emptying, from the Mastology Service of the Assis Chateaubriand Maternity School, Cear&#xe1;, Brazil. We submitted the tumors to histological processing and determined the histological (HG), tubular (TG) and nuclear (NG) grades, and the mitotic index (MI) by the classification of Scarff-Bloom-Richadson, verified the presence of angiolymphatic invasion (AI) and measured the largest tumor diameter (TD). We then correlated these variables with the presence of axillary metastases.<br><br>RESULTS: the mean patients'age was 56.81 years &#xb1; 13.28. Tumor size ranged from 0.13 to 22 cm, with an average of 2.23cm &#xb1; 2.79. HG3, TG3 and NG3 prevailed, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution, respectively 82 (37.2%), 68 (31%) and 70 (31.8%). We observed no relation between the HG, TG and NG with the occurrence of axillary metastases (p=0.07, p=0.22 and p=0.21, respectively). Mitotic indices 2 and 3 were related with the occurrence of axillary metastases (p=0.03). Tumors larger than 2cm and cases that presented angiolymphatic invasion had a higher index of axillary metastases (p=0.0003 and p<0.0001).<br><br>CONCLUSION: elevated mitotic indexes, tumors with a diameter greater than 2cm and the presence of angiolymphatic invasion were individuallyassociatedwith the occurrence of axillary metastases.},
}
@article {pmid28652380,
year = {2017},
author = {Gil Del Alcazar, CR and Huh, SJ and Ekram, MB and Trinh, A and Liu, LL and Beca, F and Zi, X and Kwak, M and Bergholtz, H and Su, Y and Ding, L and Russnes, HG and Richardson, AL and Babski, K and Min Hui Kim, E and McDonnell, CH and Wagner, J and Rowberry, R and Freeman, GJ and Dillon, D and Sorlie, T and Coussens, LM and Garber, JE and Fan, R and Bobolis, K and Allred, DC and Jeong, J and Park, SY and Michor, F and Polyak, K},
title = {Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.},
journal = {Cancer discovery},
volume = {7},
number = {10},
pages = {1098-1115},
pmid = {28652380},
issn = {2159-8290},
support = {F32 CA156991/CA/NCI NIH HHS/United States ; R35 CA197623/CA/NCI NIH HHS/United States ; U54 CA193461/CA/NCI NIH HHS/United States ; },
mesh = {B7-H1 Antigen/genetics ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*immunology ; CD3 Complex/genetics ; Carcinoma, Ductal, Breast/genetics/*immunology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*immunology ; Disease Progression ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Leukocyte Common Antigens/genetics ; Receptor, ErbB-2/genetics ; T-Lymphocytes/*immunology ; Tumor Microenvironment ; },
abstract = {To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45[+]CD3[+] T cells demonstrated a decrease in CD8[+] signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB[+]CD8[+] T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2[+] breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR.See related commentary by Speiser and Verdeil, p. 1062This article is highlighted in the In This Issue feature, p. 1047.},
}
@article {pmid28647915,
year = {2017},
author = {Kizy, S and Huang, JL and Marmor, S and Tuttle, TM and Hui, JYC},
title = {Impact of the 21-gene recurrence score on outcome in patients with invasive lobular carcinoma of the breast.},
journal = {Breast cancer research and treatment},
volume = {165},
number = {3},
pages = {757-763},
doi = {10.1007/s10549-017-4355-9},
pmid = {28647915},
issn = {1573-7217},
mesh = {Adolescent ; Adult ; Aged ; *Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Carcinoma, Lobular/*genetics/*mortality/pathology ; Female ; *Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Young Adult ; },
abstract = {PURPOSE: Invasive lobular carcinoma (ILC) of the breast has unique clinicopathologic characteristics, compared to invasive ductal carcinoma. The role of the 21-gene Recurrence Score (RS) has not been clearly defined for ILC. We sought to determine the prognostic value of RS and the impact of adjuvant chemotherapy on long-term survival in patients with ILC.<br><br>METHODS: Utilizing the Surveillance, Epidemiology and End Results database from 2004 to 2013, we identified records of women aged 18-74&#xa0;years, diagnosed with estrogen receptor (ER)-positive ILC (stage I to III) with RS available. We categorized patients into risk groups based on the traditional RS cutoffs and into those of the Trial Assigning Individualized Options for Treatment (TAILORx). Five-year breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier method and Cox proportional hazards models.<br><br>RESULTS: Of the 7316 women included, 21% were in the low-risk; 71%, intermediate-risk; and 8%, high-risk groups as per TAILORx RS cutoffs. The 5-year BCSS was 99% in the low-risk, 99% in the intermediate-risk, and 96% in the high-risk groups. A high-risk RS as per TAILORx cutoff was independently associated with increased mortality (hazard ratio [HR] of death 2.37, 95% confidence interval [CI] 1.14-4.95) when compared to a low-risk RS. In both the high-risk and intermediate-risk groups, adjuvant chemotherapy was not significantly associated with the HR of death (high-risk, HR 1.14, 95% CI 0.55-2.38; intermediate-risk, HR 1.08, 95% CI 0.62-1.87).<br><br>CONCLUSION: For patients with ER-positive ILC, 8% were in the high-risk and 72% were in the intermediate-risk groups as per the TAILORx RS cutoffs. In the high-risk group, the RS predicted a lower 5-year BCSS. Adjuvant chemotherapy did not seem to confer a survival benefit for either the intermediate- or the high-risk cohorts.},
}
@article {pmid28633434,
year = {2017},
author = {Singh, DK and Gholamalamdari, O and Jadaliha, M and Ling Li, X and Lin, YC and Zhang, Y and Guang, S and Hashemikhabir, S and Tiwari, S and Zhu, YJ and Khan, A and Thomas, A and Chakraborty, A and Macias, V and Balla, AK and Bhargava, R and Janga, SC and Ma, J and Prasanth, SG and Lal, A and Prasanth, KV},
title = {PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes.},
journal = {Carcinogenesis},
volume = {38},
number = {10},
pages = {966-975},
pmid = {28633434},
issn = {1460-2180},
support = {R01 GM088252/GM/NIGMS NIH HHS/United States ; R01 GM099669/GM/NIGMS NIH HHS/United States ; R01 GM123314/GM/NIGMS NIH HHS/United States ; R01 HG007352/HG/NHGRI NIH HHS/United States ; },
mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Breast Neoplasms/*genetics/mortality/*pathology ; Cell Cycle/*genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Chromatin/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Oncogenes ; Promoter Regions, Genetic ; RNA Polymerase II/genetics/metabolism ; Tissue Array Analysis ; Transcription Factors/*genetics/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; },
abstract = {Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.},
}
@article {pmid28631956,
year = {2017},
author = {Siciliano, M and Santangelo, G and Trojsi, F and Di Somma, C and Patrone, M and Femiano, C and Monsurrò, MR and Trojano, L and Tedeschi, G},
title = {Coping strategies and psychological distress in caregivers of patients with Amyotrophic Lateral Sclerosis (ALS).},
journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration},
volume = {18},
number = {5-6},
pages = {367-377},
doi = {10.1080/21678421.2017.1285316},
pmid = {28631956},
issn = {2167-9223},
mesh = {*Adaptation, Psychological ; Adult ; Aged ; Amyotrophic Lateral Sclerosis/*psychology/*therapy ; Caregivers/*psychology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Quality of Life/psychology ; Stress, Psychological/*psychology/*therapy ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) causes distress in caregivers. The present study aims to examine the association between coping strategies and psychological distress in caregivers of ALS patients.<br><br>METHODS: Coping strategies were assessed in 96 ALS informal caregivers by means of the Coping Inventory for Stressful Situations. Data about caregivers' demographic characteristics, levels of burden, depression and anxiety (psychological distress) were also gathered by standardised questionnaires. Patients' clinical, cognitive and behavioural disturbances were evaluated by ALS specific assessment tools.<br><br>RESULTS: Sequential logistic regression analysis showed that emotion-oriented coping strategy was significantly associated with high levels of depressive (p&#x2009;<&#x2009;0.01) and anxiety (p&#x2009;<&#x2009;0.05) symptoms and high levels of burden (p&#x2009;<&#x2009;0.05), after controlling for all other variables. Moreover, a significant relationship of patients' functional dependence levels with burden experienced by caregivers was observed. No relationships were detected between task-oriented and avoidance-oriented coping strategies and caregivers' levels of psychological distress.<br><br>CONCLUSIONS: The present study supported the mediating effects of coping strategies on intensity of burden, depression and anxiety experienced by ALS caregivers. These findings suggest that interventions aimed at reducing utilisation of maladaptive coping strategies may improve well-being in ALS caregivers, and, possibly, management of symptoms in ALS patients.},
}
@article {pmid28628772,
year = {2017},
author = {Carbognin, L and Sperduti, I and Fabi, A and Dieci, MV and Kadrija, D and Griguolo, G and Pilotto, S and Guarneri, V and Zampiva, I and Brunelli, M and Orvieto, E and Nortilli, R and Fiorio, E and Parolin, V and Manfrin, E and Caliò, A and Nisticò, C and Pellini, F and Scarpa, A and Pollini, GP and Conte, P and Tortora, G and Bria, E},
title = {Prognostic impact of proliferation for resected early stage 'pure' invasive lobular breast cancer: Cut-off analysis of Ki67 according to histology and clinical validation.},
journal = {Breast (Edinburgh, Scotland)},
volume = {35},
number = {},
pages = {21-26},
doi = {10.1016/j.breast.2017.06.005},
pmid = {28628772},
issn = {1532-3080},
mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/*pathology ; Carcinoma, Lobular/*immunology/*pathology ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Analysis ; },
abstract = {INTRODUCTION: The intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage 'pure' invasive lobular carcinoma (ILC).<br><br>METHODS: Clinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well.<br><br>RESULTS: Data from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p&#xa0;=&#xa0;0.007) and 79.4% and 69.2% (p&#xa0;=&#xa0;0.03) for patients with Ki67&#xa0;&#x2264;&#xa0;4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p&#xa0;=&#xa0;0.02, DFS was 84.0% and 52.6%, p&#xa0;=&#xa0;0.0003, for patients with Ki67&#xa0;&#x2264;&#xa0;14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap.<br><br>CONCLUSIONS: Despite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology.},
}
@article {pmid28625415,
year = {2018},
author = {de Zárraga Mata, C and Thomas Salom, G and Vilella Martorell, A and Salvà Ramonell, F and Maura Oliver, &#xc1;L and Dolz Abadía, C},
title = {Gastric metastatic extension of invasive ductal carcinoma of the breast with atypical endoscopic presentation.},
journal = {Gastroenterologia y hepatologia},
volume = {41},
number = {5},
pages = {304-305},
doi = {10.1016/j.gastrohep.2017.04.006},
pmid = {28625415},
issn = {0210-5705},
mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary/therapy ; Chemoradiotherapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; *Gastroscopy ; Humans ; Image-Guided Biopsy ; Incidental Findings ; Lymphatic Metastasis ; Mastectomy, Segmental ; Stomach Neoplasms/*diagnostic imaging/therapy ; },
}
@article {pmid28623240,
year = {2017},
author = {Vegiopoulos, A and Rohm, M and Herzig, S},
title = {Adipose tissue: between the extremes.},
journal = {The EMBO journal},
volume = {36},
number = {14},
pages = {1999-2017},
pmid = {28623240},
issn = {1460-2075},
mesh = {Adipokines ; Adipose Tissue/*pathology ; Animals ; Atrophy/pathology/physiopathology ; *Energy Metabolism ; Homeostasis ; Humans ; *Lipid Metabolism ; Obesity/pathology/physiopathology ; },
abstract = {Adipose tissue represents a critical component in healthy energy homeostasis. It fulfills important roles in whole-body lipid handling, serves as the body's major energy storage compartment and insulation barrier, and secretes numerous endocrine mediators such as adipokines or lipokines. As a consequence, dysfunction of these processes in adipose tissue compartments is tightly linked to severe metabolic disorders, including obesity, metabolic syndrome, lipodystrophy, and cachexia. While numerous studies have addressed causes and consequences of obesity-related adipose tissue hypertrophy and hyperplasia for health, critical pathways and mechanisms in (involuntary) adipose tissue loss as well as its systemic metabolic consequences are far less understood. In this review, we discuss the current understanding of conditions of adipose tissue wasting and review microenvironmental determinants of adipocyte (dys)function in related pathophysiologies.},
}
@article {pmid28618949,
year = {2017},
author = {Zhao, HY and Han, Y and Wang, J and Yang, LH and Zheng, XY and Du, J and Wu, GP and Wang, EH},
title = {IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {39},
number = {6},
pages = {1010428317705769},
doi = {10.1177/1010428317705769},
pmid = {28618949},
issn = {1423-0380},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal/*genetics/pathology/surgery ; Cyclin D1/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Prognosis ; Proto-Oncogene Proteins c-myc/genetics ; Survival Analysis ; Wnt Signaling Pathway/genetics ; beta Catenin/genetics ; ras GTPase-Activating Proteins/*genetics ; },
abstract = {IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.},
}
@article {pmid28615042,
year = {2017},
author = {Darekar, A and Lamontagne, A and Fung, J},
title = {Locomotor circumvention strategies are altered by stroke: I. Obstacle clearance.},
journal = {Journal of neuroengineering and rehabilitation},
volume = {14},
number = {1},
pages = {56},
pmid = {28615042},
issn = {1743-0003},
support = {MOP- 77548//Canadian Institutes of Health Research/International ; },
mesh = {Adult ; Aged ; Female ; Gait ; Humans ; *Locomotion ; Male ; Middle Aged ; Orientation ; Paresis/etiology/physiopathology ; Psychomotor Performance ; Stroke/*psychology ; Stroke Rehabilitation/methods ; User-Computer Interface ; Walking ; },
abstract = {BACKGROUND: Functional locomotion requires the ability to adapt to environmental challenges such as the presence of stationary or moving obstacles. Difficulties in obstacle circumvention often lead to restricted community ambulation in individuals with stroke. The objective of this study was to contrast obstacle circumvention strategies between post-stroke (n = 12) and healthy individuals (n = 12) performing locomotor and perceptuomotor (joystick navigation) tasks with different obstacle approaches.<br><br>METHODS: Participants walked and navigated with a joystick towards a central target, in a virtual environment simulating a large room, while avoiding an obstacle that either remained stationary at the pre-determined point of intersection or moved from head-on or diagonally 30&#xb0; left/right. The outcome measures included dynamic clearance (DC), instantaneous distance from obstacle at crossing (IDC), number of collisions and preferred side of circumvention. These measures were compared between groups (stroke vs. healthy), obstacle parameter (stationary vs. moving head-on) and direction of approach (left/paretic vs. right/non-paretic).<br><br>RESULTS: DC was significantly larger when circumventing a moving obstacle that approached head-on as compared to a stationary obstacle for both groups during both tasks, while not significantly different in either diagonal approach in either group. IDC was smaller in the stroke group while walking and larger in both groups during joystick navigation when avoiding moving as compared to stationary obstacle. IDC was significantly larger in the stroke group compared to controls for diagonal approaches during walking, wherein two different strategies emerged amongst individuals with stroke: circumventing to the same (Vsame n&#xa0;=&#xa0;6) or opposite (Vopp n&#xa0;=&#xa0;4) side of obstacle approach. This behavior was not seen in the perceptuomotor task, wherein post-stroke participants circumvented to opposite side of the obstacle approach as seen in healthy participants. In the locomotor task, the Vsame subgroup that had greater functional limitations used larger DC as compared to the Vopp subgroup and healthy individuals. The remaining two individuals with stroke collided with obstacles in >50% trials of either obstacle approach. The underlying mechanisms for collision were however different for both individuals.<br><br>CONCLUSION: Avoidance strategies in individuals with stroke can vary depending on the individual locomotor capabilities and obstacle characteristics.},
}
@article {pmid28592128,
year = {2017},
author = {Li, J and Zhang, X and Zheng, L and Liu, Y},
title = {Association of nuclear FOXP3 expression with low Ki67 index and better prognosis in patients with breast invasive ductal carcinoma.},
journal = {Neoplasma},
volume = {64},
number = {5},
pages = {754-761},
doi = {10.4149/neo_2017_514},
pmid = {28592128},
issn = {0028-2685},
mesh = {Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Female ; Forkhead Transcription Factors/genetics/*metabolism ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/*metabolism ; Prognosis ; },
abstract = {Recent studies have provided clear evidence that some types of human cancer cells expressed Forkhead Box Protein 3 (FOXP3). However, the presence and role of FOXP3 in breast cancer are still contradictory up to now. In this study, we detected the expression of FOXP3 protein by immunohistochemistry in 123 cases of breast invasive ductal carcinoma. It exhibited that the subcellular localization of FOXP3 expression in breast cancer cells is heterogeneous. In nucleus, FOXP3 expression ratio was 47.97% (59/123) and the nuclear FOXP3 expression was significantly associated with lower Ki67 index (P=0.041), negative vessel tumor embolus (P=0.024). It was also significantly correlated with the molecular subtypes of breast cancer (P=0.002), displaying the highest ratio in the Luminal A subtype (68.18%). Kaplan-Meier analysis indicated that high nuclear FOXP3 expression was associated with better overall survival (OS) (94.92% vs. 82.81%, P=0.022) and disease-free survival (DFS) (91.53% vs. 76.56%, P=0.026). Moreover, nuclear FOXP3 represented an independent prognostic factor for OS (P =0.033) in multivariate analysis. However, in cytoplasm, FOXP3 expression ratio was 63.41% (78/123) and no statistic prognostic significance was found. Thus, our data demonstrated that nuclear FOXP3 expression correlated with low Ki-67 index and better outcome in breast invasive ductal carcinoma, indicating that FOXP3 acted as a potential prognostic marker for breast cancer.},
}
@article {pmid28591263,
year = {2017},
author = {Rodrigues, FT and Klemig, LR and Cardozo, MRP and Alves, PC and Aguiar, VM and Lessa, CS},
title = {Myiasis associated with an invasive ductal carcinoma of the left breast: case study.},
journal = {Revista do Instituto de Medicina Tropical de Sao Paulo},
volume = {59},
number = {},
pages = {e35},
pmid = {28591263},
issn = {1678-9946},
mesh = {Adult ; Animals ; Antiparasitic Agents/therapeutic use ; Breast Neoplasms/*complications/parasitology ; Carcinoma, Ductal/*complications/parasitology ; Female ; Humans ; Ivermectin/therapeutic use ; Larva ; Myiasis/*complications/diagnosis/drug therapy ; },
abstract = {Most breast cancers originate in the ductal epithelium and are referred to as invasive ductal carcinoma. In this study we report on the clinical procedures adopted to diagnose myiasis in association with infiltrating metastatic breast carcinoma in a female patient. A 41 years old woman came to the Federal Hospital of Andaraí complaining of intense itching, warmth, redness and hardening of the breast, which had acquired the aspect of an orange peel. A lesion in the left breast was cavitated, dimpled, had fetid odor, and had fibrotic and infected air nodules filled with exudate and Dipteran larvae. The tissue was cleaned and 33 larvae were extracted. The patient was hospitalized and received Ivermectin. Eighteen of the larvae extracted from the patient were placed in 70% alcohol, and twelve were placed in a container with sterile wood shavings under controlled conditions until they metamorphosed into adults. The taxonomic identification of the flies revealed that the culprit was Cochliomyia hominivorax. A histopathological exam conducted three months earlier had revealed infiltrating ductal carcinoma. Two months after the myiasis treatment, the breast tissue had healed. The patient had waited ten days from the onset of the myiasis to seek treatment, and that delay interfered negatively in the prognosis of both the neoplasm and the myiasis. This study is relevant to public health in view of the strong social impact of myiasis.},
}
@article {pmid28576605,
year = {2017},
author = {Siciliano, M and De Micco, R and Trojano, L and De Stefano, M and Baiano, C and Passaniti, C and De Mase, A and Russo, A and Tedeschi, G and Tessitore, A},
title = {Cognitive impairment is associated with Hoehn and Yahr stages in early, de novo Parkinson disease patients.},
journal = {Parkinsonism &amp; related disorders},
volume = {41},
number = {},
pages = {86-91},
doi = {10.1016/j.parkreldis.2017.05.020},
pmid = {28576605},
issn = {1873-5126},
mesh = {Aged ; Cognition Disorders/*diagnosis/*etiology ; Executive Function ; Female ; Humans ; Male ; Mental Recall ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/*complications ; *Severity of Illness Index ; Statistics, Nonparametric ; },
abstract = {INTRODUCTION: The relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages.<br><br>METHODS: Forty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II.<br><br>RESULTS: Patients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p&#xa0;=&#xa0;0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p&#xa0;<&#xa0;0.0001), 10 points Clock Drawing Test (p&#xa0;=&#xa0;0.002), and Rey-Osterrieth Complex Figure&#xa0;Test -copy (p&#xa0;<&#xa0;0.0001). ORs of having cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II.<br><br>CONCLUSION: In de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI.},
}
@article {pmid28567703,
year = {2017},
author = {Baglia, ML and Malone, KE and Tang, MC and Li, CI},
title = {Alcohol Intake and Risk of Breast Cancer by Histologic Subtype and Estrogen Receptor Status Among Women Aged 55 to 74 Years.},
journal = {Hormones &amp; cancer},
volume = {8},
number = {4},
pages = {211-218},
pmid = {28567703},
issn = {1868-8500},
support = {R01 CA105041/CA/NCI NIH HHS/United States ; },
mesh = {Age Factors ; Aged ; *Alcohol Drinking/adverse effects ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/*etiology/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Population Surveillance ; Receptors, Estrogen/*metabolism ; Risk ; SEER Program ; Socioeconomic Factors ; },
abstract = {Previous studies suggest that alcohol consumption and risk of breast cancer may differ by histologic subtype and hormone receptor status, though results are not entirely consistent. In this population-based case-control study, we evaluated the association between alcohol consumption and risk of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and invasive ductal-lobular carcinoma (IDLC) overall and by estrogen receptor (ER) status, among women aged 55-74 years of age. Using polytomous regression, associations between current alcohol consumption, overall and by type of alcohol, and breast cancer risk were evaluated in 891 controls and 905 IDC, 567 ILC, and 489 IDLC cases. Current alcohol use was moderately associated with risk of ILC (odds ratio = 1.25, 95% confidence interval 0.99, 1.58) with a positive dose-response relationship based on average number of drinks per week consumed (P trend = 0.0005). When further stratified by ER status, alcohol use was positively associated with risk of ER+ ILC (P trend = 0.002) and ER+ IDC (P trend = 0.02), but inversely associated with risk of ER-IDC (P trend = 0.01). No association between alcohol and risk of IDLC tumors was observed. While the link between alcohol consumption and breast cancer risk is well established, our results suggest that the increased risk associated with alcohol is largely limited to ER+ ILC and ER+ IDC. Thus, avoiding or moderating alcohol consumption may be one way that women can lower their risks of these forms of breast cancer.},
}
@article {pmid28567637,
year = {2017},
author = {Lambein, K and Van Bockstal, M and Vandemaele, L and Van den Broecke, R and Cocquyt, V and Geenen, S and Denys, H and Libbrecht, L},
title = {Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {471},
number = {5},
pages = {575-587},
pmid = {28567637},
issn = {1432-2307},
mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Disease Progression ; Female ; Gene Amplification ; Humans ; Middle Aged ; Receptor, ErbB-2/*genetics ; },
abstract = {Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.},
}
@article {pmid28561207,
year = {2017},
author = {Rice, GI and Kitabayashi, N and Barth, M and Briggs, TA and Burton, ACE and Carpanelli, ML and Cerisola, AM and Colson, C and Dale, RC and Danti, FR and Darin, N and De Azua, B and De Giorgis, V and De Goede, CGL and Desguerre, I and De Laet, C and Eslahi, A and Fahey, MC and Fallon, P and Fay, A and Fazzi, E and Gorman, MP and Gowrinathan, NR and Hully, M and Kurian, MA and Leboucq, N and Lin, JS and Lines, MA and Mar, SS and Maroofian, R and Martí-Sanchez, L and McCullagh, G and Mojarrad, M and Narayanan, V and Orcesi, S and Ortigoza-Escobar, JD and Pérez-Dueñas, B and Petit, F and Ramsey, KM and Rasmussen, M and Rivier, F and Rodríguez-Pombo, P and Roubertie, A and Stödberg, TI and Toosi, MB and Toutain, A and Uettwiller, F and Ulrick, N and Vanderver, A and Waldman, A and Livingston, JH and Crow, YJ},
title = {Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease.},
journal = {Neuropediatrics},
volume = {48},
number = {3},
pages = {166-184},
pmid = {28561207},
issn = {1439-1899},
support = {309449/ERC_/European Research Council/International ; K12 NS001692/NS/NINDS NIH HHS/United States ; MR/M501803/1/MRC_/Medical Research Council/United Kingdom ; TRF-2016-09-002/DH_/Department of Health/United Kingdom ; },
mesh = {Adenosine Deaminase/*genetics ; Adolescent ; Adult ; Autoimmune Diseases of the Nervous System/diagnostic imaging/*genetics/*immunology ; Biomarkers/metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interferon Type I/*metabolism ; Male ; Mutation ; Nervous System Malformations/diagnostic imaging/*genetics/*immunology ; Phenotype ; RNA-Binding Proteins/*genetics ; Young Adult ; },
abstract = {We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi-Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64-25.71) compared with controls (median: 0.93, IQR: 0.57-1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context.},
}
@article {pmid28560596,
year = {2017},
author = {Petruolo, OA and Pilewskie, M and Patil, S and Barrio, AV and Stempel, M and Wen, HY and Morrow, M},
title = {Standard Pathologic Features Can Be Used to Identify a Subset of Estrogen Receptor-Positive, HER2 Negative Patients Likely to Benefit from Neoadjuvant Chemotherapy.},
journal = {Annals of surgical oncology},
volume = {24},
number = {9},
pages = {2556-2562},
pmid = {28560596},
issn = {1534-4681},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*drug therapy/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary/surgery ; Carcinoma, Lobular/*drug therapy/metabolism/secondary/surgery ; Chemotherapy, Adjuvant ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; },
abstract = {BACKGROUND: The benefit of neoadjuvant chemotherapy (NAC) in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers and in invasive lobular carcinoma (ILC) is uncertain due to the low rates of pathologic complete response (pCR).<br><br>OBJECTIVE: The aim of this study was to determine if pathologic features can identify subsets likely to benefit from NAC.<br><br>METHODS: Patients with stage I-III ER+, HER2- breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs. non-HP).<br><br>RESULTS: From 2007 to 2016, 402 ER+/HER2- cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II-III, and 75% were cN+. Overall pCR rate was 5%; breast pCR in 7% and nodal pCR in 15% of cN+ patients (p&#xa0;<&#xa0;0.0001). Patients with ILC initially ineligible for BCS (n&#xa0;=&#xa0;56) were less likely to downstage than those with invasive ductal carcinoma (IDC; n&#xa0;=&#xa0;183, 16 vs. 48%, p&#xa0;&#x2264;&#xa0;0.0001), with a similar trend in the axilla (p&#xa0;=&#xa0;0.086). The rates of BCS eligibility after NAC were highest in PR-/HP patients (62%) and lowest in PR+/non-HP patients (29%) [p&#xa0;=&#xa0;0.005]. In the axilla, nodal pCR among cN+ patients (n&#xa0;=&#xa0;301) ranged from 0 to 35% (p&#xa0;<&#xa0;0.0001) within these groups, and was most frequent in PR-/HP patients.<br><br>CONCLUSIONS: ER+/HER2- patients most likely to benefit from NAC are those with PR- and HP tumors. Patients with ILC are unlikely to downstage in the breast or axilla compared with IDC. The use of these criteria can assist in defining the initial treatment approach.},
}
@article {pmid28554530,
year = {2017},
author = {Hidmark, A and Spanidis, I and Fleming, TH and Volk, N and Eckstein, V and Groener, JB and Kopf, S and Nawroth, PP and Oikonomou, D},
title = {Electrical Muscle Stimulation Induces an Increase of VEGFR2 on Circulating Hematopoietic Stem Cells in Patients With Diabetes.},
journal = {Clinical therapeutics},
volume = {39},
number = {6},
pages = {1132-1144.e2},
doi = {10.1016/j.clinthera.2017.05.340},
pmid = {28554530},
issn = {1879-114X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Count ; Diabetes Mellitus/blood/metabolism/*therapy ; *Electric Stimulation Therapy ; Female ; Hematopoietic Stem Cells/*metabolism ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; Vascular Endothelial Growth Factor Receptor-2/*metabolism ; Young Adult ; },
abstract = {PURPOSE: External electric muscle stimulation (EMS) of the thigh muscles was found to reduce pain resulting from diabetic neuropathy (DN), a vascular complication of diabetes. This study investigated circulating hematopoietic stem cells (HSCs) after EMS treatment. Impaired function of HSCs and the subpopulation endothelial progenitor cells (EPCs), important for neovascularization and endothelial repair, has been associated with DN.<br><br>METHODS: Twenty-four patients with painful DN were treated 3 times with EMS over a period of 1 week. Blood samples were collected before and after the first EMS treatment. Before a fourth treatment, neuropathic pain was evaluated and a third blood sample was collected. Cells were used for flow cytometry.<br><br>FINDINGS: Patients with painful DN reported that the pain decreased after 3 times of 1-hour treatments with EMS (Neuropathy Symptom Score: from 8 to 6, P = 0.001; Neuropathy Disability Score: from 5.5 to 5, P = 0.027, n = 24). At the end of the study, diastolic blood pressure had decreased from 80 to 70 mm Hg (P = 0.043), and plasma adrenaline and noradrenaline metabolites metanephrine and normetanephrine were reduced (both P &#x2264; 0.01; n = 21). A single EMS treatment caused an immediate and transient decrease in the frequency of CD34[+] HSCs in circulation (-20%; P < 0.001; n = 27). In 9 of the patients with DN, the proportion of HSCs expressing vascular endothelial growth factor receptor 2 (VEGFR2; defining the HSCs as EPCs) increased by 36% (P = 0.011) after EMS treatment. Proteins required for binding to endothelium (junctional adhesion molecule A and CD31), homing toward hypoxic tissue (C-X-C chemokine receptor type 4), and endothelial differentiation (CD31) were increased on HSCs immediately after EMS treatment. An increased frequency of VEGFR2 expression was also observed on HSCs of 6 healthy control volunteers (34%; P = 0.046) after EMS treatment, but not after sham treatment.<br><br>IMPLICATIONS: Three EMS treatments decreased symptoms of pain caused by DN and reduced diastolic blood pressure and biomarkers of stress. A single EMS treatment increased molecules mediating attachment and differentiation on the surface of HSCs in circulation. We hypothesize that the EMS-induced increase in surface attachment molecules on the HSCs caused the HSCs to leave circulation and that EMS treatment improves the function of HSCs and EPCs in vivo.},
}
@article {pmid28543784,
year = {2017},
author = {Chaudhuri, RK and Bojanowski, K},
title = {Improvement of hydration and epidermal barrier function in human skin by a novel compound isosorbide dicaprylate.},
journal = {International journal of cosmetic science},
volume = {39},
number = {5},
pages = {518-526},
doi = {10.1111/ics.12405},
pmid = {28543784},
issn = {1468-2494},
mesh = {Administration, Topical ; Aquaporin 3/metabolism ; Body Water ; Cadherins/genetics ; Caprylates/administration &amp; dosage/*pharmacology ; Cell Differentiation/drug effects ; Emollients/administration &amp; dosage ; Epidermis/*drug effects/metabolism ; Glycerol/administration &amp; dosage ; Humans ; Hyaluronan Receptors/metabolism ; Keratinocytes/cytology/drug effects ; Oligonucleotide Array Sequence Analysis ; Placebos ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; Up-Regulation/drug effects ; Water/metabolism ; },
abstract = {OBJECTIVE: The study involved the synthesis of a novel derivative of caprylic acid - isosorbide dicaprylate (IDC) - and the evaluation of its potential in improving water homoeostasis and epidermal barrier function in human skin.<br><br>METHODS: The effect of IDC on gene expression was assayed in skin organotypic cultures by DNA microarrays. The results were then confirmed for a few key genes by quantitative PCR, immuno- and cytochemistry. Final validation of skin hydration properties was obtained by four separate clinical studies. Level of hydration was measured by corneometer either by using 2% IDC lotion alone vs placebo or in combination with 2% glycerol lotion vs 2% glycerol only. A direct comparison in skin hydration between 2% IDC and 2% glycerol lotions was also carried out. The epidermal barrier function improvement was assessed by determining changes in transepidermal water loss (TEWL) on the arms before and after treatment with 2% IDC lotion versus placebo.<br><br>RESULTS: IDC was found to upregulate the expression of AQP3, CD44 and proteins involved in keratinocyte differentiation as well as the formation and function of stratum corneum. A direct comparison between 2% IDC versus 2% glycerol lotions revealed a three-fold advantage of IDC in providing skin hydration. Severely dry skin treated with 2% IDC in combination with 2% glycerol showed 133% improvement, whereas 35% improvement was observed with moderately dry human skin.<br><br>CONCLUSION: Topical isosorbide dicaprylate favourably modulates genes involved in the maintenance of skin structure and function, resulting in superior clinical outcomes. By improving skin hydration and epidermal permeability barrier, it offers therapeutic applications in skin ageing.},
}
@article {pmid28541858,
year = {2017},
author = {Jean-Louis, CJ and Masdon, J and Smith, B and Battles, O and Dale, P},
title = {The Pathologic Finding of Combined Lobular Carcinoma In Situ and Invasive Lobular Cancer May Indicate more than Just a High-Risk Marker Role of Lobular Carcinoma In Situ.},
journal = {The American surgeon},
volume = {83},
number = {5},
pages = {482-485},
pmid = {28541858},
issn = {1555-9823},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Carcinoma In Situ/*epidemiology/pathology/therapy ; Breast Neoplasms/*epidemiology/*pathology/therapy ; Carcinoma, Lobular/*epidemiology/pathology/therapy ; Female ; Humans ; Incidence ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*epidemiology/pathology/therapy ; Retrospective Studies ; Risk Factors ; },
abstract = {For years, lobular carcinoma In Situ (LCIS) has been considered a high-risk marker for developing breast cancer. It is well known that ductal carcinoma In Situ is a precursor for the development of invasive ductal carcinoma, and ductal carcinoma In Situ is reported to be present in invasive ductal carcinoma in at least 40 per cent of cases. A similar relationship between LCIS and invasive lobular carcinoma (ILC) remains in question. This study evaluates the incidence of synchronous LCIS and ILC at our institution. This is a retrospective review of our tumor registry database of women diagnosed with LCIS or ILC from 2000 to 2014. Pathology reports were evaluated to determine the incidence of pure ILC and mixed ILC/LCIS. Those with both LCIS/ILC (mixed group) and those with pure ILC (pure group) were compared for age, surgical intervention, lymph node involvement, tumor size, nuclear grade, and margins between these two groups. A total of 182 women were identified with LCIS, ILC, or mixed LCIS and ILC. There were 76 subjects with pure ILC and 90 with mixed LCIS and ILC. The median and age range for each group were 63.6 (range: 40-97) for the mixed and 64.1 (range: 40-86) for pure groups. Tumor size was evaluated for each group and the median tumor size was 2.5 cm (range: 0.1-7.0cm) for the mixed group and 3.0 cm (range: 0.5-12.5 cm) for the pure group. Nodal involvement was present in 35.23 per cent of the mixed group and 46.3 per cent in the pure group. Surgical treatment for each group was similar, with mastectomy being the preferred surgical option over breast conservation therapy in the mixed and pure groups, 67.07 and 64.71 per cent, respectively. Presently, LCIS is considered a marker, or risk factor, for development of future breast cancer. This retrospective study does identify a strong relationship, 54 per cent, between LCIS and ILC at diagnosis. This high percentage of concurrent LCIS and ILC in surgical/pathological specimens supports the notion that LCIS may in fact have a precursory role in development of invasive lobular carcinoma of the breast. Additional studies to further investigate this relationship between LCIS and ILC, including genomic analysis, are presently underway.},
}
@article {pmid28532133,
year = {2017},
author = {Elyasinia, F and Keramati, MR and Ahmadi, F and Rezaei, S and Ashouri, M and Parsaei, R and Yaghoubi, M and Elyasinia, F and Aboutorabi, A and Kaviani, A},
title = {Neutrophil-Lymphocyte Ratio in Different Stages of Breast Cancer.},
journal = {Acta medica Iranica},
volume = {55},
number = {4},
pages = {228-232},
pmid = {28532133},
issn = {1735-9694},
mesh = {Adult ; Aged ; Blood Platelets ; Breast Neoplasms/*pathology ; Cross-Sectional Studies ; Female ; Humans ; Inflammation/*pathology ; Iran ; Lymphocytes/*metabolism/pathology ; Middle Aged ; Neoplasm Staging ; Neutrophils/*metabolism ; Prognosis ; },
abstract = {Despite many advances in the treatment of breast cancer, it is still the second most common cause of death in women in the United States. It has been shown that inflammation plays a major role in the treatment of these cancers and inflammatory factors enhance tumor growth, invasion, metastasis, and vascularization. In this study, we would like to analyze peripheral blood neutrophil-lymphocyte ratio (NLR) in breast cancer patients and its correlation with disease staging. This cross-sectional analytic study was conducted in Imam Hospital, affiliated with Tehran University of Medical Sciences; a total of 195 female patients with breast cancer met the inclusion criteria. All of the patients had a complete blood count with leukocyte differential performed before chemotherapy. Medical records including pathology reports were also available. Data for all patients were collected prior to any surgical intervention. Exclusion criteria included clinical evidence of active infection, presence of hematological disorders, acute as well as chronic inflammatory or autoimmune diseases, or prior steroid therapy. Higher platelet count was significantly associated with the higher stage. The stage was not associated with the hemoglobin level. There was no association between the tumor size and age of patients with NLR. There was a significant relationship between NLR and IDC. There was a significant relationship between IDC and NLRs of less than 8.1 and greater than 3.3. There was a significant relationship between NLR and vascular invasion. There was no association between NLR and estrogen receptor and HER2. There was no significant relationship between the PLR and the cancer stage. In this study, NLR showed a significant relation with the disease staging. As the NLR increases the stage increases as well. Therefore, this ratio may be helpful in the preoperative evaluation of patients with breast cancer.},
}
@article {pmid28531310,
year = {2017},
author = {Lu, XM and Batugedara, G and Lee, M and Prudhomme, J and Bunnik, EM and Le Roch, KG},
title = {Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.},
journal = {Nucleic acids research},
volume = {45},
number = {13},
pages = {7825-7840},
pmid = {28531310},
issn = {1362-4962},
support = {R01 AI106775/AI/NIAID NIH HHS/United States ; S10 OD016290/OD/NIH HHS/United States ; },
mesh = {Animals ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; *Genes, Protozoan ; Humans ; Malaria, Falciparum/blood/parasitology ; Plasmodium falciparum/*genetics/growth &amp; development/pathogenicity ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Protozoan/*genetics/metabolism ; Sequence Analysis, RNA ; Transcription, Genetic ; },
abstract = {Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P. falciparum. Our findings indicate that the majority of genes are transcribed simultaneously during the trophozoite stage of the IDC and that only a small subset of genes is subject to differential transcriptional timing. RNA polymerase II is engaged with promoter regions prior to this transcriptional burst, suggesting that Pol II pausing plays a dominant role in gene regulation. In addition, we found that the overall transcriptional program during gametocyte differentiation is surprisingly similar to the IDC, with the exception of relatively small subsets of genes. Results from this study suggest that further characterization of the molecular players that regulate stage-specific gene expression and Pol II pausing will contribute to our continuous search for novel antimalarial drug targets.},
}
@article {pmid28512126,
year = {2017},
author = {Lo, PK and Zhang, Y and Yao, Y and Wolfson, B and Yu, J and Han, SY and Duru, N and Zhou, Q},
title = {Tumor-associated myoepithelial cells promote the invasive progression of ductal carcinoma in situ through activation of TGFβ signaling.},
journal = {The Journal of biological chemistry},
volume = {292},
number = {27},
pages = {11466-11484},
pmid = {28512126},
issn = {1083-351X},
support = {R01 CA157779/CA/NCI NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; R25 GM055036/GM/NIGMS NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Line, Tumor ; Epithelial Cells/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Mice ; Mice, Nude ; MicroRNAs/metabolism ; Myeloid Cells/*metabolism/pathology ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Neoplasm Transplantation ; RNA, Neoplasm/metabolism ; *Signal Transduction ; Transforming Growth Factor beta/*metabolism ; },
abstract = {The normal myoepithelium has a tumor-suppressing nature and inhibits the progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC). Conversely, a growing number of studies have shown that tumor-associated myoepithelial cells have a tumor-promoting effect. Moreover, the exact role of tumor-associated myoepithelial cells in the DCIS-to-IDC development remains undefined. To address this, we explored the role of tumor-associated myoepithelial cells in the DCIS-to-IDC progression. We developed a direct coculture system to study the cell-cell interactions between DCIS cells and tumor-associated myoepithelial cells. Coculture studies indicated that tumor-associated myoepithelial cells promoted the invasive progression of a DCIS cell model in vitro, and mechanistic studies revealed that the interaction with DCIS cells stimulated tumor-associated myoepithelial cells to secrete TGFβ1, which subsequently contributed to activating the TGFβ/Smads pathway in DCIS cells. We noted that activation of the TGFβ signaling pathway promoted the epithelial-mesenchymal transition, basal-like phenotypes, stemness, and invasiveness of DCIS cells. Importantly, xenograft studies further demonstrated that tumor-associated myoepithelial cells enhanced the DCIS-to-IDC progression in vivo Furthermore, we found that TGFβ-mediated induction of oncogenic miR-10b-5p expression and down-regulation of RB1CC1, a miR-10b-5p-targeted tumor-suppressor gene, contributed to the invasive progression of DCIS. Our findings provide the first experimental evidence to directly support the paradigm that altered DCIS-associated myoepithelial cells promote the invasive progression of DCIS into IDC via TGFβ signaling activation.},
}
@article {pmid28511883,
year = {2017},
author = {Chua, MLK and Lo, W and Pintilie, M and Murgic, J and Lalonde, E and Bhandari, V and Mahamud, O and Gopalan, A and Kweldam, CF and van Leenders, GJLH and Verhoef, EI and Hoogland, AM and Livingstone, J and Berlin, A and Dal Pra, A and Meng, A and Zhang, J and Orain, M and Picard, V and Hovington, H and Bergeron, A and Lacombe, L and Fradet, Y and Têtu, B and Reuter, VE and Fleshner, N and Fraser, M and Boutros, PC and van der Kwast, TH and Bristow, RG},
title = {A Prostate Cancer "Nimbosus": Genomic Instability and SChLAP1 Dysregulation Underpin Aggression of Intraductal and Cribriform Subpathologies.},
journal = {European urology},
volume = {72},
number = {5},
pages = {665-674},
doi = {10.1016/j.eururo.2017.04.034},
pmid = {28511883},
issn = {1873-7560},
support = {//CIHR/Canada ; },
mesh = {Adenocarcinoma/*genetics/mortality/pathology/therapy ; Biomarkers, Tumor/*genetics ; Disease Progression ; Disease-Free Survival ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; *Genomic Instability ; Humans ; Kaplan-Meier Estimate ; Male ; Neoplasm Invasiveness ; Netherlands ; New York City ; Ontario ; Phenotype ; Proportional Hazards Models ; Prostatic Neoplasms/*genetics/mortality/pathology/therapy ; Quebec ; RNA, Long Noncoding/*genetics ; Risk Factors ; Time Factors ; Transcriptome ; Treatment Outcome ; Tumor Hypoxia ; },
abstract = {BACKGROUND: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent unfavorable subpathologies in localized prostate cancer. We recently showed that IDC shares a clonal ancestry with the adjacent glandular adenocarcinoma.<br><br>OBJECTIVE: We investigated for the co-occurrence of "aggression" factors, genomic instability and hypoxia, and performed gene expression profiling of these tumors.<br><br>A total of 1325 men were treated for localized prostate cancer from four academic institutions (University Health Network, CHU de Qu&#xe9;bec-Universit&#xe9; Laval, Memorial Sloan Kettering Cancer Center [MSKCC], and Erasmus Medical Center). Pathological specimens were centrally reviewed. Gene copy number and expression, and intraprostatic oxygenation were assessed.<br><br>IDC/CA was separately assessed for biochemical relapse risk in the Canadian and MSKCC cohorts. Both cohorts were pooled for analyses on metastasis.<br><br>RESULTS AND LIMITATION: Presence of IDC/CA independently predicted for increased risks of biochemical relapse (HRCanadian 2.17, p<0.001; HRMSKCC 2.32, p=0.0035) and metastasis (HRpooled 3.31, p<0.001). IDC/CA+ cancers were associated with an increased percentage of genome alteration (PGA [median] 7.2 vs 3.0, p<0.001), and hypoxia (64.0% vs 45.5%, p=0.17). Combinatorial genomic-pathological indices offered the strongest discrimination for metastasis (C-index 0.805 [clinical+IDC/CA+PGA] vs 0.786 [clinical+IDC/CA] vs 0.761 [clinical]). Profiling of mRNA abundance revealed that long noncoding RNA, SChLAP1, was the only gene expressed at >3-fold higher (p<0.0001) in IDC/CA+ than in IDC/CA- tumors, independently corroborated by increased SChLAP1 RNA in situ hybridization signal. Optimal treatment intensification for IDC/CA+ prostate cancer requires prospective testing.<br><br>CONCLUSIONS: The poor outcome associated with IDC and CA subpathologies is associated with a constellation of genomic instability, SChLAP1 expression, and hypoxia. We posit a novel concept in IDC/CA+ prostate cancer, "nimbosus" (gathering of stormy clouds, Latin), which manifests as increased metastatic capacity and lethality.<br><br>PATIENT SUMMARY: A constellation of unfavorable molecular characteristics co-occur with intraductal and cribriform subpathologies in prostate cancer. Modern imaging for surveillance and treatment intensification trials should be considered in this adverse subgroup.},
}
@article {pmid28506312,
year = {2017},
author = {Sameni, M and Cavallo-Medved, D and Franco, OE and Chalasani, A and Ji, K and Aggarwal, N and Anbalagan, A and Chen, X and Mattingly, RR and Hayward, SW and Sloane, BF},
title = {Pathomimetic avatars reveal divergent roles of microenvironment in invasive transition of ductal carcinoma in situ.},
journal = {Breast cancer research : BCR},
volume = {19},
number = {1},
pages = {56},
pmid = {28506312},
issn = {1465-542X},
support = {P30 CA022453/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R01 DK110314/DK/NIDDK NIH HHS/United States ; U01 CA151924/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/*genetics/pathology ; Cancer-Associated Fibroblasts/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-6/*genetics ; Mice ; Neoplasm Invasiveness/genetics/pathology ; Plasminogen Activator Inhibitor 1/*genetics ; Proteome/genetics ; Receptors, Urokinase Plasminogen Activator/*genetics ; Tissue Array Analysis ; Tumor Microenvironment/genetics ; Urokinase-Type Plasminogen Activator/*genetics ; Xenograft Model Antitumor Assays ; },
abstract = {BACKGROUND: The breast tumor microenvironment regulates progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is unclear how interactions between breast epithelial and stromal cells can drive this progression and whether there are reliable microenvironmental biomarkers to predict transition of DCIS to IDC.<br><br>METHODS: We used xenograft mouse models and a 3D pathomimetic model termed mammary architecture and microenvironment engineering (MAME) to study the interplay between human breast myoepithelial cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression.<br><br>RESULTS: Our results show that MEPs suppress tumor formation by DCIS cells in vivo even in the presence of CAFs. In the in vitro MAME model, MEPs reduce the size of 3D DCIS structures and their degradation of extracellular matrix. We further show that the tumor-suppressive effects of MEPs on DCIS are linked to inhibition of urokinase plasminogen activator (uPA)/urokinase plasminogen activator receptor (uPAR)-mediated proteolysis by plasminogen activator inhibitor 1 (PAI-1) and that they can lessen the tumor-promoting effects of CAFs by attenuating interleukin 6 (IL-6) signaling pathways.<br><br>CONCLUSIONS: Our studies using MAME are, to our knowledge, the first to demonstrate a divergent interplay between MEPs and CAFs within the DCIS tumor microenvironment. We show that the tumor-suppressive actions of MEPs are mediated by PAI-1, uPA and its receptor, uPAR, and are sustained even in the presence of the CAFs, which themselves enhance DCIS tumorigenesis via IL-6 signaling. Identifying tumor microenvironmental regulators of DCIS progression will be critical for defining a robust and predictive molecular signature for clinical use.},
}
@article {pmid28484924,
year = {2017},
author = {Turner-Ivey, B and Smith, EL and Rutkovsky, AC and Spruill, LS and Mills, JN and Ethier, SP},
title = {Development of mammary hyperplasia, dysplasia, and invasive ductal carcinoma in transgenic mice expressing the 8p11 amplicon oncogene NSD3.},
journal = {Breast cancer research and treatment},
volume = {164},
number = {2},
pages = {349-358},
pmid = {28484924},
issn = {1573-7217},
support = {P30 CA138313/CA/NCI NIH HHS/United States ; R01 CA100724/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Carcinoma, Ductal, Breast/genetics/*pathology ; Cell Transformation, Neoplastic/genetics/*pathology ; Female ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Hyperplasia ; Lactation ; Mammary Neoplasms, Experimental/genetics/*pathology ; Mice ; Mice, Transgenic ; Neoplasm Grading ; Nuclear Proteins/*genetics ; Promoter Regions, Genetic ; },
abstract = {PURPOSE: NSD3 has been implicated as a candidate driver oncogene from the 8p11-p12 locus, and we have previously published evidence for its amplification and overexpression in human breast cancer. This aim of this study was to further characterize the transforming function of NSD3 in vivo.<br><br>METHODS: We generated a transgenic mouse model in which NSD3 gene expression was driven by the MMTV promoter and expressed in mammary epithelium of FVB mice. Mammary glands were fixed and whole mounts were stained with carmine to visualize gland structure. Mammary tumors were formalin-fixed, and paraffin embedded (FFPE) tumors were stained with hematoxylin and eosin.<br><br>RESULTS: Pups born to transgenic females were significantly underdeveloped compared to pups born to WT females due to a lactation defect in transgenic female mice. Whole mount analysis of the mammary glands of transgenic female mice revealed a profound defect in functional differentiation of mammary gland alveoli that resulted in the lactation defect. We followed parous and virgin NSD3 transgenic and control mice to 50&#xa0;weeks of age and observed that several NSD3 parous females developed mammary tumors. Whole mount analysis of the mammary glands of tumor-bearing mice revealed numerous areas of mammary hyperplasia and ductal dysplasia. Histological analysis showed that mammary tumors were high-grade ductal carcinomas, and lesions present in other mammary glands exhibited features of alveolar hyperplasia, ductal dysplasia, and carcinoma in situ.<br><br>CONCLUSIONS: Our results are consistent with our previous studies and demonstrate that NSD3 is a transforming breast cancer oncogene.},
}
@article {pmid28481705,
year = {2017},
author = {Poppe, MM and Agarwal, JP},
title = {Breast Reconstruction With Postmastectomy Radiation: Choices and Tradeoffs.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {35},
number = {22},
pages = {2467-2470},
doi = {10.1200/JCO.2017.72.7388},
pmid = {28481705},
issn = {1527-7755},
mesh = {*Breast Implants ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*radiotherapy/secondary/surgery ; Female ; Humans ; Lymphatic Metastasis ; *Mammaplasty/methods ; Mastectomy ; Middle Aged ; Neoplasms, Multiple Primary/pathology/*radiotherapy/surgery ; Radiotherapy, Adjuvant ; Rectus Abdominis/transplantation ; *Surgical Flaps ; Transplantation, Autologous ; },
abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old premenopausal woman presented with multifocal cancer in the right breast, with lesions at 1:00 and 4:00, the largest measuring approximately 3 cm on exam, and multiple palpable right axillary lymph nodes. A core biopsy confirmed invasive ductal carcinoma, grade 2 of 3, that was estrogen receptor positive, progesterone receptor positive, and HER2 negative. Fine needle aspiration of a right axillary node confirmed metastatic carcinoma. A positron emission tomography (PET)/ computed tomography done before starting chemotherapy demonstrated an absence of metastatic disease with expected avidity in two separate breast masses and multiple conglomerated 1-2 cm level I and II axillary lymph nodes. She received neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide, followed by paclitaxel, and had a complete clinical response with resolution of the breast and axillary masses on exam. A repeat PET/computed tomography demonstrated reduced size of the breast and axillary disease, and no significant residual PET avidity. Her breast surgeon recommended a right mastectomy with axillary node dissection. As part of her multidisciplinary treatment plan, she consulted with two plastic surgeons to discuss reconstruction options. Plastic Surgeon A advised placement of an implant at the time of mastectomy while Surgeon B contrasted the pros and cons of an autologous transverse rectus abdominis muscle flap reconstruction with an implant based reconstruction. Surgeon B believed that autologous reconstruction would yield the best long-term cosmetic outcome. Before making her surgery decision, the patient consulted with a radiation oncologist to discuss the effect radiation may have on her reconstruction outcome.},
}
@article {pmid28480663,
year = {2017},
author = {Lee, SJ and Choi, YY and Kim, C and Chung, MS},
title = {Correlations between Tumor to Background Ratio on Breast-Specific Gamma Imaging and Prognostic Factors in Breast Cancer.},
journal = {Journal of Korean medical science},
volume = {32},
number = {6},
pages = {1031-1037},
pmid = {28480663},
issn = {1598-6357},
mesh = {Adult ; Aged ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Female ; *Gamma Rays ; Humans ; Ki-67 Antigen/genetics/metabolism ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Technetium Tc 99m Sestamibi/chemistry ; },
abstract = {The purpose of this study was to investigate the correlations between tumor-to-background ratio (TBR) obtained from breast-specific gamma imaging (BSGI) and the prognostic factors of breast cancer. Sixty-seven patients with invasive ductal carcinoma who underwent preoperative BSGI were enrolled. The BSGI images were visually scored from 1 to 5 according to a breast imaging reporting and data system (BIRADS). The TBR results obtained from positive BSGI images were compared according to the following prognostic factors: tumor size; axillary lymph node metastasis; nuclear grade (NG); histologic grade (HG); subtype; Ki-67; and the expression profile of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Among 67 images, 60 were classified as a positive finding (sensitivity 89.6%). A higher TBR value was significantly correlated with tumor size ≥ 2 cm (P = 0.001), axillary lymph node metastasis (P = 0.007), high HG (P = 0.029), negative PR status (P = 0.036), and Ki-67 ≥ 14% (P = 0.007). The TBR showed a significant difference between the luminal A and non-luminal A subtypes (P = 0.007). On multivariate analysis, TBR had a high correlation with tumor size ≥ 2 cm, axillary lymph node metastasis, and negative PR status (P = 0.003, 0.048, and 0.030, respectively). A high TBR on BSGI was significantly correlated with poor prognostic factors of breast cancer. Luminal A subtype, a breast cancer subtype with more favorable prognosis, was associated with a low TBR on BSGI.},
}
@article {pmid28475000,
year = {2017},
author = {Wang, Y and Shen, H and Yin, Q and Zhang, T and Liu, Z and Zhang, W and Niu, Y},
title = {Effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel in vitro and vivo.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {39},
number = {5},
pages = {1010428317699754},
doi = {10.1177/1010428317699754},
pmid = {28475000},
issn = {1423-0380},
mesh = {Aged ; Animals ; Apoptosis/drug effects ; Breast Neoplasms/*drug therapy/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Middle Aged ; NIMA-Related Kinases/biosynthesis/*genetics ; Paclitaxel/*administration &amp; dosage ; Xenograft Model Antitumor Assays ; },
abstract = {NIMA-related kinase 2B has been known to be an important centrosome regulatory factor. The aim of this study was to investigate the effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel. We detected the expression of NIMA-related kinase 2B messenger RNA in MCF-10 cells, including MCF-10A, MCF-10AT, MCF-10DCIS.com , and MCF-10CA1a. The influence of NIMA-related kinase 2B in nude mouse was also detected. The association between NIMA-related kinase 2B and clinicopathological factors was explored in invasive ductal carcinoma tissues. NIMA-related kinase 2B was lowly expressed in the precancerous cells, MCF-10A and MCF-10AT, and it was highly expressed in carcinomatous cells, MCF-10DCIS.com and MCF-10CA1a. The upregulation of NIMA-related kinase 2B can introduce the growth of MCF-10AT cells, knockdown of NIMA-related kinase 2B could remarkably inhibit cell proliferation in MCF-10DCIS.com and MCF-10 CA1a cells. Comparing the volume of the xenografts in nude mouse, we found that the tumors treated by NIMA-related kinase 2B small interfering RNA associated with paclitaxel were the smallest among all the groups. Expression of NIMA-related kinase 2B messenger RNA was associated with higher histological grades, positive lymph node, and high Ki67 index (>20%). The partial response rates were 75.0% in NIMA-related kinase 2B negative (NIMA-related kinase 2B-) patients and 15.8% in NIMA-related kinase 2B++ patients. The progressive disease rates were 10.0% in NIMA-related kinase 2B- patients and 52.6% in NIMA-related kinase 2B++ patients (p = 0.002). Our findings suggested that NIMA-related kinase 2B could play a role in the development and progression of breast cancer. Combination treatment using NIMA-related kinase 2B small interfering RNA and paclitaxel might be a novel potential therapy method for breast cancer.},
}
@article {pmid28463676,
year = {2017},
author = {Martiniuc, A and Dumitraşcu, T and Pavel, M and Stroescu, C},
title = {Simultaneous Breast and Liver Surgery in a Patient with Stage IV Triple Positive Breast Cancer - A Case Report.},
journal = {Chirurgia (Bucharest, Romania : 1990)},
volume = {112},
number = {2},
pages = {165-171},
doi = {10.21614/chirurgia.112.2.165},
pmid = {28463676},
issn = {1221-9118},
mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology/*surgery/therapy ; Carcinoma, Ductal, Breast/metabolism/*secondary/*surgery/therapy ; Chemotherapy, Adjuvant/methods ; Female ; *Hepatectomy/methods ; Humans ; Liver Neoplasms/metabolism/*secondary/*surgery/therapy ; *Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Treatment Outcome ; },
abstract = {UNLABELLED: Introduction: In the modern context of multimodal treatment strategies for cancer patients with systemic disease, the dogma that surgery has a limited role is becoming less and less valid. Although a "œcurative" approach is not possible for the majority of the cases, however, some patients with limited systemic disease and favorable tumor biology could benefit from an aggressive combined cytotoxic and surgical strategy.<br><br>CASE REPORT: A 48-year-old patient was diagnosed with an invasive ductal carcinoma with the immunohistochemistry positive for estrogen and progesterone receptors, positive Her2 and three liver metastases. After nine cycles of chemotherapy, a favorable tumor response was identified at the level of the primary tumor as well as for the liver lesions: two of the metastases have disappeared, and the third one decreased in dimensions. The patient was operated in our unit, a lumpectomy together with a level II axillary lymph nodes dissection and a non-anatomic resection of the segment V of the liver was performed. Conclusions: A subgroup of patients with stage IV breast cancer with limited liver metastases and no extrahepatic disease might benefit from an aggressive combined cytotoxic and surgical strategy regarding disease control and overall survival.},
}
@article {pmid28462850,
year = {2017},
author = {El-Naby, NEH and Hassan Mohamed, H and Mohamed Goda, A and El Sayed Mohamed, A},
title = {Epstein-Barr virus infection and breast invasive ductal carcinoma in Egyptian women: A single center experience.},
journal = {Journal of the Egyptian National Cancer Institute},
volume = {29},
number = {2},
pages = {77-82},
doi = {10.1016/j.jnci.2017.02.002},
pmid = {28462850},
issn = {2589-0409},
mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/genetics/virology ; Carcinoma, Ductal/complications/*epidemiology/genetics/virology ; Egypt/epidemiology ; Epstein-Barr Virus Infections/complications/*epidemiology/genetics/virology ; Female ; Herpesvirus 4, Human/*pathogenicity ; Humans ; Middle Aged ; },
abstract = {BACKGROUND: A controversy of the role of Epstein-Barr virus (EBV) infection in breast carcinomas has been reported in the literature.<br><br>OBJECTIVES: We carried on this research to explore possible association between EBV infection and breast invasive ductal carcinoma (IDC) in Egyptian women attending our center.<br><br>STUDY DESIGN: This study carried out at Sohag university hospital on 84 paraffin embedded samples of breast tissue, of them 42 breast IDC as the case group and 42 breast fibroadenomas as the control group. Nested PCRand immunohistochemistry (IHC) done separately for all samples to identify the Epstein-Barr nuclear antigen-1 (EBNA-1) gene and EBV latent membrane protein-1 (LMP-1) respectively, in breast cancer cells and controls.<br><br>RESULTS: Specimen considered positive when both (EBNA-1) gene and LMP-1 were detected using PCR and IHC separately for the same sample, this was achieved by 10/42 (23.81%) of breast IDC (case group) and 6/42 (14.29%) of breast fibro-adenomas (control group) (P-value=0.4). Nodal involvement was the only parameter that demonstrated a significant statistical relationship with EBV presence in cancerous tissue with p-value=0.003.<br><br>CONCLUSION: Our research could not find a significant statistical association between EBV infection and breast IDC in Egyptian women attending our center, but, there might be an association between the existence of EBV and tumor aggressiveness.},
}
@article {pmid28434924,
year = {2017},
author = {Mori, K and Takeda, M and Kodama, Y and Kiyokawa, H and Yasojima, H and Mizutani, M and Otani, Y and Morikawa, N and Masuda, N and Mano, M},
title = {Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ.},
journal = {Human pathology},
volume = {64},
number = {},
pages = {145-155},
doi = {10.1016/j.humpath.2017.04.004},
pmid = {28434924},
issn = {1532-8392},
mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology/surgery ; Chi-Square Distribution ; Decision Support Techniques ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Logistic Models ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Predictive Value of Tests ; ROC Curve ; Receptor, ErbB-2/analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; },
abstract = {Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n=43) and pure DCIS (n=82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, "tumor thickness," extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor "thickness" was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions.},
}
@article {pmid28434900,
year = {2017},
author = {Hirai, E and Sarukawa, S and Yamamoto, K and Okamoto, M},
title = {Breast Cancer in a Pectoralis Major Myocutaneous Flap Used for the Reconstruction of Tongue Cancer: A Case Report.},
journal = {Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons},
volume = {75},
number = {7},
pages = {1569.e1-1569.e7},
doi = {10.1016/j.joms.2017.03.035},
pmid = {28434900},
issn = {1531-5053},
mesh = {Aged ; Breast Neoplasms/*etiology ; Female ; Humans ; Muscle Neoplasms/*etiology ; Myocutaneous Flap/*adverse effects ; Neoplasms, Second Primary/*etiology ; Tongue Neoplasms/*surgery ; },
abstract = {Breast cancers are the most common cancers in women. However, breast cancer occurring in a pectoralis major myocutaneous flap is extremely rare. This article describes a case of breast cancer occurring in such a flap used for reconstruction of the tongue in a 72-year-old woman. Follow-up computed tomogram depicted a slowly growing mass in the flap. Thirty-nine months postoperatively, a fine-needle aspiration biopsy specimen taken from the lesion suggested glandular carcinoma. The patient was diagnosed with breast cancer in the neck area of the flap and tumor excision was performed. Histologic examination of the excised tumor showed tumor cells arranged in cords, with tubular and cribriform carcinomas near the pectoral muscle with adipose tissue. The cytoplasm was abundant and eosinophilic. Thus, the patient was diagnosed with invasive ductal carcinoma in the pectoralis major flap. Sequential radiotherapy was performed to the neck with a total radiation dose of 50 Gy. Furthermore, the patient received oral anastrozole 1 mg daily as systemic adjuvant therapy for the receptor-positive breast malignancy. One year after surgery, the patient was alive with no evidence of disease. Including this case, only 2 cases of breast cancer in a pectoralis major myocutaneous flap used for reconstruction in the head and neck region have been reported.},
}
@article {pmid28432480,
year = {2017},
author = {Song, BI and Kim, HW and Won, KS},
title = {Predictive Value of [18]F-FDG PET/CT for Axillary Lymph Node Metastasis in Invasive Ductal Breast Cancer.},
journal = {Annals of surgical oncology},
volume = {24},
number = {8},
pages = {2174-2181},
doi = {10.1245/s10434-017-5860-0},
pmid = {28432480},
issn = {1534-4681},
mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multimodal Imaging/*methods ; Neoplasm Invasiveness ; Positron Emission Tomography Computed Tomography/*methods ; Prognosis ; ROC Curve ; *Radiopharmaceuticals ; Retrospective Studies ; Survival Rate ; },
abstract = {BACKGROUND: This study assessed whether primary tumor maximum standardized uptake value (pSUVmax) measured by [18]F-fluoro-2-deoxy-D-glucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) could improve the prediction of axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC).<br><br>METHODS: In this study, 128 IDC patients who underwent pretreatment [18]F-FDG PET/CT and surgical resection of primary tumor with sentinel lymph node biopsy, ALN dissection, or both were analyzed. All the patients were classified as five molecular subtypes. The optimal cutoff values of pSUVmax for all the patients and each molecular subtype for the prediction of ALN metastasis were determined using receiver operating characteristic (ROC) analysis. Furthermore, the prognostic accuracy of ALN metastasis was assessed using c-statistics.<br><br>RESULTS: The findings showed ALN metastasis in 52 patients (40.6%). The [18]F-FDG PET/CT procedure had a sensitivity of 48.1% and a specificity of 94.7% for ALN metastasis. In the ROC analysis of pSUVmax for ALN metastasis, the optimal cutoff value was 3.9 for all the patients, 2.8 for the luminal A subtype, 3.3 for the luminal B (human epidermal growth factor receptor 2 [HER2]-negative) subtype, 5.3 for the luminal B (HER2-positive) subtype, 12.7 for the HER2-positive subtype, and 11.5 for the triple-negative subtype. A predictive ALN metastasis model using nodal [18]F-FDG uptake finding gave a c-statistic of 0.714, and a model combination of nodal [18]F-FDG uptake finding with pSUVmax of all the patients gave a c-statistic of 0.736 (P&#xa0;=&#xa0;0.3926). However, the combination of nodal the [18]F-FDG uptake finding with the pSUVmax of each molecular subtype gave a c-statistic of 0.791 (P&#xa0;=&#xa0;0.0047).<br><br>CONCLUSIONS: Combining the pSUVmax of each molecular subtype with the nodal [18]F-FDG uptake finding can improve the prediction of ALN metastasis in IDC.},
}
@article {pmid28431271,
year = {2017},
author = {Li, Y and Gao, D and Tu, M and Luo, YZ and Deng, ZH},
title = {Investigation of pathology malpractice claims in China from 2002-2015.},
journal = {Journal of forensic and legal medicine},
volume = {48},
number = {},
pages = {30-34},
doi = {10.1016/j.jflm.2017.04.005},
pmid = {28431271},
issn = {1878-7487},
mesh = {China ; Compensation and Redress/legislation &amp; jurisprudence ; Humans ; Malpractice/*legislation &amp; jurisprudence ; Medical Errors ; Pathology, Clinical/*legislation &amp; jurisprudence ; Retrospective Studies ; },
abstract = {OBJECTIVE: To examine pathology-related medical claims in China and identify the most common errors to result in such claims.<br><br>METHOD: A retrospective analysis was performed of 71 forensic evaluation reports carried out in two Chinese institutes of forensic medicine between 2002 and 2015 due to suspicion of medical malpractice. The judicial outcomes of each case were also reviewed when available.<br><br>RESULTS: Of 71 cases, 54 cases had judicial outcomes. The most frequently claimed events were false-negative diagnoses of skin cancer, invasive ductal carcinoma of the breast, and osteosarcoma; and false positive diagnoses of uterine cervical squamous cell carcinoma, gastric carcinoma, and soft tissue carcinoma. The most common cause of error (82%, 56 of 68) was pathological misinterpretation. Plaintiffs in most cases (89%, 48 of 54) received compensation.<br><br>CONCLUSION: Our data are in agreement with other findings regarding the most frequent medical malpractice allegations related to pathology. Addressing the issues at the root of these claims would lead to a decline in the number of medical errors. Quality assurance programs and good pathologist-clinician communication may decrease the risk of litigation.},
}
@article {pmid28430808,
year = {2017},
author = {El Guerrab, A and Cayre, A and Kwiatkowski, F and Privat, M and Rossignol, JM and Rossignol, F and Penault-Llorca, F and Bignon, YJ},
title = {Quantification of hypoxia-related gene expression as a potential approach for clinical outcome prediction in breast cancer.},
journal = {PloS one},
volume = {12},
number = {4},
pages = {e0175960},
pmid = {28430808},
issn = {1932-6203},
mesh = {Breast Neoplasms/genetics/*pathology ; *Cell Hypoxia ; Female ; *Gene Expression ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies ; },
abstract = {Breast cancers are solid tumors frequently characterized by regions with low oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by "hypoxia inducible factors" that mediate transcriptional modifications involved in drug resistance and tumor progression leading to metastasis and relapse occurrence. In this study, we investigated the prognostic value of hypoxia-related gene expression in breast cancer. A systematic review was conducted to select a set of 45 genes involved in hypoxia signaling pathways and breast tumor progression. Gene expression was quantified by RT-qPCR in a retrospective series of 32 patients with invasive ductal carcinoma. Data were analyzed in relation to classical clinicopathological criteria and relapse occurrence. Coordinated overexpression of selected genes was observed in high-grade and HER2+ tumors. Hierarchical cluster analysis of gene expression significantly segregated relapsed patients (p = 0.008, Chi2 test). All genes (except one) were up-regulated and six markers were significantly expressed in tumors from recurrent patients. The expression of this 6-gene set was used to develop a basic algorithm for identifying recurrent patients according to a risk score of relapse. Analysis of Kaplan-Meier relapse-free survival curves allowed the definition of a threshold score of 2 (p = 0.021, Mantel-Haenszel test). The risk of recurrence was increased by 40% in patients with a high score. In addition to classical prognostic factors, we showed that hypoxic markers have potential prognostic value for outcome and late recurrence prediction, leading to improved treatment decision-making for patients with early-stage invasive breast cancer. It will be necessary to validate the clinical relevance of this prognostic approach through independent studies including larger prospective patient cohorts.},
}
@article {pmid28430349,
year = {2018},
author = {Xu, Y and Lan, S and Zheng, Q},
title = {Prognostic significance of infiltrating immune cell subtypes in invasive ductal carcinoma of the breast.},
journal = {Tumori},
volume = {104},
number = {3},
pages = {196-201},
doi = {10.5301/tj.5000624},
pmid = {28430349},
issn = {2038-2529},
mesh = {B-Lymphocytes/immunology/metabolism/pathology ; Biomarkers/*metabolism ; Breast Neoplasms/*immunology/metabolism/*pathology ; CD8-Positive T-Lymphocytes/immunology/metabolism/pathology ; Carcinoma, Ductal/*immunology/metabolism/*pathology ; Female ; Forkhead Transcription Factors/metabolism ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; T-Lymphocytes, Regulatory/immunology/metabolism/pathology ; },
abstract = {PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis.<br><br>MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low).<br><br>RESULTS: Kaplan-Meier survival analysis showed (a) for all patients that high tumor-infiltrating CD8+ and CD20+ B lymphocytes, low tumor-infiltrating FOXP3+ regulatory T cells (Tregs), and CD68+ macrophages all increased OS and DFS (p<0.05); (b) for both the 35 ER-negative and 45 lymph-node-negative patients, high CD8+ cytotoxic T lymphocytes (CTLs) increased OS and DFS (p<0.05). Multivariate analysis of OS and DFS showed that for all patients high CD8+ CTLs and low FOXP3+ Tregs were related to good OS and DFS (p<0.05).<br><br>CONCLUSION: High numbers of tumor-infiltrating CD8+ and low numbers of FOXP3+ T lymphocytes both could function as potential independent prognostic markers for invasive ductal breast carcinoma.},
}
@article {pmid28425682,
year = {2017},
author = {Degrate, L and Bernasconi, DP and Meroni, P and Garancini, M and Macchini, D and Romano, F and Uggeri, F and Gianotti, L},
title = {Mild acute biliary pancreatitis: the timing of cholecystectomy should not exceed index admission.},
journal = {Minerva chirurgica},
volume = {72},
number = {5},
pages = {383-390},
doi = {10.23736/S0026-4733.17.07356-4},
pmid = {28425682},
issn = {1827-1626},
mesh = {Acute Disease ; Aged ; *Cholecystectomy, Laparoscopic/methods ; Female ; Gallstones/complications/diagnosis/*surgery ; Humans ; Italy ; Male ; Middle Aged ; Pancreatitis/*diagnosis/etiology ; *Patient Selection ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Time Factors ; Treatment Outcome ; },
abstract = {BACKGROUND: Laparoscopic cholecystectomy (LC) to treat mild biliary acute pancreatitis (MBAP) during index admission is recommended. However, the optimal surgical timing is controversial, considering that patients are actually often discharged from hospital and readmitted for elective cholecystectomy. Moreover, previous studies showed an uneven patients' stratification for pancreatitis severity. The aim of this study was to determine the outcome of patients homogenously categorizedfor MBAP according to the newest pancreatitis classifications, undergoing cholecystectomy with different timing.<br><br>METHODS: We retrospectively identified all patients undergoing cholecystectomy from 2008 to 2015 for MBAP, according to the 2012 Revision of the Atlanta Classification and the Determinant-Based Classification of Acute Pancreatitis, and stratified them in two groups: index cholecystectomy (IC) and interval-delayed cholecystectomy (IDC, after at least 4 weeks).<br><br>RESULTS: One hundred and three patients were analyzed. IC was performed in 40 patients (38.8%) while IDC in 63 patients (61.2%). The two groups were similar in comorbidities and pancreatitis severity at admission. There were no differences for conversion rate, operation length, total length of hospitalization and overall complication rates. However, IDC patients had a 33.3% rate of re-hospitalization for recurrent biliary-pancreatic events while waiting for the elective procedure and showed a higher rate of acute cholecystitis at histological diagnosis than IC (11.1% vs. 0%, P=0.041).<br><br>CONCLUSIONS: Among patients affected by MBAP, homogenously assessed following the new acute pancreatitis severity scores, the performance of cholecystectomy during the index admission is the best treatment option in order to avoid further undesired hospitalizations for recurrent biliary/pancreatic events while waiting for surgery.},
}
@article {pmid28422303,
year = {2017},
author = {Tang, B and Han, CT and Gan, HL and Zhang, GM and Zhang, CZ and Yang, WY and Shen, Y and Zhu, Y and Ye, DW},
title = {Smoking increased the risk of prostate cancer with grade group ≥ 4 and intraductal carcinoma in a prospective biopsy cohort.},
journal = {The Prostate},
volume = {77},
number = {9},
pages = {984-989},
doi = {10.1002/pros.23354},
pmid = {28422303},
issn = {1097-0045},
mesh = {Aged ; Biopsy/methods/statistics &amp; numerical data ; *Carcinoma, Ductal/epidemiology/pathology ; China/epidemiology ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Prostate/*pathology ; *Prostatic Neoplasms/epidemiology/pathology ; Risk Factors ; Smoking/*epidemiology ; Statistics as Topic ; },
abstract = {OBJECTIVE: To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men.<br><br>PATIENTS AND METHODS: We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence.<br><br>RESULTS: A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group&#x2009;&#x2265;&#x2009;4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR&#x2009;=&#x2009;1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR&#x2009;=&#x2009;0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR&#x2009;=&#x2009;1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR&#x2009;=&#x2009;2.29, 95%CI: 1.14-4.59).<br><br>CONCLUSION: Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa.},
}
@article {pmid28422090,
year = {2017},
author = {Wu, Q and Ding, X and Li, J and Sun, S and Zhu, S and Wu, J and Liu, Q and Yao, F and Sun, S},
title = {Surgical treatment in Paget's disease with invasive ductal carcinoma: an observational study based on SEER.},
journal = {Scientific reports},
volume = {7},
number = {},
pages = {45510},
pmid = {28422090},
issn = {2045-2322},
mesh = {Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Humans ; Paget's Disease, Mammary/complications/*pathology/*surgery ; Prognosis ; Survival Analysis ; Treatment Outcome ; },
abstract = {The aim is to analyse the clinical presentation, treatment and outcomes in patients with Paget's disease with invasive ductal carcinoma (PD-IDC), with special emphasis on the role of surgical treatment. Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, we investigated the differences in characteristics, overall survival (OS), and breast cancer-specific mortality (BCSM) between patients with PD-IDC and those with invasive ductal carcinoma (IDC). Compared with IDC group, patients with PD-IDC had a better prognosis and lower mortality in adjusted analyses. In the multivariate analysis of cases with PD-IDC, history of ALND was significantly associated with OS while Her2 status were associated with BCSM. Further, subgroup analysis demonstrated no difference between surgical treatment subgroups for either OS or BCSM. The results demonstrated that PD-IDC appears to alter the association between prognosis and Her2 status. Meanwhile, breast-conserving surgery with radiotherapy may be a feasible treatment alternative and sentinel lymph node biopsy should be considered as an appropriate treatment for patients with PD-IDC.},
}
@article {pmid28416734,
year = {2017},
author = {Coulson, R and Liew, SH and Connelly, AA and Yee, NS and Deb, S and Kumar, B and Vargas, AC and O'Toole, SA and Parslow, AC and Poh, A and Putoczki, T and Morrow, RJ and Alorro, M and Lazarus, KA and Yeap, EFW and Walton, KL and Harrison, CA and Hannan, NJ and George, AJ and Clyne, CD and Ernst, M and Allen, AM and Chand, AL},
title = {The angiotensin receptor blocker, Losartan, inhibits mammary tumor development and progression to invasive carcinoma.},
journal = {Oncotarget},
volume = {8},
number = {12},
pages = {18640-18656},
pmid = {28416734},
issn = {1949-2553},
mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Angiotensin II Type 1 Receptor Blockers/*therapeutic use ; Animals ; Biopsy ; Breast Neoplasms/*pathology ; Carcinogenesis/metabolism ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemically induced/*drug therapy/immunology/pathology ; Cell Proliferation/drug effects ; *Disease Progression ; Female ; Humans ; Immunohistochemistry ; Interleukin-6/metabolism ; Losartan/*therapeutic use ; Mammary Neoplasms, Experimental/chemically induced/*drug therapy/immunology/pathology ; Medroxyprogesterone Acetate/toxicity ; Mice ; Neoplasm Invasiveness ; Phosphorylation ; Real-Time Polymerase Chain Reaction ; Receptor, Angiotensin, Type 1/*metabolism ; Renin-Angiotensin System/drug effects ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Tumor Burden/drug effects ; Tumor Necrosis Factor-alpha/metabolism ; Up-Regulation ; },
abstract = {Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis. However, there is no evidence, so far, of the functional contribution of AT1R to breast tumorigenesis. We explored the potential therapeutic benefit of ARB in a carcinogen-induced mouse model of breast cancer and clarified the mechanisms associated with its success.Mammary tumors were induced with 7,12-dimethylbenz[α]antracene (DMBA) and medroxyprogesterone acetate (MPA) in female wild type mice and the effects of the ARB, Losartan treatment assessed in a preventative setting (n = 15 per group). Tumor histopathology was characterised by immunohistochemistry, real-time qPCR to detect gene expression signatures, and tumor cytokine levels measured with quantitative bioplex assays. AT1R was detected with radiolabelled ligand binding assays in fresh frozen tumor samples.We showed that therapeutic inhibition of AT1R, with Losartan, resulted in a significant reduction in tumor burden; and no mammary tumor incidence in 20% of animals. We observed a significant reduction in tumor progression from DCIS to invasive cancer with Losartan treatment. This was associated with reduced tumor cell proliferation and a significant reduction in IL-6, pSTAT3 and TNFα levels. Analysis of tumor immune cell infiltrates, however, demonstrated no significant differences in the recruitment of lymphocytes or tumour-associated macrophages in Losartan or vehicle-treated mammary tumors.Analysis of AT1R expression with radiolabelled ligand binding assays in human breast cancer biopsies showed high AT1R levels in 30% of invasive ductal carcinomas analysed. Furthermore, analysis of the TCGA database identified that high AT1R expression to be associated with luminal breast cancer subtype.Our in vivo data and analysis of human invasive ductal carcinoma samples identify the AT1R is a potential therapeutic target in breast cancer, with the availability of a range of well-tolerated inhibitors currently used in clinics. We describe a novel signalling pathway critical in breast tumorigenesis, that may provide new therapeutic avenues to complement current treatments.},
}
@article {pmid28414329,
year = {2017},
author = {Fischer, K and Ruiz, HH and Jhun, K and Finan, B and Oberlin, DJ and van der Heide, V and Kalinovich, AV and Petrovic, N and Wolf, Y and Clemmensen, C and Shin, AC and Divanovic, S and Brombacher, F and Glasmacher, E and Keipert, S and Jastroch, M and Nagler, J and Schramm, KW and Medrikova, D and Collden, G and Woods, SC and Herzig, S and Homann, D and Jung, S and Nedergaard, J and Cannon, B and Tschöp, MH and Müller, TD and Buettner, C},
title = {Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.},
journal = {Nature medicine},
volume = {23},
number = {5},
pages = {623-630},
pmid = {28414329},
issn = {1546-170X},
support = {R01 DK017844/DK/NIDDK NIH HHS/United States ; R03 DK082724/DK/NIDDK NIH HHS/United States ; R01 AA023416/AA/NIAAA NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; P30 DK020541/DK/NIDDK NIH HHS/United States ; R01 AI093637/AI/NIAID NIH HHS/United States ; R01 DK099222/DK/NIDDK NIH HHS/United States ; R37 DK017844/DK/NIDDK NIH HHS/United States ; R56 DK083658/DK/NIDDK NIH HHS/United States ; 340345/ERC_/European Research Council/International ; },
mesh = {Adaptation, Physiological ; Adipocytes/drug effects/*metabolism ; Adipose Tissue/drug effects/*metabolism ; Adipose Tissue, Brown/drug effects/metabolism ; Adipose Tissue, White/drug effects/metabolism ; Animals ; Blotting, Western ; Body Composition/immunology ; Catecholamines/metabolism ; Cell Differentiation ; Culture Media, Conditioned ; Energy Metabolism/genetics ; Flow Cytometry ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Interleukin-4/immunology/pharmacology ; Macrophages/drug effects/*immunology ; Mice ; Mice, Knockout ; Norepinephrine/*metabolism ; Receptors, Adrenergic, beta-3/*metabolism ; Receptors, Cell Surface/genetics ; Thermogenesis/genetics/*immunology ; Tyrosine 3-Monooxygenase/*genetics ; Uncoupling Protein 1/genetics ; },
abstract = {Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through β3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1[-/-] and interleukin-4 receptor-α double-negative (Il4ra[-/-]) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.},
}
@article {pmid28413435,
year = {2017},
author = {San, TH and Fujisawa, M and Fushimi, S and Yoshimura, T and Ohara, T and Soe, L and Min, NW and Kyaw, O and Yang, X and Matsukawa, A},
title = {Low prevalence of human mammary tumor virus (HMTV) in breast cancer patients from Myanmar.},
journal = {Infectious agents and cancer},
volume = {12},
number = {},
pages = {20},
pmid = {28413435},
issn = {1750-9378},
abstract = {BACKGROUND: Human mammary tumor virus (HMTV) is 90-95% homologous to mouse mammary tumor virus (MMTV), one of the causal agents of murine mammary tumors. HMTV (MMTV-like) sequences were reported to be present in human breast cancers from several populations with a prevalence range of 0-78%; however, the prevalence of HMTV in breast cancers from Myanmar remains unknown.<br><br>METHODS: Fifty-eight breast cancer samples from Myanmar women were examined in this study. DNA was isolated from formalin-fixed paraffin-embedded specimens, and HMTV envelope sequences were detected by semi-nested PCR. The sequence of the PCR products was also confirmed.<br><br>RESULTS: Only 1.7% (1 of 58) of the breast cancers were positive for HMTV, and the sequence of PCR products was 98.9% identical to the reference HMTV sequence (GenBank accession No. AF243039). The tumor with HMTV was grade III invasive ductal carcinoma, 7.0&#xa0;cm in size with lymph node metastasis (T3, N1, M0).<br><br>CONCLUSIONS: We, for the first time, investigated the presence of HMTV in Myanmar breast cancer patients. In accordance with other Asian studies, the prevalence of HMTV in Myanmar was quite low, supporting the hypothesis that Asian breast cancers have different etiologies than in Western countries, where HMTV is more prevalent.},
}
@article {pmid28412522,
year = {2017},
author = {Amri, EZ and Scheideler, M},
title = {Small non coding RNAs in adipocyte biology and obesity.},
journal = {Molecular and cellular endocrinology},
volume = {456},
number = {},
pages = {87-94},
doi = {10.1016/j.mce.2017.04.009},
pmid = {28412522},
issn = {1872-8057},
mesh = {Adipocytes, Brown/*metabolism/pathology ; Adipocytes, White/*metabolism/pathology ; Adipogenesis/genetics ; Adipose Tissue/metabolism/pathology ; Animals ; Biomarkers/metabolism ; Energy Intake/genetics ; Gene Expression Regulation ; Humans ; MicroRNAs/*genetics/metabolism ; Obesity/diagnosis/*genetics/metabolism/pathology ; RNA, Small Nucleolar/*genetics/metabolism ; RNA, Transfer/*genetics/metabolism ; },
abstract = {Obesity has reached epidemic proportions world-wide and constitutes a substantial risk factor for hypertension, type 2 diabetes, cardiovascular diseases and certain cancers. So far, regulation of energy intake by dietary and pharmacological treatments has met limited success. The main interest of current research is focused on understanding the role of different pathways involved in adipose tissue function and modulation of its mass. Whole-genome sequencing studies revealed that the majority of the human genome is transcribed, with thousands of non-protein-coding RNAs (ncRNA), which comprise small and long ncRNAs. ncRNAs regulate gene expression at the transcriptional and post-transcriptional level. Numerous studies described the involvement of ncRNAs in the pathogenesis of many diseases including obesity and associated metabolic disorders. ncRNAs represent potential diagnostic biomarkers and promising therapeutic targets. In this review, we focused on small ncRNAs involved in the formation and function of adipocytes and obesity.},
}
@article {pmid28410206,
year = {2017},
author = {Fu, S and Cheng, J and Wei, C and Yang, L and Xiao, X and Zhang, D and Stewart, MD and Fu, J},
title = {Development of diagnostic SCAR markers for genomic DNA amplifications in breast carcinoma by DNA cloning of high-GC RAMP-PCR fragments.},
journal = {Oncotarget},
volume = {8},
number = {27},
pages = {43866-43877},
pmid = {28410206},
issn = {1949-2553},
mesh = {Adult ; Aged ; Base Composition ; Base Sequence ; *Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/genetics ; Cloning, Molecular ; DNA Primers ; Dipeptidases/genetics ; Female ; GPI-Linked Proteins/genetics ; *Gene Amplification ; *Genomics/methods ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger/genetics ; Random Amplified Polymorphic DNA Technique ; Sequence Analysis, DNA ; },
abstract = {Cancer is genetically heterogeneous regarding to molecular genetic characteristics and pathogenic pathways. A wide spectrum of biomarkers, including DNA markers, is used in determining genomic instability, molecular subtype determination and disease prognosis, and estimating sensitivity to different drugs in clinical practice. In a previous study, we developed highly effective DNA markers using improved random amplified polymorphic DNA (RAPD) with high-GC primers, which is a valuable approach for the genetic authentication of medicinal plants. In this study, we applied this effective DNA marker technique to generate genetic fingerprints that detect genomic alterations in human breast cancer tissues and then developed sequence-characterized amplified region (SCAR) markers. Three SCAR markers (BC10-1, BC13-4 and BC31-2) had high levels of genomic DNA amplification in breast cancer. The PHKG2 and RNF40 genes are either overlapping or close to the sequences of SCAR marker BC13-4, while SCAR marker BC10-1 is in the intron and overlap the DPEP1 gene, suggesting that alterations in the expression of these genes could contribute to cancer progression. Screening of breast cancer cell lines showed that the mRNA expression levels for the PHKG2 and DPEP1 were lower in non-tumorigenic mammary epithelial cell MCF10A, but elevated in other cell lines. The DPEP1 mRNA level in invasive ductal carcinoma specimens was significantly higher than that of the adjacent normal tissues in women. Taken together, high-GC RAMP-PCR provides greater efficacy in measuring genomic DNA amplifications, deletion or copy number variations. Furthermore, SCAR markers BC10-1 and BC13-4 might be useful diagnostic markers for breast cancer carcinomas.},
}
@article {pmid28403836,
year = {2017},
author = {Fu, G and Wang, G and Dai, X},
title = {An adaptive threshold determination method of feature screening for genomic selection.},
journal = {BMC bioinformatics},
volume = {18},
number = {1},
pages = {212},
pmid = {28403836},
issn = {1471-2105},
mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/genetics ; Computer Simulation ; Genome, Plant ; Genome-Wide Association Study ; Genomics ; *Models, Genetic ; Phenotype ; Plant Breeding ; *Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Although the dimension of the entire genome can be extremely large, only a parsimonious set of influential SNPs are correlated with a particular complex trait and are important to the prediction of the trait. Efficiently and accurately selecting these influential SNPs from millions of candidates is in high demand, but poses challenges. We propose a backward elimination iterative distance correlation (BE-IDC) procedure to select the smallest subset of SNPs that guarantees sufficient prediction accuracy, while also solving the unclear threshold issue for traditional feature screening approaches.<br><br>RESULTS: Verified through six simulations, the adaptive threshold estimated by the BE-IDC performed uniformly better than fixed threshold methods that have been used in the current literature. We also applied BE-IDC to an Arabidopsis thaliana genome-wide data. Out of 216,130 SNPs, BE-IDC selected four influential SNPs, and confirmed the same FRIGIDA gene that was reported by two other traditional methods.<br><br>CONCLUSIONS: BE-IDC accommodates both the prediction accuracy and the computational speed that are highly demanded in the genomic selection.},
}
@article {pmid28401771,
year = {2018},
author = {Brück, N and Koskivuo, I and Boström, P and Saunavaara, J and Aaltonen, R and Parkkola, R},
title = {Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.},
journal = {Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society},
volume = {107},
number = {1},
pages = {14-22},
doi = {10.1177/1457496917701669},
pmid = {28401771},
issn = {1799-7267},
mesh = {Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/mortality/*surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/mortality/*surgery ; Disease-Free Survival ; Female ; Finland ; Hospitals, University ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/*methods ; Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/pathology/surgery ; Preoperative Care/methods ; Prognosis ; Prospective Studies ; Risk Assessment ; Statistics, Nonparametric ; Survival Analysis ; Treatment Outcome ; },
abstract = {BACKGROUND AND AIMS: Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma.<br><br>MATERIAL AND METHODS: A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms.<br><br>RESULTS: In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group (p&#x2009;=&#x2009;0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group (p&#x2009;=&#x2009;0.202). The mean interval between referral and first surgical procedure was 34&#x2009;days in the magnetic resonance imaging group and 21&#x2009;days in the control group (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Preoperative magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.},
}
@article {pmid28400203,
year = {2017},
author = {Desmedt, C and Zoppoli, G and Sotiriou, C and Salgado, R},
title = {Transcriptomic and genomic features of invasive lobular breast cancer.},
journal = {Seminars in cancer biology},
volume = {44},
number = {},
pages = {98-105},
doi = {10.1016/j.semcancer.2017.03.007},
pmid = {28400203},
issn = {1096-3650},
mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; Genome, Human ; Genomics ; Humans ; Neoplasm Invasiveness/*genetics/pathology ; Prognosis ; Transcriptome/*genetics ; },
abstract = {Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets. In this review, we provide a critical overview of the literature exploring ILC, through comprehensive and multiomic methods. The first part specifically focuses on ILC transcriptomic features by reviewing the intrinsic molecular subtypes, the application of gene expression scores for the prediction of recurrence, and the identification of gene expression subtypes. The second part describes the main research efforts that lead to the identification of the genomic landscape of ILC, with a special focus to findings that differentiate ILC from IDC and carry potential clinical relevance.},
}
@article {pmid28395915,
year = {2017},
author = {Abel, S and Renz, P and Trombetta, M and Cowher, M and Day Werts, E and Julian, TB and Wegner, R},
title = {Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?.},
journal = {Practical radiation oncology},
volume = {7},
number = {3},
pages = {167-172},
doi = {10.1016/j.prro.2016.10.018},
pmid = {28395915},
issn = {1879-8519},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*radiotherapy/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Radiodermatitis/*etiology ; Radiotherapy/*adverse effects/*methods ; Retrospective Studies ; Thoracic Wall ; Treatment Failure ; },
abstract = {PURPOSE: Postmastectomy chest wall radiation therapy has historically used bolus to increase dose at the skin surface. Despite the theoretical benefits of bolus, the clinical implications of locoregional tumor control, cosmesis, and the incidence of radiodermatitis are less well characterized. We hypothesized that treatment in the presence or absence of bolus results in equivalent chest wall recurrence rates, but its presence results in more severe acute dermatologic toxicity.<br><br>METHODS AND MATERIALS: Locally advanced breast cancer patients undergoing chest wall radiation therapy were retrospectively reviewed from 2005 to 2015 (n = 106; 53 with bolus, 53 without). Outcomes including local failure, acute skin toxicity, and treatment interruptions were recorded. Median age was 59 years (range, 28-91) and median follow-up was 34 months. Histology was invasive ductal carcinoma (73%), invasive lobular carcinoma (20%), inflammatory (6%), and neuroendocrine (1%). Fifty-nine percent were T3/T4 primary tumors and 29.2% had clinical/pathologic skin involvement. Node-positive patients accounted for 80.2%. Chemotherapy was administered in 84.0%. All patients had 3-dimensional conformal radiation therapy and received a median dose of 61Gy (range, 50-63 Gy).<br><br>RESULTS: Local failure was 6.6% (n = 7) overall, with 4 failures in the bolus group and 3 in the no bolus group. No pathological factors were associated with local failure. Acute grade 2 and 3 skin toxicities (37 vs 22) and treatment interruptions (20 vs 3) were more common in the bolus group (P < .05). Mean treatment interruption (14.5 vs 5 days) was longer for patients receiving bolus. Patients undergoing treatment interruption were more likely to fail locally than patients not requiring a treatment interruption (17.4% vs 3.6%, P = .0322).<br><br>CONCLUSIONS: Bolus omission in adjuvant chest wall radiation therapy may be a reasonable approach to avoid acute skin toxicity and treatment interruptions while preserving local control; however, further study will be needed to reach a definitive conclusion.},
}
@article {pmid28391968,
year = {2017},
author = {Barzilay, S and Brunstein Klomek, A and Apter, A and Carli, V and Wasserman, C and Hadlaczky, G and Hoven, CW and Sarchiapone, M and Balazs, J and Kereszteny, A and Brunner, R and Kaess, M and Bobes, J and Saiz, P and Cosman, D and Haring, C and Banzer, R and Corcoran, P and Kahn, JP and Postuvan, V and Podlogar, T and Sisask, M and Varnik, A and Wasserman, D},
title = {Bullying Victimization and Suicide Ideation and Behavior Among Adolescents in Europe: A 10-Country Study.},
journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine},
volume = {61},
number = {2},
pages = {179-186},
doi = {10.1016/j.jadohealth.2017.02.002},
pmid = {28391968},
issn = {1879-1972},
mesh = {Adolescent ; Adolescent Behavior/*psychology ; Bullying/*statistics &amp; numerical data ; Crime Victims/*statistics &amp; numerical data ; Europe ; Female ; Humans ; Male ; Prevalence ; Protective Factors ; Self Report ; Suicide/*statistics &amp; numerical data ; Surveys and Questionnaires ; },
abstract = {PURPOSE: To examine risk and protective factors moderating the associations between three types of bullying victimization (physical, verbal, and relational bullying) with suicide ideation/attempts in a large representative sample of European adolescents.<br><br>METHODS: We analyzed cross-sectional data on 11,110 students (mean age&#xa0;= 14.9, standard deviation&#xa0;= .89) recruited from 168 schools in 10 European Union countries involved in the Saving and Empowering Young Lives in Europe study. A self-report questionnaire was used to measure victimization types, depression, anxiety, parental and peer support, and suicide ideation and attempts. For each outcome, we applied hierarchical nonlinear models controlling for sociodemographics.<br><br>RESULTS: Prevalence of victimization was 9.4% physical, 36.1% verbal, and 33.0% relational. Boys were more likely to be physically and verbally victimized, whereas girls were more prone to relational victimization. Physical victimization was associated with suicide ideation, and relational victimization was associated with suicide attempts. Other associations between victimization and suicidality (ideation/attempts) were identified through analysis of interactions with additional risk and protective factors. Specifically, verbal victimization was associated with suicide ideation among adolescents with depression who perceived low parental support. Similarly, low peer support increased the associations between verbal victimization and suicide ideation. Verbal victimization was associated with suicide attempts among adolescents with anxiety who perceived low parental support.<br><br>CONCLUSIONS: Findings support the development of prevention strategies for adolescent victims of bullying who may be at elevated risk for suicide ideation/behavior, by taking into account gender, the type of bullying, symptomatology, and availability of interpersonal support.},
}
@article {pmid28391236,
year = {2017},
author = {Weis, S and Hagel, S and Schmitz, RP and Scherag, A and Brunkhorst, FM and Forstner, C and Löffler, B and Pletz, MW},
title = {Study on the utility of a statewide counselling programme for improving mortality outcomes of patients with Staphylococcus aureus bacteraemia in Thuringia (SUPPORT): a study protocol of a cluster-randomised crossover trial.},
journal = {BMJ open},
volume = {7},
number = {4},
pages = {e013976},
pmid = {28391236},
issn = {2044-6055},
mesh = {Administration, Intravenous ; Anti-Bacterial Agents/therapeutic use ; Clinical Protocols ; Cluster Analysis ; *Counseling/methods ; Cross-Over Studies ; Germany/epidemiology ; Humans ; Patient Education as Topic ; Program Evaluation ; Quality Assurance, Health Care ; Referral and Consultation ; *Staphylococcal Infections/drug therapy/epidemiology/prevention &amp; control ; Staphylococcus aureus/*drug effects ; Telephone ; },
abstract = {INTRODUCTION: Staphylococcus aureus bacteraemia (SAB) is a frequent infection with high mortality rates. It requires specific diagnostic and therapeutic management such as prolonged intravenous administration of antibiotics and aggressive search for and control of infectious sources. Underestimation of disease severity frequently results in delayed or inappropriate management of patients with SAB leading to increased mortality rates. According to observational studies, patient counselling by infectious disease consultants (IDC) improves survival and reduces the length of hospital stay as well as complication rates. In many countries, IDC are available only in some tertiary hospitals. In this trial, we aim to demonstrate that the outcome of patients with SAB in small and medium size hospitals that do not employ IDC can be improved by unsolicited ID phone counselling. The SUPPORT trial will be the first cluster-randomised controlled multicentre trial addressing this question.<br><br>METHODS AND ANALYSIS: SUPPORT is a single-blinded, multicentre interventional, cluster-randomised, controlled crossover trial with a minimum of 15 centres that will include 250 patients with SAB who will receive unsolicited IDC counselling and 250 who will receive standard of care. Reporting of SAB will be conducted by an electronic real-time blood culture registry established for the German Federal state of Thuringia (ALERTSNet) or directly by participating centres in order to minimise time delay before counselling. Mortality, disease course and complications will be monitored for 90&#x2005;days with 30-day all-cause mortality rates as the primary outcome. Generalised linear mixed modelling will be used to detect the difference between the intervention sequences. We expect improved outcome of patients with SAB after IDC.<br><br>ETHICS AND DISSEMINATION: We obtained ethics approval from the Ethics committee of the Jena University Hospital and from the Ethics committee of the State Chamber of Physicians of Thuringia. Results will be published in a peer-reviewed journal and additionally disseminated through public media.<br><br>TRIAL REGISTRATION NUMBER: DRKS00010135.},
}
@article {pmid28388580,
year = {2017},
author = {Lian, K and Ma, C and Hao, C and Li, Y and Zhang, N and Chen, YH and Liu, S},
title = {TIPE3 protein promotes breast cancer metastasis through activating AKT and NF-κB signaling pathways.},
journal = {Oncotarget},
volume = {8},
number = {30},
pages = {48889-48904},
pmid = {28388580},
issn = {1949-2553},
mesh = {Adult ; Aged ; Animals ; Biomarkers, Tumor ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics/metabolism ; Disease Models, Animal ; Female ; Gene Expression ; Heterografts ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mice ; Middle Aged ; NF-kappa B/*metabolism ; Neoplasm Metastasis ; Neoplasm Staging ; Proto-Oncogene Proteins c-akt/*metabolism ; *Signal Transduction ; Tumor Burden ; },
abstract = {TIPE3 (TNFAIP8L3) is the transfer protein of phosphoinositide second messengers that promote cancer. Its role in breast cancer has not been evaluated. We report here that TIPE3 protein was significantly upregulated in human breast cancer tissues as compared with adjacent non-tumor tissues from the same patients. The level of TIPE3 protein in invasive ductal carcinoma was significant higher than that in ductal carcinoma in situ (DCIS), and the level of TIPE3 in lymphatic metastasized carcinoma was higher than that in invasive ductal carcinoma from the same patients. Additionally, the level of TIPE3 protein was positively correlated with the level of human epidermal growth factor receptor 2 (HER-2), and TIPE3 expression was significantly higher in high-invasive breast cancer cell lines than that in low-invasive cell lines. Importantly, TIPE3 knockdown in breast cancer cells inhibited cell proliferation, migration, and invasion in vitro, whereas TIPE3 overexpression had the opposite effect. In mice, TIPE3 expression significantly promoted the metastasis of breast cancer cells. TIPE3 expression also increased the level of MMP2 and uPA, and the activation of the AKT and NF-κB signaling pathways. These results demonstrate that TIPE3 may promote breast cancer growth and metastasis through AKT and NF-κB, and may serve as a potential biomarker for breast cancer metastasis.},
}
@article {pmid28385191,
year = {2017},
author = {Hidmark, AS and Nawroth, PP and Fleming, T},
title = {STZ causes depletion of immune cells in sciatic nerve and dorsal root ganglion in experimental diabetes.},
journal = {Journal of neuroimmunology},
volume = {306},
number = {},
pages = {76-82},
doi = {10.1016/j.jneuroim.2017.03.008},
pmid = {28385191},
issn = {1872-8421},
mesh = {Animals ; Antibiotics, Antineoplastic/toxicity ; Antigens, CD/metabolism ; Cytokines/metabolism ; Diabetes Mellitus, Experimental/chemically induced/*pathology/*physiopathology ; Disease Models, Animal ; Flow Cytometry ; Ganglia, Spinal/drug effects/*pathology ; Hyperalgesia/etiology ; Intercellular Adhesion Molecule-1/metabolism ; Leukocytes/pathology ; Macrophages/drug effects/pathology ; Mice ; Mice, Inbred C57BL ; Sciatic Nerve/drug effects/*pathology ; Streptozocin/toxicity ; Time Factors ; },
abstract = {Streptozotocin (STZ) treatment, a common model for inducing diabetes in rodent models, induces thermal hyperalgesia and neuronal toxicity independently of hyperglycemia by oxidizing and activating TRPA1 and TRPV1. Following treatment with STZ, CD45[+] immune cells were found to be depleted in sciatic nerve (SN) and DRG in mice, prior to hyperglycemia. Macrophages were also lost in DRG and NFκB-p65-activation was increased in SN macrophages. Immune cells were significantly reduced in both SN and DRG up to three weeks, post-treatment. Loss of PNS-resident macrophages in response to STZ-mediated toxicity may affect the regenerative capacity of the nerve in response to further injury caused by diabetes.},
}
@article {pmid28382159,
year = {2017},
author = {Lee, HT and Liu, SP and Lin, CH and Lee, SW and Hsu, CY and Sytwu, HK and Hsieh, CH and Shyu, WC},
title = {A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke.},
journal = {Theranostics},
volume = {7},
number = {4},
pages = {855-875},
pmid = {28382159},
issn = {1838-7640},
mesh = {Animals ; Chemokines, CXC/*metabolism ; Dendritic Cells/immunology ; Humans ; *Lymphocyte Activation ; Rats, Sprague-Dawley ; Stroke/*physiopathology ; T-Lymphocytes, Regulatory/*immunology ; },
abstract = {Inflammatory processes have a detrimental role in the pathophysiology of ischemic stroke. However, little is known about the endogenous anti-inflammatory mechanisms in ischemic brain. Here, we identify CXCL14 as a critical mediator of these mechanisms. CXCL14 levels were upregulated in the ischemic brains of humans and rodents. Moreover, hypoxia inducible factor-1α (HIF-1α) drives hypoxia- or cerebral ischemia (CI)-dependent CXCL14 expression via directly binding to the CXCL14 promoter. Depletion of CXCL14 inhibited the accumulation of immature dendritic cells (iDC) or regulatory T cells (Treg) and increased the infarct volume, whereas the supplementation of CXCL14 had the opposite effects. CXCL14 promoted the adhesion, migration, and homing of circulating CD11c[+] iDC to the ischemic tissue via the upregulation of the cellular prion protein (PrP[C]), PECAM-1, and MMPs. The accumulation of Treg in ischemic areas of the brain was mediated through a cooperative effect of CXCL14 and iDC-secreted IL-2-induced Treg differentiation. Interestingly, CXCL14 largely promoted IL-2-induced Treg differentiation. These findings indicate that CXCL14 is a critical immunomodulator involved in the stroke-induced inflammatory reaction. Passive CXCL14 supplementation provides a tractable path for clinical translation in the improvement of stroke-induced neuroinflammation.},
}
@article {pmid28375214,
year = {2017},
author = {Gallet, R and Violle, C and Fromin, N and Jabbour-Zahab, R and Enquist, BJ and Lenormand, T},
title = {The evolution of bacterial cell size: the internal diffusion-constraint hypothesis.},
journal = {The ISME journal},
volume = {11},
number = {7},
pages = {1559-1568},
pmid = {28375214},
issn = {1751-7370},
mesh = {Bacteria/*cytology/*genetics ; *Biological Evolution ; *Cell Size ; },
abstract = {Size is one of the most important biological traits influencing organismal ecology and evolution. However, we know little about the drivers of body size evolution in unicellulars. A long-term evolution experiment (Lenski's LTEE) in which Escherichia coli adapts to a simple glucose medium has shown that not only the growth rate and the fitness of the bacterium increase over time but also its cell size. This increase in size contradicts prominent 'external diffusion' theory (EDC) predicting that cell size should have evolved toward smaller cells. Among several scenarios, we propose and test an alternative 'internal diffusion-constraint' (IDC) hypothesis for cell size evolution. A change in cell volume affects metabolite concentrations in the cytoplasm. The IDC states that a higher metabolism can be achieved by a reduction in the molecular traffic time inside of the cell, by increasing its volume. To test this hypothesis, we studied a population from the LTEE. We show that bigger cells with greater growth and CO2 production rates and lower mass-to-volume ratio were selected over time in the LTEE. These results are consistent with the IDC hypothesis. This novel hypothesis offers a promising approach for understanding the evolutionary constraints on cell size.},
}
@article {pmid28365833,
year = {2017},
author = {Truin, W and Roumen, RMH and Siesling, S and van de Vijver, KK and Tjan-Heijnen, VCG and Voogd, AC},
title = {Estrogen and progesterone receptor expression levels do not differ between lobular and ductal carcinoma in patients with hormone receptor-positive tumors.},
journal = {Breast cancer research and treatment},
volume = {164},
number = {1},
pages = {133-138},
pmid = {28365833},
issn = {1573-7217},
mesh = {Aged ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/*diagnosis/genetics/pathology ; Carcinoma, Lobular/*diagnosis/genetics/pathology ; Diagnosis, Differential ; Estrogens/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Netherlands ; Progesterone/genetics ; Receptors, Estrogen/*genetics ; Receptors, Progesterone/*genetics ; Treatment Outcome ; },
abstract = {BACKGROUND: Differences in estrogen (ER) and progesterone (PR) expression between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) could be an underlying reason for the difference in chemo-sensitivity and response to hormonal therapy between ILC and IDC. The aim of this study was to investigate the differences in ER and PR expression levels between postmenopausal patients with hormonal receptor-positive ILC and IDC.<br><br>METHODS: We included all ER and/or PR receptor-positive ILC and IDC, diagnosed between January 2011 and December 2013 from the population-based Netherlands Cancer Registry. A semi-quantitative classification was used to analyze differences in ER/PR expression, which consisted of three ER expression classes: 10-69, 70-89, and &#x2265;90%. Differences in ER and PR expression levels between IDC and ILC were analyzed according to age group, tumor size, axillary nodal status, grade, and HER2 status.<br><br>RESULTS: In total, 26,339 ER and/or PR-positive breast cancers were included in the study, of which 17% were ILC and 83% IDC. In patients with IDC, 86% of the tumors showed an ER expression level of 90% or more, compared to 84% in those with ILC. In both IDC and ILC a PR expression level of 90% or more was observed in 54% of the tumors. In postmenopausal patients aged 50-69&#xa0;years no significant differences could be observed in ER and PR expression levels between ILC and IDC.<br><br>CONCLUSION: Patients with ER and PR-positive ILC and IDC have similar quantitative ER and PR expression profiles, implicating that ER/PR expression is unlikely to be a confounding factor in studies concerning chemo-sensitivity of ILC and IDC.},
}
@article {pmid28355358,
year = {2017},
author = {Carrara, GF and Scapulatempo-Neto, C and Abrahão-Machado, LF and Brentani, MM and Nunes, JS and Folgueira, MA and Vieira, RA},
title = {Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {72},
number = {3},
pages = {134-142},
pmid = {28355358},
issn = {1980-5322},
mesh = {Adult ; Breast Neoplasms/*drug therapy/pathology/*surgery ; Carcinoma/*drug therapy/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Recurrence, Local/*etiology ; Reproducibility of Results ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Survival Analysis ; Time Factors ; Treatment Outcome ; Tumor Burden ; },
abstract = {OBJECTIVE:: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer.<br><br>METHODS:: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival.<br><br>RESULTS:: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01).<br><br>CONCLUSIONS:: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.},
}
@article {pmid28353289,
year = {2017},
author = {Masferrer, L and Garre-Olmo, J and Caparrós, B},
title = {Factor structure and concurrent construct validity of ICG among bereaved substance users.},
journal = {Actas espanolas de psiquiatria},
volume = {45},
number = {2},
pages = {47-55},
pmid = {28353289},
issn = {1578-2735},
mesh = {Cross-Sectional Studies ; Female ; *Grief ; Humans ; Male ; Middle Aged ; Patient Health Questionnaire ; Psychometrics ; Reproducibility of Results ; Substance-Related Disorders/*etiology/*psychology ; },
abstract = {BACKGROUND: It is important to understand the repercussions of Complicated Grief (CG) symptoms in addictions. There are no studies to date which have examined the psychometric properties of any test of bereavement among people with substance use disorder (SUD). Participants with SUD can have a different experience of bereavement from other people and therefore could respond differently to the usual instruments which assess CG symptomatology.<br><br>METHOD: This study aims to establish the psychometric properties of the Spanish adaption of the Inventory of Complicated Grief (ICG) in a sample of 196 bereaved drug dependent patients.<br><br>RESULTS: Results indicate that the internal consistency of the Spanish ICG was high (Cronbach&#8217;s alpha=0.922). The Spanish IDC shows good psychometric properties and it is a useful tool to discriminate adaptive reactions to symptomatology of complicated grief. Four factors were identified: discomfort, non-acceptance, loneliness-isolation and presence of deceased. Those factors showed a good internal reliability (minimum Cronbach&#8217;s alpha=0.78).<br><br>CONCLUSIONS: The results of the current study confirm the multidimensionality of CG&#8217;s symptomatology construct.},
}
@article {pmid28342640,
year = {2017},
author = {Porter, LH and Lawrence, MG and Ilic, D and Clouston, D and Bolton, DM and Frydenberg, M and Murphy, DG and Pezaro, C and Risbridger, GP and Taylor, RA},
title = {Systematic Review Links the Prevalence of Intraductal Carcinoma of the Prostate to Prostate Cancer Risk Categories.},
journal = {European urology},
volume = {72},
number = {4},
pages = {492-495},
doi = {10.1016/j.eururo.2017.03.013},
pmid = {28342640},
issn = {1873-7560},
mesh = {Carcinoma/*epidemiology/pathology/therapy ; Cell Proliferation ; Humans ; Male ; Neoplasm Grading ; Prevalence ; Prostatic Neoplasms/*epidemiology/pathology/therapy ; Risk Assessment ; Risk Factors ; },
abstract = {UNLABELLED: Intraductal carcinoma of the prostate (IDC-P) is associated with poor prognosis. While it is often regarded as a rare pathology, the prevalence of IDC-P remains unclear, with variable reports from small and disparate patient populations. To determine how common IDC-P is across the spectrum of prostate cancer, we conducted a systematic review correlating IDC-P prevalence with prostate cancer risk. Electronic searches of the OVID Medline, PubMed, and Scopus literature databases identified 38 patient cohorts in 24 articles, which were divided between four prostate cancer risk categories (low, moderate, high, and recurrent or metastatic disease). This review, which included radical prostatectomy and prostate biopsy specimens from >7000 patients, revealed an unexpectedly high rate of IDC-P. The IDC-P prevalence increased from 2.1% in low-risk patient cohorts to 23.1%, 36.7%, and 56.0% in moderate-risk, high-risk, and metastatic or recurrent disease risk categories, respectively (p<0.0001). IDC-P was also highly prevalent in tumours following androgen deprivation therapy or chemotherapy (60%). Contrary to common perceptions, this study demonstrates a strong association between IDC-P prevalence and aggressive prostate cancer, with a significantly higher frequency in high-risk disease. Greater recognition and systematic reporting of IDC-P may improve patient risk stratification.<br><br>PATIENT SUMMARY: Prostate cancer can grow within ducts of the prostate, as well as in prostate tissue. By reviewing all reports describing prostate cancer growing within ducts, we found that it occurs more commonly than many scientists and clinicians appreciate, especially in aggressive prostate cancers. We conclude that there should be more awareness of this pattern of prostate cancer.},
}
@article {pmid28331761,
year = {2017},
author = {Külahcı, &#xd6; and Esen, HH and Asut, E and Güngör, S},
title = {Association of ICAM-1, VCAM-1, CYCLIN D1 and Cathepsin D with Clinicopathological Parameters in Breast Carcinoma; an Immunohistochemical Study.},
journal = {The journal of breast health},
volume = {13},
number = {1},
pages = {5-9},
pmid = {28331761},
issn = {1306-0945},
abstract = {OBJECTIVE: Breast carcinoma is the most common malignant tumor detected in women. The hypothesis that increased levels of adhesion molecules and Cathepsin D affect cancerous cells moving away the primary tumor and contributes to migration of the cancerous cell and may cause remote organ metastases is defended. The aim of the present study was to search the association of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), Cyclin D1, cathepsin D immunohistochemically with clinicopathological parameters in the patients diagnosed with invasive ductal breast carcinoma.<br><br>MATERIALS AND METHODS: The pathological slides of 153 patients diagnosed with invasive ductal carcinoma were evaluated retrospectively. Three groups were created. Group 1 consisted of patients with positive lymph node metastasis and extranodal tumor invasion; Group 2 consisted of patients with positive axillary lymph node metastasis and negative extranodal tumor invasion and Group 3 consisted of the patients with negative axillary lymph node metastasis. In all groups, 20 paraffin blocks belonging to the primary tumor in the breast were stained by ICAM-1, VCAM-1, Cyclin D1 and Cathepsin D. Findings were examined by comparing with clinicopathological parameters.<br><br>RESULTS: The highest number of metastatic axillary lymph nodes and the highest rate of cathepsin D staining were statistically found in the cases with positive axillary lymph node metastasis and extranodal tumor invasion. CerbB2 was negative in the cases with negative ICAM-1 whereas estrogen receptor and progesterone receptor were positive in the cases with positive VCAM-1.<br><br>CONCLUSION: The present study reveals significant results for the patients diagnosed with invasive ductal carcinoma through breast biopsy especially before mastectomy in terms of increased number of metastatic axillary lymph nodes and extranodal tumor invasion by immunohistochemical Cathepsin D stain without any additional invasive intervention. Results of the present study may contribute to monitoring and treatment of the patients in the future.},
}
@article {pmid28326638,
year = {2017},
author = {Mizukawa, K and Kobayashi, T and Yamada, N and Hirota, T},
title = {Intervertebral disc calcification with ossification of the posterior longitudinal ligament.},
journal = {Pediatrics international : official journal of the Japan Pediatric Society},
volume = {59},
number = {5},
pages = {622-624},
doi = {10.1111/ped.13243},
pmid = {28326638},
issn = {1442-200X},
mesh = {Calcinosis/complications/*diagnostic imaging ; Cervical Vertebrae/*diagnostic imaging ; Child ; Female ; Humans ; Ossification of Posterior Longitudinal Ligament/complications/*diagnostic imaging ; *Tomography, X-Ray Computed ; },
abstract = {A 6-year-old girl presented to hospital with a 4 day history of increasing neck pain. White blood cell count was normal with slightly raised C-reactive protein. The patient had a limited range of neck movement, and experienced enhanced pain with neck extension. X-ray and cervical computed tomography (CT) confirmed the diagnosis of cervical intervertebral disc calcification (IDC) and IDC with ossification of the posterior longitudinal ligament (OPLL), respectively. The symptoms improved after approximately 1 week following rest and oral acetaminophen. X-ray 6 months after onset confirmed the disappearance of the calcification. IDC is often reported in children, but IDC with OPLL is extremely rare and has not been previously reported in Japan. We believe that IDC with or without OPLL in children has a good prognosis when treated conservatively.},
}
@article {pmid28325697,
year = {2017},
author = {Sulaj, A and Kopf, S and Gröne, E and Gröne, HJ and Hoffmann, S and Schleicher, E and Häring, HU and Schwenger, V and Herzig, S and Fleming, T and Nawroth, PP and von Bauer, R},
title = {ALCAM a novel biomarker in patients with type 2 diabetes mellitus complicated with diabetic nephropathy.},
journal = {Journal of diabetes and its complications},
volume = {31},
number = {6},
pages = {1058-1065},
doi = {10.1016/j.jdiacomp.2017.01.002},
pmid = {28325697},
issn = {1873-460X},
mesh = {Adult ; Aged ; Antigens, CD/analysis/*blood/physiology ; Biomarkers/*blood ; Case-Control Studies ; Cell Adhesion Molecules, Neuronal/analysis/*blood/physiology ; Diabetes Mellitus, Type 2/*blood/*complications/diagnosis ; Diabetic Nephropathies/blood/*diagnosis/etiology ; Disease Progression ; Female ; Fetal Proteins/analysis/*blood/physiology ; Humans ; Kidney/physiopathology ; Male ; Middle Aged ; Prognosis ; },
abstract = {BACKGROUND &amp; AIM: Activated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN.<br><br>METHODS: A total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA. Expression of ALCAM and S100B in kidney histology from patients with DN was determined by immunohistochemistry. Cell expression of ALCAM and S100B was analyzed through confocal immunofluorescence microscopy.<br><br>RESULTS: Serum concentration of sALCAM was increased in diabetic patients with DN compared to non-diabetic (59.85&#xb1;14.99ng/ml vs. 126.88&#xb1;66.45ng/ml, P<0.0001). Moreover sALCAM correlated positively with HbA1c (R=0.31, P<0.0001), as well as with the stages of chronic kidney disease and negatively correlated with eGFR (R=-0.20, P<0.05). In diabetic patients with normal albuminuria sALCAM was increased compared to patients with DN (126.88&#xb1;66.45ng/ml vs. 197.50&#xb1;37.17ng/ml, P<0.0001). In diabetic patients, ALCAM expression was significantly upregulated in both the glomeruli and tubules (P<0.001). ALCAM expression in the glomeruli correlated with presence of sclerosis (R=0.25, P<0.001) and localized mainly in the podocytes supporting the hypothesis that membrane bound ALCAM drives diabetic nephropathy and thus explaining sALCAM decrease in diabetic patients with DN. The expression of S100B was increased significantly in the glomeruli of diabetic patients (P<0.001), but not in the tubules. S100B was as well localized in the podocytes.<br><br>CONCLUSIONS: This study identifies for the first time ALCAM as a potential mediator in the late complications of diabetes in the kidney.},
}
@article {pmid28301465,
year = {2017},
author = {Chao, LF and Singh, M and Thompson, J and Yates, JR and Hagstrom, KA},
title = {An SMC-like protein binds and regulates Caenorhabditis elegans condensins.},
journal = {PLoS genetics},
volume = {13},
number = {3},
pages = {e1006614},
pmid = {28301465},
issn = {1553-7404},
support = {P41 GM103533/GM/NIGMS NIH HHS/United States ; },
mesh = {Adenosine Triphosphatases/*genetics/metabolism ; Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/embryology/*genetics/growth &amp; development ; Caenorhabditis elegans Proteins/classification/*genetics/metabolism ; Chromosomal Proteins, Non-Histone/genetics/metabolism ; DNA-Binding Proteins/*genetics/metabolism ; Gene Expression Regulation, Developmental ; Meiosis/genetics ; Microscopy, Confocal ; Mitosis/genetics ; Multiprotein Complexes/*genetics/metabolism ; Mutation ; Nuclear Proteins/genetics/metabolism ; Phylogeny ; Protein Binding ; Protein Subunits/genetics/metabolism ; Sequence Homology, Amino Acid ; X Chromosome/genetics ; },
abstract = {Structural Maintenance of Chromosomes (SMC) family proteins participate in multisubunit complexes that govern chromosome structure and dynamics. SMC-containing condensin complexes create chromosome topologies essential for mitosis/meiosis, gene expression, recombination, and repair. Many eukaryotes have two condensin complexes (I and II); C. elegans has three (I, II, and the X-chromosome specialized condensin IDC) and their regulation is poorly understood. Here we identify a novel SMC-like protein, SMCL-1, that binds to C. elegans condensin SMC subunits, and modulates condensin functions. Consistent with a possible role as a negative regulator, loss of SMCL-1 partially rescued the lethal and sterile phenotypes of a hypomorphic condensin mutant, while over-expression of SMCL-1 caused lethality, chromosome mis-segregation, and disruption of condensin IDC localization on X chromosomes. Unlike canonical SMC proteins, SMCL-1 lacks hinge and coil domains, and its ATPase domain lacks conserved amino acids required for ATP hydrolysis, leading to the speculation that it may inhibit condensin ATPase activity. SMCL-1 homologs are apparent only in the subset of Caenorhabditis species in which the condensin I and II subunit SMC-4 duplicated to create the condensin IDC- specific subunit DPY-27, suggesting that SMCL-1 helps this lineage cope with the regulatory challenges imposed by evolution of a third condensin complex. Our findings uncover a new regulator of condensins and highlight how the duplication and divergence of SMC complex components in various lineages has created new proteins with diverse functions in chromosome dynamics.},
}
@article {pmid28296665,
year = {2018},
author = {Boufelli, G and Giannotti, MA and Ruiz, CA and Barros, N and Chala, LF and Maesaka, JY and Goncalves, R and Bresciani, BH and Vianna, P and Soares, JM and Baracat, EC and Filassi, JR},
title = {Papillomas of the breast: factors associated with underestimation.},
journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)},
volume = {27},
number = {4},
pages = {310-314},
pmid = {28296665},
issn = {1473-5709},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Papillary/*diagnosis/diagnostic imaging/surgery ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Mammography/*methods ; Middle Aged ; Prognosis ; Risk Assessment/*methods ; Risk Factors ; Ultrasonography, Mammary/*methods ; },
abstract = {The distinction between benign and malignant papilloma of the breast through percutaneous needle biopsy can be difficult because of limited samples; the underestimation rate can be up to 25%. The aim of this study is to identify clinical and histological factors associated with underestimation, invasive ductal carcinoma, or ductal in-situ carcinoma (DCIS) of the breast found in surgical specimens from papillary lesions. This may contribute toward selection of patients for a follow-up strategy without the need for surgical excision. From a database of 3563 patients, we identified 85 with intraductal papilloma between 2007 and 2013 who had undergone breast-imaging studies, percutaneous needle biopsy, and surgical resection of the lesion. Central papillomas normally present with a palpable mass, whereas peripheral papillomas generally do not have clinical manifestations (microcalcifications); both central and peripheral papillomas were related to atypical lesions, 13.5 and 15.4%, respectively. Among the 59 cases of central papillomas, there were four cases of underestimation, three DCIS and one invasive ductal carcinoma (6.8%). Among the 26 cases of peripheral papillomas, there was one case of DCIS (3.8%), with a total underestimation rate of 5.8%; all underestimated lesions measured more than 1 cm. The median size was 11 mm at mammography and 19 mm at ultrasound. Our data suggest that lesions less than 1 cm in size, without atypia and concordant imaging and clinical findings, may not require surgical resection.},
}
@article {pmid28292037,
year = {2016},
author = {Khalil, AI and Bendahhou, K and Mestaghanmi, H and Saile, R and Benider, A},
title = {[Breast cancer in Morocco: phenotypic profile of tumors].},
journal = {The Pan African medical journal},
volume = {25},
number = {},
pages = {74},
pmid = {28292037},
issn = {1937-8688},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*pathology/therapy ; Breast Neoplasms, Male/epidemiology/*pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/*pathology/therapy ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Neoplasm Staging ; Phenotype ; Young Adult ; },
abstract = {Breast cancer is most common in women and it is among the leading causes of cancer related deaths. The curability of this type of tumor is increasing thanks to screening programs and treatment advances which have certainly enhanced patient survival. But challenges remain, particularly in respect of phenotypic instability of cancer cells. The aim of this study was to analyse the phenotypic profile of breast cancer in patients treated at Mohammed VI Cancer Treatment Center over the years 2013-2014. We conducted a cross-sectional study over a two-year period, including the cases of breast cancer treated in our Center. Data were collected from patients medical records and analyzed using Epi Info software. 1277 patients were treated in our Center. 99.5% were females, mean age 50.20 ± 11.34 years. The most common histological type was invasive ductal carcinoma (80.7% of cases). It was diagnosed at an early stage (56,9%). The most common molecular phenotype was luminal A (41.4% of cases). Luminal B, HER2 and triple negatives occurred in 10.4%, 6.3%, 11.2% of cases respectively. The study of tumor phenotype in patients with breast cancer helps clinician make treatment choice and policy makers implement programs against this disease.},
}
@article {pmid28291966,
year = {2017},
author = {Miyazaki, T and Ohishi, Y and Miyasaka, Y and Oda, Y and Aishima, S and Ozono, K and Abe, A and Nagai, E and Nakamura, M and Oda, Y},
title = {Molecular Characteristics of Pancreatic Ductal Adenocarcinomas with High-Grade Pancreatic Intraepithelial Neoplasia (PanIN) Are Different from Those without High-Grade PanIN.},
journal = {Pathobiology : journal of immunopathology, molecular and cellular biology},
volume = {84},
number = {4},
pages = {192-201},
doi = {10.1159/000455194},
pmid = {28291966},
issn = {1423-0291},
mesh = {Aged ; Carcinoma in Situ/*complications ; Carcinoma, Pancreatic Ductal/complications/*genetics/metabolism/*pathology ; Humans ; Middle Aged ; Pancreas/metabolism/pathology ; Pancreatic Neoplasms/complications/*genetics/metabolism/pathology ; Prognosis ; Proto-Oncogene Proteins p21(ras)/*genetics ; Smad4 Protein/metabolism ; Tumor Suppressor Protein p53/metabolism ; },
abstract = {AIMS: We reported that pancreatic ductal adenocarcinomas (PDACs) without high-grade pancreatic intraepithelial neoplasia (PanIN) in the vicinity had worse prognoses than PDACs with high-grade PanIN. However, the molecular characteristics of PDACs with and without high-grade PanIN have not been compared. The aim of this study is to clarify the molecular characteristics of PDACs with and without high-grade PanIN.<br><br>METHOD AND RESULTS: We reviewed all of a consecutive series of 100 patients with PDACs and divided them into 2 groups: the PDACs with PanIN-2 or PanIN-3 in the background (the PanIN-high group, n = 60) and the PDACs without PanIN-2 or PanIN-3 in the background (the PanIN-low group, n = 40). We evaluated the p53, p16, and SMAD4 expressions in the invasive ductal carcinoma (IDC) components by immunohistochemical staining. KRAS mutation was also analyzed in 80 tumors. The PanIN-low group showed significantly more frequent "high p53 expression" and "loss of SMAD4 expression" than the PanIN-high group (p = 0.048 and p = 0.019, respectively). Loss of p16 expression was not significantly different between the groups. The rate of KRAS wild type was significantly higher in the PanIN-low group than the PanIN-high group (p = 0.024).<br><br>CONCLUSIONS: Our results demonstrated that the molecular characteristics in the PDACs with high-grade PanIN were different from those in the PDACs without high-grade PanIN. PDACs without high-grade PanIN may develop via a pathway other than the PanIN-carcinoma sequence.},
}
@article {pmid28291131,
year = {2017},
author = {Konstantinova, AM and Shelekhova, KV and Imyanitov, EN and Iyevleva, A and Kacerovska, D and Michal, M and Kazakov, DV},
title = {Study of Selected BRCA1, BRCA2, and PIK3CA Mutations in Benign and Malignant Lesions of Anogenital Mammary-Like Glands.},
journal = {The American Journal of dermatopathology},
volume = {39},
number = {5},
pages = {358-362},
doi = {10.1097/DAD.0000000000000725},
pmid = {28291131},
issn = {1533-0311},
mesh = {Aged ; Aged, 80 and over ; Anus Neoplasms/genetics/pathology ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Biopsy, Needle ; Class I Phosphatidylinositol 3-Kinases/*genetics ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Mammary Glands, Human/pathology ; Middle Aged ; Mutation ; Paget Disease, Extramammary/*genetics/*pathology ; Prognosis ; Retrospective Studies ; Risk Assessment ; Vulvar Neoplasms/genetics/pathology ; },
abstract = {Anogenital mammary-like glands (AGMLGs) are nowadays considered a normal component of the anogenital area. Lesions involving AGMLGs are histopathologically very similar to their mammary counterparts, but the information on molecular biological mechanisms in these vulvar/perianal tumors is scarce. Mutations in the PI3K-AKT cascade have been found in hidradenoma papilliferum. The authors studied selected BRCA1, BRCA2, and PIK3CA mutations in series of benign and malignant neoplasms thought to be associated with AGMLGs, including 9 cases of primary extramammary Paget disease, 3 different cases of mammary-type carcinoma (adenoid cystic like, tubulolobular, and invasive ductal like), and 5 cases of hidradenoma papilliferum. No BRCA mutation was detected, whereas 3 neoplasms yielded PIK3CA mutation, including extramammary Paget disease, mammary-type invasive ductal carcinoma, and tubulolobular carcinoma. Our study expands the spectrum of lesions of AGMLGs harboring mutations in genes encoding the PI3K-AKT cascade. Further studies of the whole BRCA1 and BRCA2 genes using a larger cohort are needed to clarify their role in the pathogenesis of AGMLG lesions.},
}
@article {pmid28274688,
year = {2017},
author = {Li, X and Lu, P and Li, B and Zhang, W and Yang, R and Chu, Y and Luo, K},
title = {Interleukin 2 and interleukin 10 function synergistically to promote CD8[+] T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer.},
journal = {The international journal of biochemistry &amp; cell biology},
volume = {87},
number = {},
pages = {1-7},
pmid = {28274688},
issn = {1878-5875},
mesh = {Breast Neoplasms/immunology/*pathology ; CD4 Antigens/metabolism ; CD4-Positive T-Lymphocytes/*cytology/*drug effects/immunology ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Synergism ; Female ; Humans ; Interleukin-10/*pharmacology ; Interleukin-2/*pharmacology ; Interleukin-2 Receptor alpha Subunit/metabolism ; Middle Aged ; T-Lymphocytes, Regulatory/*cytology/*drug effects/immunology/metabolism ; },
abstract = {The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8[+] T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8[+] T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls. Upon prolonged TCR stimulation, peripheral blood CD8[+] T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of IL-2 and/or IL-10. The cytotoxicity of TCR-activated CD8[+] T cells was also enhanced by exogenous IL-2 and/or IL-10. Interestingly, IL-2 and IL-10 demonstrated synergistic effects, since the enhancement in CD8[+] T cell function when both cytokines were added was greater than the sum of the improvements mediated by each individual cytokine. IL-10 by itself could not promote the proliferation of CD8[+] T cells but could significantly enhance IL-2-mediated promotion of CD8[+] T cell proliferation. In addition, the cytotoxicity of tumor-infiltrating CD8[+] T cells in breast tumor was elevated when both IL-2 and IL-10 were present but not when either one was absent. This synergistic effect was stopped by CD4[+]CD25[+] regulatory T cells (Treg), which depleted IL-2 in a cell number-dependent manner. Together, these results demonstrated that IL-2 and IL-10 could work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8[+] T cells, an effect suppressible by CD4[+]CD25[+] Treg cells.},
}
@article {pmid28272456,
year = {2017},
author = {Zhang, J and Naik, HS and Assefa, T and Sarkar, S and Reddy, RV and Singh, A and Ganapathysubramanian, B and Singh, AK},
title = {Computer vision and machine learning for robust phenotyping in genome-wide studies.},
journal = {Scientific reports},
volume = {7},
number = {},
pages = {44048},
pmid = {28272456},
issn = {2045-2322},
mesh = {*Artificial Intelligence ; Genome-Wide Association Study/*methods ; Image Processing, Computer-Assisted ; *Machine Learning ; Phenotype ; Quantitative Trait Loci ; Glycine max/*genetics/metabolism ; Stress, Physiological ; },
abstract = {Traditional evaluation of crop biotic and abiotic stresses are time-consuming and labor-intensive limiting the ability to dissect the genetic basis of quantitative traits. A machine learning (ML)-enabled image-phenotyping pipeline for the genetic studies of abiotic stress iron deficiency chlorosis (IDC) of soybean is reported. IDC classification and severity for an association panel of 461 diverse plant-introduction accessions was evaluated using an end-to-end phenotyping workflow. The workflow consisted of a multi-stage procedure including: (1) optimized protocols for consistent image capture across plant canopies, (2) canopy identification and registration from cluttered backgrounds, (3) extraction of domain expert informed features from the processed images to accurately represent IDC expression, and (4) supervised ML-based classifiers that linked the automatically extracted features with expert-rating equivalent IDC scores. ML-generated phenotypic data were subsequently utilized for the genome-wide association study and genomic prediction. The results illustrate the reliability and advantage of ML-enabled image-phenotyping pipeline by identifying previously reported locus and a novel locus harboring a gene homolog involved in iron acquisition. This study demonstrates a promising path for integrating the phenotyping pipeline into genomic prediction, and provides a systematic framework enabling robust and quicker phenotyping through ground-based systems.},
}
@article {pmid28264146,
year = {2017},
author = {Yao, X and Gan, Y and Chang, E and Hibshoosh, H and Feldman, S and Hendon, C},
title = {Visualization and tissue classification of human breast cancer images using ultrahigh-resolution OCT.},
journal = {Lasers in surgery and medicine},
volume = {49},
number = {3},
pages = {258-269},
pmid = {28264146},
issn = {1096-9101},
support = {DP2 HL127776/HL/NHLBI NIH HHS/United States ; },
mesh = {Biopsy, Needle ; Breast/*diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/pathology/*surgery ; Cross-Sectional Studies ; Female ; Humans ; *Imaging, Three-Dimensional ; Immunohistochemistry ; In Vitro Techniques ; Mastectomy/methods ; Reference Values ; Sampling Studies ; Tomography, Optical Coherence/*methods ; },
abstract = {BACKGROUND AND OBJECTIVE: Breast cancer is one of the most common cancers, and recognized as the third leading cause of mortality in women. Optical coherence tomography (OCT) enables three dimensional visualization of biological tissue with micrometer level resolution at high speed, and can play an important role in early diagnosis and treatment guidance of breast cancer. In particular, ultra-high resolution (UHR) OCT provides images with better histological correlation. This paper compared UHR OCT performance with standard OCT in breast cancer imaging qualitatively and quantitatively. Automatic tissue classification algorithms were used to automatically detect invasive ductal carcinoma in ex vivo human breast tissue.<br><br>Human breast tissues, including non-neoplastic/normal tissues from breast reduction and tumor samples from mastectomy specimens, were excised from patients at Columbia University Medical Center. The tissue specimens were imaged by two spectral domain OCT systems at different wavelengths: a home-built ultra-high resolution (UHR) OCT system at 800&#x2009;nm (measured as 2.72&#x2009;&#x3bc;m axial and 5.52&#x2009;&#x3bc;m lateral) and a commercial OCT system at 1,300&#x2009;nm with standard resolution (measured as 6.5&#x2009;&#x3bc;m axial and 15&#x2009;&#x3bc;m lateral), and their imaging performances were analyzed qualitatively. Using regional features derived from OCT images produced by the two systems, we developed an automated classification algorithm based on relevance vector machine (RVM) to differentiate hollow-structured adipose tissue against solid tissue. We further developed B-scan based features for RVM to classify invasive ductal carcinoma (IDC) against normal fibrous stroma tissue among OCT datasets produced by the two systems. For adipose classification, 32 UHR OCT B-scans from 9 normal specimens, and 28 standard OCT B-scans from 6 normal and 4 IDC specimens were employed. For IDC classification, 152 UHR OCT B-scans from 6 normal and 13 IDC specimens, and 104 standard OCT B-scans from 5 normal and 8 IDC specimens were employed.<br><br>RESULTS: We have demonstrated that UHR OCT images can produce images with better feature delineation compared with images produced by 1,300&#x2009;nm OCT system. UHR OCT images of a variety of tissue types found in human breast tissue were presented. With a limited number of datasets, we showed that both OCT systems can achieve a good accuracy in identifying adipose tissue. Classification in UHR OCT images achieved higher sensitivity (94%) and specificity (93%) of adipose tissue than the sensitivity (91%) and specificity (76%) in 1,300&#x2009;nm OCT images. In IDC classification, similarly, we achieved better results with UHR OCT images, featured an overall accuracy of 84%, sensitivity of 89% and specificity of 71% in this preliminary study.<br><br>CONCLUSION: In this study, we provided UHR OCT images of different normal and malignant breast tissue types, and qualitatively and quantitatively studied the texture and optical features from OCT images of human breast tissue at different resolutions. We developed an automated approach to differentiate adipose tissue, fibrous stroma, and IDC within human breast tissues. Our work may open the door toward automatic intraoperative OCT evaluation of early-stage breast cancer. Lasers Surg. Med. 49:258-269, 2017. &#xa9; 2017 Wiley Periodicals, Inc.},
}
@article {pmid28240310,
year = {2017},
author = {Sowrirajan, B and Saito, Y and Poudyal, D and Chen, Q and Sui, H and DeRavin, SS and Imamichi, H and Sato, T and Kuhns, DB and Noguchi, N and Malech, HL and Lane, HC and Imamichi, T},
title = {Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47[phox].},
journal = {Scientific reports},
volume = {7},
number = {},
pages = {43441},
pmid = {28240310},
issn = {2045-2322},
support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; },
mesh = {Cell Differentiation/drug effects ; Dendritic Cells/cytology/*drug effects/immunology ; Gene Expression Regulation ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-4/pharmacology ; Interleukins/*pharmacology ; Macrophage Activation/drug effects ; Macrophage Colony-Stimulating Factor/pharmacology ; Macrophages/cytology/*drug effects/immunology ; NADPH Oxidases/*genetics/immunology ; Phosphorylation/drug effects ; Primary Cell Culture ; Signal Transduction ; Superoxide Dismutase/genetics/immunology ; Superoxides/immunology/*metabolism ; },
abstract = {Interleukin (IL)-27, a member of the IL-12 cytokine family, plays an important and diverse role in the function of the immune system. We have previously demonstrated that IL-27 is an anti-viral cytokine which inhibits HIV-1, HIV-2, Influenza virus and herpes simplex virus infection, and enhances the potential of reactive oxygen species (ROS) generating activity during differentiation of monocytes to macrophages. In this study, we further investigated the mechanism of the enhanced potential for ROS generation by IL-27. Real time PCR, western blot and knock down assays demonstrate that IL-27 is able to enhance the potential of superoxide production not only during differentiation but also in terminally differentiated-macrophages and immature dendritic cells (iDC) in association with the induction of p47[phox], a cytosolic component of the ROS producing enzyme, NADPH oxidase, and the increase in amounts of phosphorylated p47[phox] upon stimulation. We also demonstrate that IL-27 is able to induce extracellular superoxide dismutase during differentiation of monocytes but not in terminal differentiated macrophages. Since ROS plays an important role in a variety of inflammation, our data demonstrate that IL-27 is a potent regulator of ROS induction and may be a novel therapeutic target.},
}
@article {pmid28224328,
year = {2017},
author = {Santangelo, G and Lagravinese, G and Battini, V and Chiorri, C and Siciliano, M and Abbruzzese, G and Vitale, C and Barone, P},
title = {The Parkinson's Disease-Cognitive Rating Scale (PD-CRS): normative values from 268 healthy Italian individuals.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {38},
number = {5},
pages = {845-853},
pmid = {28224328},
issn = {1590-3478},
mesh = {Adult ; Age Factors ; Aged ; Cognition Disorders/*diagnosis/*etiology ; Educational Status ; Female ; Healthy Volunteers ; Humans ; Italy ; Male ; Middle Aged ; *Neuropsychological Tests ; Parkinson Disease/*complications ; Reference Values ; Severity of Illness Index ; Young Adult ; },
abstract = {The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a cognitive screening battery that includes subtests to assess cortical and subcortical functions. It is a valid screening tool for mild cognitive impairment (MCI) in Parkinson's disease (PD) and is recommended for diagnosing PD-MCI-Level I. Until now, no study has provided population-based norms for the Italian population. The aim of the present study was to collect normative values in a sample of Italian healthy subjects. Two hundred and sixty-eight (125 men) participants of different ages (age range 30-79 years) and educational levels (from primary school to university) underwent the PD-CRS. Regression-based norming was used to explore the influence of demographic variables (age, education level, and gender) on PD-CRS total score, frontal-subcortical and instrumental-cortical sub-scores, and score achieved on each task of the PD-CRS. Multiple linear regression analysis revealed that age and education significantly predicted the total score, the two sub-scores and the score on each task of the PD-CRS. No significant effect of gender was found. From the derived linear equations, a correction grid for raw scores was developed. Inferential cut-off scores, estimated using a non-parametric technique, were 71.25 for PD-CRS total score and 46.25 and 20.17 for frontal-subcortical and instrumental-cortical sub-score, respectively. Since the use of adjusted scores is more informative when they are standardized, we have converted adjusted scores into equivalent scores. The present study provides normative data for the PD-CRS, being useful and recommended by Movement Disorders Society task force to identify PD-MCI-Level I, at several stages of the disease.},
}
@article {pmid28214265,
year = {2017},
author = {Picillo, M and Santangelo, G and Erro, R and Cozzolino, A and Amboni, M and Vitale, C and Barone, P and Pellecchia, MT},
title = {Association between dopaminergic dysfunction and anxiety in de novo Parkinson's disease.},
journal = {Parkinsonism &amp; related disorders},
volume = {37},
number = {},
pages = {106-110},
doi = {10.1016/j.parkreldis.2017.02.010},
pmid = {28214265},
issn = {1873-5126},
mesh = {Aged ; Anxiety/diagnostic imaging/*etiology ; Chi-Square Distribution ; Cohort Studies ; Cross-Sectional Studies ; Dopamine/*metabolism ; Dopamine Plasma Membrane Transport Proteins/*metabolism ; Female ; Humans ; International Cooperation ; Male ; Middle Aged ; Parkinson Disease/*complications/diagnostic imaging/*metabolism ; Psychiatric Status Rating Scales ; Statistics as Topic ; Tomography, Emission-Computed, Single-Photon ; },
abstract = {OBJECTIVES: To explore the relationships between nigrostriatal dysfunction and neuropsychiatric symptoms (including anxiety, depression and apathy) in a large cohort of newly diagnosed, drug-naïve Parkinson disease (PD) patients compared to a cohort of healthy controls (HC).<br><br>METHODS: This is a cross-sectional analysis of the Parkinson's Progression Markers Initiative (PPMI) cohort at baseline, including 405 PD patients and 187 HC. Nigrostriatal degeneration was evaluated by means of SPECT DAT scan. Relationships between neuropsychiatric symptoms and DAT uptakes were analysed by means of stepwise multiple regression analysis.<br><br>RESULTS: In the PD group, lower DAT uptake in the right caudate was associated with higher STAI trait subscore (&#x3b2;&#xa0;=&#xa0;-2.939, 95%CI:&#xa0;-4.634 to&#xa0;-1.254, p&#xa0;=&#xa0;0.001). Depression and apathy scores were not related with DAT uptakes. No associations were found in the HC group.<br><br>CONCLUSIONS: Our cross-sectional analysis of the PPMI data shows that lower caudate DAT uptake is associated with higher level of anxiety. The data strengthens the relationship between dopaminergic dysfunction and neuropsychiatric symptoms in early PD.},
}
@article {pmid28207532,
year = {2017},
author = {Zhong, J and Lei, J and Jiang, K and Li, Z and Gong, R and Zhu, J},
title = {Synchronous papillary thyroid carcinoma and breast ductal carcinoma: A rare case report and literature review.},
journal = {Medicine},
volume = {96},
number = {7},
pages = {e6114},
pmid = {28207532},
issn = {1536-5964},
mesh = {Breast Neoplasms/*complications/pathology/surgery ; Carcinoma/*complications/pathology/surgery ; Carcinoma, Ductal, Breast/*complications/pathology/surgery ; Carcinoma, Papillary ; Female ; Humans ; Lymph Node Excision ; Mastectomy ; Middle Aged ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/*complications/pathology/surgery ; Thyroidectomy ; },
abstract = {BACKGROUND: The incidences of both thyroid cancer and breast cancer have been rising in recent years; however, it is very rare to find a single person with both of these cancers. Only a few cases of synchronous thyroid and breast cancer have been published, and even fewer cases have been reported in older patients (>60 years).<br><br>CASE SUMMARY: The current study presents a case of synchronous papillary thyroid carcinoma and breast ductal carcinoma in an elderly patient. The patient first underwent a mastectomy and axillary lymphadenectomy in our department, followed by a total thyroidectomy and lymphadenectomy of the left lateral region of the neck 1 month later. Postoperative pathological examination identified invasive ductal carcinoma of the breast and papillary carcinoma of the thyroid. Over almost half a year of follow-up, the patient has exhibited no evidence of recurrence or metastasis, as demonstrated by careful ultrasound examinations. Herein, we not only report this case but also present a systematic review of the causes, diagnosis, and treatment of synchronous breast and thyroid cancer.<br><br>CONCLUSION: Although synchronous primary tumors of the thyroid and breast are very rare, they remain a possibility; therefore, more attention should be paid to these cases.},
}
@article {pmid28198519,
year = {2017},
author = {Jeong, YJ and Jung, JW and Cho, YY and Park, SH and Oh, HK and Kang, S},
title = {Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT.},
journal = {Nuclear medicine review. Central &amp; Eastern Europe},
volume = {20},
number = {1},
pages = {32-38},
doi = {10.5603/NMR.a2016.0043},
pmid = {28198519},
issn = {1644-4345},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnostic imaging/*metabolism/mortality ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Middle Aged ; Molecular Imaging/methods ; Positron Emission Tomography Computed Tomography/methods/statistics &amp; numerical data ; Prevalence ; Radiopharmaceuticals/pharmacokinetics ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Tumor Hypoxia ; },
abstract = {BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed.<br><br>MATERIAL AND METHODS: Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method.<br><br>RESULTS: pSUVmax was significantly higher in patients with HIF-1a expression &#x2265; 2 compared to patients with HIF-1a expression < 2 (5.2 &#xb1; 4.5 vs. 3.7 &#xb1; 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 &#xb1; 4.4 vs. 4.1 &#xb1; 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001).<br><br>CONCLUSIONS: pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell.},
}
@article {pmid28188401,
year = {2017},
author = {Walter, H},
title = {[Research domain criteria (RDoC) : Psychiatric research as applied cognitive neuroscience].},
journal = {Der Nervenarzt},
volume = {88},
number = {5},
pages = {538-548},
pmid = {28188401},
issn = {1433-0407},
mesh = {Biomedical Research/*organization &amp; administration ; Cognitive Neuroscience/*methods/*organization &amp; administration ; *Diagnostic and Statistical Manual of Mental Disorders ; Germany ; *Models, Organizational ; Patient Care Team/*organization &amp; administration ; Psychiatry/*organization &amp; administration ; Research Design ; },
abstract = {BACKGROUND: Just before the official launch of the DSM-5 in 2013, the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health was made public and is becoming increasingly more important in psychiatric research.<br><br>OBJECTIVE: The aim of this paper is to clarify the conceptual approach of RDoC, to systematically discuss limitations, to present exemplary RDoC-based studies and to consider the relevance of the RDoC concepts for clinicians and scientists.<br><br>MATERIAL AND METHODS: The is a&#xa0;qualitative introduction and review article with a critical discussion.<br><br>RESULTS AND DISCUSSION: The RDoC initiative was not conceived as an alternative diagnostic manual to DSM-5 or IDC-10/11 for use in clinical practice. It is a&#xa0;new systematic framework for psychiatric research based on the most recent results of cognitive neuroscience and aims to map mental disorders dimensionally and transdiagnostically. Despite some weaknesses, it is currently the most elaborated and scientifically grounded approach for multidisciplinary research on mental disorders. In contrast to the purely symptom-based DSM and ICD approaches, which are agnostic with respect to the pathogenesis of mental diseases, the explicit aim of the RDoC initiative is to systematize biological knowledge about risk factors and causes of mental disorders; therefore, it has a&#xa0;much greater potential to develop new and individualized therapeutic strategies based on disease mechanisms.},
}
@article {pmid28173783,
year = {2017},
author = {Effi, AB and Aman, NA and Koui, BS and Koffi, KD and Traoré, ZC and Kouyate, M},
title = {Immunohistochemical determination of estrogen and progesterone receptors in breast cancer: relationship with clinicopathologic factors in 302 patients in Ivory Coast.},
journal = {BMC cancer},
volume = {17},
number = {1},
pages = {115},
pmid = {28173783},
issn = {1471-2407},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*metabolism ; Cote d'Ivoire ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Prospective Studies ; Receptors, Estrogen/*analysis/genetics ; Receptors, Progesterone/*analysis/genetics ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer is a heterogeneous and a hormone-dependent disease. The detection of the estrogen receptor (ER) and progesterone receptor (PgR) is crucial for prognostic evaluation and treatment choice of breast cancer for clinical practice. The purpose of this study was to evaluate the expression of the hormonal receptors, their distribution, and their correlation with clinicopathologic prognostic parameters for the improvement of the patients' treatment in Ivory Coast.<br><br>METHODS: The 20-month prospective study included 302 patients who were diagnosed with primary invasive breast carcinomas at the Central Laboratory in Abidjan. The paraffin-embedded blocks of these patients were examined by immunohistochemistry to assess the ER and PgR status. The one-way analysis of variance and Chi-Square Test were used to analyze the data.<br><br>RESULTS: The mean age of patients at diagnosis was 48&#x2009;&#xb1;&#x2009;11&#xa0;years. The majority of the women were premenopausal in 180 cases (59.9%). The predominant histologic type was invasive ductal carcinoma not otherwise specified (IDC NOS) in 247 cases (82%). Tumor grade 2 was more frequent in 166 cases (55%). Among 302 patients, 169 (56%) and 154 (49%) expressed ER and PgR respectively. The ER+PgR+ group with 131 cases (43%) was predominant, followed by 116 cases (38%) of ER-PgR-. The expression of ER and PgR was correlated with the age of the patients (p&#x2009;=&#x2009;0.026) and the tumor grade (p&#x2009;=&#x2009;0.0004). However, there was not statistically significant correlation between ER/PgR and the menopausal status of patients (p&#x2009;=&#x2009;0.149), nor between ER/PgR and the histologic type (p&#x2009;=&#x2009;0.523).<br><br>CONCLUSION: The ER+PgR+ and ER-PgR- are the most common subgroups in women with breast cancer in Ivory Coast. The hormonal receptor status is associated with the age and the histologic grade in breast cancer patients. The systematic use of hormonal treatment should be reevaluated. A further study should be done to investigate the reasons of high rate of ER-PgR- in breast cancer patients in Ivory Coast.},
}
@article {pmid28169235,
year = {2016},
author = {Rohilla, M and Bal, A and Singh, G and Joshi, K},
title = {Prediction of heterogeneity in breast cancer immunophenotype at ductal carcinoma in situ stage?.},
journal = {Journal of cancer research and therapeutics},
volume = {12},
number = {4},
pages = {1249-1256},
doi = {10.4103/0973-1482.199541},
pmid = {28169235},
issn = {1998-4138},
mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Carcinoma In Situ/*diagnosis/genetics/*metabolism ; Breast Neoplasms/*diagnosis/genetics/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; *Immunophenotyping ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Tumor Burden ; Young Adult ; },
abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) is considered a heterogeneous lesion at the molecular level. However, there is a paucity of literature about the existence of molecular subtypes in DCIS which can predict their biological behavior at the preinvasive stage.<br><br>MATERIALS AND METHODS: Precise prevalence of molecular subtypes of pure DCIS and DCIS component of infiltrating duct carcinoma (IDC) was evaluated using immunohistochemistry and correlated with known prognostic factors.<br><br>RESULTS: DCIS cases were classified as luminal A (46.6% in each group), luminal B (pure DCIS 20% and DCIS component of IDC 13.3%), HER2 overexpressing, basal and nonbasal (pure DCIS 3.3% and 26.6% and DCIS component of IDC 3.3% and 33.3%, respectively), and triple negative, nonbasal (pure DCIS and DCIS component of IDC 3.3% each). The molecular phenotype of DCIS correlated well with that of the coexisting IDC.<br><br>CONCLUSIONS: This study demonstrated molecular heterogeneity in DCIS; however, similar molecular phenotypes were seen in the coexisting IDC suggesting that DCIS is a precursor lesion and can predict phenotype of the invasive component. This also suggests that the invasiveness of DCIS is not dependent solely on the molecular character of the tumor epithelial cells, but factors such as tumor microenvironment may play a role.},
}
@article {pmid28167700,
year = {2017},
author = {Zhang, X and Ivanova, A and Vandepoele, K and Radomiljac, J and Van de Velde, J and Berkowitz, O and Willems, P and Xu, Y and Ng, S and Van Aken, O and Duncan, O and Zhang, B and Storme, V and Chan, KX and Vaneechoutte, D and Pogson, BJ and Van Breusegem, F and Whelan, J and De Clercq, I},
title = {The Transcription Factor MYB29 Is a Regulator of ALTERNATIVE OXIDASE1a.},
journal = {Plant physiology},
volume = {173},
number = {3},
pages = {1824-1843},
pmid = {28167700},
issn = {1532-2548},
mesh = {Antimycin A/pharmacology ; Arabidopsis/enzymology/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Cell Nucleus/genetics/metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation, Plant/drug effects/*genetics ; Gene Ontology ; Gene Regulatory Networks ; Immunoblotting ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/*genetics/metabolism ; Mutation ; Oxidoreductases/*genetics/metabolism ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; Protein Binding ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/genetics ; Transcription Factors/*genetics/metabolism ; },
abstract = {Plants sense and integrate a variety of signals from the environment through different interacting signal transduction pathways that involve hormones and signaling molecules. Using ALTERNATIVE OXIDASE1a (AOX1a) gene expression as a model system of retrograde or stress signaling between mitochondria and the nucleus, MYB DOMAIN PROTEIN29 (MYB29) was identified as a negative regulator (regulator of alternative oxidase1a 7 [rao7] mutant) in a genetic screen of Arabidopsis (Arabidopsis thaliana). rao7/myb29 mutants have increased levels of AOX1a transcript and protein compared to wild type after induction with antimycin A. A variety of genes previously associated with the mitochondrial stress response also display enhanced transcript abundance, indicating that RAO7/MYB29 negatively regulates mitochondrial stress responses in general. Meta-analysis of hormone-responsive marker genes and identification of downstream transcription factor networks revealed that MYB29 functions in the complex interplay of ethylene, jasmonic acid, salicylic acid, and reactive oxygen species signaling by regulating the expression of various ETHYLENE RESPONSE FACTOR and WRKY transcription factors. Despite an enhanced induction of mitochondrial stress response genes, rao7/myb29 mutants displayed an increased sensitivity to combined moderate light and drought stress. These results uncover interactions between mitochondrial retrograde signaling and the regulation of glucosinolate biosynthesis, both regulated by RAO7/MYB29. This common regulator can explain why perturbation of the mitochondrial function leads to transcriptomic responses overlapping with responses to biotic stress.},
}
@article {pmid28165048,
year = {2017},
author = {Johanning, GL and Malouf, GG and Zheng, X and Esteva, FJ and Weinstein, JN and Wang-Johanning, F and Su, X},
title = {Expression of human endogenous retrovirus-K is strongly associated with the basal-like breast cancer phenotype.},
journal = {Scientific reports},
volume = {7},
number = {},
pages = {41960},
pmid = {28165048},
issn = {2045-2322},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; P50 CA100632/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Basal Cell/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Databases, Factual ; Endogenous Retroviruses/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Viral ; Genome, Human ; Humans ; Viral Envelope Proteins/*genetics ; },
abstract = {Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus. Expression of the HERV-K envelope gene (env) was highly significantly increased in basal tumors in comparison with the also-upregulated expression of other HERV-K genes. Analysis of reverse-phase protein array data indicated that increased expression of HERV-K is associated with decreased mutation of H-Ras (wild-type). Our results show elevation of HERV-K expression exclusively in the basal subtype of IDC breast cancer (as opposed to the other subtypes) and suggest HERV-K as a possible target for cancer vaccines or immunotherapy against this highly aggressive form of breast cancer.},
}
@article {pmid28162815,
year = {2017},
author = {Roobol, MJ and Verbeek, JFM and van der Kwast, T and Kümmerlin, IP and Kweldam, CF and van Leenders, GJLH},
title = {Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator for Initial Prostate Biopsy by Incorporating the 2014 International Society of Urological Pathology Gleason Grading and Cribriform growth.},
journal = {European urology},
volume = {72},
number = {1},
pages = {45-51},
doi = {10.1016/j.eururo.2017.01.033},
pmid = {28162815},
issn = {1873-7560},
mesh = {Adenocarcinoma/mortality/*pathology/therapy ; Aged ; Area Under Curve ; Biopsy ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology/therapy ; Clinical Decision-Making ; *Decision Support Techniques ; Humans ; Logistic Models ; Male ; Middle Aged ; *Mobile Applications ; Multivariate Analysis ; *Neoplasm Grading ; Patient Selection ; Predictive Value of Tests ; Prostatic Neoplasms/mortality/*pathology/therapy ; ROC Curve ; Reproducibility of Results ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; Unnecessary Procedures ; },
abstract = {BACKGROUND: The survival rate for men with International Society of Urological Pathology (ISUP) grade 2 prostate cancer (PCa) without invasive cribriform (CR) and intraductal carcinoma (IDC) is similar to that for ISUP grade 1. If updated into the European Randomized Study of Screening for Prostate Cancer (ERSPC Rotterdam) risk calculator number 3 (RC3), this may further improve upfront selection of men who need a biopsy.<br><br>OBJECTIVE: To improve the number of possible biopsies avoided, while limiting undiagnosed clinically important PCa by applying the updated RC3 for risk-based patient selection.<br><br>The RC3 is based on the first screening round of the ERSPC Rotterdam, which involved 3616 men. In 2015, histopathologic slides for PCa cases (n=885) were re-evaluated. Low-risk (LR) PCa was defined as ISUP grade 1 or 2 without CR/IDC. High-risk (HR) PCa was defined as ISUP grade 2 with CR/IDC and PCa with ISUP grade&#x2265;3.<br><br>We updated the RC3 using multinomial logistic regression analysis, including data on age, PSA, digital rectal examination, and prostate volume, for predicting LR and HR PCa. Predictive accuracy was quantified using receiver operating characteristic analysis and decision curve analysis.<br><br>RESULTS AND LIMITATIONS: Men without PCa could effectively be distinguished from men with LR PCa and HR PCa (area under the curve 0.70, 95% confidence interval [CI] 0.68-0.72 and 0.92, 95% CI 0.90-0.94). At a 1% risk threshold, the updated calculator would lead to a 34% reduction in unnecessary biopsies, while only 2% of HR PCa cases would be undiagnosed.<br><br>CONCLUSIONS: A relatively simple risk stratification tool augmented with a highly sensitive contemporary pathologic biopsy classification would result in a considerable decrease in unnecessary prostate biopsies and overdiagnosis of potentially indolent disease.<br><br>PATIENT SUMMARY: We improved a well-known prostate risk calculator with a new pathology classification system that better reflects disease burden. This new risk calculator allows individualized prediction of the chance of having (potentially aggressive) biopsy-detectable prostate cancer and can guide shared decision-making when considering prostate biopsy.},
}
@article {pmid28153863,
year = {2017},
author = {Ng, CKY and Piscuoglio, S and Geyer, FC and Burke, KA and Pareja, F and Eberle, CA and Lim, RS and Natrajan, R and Riaz, N and Mariani, O and Norton, L and Vincent-Salomon, A and Wen, YH and Weigelt, B and Reis-Filho, JS},
title = {The Landscape of Somatic Genetic Alterations in Metaplastic Breast Carcinomas.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {23},
number = {14},
pages = {3859-3870},
pmid = {28153863},
issn = {1557-3265},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/genetics ; Cadherins/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Metaplasia/*genetics/pathology ; Mutation ; Nuclear Proteins/genetics ; PTEN Phosphohydrolase/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Proto-Oncogene Proteins c-akt/genetics ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/genetics ; Transcription Factors/genetics ; Triple Negative Breast Neoplasms/*genetics/pathology ; Tumor Suppressor Protein p53/genetics ; Exome Sequencing ; Wnt Signaling Pathway/genetics ; },
abstract = {Purpose: Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic type of breast cancer, predominantly of triple-negative phenotype, and characterized by the presence of malignant cells showing squamous and/or mesenchymal differentiation. We sought to define the repertoire of somatic genetic alterations and the mutational signatures of MBCs.Experimental Design: Whole-exome sequencing was performed in 35 MBCs, with 16, 10, and 9 classified as harboring chondroid, spindle, and squamous metaplasia as the predominant metaplastic component. The genomic landscape of MBCs was compared with that of triple-negative invasive ductal carcinomas of no special type (IDC-NST) from The Cancer Genome Atlas. Wnt and PI3K/AKT/mTOR pathway activity was assessed using a qPCR assay.Results: MBCs harbored complex genomes with frequent TP53 (69%) mutations. In contrast to triple-negative IDC-NSTs, MBCs more frequently harbored mutations in PIK3CA (29%), PIK3R1 (11%), ARID1A (11%), FAT1 (11%), and PTEN (11%). PIK3CA mutations were not found in MBCs with chondroid metaplasia. Compared with triple-negative IDC-NSTs, MBCs significantly more frequently harbored mutations in PI3K/AKT/mTOR pathway-related (57% vs. 22%) and canonical Wnt pathway-related (51% vs. 28%) genes. MBCs with somatic mutations in PI3K/AKT/mTOR or Wnt pathway-related genes displayed increased activity of the respective pathway.Conclusions: MBCs are genetically complex and heterogeneous, and are driven by a repertoire of somatic mutations distinct from that of triple-negative IDC-NSTs. Our study highlights the genetic basis and the importance of PI3K/AKT/mTOR and Wnt pathway dysregulation in MBCs and provides a rationale for the metaplastic phenotype and the reported responses to PI3K/AKT/mTOR inhibitors in these tumors. Clin Cancer Res; 23(14); 3859-70. ©2017 AACR.},
}
@article {pmid28133686,
year = {2017},
author = {Uçar, FM and Açar, B},
title = {Neutrophil to lymphocyte ratio predicts appropriate therapy in idiopathic dilated cardiomyopathy patients with primary prevention implantable cardioverter defibrillator.},
journal = {Saudi medical journal},
volume = {38},
number = {2},
pages = {143-148},
pmid = {28133686},
issn = {1658-3175},
mesh = {Cardiac Pacing, Artificial/methods ; Cardiomyopathy, Dilated/diagnostic imaging/immunology/*therapy ; *Defibrillators, Implantable/statistics &amp; numerical data ; Echocardiography ; Female ; Humans ; *Leukocyte Count ; *Lymphocyte Count ; Male ; Middle Aged ; *Neutrophils ; Primary Prevention ; Retrospective Studies ; },
abstract = {OBJECTIVES: To investigate whether an inflammatory marker of neutrophil to lymphocyte ratio (NLR) predicts appropriate implantable cardioverter defibrillator (ICD) therapy (shock or anti tachycardia pacing) in idiopathic dilated cardiomyopathy (IDC) patients.<br><br>METHODS: We retrospectively examined IDC patients (mean age: 58.3 &#xb1; 11.8 years, 81.5% male) with ICD who admitted to outpatient clinic for pacemaker control at 2 tertiary care hospitals in Ankara and Edirne, Turkey from January 2013-2015. All ICDs were implanted for primary prevention. Hematological and biochemical parameters were measured prior procedure.&#xa0;Results: Over a median follow-up period of 43 months (Range 7-125), 68 (33.1%) patients experienced appropriate ICD therapy. The NLR was increased in patients that received appropriate therapy (4.39 &#xb1; 2.94 versus 2.96 &#xb1; 1.97, p less than&#xa0;0.001).To identify independent risk factors for appropriate therapy, a multivariate linear regression model was conducted and age (&#x3b2;=0.163, p=0.013), fasting glucose (&#x3b2;=0.158, p=0.017), C-reactive protein (CRP) (&#x3b2;=0.289, p less than&#xa0;0.001) and NLR (&#x3b2;=0.212, p less than&#xa0;0.008) were found to be independent risk factors for appropriate ICD therapy.&#xa0;Conclusions: Before ICD implantation by using NLR and CRP, arrhythmic episodes may be predictable and better antiarrhythmic medical therapy optimization may protect these IDC patients from unwanted events.},
}
@article {pmid28133285,
year = {2016},
author = {Watanabe, M and Enomoto, K and Sakurai, K},
title = {[Primary Breast Cancer in a Man].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {43},
number = {12},
pages = {2249-2251},
pmid = {28133285},
issn = {0385-0684},
mesh = {*Adenocarcinoma, Scirrhous/diagnostic imaging/secondary/surgery ; Aged ; Axilla/pathology ; Biopsy, Large-Core Needle ; Breast Neoplasms, Male/diagnostic imaging/*pathology/surgery ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Mammography ; Mastectomy ; Neoplasm Invasiveness ; },
abstract = {A 76-year-old man noticed a tumor under his right nipple. Mammography revealed an irregularly shaped nodule in the right breast. Ultrasonography showed a 20mm irregularly shaped nodule in the central area. MRI showed an 18mm irregularly shaped nodule in the central area with skin invasion. On core needle biopsy, the tumor was diagnosed as an invasive ductal carcinoma of the right breast. The patient underwent a mastectomy and axillary lymph node dissection. Histopathologically, the patient was diagnosed with invasive ductal carcinoma(scirrhous carcinoma). The tumor was positive for both ER and PgR, and the HER2 score was 1. The Ki-67 index was 20-30%. Male breast carcinoma accounts for approximately 1.0% of all breast carcinomas. The most common complaint is elastic, hard nodules with no pain. Postoperative therapy for male breast cancer is similar to that for female cancer. This patient underwent a mastectomy and lymph node dissection. After surgery, tamoxifen was administered as adjuvant therapy. There has been no evidence of recurrence for 4 months after the surgery.},
}
@article {pmid28133282,
year = {2016},
author = {Asano, Y and Kashiwagi, S and Goto, W and Takada, K and Morisaki, T and Takashima, T and Noda, S and Onoda, N and Ohsawa, M and Hirakawa, K and Ohira, M},
title = {[Pathological Complete Response Obtained by Eribulin Chemotherapy in a Case of Advanced Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {43},
number = {12},
pages = {2240-2242},
pmid = {28133282},
issn = {0385-0684},
mesh = {Adult ; Biopsy, Fine-Needle ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Female ; Furans/*therapeutic use ; Humans ; Ketones/*therapeutic use ; Lymphatic Metastasis ; Neoadjuvant Therapy ; },
abstract = {A goal for treating advanced disease is prolonging survival while maintaining a good quality of life(QOL). Eribulin chemotherapy may be suitable for this purpose. We report a case of advanced breast cancer with pathological complete response (pCR)obtained by eribulin chemotherapy. The patient was a 43-year-old woman who complained of a right mammary mass. A tumor measuring approximately 3 cm was palpated, and breast cancer was detected via ultrasound examination. Core needle biopsy indicated invasive ductal carcinoma based on histopathological findings. A metastasis to the supraclavicular lymph node was observed and was found to be malignant via fine-needle aspiration cytology. The patient was diagnosed with advanced breast cancer cT2N3M0, stage III C, Luminal B like. She underwent primary systemic therapy with 6 cycles of eribulin. The patient exhibited a clinical complete response to eribulin chemotherapy. Thereafter, a right mastectomy with level 3 axillary lymph node dissection was performed. Pathological diagnosis of the surgical specimen was pCR. At present, 3 years after surgery, the patient has no recurrence.},
}
@article {pmid28133210,
year = {2016},
author = {Tokunou, K and Yamamoto, T and Yamamoto, H and Kamei, R and Kitamura, Y and Ando, S},
title = {[A Case of Male Hereditary Breast Cancer Involving a Sentinel Lymph Node Biopsy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {43},
number = {12},
pages = {2026-2028},
pmid = {28133210},
issn = {0385-0684},
mesh = {Antineoplastic Agents, Hormonal/therapeutic use ; BRCA2 Protein/genetics ; Breast Neoplasms/drug therapy/genetics/*pathology/surgery ; Breast Neoplasms, Male/drug therapy/genetics/*pathology/surgery ; Combined Modality Therapy ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Sentinel Lymph Node Biopsy ; Tamoxifen/therapeutic use ; Treatment Outcome ; },
abstract = {We report a rare case of male hereditary breast cancer in which a sentinel lymph node biopsy was performed. A 62-yearold man was admitted to our hospital because of a palpable tumor in his right breast. Both his younger sister and daughter had had breast cancer. Genetic testing revealed a morbid mutation in the BRCA2 gene. The tumor was palpated to an elastic hard mass and had a clear border in the right DCE area. We performed a core needle biopsy and diagnosed invasive ductal carcinoma, specifically, cT1cN0cM0, cStage I hereditary breast cancer. The patient underwent mastectomy and a sentinel lymph node biopsy. Nine days later, tamoxifen therapy was initiated. There has been no sign of recurrence during the 9 months after the operation.},
}
@article {pmid28108967,
year = {2017},
author = {Inoue, M and Nakagomi, H and Nakada, H and Furuya, K and Ikegame, K and Watanabe, H and Omata, M and Oyama, T},
title = {Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {24},
number = {5},
pages = {667-672},
doi = {10.1007/s12282-017-0753-4},
pmid = {28108967},
issn = {1880-4233},
mesh = {Adult ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/drug therapy/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology/secondary ; Carcinoma, Lobular/drug therapy/mortality/*pathology/secondary ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*epidemiology/pathology/secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy/mortality/*pathology ; Peritoneal Neoplasms/*epidemiology/pathology/secondary ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Treatment Outcome ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial.<br><br>METHODS: We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor-node-metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression at the primary site between ILC and IDC. We then selected the patients in the ER[+] or PR[+]/HER2[-] subtype specifically and compared sites of recurrence, and the survival curve starting from the point of development of metastatic disease.<br><br>RESULTS: The clinical stage was significantly higher in the ILC patients than in the IDC (p&#xa0;=&#xa0;0.001). The mean (&#xb1;SD) of DFS for the ILC and IDC patients was 2.6&#xa0;&#xb1;&#xa0;0.6 and 2.4&#xa0;&#xb1;&#xa0;0.3&#xa0;years, respectively, with no significant difference (p&#xa0;=&#xa0;0.18). However, the hormone receptor status was same between both groups; the rate of HER2 positivity was significantly lower in the ILC group (0%) than in the IDC group (16.2%) (p&#xa0;=&#xa0;0.05). In ER[+] or PR[+]/HER2[-] subtype, the mean DFS for the ILC and IDC was 2.9&#xa0;&#xb1;&#xa0;0.6 and 3.1&#xa0;&#xb1;&#xa0;0.3&#xa0;years, and the median survival time after the recurrence for ILC and IDC patients was 4.2&#xa0;&#xb1;&#xa0;0.7 and 5.6&#xa0;&#xb1;&#xa0;0.7&#xa0;years, respectively, with no significant difference (p&#xa0;=&#xa0;0.77). The frequency of lung metastases was significantly lower in the ILC group (6.3%) than in the IDC group (53.7%) (p&#xa0;<&#xa0;0.01), while the frequency of peritoneal metastases was significantly higher in the ILC group (68.8%) than in the IDC group (1%) (p&#xa0;=&#xa0;0.00). Of note, the prognosis after the diagnosis of peritoneal metastases was poor, with a median survival time of 19&#xa0;&#xb1;&#xa0;9&#xa0;months and resistance to hormone therapy.<br><br>CONCLUSIONS: The extremely high rate (68.8%) of peritoneal metastases was observed in long-term follow-up for the metastatic breast cancer patients with ILC. We need to reveal the definitive feature of ILC and develop new therapeutic strategies to prevent the dissemination of ILCs.},
}
@article {pmid28104032,
year = {2017},
author = {Hong, J and Chen, XS and Wu, JY and Huang, O and Zhu, L and He, JR and Fang, Q and Chen, WG and Li, YF and Shen, KW},
title = {[Analysis of the factors influencing adjuvant chemotherapy decisions for triple negative breast cancer].},
journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]},
volume = {39},
number = {1},
pages = {39-43},
doi = {10.3760/cma.j.issn.0253-3766.2017.01.008},
pmid = {28104032},
issn = {0253-3766},
mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Ductal, Breast/*drug therapy/pathology/secondary ; Chemotherapy, Adjuvant/statistics &amp; numerical data ; Consensus ; Cyclophosphamide/administration &amp; dosage ; *Decision Making ; Docetaxel ; Epirubicin/administration &amp; dosage ; Female ; Fluorouracil/administration &amp; dosage ; Humans ; Middle Aged ; Paclitaxel/administration &amp; dosage ; Patient Care Team/statistics &amp; numerical data ; Platinum Compounds/administration &amp; dosage ; Retrospective Studies ; Taxoids/administration &amp; dosage ; Treatment Outcome ; Triple Negative Breast Neoplasms/*drug therapy/pathology ; },
abstract = {Objective: To analyze adjuvant chemotherapy decisions for triple negative breast cancer (TNBC), and explore the influencing factors in the multidisciplinary treatment (MDT) modality. Methods: A retrospective analysis was performed. The cases with invasive TNBC who underwent surgery and MDT discussion for adjuvant treatment in Ruijin Hospital, from April 2013 to June 2015, were recruited. The patients' clinicopathological characteristics were analyzed and adjuvant treatment suggestions from MDT were obtained. Here the chemotherapy decision alteration was defined as a disagreement in chemotherapy or not, or inconsistence in regimens between the attending doctor and the multidisciplinary team. Results: A total of 194 patients aged ≤70 years old were enrolled in the multidisciplinary discussion, and 187 patients (96.4%) were suggested to receive chemotherapy. When compared the opinions of the attending doctor to suggestions of the multidisciplinary team, we found that the percentage of chemotherapy decision alteration reached 22.7% (39/172), of which 94.9% (37/39) were inconsistence in chemotherapy regimens. There were 119 patients who were recommended to receive epirubicin plus cyclophosphamide (EC) followed by docetaxel (T) or weekly paclitaxel (wP) regimens. Before the announcement of results for the E1199 trial, EC-T accounted for 62.5% (55/88), and EC-wP accounted for 37.5% (33/88) for this group of patients. After that, the proportion of EC-T was decreased to 22.6% (7/31) and proportion of EC-wP increased to 77.4%(24/31) (P<0.001). In addition, a total of 20 patients were suggested to receive platinum based chemotherapy. The proportions were 9.3% in cases with invasive ductal carcinoma, and 33.3% in cases with metaplastic carcinoma, respectively (P=0.016). Conclusions: The adjuvant chemotherapy decision for TNBC patients is altered in 22.7% of the patients after MDT discussion. After the announcement of SABCS E1199 results, more patients are suggested to receive EC followed by weekly paclitaxel. There is a lack of detailed evidence for platinum based adjuvant chemotherapy for TNBC, and more patients with metaplastic carcinoma receive platinum based adjuvant chemotherapy.},
}
@article {pmid28097781,
year = {2017},
author = {Felts, JL and Zhu, J and Han, B and Smith, SJ and Truica, CI},
title = {An Analysis of Oncotype DX Recurrence Scores and Clinicopathologic Characteristics in Invasive Lobular Breast Cancer.},
journal = {The breast journal},
volume = {23},
number = {6},
pages = {677-686},
doi = {10.1111/tbj.12751},
pmid = {28097781},
issn = {1524-4741},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*mortality/pathology ; Carcinoma, Ductal, Breast/genetics/*mortality/pathology ; Carcinoma, Lobular/genetics/*mortality/pathology ; Cohort Studies ; Disease-Free Survival ; Female ; Gene Expression Profiling/economics/*methods ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Recurrence, Local/genetics/*mortality/pathology ; Neoplasm Staging ; Pennsylvania ; Registries ; Retrospective Studies ; Sensitivity and Specificity ; },
abstract = {The Oncotype DX breast cancer assay (Genomic Health, Redwood City, CA) is increasingly being used to guide treatment decisions for patients with early stage, hormone-positive, Her-2-negative breast cancer. The utility of the Oncotype DX in decision making for treatment of invasive lobular carcinoma (ILC) has not been investigated as the results reported by Genomic Health are largely in a population with invasive ductal carcinoma (IDC). The authors hypothesized that the Oncotype DX recurrence score (RS) distribution for ILC is different than that for IDC. We performed a retrospective analysis of early stage breast cancer patients treated at Penn State Cancer Institute from 2001 to 2011 and identified 102 patients with ILC. We also pulled RS data from our institution's prospective registry of consecutive patients with early stage IDC treated during the same time period. Median follow-up was 55 months. We found that the RS distribution for ILC differed significantly from that of IDC (p = 0.024). We also found a statistically significant difference in the RS distribution between the pure ILC and pleomorphic ILC subtypes (p = 0.027). The Oncotype DX RS distribution in ILC is unique, differing significantly from that in ductal carcinoma. Consequently, the clinical usefulness and cost-effectiveness of the Oncotype DX in guiding treatment for ILC should be further investigated.},
}
@article {pmid28087477,
year = {2017},
author = {Xiao, M and Xu, Q and Lou, C and Qin, Y and Ning, X and Liu, T and Zhao, X and Jia, S and Huang, Y},
title = {Overexpression of TNFAIP8 is associated with tumor aggressiveness and poor prognosis in patients with invasive ductal breast carcinoma.},
journal = {Human pathology},
volume = {62},
number = {},
pages = {40-49},
doi = {10.1016/j.humpath.2016.12.020},
pmid = {28087477},
issn = {1532-8392},
mesh = {Apoptosis Regulatory Proteins/*analysis/genetics ; Biomarkers, Tumor/*analysis/genetics ; Blotting, Western ; Breast Neoplasms/*chemistry/genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/secondary/surgery ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Logistic Models ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Odds Ratio ; Proportional Hazards Models ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Treatment Outcome ; Up-Regulation ; },
abstract = {Tumor necrosis factor α-induced protein 8 (TNFAIP8), a transcription factor nuclear factor κB-inducible, antiapoptotic and oncogenic molecule, is associated with prognosis of several human malignancies. However, the relationship between TNFAIP8 and the prognosis of the invasive ductal carcinoma (IDC) of the breast remains unclear. TNFAIP8 expression was evaluated using real-time polymerase chain reaction (PCR) and Western blot analysis in 20 fresh IDC tissues and immunohistochemical analysis in 351 paraffin-embedded IDC tissues. Real-time PCR and Western blot analysis demonstrated that both TNFAIP8 messenger RNA and protein were up-regulated in IDC tissues compared with the paired adjacent noncancerous tissues. Immunohistochemistry revealed that TNFAIP8 expression was significantly correlated with some clinicopathological factors, including axillary lymph node metastasis (P=.001), advanced TNM stage (P<.001), high histologic grade (P<.001), molecular subtype (P<.001), and postoperative recurrence (P<.001). Univariate and multivariate logistic regression analyses demonstrated that TNFAIP8 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 1.818; 95% confidence interval, 1.167-2.832; P=.008). Moreover, Kaplan-Meier analysis indicated that IDC patients with high TNFAIP8 expression had a shorter survival time than did those with low TNFAIP8 expression, and multivariate analysis indicated that TNFAIP8 was an independent prognostic factor for overall survival and disease-free survival in IDC (P=.041 and P=.020, respectively). Therefore, TNFAIP8 overexpression may contribute to tumor progression, and it may be a novel prognostic biomarker for the patients with IDC.},
}
@article {pmid28067867,
year = {2017},
author = {Taylor, RA and Fraser, M and Livingstone, J and Espiritu, SM and Thorne, H and Huang, V and Lo, W and Shiah, YJ and Yamaguchi, TN and Sliwinski, A and Horsburgh, S and Meng, A and Heisler, LE and Yu, N and Yousif, F and Papargiris, M and Lawrence, MG and Timms, L and Murphy, DG and Frydenberg, M and Hopkins, JF and Bolton, D and Clouston, D and McPherson, JD and van der Kwast, T and Boutros, PC and Risbridger, GP and Bristow, RG},
title = {Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories.},
journal = {Nature communications},
volume = {8},
number = {},
pages = {13671},
pmid = {28067867},
issn = {2041-1723},
mesh = {Aged ; BRCA2 Protein/deficiency/*genetics ; Carcinoma, Ductal/*genetics/metabolism/pathology/surgery ; DNA Mutational Analysis ; Epigenesis, Genetic ; Evolution, Molecular ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Genomic Instability ; *Germ-Line Mutation ; Heterozygote ; Humans ; Male ; Mediator Complex/*genetics/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prostate/metabolism/pathology/surgery ; Prostatectomy ; Prostatic Neoplasms/*genetics/metabolism/pathology/surgery ; Protein Isoforms/genetics/metabolism ; Retrospective Studies ; Whole Genome Sequencing ; },
abstract = {Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.},
}
@article {pmid28062852,
year = {2017},
author = {Diaz-Vera, J and Palmer, S and Hernandez-Fernaud, JR and Dornier, E and Mitchell, LE and Macpherson, I and Edwards, J and Zanivan, S and Norman, JC},
title = {A proteomic approach to identify endosomal cargoes controlling cancer invasiveness.},
journal = {Journal of cell science},
volume = {130},
number = {4},
pages = {697-711},
pmid = {28062852},
issn = {1477-9137},
support = {12935/CRUK_/Cancer Research UK/United Kingdom ; C596/A12935/CRUK_/Cancer Research UK/United Kingdom ; C596/A18277/CRUK_/Cancer Research UK/United Kingdom ; MR/P01058X/1/MRC_/Medical Research Council/United Kingdom ; C596/A17196/CRUK_/Cancer Research UK/United Kingdom ; 18277/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Amino Acids/metabolism ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Endosomes/*metabolism ; Female ; Gene Knockdown Techniques ; Humans ; Intracellular Membranes/metabolism ; Isotope Labeling ; Models, Biological ; Neoplasm Grading ; Neoplasm Invasiveness ; Neuropilin-2/metabolism ; Protein Binding ; Protein Transport ; Proteomics/*methods ; R-SNARE Proteins/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Estrogen/metabolism ; SNARE Proteins/metabolism ; Survival Analysis ; rab GTP-Binding Proteins/genetics/metabolism ; },
abstract = {We have previously shown that Rab17, a small GTPase associated with epithelial polarity, is specifically suppressed by ERK2 (also known as MAPK1) signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this, are unknown. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to a highly selective reduction in the cellular levels of a v-SNARE (Vamp8). Moreover, proteomics and immunofluorescence indicate that Vamp8 is associated with Rab17 at late endosomes. Reduced levels of Vamp8 promote transition between ductal carcinoma in situ (DCIS) and a more invasive phenotype. We developed an unbiased proteomic approach to elucidate the complement of receptors that redistributes between endosomes and the plasma membrane, and have pin-pointed neuropilin-2 (NRP2) as a key pro-invasive cargo of Rab17- and Vamp8-regulated trafficking. Indeed, reduced Rab17 or Vamp8 levels lead to increased mobilisation of NRP2-containing late endosomes and upregulated cell surface expression of NRP2. Finally, we show that NRP2 is required for the basement membrane disruption that accompanies the transition between DCIS and a more invasive phenotype.},
}
@article {pmid28041875,
year = {2017},
author = {Khan, A and Dellago, H and Terlecki-Zaniewicz, L and Karbiener, M and Weilner, S and Hildner, F and Steininger, V and Gabriel, C and Mück, C and Jansen-Dürr, P and Hacobian, A and Scheideler, M and Grillari-Voglauer, R and Schosserer, M and Grillari, J},
title = {SNEV[hPrp19/hPso4] Regulates Adipogenesis of Human Adipose Stromal Cells.},
journal = {Stem cell reports},
volume = {8},
number = {1},
pages = {21-29},
pmid = {28041875},
issn = {2213-6711},
support = {P40 OD010440/OD/NIH HHS/United States ; },
mesh = {Adipogenesis/*genetics ; Adipose Tissue/*cytology ; Animals ; Caenorhabditis elegans ; Cell Differentiation/*genetics ; DNA Damage ; DNA Repair Enzymes/*genetics/metabolism ; Gene Expression ; Gene Knockdown Techniques ; Humans ; Insulin/metabolism ; Nuclear Proteins/*genetics/metabolism ; Oxidative Stress ; PPAR gamma/metabolism ; RNA Splicing Factors/*genetics/metabolism ; Stromal Cells/*cytology/*metabolism ; },
abstract = {Aging is accompanied by loss of subcutaneous adipose tissue. This may be due to reduced differentiation capacity or deficiency in DNA damage repair (DDR) factors. Here we investigated the role of SNEV[hPrp19/hPso4], which was implicated in DDR and senescence evasion, in adipogenic differentiation of human adipose stromal cells (hASCs). We showed that SNEV is induced during adipogenesis and localized both in the nucleus and in the cytoplasm. Knockdown of SNEV perturbed adipogenic differentiation and led to accumulation of DNA damage in hASCs upon oxidative stress. In addition, we demonstrated that SNEV is required for fat deposition in Caenorhabditis elegans. Consequently, we tested other DDR factors and found that WRN is also required for adipogenesis in both models. These results demonstrate that SNEV regulates adipogenesis in hASCs and indicate that DDR capacity in general might be a pre-requisite for this process.},
}
@article {pmid29873455,
year = {2017},
author = {Mileski, M and Ayala, L and Campuzano, E and Joy, A and Ornelas, S and Ortiz, M and Saenz, J},
title = {Quality of Life Considerations During Cancer Treatment in Invasive Ductal Carcinoma Patients: A Systemic Review.},
journal = {The ABNF journal : official journal of the Association of Black Nursing Faculty in Higher Education, Inc},
volume = {28},
number = {1},
pages = {9-13},
pmid = {29873455},
issn = {1046-7041},
mesh = {Female ; Humans ; *Breast Neoplasms/psychology/therapy ; *Carcinoma, Ductal, Breast/psychology/therapy ; *Quality of Life ; },
abstract = {Breast cancer is the number two leading cause of death in women all over the world and is often associated with poor quality of life (QOL). The positive and negative QOL factors influence the overall health and well-being of those affected with invasive ductal carcinoma (IDC). This literature review was structured to identify and understand both the positive and negative QOL factors throughout breast cancer treatment, as well as post breast cancer treatment. Systemic searches were done of three databases to gather data in breast cancer treatment from 2010-2015. Results identified the positive and negative factors associated with the QOL in relation to breast cancer treatment. The most prevalent positive QOL factors included patient expectations, decreased side effects, and increased survival rate. The most prevalent negative QOL factors included treatment, specific side effects and decreased quality of life. This review may guide healthcare professionals in incorporating new practices and identifying the best regimen to improving QOL. The positive and negative QOL factors, in relation to treatment, are important because they help healthcare professionals understand how those factors impact the overall health and well-being of individuals with IDC.},
}
@article {pmid28032317,
year = {2017},
author = {Kim, GJ and Lee, JY and Choi, HG and Kim, SY and Kim, E and Shim, SH and Nam, JW and Kim, SH and Choi, H},
title = {Cinnamomulactone, a new butyrolactone from the twigs of Cinnamomum cassia and its inhibitory activity of matrix metalloproteinases.},
journal = {Archives of pharmacal research},
volume = {40},
number = {3},
pages = {304-310},
doi = {10.1007/s12272-016-0877-7},
pmid = {28032317},
issn = {1976-3786},
mesh = {4-Butyrolactone/*analogs &amp; derivatives/chemistry/pharmacology ; Arthritis, Rheumatoid/enzymology ; Cell Survival/drug effects ; Cinnamomum/*chemistry ; Dexamethasone/pharmacology ; Fibroblasts/drug effects ; Humans ; Interleukin-1beta/biosynthesis/genetics ; Matrix Metalloproteinase 1/biosynthesis/genetics ; Matrix Metalloproteinase 3/biosynthesis/genetics ; Matrix Metalloproteinase Inhibitors/chemistry/*pharmacology ; Plant Extracts/chemistry/pharmacology ; Plant Stems/chemistry ; Spectrophotometry, Ultraviolet ; Tumor Necrosis Factor-alpha/pharmacology ; },
abstract = {Cinnamomum cassia (Lauraceae) has long been used as one of the most frequently used traditional oriental medicines for the treatment of gastritis, diabetes, blood circulation disturbance and inflammatory diseases. Cinnamomulactone (1), a new butyrolactone was isolated from the twigs of C. cassia together with nine known compounds, coumarin (2), trans-cinnamic acid (3), cinnamaldehyde (4), 2-hydroxycinnamaldehyde (5), 2-methoxycinnamaldehyde (6), 2-hydroxy-cinnamyl alcohol (7), benzoic acid (8), (+)-syringaresinol (9) and phenethyl (E)-3-[4-methoxyphenyl]-2-propenoate (10). The planar structure of 1 was elucidated on the basis of spectroscopic data analysis and its configurations were determined by coupling constant ([3] J HH) analysis and a comparison with specific rotation data of related compounds on the literatures. The structures of known compounds were confirmed by the comparison of their spectroscopic data to the reported values. Compound 10 was isolated for the first time from this plant. Compounds 1, 2, 4, and 9 showed inhibitory activity against matrix metalloproteinases (MMPs) gene expression. Among them, compound 1 has been revealed to suppress the gene expression of MMP-3 and interleukin (IL)-1β as well as MMP-1 in tumor necrosis factor (TNF)-α stimulated rheumatoid arthritis synovial fibroblasts.},
}
@article {pmid28031185,
year = {2017},
author = {Zhu, L and Ding, Y and Chen, CY and Wang, L and Huo, Z and Kim, S and Sotiriou, C and Oesterreich, S and Tseng, GC},
title = {MetaDCN: meta-analysis framework for differential co-expression network detection with an application in breast cancer.},
journal = {Bioinformatics (Oxford, England)},
volume = {33},
number = {8},
pages = {1121-1129},
pmid = {28031185},
issn = {1367-4811},
support = {R01 CA190766/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*genetics ; Computational Biology/*methods ; Computer Simulation ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Genes, Neoplasm ; Humans ; Receptors, Estrogen/metabolism ; Sample Size ; },
abstract = {MOTIVATION: Gene co-expression network analysis from transcriptomic studies can elucidate gene-gene interactions and regulatory mechanisms. Differential co-expression analysis helps further detect alterations of regulatory activities in case/control comparison. Co-expression networks estimated from single transcriptomic study is often unstable and not generalizable due to cohort bias and limited sample size. With the rapid accumulation of publicly available transcriptomic studies, co-expression analysis combining multiple transcriptomic studies can provide more accurate and robust results.<br><br>RESULTS: In this paper, we propose a meta-analytic framework for detecting differentially co-expressed networks (MetaDCN). Differentially co-expressed seed modules are first detected by optimizing an energy function via simulated annealing. Basic modules sharing common pathways are merged into pathway-centric supermodules and a Cytoscape plug-in (MetaDCNExplorer) is developed to visualize and explore the findings. We applied MetaDCN to two breast cancer applications: ER+/ER- comparison using five training and three testing studies, and ILC/IDC comparison with two training and two testing studies. We identified 20 and 4 supermodules for ER+/ER- and ILC/IDC comparisons, respectively. Ranking atop are 'immune response pathway' and 'complement cascades pathway' for ER comparison, and 'extracellular matrix pathway' for ILC/IDC comparison. Without the need for prior information, the results from MetaDCN confirm existing as well as discover novel disease mechanisms in a systems manner.<br><br>R package 'MetaDCN' and Cytoscape App 'MetaDCNExplorer' are available at http://tsenglab.biostat.pitt.edu/software.htm .<br><br>CONTACT: ctseng@pitt.edu.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
}
@article {pmid28027219,
year = {2017},
author = {Myckatyn, TM and Wagner, IJ and Mehrara, BJ and Crosby, MA and Park, JE and Qaqish, BF and Moore, DT and Busch, EL and Silva, AK and Kaur, S and Ollila, DW and Lee, CN},
title = {Cancer Risk after Fat Transfer: A Multicenter Case-Cohort Study.},
journal = {Plastic and reconstructive surgery},
volume = {139},
number = {1},
pages = {11-18},
pmid = {28027219},
issn = {1529-4242},
support = {K07 CA154850/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; T32 CA009001/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/*adverse effects/*methods ; *Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*etiology ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Subcutaneous Fat/*transplantation ; },
abstract = {BACKGROUND: Fat transfer is an increasingly popular method for refining postmastectomy breast reconstructions. However, concern persists that fat transfer may promote disease recurrence. Adipocytes are derived from adipose-derived stem cells and express adipocytokines that can facilitate active breast cancer cells in laboratory models. The authors sought to evaluate the association between fat transfer to the reconstructed breast and cancer recurrence in patients diagnosed with local or regional invasive breast cancers.<br><br>METHODS: A multicenter, case-cohort study was performed. Eligible patients from four centers (Memorial Sloan Kettering, M. D. Anderson Cancer Center, Alvin J. Siteman Cancer Center, and the University of Chicago) were identified by each site's institutional tumor registry or cancer data warehouse. Eligibility criteria were as follows: mastectomy with immediate breast reconstruction between 2006 and 2011, age older than 21 years, female sex, and incident diagnosis of invasive ductal carcinoma (stage I, II, or III). Cases consisted of all recurrences during the study period, and controls consisted of a 30 percent random sample of the study population. Cox proportional hazards regression was used to evaluate for association between fat transfer and time to recurrence in bivariate and multivariate models.<br><br>RESULTS: The time to disease recurrence unadjusted hazard ratio for fat transfer was 0.99 (95 percent CI, 0.56 to 1.7). After adjustment for age, body mass index, stage, HER2/Neu receptor status, and estrogen receptor status, the hazard ratio was 0.97 (95 percent CI, 0.54 to 1.8).<br><br>CONCLUSION: In this population of breast cancer patients who had mastectomy with immediate reconstruction, fat transfer was not associated with a higher risk of cancer recurrence.<br><br>Therapeutic, III.},
}
@article {pmid28018301,
year = {2016},
author = {Li, J and Sun, L and Xu, F and Qi, H and Shen, C and Jiao, W and Xiao, J and Li, Q and Xu, B and Shen, A},
title = {Screening and Identification of APOC1 as a Novel Potential Biomarker for Differentiate of Mycoplasma pneumoniae in Children.},
journal = {Frontiers in microbiology},
volume = {7},
number = {},
pages = {1961},
pmid = {28018301},
issn = {1664-302X},
abstract = {Background: Although Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) in children, the currently used diagnostic methods are not optimal. Proteomics is increasingly being used to study the biomarkers of infectious diseases. Methods: Label-free quantitative proteomics and liquid chromatography-mass/mass spectrometry were used to analyze the fold change of protein expression in plasma of children with MP pneumonia (MPP), infectious disease control (IDC), and healthy control (HC) groups. Selected proteins that can distinguish MPP from HC and IDC were further validated by enzyme-linked immunosorbent assay (ELISA). Results: After multivariate analyses, 27 potential plasma biomarkers were identified to be expressed differently among child MPP, HC, and IDC groups. Among these proteins, SERPINA3, APOC1, ANXA6, KNTC1, and CFLAR were selected for ELISA verification. SERPINA3, APOC1, and CFLAR levels were significantly different among the three groups and the ratios were consistent with the trends of proteomics results. A comparison of MPP patients and HC showed APOC1 had the largest area under the curve (AUC) of 0.853, with 77.6% sensitivity and 81.1% specificity. When APOC1 levels were compared between MPP and IDC patients, it also showed a relatively high AUC of 0.882, with 77.6% sensitivity and 85.3% specificity. Conclusion: APOC1 is a potential biomarker for the rapid and noninvasive diagnosis of MPP in children. The present finding may offer new insights into the pathogenesis and biomarker selection of MPP in children.},
}
@article {pmid28008158,
year = {2017},
author = {Chen, QX and Li, JJ and Wang, XX and Lin, PY and Zhang, J and Song, CG and Shao, ZM},
title = {Similar outcomes between adenoid cystic carcinoma of the breast and invasive ductal carcinoma: a population-based study from the SEER 18 database.},
journal = {Oncotarget},
volume = {8},
number = {4},
pages = {6206-6215},
pmid = {28008158},
issn = {1949-2553},
mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Carcinoma, Adenoid Cystic/chemistry/mortality/secondary/*therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/secondary/*therapy ; Cell Differentiation ; Chi-Square Distribution ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Propensity Score ; Proportional Hazards Models ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/chemistry/mortality/pathology/*therapy ; United States/epidemiology ; Young Adult ; },
abstract = {Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients.},
}
@article {pmid27988039,
year = {2017},
author = {Bobbo, M and Pinamonti, B and Merlo, M and Stolfo, D and Iorio, A and Ramani, F and Barbati, G and Carriere, C and Massa, L and Poli, S and Scapol, S and Gigli, M and Di Lenarda, A and Sinagra, G},
title = {Comparison of Patient Characteristics and Course of Hypertensive Hypokinetic Cardiomyopathy Versus Idiopathic Dilated Cardiomyopathy.},
journal = {The American journal of cardiology},
volume = {119},
number = {3},
pages = {483-489},
doi = {10.1016/j.amjcard.2016.10.014},
pmid = {27988039},
issn = {1879-1913},
mesh = {Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Amiodarone/therapeutic use ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Anti-Arrhythmia Agents/therapeutic use ; Cardiomyopathies/etiology/physiopathology/therapy ; Cardiomyopathy, Dilated/*physiopathology/therapy ; Cause of Death ; Disease Progression ; Female ; Heart Failure/etiology/*physiopathology/therapy ; Heart Transplantation ; Heart-Assist Devices ; Humans ; Hypertension/complications ; Hypertrophy, Left Ventricular/etiology/*physiopathology/therapy ; Male ; Middle Aged ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Mortality ; Retrospective Studies ; Stroke Volume ; Tachycardia, Ventricular/epidemiology ; Ventricular Dysfunction, Left/etiology/*physiopathology/therapy ; Ventricular Fibrillation/epidemiology ; Ventricular Remodeling ; },
abstract = {Hypertensive hypokinetic cardiomyopathy (HHC) is defined by left ventricular (LV) systolic dysfunction with a history of systemic hypertension as the only possible cause. Although commonly encountered in clinical practice, its characterization and differences with true idiopathic dilated cardiomyopathy (IDC) are lacking. The aim of this study was to characterize the clinical instrumental features and the natural history of HHC. We analyzed the data of 4,191 patients referred to our center for newly diagnosed LV systolic dysfunction from 2005 to 2010. Of them, 310 presented idiopathic LV systolic dysfunction (LV ejection fraction <50%): 136 (44%) had a history of systemic hypertension and were defined HHC. The remaining 174 patients were considered IDC. Compared with patients with IDC, those with HHC were older (63 ± 11 vs 47 ± 14 years, p <0.001), with worse comorbidity profile, higher blood pressure, and increased LV mass. During follow-up, patients with HHC showed earlier and higher proportion of LV reverse remodeling (46% vs 21% at 6 months' follow-up). Moreover, they had a better long-term survival free from cardiovascular death/ventricular assist device/heart transplant/malignant ventricular arrhythmias (5.1 vs 12.6 in HHC and IDC, p = 0.03). Indeed, their mortality was mainly driven by noncardiovascular causes (at 10 years 9.6% vs 1.7% in HHC and IDC, p <0.001). In conclusion, HHC has a high prevalence among patients with "idiopathic" LV dysfunction. The natural history of patients with HHC is characterized by a rapid response to optimal therapy for heart failure, a favorable cardiovascular outcome, and a relevant incidence of noncardiovascular events.},
}
@article {pmid27979331,
year = {2017},
author = {Loft, A and Forss, I and Mandrup, S},
title = {Genome-Wide Insights into the Development and Function of Thermogenic Adipocytes.},
journal = {Trends in endocrinology and metabolism: TEM},
volume = {28},
number = {2},
pages = {104-120},
doi = {10.1016/j.tem.2016.11.005},
pmid = {27979331},
issn = {1879-3061},
mesh = {Adipocytes/*metabolism ; Adipogenesis/genetics/*physiology ; Adipose Tissue, Brown/metabolism ; Animals ; High-Throughput Nucleotide Sequencing ; Humans ; Thermogenesis/genetics/*physiology ; },
abstract = {Brown and brown-like adipocytes are specialized adipocytes with a high capacity to convert metabolic energy to heat. This function is not only eminent in supporting organismal thermogenesis, but may also have potential in the fight against obesity. The latter has spurred a massive interest in understanding the development and regulation of these thermogenic adipocytes. Here, we review how genome-wide studies based on next-generation sequencing have provided insight into how the chromatin and transcriptional landscapes are established in thermogenic adipocytes and how thermogenic signals can change the genomic programming of white adipocytes. Furthermore, we discuss how the integration of genomic data can be used to discover novel transcriptional pathways that may be modulated as part of therapeutic strategies for the treatment of obesity.},
}
@article {pmid27956549,
year = {2017},
author = {Morgenstern, J and Fleming, T and Schumacher, D and Eckstein, V and Freichel, M and Herzig, S and Nawroth, P},
title = {Loss of Glyoxalase 1 Induces Compensatory Mechanism to Achieve Dicarbonyl Detoxification in Mammalian Schwann Cells.},
journal = {The Journal of biological chemistry},
volume = {292},
number = {8},
pages = {3224-3238},
pmid = {27956549},
issn = {1083-351X},
mesh = {Aldehyde Reductase/*metabolism ; Animals ; Cells, Cultured ; Gene Deletion ; Gene Knockout Techniques ; Glycation End Products, Advanced/*metabolism ; Lactoylglutathione Lyase/genetics/*metabolism ; Mice ; Oxidative Stress ; Pyruvaldehyde/*metabolism ; Schwann Cells/cytology/*metabolism ; },
abstract = {The glyoxalase system is a highly specific enzyme system existing in all mammalian cells that is responsible for the detoxification of dicarbonyl species, primarily methylglyoxal (MG). It has been implicated to play an essential role in preventing the increased formation of advanced glycation end products under certain pathological conditions. We have established the first glyoxalase 1 knock-out model (GLO1[-/-]) in mammalian Schwann cells using the CRISPR/Cas9 technique to investigate compensatory mechanisms. Neither elevated concentrations of MG nor associated protein modifications were observed in GLO1[-/-] cells. Alternative detoxification of MG in GLO1[-/-] is achieved by increased catalytic efficiency of aldose reductase toward hemithioacetal (product of glutathione and MG), which is most likely caused by S-nitrosylation of aldose reductase. The hemithioacetal is mainly converted into lactaldehyde, which is paralleled by a loss of reduced glutathione. Inhibition of aldose reductase in GLO1[-/-] cells is associated with an increased sensitivity against MG, elevated intracellular MG levels, associated modifications, as well as increased oxidative stress. Our data suggest that aldose reductase can compensate for the loss of GLO1. This might be of clinical importance within the context of neuronal diseases caused by an impaired glyoxalase system and elevated levels of dicarbonyl species, such as MG.},
}
@article {pmid27928699,
year = {2017},
author = {Eaton, AA and Pesce, CE and Murphy, JO and Stempel, MM and Patil, SM and Brogi, E and Hudis, CA and El-Tamer, M},
title = {Estimating the OncotypeDX score: validation of an inexpensive estimation tool.},
journal = {Breast cancer research and treatment},
volume = {161},
number = {3},
pages = {435-441},
pmid = {27928699},
issn = {1573-7217},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Female ; Gene Expression Profiling/*methods/standards ; Genetic Testing/*methods/standards ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Reproducibility of Results ; Risk Factors ; Young Adult ; },
abstract = {BACKGROUND: OncotypeDX, a multi-gene expression assay, has been incorporated into clinical practice as a prognostic and predictive tool. However, its use in resource-constrained international healthcare systems is limited. Here we develop and validate a simplified model using clinicopathologic criteria to predict OncotypeDX score.<br><br>METHODS: Patients with estrogen receptor (ER) and/or progesterone receptor (PR)-positive and HER2-negative invasive ductal carcinoma for whom the OncotypeDX test was successfully performed between 09/2008 and 12/2011 were retrospectively identified. Tumor size, nuclear and histologic grade, lymphovascular invasion, and ER and PR status were extracted from pathology reports. Data were split into a training dataset comprising women tested 09/2008-04/2011, and a validation dataset comprising women tested 04/2011-12/2011. Using the training dataset, linear regression analysis was used to identify factors associated with OncotypeDX score, and to create a simplified risk score and identify risk cutoffs.<br><br>RESULTS: Estrogen and progesterone receptors, tumor size, nuclear and histologic grades, and lymphovascular involvement were independently associated with OncotypeDX. The full model explained 39% of the variation in the test data, and the simplified risk score and cutoffs assigned 57% of patients in the test data to the correct risk category (OncotypeDX score&#xa0;<18, 18-30, >30). 41% of patients were predicted to have OncotypeDX score&#xa0;<18, of these 83, 16, and 2% had true scores of&#xa0;<18, 18-30, and&#xa0;>30, respectively.<br><br>CONCLUSIONS: Awaiting an inexpensive test that is prognostic and predictive, our simplified tool allows clinicians to identify a fairly large group of patients (41%) with very low chance of having high-risk disease (2%).},
}
@article {pmid27924790,
year = {2017},
author = {Li, BK and Chen, BS and Xin, YH and Liu, CX and Zheng, SB and Xu, YW and Li, HL and Zou, Y and Li, LP},
title = {Can the lower urinary tract storage symptoms be completely resolved after plasmakinetic enucleation of the prostate?.},
journal = {Asian journal of andrology},
volume = {19},
number = {6},
pages = {655-658},
pmid = {27924790},
issn = {1745-7262},
mesh = {Aged ; Humans ; Lower Urinary Tract Symptoms/etiology/physiopathology/*surgery ; Male ; Middle Aged ; Prostate/physiopathology/*surgery ; Prostatic Hyperplasia/complications/physiopathology/*surgery ; Quality of Life ; Transurethral Resection of Prostate/*methods ; Treatment Outcome ; Urodynamics/physiology ; },
abstract = {The aim of this study was to determine whether the lower urinary tract storage symptoms of benign prostatic obstruction (BPO) could be completely resolved after plasmakinetic enucleation of the prostate (PKEP) and the possible predictors of persistent symptoms. Two hundred and sixty-seven cases of BPO performed PKEP from July 2008 to June 2009 were retrospectively analyzed. Five-year postoperative data were collected and compared with the preoperative data. According to the urodynamic results, the patients were divided into involuntary detrusor contraction (IDC) group (n = 95) and no IDC group (n = 172) preoperatively; the patients with IDC were divided into IDC-persistent group (n = 33) and IDC-resolved group (n = 62) after PKEP. The predictors of persistent IDC were analyzed. Compared with the preoperative data, the 5-year postoperative data showed that the IDC rate was lower (P = 0.000), Overactive Bladder Symptom Score (OABSS) was lower (P = 0.000), maximum cystometric capacity (MCC) was larger (P = 0.000), Prostate volume (PV) was smaller (P = 0.000), and prostate-specific antigen (PSA) was lower (P = 0.000). Compared with the no IDC group, the IDC group showed that the age was older (P = 0.016), MCC was smaller (P = 0.004), PSA was higher (P = 0.016), and Chronic Inflammation rate was higher (P = 0.004). Compared with IDC-resolved group after PKEP, IDC-persistent group showed that the age was older (P = 0.019), MCC was smaller (P = 0.000), PSA was higher (P = 0.013), and Chronic Inflammation rate was higher (P = 0.032). The present study shows that the storage symptoms are still needed to be focused on after PKEP. The advanced patient age, MCC, PSA, and chronic inflammation may be the important clinical predictors of persistent IDC.},
}
@article {pmid27923458,
year = {2016},
author = {Scheideler, M},
title = {MicroRNAs in adipocyte formation and obesity.},
journal = {Best practice &amp; research. Clinical endocrinology &amp; metabolism},
volume = {30},
number = {5},
pages = {653-664},
doi = {10.1016/j.beem.2016.11.009},
pmid = {27923458},
issn = {1878-1594},
mesh = {Adipocytes, Brown/cytology/*metabolism ; Animals ; Energy Metabolism ; Humans ; MicroRNAs/*genetics/metabolism ; Obesity/*genetics/metabolism ; },
abstract = {The worldwide epidemic of obesity demands novel and more effective therapeutic approaches. Fat cells are at the core of energy metabolism trying either to cope with a positive energy balance by hypertrophy and hyperplasia of energy storing white adipocytes or to counteract obesity by the induction of non-shivering thermogenesis in energy combusting brite/brown adipocytes. However, the comprehensive regulatory network of adipocyte formation remains to be elucidated. MicroRNAs are an emerging class of important regulatory determinants in many biological processes and diseases, including adipocyte formation and obesity. In this review, microRNAs governing the formation of white, brite and brown adipocytes as well as candidates with impact on obesity are overviewed, concluded with recommendations for further research that considers prerequisites for successful therapeutic applications.},
}
@article {pmid27916938,
year = {2016},
author = {Pehserl, AM and Ress, AL and Stanzer, S and Resel, M and Karbiener, M and Stadelmeyer, E and Stiegelbauer, V and Gerger, A and Mayr, C and Scheideler, M and Hutterer, GC and Bauernhofer, T and Kiesslich, T and Pichler, M},
title = {Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells.},
journal = {International journal of molecular sciences},
volume = {17},
number = {12},
pages = {},
pmid = {27916938},
issn = {1422-0067},
mesh = {Animals ; Caco-2 Cells ; Cell Cycle Checkpoints/drug effects ; Colorectal Neoplasms/*drug therapy/genetics/pathology ; Drug Resistance, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*biosynthesis/genetics ; Mutation ; Niacinamide/administration &amp; dosage/*analogs &amp; derivatives ; Phenylurea Compounds/*administration &amp; dosage ; Proto-Oncogene Proteins p21(ras)/genetics ; Sorafenib ; },
abstract = {MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720) and two small RNAs (SNORD 13 and hsa-miR-3182) were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720) were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle-arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies.},
}
@article {pmid27909910,
year = {2016},
author = {Berriel Diaz, M and Herzig, S and Schafmeier, T},
title = {Biological Mechanisms for the Effect of Obesity on Cancer Risk: Experimental Evidence.},
journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer},
volume = {208},
number = {},
pages = {219-242},
doi = {10.1007/978-3-319-42542-9_12},
pmid = {27909910},
issn = {0080-0015},
mesh = {Adipokines/*metabolism ; Adipose Tissue/*metabolism/physiopathology ; Adiposity ; Animals ; Biomarkers, Tumor/*metabolism ; Cell Transformation, Neoplastic/*metabolism/pathology ; Energy Metabolism ; Gastrointestinal Microbiome ; Humans ; Inflammation Mediators/metabolism ; Neoplasms/*etiology/metabolism/pathology ; Obesity/*complications/metabolism/physiopathology ; Risk Factors ; Signal Transduction ; },
abstract = {Multiple epidemiological studies demonstrated that overweight and obesity significantly increase the risk of several types of cancer. As the prevalence of obesity is dramatically rising, it is expected that it will represent one of the major lifestyle-associated risk factors for cancer development in the near future. Numerous recent studies expanded knowledge about key players and pathways, which are deregulated in the obese state and potentially promote cancer initiation, progression and aggressiveness via remote and local effects. These players include (but are not limited to) insulin/IGF, adipokines and inflammatory signaling molecules as well as metabolites. Nevertheless, the detailed mechanisms linking obesity and malignant transformation at the systemic, cellular and molecular level still demand further investigation. Additionally, dysfunctional molecular metabolic pathways appear to be specific for distinct cancer entities, thereby yet precluding definition of a common principle. This chapter will present an overview of the current knowledge of molecular nodes linking obesity and cancer and will briefly touch upon potential therapy options addressing metabolic cancer etiologies.},
}
@article {pmid27903648,
year = {2017},
author = {Pfaff, DH and Fleming, T and Nawroth, P and Teleman, AA},
title = {Evidence Against a Role for the Parkinsonism-associated Protein DJ-1 in Methylglyoxal Detoxification.},
journal = {The Journal of biological chemistry},
volume = {292},
number = {2},
pages = {685-690},
pmid = {27903648},
issn = {1083-351X},
support = {P40 OD018537/OD/NIH HHS/United States ; },
mesh = {Animals ; Cell Line ; Cell Survival ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Nerve Tissue Proteins/genetics/*metabolism ; Protein Deglycase DJ-1 ; Pyruvaldehyde/*pharmacokinetics/*toxicity ; },
abstract = {Methylglyoxal (MG) is a reactive metabolite that forms adducts on cysteine, lysine and arginine residues of proteins, thereby affecting their function. Methylglyoxal is detoxified by the Glyoxalase system, consisting of two enzymes, Glo1 and Glo2, that act sequentially to convert MG into d-lactate. Recently, the Parkinsonism-associated protein DJ-1 was described in vitro to have glyoxalase activity, thereby detoxifying the MG metabolite, or deglycase activity, thereby removing the adduct formed by MG on proteins. Since Drosophila is an established model system to study signaling, neurodegeneration, and metabolic regulation in vivo, we asked whether DJ-1 contributes to MG detoxification in vivo Using both DJ-1 knockdown in Drosophila cells in culture, and DJ-1β knock-out flies, we could detect no contribution of DJ-1 to survival to MG challenge or to accumulation of MG protein adducts. Furthermore, we provide data suggesting that the previously reported deglycation activity of DJ-1 can be ascribed to a TRIS buffer artifact.},
}
@article {pmid27900579,
year = {2017},
author = {Saito, R and Miki, Y and Hata, S and Ishida, T and Suzuki, T and Ohuchi, N and Sasano, H},
title = {Aryl hydrocarbon receptor induced intratumoral aromatase in breast cancer.},
journal = {Breast cancer research and treatment},
volume = {161},
number = {3},
pages = {399-407},
doi = {10.1007/s10549-016-4063-x},
pmid = {27900579},
issn = {1573-7217},
mesh = {Adult ; Aged ; Aromatase/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Estrogens/biosynthesis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Ligands ; MCF-7 Cells ; Middle Aged ; Receptors, Aryl Hydrocarbon/*metabolism ; },
abstract = {PURPOSE: Aryl hydrocarbon receptor (AhR) inhibits estrogen receptor (ER) pathway, which may suppress estrogen-dependent cell proliferation. However, the correlation between AhR stimulation and intratumoral estrogen synthesis, especially through aromatase, has not been reported to date. In the present study, we examined this correlation in breast cancer cells.<br><br>METHODS: We examined AhR and aromatase immunoreactivity in 29 patients with invasive ductal carcinoma. We performed in vitro studies using three breast carcinoma cell lines, MCF-7, T47D, and MDA-MB-231.<br><br>RESULTS: AhR stimulation induced the mRNA expression of the aromatase gene in vitro in three breast carcinoma cell lines, and increased estrogen synthesis in MCF-7 cell line. Results of microarray analysis showed that AhR-induced aromatase expression was associated with BRCA1 induction. Analysis of patients with breast cancer showed a significant positive correlation between intratumoral AhR and aromatase status. We also compared the effects of AhR stimulation on the induction of intratumoral estrogen synthesis and inhibition of the ER signaling pathway, because AhR exerts contradictory effects on estrogen action in breast carcinoma cells. AhR-induced aromatase expression persisted for a significantly longer duration than AhR-induced ER pathway inhibition. Moreover, breast carcinoma cells treated with an AhR agonist tended to show earlier cell proliferation after removing the agonist than cells not treated with the AhR agonist.<br><br>CONCLUSION: The results of the present study suggest that AhR stimulates estrogen-dependent progression of breast carcinoma by inducing aromatase expression under some conditions. These results provide new insights on the possible roles of environmental toxins in breast cancer development.},
}
@article {pmid27890770,
year = {2017},
author = {Woulfe, KC and Siomos, AK and Nguyen, H and SooHoo, M and Galambos, C and Stauffer, BL and Sucharov, C and Miyamoto, S},
title = {Fibrosis and Fibrotic Gene Expression in Pediatric and Adult Patients With Idiopathic Dilated Cardiomyopathy.},
journal = {Journal of cardiac failure},
volume = {23},
number = {4},
pages = {314-324},
pmid = {27890770},
issn = {1532-8414},
support = {R21 HL097123/HL/NHLBI NIH HHS/United States ; T35 HL007715/HL/NHLBI NIH HHS/United States ; T32 HL007171/HL/NHLBI NIH HHS/United States ; R01 HL126928/HL/NHLBI NIH HHS/United States ; R01 HL107715/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; },
mesh = {Age Factors ; Cardiomyopathy, Dilated/*complications ; Child ; Female ; Fibrosis ; Galectin 3/analysis ; Gene Expression Profiling ; *Heart Failure/etiology/metabolism/pathology ; *Heart Ventricles/metabolism/pathology ; Humans ; Interleukin-1/analysis ; Male ; Matrix Metalloproteinase 2/analysis ; MicroRNAs/*genetics ; Middle Aged ; *Myocardium/metabolism/pathology ; Signal Transduction ; Statistics as Topic ; Tissue Inhibitor of Metalloproteinases/analysis ; },
abstract = {BACKGROUND: Although fibrosis seems to be prognostic for adverse outcomes in adults with idiopathic dilated cardiomyopathy (IDC), little is known about the prevalence and development of fibrosis in pediatric IDC hearts. We hypothesized that there is less activation of fibrosis at a molecular level in pediatric IDC hearts than in failing adult hearts.<br><br>METHODS AND RESULTS: Pediatric hearts were analyzed histologically to determine the prevalence of fibrosis. Left ventricular tissue from adult and pediatric IDC hearts and adult and pediatric nonfailing (NF) hearts were subjected to quantitative reverse-transcription polymerase chain reaction to study the expression of important mRNAs that affect fibrosis. We found age-specific differences between IDC and NF hearts in the regulation of noncoding galectin-3, Corin, matrix metalloproteinase (MMP) 2, MMP-9, tissue inhibitor of metalloproteinase (TIMP) 2, and TIMP-3. We also found markers that were similarly altered in both adult and pediatric IDC hearts (interleukin-1 receptor-like 1 receptor, TIMP-1, and TIMP-4). Finally, microRNAs 29a-c were significantly decreased in the pediatric IDC patients.<br><br>CONCLUSIONS: Pediatric IDC patients demonstrate age-specific differences in the molecular pathways implicated in fibrosis in the adult heart. At the ultrastructural level the unique gene expression pattern appears to limit fibrosis in the failing pediatric heart.},
}
@article {pmid27886676,
year = {2016},
author = {Kawashima, H and Ariizumi, T and Saijo, Y and Moriyama, M and Umezu, H and Ikeda, Y and Ogose, A and Endo, N},
title = {Chromosomal rearrangements in myoepithelial carcinoma of the breast that presented as metachronic double cancer with invasive ductal carcinoma in the ipsilateral breast.},
journal = {Cancer genetics},
volume = {209},
number = {11},
pages = {501-505},
doi = {10.1016/j.cancergen.2016.10.005},
pmid = {27886676},
issn = {2210-7762},
mesh = {Breast Neoplasms/*genetics/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*genetics/radiotherapy ; *Chromosome Aberrations ; Cytogenetic Analysis ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Myoepithelioma/*genetics/radiotherapy/surgery ; Neoplasm Recurrence, Local/genetics/radiotherapy ; Neoplasms, Second Primary/genetics/radiotherapy ; },
abstract = {Myoepithelial carcinoma of the breast is an extremely rare tumor composed entirely of malignant spindle cells with myoepithelial differentiation. The majority of previously reported cases have mainly described the clinicopathological features of the disease, and few have presented cytogenetic data. We herein present the case of a 48-year-old woman who was admitted with a left-sided breast lump in the inner upper quadrant that was initially diagnosed as a myoepithelioma with potentially malignant disorder. At 12 months after resection, she complained about a newly developed solid mass in the subareolar region of the ipsilateral breast that was diagnosed as an invasive ductal carcinoma. In addition, 16 months after the initial admission, a re-growing remnant lesion recurred in the inner upper quadrant and was ultimately diagnosed as a myoepithelial carcinoma. Lymph node metastasis of the myoepithelial carcinoma was also observed in her left axillary region 11 months after local recurrence. A cytogenetic analysis showed recurring specific chromosomal alterations both in the locally recurrent and in the lymph-node metastatic lesion: 48, XX, t(5;18)(q13;q23),del(6)(q?),+14. + mar1. To our knowledge, this is the first published report of clonal chromosomal rearrangements in myoepithelial carcinoma of the breast that presented as metachronic double cancer with invasive ductal carcinoma in the ipsilateral breast.},
}
@article {pmid27866023,
year = {2017},
author = {Takagi, H and Ando, T and Umemoto, T and , },
title = {Direct and adjusted indirect comparisons of perioperative mortality after sutureless or rapid-deployment aortic valve replacement versus transcatheter aortic valve implantation.},
journal = {International journal of cardiology},
volume = {228},
number = {},
pages = {327-334},
doi = {10.1016/j.ijcard.2016.11.253},
pmid = {27866023},
issn = {1874-1754},
mesh = {Aortic Valve Stenosis/diagnostic imaging/mortality/*surgery ; Cardiac Catheterization/methods ; Female ; Humans ; Male ; *Patient Safety ; Prognosis ; Randomized Controlled Trials as Topic ; Survival Analysis ; },
abstract = {OBJECTIVES: To determine which procedure, aortic valve replacement (AVR) with a sutureless or rapid-deployment prosthesis (SL-AVR) or transcatheter aortic valve implantation (TAVI), achieves better perioperative survival for severe aortic stenosis (AS), we conducted direct-comparison meta-analyses (DC-MAs) and an adjusted indirect-comparison meta-analysis (IDC-MA).<br><br>METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through April 2016. Eligible studies were randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. We performed a DC-MA-[A] of SL-AVR versus TAVI, a DC-MA-[B] of SL-AVR versus conventional AVR (C-AVR), and a DC-MA-[C] TAVI versus C-AVR. Then, we computed a IDC-MA-[A'] of TAVI versus SL-AVR from the results of the DC-MA-[B] and the DC-MA-[C].<br><br>RESULTS: We identified 6 RCTs and 30 PSM studies enrolling a total of 15,887 patients. The 3 DC-MAs demonstrated significantly lower perioperative (30-day or in-hospital) all-cause mortality after SL-AVR than after TAVI (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.28 to 0.80; p=0.005) and no significant differences between SL-AVR and C-AVR (OR, 1.07; 95% CI, 0.60 to 1.94; p=0.81) and between TAVI and C-AVR (1.07; 95% CI, 0.90 to 1.27; p=0.45). The computed IDC-MA-[A'] indicated no significant difference in mortality between SL-AVR and TAVI (1.01; 95% CI, 0.54 to 1.86). Combining the results of the DC-MA-[A] and IDC-MA [A'] showed significantly lower mortality after SL-AVR than after TAVI (OR, 0.65; 95% CI, 0.44 to 0.97; p=0.03).<br><br>CONCLUSIONS: For patients with severe AS, SL-AVR may achieve better perioperative survival than TAVI.},
}
@article {pmid27864119,
year = {2017},
author = {Dai, H and Gallagher, D and Schmitt, S and Pessetto, ZY and Fan, F and Godwin, AK and Tawfik, O},
title = {Role of miR-139 as a surrogate marker for tumor aggression in breast cancer.},
journal = {Human pathology},
volume = {61},
number = {},
pages = {68-77},
doi = {10.1016/j.humpath.2016.11.001},
pmid = {27864119},
issn = {1532-8392},
mesh = {Biomarkers, Tumor/classification/*genetics ; Biopsy ; Breast Neoplasms/blood/*genetics/mortality/pathology ; Carcinoma, Ductal, Breast/blood/*genetics/mortality/pathology ; Cell Proliferation ; Disease Progression ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; MicroRNAs/blood/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Phenotype ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Survival Analysis ; Tumor Burden ; },
abstract = {MicroRNAs are non-protein coding molecules that play a key role in oncogenesis, tumor progression, and metastasis in many types of malignancies including breast cancer. In the current study, we studied the expression of microRNA-139-5p (miR-139) in invasive ductal carcinoma (IDC) of the breast and correlated its expression with tumor grade, molecular subtype, hormonal status, human epidermal growth factor receptor 2 status, proliferation index, tumor size, lymph node status, patient's age, and overall survival in 74 IDC cases. In addition, we compared and correlated miR-139 expression in 18 paired serum and tissue samples from patients with IDC to assess its value as a serum marker. Our data showed that miR-139 was down-regulated in all tumor tissue samples compared with control. More pronounced down-regulation was seen in tumors that were higher grade, estrogen receptor negative, progesterone receptor negative, more proliferative, or larger in size (P < .05). Although not statistically significant, lower miR-139 level was frequently associated with human epidermal growth factor receptor 2 overexpression. In addition, significantly lower miR-139 tissue level was seen in patients who were deceased (P = .027), although older age (>50 years) and positive local nodal disease did not adversely affect miR-139 expression. In contrast, serum miR-139 profile of the patients appeared similar to that of normal control. In conclusion, our study demonstrated that down-regulation of miR-139 was associated with aggressive tumor behavior and disease progression in breast cancer. miR-139 may serve as a risk assessment biomarker in tailoring treatment options.},
}
@article {pmid27862063,
year = {2016},
author = {Tasharrofi, B and Soudyab, M and Nikpayam, E and Iranpour, M and Mirfakhraie, R and Sarrafzadeh, S and Geranpayeh, L and Azargashb, E and Sayad, A and Ghafouri-Fard, S},
title = {Comparative expression analysis of hypoxia-inducible factor-alpha and its natural occurring antisense in breast cancer tissues and adjacent noncancerous tissues.},
journal = {Cell biochemistry and function},
volume = {34},
number = {8},
pages = {572-578},
doi = {10.1002/cbf.3230},
pmid = {27862063},
issn = {1099-0844},
mesh = {Adolescent ; Adult ; Breast Neoplasms/*genetics ; Child ; Demography ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism ; Middle Aged ; RNA, Antisense/*genetics/metabolism ; },
abstract = {Hypoxia-inducible factors (HIFs) have been shown to be upregulated in tumor tissues and linked with tumor progression and metastasis in breast cancer. Among regulatory mechanisms for HIF expression is a natural occurring antisense named aHIF, which has been shown to be overexpressed in breast cancer and influence the level of the HIF-1α transcript. In the present study, we analyzed the expression of HIF-1α and aHIF in breast cancer tissues versus adjacent noncancer tissues (ANCTs) in relation with the clinical and biological behavior of the tumors. aHIF has been shown to be expressed in 67.4% of invasive ductal carcinoma samples, while none of ANCTs showed its expression. HIF-1α has been expressed in all of tumors and 90% of ANCTs. Comparison of HIF-1α expression level between tumor and ANCT tissues showed a total upregulation in tumor samples. No statistically significant association has been found between the level of HIF-1α expression in tumor samples and clinicopathologic and demographic characteristics such as age, tumor size, estrogen receptor status, progesterone receptor status, HER2/neu expression level, lymph node status, histological grade, and stage except for a weak correlation between HIF-1α expression and Ki-67 status. Besides, we could not detect any significant correlation between relative expression of HIF-1α and aHIF in tumor samples. Collectively, these data suggest that aHIF overexpression can be used as a potential biomarker in breast cancer. However, further studies are needed for the evaluation of its mechanism of action in regulation of HIF-1α expression in different pathological conditions. HIF-1α overexpression results in the upregulation of several genes that participated in cancer-associated pathways such as proliferation, angiogenesis, and glucose metabolism. We showed that HIF-1α is upregulated in breast tumor samples compared with adjacent noncancerous tissues. Its expression has been associated with Ki-67 status. Its natural occurring antisense is only expressed in tumor tissues. Thus, it can be used as a potential biomarker in breast cancer.},
}
@article {pmid27861897,
year = {2017},
author = {Casasent, AK and Edgerton, M and Navin, NE},
title = {Genome evolution in ductal carcinoma in situ: invasion of the clones.},
journal = {The Journal of pathology},
volume = {241},
number = {2},
pages = {208-218},
pmid = {27861897},
issn = {1096-9896},
support = {R01 CA169244/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma in Situ/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics ; Disease Progression ; Female ; *Genomics ; Humans ; },
abstract = {Ductal carcinoma in situ (DCIS) is the most frequently diagnosed early-stage breast cancer. Only a subset of patients progress to invasive ductal carcinoma (IDC), and this presents a formidable clinical challenge for determining which patients to treat aggressively and which patients to monitor without therapeutic intervention. Understanding the molecular and genomic basis of invasion has been difficult to study in DCIS cancers due to several technical obstacles, including low tumour cellularity, lack of fresh-frozen tissues, and intratumour heterogeneity. In this review, we discuss the role of intratumour heterogeneity in the progression of DCIS to IDC in the context of three evolutionary models: independent lineages, evolutionary bottlenecks, and multiclonal invasion. We examine the evidence in support of these models and their relevance to the diagnosis and treatment of patients with DCIS. We also discuss how emerging technologies, such as single-cell sequencing, STAR-FISH, and imaging mass spectrometry, are likely to provide new insights into the evolution of this enigmatic disease. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.},
}
@article {pmid27856072,
year = {2017},
author = {Gesser-Edelsburg, A and Walter, N and Shir-Raz, Y and Sassoni Bar-Lev, O and Rosenblat, S},
title = {The behind-the-scenes activity of parental decision-making discourse regarding childhood vaccination.},
journal = {American journal of infection control},
volume = {45},
number = {3},
pages = {267-271},
doi = {10.1016/j.ajic.2016.10.009},
pmid = {27856072},
issn = {1527-3296},
mesh = {Adult ; Attitude to Health ; *Decision Making ; Female ; Humans ; Male ; Medication Adherence/*psychology ; Middle Aged ; Parents/*psychology ; *Patient Acceptance of Health Care ; Surveys and Questionnaires ; Vaccination/*psychology ; },
abstract = {BACKGROUND: Vaccine compliance has long been a cause for concern for health authorities throughout the world. However very little effort has been made to examine parental discourse during the decision-making process.<br><br>METHODS: An online survey was conducted (N&#x2009;=&#x2009;437) to examine predictors of parents' attitudes regarding childhood vaccination.<br><br>RESULTS: Hesitant parents were 4 times more likely to conduct intrafamily discussion regarding vaccination compared with provaccination parents (Exp[B]&#x2009;=&#x2009;4.26). There were no significant differences between hesitant and antivaccination parents with respect to intrafamily discussion. Hesitant parents were also 4 times more likely than provaccination parents to report intrafamily disagreements regarding vaccination (Exp[B]&#x2009;=&#x2009;4.27). They were also twice as likely as antivaccination parents to express disagreements regarding vaccination within their families (Exp[B]&#x2009;=&#x2009;2.33). Likewise, Jewish parents were significantly more likely to define themselves as vaccination-hesitant, whereas Muslim parents were significantly more likely to be provaccination.<br><br>CONCLUSIONS: To improve the way health organizations communicate information about vaccines and increase parental trust in immunization programs, we should not only look at the level of understanding, perceptions, and biases of different groups, but also thoroughly examine parents' decision-making processes and the discourse during this process. We must communicate risk to all groups, including the provaccination group, to improve parents' decision making and the process of informed consent.},
}
@article {pmid27847402,
year = {2016},
author = {Dyachenko, L and Havrysh, K and Lytovchenko, A and Dosenko, I and Antoniuk, S and Filonenko, V and Kiyamova, R},
title = {Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades.},
journal = {Disease markers},
volume = {2016},
number = {},
pages = {5128720},
pmid = {27847402},
issn = {1875-8630},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/*blood/genetics/immunology ; Autoantibodies/*blood ; Base Sequence ; Biomarkers, Tumor/*blood/immunology ; Breast Neoplasms/blood/*immunology/pathology ; Carcinoma, Ductal, Breast/blood/immunology/pathology ; Carcinoma, Lobular/blood/immunology/pathology ; Carcinoma, Medullary/blood/immunology/pathology ; Case-Control Studies ; DNA-Binding Proteins/*blood/genetics/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Gene Library ; Humans ; Middle Aged ; Molecular Chaperones ; Neoplasm Grading ; Neoplasm Staging ; Nuclear Pore Complex Proteins/blood/genetics/immunology ; Oncogene Proteins/*blood/genetics/immunology ; Prognosis ; RNA-Binding Proteins/blood/genetics/immunology ; Young Adult ; },
abstract = {Purpose. To investigate a frequency of antibody response to SEREX-identified medullary breast carcinoma autoantigens ZRF1 and KRR1 in sera of breast cancer patients taking into account clinical and molecular characteristics of tumors for opening of new perspectives in creation of minimally invasive immunological tests for cancer diagnostics. Methods. Enzyme-linked immunosorbent assay and bioinformatics analysis. Results. Increased frequency of antibody response was found in sera of breast cancer patients to ZRF and KRR1 antigens. The antibody response to these antigens was higher in sera of patients with invasive ductal carcinoma than in sera of patients with other histological types of breast tumors. Moreover, more frequent antibody response to ZRF antigen was found in sera of patients with less aggressive tumors. The sequence analysis of ZRF1 antigen SEREX clones obtained from cDNA libraries of different tumors demonstrates that they encode different protein isoforms. Conclusion. Tumor-associated antigens KRR1 and ZRF1 and their cognate autoantibodies could be considered as potential molecular markers of breast cancer which need to be further investigated.},
}
@article {pmid27842678,
year = {2016},
author = {Seithe, T and Braun, J and Wolf, M and Vahldiek, J and Wolny, D and Auer, J and Pociej, J and Heine, O and Hamm, B and de Bucourt, M},
title = {Diagnostic efficacy and safety of gadoteric acid MR mammography in 1537 patients.},
journal = {European journal of radiology},
volume = {85},
number = {12},
pages = {2281-2287},
doi = {10.1016/j.ejrad.2016.10.013},
pmid = {27842678},
issn = {1872-7727},
mesh = {Administration, Intravenous ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/*diagnostic imaging ; Breast Neoplasms/diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging ; *Contrast Media/administration &amp; dosage/adverse effects ; Deglutition Disorders/chemically induced ; Early Detection of Cancer ; Exanthema/chemically induced ; Female ; Humans ; Image Enhancement/methods ; Magnetic Resonance Imaging/*methods ; Male ; *Meglumine/administration &amp; dosage/adverse effects ; Middle Aged ; *Organometallic Compounds/administration &amp; dosage/adverse effects ; Product Surveillance, Postmarketing ; Safety ; Tachycardia/chemically induced ; Urticaria/chemically induced ; Young Adult ; },
abstract = {OBJECTIVES: To perform a large-scale multicenter post-marketing surveillance study for analyzing diagnostic effectiveness and safety of intravenous (IV) gadoteric acid (Dotarem[®]) in magnetic resonance (MR) mammography under daily practice conditions.<br><br>MATERIALS AND METHODS: Patients underwent high-resolution MR mammography with gadoteric acid in 15 German centers. Radiologists used a standardized questionnaire to report data including patient demographics and medical history, characteristics of MR examination and results in terms of diagnosis and safety for the patient.<br><br>RESULTS: A total of 1537 patients were examined. In 99.2% of all patients, a diagnosis was established. In 91.6% of all patients, image quality was excellent or good. Histopathological examinations were performed for 232 of 1537 patients (15.1%) with invasive ductal carcinoma being the most frequent diagnosis (109 patients, 47.0%). Based on histopathology as the standard of reference, IV gadoteric acid-enhanced MR mammography confirmed diagnoses of invasive ductal carcinoma in 93.5% of the patients. Adverse drug reactions occurred in 5 of 1537 patients (0.3%) and were classified as serious in one case (tachycardia, dysphagia, urticaria, rash). All patients with adverse drug reactions fully recovered after the examination.<br><br>CONCLUSION: This noninterventional surveillance study shows IV gadoteric acid to be a safe and effective contrast agent for use in MR mammography.},
}
@article {pmid27840910,
year = {2016},
author = {Gomulkiewicz, A and Jablonska, K and Pula, B and Grzegrzolka, J and Borska, S and Podhorska-Okolow, M and Wojnar, A and Rys, J and Ambicka, A and Ugorski, M and Zabel, M and Dziegiel, P},
title = {Expression of metallothionein 3 in ductal breast cancer.},
journal = {International journal of oncology},
volume = {49},
number = {6},
pages = {2487-2497},
doi = {10.3892/ijo.2016.3759},
pmid = {27840910},
issn = {1791-2423},
mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Female ; Fibrocystic Breast Disease/*pathology ; Humans ; Immunohistochemistry ; MCF-7 Cells ; Metallothionein 3 ; Middle Aged ; Nerve Tissue Proteins/biosynthesis/genetics/*metabolism ; Real-Time Polymerase Chain Reaction ; },
abstract = {Metallothionein 3 (MT-3) has the ability to regulate the growth of nerve cells, but the significance of MT-3 expression outside the central nervous system and its participation in carcinogenesis have not yet been clarified. The aim of our study was to investigate the expression of MT-3 in ductal breast cancer and to determine its relationship with well-defined clinicopathological factors in this type of tumor. The study was conducted on 134 cases of invasive ductal breast carcinoma (IDC), 42 samples of non-malignant breast tissue (NMBT), and 26 cases of mastopathy. Moreover, selected breast cancer cell lines (MCF-7, SKBR-3, MDA-MB-231, BO2) and normal human breast epithelial cells (hTERT-HME1) were used. The expression of MT-3 was examined on the protein level using immunohistochemistry and on the mRNA level using real-time PCR. It was shown that the MT-3 protein in cells of IDC and mastopathy appeared in the cytoplasm as well as in the cell nuclei. Both the cytoplasmic and nuclear expression of MT-3 was significantly lower in IDC than in the mastopathies (p<0.0001 and p<0.001). However, no significant correlation was demonstrated between the level of MT-3 protein and the studied clinicopathological factors. The mRNA expression of MT-3 in IDC was also lower than in non‑malignant breast tissue (p<0.0001). Furthermore, in the cases of IDC with lymph node metastasis, the level of MT-3 mRNA was significantly lower than in the cases without metastasis (p=0.0199). The expression of MT-3 mRNA in breast cancer cell lines was significantly lower than in the normal human breast epithelial cell line (p<0.001). These results suggest that MT-3 may play a role in the malignant transformation of breast epithelial cells and in tumor progression.},
}
@article {pmid27837608,
year = {2016},
author = {Panagiotopoulos, N and Lagoudianakis, E and Pappas, A and Filis, K and Salemis, N and Manouras, A and Kontzoglou, K and Zografos, G},
title = {Lymphovascular infiltration in the tumor bed is a useful marker of biological behavior in breast cancer.},
journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology},
volume = {21},
number = {5},
pages = {1082-1089},
pmid = {27837608},
issn = {1107-0625},
mesh = {Aged ; Biomarkers, Tumor/analysis ; Blood Vessels/chemistry/*pathology ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Lymphatic Vessels/chemistry/*pathology ; Mastectomy ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Proportional Hazards Models ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Burden ; },
abstract = {PURPOSE: Tumor cells can metastasize by entering existing vessels or new vessels actively recruited into the primary tumor. Invasion of the lymphatics and blood vessels in the periphery of the tumor seems to be a prerequisite step in the metastatic process. The aim of this study was to correlate peripheral lymphatic vessel infiltration (PLI) and peripheral blood vessel infiltration (PVI) in a cohort of patients with invasive ductal carcinoma of the breast with various other prognostic parameters and outcome.<br><br>METHODS: The study population consisted of 236 female patients with invasive ductal breast carcinomas, who had been operated between 2011 and 2013. The registered data included age at diagnosis, histological subtype, tumor size, TNM stage, histological grade, estrogen (ER) and progesterone receptors (PR), HER-2, p53, and PLI and PVI.<br><br>RESULTS: Pathological examination revealed that 22.5% of the patients had PVI and 37.3% had PLI at the tumor front. PVI correlated with younger age (p<0.05), higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05), higher N stage (p<0.05) and positive Ki67 expression (p<0.05). Similarly, PLI correlated with higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05) and higher N stage (p<0.05). Statistical analysis did not reveal significant correlation between the presence of tumor blood and lymphatic vessels with infiltration in overall (OS) and disease-free survival (DFS).<br><br>CONCLUSIONS: PLI and PVI are important markers of worse clinical outcome as shown by their association with other established factors, but no association with recurrence and survival could be proven.},
}
@article {pmid27837296,
year = {2017},
author = {Timbrell, S and Al-Himdani, S and Shaw, O and Tan, K and Morris, J and Bundred, N},
title = {Comparison of Local Recurrence After Simple and Skin-Sparing Mastectomy Performed in Patients with Ductal Carcinoma In Situ.},
journal = {Annals of surgical oncology},
volume = {24},
number = {4},
pages = {1071-1076},
pmid = {27837296},
issn = {1534-4681},
mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*surgery ; Carcinoma, Intraductal, Noninfiltrating/*surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Margins of Excision ; Mastectomy, Simple/*methods ; Middle Aged ; *Neoplasm Recurrence, Local/etiology ; Neoplasm, Residual ; Organ Sparing Treatments ; Retrospective Studies ; Risk Factors ; },
abstract = {BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) is increasing with the use of screening mammography, and approximately 30% of all women diagnosed with DCIS are treated by mastectomy. There is increasing use of a skin-sparing mastectomy (SSM) approach to surgically excise DCIS as this facilitates immediate breast reconstruction. The rates of locoregional recurrence (LRR) after simple mastectomy performed for pure DCIS are historically reported as 1%; however, international data suggest that LRR after SSM may be higher.<br><br>METHODS: To determine our rates of LRR and compare the effect of the type of mastectomy performed, we undertook a retrospective review of all patients who underwent a mastectomy for pure DCIS at our institution between 2000 and 2010.<br><br>RESULTS: In total, 199 patients underwent a mastectomy for pure DCIS (with eight local recurrences), all of which were invasive ductal carcinoma. The recurrences all occurred after SSM, which was associated with a higher 5-year LRR of 5.9% (5/102) compared with 0% in the simple mastectomy group (0/97; p&#xa0;=&#xa0;0.012), log-rank. Univariate analysis showed the two factors that predicted the risk of recurrence were a young age at mastectomy and close or involved margins.<br><br>CONCLUSIONS: These data highlight the importance of achieving clear margins, especially in young women with estrogen receptor-negative DCIS who have a higher risk of invasive recurrence. Women undergoing a mastectomy for DCIS should be counseled as to the importance of achieving clear margins and the potential increased need for further excision, post-mastectomy radiotherapy and post-reconstruction mammography in order to prevent LRR after SSM.},
}
@article {pmid27835573,
year = {2016},
author = {Sang, J and Yi, D and Tang, X and Zhang, Y and Huang, T},
title = {The associations between mast cell infiltration, clinical features and molecular types of invasive breast cancer.},
journal = {Oncotarget},
volume = {7},
number = {49},
pages = {81661-81669},
pmid = {27835573},
issn = {1949-2553},
mesh = {Age Factors ; Breast Neoplasms/chemistry/classification/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/classification/*pathology/therapy ; Carcinoma, Lobular/chemistry/*pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Lymphatic Metastasis ; Mast Cells/chemistry/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Risk Factors ; Tumor Burden ; },
abstract = {Associations between mast cell infiltration and the clinical features and known molecular profile of breast cancer remain unclear. The distribution difference of mast cell was evaluated, in 219 patients with no special type of invasive carcinoma, using sorts of age, max diameter of cancer, histological type, lymph node metastasis as well as the expressions of estrogen receptor (ER), progestogen receptor (PR), human epidermal growth factor receptor 2 (HER-2) and nuclear protein Ki67. The mast cell density (MCD) in patients younger than 50 years old was significantly higher than that in patients with age ≥ 50. The MCD in ER or PR positive patients was significantly higher than MCD in ER or PR negative patients. The MCD in patients with Ki67 ≤ 14% was also significantly higher than MDC in patients with Ki67 > 14%. The MCD of patients with invasive ductal carcinoma was significantly higher than MCD of patients with invasive lobular carcinoma. No significant distribution difference of MCD was found to be associated with max diameter of cancer, lymph node metastasis and HER-2. Further analysis found that MDC was significantly higher in patients after neo-adjuvant chemotherapy. The distribution difference of mast cell widely exists in patients with distinct clinical features, the role of mast cell in breast cancer need further research with detailed and reasonable classification to clarify.},
}
@article {pmid27827363,
year = {2016},
author = {Ekim Üstünel, B and Friedrich, K and Maida, A and Wang, X and Krones-Herzig, A and Seibert, O and Sommerfeld, A and Jones, A and Sijmonsma, TP and Sticht, C and Gretz, N and Fleming, T and Nawroth, PP and Stremmel, W and Rose, AJ and Berriel-Diaz, M and Blüher, M and Herzig, S},
title = {Control of diabetic hyperglycaemia and insulin resistance through TSC22D4.},
journal = {Nature communications},
volume = {7},
number = {},
pages = {13267},
pmid = {27827363},
issn = {2041-1723},
mesh = {Animals ; Blood Glucose/*metabolism ; Cell Line ; Diabetes Mellitus, Type 2/blood/*genetics ; Female ; Gene Expression Regulation ; Humans ; Hyperglycemia/blood/*genetics ; Insulin Resistance/*genetics ; Lipocalins/genetics/metabolism ; Liver/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Transcription Factors/*genetics/metabolism ; },
abstract = {Obesity-related insulin resistance represents the core component of the metabolic syndrome, promoting glucose intolerance, pancreatic beta cell failure and type 2 diabetes. Efficient and safe insulin sensitization and glucose control remain critical therapeutic aims to prevent diabetic late complications Here, we identify transforming growth factor beta-like stimulated clone (TSC) 22 D4 as a molecular determinant of insulin signalling and glucose handling. Hepatic TSC22D4 inhibition both prevents and reverses hyperglycaemia, glucose intolerance and insulin resistance in diabetes mouse models. TSC22D4 exerts its effects on systemic glucose homeostasis-at least in part-through the direct transcriptional regulation of the small secretory protein lipocalin 13 (LCN13). Human diabetic patients display elevated hepatic TSC22D4 expression, which correlates with decreased insulin sensitivity, hyperglycaemia and LCN13 serum levels. Our results establish TSC22D4 as a checkpoint in systemic glucose metabolism in both mice and humans, and propose TSC22D4 inhibition as an insulin sensitizing option in diabetes therapy.},
}
@article {pmid27825140,
year = {2017},
author = {Lu, DG and Ma, YM and Zhu, AJ and Han, YW},
title = {An early biomarker and potential therapeutic target of RUNX 3 hypermethylation in breast cancer, a system review and meta-analysis.},
journal = {Oncotarget},
volume = {8},
number = {13},
pages = {22166-22174},
pmid = {27825140},
issn = {1949-2553},
mesh = {Animals ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/*genetics ; Core Binding Factor Alpha 3 Subunit/*genetics ; *DNA Methylation ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; },
abstract = {Runt-related transcription factor 3 (RUNX3) methylation plays an important role in the carcinogenesis of breast cancer (BC). However, the association between RUNX3 hypermethylation and significance of BC remains under investigation. The purpose of this study is to perform a meta-analysis and literature review to evaluate the clinicopathological significance of RUNX3 hypermethylation in BC. A comprehensive literature search was performed in Medline, Web of Science, EMBASE, Cochrane Library Database, CNKI and Google scholar. A total of 10 studies and 747 patients were included for the meta-analysis. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were evaluated and summarized respectively. RUNX3 hypermethylation was significantly correlated with the risk of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), OR was 50.37, p < 0.00001 and 22.66, p < 0.00001 respectively. Interestingly, the frequency of RUNX3 hypermethylation increased in estrogen receptor (ER) positive BC, OR was 12.12, p = 0.005. High RUNX3 mRNA expression was strongly associated with better relapse-free survival (RFS) in BC patients. In summary, RUNX3 methylation could be a promising early biomarker for the diagnosis of BC. High RUNX3 mRNA expression is correlated to better RFS in BC patients. RUNX3 could be a potential therapeutic target for the development of personalized therapy.},
}
@article {pmid27822759,
year = {2016},
author = {Autenshlyus, AI and Kunts, TA and Karpukhina, KV and Mikhaylova, ES and Varaksin, NA and Marinkin, IO and Lyakhovich, VV},
title = {Cytokine pattern of the breast tumor supernatant.},
journal = {Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections},
volume = {470},
number = {1},
pages = {247-248},
pmid = {27822759},
issn = {1608-3105},
mesh = {Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Cell Fractionation ; Cytokines/*immunology ; Female ; Fibroadenoma/*immunology ; Humans ; Inflammation Mediators/*immunology ; Tumor Cells, Cultured ; Tumor Microenvironment/*immunology ; },
abstract = {Cytokine production was evaluated in supernatants of cultured tumor cells that were obtained by biopsy of the breast invasive ductal carcinoma (IDC) and breast fibroadenoma (FA) and grown in vitro. In the IDC supernatants, the concentrations of pro-inflammatory (pro-oncogenic) cytokines IL-17, IL-18, and IFNγ and of IL-1 receptor antagonist were significantly higher than in the FA cell supernatants. The concentrations of anti-inflammatory cytokine IL-10 and MCP-1 protein in supernatants of IDC cells were significantly lower than those determined in FA supernatants.},
}
@article {pmid27613186,
year = {2016},
author = {Ilahi, NE and Anwar, S and Noreen, M and Hashmi, SN and Murad, S},
title = {Detection of human papillomavirus-16 DNA in archived clinical samples of breast and lung cancer patients from North Pakistan.},
journal = {Journal of cancer research and clinical oncology},
volume = {142},
number = {12},
pages = {2497-2502},
pmid = {27613186},
issn = {1432-1335},
mesh = {Adult ; Aged ; Breast Neoplasms/complications/epidemiology/*virology ; DNA, Viral/*isolation &amp; purification ; Female ; Human papillomavirus 16/genetics/*isolation &amp; purification ; Humans ; Lung Neoplasms/complications/epidemiology/*virology ; Middle Aged ; Pakistan/epidemiology ; Papillomavirus Infections/*complications/epidemiology/genetics ; Prevalence ; Registries ; Retrospective Studies ; },
abstract = {PURPOSE: Over the past few decades, human papillomavirus (HPV) has been recorded as a key player in the development of various genital cancers, most notably cervical cancer. It has also been associated with some non-genital cancers. A subset of oropharyngeal cancers are known to be caused by HPV. Its aetiological involvement has been suggested for breast and lung cancer as well. However, reports regarding the HPV DNA detection vary widely from different parts of the world. Due to scarcity of local data in this regard, the current study aimed at retrospective detection of HPV presence in the archival samples of breast and lung cancer patients from north part of the country.<br><br>METHODS: A total of 55 formalin-fixed paraffin-embedded tissue sections of invasive ductal carcinoma of breast&#xa0;(n&#xa0;=&#xa0;46) and lung (n&#xa0;=&#xa0;9) were collected for this study. Genotyping for HPV16 and 18 was carried out through PCR.<br><br>RESULTS: HPV16 DNA was found in both breast and lung carcinoma samples with the prevalence rate of 17 and 11&#xa0;%, respectively. An interesting association&#xa0;was found between ER/PR (Oestrogen/Progesterone receptor) and HER2/Neu (Human epidermal growth factor receptor-2) positivity with HPV occurrence in breast tumours.<br><br>CONCLUSION: Current study shows the presence of HPV16 DNA in archived clinical biopsy sections from breast and lung cancers (17, 11&#xa0;%), respectively. A positive correlation of HPV16 presence was found with ER/PR and HER2-positive breast cancers. These initial findings warrant further investigation in order to determine HPV prevalence and aetiological role in local cancers, especially in ER/PR/HER2-positive breast cancers on a larger scale.},
}
@article {pmid27785066,
year = {2016},
author = {Meng, L and Xu, Y and Xu, C and Zhang, W},
title = {Biomarker discovery to improve prediction of breast cancer survival: using gene expression profiling, meta-analysis, and tissue validation.},
journal = {OncoTargets and therapy},
volume = {9},
number = {},
pages = {6177-6185},
pmid = {27785066},
issn = {1178-6930},
abstract = {PURPOSE: Breast cancer is the leading cause of cancer death worldwide in women. The molecular mechanism for human breast cancer is unknown. Gene microarray has been widely used in breast cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis survival. So far, the valuable multigene signatures in clinical practice are unclear, and the biological importance of individual genes is difficult to detect, as the described signatures virtually do not overlap. Early prognosis of this disease, breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS), is vital in breast surgery.<br><br>METHODS: Thus, this study reports gene expression profiling in large breast cancer cohorts from Gene Expression Omnibus, including GSE29044 (N=138) and GSE10780 (N=185) test series and four independent validation series GSE21653 (N=266), GSE20685 (N=327), GSE26971 (N=276), and GSE12776 (N=204). Significantly differentially expressed genes in human breast IDC and breast DCIS were detected by transcriptome microarray analysis.<br><br>RESULTS: We created a set of three genes (MAMDC2, TSHZ2, and CLDN11) that were significantly correlated with disease-free survival of breast cancer patients using a univariate Cox regression model (significance level P<0.01) in a meta-analysis. Based on the risk score of the three genes, the test series patients could be separated into low-risk and high-risk groups with significantly different survival times. This signature was validated in the other three cohorts. The prognostic value of this three-gene signature was confirmed in the internal validation series and another four independent breast cancer data sets. The prognostic impact of one of the three genes, CLDN11, was confirmed by immunohistochemistry. CLDN11 was significantly overexpressed in human breast IDC as compared with normal breast tissues and breast DCIS.<br><br>CONCLUSION: Using novel gene expression profiling together with a meta-analysis validation approach, we have identified a three-gene signature with independent prognostic impact. Furthermore, CLDN11 may offer a biomarker to predict prognosis as well as a new target for prognostic and therapeutic intervention for human breast IDC.},
}
@article {pmid26642960,
year = {2016},
author = {Endo, Y and Dong, Y and Kondo, N and Yoshimoto, N and Asano, T and Hato, Y and Nishimoto, M and Kato, H and Takahashi, S and Nakanishi, R and Toyama, T},
title = {HER2 mutation status in Japanese HER2-positive breast cancer patients.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {23},
number = {6},
pages = {902-907},
doi = {10.1007/s12282-015-0659-y},
pmid = {26642960},
issn = {1880-4233},
mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Asian People/genetics ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*drug therapy/*genetics/pathology ; Female ; Humans ; Middle Aged ; *Mutation ; Receptor, ErbB-2/antagonists &amp; inhibitors/*genetics/metabolism ; Trastuzumab/therapeutic use ; Treatment Outcome ; },
abstract = {BACKGROUND: Human epidermal growth factor receptor 2 (HER2) gene amplification/overexpression is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-HER2 agents. HER2 somatic mutations have been reported, and these may influence the effect of HER2-targeted drugs.<br><br>METHODS: Here, we sought HER2 mutations in a group of 135 Japanese breast cancer patients with HER2-positive tumors. We analyzed HER2 mutations by direct Sanger sequencing of two major areas, the extracellular domain at position 309-310 and the kinase domain between 755 and 781.<br><br>RESULTS: Two patients with the HER2 somatic mutation S310F in the extracellular domain were found in this series. One patient with the S310F mutation had a node-negative invasive ductal carcinoma classified as HER2 2+ by the HercepTest and fluorescence in situ hybridization (FISH) positive, and which was estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative. Another patient with the S310F mutation had an apocrine carcinoma with seven lymph nodes positive for metastasis, classified as HER2 3+ by the HercepTest, but which was FISH-negative, as well as ER-negative and PgR-negative. Both patients had received adjuvant single-agent trastuzumab therapy, and had no local recurrence or distant metastasis for five and three years after surgery, respectively.<br><br>CONCLUSIONS: Our data show that HER2 mutations are rare in HER2-positive Japanese breast cancer patients. The two mutations found in this study were identical, S310F. We suggest that in vitro experiments to determine whether the S310F mutation could be involved in resistance to anti-HER2 drugs are worthwhile in future.},
}
@article {pmid27781130,
year = {2016},
author = {Paiva, C and Garcia, J and Silva, C and Araújo, A and Araújo, A and Santos, MD},
title = {Single Jejunum Metastasis from Breast Cancer Arising Twelve Years after the Initial Treatment.},
journal = {Case reports in oncological medicine},
volume = {2016},
number = {},
pages = {8594652},
pmid = {27781130},
issn = {2090-6706},
abstract = {Metastatic involvement of gastrointestinal tract from breast cancer is a rare event. We report the case of a 61-year-old woman presenting with bowel obstruction, related to metastasis of a primary breast cancer she had 12 years earlier (a triple-negative invasive ductal carcinoma treated with surgery and chemotherapy). Bowel obstruction was caused by a 20-centimeter tumor in the jejunum, involving also the transverse colon. The patient underwent en bloc resection of tumor with jejunum and transverse bowel segment and received adjuvant chemotherapy with carboplatin and paclitaxel. Twenty months later, she was alive without disease recurrence.},
}
@article {pmid27776915,
year = {2017},
author = {Mendler, M and Riedinger, C and Schlotterer, A and Volk, N and Fleming, T and Herzig, S and Nawroth, PP and Morcos, M},
title = {Reduction in ins-7 gene expression in non-neuronal cells of high glucose exposed Caenorhabditis elegans protects from reactive metabolites, preserves neuronal structure and head motility, and prolongs lifespan.},
journal = {Journal of diabetes and its complications},
volume = {31},
number = {2},
pages = {304-310},
doi = {10.1016/j.jdiacomp.2016.09.014},
pmid = {27776915},
issn = {1873-460X},
mesh = {Animals ; Behavior, Animal ; Caenorhabditis elegans/enzymology/growth &amp; development/*metabolism ; Caenorhabditis elegans Proteins/agonists/*antagonists &amp; inhibitors/genetics/*metabolism ; Feedback, Physiological ; *Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Gene Knockout Techniques ; Glucose/*poisoning ; Glycation End Products, Advanced/metabolism ; Lactoylglutathione Lyase/antagonists &amp; inhibitors/genetics/*metabolism ; Longevity ; Mutation ; Neuroprotection ; Osmolar Concentration ; *Oxidative Stress ; Peptide Hormones/agonists/*antagonists &amp; inhibitors/genetics/metabolism ; RNA Interference ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/antagonists &amp; inhibitors/genetics/*metabolism ; Survival Analysis ; },
abstract = {BACKGROUND: Glucose derived metabolism generates reactive metabolites affecting the neuronal system and lifespan in C. elegans. Here, the role of the insulin homologue ins-7 and its downstream effectors in the generation of high glucose induced neuronal damage and shortening of lifespan was studied.<br><br>RESULTS: In C. elegans high glucose conditions induced the expression of the insulin homologue ins-7. Abrogating ins-7 under high glucose conditions in non-neuronal cells decreased reactive oxygen species (ROS)-formation and accumulation of methylglyoxal derived advanced glycation endproducts (AGEs), prevented structural neuronal damage and normalised head motility and lifespan. The restoration of lifespan by decreased ins-7 expression was dependent on the concerted action of sod-3 and glod-4 coding for the homologues of iron-manganese superoxide dismutase and glyoxalase 1, respectively.<br><br>CONCLUSIONS: Under high glucose conditions mitochondria-mediated oxidative stress and glycation are downstream targets of ins-7. This impairs the neuronal system and longevity via a non-neuronal/neuronal crosstalk by affecting sod-3 and glod-4, thus giving further insight into the pathophysiology of diabetic complications.},
}
@article {pmid27633896,
year = {2016},
author = {Ratajczak-Wielgomas, K and Grzegrzolka, J and Piotrowska, A and Gomulkiewicz, A and Witkiewicz, W and Dziegiel, P},
title = {Periostin expression in cancer-associated fibroblasts of invasive ductal breast carcinoma.},
journal = {Oncology reports},
volume = {36},
number = {5},
pages = {2745-2754},
doi = {10.3892/or.2016.5095},
pmid = {27633896},
issn = {1791-2431},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*biosynthesis/genetics ; Cancer-Associated Fibroblasts/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating ; Cell Adhesion/genetics ; Cell Adhesion Molecules/*biosynthesis/genetics ; Cell Proliferation ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; },
abstract = {Periostin (POSTN) is a secreted cell adhesion glycoprotein that plays an important role in proliferation, adhesion and migration processes, as well as in regulation of mechanisms related to epithelial-mesenchymal transition (EMT). It also plays a key role in angio- and lymphangiogenesis and in formation of distant metastases. The aim of this work was to determine expression of POSTN in invasive ductal breast carcinoma (IDC) and in non-invasive ductal carcinoma in situ (DCIS) and to correlate its expression with clinicopathological parameters. Material for immunohistochemical studies (IHC) comprise of 70 IDC cases, 44 DCIS cases and 21 cases of fibrocystic change (FC). Frozen (-80˚C) fragments of tumours taken from 41 patients with IDC were used for molecular studies (real-time PCR), including 11 cases of IDC subjected to laser capture microdissection (LCM). POSTN expression was shown mainly in tumour stromal cells, i.e. cancer-associated fibroblasts (CAFs). Statistically significant higher level of POSTN expression in CAFs in IDC as compared to FC (p<0.0001) was observed. Additionally, statistically elevated expression level of POSTN in CAFs in IDC relative to DCIS (p<0.0001) and significantly increased expression of POSTN in CAFs in DCIS in comparison to FC (p=0.0158) was also shown. High level of POSTN expression in CAFs in IDC (>8 IRS points) was significantly correlated with tumour malignancy grade (G) (p=0.0070). Moreover, higher POSTN expression by CAFs was associated with patient shorter overall survival. Significant increase of POSTN expression on mRNA and protein level in CAFs in IDC with the growing malignancy grade of the tumours (G) was shown. Furthermore, with the use of LCM method, statistically significant higher expression of mRNA POSTN in stromal cells relative to cancer cells (p<0.001) was noted. POSTN might be a factor playing an important role in the mechanism of IDC progression.},
}
@article {pmid27775181,
year = {2017},
author = {Kaya, Z and Akkiprik, M and Karabulut, S and Peker, I and Gullu Amuran, G and Ozmen, T and Gulluoglu, BM and Kaya, H and Ozer, A},
title = {Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.},
journal = {Journal of clinical laboratory analysis},
volume = {31},
number = {5},
pages = {},
pmid = {27775181},
issn = {1098-2825},
mesh = {Breast/*chemistry ; Breast Neoplasms/chemistry/*epidemiology/*genetics/mortality ; Cohort Studies ; DNA Methylation ; Female ; Humans ; Insulin-Like Growth Factor Binding Proteins/*genetics ; Middle Aged ; Survival Analysis ; Telomere/chemistry/*genetics ; Turkey ; },
abstract = {BACKGROUND: Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL.<br><br>METHODS: Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting.<br><br>RESULTS: Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters.<br><br>CONCLUSION: These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.},
}
@article {pmid27406466,
year = {2016},
author = {El-Hage, A and Ruel, C and Afif, W and Wissanji, H and Hogue, JC and Desbiens, C and Leblanc, G and Poirier, &#xc9;},
title = {Metastatic pattern of invasive lobular carcinoma of the breast-Emphasis on gastric metastases.},
journal = {Journal of surgical oncology},
volume = {114},
number = {5},
pages = {543-547},
doi = {10.1002/jso.24362},
pmid = {27406466},
issn = {1096-9098},
mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Canada ; Carcinoma, Lobular/epidemiology/*secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Stomach Neoplasms/epidemiology/*secondary ; },
abstract = {BACKGROUND AND OBJECTIVES: Breast invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have different metastatic patterns, but the exact pattern of metastases from ILC is poorly known. This study aimed to determine the frequency of ILC metastases in atypical locations, with an emphasis on gastric metastases.<br><br>METHODS: Patients with ILC treated at the Saint-Sacrement Hospital (Quebec City, Canada) and the Maisonneuve-Rosemont Hospital (Montreal, Canada) between January 2003 and December 2009 were retrospectively reviewed. Demographic, clinical, and follow-up data were retrieved from the medical charts. Metastases that were diagnosed during follow-up were recorded.<br><br>RESULTS: Among the 481 patients with ILC, 74 (15.4%) were diagnosed with metastases after a median follow-up of 46 months. Among these 74 patients, 41.9% had metastases in atypical sites. Five patients were diagnosed with histologically confirmed gastric metastases of ILC.<br><br>CONCLUSION: Metastases of breast ILC to atypical sites might be more frequent than previously reported. Clinicians should keep a high level of suspicion when a patient with a history of ILC develops digestive symptoms. It is important to differentiate metastases from a primary GI tumor by using immunohistochemical markers. J. Surg. Oncol. 2016;114:543-547. &#xa9; 2016 Wiley Periodicals, Inc.},
}
@article {pmid27760942,
year = {2016},
author = {Matsuoka, A and Hirano, A and Hattori, A and Ogura, K and Inoue, H and Yukawa, H and Sakaguchi, S and Tanaka, N and Kodera, A and Kamimura, M and Naritaka, Y and Shimizu, T},
title = {[Ethinylestradiol Following Everolimus plus Exemestane Was Effective in Postmenopausal Endocrine-Responsive Metastatic Breast Cancer - A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {43},
number = {10},
pages = {1219-1222},
pmid = {27760942},
issn = {0385-0684},
mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Estrogen Replacement Therapy ; Ethinyl Estradiol/administration &amp; dosage ; Everolimus/administration &amp; dosage ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Lymph Node Excision ; Mastectomy ; Postmenopause ; },
abstract = {A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin.Then, estrogen therapy with ethinylestradiol(EE2)was started in December 2013.T he pleural effusion disappeared and the liver metastases were reduced.After 11 months of progression-free survival(PFS), regrowth of the liver metastases was seen.Thus, everolimus plus exemestane was administered, and approximately 8 months of PFS was obtained.Therefore, both EE2 and everolimus are effective therapy even for heavily pretreated metastatic breast cancer.},
}
@article {pmid27760180,
year = {2016},
author = {Fu, J and Wu, L and Jiang, M and Li, D and Jiang, T and Hong, Z and Wang, F and Li, S},
title = {Clinical Nomogram for Predicting Survival Outcomes in Early Mucinous Breast Cancer.},
journal = {PloS one},
volume = {11},
number = {10},
pages = {e0164921},
pmid = {27760180},
issn = {1932-6203},
mesh = {Adenocarcinoma, Mucinous/*epidemiology/metabolism/mortality ; Aged ; Analysis of Variance ; Breast Neoplasms/*epidemiology/metabolism/mortality ; Carcinoma, Ductal, Breast/*epidemiology/metabolism/mortality ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Prognosis ; Receptors, Estrogen/*metabolism ; Risk Factors ; SEER Program ; Survival Analysis ; },
abstract = {BACKGROUND: The features related to the prognosis of patients with mucinous breast cancer (MBC) remain controversial. We aimed to explore the prognostic factors of MBC and develop a nomogram for predicting survival outcomes.<br><br>METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was searched to identify 139611 women with resectable breast cancer from 1990 to 2007. Survival curves were generated using Kaplan-Meier methods. The 5-year and 10-year cancer-specific survival (CSS) rates were calculated using the Life-Table method. Based on Cox models, a nomogram was constructed to predict the probabilities of CSS for an individual patient. The competing risk regression model was used to analyse the specific survival of patients with MBC.<br><br>RESULTS: There were 136569 (97.82%) infiltrative ductal cancer (IDC) patients and 3042 (2.18%) MBC patients. Patients with MBC had less lymph node involvement, a higher frequency of well-differentiated lesions, and more estrogen receptor (ER)-positive tumors. Patients with MBC had significantly higher 5 and10-year CSS rates (98.23 and 96.03%, respectively) than patients with IDC (91.44 and 85.48%, respectively). Univariate and multivariate analyses showed that MBC was an independent factor for better prognosis. As for patients with MBC, the event of death caused by another disease exceeded the event of death caused by breast cancer. A competing risk regression model further showed that lymph node involvement, poorly differentiated grade and advanced T-classification were independent factors of poor prognosis in patients with MBC. The Nomogram can accurately predict CSS with a high C-index (0.816). Risk scores developed from the nomogram can more accurately predict the prognosis of patients with MBC (C-index = 0.789) than the traditional TNM system (C-index = 0.704, P< 0.001).<br><br>CONCLUSIONS: Patients with MBC have a better prognosis than patients with IDC. Nomograms could help clinicians make more informed decisions in clinical practice. The competing risk regression model, as a more rational model, is recommended for use in the survival analysis of patients with MBC in the future.},
}
@article {pmid27219913,
year = {2016},
author = {Santangelo, G and Sacco, R and Siciliano, M and Bisecco, A and Muzzo, G and Docimo, R and De Stefano, M and Bonavita, S and Lavorgna, L and Tedeschi, G and Trojano, L and Gallo, A},
title = {Anxiety in Multiple Sclerosis: psychometric properties of the State-Trait Anxiety Inventory.},
journal = {Acta neurologica Scandinavica},
volume = {134},
number = {6},
pages = {458-466},
doi = {10.1111/ane.12564},
pmid = {27219913},
issn = {1600-0404},
mesh = {Adult ; Anxiety/epidemiology/etiology/*psychology ; Depression/epidemiology/etiology/psychology ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/complications/*psychology ; *Neuropsychological Tests ; Prevalence ; *Psychiatric Status Rating Scales ; Psychometrics ; Reference Values ; Sex Characteristics ; },
abstract = {OBJECTIVE: The aims of the present study were to examine psychometric properties of the Spielberger State-Trait Anxiety Inventory (STAI-Y-1 and STAI-Y-2, respectively) in a Multiple Sclerosis (MS) population and to identify a cut-off score to detect those MS patients with high level of state and/or trait anxiety who could be more vulnerable to development of depression and/or cognitive defects.<br><br>MATERIAL AND METHODS: The STAI-Y-1 and STAI-Y-2 was completed by a group of patients (n = 175) affected by MS and a group of healthy subjects (n = 150) matched for age, educational level, and gender. In MS patients internal consistency, divergent and discriminant validities were evaluated. Construct validity was examined by exploratory factor analysis for each scale.<br><br>RESULTS: There was no missing data, no floor or ceiling effects for both scales. The two scales showed high internal consistency, good divergent, and Known-groups validities. To identify high levels of state and trait anxiety in a patient with MS, we proposed three gender specific screening cut-off values (1, 1.5, 2 SD) for the STAI-Y-1 and the STAI-Y-2.<br><br>CONCLUSIONS: The findings showed that the STAI-Y-1 and the STAI-Y-2 are a valid tool for clinical use in MS patients and can be useful to measure the severity of anxiety and to identify those patients with high anxiety to introduce them in specific non-pharmacological intervention.},
}
@article {pmid27755404,
year = {2017},
author = {Sakamoto, Y and Fujita, S and Adachi, M and Sakamoto, H and Naruse, T and Yanamoto, S and Ikeda, T and Umeda, M},
title = {Carcinoma Ex Pleomorphic Adenoma of the Tongue: Difficulty in Diagnosis Between Metastasis of Breast Cancer and Salivary Tumor.},
journal = {The Journal of craniofacial surgery},
volume = {28},
number = {2},
pages = {e182-e185},
doi = {10.1097/SCS.0000000000003136},
pmid = {27755404},
issn = {1536-3732},
mesh = {Adenocarcinoma/*diagnosis/etiology/pathology ; Adenoma, Pleomorphic/complications/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Diagnosis, Differential ; Female ; Glossectomy ; Humans ; Middle Aged ; Neoplasms, Second Primary/*diagnosis/etiology/pathology ; Salivary Gland Neoplasms/complications/*pathology ; Tongue Neoplasms/*diagnosis/etiology/pathology ; },
abstract = {Carcinoma ex pleomorphic adenoma (CEPA) is a carcinoma that shows histologic evidence of arising in or from a benign pleomorphic adenoma. Carcinoma ex pleomorphic adenoma often occurs in parotid glands, but is extremely rarely in the tongue. A 53-year-old Japanese woman was referred to the Department of Oral and Maxillofacial Surgery, Nagasaki University Hospital, because of tumor of the right dorsum tongue. She had a history of surgery of breast cancer (invasive ductal carcinoma) and it was disseminated to the lung and bone. Macroscopic examination revealed an oval tumor with a smooth mucosal surface of 10 mm in diameter in the right dorsum tongue. A clinical diagnosis was metastasis from breast cancer or primary salivary gland tumor. Histologic diagnosis of the biopsy specimen was CEPA. She underwent partial glossectomy under general anesthesia. The final diagnosis of surgical materials was CEPA based on the differential diagnosis from breast carcinoma. She is alive bearing disseminated breast carcinoma without recurrence of CEPA at 6 months after glossectomy.},
}
@article {pmid27727404,
year = {2016},
author = {Gabanti, E and Bruno, F and Scaramuzzi, L and Mangione, F and Zelini, P and Gerna, G and Lilleri, D},
title = {Predictive value of human cytomegalovirus (HCMV) T-cell response in the control of HCMV infection by seropositive solid-organ transplant recipients according to different assays and stimuli.},
journal = {The new microbiologica},
volume = {39},
number = {4},
pages = {247-258},
pmid = {27727404},
issn = {1121-7138},
mesh = {Adult ; Aged ; Antigens, Viral ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cytomegalovirus Infections/*immunology/*prevention &amp; control ; Enzyme-Linked Immunospot Assay ; Female ; Humans ; Male ; Middle Aged ; Organ Transplantation/*adverse effects ; Predictive Value of Tests ; T-Lymphocytes/*physiology ; Young Adult ; },
abstract = {Human cytomegalovirus (HCMV) is still the most common viral infection in solid-organ transplant recipients (SOTR). Our study aimed to identify the predictive values of the T-cell response able to protect from HCMV disease, according to different assays. Viral DNA was determined by real-time PCR. The T-cell immune response to HCMV infection was investigated in SOTR according to the following assays and stimuli: cytokine flow cytometry (CFC) after peripheral blood mononuclear cell (PBMC) stimulation with autologous HCMV-infected dendritic cells (iDC) vs three ELISPOT assays using PBMCs stimulated with: 1. HCMV-infected cell lysate (iCL); 2. a pool of 34 epitopic peptides (PP) from different HCMV proteins; 3. a commercial pp65 peptide pool (CPM). ELISPOT results were normalized to T-cell counts. Overall, 51 SOTR were enrolled: 29 (57%) had low viral load (LVL) self-resolving infections, 19 (37%) high viral load (HVL) infections treated with antiviral drugs, and 3 (6%) tissue-invasive disease (TID). At DNAemia peak, ROC analysis showed that CFC-iDC CD4+ and the ELISPOT-iCL assays yielded overlapping area under the curve (AUC) results. The time needed to reconstitute protective T-cell immunity in SOTR with HVL infections was significantly longer with each assay compared to LVL infections. Using the CFC-iDC assay as a reference test (requiring 7 days to complete), the 24h ELISPOT-iCL assay provides similar results in terms of protection prediction from HCMV infection.},
}
@article {pmid27720394,
year = {2016},
author = {Nogués, L and Reglero, C and Rivas, V and Salcedo, A and Lafarga, V and Neves, M and Ramos, P and Mendiola, M and Berjón, A and Stamatakis, K and Zhou, XZ and Lu, KP and Hardisson, D and Mayor, F and Penela, P},
title = {G Protein-coupled Receptor Kinase 2 (GRK2) Promotes Breast Tumorigenesis Through a HDAC6-Pin1 Axis.},
journal = {EBioMedicine},
volume = {13},
number = {},
pages = {132-145},
pmid = {27720394},
issn = {2352-3964},
support = {R01 CA167677/CA/NCI NIH HHS/United States ; },
mesh = {Acetylation ; Animals ; Apoptosis/genetics ; Breast Neoplasms/genetics/*metabolism/mortality/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival/genetics ; Cell Transformation, Neoplastic/*metabolism ; Disease Models, Animal ; Female ; G-Protein-Coupled Receptor Kinase 2/genetics/*metabolism ; Gene Expression ; Histone Deacetylase 6 ; Histone Deacetylases/genetics/*metabolism ; Humans ; Mice, Transgenic ; Models, Biological ; NIMA-Interacting Peptidylprolyl Isomerase/*metabolism ; Prognosis ; RNA Interference ; RNA, Small Interfering/genetics ; *Signal Transduction ; Tumor Burden ; },
abstract = {In addition to oncogenic drivers, signaling nodes can critically modulate cancer-related cellular networks to strength tumor hallmarks. We identify G-protein-coupled receptor kinase 2 (GRK2) as a relevant player in breast cancer. GRK2 is up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a proportion of invasive ductal carcinoma patients. Increased GRK2 functionality promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6) leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of tumor progression, thereby enhancing its stability and functional interaction with key mitotic regulators. Interestingly, a correlation between GRK2 expression and Pin1 levels and de-acetylation status is detected in breast cancer patients. Activation of the HDAC6-Pin1 axis underlies the positive effects of GRK2 on promoting growth factor signaling, cellular proliferation and anchorage-independent growth in both luminal and basal breast cancer cells. Enhanced GRK2 levels promote tumor growth in mice, whereas GRK2 down-modulation sensitizes cells to therapeutic drugs and abrogates tumor formation. Our data suggest that GRK2 acts as an important onco-modulator by strengthening the functionality of key players in breast tumorigenesis such as HDAC6 and Pin1.},
}
@article {pmid27718416,
year = {2016},
author = {Fives, C and O'Neill, CJ and Murphy, R and Corrigan, MA and O'Sullivan, MJ and Feeley, L and Bennett, MW and O'Connell, F and Browne, TJ},
title = {When pathological and radiological correlation is achieved, excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted.},
journal = {Breast (Edinburgh, Scotland)},
volume = {30},
number = {},
pages = {125-129},
doi = {10.1016/j.breast.2016.09.006},
pmid = {27718416},
issn = {1532-3080},
mesh = {Adult ; Aftercare ; Aged ; Biopsy, Large-Core Needle ; Breast Carcinoma In Situ/complications/diagnostic imaging/pathology/*therapy ; Breast Neoplasms/complications/diagnostic imaging/pathology/*therapy ; Cohort Studies ; Disease Management ; Female ; Fibroadenoma/complications/diagnostic imaging/pathology/*therapy ; Humans ; Hyperplasia ; Mammography ; *Mastectomy, Segmental ; Middle Aged ; Retrospective Studies ; *Watchful Waiting ; },
abstract = {BACKGROUND: The diagnosis and management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) remains controversial. Current management options after a core needle biopsy (CNB) with lobular neoplasia (LN) incorporating both ALH and LCIS include excision biopsy or careful clinical and radiologic follow up.<br><br>METHODS: A retrospective analysis of the surgical database at Cork University Hospital was performed to identify all core needle biopsies from January 1st 2010 to 31st December 2013 with a diagnosis of FA who subsequently underwent surgical excision biopsy. All cases with associated LN including ALH and classical LCIS were selected. We excluded cases with coexistent ductal carcinoma in situ (DCIS), invasive carcinoma, LN associated with necrosis, pleomorphic lobular carcinoma in situ (PLCIS) or lesions which would require excision in their own right (papilloma, radial scar, atypical ductal hyperplasia (ADH) or flat epithelial atypia (FEA)). Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded.<br><br>RESULTS: 2878 consecutive CNB with a diagnosis of FA were identified. 25 cases had a diagnosis of concomitant ALH or classical LCIS. Our study cohort consisted of 21 women with a mean age 53 years (age range 41-70 years). The core biopsy diagnosis was of LCIS and FA in 16 cases and ALH and FA in 5 cases. On excision biopsy, a FA was confirmed in all 21 cases. In addition to the FA, residual LCIS was present in 14 cases with residual ALH in 2 cases. One of the twenty-one cases (4.8%) was upgraded to invasive ductal carcinoma on excision.},
}
@article {pmid27708222,
year = {2016},
author = {Elias, EV and de Castro, NP and Pineda, PH and Abuázar, CS and Bueno de Toledo Osorio, CA and Pinilla, MG and da Silva, SD and Camargo, AA and Silva, WA and E Ferreira, EN and Brentani, HP and Carraro, DM},
title = {Epithelial cells captured from ductal carcinoma in situ reveal a gene expression signature associated with progression to invasive breast cancer.},
journal = {Oncotarget},
volume = {7},
number = {46},
pages = {75672-75684},
pmid = {27708222},
issn = {1949-2553},
mesh = {Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Disease Progression ; Epithelial Cells/metabolism ; Female ; Gene Expression Profiling ; Genetic Association Studies ; Humans ; Neoplasm Staging ; Reproducibility of Results ; *Transcriptome ; },
abstract = {Breast cancer biomarkers that can precisely predict the risk of progression of non-invasive ductal carcinoma in situ (DCIS) lesions to invasive disease are lacking. The identification of molecular alterations that occur during the invasion process is crucial for the discovery of drivers of transition to invasive disease and, consequently, biomarkers with clinical utility. In this study, we explored differences in gene expression in mammary epithelial cells before and after the morphological manifestation of invasion, i.e., early and late stages, respectively. In the early stage, epithelial cells were captured from both pre-invasive lesions with distinct malignant potential [pure DCIS as well as the in situ component that co-exists with invasive breast carcinoma lesions (DCIS-IBC)]; in the late stage, epithelial cells were captured from the two distinct morphological components of the same sample (in situ and invasive components). Candidate genes were identified using cDNA microarray and rapid subtractive hybridization (RaSH) cDNA libraries and validated by RT-qPCR assay using new samples from each group. These analyses revealed 26 genes, including 20 from the early and 6 from the late stage. The expression profile based on the 20 genes, marked by a preferential decrease in expression level towards invasive phenotype, discriminated the majority of DCIS samples. Thus, this study revealed a gene expression signature with the potential to predict DCIS progression and, consequently, provides opportunities to tailor treatments for DCIS patients.},
}
@article {pmid27692597,
year = {2016},
author = {den Boer, SL and Rizopoulos, D and du Marchie Sarvaas, GJ and Backx, AP and Ten Harkel, AD and van Iperen, GG and Rammeloo, LA and Tanke, RB and Boersma, E and Helbing, WA and Dalinghaus, M},
title = {Usefulness of Serial N-terminal Pro-B-type Natriuretic Peptide Measurements to Predict Cardiac Death in Acute and Chronic Dilated Cardiomyopathy in Children.},
journal = {The American journal of cardiology},
volume = {118},
number = {11},
pages = {1723-1729},
doi = {10.1016/j.amjcard.2016.08.053},
pmid = {27692597},
issn = {1879-1913},
mesh = {Acute Disease ; Adolescent ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/mortality ; Child ; Child, Preschool ; Chronic Disease ; Death, Sudden, Cardiac/*epidemiology ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Natriuretic Peptide, Brain/*blood ; Netherlands/epidemiology ; Peptide Fragments/*blood ; Prognosis ; Retrospective Studies ; *Risk Assessment ; Risk Factors ; Survival Rate/trends ; },
abstract = {N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001). Furthermore, at any time, the slope of log10(NT-proBNP) was significantly predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP ≥7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP ≥924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome.},
}
@article {pmid27689969,
year = {2016},
author = {Vaidya, JS and Wenz, F and Bulsara, M and Tobias, JS and Joseph, DJ and Saunders, C and Brew-Graves, C and Potyka, I and Morris, S and Vaidya, HJ and Williams, NR and Baum, M},
title = {An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial).},
journal = {Health technology assessment (Winchester, England)},
volume = {20},
number = {73},
pages = {1-188},
doi = {10.3310/hta20730},
pmid = {27689969},
issn = {2046-4924},
support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; },
abstract = {BACKGROUND: Based on our laboratory work and clinical trials we hypothesised that radiotherapy after lumpectomy for breast cancer could be restricted to the tumour bed. In collaboration with the industry we developed a new radiotherapy device and a new surgical operation for delivering single-dose radiation to the tumour bed - the tissues at highest risk of local recurrence. We named it TARGeted Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and safety in pilot studies.<br><br>OBJECTIVE: To compare TARGIT within a risk-adapted approach with whole-breast external beam radiotherapy (EBRT) over several weeks.<br><br>DESIGN: The TARGeted Intraoperative radioTherapy Alone (TARGIT-A) trial was a pragmatic, prospective, international, multicentre, non-inferiority, non-blinded, randomised (1&#x2009;:&#x2009;1 ratio) clinical trial. Originally, randomisation occurred before initial lumpectomy (prepathology) and, if allocated TARGIT, the patient received it during the lumpectomy. Subsequently, the postpathology stratum was added in which randomisation occurred after initial lumpectomy, allowing potentially easier logistics and a more stringent case selection, but which needed a reoperation to reopen the wound to give TARGIT as a delayed procedure. The risk-adapted approach meant that, in the experimental arm, if pre-specified unsuspected adverse factors were found postoperatively after receiving TARGIT, EBRT was recommended. Pragmatically, this reflected how TARGIT would be practised in the real world.<br><br>SETTING: Thirty-three centres in 11 countries.<br><br>PARTICIPANTS: Women who were aged &#x2265;&#x2009;45 years with unifocal invasive ductal carcinoma preferably &#x2264;&#x2009;3.5&#x2009;cm in size.<br><br>INTERVENTIONS: TARGIT within a risk-adapted approach and whole-breast EBRT.<br><br>MAIN OUTCOME MEASURES: The primary outcome measure was absolute difference in local recurrence, with a non-inferiority margin of 2.5%. Secondary outcome measures included toxicity and breast cancer-specific and non-breast-cancer mortality.<br><br>RESULTS: In total, 3451 patients were recruited between March 2000 and June 2012. The following values are 5-year Kaplan-Meier rates for TARGIT compared with EBRT. There was no statistically significant difference in local recurrence between TARGIT and EBRT. TARGIT was non-inferior to EBRT overall [TARGIT 3.3%, 95% confidence interval (CI) 2.1% to 5.1% vs. EBRT 1.3%, 95% CI 0.7% to 2.5%; p&#x2009;=&#x2009;0.04; Pnon-inferiority&#x2009;=&#x2009;0.00000012] and in the prepathology stratum (n&#x2009;=&#x2009;2298) when TARGIT was given concurrently with lumpectomy (TARGIT 2.1%, 95% CI 1.1% to 4.2% vs. EBRT 1.1%, 95% CI 0.5% to 2.5%; p&#x2009;=&#x2009;0.31; Pnon-inferiority&#x2009;=&#x2009;0.0000000013). With delayed TARGIT postpathology (n&#x2009;=&#x2009;1153), the between-group difference was larger than 2.5% and non-inferiority was not established for this stratum (TARGIT 5.4%, 95% CI 3.0% to 9.7% vs. EBRT 1.7%, 95% CI 0.6% to 4.9%; p&#x2009;=&#x2009;0.069; Pnon-inferiority&#x2009;=&#x2009;0.06640]. The local recurrence-free survival was 93.9% (95% CI 90.9% to 95.9%) when TARGIT was given with lumpectomy compared with 92.5% (95% CI 89.7% to 94.6%) for EBRT (p&#x2009;=&#x2009;0.35). In a planned subgroup analysis, progesterone receptor (PgR) status was found to be the only predictor of outcome: hormone-responsive patients (PgR positive) had similar 5-year local recurrence with TARGIT during lumpectomy (1.4%, 95% CI 0.5% to 3.9%) as with EBRT (1.2%, 95% CI 0.5% to 2.9%; p&#x2009;=&#x2009;0.77). Grade 3 or 4 radiotherapy toxicity was significantly reduced with TARGIT. Overall, breast cancer mortality was much the same between groups (TARGIT 2.6%, 95% CI 1.5% to 4.3% vs. EBRT 1.9%, 95% CI 1.1% to 3.2%; p&#x2009;=&#x2009;0.56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1.4%, 95% CI 0.8% to 2.5% vs. 3.5%, 95% CI 2.3% to 5.2%; p&#x2009;=&#x2009;0.0086), attributable to fewer deaths from cardiovascular causes and other cancers, leading to a trend in reduced overall mortality in the TARGIT arm (3.9%, 95% CI 2.7% to 5.8% vs. 5.3%, 95% CI 3.9% to 7.3%; p&#x2009;=&#x2009;0.099]. Health economic analyses suggest that TARGIT was statistically significantly less costly than EBRT, produced similar quality-adjusted life-years, had a positive incremental net monetary benefit that was borderline statistically significantly different from zero and had a probability of >&#x2009;90% of being cost-effective. There appears to be little uncertainty in the point estimates, based on deterministic and probabilistic sensitivity analyses. If TARGIT were given instead of EBRT in suitable patients, it might potentially reduce costs to the health-care providers in the UK by &#xa3;8-9.1 million each year. This does not include environmental, patient and societal costs.<br><br>LIMITATIONS: The number of local recurrences is small but the number of events for local recurrence-free survival is not as small (TARGIT 57 vs. EBRT 59); occurrence of so few events (<&#x2009;3.5%) also implies that both treatments are effective and any difference is unlikely to be large. Not all 3451 patients were followed up for 5 years; however, more than the number of patients required to answer the main trial question (n&#x2009;=&#x2009;585) were followed up for >&#x2009;5 years.<br><br>CONCLUSIONS: For patients with breast cancer (women who are aged &#x2265;&#x2009;45 years with hormone-sensitive invasive ductal carcinoma that is up to 3.5&#x2009;cm in size), TARGIT concurrent with lumpectomy within a risk-adapted approach is as effective as, safer than and less expensive than postoperative EBRT.<br><br>FUTURE WORK: The analyses will be repeated with longer follow-up. Although this may not change the primary result, the larger number of events may confirm the effect on overall mortality and allow more detailed subgroup analyses. The TARGeted Intraoperative radioTherapy Boost (TARGIT-B) trial is testing whether or not a tumour bed boost given intraoperatively (TARGIT) boost is superior to a tumour bed boost given as part of postoperative EBRT.<br><br>TRIAL REGISTRATION: Current Controlled Trials ISRCTN34086741 and ClinicalTrials.gov NCT00983684.<br><br>FUNDING: University College London Hospitals (UCLH)/University College London (UCL) Comprehensive Biomedical Research Centre, UCLH Charities, Ninewells Cancer Campaign, National Health and Medical Research Council and German Federal Ministry of Education and Research (BMBF). From September 2009 this project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 73. See the NIHR Journals Library website for further project information.},
}
@article {pmid27689750,
year = {2016},
author = {Na, N and Luo, Y and Zhao, D and Yang, S and Hong, L and Li, H and Miao, B and Qiu, J},
title = {Prolongation of kidney allograft survival regulated by indoleamine 2, 3-dioxygenase in immature dendritic cells generated from recipient type bone marrow progenitors.},
journal = {Molecular immunology},
volume = {79},
number = {},
pages = {22-31},
doi = {10.1016/j.molimm.2016.09.005},
pmid = {27689750},
issn = {1872-9142},
mesh = {Allografts/immunology ; Animals ; Blotting, Western ; Dendritic Cells/enzymology/*immunology ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Graft Survival ; Hematopoietic Stem Cells/enzymology/immunology ; Immune Tolerance/*immunology ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*immunology/metabolism ; *Kidney Transplantation ; Lymphocyte Culture Test, Mixed ; Male ; Rats ; T-Lymphocytes, Regulatory/immunology ; Transplantation Immunology/*immunology ; },
abstract = {Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance. In this study, BN rat recipients were pre-injected with donor renal alloantigen-treated recipient iDCs before kidney transplantation. The renal allograft exhibited a lighter renal rejection response, prolonged graft survival time, and an increasing content of CD4[+]CD25[+]Foxp3[+] regulatory T cells (Tregs). Additionally, up-regulated secretion of Th2 cytokines were found in recipient sera post-transplantation. Transfection of si-IDO1 RNA into renal-antigen-treated recipient iDCs reversed these changes, which suggested that IDO channel signaling may be involved in iDC-induced allograft immunotolerance. These results suggested that iDC-induced and IDO-mediated allograft immunotolerance might be a potentially feasible tactic to prolong allograft survival, in addition to immunosuppressive drugs.},
}
@article {pmid27688086,
year = {2016},
author = {Wang, D and Fu, L and Shah, W and Zhang, J and Yan, Y and Ge, X and He, J and Wang, Y and Li, X},
title = {Presence of high risk HPV DNA but indolent transcription of E6/E7 oncogenes in invasive ductal carcinoma of breast.},
journal = {Pathology, research and practice},
volume = {212},
number = {12},
pages = {1151-1156},
doi = {10.1016/j.prp.2016.09.009},
pmid = {27688086},
issn = {1618-0631},
mesh = {Breast Neoplasms/genetics/pathology/*virology ; Carcinoma, Ductal, Breast/genetics/pathology/*virology ; DNA, Viral/*genetics ; Female ; Human Papillomavirus DNA Tests ; Humans ; Middle Aged ; Oncogenes/*genetics ; Papillomaviridae/*genetics ; Papillomavirus Infections/virology ; },
abstract = {BACKGROUND AND AIMS: The causative role of high risk human papillomavirus (HR-HPV) in breast cancer development is controversial, though a number of reports have identified HR-HPV DNA in breast cancer specimens. Nevertheless, most studies to date have focused primarily on viral DNA rather than the viral transcription. The aim of this study was to investigate the presence of HR-HPV in breast cancer tissues at HPV DNA level and HPV oncogenes mRNA level by in situ hybridization (ISH).<br><br>METHODS: One hundred and forty six (146) cases of breast invasive ductal carcinoma(IDC) and 83 cases of benign breast lesions were included in the study. Type specific oligonucleotide probes were used for the DNA detection of HPV 16,18 and 58 by ISH. HR-HPV oncogenes mRNA was assayed by novel RNAscope HR-HPV HR7 assay ISH. p16 protein expression was evaluated by immunohistochemistry (IHC).<br><br>RESULTS: HR-HPV 16,18 and 58 DNA were detected in 52 out of 146 (35.6%) IDC and in 3 out of 83 (3.6%) benign breast lesions by ISH. The HR-HPV mRNAs was detected only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16 over-expression did not correlate with the HPV DNA positive breast cancer samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731).<br><br>CONCLUSIONS: HR-HPVs certainly exist in breast cancer tissue with less active transcription, which implies that the causal role of HPV in breast cancer development need further study.},
}
@article {pmid27683971,
year = {2017},
author = {Detremerie, C and Timmermans, F and De Pauw, M and Gheeraert, P and Hemelsoet, D and Toeback, J and Bové, T and Vandecasteele, E},
title = {Stroke due to non-bacterial thrombotic endocarditis as initial presentation of breast invasive ductal carcinoma.},
journal = {Acta clinica Belgica},
volume = {72},
number = {4},
pages = {268-273},
doi = {10.1080/17843286.2016.1219012},
pmid = {27683971},
issn = {2295-3337},
mesh = {Aged ; Breast Neoplasms/*complications/*diagnosis ; Carcinoma, Ductal, Breast/*complications/*diagnosis ; Endocarditis, Non-Infective/diagnostic imaging/*etiology ; Female ; Humans ; Stroke/diagnostic imaging/*etiology ; },
abstract = {We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early-stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma.},
}
@article {pmid27682634,
year = {2016},
author = {Pellecchia, MT and Savastano, R and Moccia, M and Picillo, M and Siano, P and Erro, R and Vallelunga, A and Amboni, M and Vitale, C and Santangelo, G and Barone, P},
title = {Lower serum uric acid is associated with mild cognitive impairment in early Parkinson's disease: a 4-year follow-up study.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {123},
number = {12},
pages = {1399-1402},
pmid = {27682634},
issn = {1435-1463},
mesh = {Aged ; Cognitive Dysfunction/*blood/diagnostic imaging/*etiology ; Female ; Humans ; Italy ; Logistic Models ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/blood/*complications/diagnostic imaging ; Severity of Illness Index ; Tomography, X-Ray Computed ; Uric Acid/*metabolism ; },
abstract = {Cognitive deficits are common in Parkinson's disease (PD) and many patients eventually develop dementia; however, its occurrence is unpredictable. Serum uric acid (UA) has been proposed as a biomarker of PD, both in the preclinical and clinical phase of the disease. The aim of this pilot study was to evaluate relationships between baseline serum UA levels and occurrence of mild cognitive impairment (MCI) at 4-year follow-up in a cohort of early PD patients. Early PD patients, not presenting concomitant diseases, cognitive impairment or treatment possibly interfering with UA levels, underwent neuropsychological testing at baseline and 4-year follow-up. UA levels were determined in serum at baseline. MCI was found in 23 out of 42 PD patients completing 4-year follow-up. Patients presenting MCI had significantly higher age at onset and lower Frontal Assessment Battery scores at baseline as compared with patients cognitively intact. Logistic regression analysis showed that both serum UA levels (OR = 0.54, p = 0.044) and age (OR = 1.16, p = 0.009) contribute to the occurrence of MCI at 4-year follow-up. Our pilot study suggests that lower levels of serum UA in the early disease stages are associated to the later occurrence of MCI. These results need to be confirmed by further studies on larger samples.},
}
@article {pmid27670952,
year = {2017},
author = {Firat, D and Ozturk, G and Demirbas, E and Idiz, O and Isik, A and Eken, H},
title = {Auto-Amputation of the Breast; a Rare Case Caused by Invasive Ductal Carcinoma.},
journal = {The breast journal},
volume = {23},
number = {1},
pages = {102-103},
doi = {10.1111/tbj.12696},
pmid = {27670952},
issn = {1524-4741},
mesh = {Aged ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Thorax/diagnostic imaging ; Tomography, X-Ray Computed ; },
}
@article {pmid27668497,
year = {2016},
author = {Lee, HS and Ha, JY and Choi, W and Yoon, KC},
title = {Bilateral Corneal Epithelial Lesions Associated with Paclitaxel.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {93},
number = {10},
pages = {1333-1336},
doi = {10.1097/OPX.0000000000000945},
pmid = {27668497},
issn = {1538-9235},
abstract = {PURPOSE: An antineoplastic drug, paclitaxel, is widely used in small cell lung cancer, breast cancer, and ovarian cancer. We report a case of bilateral, vision-impairing corneal epithelial lesions that developed in a patient receiving paclitaxel monotherapy for breast cancer.<br><br>CASE REPORT: A 45-year-old woman presented with a 1-month history of bilateral visual disturbances. She had been receiving paclitaxel chemotherapy after modified radical mastectomy for invasive ductal carcinoma in her left breast. Best-corrected visual acuity was 20/100 in the right eye and 20/40 in the left eye. Slit-lamp examination revealed irregular triangular corneal lesions in both eyes. The lesions extended to the center of the cornea involving the visual axis and showed late staining with fluorescein dye. The lesions resolved 5 months after discontinuation of paclitaxel chemotherapy, and best-corrected visual acuity was restored to 20/20 in both eyes.<br><br>CONCLUSIONS: Microtubule-stabilizing chemotherapeutic drugs such as paclitaxel can cause visually significant corneal lesions, and these lesions appear to be reversible with discontinuation of the drug. This case highlights the need for regular ophthalmologic examinations for the detection of this reversible adverse ocular reaction.},
}
@article {pmid27630343,
year = {2016},
author = {Do, SI and Yoon, G and Kim, HS and Kim, K and Lee, H and Do, IG and Kim, DH and Chae, SW and Sohn, JH},
title = {Increased Brahma-related Gene 1 Expression Predicts Distant Metastasis and Shorter Survival in Patients with Invasive Ductal Carcinoma of the Breast.},
journal = {Anticancer research},
volume = {36},
number = {9},
pages = {4873-4882},
doi = {10.21873/anticanres.11051},
pmid = {27630343},
issn = {1791-7530},
mesh = {Adult ; Aged ; Biomarkers, Tumor/biosynthesis/*genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Helicases/biosynthesis/*genetics ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/pathology ; Nuclear Proteins/biosynthesis/*genetics ; Prognosis ; Transcription Factors/biosynthesis/*genetics ; },
abstract = {BACKGROUND: Previous studies have demonstrated aberrant Brahma-related gene 1 (BRG1) expression in various tumor types. Increased BRG1 expression has recently been shown to correlate with aggressive oncogenic behavior in many different types of human cancer. However, the role of BRG1 in breast cancer development and progression is not fully understood.<br><br>MATERIALS AND METHODS: We evaluated BRG1 expression in 224 patients with invasive ductal carcinoma (IDC) of the breast using tissue microarray samples and immunohistochemistry. We also investigated whether BRG1 expression status is associated with clinicopathological characteristics and outcomes of patients with IDC.<br><br>RESULTS: Among the 224 patients with IDC, 37.5% (84/224) exhibited high BRG1 expression. IDC exhibited significantly higher BRG1 expression compared to ductal carcinoma in situ (p=0.009) and normal breast tissue (p=0.005). High BRG1 expression in IDC significantly correlated with higher histological grade (p=0.035) and presence of distant metastasis (p=0.002). Furthermore, high BRG1 expression was an independent factor for predicting distant metastasis (relative risk=4.079; p=0.007). In addition, high BRG1 expression predicted shorter overall (p=0.011) and recurrence-free (p=0.003) survival in patients with IDC. In particular, BRG1 had a significant prognostic value in predicting recurrence-free survival of patients with IDC with lymph node metastasis or stage III disease.<br><br>CONCLUSION: BRG1 is involved in the progression and metastasis of breast cancer and can serve as a novel biomarker predictive of distant metastasis and patient outcomes.},
}
@article {pmid27628551,
year = {2016},
author = {Hamaoka, A and Matsuda, T and Konishi, E and Taguchi, T},
title = {[A Case of Luminal-HER2 Advanced Breast Cancer with Liver Metastasis Showed Pathological Complete Response to the Therapy with Pertuzumab plus Trastuzumab plus Docetaxel].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {43},
number = {9},
pages = {1097-1100},
pmid = {27628551},
issn = {0385-0684},
mesh = {Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/surgery ; Combined Modality Therapy ; Docetaxel ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Phenobarbital/analysis/metabolism ; Receptor, ErbB-2/analysis/metabolism ; Taxoids/administration &amp; dosage ; Trastuzumab/administration &amp; dosage ; Treatment Outcome ; },
abstract = {A 56-year-old woman noticed a mass on her left breast and visited our hospital. An irregular mass of 3 cm with associated axillary lymphadenopathy was detected under the nipple of the left breast. After further evaluations, the diagnosis was an invasive ductal carcinoma(scirrhous carcinoma)ofLuminal -HER2 type with liver metastases(cT4bN1M1, Stage IV). Treatment was initiated with a combination ofpertuzumab, trastuzumab, and docetaxel(PTD). The primary tumor showed a clinical complete response, and the liver metastases and the axillary lymph node metastases showed a partial response. Docetaxel was excluded after the 8th cycle because the patient experienced severe edema. After 15 cycles of therapy, the primary tumor was resected, and pathological examination revealed a pathological complete response ofthe primary lesion. Thus, PTD combination therapy is effective for Stage IV metastatic breast cancer ofthe Luminal-HER2 type.},
}
@article {pmid27625208,
year = {2016},
author = {Hidalgo, IH and Fleming, T and Eckstein, V and Herzig, S and Nawroth, PP and Tyedmers, J},
title = {Characterization of aggregate load and pattern in living yeast cells by flow cytometry.},
journal = {BioTechniques},
volume = {61},
number = {3},
pages = {137-148},
doi = {10.2144/000114452},
pmid = {27625208},
issn = {1940-9818},
mesh = {Flow Cytometry/*methods ; Green Fluorescent Proteins/analysis/chemistry/genetics/metabolism ; High-Throughput Screening Assays ; Peptide Termination Factors/analysis/chemistry/genetics/metabolism ; *Protein Aggregates ; Recombinant Fusion Proteins/analysis/chemistry/genetics/metabolism ; Saccharomyces cerevisiae/*chemistry/cytology/metabolism ; Saccharomyces cerevisiae Proteins/analysis/chemistry/genetics/metabolism ; },
abstract = {Protein aggregation is both a hallmark of and a driving force for a number of diseases. It is therefore important to identify the nature of these aggregates and the mechanism(s) by which the cell counteracts their detrimental properties. Currently, the study of aggregation in vivo is performed primarily using fluorescently tagged versions of proteins and analyzing the aggregates by fluorescence microscopy. While this strategy is considered the gold standard, it has several limitations, particularly with respect to its suitability for high-throughput screening (HTS). Here, using a GFP fusion of the well-characterized yeast prion amyloid protein [PSI+], we demonstrate that flow cytometry, which utilizes the same physical principles as fluorescence microscopy, can be used to determine the aggregate load and pattern in live and fixed yeast cells. Furthermore, our approach can easily be applied to high-throughput analyses such as screenings with a yeast deletion library.},
}
@article {pmid27589880,
year = {2017},
author = {Jay, AM and Hamame, AS and Dul, C and Wesen, C},
title = {Breast Cancer in a 19-Year-Old Female Adolescent Identified with Li-Fraumeni Syndrome.},
journal = {Journal of pediatric and adolescent gynecology},
volume = {30},
number = {1},
pages = {e5-e6},
doi = {10.1016/j.jpag.2016.08.011},
pmid = {27589880},
issn = {1873-4332},
mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Humans ; Li-Fraumeni Syndrome/*genetics ; *Tumor Suppressor Protein p53 ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer is rare in adolescents. In one study, breast carcinoma accounted for 0.02% of breast masses surgically removed in young women. We report a case of breast cancer in a 19-year-old woman who was found to have Li-Fraumeni Syndrome.<br><br>CASE: The patient presented with a new, hard, nonmobile lump in the right breast which prompted her to seek medical attention. A biopsy identified invasive ductal carcinoma. Genetic testing showed a p53 mutation associated with Li-Fraumeni syndrome.<br><br>SUMMARY AND CONCLUSION: Although breast masses in young women are mostly benign, one must entertain the possibility of more serious conditions when a breast mass is identified with concerning medical or physical findings. Genetic testing might be informative for such patients.},
}
@article {pmid27576528,
year = {2016},
author = {Calhoun, BC and Portier, B and Wang, Z and Minca, EC and Budd, GT and Lanigan, C and Tubbs, RR and Morrison, LE},
title = {MET and PTEN gene copy numbers and Ki-67 protein expression associate with pathologic complete response in ERBB2-positive breast carcinoma patients treated with neoadjuvant trastuzumab-based therapy.},
journal = {BMC cancer},
volume = {16},
number = {1},
pages = {695},
pmid = {27576528},
issn = {1471-2407},
mesh = {Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Area Under Curve ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Chemotherapy, Adjuvant/methods ; Female ; Gene Dosage ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Ki-67 Antigen/biosynthesis ; Middle Aged ; Neoadjuvant Therapy/methods ; PTEN Phosphohydrolase/genetics ; Prognosis ; Proto-Oncogene Proteins c-met/genetics ; ROC Curve ; Receptor, ErbB-2 ; Sensitivity and Specificity ; Trastuzumab/*therapeutic use ; Treatment Outcome ; },
abstract = {BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy for breast cancer is associated with improved prognosis in aggressive tumor subtypes, including ERBB2- positive tumors. Recent adoption of pCR as a surrogate endpoint for clinical trials in early stage breast cancer in the neoadjuvant setting highlights the need for biomarkers that, alone or in combination, help predict the likelihood of response to treatment.<br><br>METHODS: Biopsy specimens from 29 patients with invasive ductal carcinoma treated with trastuzumab-based therapy prior to definitive resection and pathologic staging were evaluated by dual color bright field in situ hybridization (dual ISH) using probes for MET, TOP2A, PTEN, and PIK3CA genes, each paired with centromeric probes to their respective chromosomes (chromosomes 7, 17, 10, and 3). Ki-67 expression was assessed by immunohistochemistry (IHC). Various parameters describing copy number alterations were evaluated for each gene and centromere probe to identify the optimal parameters for clinical relevance. Combinations of ISH parameters and IHC expression for Ki-67 were also evaluated.<br><br>RESULTS: Of the four genes and their respective chromosomes evaluated by ISH, two gene copy number parameters provided statistically significant associations with pCR: MET gain or loss relative to chromosome 7 (AUC&#x2009;=&#x2009;0.791, sensitivity&#x2009;=&#x2009;92&#xa0;% and specificity&#x2009;=&#x2009;67&#xa0;% at optimal cutoff, p&#x2009;=&#x2009;0.0032) and gain of PTEN (AUC&#x2009;=&#x2009;0.674, sensitivity&#x2009;=&#x2009;38&#xa0;% and specificity&#x2009;=&#x2009;100&#xa0;% at optimal cutoff, p&#x2009;=&#x2009;0.039). Ki-67 expression was also found to associate significantly with pCR (AUC&#x2009;=&#x2009;0.726, sensitivity&#x2009;=&#x2009;100&#xa0;% and specificity&#x2009;=&#x2009;42&#xa0;% at optimal cutoff, p&#x2009;=&#x2009;0.0098). Combining gain or loss of MET relative to chromosome 7 with Ki-67 expression further improved the association with pCR (AUC&#x2009;=&#x2009;0.847, sensitivity&#x2009;=&#x2009;92&#xa0;% and specificity&#x2009;=&#x2009;83&#xa0;% at optimal cutoffs, p&#x2009;=&#x2009;0.0006).<br><br>CONCLUSIONS: An immunogenotypic signature of low complexity comprising MET relative copy number and Ki-67 expression generated by dual ISH and IHC may help predict pCR in ERBB2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. These findings require validation in additional patient cohorts.},
}
@article {pmid27571348,
year = {2016},
author = {Rohm, M and Schäfer, M and Laurent, V and Üstünel, BE and Niopek, K and Algire, C and Hautzinger, O and Sijmonsma, TP and Zota, A and Medrikova, D and Pellegata, NS and Ryden, M and Kulyte, A and Dahlman, I and Arner, P and Petrovic, N and Cannon, B and Amri, EZ and Kemp, BE and Steinberg, GR and Janovska, P and Kopecky, J and Wolfrum, C and Blüher, M and Berriel Diaz, M and Herzig, S},
title = {An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice.},
journal = {Nature medicine},
volume = {22},
number = {10},
pages = {1120-1130},
pmid = {27571348},
issn = {1546-170X},
mesh = {AMP-Activated Protein Kinases/*metabolism/pharmacology ; Adipocytes, White/*drug effects/metabolism ; Adipose Tissue, White/*drug effects/metabolism ; Animals ; Apoptosis Regulatory Proteins/*drug effects/metabolism ; Cachexia/etiology/*metabolism ; Cells, Cultured ; In Vitro Techniques ; Lipid Metabolism/*drug effects ; Lipogenesis/drug effects ; Lipolysis/drug effects ; Mice ; Neoplasms/complications/*metabolism ; Peptide Fragments/*pharmacology ; Thermogenesis/drug effects ; Uncoupling Protein 1/drug effects/metabolism ; },
abstract = {Cachexia represents a fatal energy-wasting syndrome in a large number of patients with cancer that mostly results in a pathological loss of skeletal muscle and adipose tissue. Here we show that tumor cell exposure and tumor growth in mice triggered a futile energy-wasting cycle in cultured white adipocytes and white adipose tissue (WAT), respectively. Although uncoupling protein 1 (Ucp1)-dependent thermogenesis was dispensable for tumor-induced body wasting, WAT from cachectic mice and tumor-cell-supernatant-treated adipocytes were consistently characterized by the simultaneous induction of both lipolytic and lipogenic pathways. Paradoxically, this was accompanied by an inactivated AMP-activated protein kinase (Ampk), which is normally activated in peripheral tissues during states of low cellular energy. Ampk inactivation correlated with its degradation and with upregulation of the Ampk-interacting protein Cidea. Therefore, we developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk. Thus, our data establish the Ucp1-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.},
}
@article {pmid27571158,
year = {2016},
author = {Barone, P and Santangelo, G and Amboni, M and Pellecchia, MT and Vitale, C},
title = {Pisa syndrome in Parkinson's disease and parkinsonism: clinical features, pathophysiology, and treatment.},
journal = {The Lancet. Neurology},
volume = {15},
number = {10},
pages = {1063-1074},
doi = {10.1016/S1474-4422(16)30173-9},
pmid = {27571158},
issn = {1474-4465},
mesh = {Aged ; Aged, 80 and over ; *Dystonia/etiology/physiopathology/therapy ; Female ; Humans ; Male ; Middle Aged ; Parkinsonian Disorders/*complications ; *Spinal Curvatures/etiology/physiopathology/therapy ; },
abstract = {Pisa syndrome is defined as a reversible lateral bending of the trunk with a tendency to lean to one side. It is a frequent and often disabling complication of Parkinson's disease, and has also been described in several atypical forms of parkinsonism and in neurodegenerative and psychiatric disorders after drug exposure and surgical procedures. Although no consistent diagnostic criteria for Pisa syndrome are available, most investigations have adopted an arbitrary cutoff of at least 10° of lateral flexion for the diagnosis of the syndrome. Pathophysiological mechanisms underlying Pisa syndrome have not been fully explained. One hypothesis emphasises central mechanisms, whereby Pisa syndrome is thought to be caused by alterations in sensory-motor integration pathways; by contrast, a peripheral hypothesis emphasises the role of anatomical changes in the musculoskeletal system. Furthermore, several drugs are reported to induce Pisa syndrome, including antiparkinsonian drugs. As Pisa syndrome might be reversible, clinicians need to be able to recognise this condition early to enable prompt management. Nevertheless, further research is needed to determine optimum treatment strategies.},
}
@article {pmid27569097,
year = {2016},
author = {Arfaoui, A and Douik, H and Kablouti, G and Chaaben, A and Handiri, N and Zid, Z and Ouni, N and Zouiouch, F and Ayari, F and Mamoghli, T and Bouassida, J and Harzallah, L and Guemira, F},
title = {MDM2 344T&gt;A polymorphism; could it be a predictive marker of anthracycline resistance?.},
journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology},
volume = {21},
number = {3},
pages = {732-739},
pmid = {27569097},
issn = {1107-0625},
mesh = {Adult ; Aged ; Aged, 80 and over ; Anthracyclines/*therapeutic use ; Breast Neoplasms/*drug therapy/genetics ; Drug Resistance, Neoplasm ; Female ; Genes, p53 ; Humans ; Middle Aged ; *Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins c-mdm2/*genetics ; },
abstract = {PURPOSE: To find a possible association between the Mouse Double Minute 2(MDM2) 344T>A, alone and in combination with p53 72 Arg/Pro polymorphism, and resistance to anthracycline-based chemotherapy of breast cancer in Tunisia.<br><br>METHODS: This study enrolled 542 patients with invasive ductal carcinoma (IDC) treated with anthracycline-based chemotherapy. Genomic DNA was isolated from whole blood, using the phenol chloroform method. Anthracycline response was scored according to the World Health Organization (WHO). MDM2 344T>A polymorphism was genotyped using real time polymerase chain reaction (RT-PCR) with the TaqMan method. Data was statistically analyzed using the x2 test.<br><br>RESULTS: Response was evaluated in 400 patients, of whom a quarter was found to be resistant to chemotherapy. Genetic data revealed that resistance to anthracycline-based chemotherapy did not seem to be correlated with 344T>A polymorphism in the studied population. Also, no significant association was found between the single nucleotide polymorphism (SNP) 344T>A status and clinicopathologic parameters (p>0.05 for all comparisons). Moreover, analysis of p53 rs1042522 and MDM2 rs1196333 combination showed no significant association between these two genetic variants and anthracycline resistance (p=0.2).<br><br>CONCLUSIONS: Our findings provide no evidence indicating that SNP 344 T>A may affect response to anthracycline-based chemotherapy. However, the results obtained from the combination of SNPs 344T>A of MDM2 and 72 Arg/Pro of p53, do not support the hypothesis of the prominent role of common p53 and MDM2 variations in the genetic mechanisms of chemotherapy resistance in breast cancer.},
}
@article {pmid27562113,
year = {2016},
author = {Li, Z and Liu, Q and Piao, J and Hua, F and Wang, J and Jin, G and Lin, Z and Zhang, Y},
title = {Clinicopathological implications of Tiam1 overexpression in invasive ductal carcinoma of the breast.},
journal = {BMC cancer},
volume = {16},
number = {1},
pages = {681},
pmid = {27562113},
issn = {1471-2407},
mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*genetics/mortality/*pathology ; Cell Line, Tumor ; Disease Progression ; Female ; *Gene Expression ; Guanine Nucleotide Exchange Factors/*genetics/metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; },
abstract = {BACKGROUND: T-lymphoma invasion and metastasis-inducing protein 1 (Tiam1) has been implicated in tumor occurrence and progression. Recent studies have shown that high expression levels of Tiam1 protein appear to be associated with the progression of numerous human tumors. This study attempted to explore the role of Tiam1 protein in tumor progression and the prognostic evaluation of breast cancer.<br><br>METHODS: The localization of the Tiam1 protein was determined in the MDA-MB-231 breast cancer cell line using immunofluorescence (IF) staining. In addition, a total of 283 breast tissue samples, including 153 breast cancer tissues, 67 ductal carcinoma in situ (DCIS) and 63 adjacent non-tumor breast tissues, were analyzed by immunohistochemical (IHC) staining of the Tiam1 protein. The correlation between Tiam1 expression and clinicopathological characteristics was evaluated by Chi-square test and Fisher's exact tests. Disease-free survival (DFS) and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier method. Additionally, univariate and multivariate analyses were performed by the Cox proportional hazards regression models.<br><br>RESULTS: Tiam1 protein showed a mainly cytoplasmic staining pattern in breast cancer cells; however, nuclear staining was also observed. Tiam1 protein expression was significantly higher in breast cancers (42.5&#xa0;%, 65/153) and DCIS (40.3&#xa0;%, 27/67) than in adjacent non-tumor tissues (12.7&#xa0;%, 8/63). In addition, Tiam1 associated with tumor stage and Ki-67 expression, but negatively correlated with receptor tyrosine-protein kinase erbB-2 (Her2) expression. Moreover, survival analyses showed that DFS and 10-year OS rates were significantly lower in breast cancer patients with high Tiam1 expression than those with low Tiam1 expression. Univariate analysis suggested that molecular types, clinical stage, Her2 expression levels and Tiam1 expression levels were also significantly associated with DFS and 10-year OS rates of breast cancer patients. Furthermore, multivariate analysis suggested that Tiam1 expression is a significant independent prognostic factor along with tumor stage in patients with breast cancer.<br><br>CONCLUSIONS: Tiam1 expression is frequently up-regulated in breast cancer. Tiam1 expression correlated with clinicopathological parameters, suggesting that it may be a useful prognostic biomarker and potential therapeutic target for patients with breast cancer.},
}
@article {pmid27556047,
year = {2016},
author = {Zhang, L and Xia, CQ},
title = {PD-1/PD-L1 Interaction Maintains Allogeneic Immune Tolerance Induced by Administration of Ultraviolet B-Irradiated Immature Dendritic Cells.},
journal = {Journal of immunology research},
volume = {2016},
number = {},
pages = {2419621},
pmid = {27556047},
issn = {2314-7156},
mesh = {Adoptive Transfer ; Animals ; B7-H1 Antigen/*metabolism ; Graft Survival/immunology ; *Immune Tolerance/radiation effects ; Isoantigens/*immunology ; Lymphocyte Activation/immunology ; Mice ; Programmed Cell Death 1 Receptor/*metabolism ; Protein Binding ; Skin Transplantation ; T-Lymphocyte Subsets/immunology/metabolism ; *Ultraviolet Rays ; },
abstract = {Our previous study demonstrated that transfusion of ultraviolet B-irradiated immature dendritic cells (UVB-iDCs) induced alloantigen-specific tolerance between two different strains of mice. Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been suggested to play an important role in maintaining immune tolerance. In the present study, we seek to address whether PD-1/PD-L1 plays a role in the maintenance of UVB-iDC-induced tolerance. We first observe that the UVB-iDC-induced alloantigen-specific tolerance can be maintained for over 6 weeks. Supporting this, at 6 weeks after tolerance induction completion, alloantigen-specific tolerance is still able to be transferred to syngeneic naïve mice through adoptive transfer of CD4+ T cells. Furthermore, skin transplantation study shows that the survival of allogeneic grafts is prolonged in those tolerant recipients. Further studies show that PD-1/PD-L1 interaction is essential for maintaining the induced tolerance as blockade of PD-1/PD-L1 by anti-PD-L1 antibodies largely breaks the tolerance at both cellular and humoral immunological levels. Importantly, we show that PD-1/PD-L1 interaction in tolerant mice is also essential for controlling alloantigen-responding T cells, which have never experienced alloantigens. The above findings suggest that PD-1/PD-L1 plays a crucial role in maintaining immune tolerance induced by UVB-iDCs, as well as in actively controlling effector T cells specific to alloantigens.},
}
@article {pmid27550996,
year = {2016},
author = {Zwack, PJ and De Clercq, I and Howton, TC and Hallmark, HT and Hurny, A and Keshishian, EA and Parish, AM and Benkova, E and Mukhtar, MS and Van Breusegem, F and Rashotte, AM},
title = {Cytokinin Response Factor 6 Represses Cytokinin-Associated Genes during Oxidative Stress.},
journal = {Plant physiology},
volume = {172},
number = {2},
pages = {1249-1258},
pmid = {27550996},
issn = {1532-2548},
mesh = {Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Chlorophyll/chemistry/metabolism ; Cytokinins/*metabolism ; Fluorescence ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant/drug effects/*genetics ; Gene Ontology ; Hydrogen Peroxide/pharmacology ; Mutation ; Oxidants/pharmacology ; *Oxidative Stress ; Plant Leaves/genetics/metabolism ; Plants, Genetically Modified ; Protein Binding ; Reverse Transcriptase Polymerase Chain Reaction ; Seedlings/genetics/metabolism ; Transcription Factors/*genetics/metabolism ; Two-Hybrid System Techniques ; },
abstract = {Cytokinin is a phytohormone that is well known for its roles in numerous plant growth and developmental processes, yet it has also been linked to abiotic stress response in a less defined manner. Arabidopsis (Arabidopsis thaliana) Cytokinin Response Factor 6 (CRF6) is a cytokinin-responsive AP2/ERF-family transcription factor that, through the cytokinin signaling pathway, plays a key role in the inhibition of dark-induced senescence. CRF6 expression is also induced by oxidative stress, and here we show a novel function for CRF6 in relation to oxidative stress and identify downstream transcriptional targets of CRF6 that are repressed in response to oxidative stress. Analysis of transcriptomic changes in wild-type and crf6 mutant plants treated with H2O2 identified CRF6-dependent differentially expressed transcripts, many of which were repressed rather than induced. Moreover, many repressed genes also show decreased expression in 35S:CRF6 overexpressing plants. Together, these findings suggest that CRF6 functions largely as a transcriptional repressor. Interestingly, among the H2O2 repressed CRF6-dependent transcripts was a set of five genes associated with cytokinin processes: (signaling) ARR6, ARR9, ARR11, (biosynthesis) LOG7, and (transport) ABCG14. We have examined mutants of these cytokinin-associated target genes to reveal novel connections to oxidative stress. Further examination of CRF6-DNA interactions indicated that CRF6 may regulate its targets both directly and indirectly. Together, this shows that CRF6 functions during oxidative stress as a negative regulator to control this cytokinin-associated module of CRF6-dependent genes and establishes a novel connection between cytokinin and oxidative stress response.},
}
@article {pmid27533259,
year = {2016},
author = {Gaui, EN and Klein, CH and Oliveira, GM},
title = {Proportional Mortality due to Heart Failure and Ischemic Heart Diseases in the Brazilian Regions from 2004 to 2011.},
journal = {Arquivos brasileiros de cardiologia},
volume = {107},
number = {3},
pages = {230-238},
pmid = {27533259},
issn = {1678-4170},
mesh = {Adolescent ; Adult ; Age Distribution ; Age Factors ; Aged ; Aged, 80 and over ; Brazil/epidemiology ; Cause of Death ; Child ; Child, Preschool ; Chronic Disease ; Female ; Heart Failure/*mortality ; Humans ; Infant ; Male ; Middle Aged ; Myocardial Ischemia/*mortality ; Risk Factors ; Sex Distribution ; Sex Factors ; Time Factors ; Young Adult ; },
abstract = {BACKGROUND:: Heart failure (HF) and ischemic heart diseases (IHD) are important causes of death in Brazil.<br><br>OBJECTIVE:: To assess proportional mortality (PM) due to HF and IHD as underlying causes stratified by sex and age groups in the Brazilian geoeconomic regions from 2004 to 2011.<br><br>METHODS:: Data from death certificates were obtained in the DATASUS site under the following International Statistical Classification of Diseases and Related Health Problems codes, 10th Revision: 1) from chapter IX: I20 to I24 for acute IHD, I25 for chronic IHD, and I50 for HF; and 2) from chapter XVIII, for ill-defined causes (IDC).<br><br>RESULTS:: Proportional mortality due to HF increased with age in both sexes and all regions, the highest percentages being found among elderly women. Among men, the highest percentages were observed in the West-Central region up to the ninth decade, but, among the eldest individuals, the highest percentages were identified in the Southern region. Among women, the regions did not differ up to the age group of 70-79 years, although the West-Central region took the lead from 50 to 79 years; however, from the age of 80 years on, the Southern region showed the highest PM due to HF. Proportional mortality due to acute IHD in all Brazilian regions and in both sexes increased up to the age group of 60-69 years, from which it decreased. Among men, the Southeastern region had the highest percentages in the age group of 50-59 years, while women had lower PM due to acute IHD than men in all regions. In both sexes, PM due to chronic IHD increased with age in the Southern and Southeastern regions, which did not happen in the others, while the Southern region had the highest rate of all regions for all age groups.<br><br>CONCLUSIONS:: Regional differences were more prominent at more advanced ages, especially when deaths due to IDC were excluded.<br><br>FUNDAMENTO:: Insufici&#xea;ncia card&#xed;aca (IC) e doen&#xe7;as isqu&#xea;micas do cora&#xe7;&#xe3;o (DIC) s&#xe3;o importantes causas de morte no Brasil.<br><br>OBJETIVO:: Avaliar a mortalidade proporcional (MP) por IC e DIC, como causas b&#xe1;sicas, estratificada por sexo e faixa et&#xe1;ria nas regi&#xf5;es brasileiras de 2004 a 2011.<br><br>M&#xc9;TODOS:: As informa&#xe7;&#xf5;es das declara&#xe7;&#xf5;es de &#xf3;bito foram obtidas no site do DATASUS, codificadas conforme a Classifica&#xe7;&#xe3;o Estat&#xed;stica Internacional de Doen&#xe7;as e Problemas Relacionados &#xe0; Sa&#xfa;de, 10&#xaa; Revis&#xe3;o: 1) do Cap&#xed;tulo IX: I20 a I24 para DIC aguda, I25 para DIC cr&#xf4;nica, e I50 para IC; e 2) do Cap&#xed;tulo XVIII, para causas mal definidas (CMD).<br><br>RESULTADOS:: A MP por IC aumentou com a idade nos dois sexos e em todas as regi&#xf5;es, as mais altas porcentagens sendo encontradas entre as mulheres mais idosas. Entre os homens, as mais altas porcentagens foram observadas na regi&#xe3;o Centro-Oeste at&#xe9; a nona d&#xe9;cada; entre os mais idosos, por&#xe9;m, as mais altas porcentagens foram identificadas na regi&#xe3;o Sul. Entre as mulheres, as regi&#xf5;es n&#xe3;o diferiram at&#xe9; a faixa et&#xe1;ria de 70-79 anos, embora a regi&#xe3;o Centro-Oeste tenha liderado dos 50 aos 79 anos; entretanto, a partir dos 80 anos, a regi&#xe3;o Sul apresentou a mais alta MP por IC. Em todas as regi&#xf5;es brasileiras e nos dois sexos, a MP por DIC aguda aumentou at&#xe9; a faixa et&#xe1;ria de 60-69 anos, a partir da qual diminuiu. Entre os homens, a regi&#xe3;o Sudeste apresentou as mais altas porcentagens na faixa et&#xe1;ria de 50-59 anos, enquanto as mulheres tiveram menor MP por DIC aguda em compara&#xe7;&#xe3;o aos homens em todas as regi&#xf5;es. Nos dois sexos, a MP por DIC cr&#xf4;nica aumentou com a idade nas regi&#xf5;es Sul e Sudeste, mas n&#xe3;o nas demais, enquanto a regi&#xe3;o Sul apresentou a mais alta MP entre todas as regi&#xf5;es para todas as faixas et&#xe1;rias.<br><br>CONCLUS&#xd5;ES:: Diferen&#xe7;as regionais foram mais marcantes nas idades mais avan&#xe7;adas, especialmente quando exclu&#xed;das as mortes por CMD.},
}
@article {pmid27521604,
year = {2016},
author = {Lee, JH and Kim, JE and Kim, BG and Han, HH and Kang, S and Cho, NH},
title = {STAT3-induced WDR1 overexpression promotes breast cancer cell migration.},
journal = {Cellular signalling},
volume = {28},
number = {11},
pages = {1753-1760},
doi = {10.1016/j.cellsig.2016.08.006},
pmid = {27521604},
issn = {1873-3913},
mesh = {Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Line, Tumor ; *Cell Movement ; Female ; Gene Expression Regulation, Neoplastic ; HEK293 Cells ; Humans ; Microfilament Proteins/genetics/*metabolism ; Neoplasm Invasiveness ; Promoter Regions, Genetic/genetics ; Protein Binding ; STAT3 Transcription Factor/*metabolism ; Survival Analysis ; Up-Regulation ; },
abstract = {WD repeat domain 1 (WDR1), a protein that assists cofilin-mediated actin filament disassembly, is overexpressed in the invading front of invasive ductal carcinoma (IDC), but its implication of overexpression and how to be regulated have not been studied. In our study, we demonstrated that STAT3 bound to the 5' upstream sequence (-1971 to -1964), a putative promoter region, of WDR1 gene, and its activation induced WDR1 overexpression in breast cancer cells. The exogenous overexpression of WDR1 increased the migration of MDA-MB-231, which was attenuated by WDR1 knockdown. In the analysis of breast cancer patients, WDR1 overexpression was associated with a shorter distant metastasis-free survival (DMFS), more specifically in basal-like tumors.},
}
@article {pmid27521488,
year = {2016},
author = {Georgiou, GP and Provatopoulou, X and Kalogera, E and Siasos, G and Menenakos, E and Zografos, GC and Gounaris, A},
title = {Serum resistin is inversely related to breast cancer risk in premenopausal women.},
journal = {Breast (Edinburgh, Scotland)},
volume = {29},
number = {},
pages = {163-169},
doi = {10.1016/j.breast.2016.07.025},
pmid = {27521488},
issn = {1532-3080},
mesh = {Adiponectin/blood ; Adult ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*etiology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leptin/blood ; Logistic Models ; Middle Aged ; Premenopause/*blood ; Resistin/*blood ; Risk Factors ; Statistics, Nonparametric ; },
abstract = {BACKGROUND: Adipokines have been suggested as potential mediators linking obesity and breast cancer. Resistin is the least-studied adipokine with diverse findings regarding its association with disease development and progression. The present study aimed to determine resistin serum levels in breast cancer in relation to the histological type of disease and to investigate their association with breast cancer risk.<br><br>METHODS: The study included 216 women, of which 163 were diagnosed with breast cancer (58 with IDC, 52 with DCIS and 53 with LN) and 53 were healthy. Serum levels of resistin, leptin and adiponectin were quantitatively determined in duplicates by ELISA. Differences in resistin levels among patient groups were evaluated with Kruskal-Wallis and Mann-Whitney tests. The association of resistin with breast cancer risk was evaluated by multiple logistic regression analysis.<br><br>RESULTS: Resistin levels varied between histological types of breast cancer (p&#xa0;=&#xa0;0.044). Significant differences in serum resistin were observed in IDC patients compared to those with DCIS and to controls (p&#xa0;<&#xa0;0.014 and p&#xa0;<&#xa0;0.03, respectively). Decreased levels of resistin, adiponectin and leptin were observed in premenopausal patients. Resistin was associated with a reduced risk for ductal carcinoma only in premenopausal women (OR: 0.364, 95% CI: 0.154-0.862, p&#xa0;<&#xa0;0.022).<br><br>CONCLUSION: Our findings indicate that resistin levels were inversely related to breast cancer risk in premenopausal women, supporting a protective role of resistin for these patients. Further advances in adipokine research may lead to tangible benefits for overweight/obese women at an increased risk for breast cancer.},
}
@article {pmid27517320,
year = {2016},
author = {Fu, Z and Chen, S and Liu, S and Han, S and Gao, X and Li, D and Li, D},
title = {DcR3 gene polymorphisms are associated with sporadic breast infiltrating ductal carcinoma in Northeast Chinese women.},
journal = {Oncotarget},
volume = {7},
number = {36},
pages = {57970-57977},
pmid = {27517320},
issn = {1949-2553},
mesh = {Adult ; Alleles ; Asian People/genetics ; Breast Neoplasms/ethnology/*genetics/pathology ; Carcinoma, Ductal, Breast/ethnology/*genetics/pathology ; Case-Control Studies ; China ; Female ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Lymphatic Metastasis ; Middle Aged ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptors, Tumor Necrosis Factor, Member 6b/*genetics ; },
abstract = {Decoy Receptor 3 (DcR3), also called TNFRSF6β, is a member of the tumor necrosis factor receptor superfamily and is a soluble receptor for FasL. DcR3 is overexpressed in cancers and contributes to tumorigenesis through immune suppression and promotion of angiogenesis. We found that DcR3 is overexpressed in breast infiltrating ductal carcinoma (IDC) cells as compared with normal controls. We also conducted a case-control study analyzing associations of DcR3 polymorphisms with breast IDC risk. Subjects included 531 females with breast IDC and 592 age-matched healthy controls. Four DcR3 single nucleotide polymorphism loci with minor frequencies of more than 5% (rs3208008, rs41309931, rs2297441 and rs1291207) were genotyped using polymerase chain reaction restriction fragment length polymorphism and sequencing. Our results revealed significant differences in rs41309931genotypes and alleles (P < 0.01). Based on Haploview software analysis, the haplotype block Ars3208008 Grs41309931 Grs2297441 Ars1291207 exhibited the highest frequency, but, haplotype blocks Ars3208008 Trs41309931 Grs2297441 Ars1291207 and Crs3208008 Grs41309931 Grs2297441 Ars1291207 were associated with breast IDC risk. This study also detected associations between DcR3 gene polymorphisms and the clinicopathological features of breast IDC, including lymph node metastasis and C-erbB2, P53, estrogen receptor and progesterone receptor status. These data indicate that DcR3 gene polymorphisms are associated with sporadic breast IDC risk in Northeast Chinese females.},
}
@article {pmid27510020,
year = {2016},
author = {Baloch, AH and Khosa, AN and Bangulzai, N and Shuja, J and Naseeb, HK and Jan, M and Marghazani, IB and Kakar, M and Baloch, DM and Cheema, AM and Ahmad, J},
title = {Novel Nonsense Variants c.58C&gt;T (p.Q20X) and c.256G&gt;T (p.E85X) in the CHEK2 Gene Identified in Breast Cancer Patients from Balochistan.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {17},
number = {7},
pages = {3623-3626},
pmid = {27510020},
issn = {2476-762X},
mesh = {Adult ; Breast Neoplasms/*genetics ; Checkpoint Kinase 2/*genetics ; Exons/genetics ; Female ; Genetic Predisposition to Disease/genetics ; Humans ; Middle Aged ; Mutation/*genetics ; Pakistan ; },
abstract = {Breast cancer is very common and the leading cause of cancer deaths among women globally. Hereditary cases account for 510% of the total burden and CHEK2, which plays crucial role in response to DNA damage to promote cell cycle arrest and repair or induce apoptosis, is considered as a moderate penetrance breast cancer risk gene. Our objective in the current study was to analyze mutations in related to breast cancer. A total of 271 individuals including breast cancer patients and normal subjects were enrolled and all 14 exons of CHEK2 were amplified and sequenced. The majority of the patients (>95%) were affected with invasive ductal carcinoma (IDC), 52.1% were diagnosed with grade III tumors and 56.2% and 27.5% with advanced stages III and IV. Two novel nonsense variants i.e. c.58C>T (P.Q20X) and c.256G>T (p.E85X) at exon 1 and 2 in two breast cancer patients were identified, both novel and not reported elsewhere.},
}
@article {pmid27503013,
year = {2016},
author = {Li, SN and Zhang, XL and Cai, GL and Lin, RW and Jiang, H and Chen, JZ and Xu, B and Huang, W},
title = {Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic Dilated Cardiomyopathy.},
journal = {Chinese medical journal},
volume = {129},
number = {16},
pages = {1904-1911},
pmid = {27503013},
issn = {2542-5641},
mesh = {Aged ; Cardiomyopathy, Dilated/pathology/*physiopathology ; Electrocardiography ; Female ; Heart Failure/pathology/physiopathology ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors ; },
abstract = {BACKGROUND: Current risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC.<br><br>METHODS: A prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality.<br><br>RESULTS: During a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90&#xb0; died compared to 31 of 193 patients with QRS-T angles &#x2264;90&#xb0; (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 &#xb1; 53.4&#xb0; vs. 107.2 &#xb1; 54.4&#xb0;, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class.<br><br>CONCLUSIONS: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation.},
}
@article {pmid27483711,
year = {2016},
author = {Ursaru, M and Jari, I and Gheorghe, L and Naum, AG and Scripcariu, V and Negru, D},
title = {BILATERAL BREAST CANCER: DIAGNOSIS AND PROGNOSIS.},
journal = {Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi},
volume = {120},
number = {2},
pages = {316-320},
pmid = {27483711},
issn = {0048-7848},
mesh = {Adult ; Breast Neoplasms/*diagnosis/mortality/surgery ; Carcinoma, Ductal, Breast/*diagnosis/mortality/surgery ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*diagnosis/mortality/surgery ; Neoplasm Staging ; Neoplasms, Multiple Primary/*diagnosis/mortality/surgery ; Neoplasms, Second Primary/*diagnosis/mortality/surgery ; Prognosis ; Retrospective Studies ; Treatment Outcome ; },
abstract = {AIM: To assess bilateral breast cancer patients, initially diagnosed with stage II unilateral breast cancer.<br><br>MATERIAL AND METHODS: 113 patients with stage 0-II breast cancer diagnosed between 1983 and 2011 were assessed. Of these, 8 patients had bilateral breast cancer: 7 patients with metachronous bilateral breast cancer and 1 patient with synchronous breast cancer. Breast ultrasound, mammography, computed tomography and magnetic resonance imaging were used to diagnose recurrence, loco regional and distant metastasis.<br><br>RESULTS: Age at diagnosis ranged from 37 to 59 years, with a maximum age incidence in the 4th decade (age between: 31-40 years). The average time interval between the two breast cancers was 8.125 years. The most common histological type was invasive ductal carcinoma. All eight patients with bilateral breast cancer had at least one type of recurrence/metastasis, mostly in the liver, and statistically the pleuropulmonary and liver metastases were the most frequent causes of death.<br><br>CONCLUSIONS: Patients in the 4th decade diagnosed with unilateral breast cancer are at risk of developing bilateral breast cancer. In metachronous breast cancer, the time interval between the detection of the second breast cancer and death is directly proportional to the time interval between the two breast cancers. TASTASES, DEATH.},
}
@article {pmid27479041,
year = {2016},
author = {Sabiani, L and Houvenaeghel, G and Heinemann, M and Reyal, F and Classe, JM and Cohen, M and Garbay, JR and Giard, S and Charitansky, H and Chopin, N and Rouzier, R and Daraï, E and Coutant, C and Azuar, P and Gimbergues, P and Villet, R and Tunon de Lara, C and Lambaudie, E},
title = {Breast cancer in young women: Pathologic features and molecular phenotype.},
journal = {Breast (Edinburgh, Scotland)},
volume = {29},
number = {},
pages = {109-116},
doi = {10.1016/j.breast.2016.07.007},
pmid = {27479041},
issn = {1532-3080},
mesh = {Adult ; *Age Factors ; Breast Neoplasms/chemistry/drug therapy/*pathology ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; France ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/etiology ; *Phenotype ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Retrospective Studies ; Risk Factors ; },
abstract = {PURPOSE: Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications.<br><br>METHODS: We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected.<br><br>RESULTS: 5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients &#x2264;35 years old. Triple negative and HER2 tumors were predominantly found in patients &#x2264;35 (22.2% and 22.1%, p&#xa0;<&#xa0;0.01). A young age &#x2264;40 years (p&#xa0;<&#xa0;0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or &#x2264;35 years (p&#xa0;<&#xa0;0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age &#x2264;35 (p&#xa0;<&#xa0;0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p&#xa0;<&#xa0;0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p&#xa0;<&#xa0;0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p&#xa0;<&#xa0;0.01).<br><br>CONCLUSION: Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy.},
}
@article {pmid27460667,
year = {2016},
author = {Fu, L and Luo, S and Cai, S and Hong, W and Guo, Y and Wu, J and Liu, T and Zhao, C and Li, F and Huang, H and Huang, M and Wang, J},
title = {Identification of LAMP2 Mutations in Early-Onset Danon Disease With Hypertrophic Cardiomyopathy by Targeted Next-Generation Sequencing.},
journal = {The American journal of cardiology},
volume = {118},
number = {6},
pages = {888-894},
doi = {10.1016/j.amjcard.2016.06.037},
pmid = {27460667},
issn = {1879-1913},
mesh = {Adolescent ; Age of Onset ; Blotting, Western ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Hypertrophic/*genetics/metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Codon, Nonsense ; Female ; Fluorescent Antibody Technique ; Genotype ; Glycogen Storage Disease Type IIb/*genetics/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Lysosomal-Associated Membrane Protein 2/*genetics/metabolism ; Male ; Muscle, Skeletal/metabolism ; *Mutation ; Myocardium/metabolism ; Phenotype ; Sequence Analysis, DNA ; Wolff-Parkinson-White Syndrome/genetics ; },
abstract = {Danon disease is an X-linked disorder with the clinical triad of cardiomyopathy, skeletal myopathy, and mental retardation. Early diagnosis of this disease remains a challenge, especially in the pediatric population. In this study, we developed a targeted panel-based next generation sequencing pipeline to identify mutations by sequencing of selected candidate genes in 136 pediatric patients with either hypertrophic cardiomyopathy (HC) or idiopathic dilated cardiomyopathy (IDC). This led to the identification of lysosome-associated membrane protein 2 (LAMP2) mutations in 4 of the 64 (6%) probands with HC, including 3 novel nonsense mutations (p.Q240X, p.S250X, and p.G22X). No LAMP2 mutation was detected in the other 72 probands with IDC. All 4 probands and one additional affected family member (2 men and 3 women) had an early-onset age and presented either HC alone or combined with Wolff-Parkinson-White syndrome and skeletal myopathy. Immunofluorescence staining and Western blot analysis revealed absent LAMP2 expression in both cardiac and skeletal muscle samples of the first proband and severely decreased LAMP2 expression in the skeletal muscle samples of the second proband. In conclusion, cardiomyopathy in the patients with Danon disease may occur during early childhood and tend to be HC rather than IDC in both affected men and women. Therefore, Danon disease should be considered as one of the leading causes of unexplained ventricular hypertrophy in pediatric patients. The inclusion of LAMP2 gene in cardiomyopathy genetic screening panels may contribute to early diagnosis of Danon disease.},
}
@article {pmid27453513,
year = {2016},
author = {Merlo, M and Anzini, M and Bussani, R and Artico, J and Barbati, G and Stolfo, D and Gigli, M and Muça, M and Naso, P and Ramani, F and Di Lenarda, A and Pinamonti, B and Sinagra, G},
title = {Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.},
journal = {The American journal of cardiology},
volume = {118},
number = {6},
pages = {895-900},
doi = {10.1016/j.amjcard.2016.05.063},
pmid = {27453513},
issn = {1879-1913},
mesh = {Adult ; Cardiomyopathy, Dilated/*etiology/mortality/surgery ; Cohort Studies ; Female ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Mortality ; Multivariate Analysis ; Myocarditis/*complications ; Prognosis ; Proportional Hazards Models ; Protective Factors ; Risk Factors ; Ventricular Dysfunction, Left/*etiology/mortality/surgery ; },
abstract = {Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC.},
}
@article {pmid27435300,
year = {2017},
author = {Monica, MA and Baccarini, P and Cucchi, MC and Lacava, N and Foschini, MP},
title = {Endobronchial Pagetoid Spread of a Breast Carcinoma Metastatic to the Lung.},
journal = {International journal of surgical pathology},
volume = {25},
number = {1},
pages = {83-86},
doi = {10.1177/1066896916660619},
pmid = {27435300},
issn = {1940-2465},
mesh = {Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology ; Bronchi/pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*secondary ; Neoplasm Invasiveness/*pathology ; },
abstract = {A case of endobronchial pagetoid spread of a breast carcinoma metastatic to the lung is described. A 73-year-old woman underwent wedge lung resection after the cytological diagnosis of lung metastasis from ductal invasive breast carcinoma. The breast carcinoma had been surgically removed 6 years previously; at the time of diagnosis it was a T1N0, grade 3 invasive ductal carcinoma, with HER-2 amplification. The lung metastasis measured 1,9 cm and showed the same histology and biological profile of the primary tumor. In addition, numerous neoplastic cells, with large cytoplasm and atypical nuclei, appear to spread along the mucosa of the bronchi adjacent to the metastatic lesion as well as that of the main lobar bronchus, intermingled with the columnar ciliated cells. The neoplastic elements were negative for TTF-1 and strongly HER-2 positive; these features appeared consistent with endobronchial pagetoid spread by the metastatic breast carcinomatous cells.},
}
@article {pmid27430170,
year = {2016},
author = {Liu, L and Li, D and Chen, S and Zhao, R and Pang, D and Li, D and Fu, Z},
title = {B7-H4 expression in human infiltrating ductal carcinoma‑associated macrophages.},
journal = {Molecular medicine reports},
volume = {14},
number = {3},
pages = {2135-2142},
doi = {10.3892/mmr.2016.5510},
pmid = {27430170},
issn = {1791-3004},
mesh = {Biomarkers, Tumor ; Breast Neoplasms/immunology/*metabolism/*pathology ; Carcinoma, Ductal, Breast/immunology/*metabolism/*pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Interleukin-10/metabolism ; Interleukin-6/metabolism ; Macrophages/immunology/*metabolism/pathology ; Middle Aged ; Neoplasm Staging ; Phenotype ; Tumor Microenvironment ; V-Set Domain-Containing T-Cell Activation Inhibitor 1/genetics/*metabolism ; },
abstract = {B7-H4 is a co‑inhibitory molecule of the B7 family, which is expressed on antigen‑presenting cells (APCs) and is able to limit the T‑cell immune response. Macrophages act as professional APCs and are important for immunoregulation of the tumor microenvironment in breast cancer. In order to identify the association between the presence of B7‑H4 on macrophages and infiltrating ductal carcinoma (IDC), the present study investigated the expression of B7‑H4 on macrophages with different polarizations. The expression levels of B7‑H4 in IDC tissues were determined using immunohistochemistry, and the expression of B7‑H4 on macrophages in the breast IDC microenvironment were determined using western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The expression levels of interleukin (IL)‑6 and IL‑10 were detected in IDC tissues and the supernatants of polarized macrophages using an enzyme‑linked immunosorbent assay and RT‑qPCR. The present study demonstrated that B7‑H4 was overexpressed in IDC tissues and macrophages. In vitro, M1 and M2 macrophages exhibited different expression levels of B7‑H4. IL‑6 and ‑10 exhibited higher expression in the IDC tissues compared with in distal pericarcinomatous tissues. In conclusion, B7‑H4 exhibited overexpression in IDC tissues and cultured macrophage cells. Furthermore, M2 macrophages exhibited higher expression levels of B7‑H4 compared with the M1 subtype. In addition, IL‑6 and ‑10 may be associated with B7‑H4 expression on macrophages of different polarizations in the IDC microenvironment.},
}
@article {pmid27415582,
year = {2016},
author = {Laudanski, K and Zawadka, M and Lapko, N},
title = {The Ability of Precursory Monocytes (MO) to Differentiate Varies Among Individuals But Is Stable Over Time.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {22},
number = {},
pages = {2463-2470},
pmid = {27415582},
issn = {1643-3750},
mesh = {Adult ; Antigens, CD1/immunology ; Cell Differentiation/immunology ; Cells, Cultured ; Dendritic Cells/cytology/immunology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology ; Humans ; Interleukin-4/immunology ; Lymphocyte Culture Test, Mixed ; Macrophage Colony-Stimulating Factor/immunology ; Macrophages/cytology/immunology ; Male ; Middle Aged ; Monocytes/*cytology/immunology ; T-Lymphocytes/cytology/immunology ; },
abstract = {BACKGROUND The ability to generate dendritic cells (DCs) from precursory monocytes (MOs) was a breakthrough in the field of immunology. However, it is unknown whether the ability of MOs to differentiate into immature DCs (iDCs) differs across subjects or is time dependent. Given that the study of immune system function is gaining recognition in the field of clinical medicine, it is important to know how certain immunologic features vary over time. MATERIAL AND METHODS This study investigates how much individuals' MO-to-iDC differentiation potential changes over time. We estimated this potential by measuring the expression of an iDC marker (CD1a), cytokine secretion (interleukin [IL]-12p70), and the ability of IL-4 and granulocyte macrophage colony-stimulating factor (GM-CSF) differentiation MOs to stimulate T cells. We collected MOs obtained from different subjects (n=17) at least 1 month apart. Furthermore, we investigated several variables (expression for cytokine receptors, timing, and emergence of DC-related transcriptional factor PU.1). RESULTS The ability of MOs to become DCs under the influence of IL-4 and GM-CSF varied greatly between individuals (range of CD1a expression, 20-80%) but was stable over time (change of CD1a expression between sampling, ~5%). A similar pattern emerged when production of IL-12p70 was analyzed. The ability to stimulate T cells was variable and depended on the T-cell source. The ability of MOs to become iDCs was not linked to the surface expression of receptors for IL-4 and GM-CSF but rather to the activation of PU.1 in the precursory MO. It took 5 days for all committed MOs to become iDCs under in vitro influence of IL-4 and GM-CSF. CONCLUSIONS We concluded that the potential of MO to become iDC is an individual feature and depends on activation of PU.1.},
}
@article {pmid27404457,
year = {2016},
author = {Lumachi, F and Basso, SM and Camozzi, V and Tozzoli, R and Spaziante, R and Ermani, M},
title = {Bone turnover markers in women with early stage breast cancer who developed bone metastases. A prospective study with multivariate logistic regression analysis of accuracy.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {460},
number = {},
pages = {227-230},
doi = {10.1016/j.cca.2016.07.005},
pmid = {27404457},
issn = {1873-3492},
mesh = {Aged ; Alkaline Phosphatase/analysis ; Biomarkers, Tumor/analysis ; Bone Neoplasms/diagnosis/*secondary ; *Bone Remodeling ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Case-Control Studies ; Female ; Humans ; Logistic Models ; Middle Aged ; Peptide Fragments/analysis ; Postmenopause ; Procollagen/analysis ; Prospective Studies ; Tartrate-Resistant Acid Phosphatase/analysis ; },
abstract = {BACKGROUND: The skeleton is the most common site of metastasis for breast cancer and the periodic measurement of circulating bone turnover markers (BTMs) can be useful. The aim of this study was to prospectively evaluate the diagnostic accuracy of a panel of BTMs in the early detection of bone metastases (BMs).<br><br>METHODS: We reviewed the medical records of 297 postmenopausal women with early stage luminal-type invasive ductal carcinoma (IDC). Twenty-six patients who developed isolated BMs during follow-up and 24 randomly selected controls were studied. The two groups were matched according to age, final disease staging, and follow-up. All patients underwent periodic measurement of total and bone-specific (BSAP) alkaline phosphatase, CTX, ICTP, osteocalcin, NTX, PINP, and TRACP5b.<br><br>RESULTS: Only BSAP, CTX, PINP, and TRACP5b were significantly (p<0.05) associated with the group, and the logistic regression analysis excluded CTX from the model. The AUC (ROC curve) for TRACP5b alone, which was the most accurate marker, and for the combination of BSAP+PINP+TRACP5b was 0.784 (95% CI: 0.651-0.916) and 0.889 (95% CI: 0.798-0.981), respectively.<br><br>CONCLUSION: According to our results, the measurement of these three markers together should be performed in all postmenopausal patients with luminal-type IDC, when an early diagnosis of BMs is required.},
}
@article {pmid27401634,
year = {2016},
author = {Divatia, MK and Ro, JY},
title = {Intraductal Carcinoma of the Prostate Gland: Recent Advances.},
journal = {Yonsei medical journal},
volume = {57},
number = {5},
pages = {1054-1062},
pmid = {27401634},
issn = {1976-2437},
mesh = {Carcinoma, Acinar Cell/chemistry/*diagnosis/pathology ; Carcinoma, Ductal/chemistry/*diagnosis/pathology ; Carcinoma, Transitional Cell/chemistry/*diagnosis/pathology ; Diagnosis, Differential ; Humans ; Male ; Neoplasm Grading ; Prostatic Intraepithelial Neoplasia/chemistry/*diagnosis/pathology ; Prostatic Neoplasms/chemically induced/*diagnosis/*pathology ; Tumor Burden ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) is characterized by prostatic carcinoma involving ducts and/or acini. The presence of IDC-P is usually associated with a high-grade Gleason score, large tumor volume, and adverse prognostic parameters, including extraprostatic extension and seminal vesicle invasion. When present, IDC-P is associated with worse outcomes, regardless of treatment status. IDC-P is included in a broader diagnostic category of atypical cribriform lesions of the prostate gland. This category of lesions also includes high-grade prostatic intraepithelial neoplasia (HGPIN), urothelial carcinoma involving prostatic ducts or acini, and prostatic ductal adenocarcinoma, amongst other intraductal proliferations. Differentiating between these entities is important as they have differing therapeutic and prognostic implications for patients, although differential diagnosis thereof is not always straightforward. The present review discusses IDC-P in regards to its morphological characteristics, molecular features, and clinical outcomes. Given the current state of knowledge, the presence of IDC-P should be evaluated and documented correctly in both radical prostatectomy and needle biopsy specimens, and the clinical implications thereof should be taken into consideration during treatment and follow up.},
}
@article {pmid27401580,
year = {2016},
author = {Turner, RB and Valcarlos, E and Won, R and Chang, E and Schwartz, J},
title = {Impact of Infectious Diseases Consultation on Clinical Outcomes of Patients with Staphylococcus aureus Bacteremia in a Community Health System.},
journal = {Antimicrobial agents and chemotherapy},
volume = {60},
number = {10},
pages = {5682-5687},
pmid = {27401580},
issn = {1098-6596},
mesh = {Adult ; Aged ; Bacteremia/*drug therapy/mortality ; Cohort Studies ; Community Health Services ; Female ; Hospitals ; Humans ; Male ; Middle Aged ; Mortality ; Oregon ; Quality of Health Care ; Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/*drug therapy/mortality ; Staphylococcus aureus/*pathogenicity ; Treatment Outcome ; },
abstract = {Staphylococcus aureus bacteremia (SAB) causes high rates of morbidity and death. Several studies in academic health settings have demonstrated that consultations from infectious diseases specialists improve the quality of care and clinical outcomes for SAB. Few data that describe the impact in resource-limited settings such as community hospitals are available. This retrospective cohort study evaluated the adherence to quality-of-care indicators and the clinical outcomes for SAB in a five-hospital community health system (range of 95 to 272 available beds per hospital), for patients with versus without infectious diseases consultation (IDC). IDC was provided if requested by the attending physician. The primary outcome was the incidence of treatment failure, defined as 30-day in-hospital death or 90-day SAB recurrence. Other outcomes included adherence to quality-of-care indicators. A total of 473 adult patients with SAB were included, with 369 (78%) receiving IDC. We identified substantial differences in baseline characteristics between the IDC group and the no-IDC group, including greater incidences of complicated bacteremia and intravenous drug users in the IDC group, with similar rates of severe illness (measured by Pitt bacteremia scores). Adherence to quality-of-care indicators was greater for patients with IDC (P < 0.001). After adjustment for other predicting variables, IDC was associated with a lower rate of treatment failure (adjusted odds ratio, 0.42 [95% confidence interval, 0.20 to 0.86]; P = 0.018). IDC provided better quality of care and better clinical outcomes for patients with SAB who were treated at small, resource-limited, community hospitals.},
}
@article {pmid27383477,
year = {2016},
author = {Sopik, V and Iqbal, J and Sun, P and Narod, SA},
title = {Impact of a prior diagnosis of DCIS on survival from invasive breast cancer.},
journal = {Breast cancer research and treatment},
volume = {158},
number = {2},
pages = {385-393},
doi = {10.1007/s10549-016-3894-9},
pmid = {27383477},
issn = {1573-7217},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/epidemiology ; Carcinoma, Ductal, Breast/*diagnosis/epidemiology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology ; Child ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; SEER Program ; Survival Analysis ; Young Adult ; },
abstract = {A diagnosis of invasive breast cancer after DCIS can be described as a new primary cancer or as a local invasive recurrence. It is of interest to determine if, among women with early-stage breast cancer, a past history of DCIS influences survival. We retrieved the records of 306,249 women diagnosed with stage I or stage II breast cancer between 2004 and 2012, in the surveillance, epidemiology, and end results registries database, of whom 5395 had a previous diagnosis of DCIS. For each patient, we extracted information on the year of diagnosis, age at diagnosis, tumor size, nodal status, grade, estrogen receptor status, type of surgery (lumpectomy/mastectomy), use of radiotherapy (no/yes), prior DCIS (no/yes), cause of death, and follow-up time. For each case with prior DCIS, we recorded information on the year of diagnosis of DCIS, laterality of DCIS, and treatments received for DCIS. We matched 3979 patients with a prior DCIS to 3979 patients without a prior DCIS, according to the various prognostic features of the invasive cancer. We estimated the risk of death from breast cancer for patients with invasive ductal carcinoma, with and without a prior diagnosis of DCIS. We identified 306,249 women with stage I/II breast cancer, of whom 2335 had a prior ipsilateral DCIS and 3060 had a prior contralateral DCIS. Breast cancer-specific survival at 9 years was 94.6 % for patients with a prior DCIS (ipsilateral or contralateral) and was 95.2 % for patients with no prior DCIS (p = 0.32). In a matched analysis (3979 matched pairs), the hazard ratio for death from breast cancer for patients with a prior ipsilateral DCIS, compared to patients with no prior DCIS, was 0.91 (95 % CI = 0.49-1.68; p = 0.75). A prior diagnosis of ipsilateral DCIS does not impact upon the prognosis of women with early-stage invasive breast cancer. This suggests that primary breast cancers and local invasive recurrences following DCIS are similar conditions and should be treated in the same way.},
}
@article {pmid27376491,
year = {2016},
author = {Koca, &#x130; and Özgür, A and Er, M and Gümüş, M and Açikalin Coşkun, K and Tutar, Y},
title = {Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis.},
journal = {European journal of medicinal chemistry},
volume = {122},
number = {},
pages = {280-290},
doi = {10.1016/j.ejmech.2016.06.032},
pmid = {27376491},
issn = {1768-3254},
mesh = {Adenosine Triphosphatases/antagonists &amp; inhibitors ; Adenosine Triphosphate/metabolism ; Antineoplastic Agents/chemical synthesis/chemistry/pharmacology ; Bone Neoplasms/pathology/*secondary ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; *Drug Design ; HSP90 Heat-Shock Proteins/*antagonists &amp; inhibitors/chemistry ; Humans ; Hydrolysis/drug effects ; Molecular Docking Simulation ; Protein Conformation, beta-Strand ; Thiourea/*chemical synthesis/chemistry/*pharmacology ; },
abstract = {Invasive ductal carcinoma is the most common breast malignancies tumors and has tendency to bone metastases. Many oncogenic client proteins involved in formation of metastatic pathways. Stabilization, regulation, and maintenance of these oncogenic client proteins are provided with Heat Shock Protein 90 (Hsp90). Hsp90 perform these processes through its ATP binding and subsequent hydrolysis energy. Therefore, designing Hsp90 inhibitors is a novel cancer treatment method. However, many Hsp90 inhibitors have solubility problems and showed adverse effects in clinical trials. Thus, we designed and synthesized novel pyrimidinyl acyl thiourea derivatives to selectively inhibit Hsp90 alpha in human invasive ductal breast (MCF-7) and human bone osteosarcoma (Saos-2) cell lines. In vitro experiments showed that the compounds inhibited cell proliferation, ATP hydrolysis, and exhibited cytotoxic effect on these cancer cell lines. Further, gene expression was analyzed by microarray studies on MCF-7 cell lines. Several genes that play vital roles in breast cancer pathogenesis displayed altered gene expression in the presence of a selected pyrimidinyl acyl thiourea compound. Molecular docking studies were also performed to determine interaction between Hsp90 ATPase domain and pyrimidinyl acyl thiourea derivatives. The results indicated that the compounds are able to interact with Hsp90 ATP binding pocket and inhibit ATPase function. The designed compounds powerfully inhibit Hsp90 by an average of 1 μM inhibition constant. And further, the compounds perturb Hsp90 N terminal domain proper orientation and ATP may not provide required conformational change for Hsp90 function as evidenced by in silico experiments. Therefore, the designed compounds effectively inhibited both invasive ductal breast carcinoma and bone metastasis. Pyrimidinyl acyl thiourea derivatives may provide a drug template for effective treatment of invasive ductal breast carcinoma and its bone metastasis as well as new therapeutic perspective for drug design.},
}
@article {pmid27374087,
year = {2016},
author = {Duru, N and Gernapudi, R and Lo, PK and Yao, Y and Wolfson, B and Zhang, Y and Zhou, Q},
title = {Characterization of the CD49f+/CD44+/CD24- single-cell derived stem cell population in basal-like DCIS cells.},
journal = {Oncotarget},
volume = {7},
number = {30},
pages = {47511-47525},
pmid = {27374087},
issn = {1949-2553},
support = {R01 CA157779/CA/NCI NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/etiology/*pathology ; CD24 Antigen/*analysis ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Cell Line, Tumor ; Cell Movement ; DNA Methylation ; Female ; Humans ; Hyaluronan Receptors/*analysis ; Integrin alpha6/*analysis ; Mice ; Neoplastic Stem Cells/*pathology ; Octamer Transcription Factor-3/physiology ; SOXB1 Transcription Factors/physiology ; },
abstract = {The molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, by applying a novel single-cell clonogenic approach with the CD49f+/CD44+/CD24- surface markers, we characterized the aggressive clones that have enhanced self-renewal, migratory and invasive capacities derived from a human DCIS model cell line MCF10DCIS. The aggressive clones had elevated ALDH1 activity, lower global DNA methylation and increased expression of stem cell related genes, especially concurrent activation of SOX2/OCT4. In addition, we showed that the aggressive clones have increased expression of lincRNA-RoR and miR-10b compared to non-aggressive clones, which enhance their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. Our data suggest that lincRNA-RoR and miR10b could be used to distinguish aggressive clones from non-aggressive clones within the heterogeneous CD49f+/CD44+/CD24- DCIS population. Our findings also provide the foundation to develop new chemoprevention agents for DCIS-IDC transition.},
}
@article {pmid27362268,
year = {2016},
author = {Gertz, EM and Chowdhury, SA and Lee, WJ and Wangsa, D and Heselmeyer-Haddad, K and Ried, T and Schwartz, R and Schäffer, AA},
title = {FISHtrees 3.0: Tumor Phylogenetics Using a Ploidy Probe.},
journal = {PloS one},
volume = {11},
number = {6},
pages = {e0158569},
pmid = {27362268},
issn = {1932-6203},
support = {R01 CA140214/CA/NCI NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; *Databases, Genetic ; Female ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Ploidies ; Uterine Cervical Neoplasms/*genetics/pathology ; },
abstract = {Advances in fluorescence in situ hybridization (FISH) make it feasible to detect multiple copy-number changes in hundreds of cells of solid tumors. Studies using FISH, sequencing, and other technologies have revealed substantial intra-tumor heterogeneity. The evolution of subclones in tumors may be modeled by phylogenies. Tumors often harbor aneuploid or polyploid cell populations. Using a FISH probe to estimate changes in ploidy can guide the creation of trees that model changes in ploidy and individual gene copy-number variations. We present FISHtrees 3.0, which implements a ploidy-based tree building method based on mixed integer linear programming (MILP). The ploidy-based modeling in FISHtrees includes a new formulation of the problem of merging trees for changes of a single gene into trees modeling changes in multiple genes and the ploidy. When multiple samples are collected from each patient, varying over time or tumor regions, it is useful to evaluate similarities in tumor progression among the samples. Therefore, we further implemented in FISHtrees 3.0 a new method to build consensus graphs for multiple samples. We validate FISHtrees 3.0 on a simulated data and on FISH data from paired cases of cervical primary and metastatic tumors and on paired breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Tests on simulated data show improved accuracy of the ploidy-based approach relative to prior ploidyless methods. Tests on real data further demonstrate novel insights these methods offer into tumor progression processes. Trees for DCIS samples are significantly less complex than trees for paired IDC samples. Consensus graphs show substantial divergence among most paired samples from both sets. Low consensus between DCIS and IDC trees may help explain the difficulty in finding biomarkers that predict which DCIS cases are at most risk to progress to IDC. The FISHtrees software is available at ftp://ftp.ncbi.nih.gov/pub/FISHtrees.},
}
@article {pmid27358153,
year = {2016},
author = {Alessio, C and Scali, E and Manti, F and Amoruso, GF and Marchese, S and Riga, B and Bottoni, U and Tamburrini, O},
title = {An unusual case of mammary Paget’s disease in a woman with psoriasis.},
journal = {Journal of biological regulators and homeostatic agents},
volume = {30},
number = {2},
pages = {589-592},
pmid = {27358153},
issn = {0393-974X},
mesh = {Breast Neoplasms/*etiology ; Female ; Humans ; Middle Aged ; Paget's Disease, Mammary/*etiology ; Psoriasis/*complications ; },
abstract = {Mammary Paget’s disease (MPD) is a malignant breast tumor, which is characterized by intraepidermal infiltration from malignant glandular epithelial cells. Often it may include an underlying ductal carcinoma in situ or an invasive ductal carcinoma. Clinically it appears as an erythematous patch, moist or crusted, with or without desquamation that in some cases becomes ulcerated, causing infiltration and inversion of the nipple. We report the clinical case of a 60-year-old woman, treated in our department for psoriasis, presenting with erythema of nipple and areola with nipple erosion, ulceration and poor secretion. Suspecting Paget’s disease of the nipple, radiological exams (mammography and breast MRI) were performed. A biopsy for histological examination was carried out and confirmed the diagnosis of mammary Paget’s disease. MPD is sometimes difficult to diagnose both clinically and radiologically, therefore it is important to distinguish from other conditions: in literature MPD is reported in differential diagnosis with psoriasis given its similar clinical features, and in some cases MPD has been treated with topical and systemic steroids due to a wrong diagnosis. However, the concomitance, in the same individual, of mammary Paget’s disease and psoriasis has never been described.},
}
@article {pmid27355204,
year = {2016},
author = {Winn, JS and Baker, MG and Fanous, IS and Slack-Davis, JK and Atkins, KA and Dillon, PM},
title = {Lobular Breast Cancer and Abdominal Metastases: A Retrospective Review and Impact on Survival.},
journal = {Oncology},
volume = {91},
number = {3},
pages = {135-142},
doi = {10.1159/000447264},
pmid = {27355204},
issn = {1423-0232},
mesh = {Abdominal Neoplasms/*secondary/therapy ; Age Factors ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/*pathology/therapy ; Breast Neoplasms, Male/pathology/therapy ; Carcinoma, Ductal, Breast/*secondary/therapy ; Carcinoma, Lobular/*secondary/therapy ; Disease-Free Survival ; Female ; Humans ; Male ; Mastectomy, Segmental ; Middle Aged ; *Neoplasm Recurrence, Local/etiology ; Neoplasm Staging ; Neoplasm, Residual ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Survival Rate ; },
abstract = {BACKGROUND: The predominant breast cancer subtypes, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), have similar recurrence and survival rates but differing patterns of metastatic recurrence.<br><br>METHODS: A retrospective review of breast cancers treated at an academic medical center from 1999 to 2012 was performed. Demographic, pathologic, treatment, and follow-up data were collected for 179 ILC and 358 IDC patients (1:2 stage-matched). The median follow-up was 4.7 years.<br><br>RESULTS: The baseline characteristics were similar in the two groups. ILC was more likely to be hormone-receptor-positive/HER2-negative and mammographically occult. The number of surgical resections, breast conservation rate, systemic treatment, and taxane use was similar between the groups. The overall recurrence rate was the same. ILC recurred more often in the abdominal cavity (24.3% in ILC vs. 4.1% in IDC, p = 0.001). The disease-free survival and overall survival were equal. On multivariate analysis, age, stage of disease, hormone receptor status, and systemic therapy were associated with survival, but histology was not.<br><br>CONCLUSIONS: Compared to ductal breast cancers, lobular breast cancers recur more often in the abdominal cavity. Both ILC and IDC have comparable surgical and medical treatment outcomes and survival. Our data suggest that enhanced surveillance and imaging might be useful in ILC.},
}
@article {pmid27353975,
year = {2016},
author = {Timpano, H and Chan Ho Tong, L and Gautier, V and Lalucque, H and Silar, P},
title = {The PaPsr1 and PaWhi2 genes are members of the regulatory network that connect stationary phase to mycelium differentiation and reproduction in Podospora anserina.},
journal = {Fungal genetics and biology : FG &amp; B},
volume = {94},
number = {},
pages = {1-10},
doi = {10.1016/j.fgb.2016.06.006},
pmid = {27353975},
issn = {1096-0937},
mesh = {Fungal Proteins/genetics ; *Gene Expression Regulation, Fungal ; *Gene Regulatory Networks ; Genetic Complementation Test ; Mutation ; Mycelium/*genetics/growth &amp; development ; Phosphorylation ; Podospora/*genetics/growth &amp; development ; },
abstract = {In filamentous fungi, entrance into stationary phase is complex as it is accompanied by several differentiation and developmental processes, including the synthesis of pigments, aerial hyphae, anastomoses and sporophores. The regulatory networks that control these processes are still incompletely known. The analysis of the "Impaired in the development of Crippled Growth (IDC)" mutants of the model filamentous ascomycete Podospora anserina has already yielded important information regarding the pathway regulating entrance into stationary phase. Here, the genes affected in two additional IDC mutants are identified as orthologues of the Saccharomyces cerevisiae WHI2 and PSR1 genes, known to regulate stationary phase in this yeast, arguing for a conserved role of these proteins throughout the evolution of ascomycetes.},
}
@article {pmid27333920,
year = {2016},
author = {Onodera, Y and Takagi, K and Miki, Y and Takayama, K and Shibahara, Y and Watanabe, M and Ishida, T and Inoue, S and Sasano, H and Suzuki, T},
title = {TACC2 (transforming acidic coiled-coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation.},
journal = {Cancer medicine},
volume = {5},
number = {8},
pages = {1973-1982},
pmid = {27333920},
issn = {2045-7634},
mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Breast Neoplasms/*metabolism/*mortality/pathology ; Carrier Proteins/genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gonadal Steroid Hormones/metabolism ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Tumor Suppressor Proteins/genetics/metabolism ; },
abstract = {Transforming acidic coiled-coil protein 2 (TACC2) belongs to TACC family proteins and involved in a variety of cellular processes through interactions with some molecules involved in centrosomes/microtubules dynamics. Mounting evidence suggests that TACCs is implicated in the progression of some human malignancies, but significance of TACC2 protein in breast carcinoma is still unknown. Therefore, in this study, we examined the clinical significance of TACC2 in breast carcinoma and biological functions by immunohistochemistry and in vitro experiments. Immunohistochemistry for TACC2 was performed in 154 cases of invasive ductal carcinoma. MCF-7 and MDA-MB-453 breast carcinoma cell lines were transfected with small interfering RNA (siRNA) for TACC2, and subsequently, cell proliferation, 5-Bromo-2'-deoxyuridine (BrdU), and invasion assays were performed. TACC2 immunoreactivity was detected in 78 out of 154 (51%) breast carcinoma tissues, and it was significantly associated with Ki-67 LI. The immunohistochemical TACC2 status was significantly associated with increased incidence of recurrence and breast cancer-specific death of the patients, and multivariate analyses demonstrated TACC2 status as an independent prognostic factor for both disease-free and breast cancer-specific survival. Subsequent in vitro experiments showed that TACC2 significantly increased the proliferation activity of MCF-7 and MDA-MB-453. These results suggest that TACC2 plays an important role in the cell proliferation of breast carcinoma and therefore immunohistochemical TACC2 status is a candidate of worse prognostic factor in breast cancer cases.},
}
@article {pmid27323669,
year = {2016},
author = {Gautheron, J and Vucur, M and Schneider, AT and Severi, I and Roderburg, C and Roy, S and Bartneck, M and Schrammen, P and Diaz, MB and Ehling, J and Gremse, F and Heymann, F and Koppe, C and Lammers, T and Kiessling, F and Van Best, N and Pabst, O and Courtois, G and Linkermann, A and Krautwald, S and Neumann, UP and Tacke, F and Trautwein, C and Green, DR and Longerich, T and Frey, N and Luedde, M and Bluher, M and Herzig, S and Heikenwalder, M and Luedde, T},
title = {The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance.},
journal = {Nature communications},
volume = {7},
number = {},
pages = {11869},
pmid = {27323669},
issn = {2041-1723},
support = {208237/ERC_/European Research Council/International ; },
mesh = {Adipocytes/enzymology/pathology ; Adipose Tissue, White/*enzymology/pathology ; Animals ; Apoptosis/genetics ; Body Mass Index ; Caspase 8/genetics/metabolism ; Choline/metabolism ; Choline Deficiency/enzymology/etiology/*genetics/pathology ; Diet, High-Fat ; Gene Expression Regulation ; Glucose Intolerance/enzymology/etiology/*genetics/pathology ; Homeostasis ; Humans ; Inflammation ; Insulin/metabolism ; Insulin Resistance ; Intra-Abdominal Fat/*enzymology/pathology ; Male ; Mice ; Necrosis/*enzymology/genetics/pathology ; Obesity/enzymology/etiology/*genetics/pathology ; Receptor-Interacting Protein Serine-Threonine Kinases/*genetics/metabolism ; },
abstract = {Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting that it might be a privileged pharmacological target. However, its function in glucose homeostasis and obesity has been unknown. Here we show that RIPK3 is over expressed in the white adipose tissue (WAT) of obese mice fed with a choline-deficient high-fat diet. Genetic inactivation of Ripk3 promotes increased Caspase-8-dependent adipocyte apoptosis and WAT inflammation, associated with impaired insulin signalling in WAT as the basis for glucose intolerance. Similarly to mice, in visceral WAT of obese humans, RIPK3 is overexpressed and correlates with the body mass index and metabolic serum markers. Together, these findings provide evidence that RIPK3 in WAT maintains tissue homeostasis and suppresses inflammation and adipocyte apoptosis, suggesting that systemic targeting of necroptosis might be associated with the risk of promoting insulin resistance in obese patients.},
}
@article {pmid27306813,
year = {2016},
author = {Terasawa, R and Iwamoto, M and Tanaka, S and Kimura, K and Takahashi, Y and Fujioka, H and Sato, N and Kawaguchi, K and Ikari, A and Maezawa, S and Tominaga, T and Matsuda, J and Umezaki, N and Uchiyama, K},
title = {[A Case of Squamous Cell Carcinoma of the Breast].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {43},
number = {6},
pages = {749-752},
pmid = {27306813},
issn = {0385-0684},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Squamous Cell/*diagnosis/therapy ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Fatal Outcome ; Female ; Humans ; Recurrence ; Thoracic Wall/*pathology ; },
abstract = {Squamous cell carcinoma(SCC)of the breast is a rare disease. We encountered a case of SCC of the breast that relapsed in the early postoperative period and rapidly progressed thereafter. A 38-year-old woman visited our hospital presenting with a tumor in the left breast consisting of a 5-cm mass with an irregularly sharped wall. Fine needle biopsy examination showed squamous cell carcinoma. A modified radical mastectomy by Auchincloss's method was performed on the left breast. SCC was confirmed by histological examination. Two months later, local recurrence on the chest wall was found during adjuvant chemotherapy. Thereafter, the disease rapidly progressed, and finally, the patient died of respiratory failure caused by lung metastasis. The prognosis of SCC of the breast is recognized as being more unfavorable than that of invasive ductal carcinoma. We should develop an effective chemotherapeutic strategy for this disease.},
}
@article {pmid27284958,
year = {2016},
author = {Ross, JS and Gay, LM and Wang, K and Ali, SM and Chumsri, S and Elvin, JA and Bose, R and Vergilio, JA and Suh, J and Yelensky, R and Lipson, D and Chmielecki, J and Waintraub, S and Leyland-Jones, B and Miller, VA and Stephens, PJ},
title = {Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: An emerging opportunity for anti-HER2 targeted therapies.},
journal = {Cancer},
volume = {122},
number = {17},
pages = {2654-2662},
doi = {10.1002/cncr.30102},
pmid = {27284958},
issn = {1097-0142},
mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/drug therapy/*genetics/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/secondary ; Carcinoma, Lobular/drug therapy/genetics/secondary ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic/drug effects ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Middle Aged ; *Molecular Targeted Therapy ; Mutation/*genetics ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/drug therapy/*genetics/pathology ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/antagonists &amp; inhibitors/*genetics ; },
abstract = {BACKGROUND: Activating, nonamplification ERBB2 mutations (ERBB2mut) are not detected by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but are detected by DNA sequencing and may predict clinical responses to human epidermal growth factor receptor (HER2)-targeted therapy. The authors queried 5605 advanced/metastatic breast cancers (mBC) to uncover the frequency of ERBB2mut genomic alterations. Clinical responses to anti-HER2 therapeutics were identified.<br><br>METHODS: DNA was extracted from 40&#x2009;&#xb5;m of formalin-fixed paraffin-embedded (FFPE) sections. Comprehensive genomic profiling (CGP) was used to evaluate up to 315 genes (592&#xd7; mean coverage depth). Results were analyzed for base substitutions, short indels, copy number changes, and selected rearrangements.<br><br>RESULTS: Of 5605 cases, 698 (12.5%) featured ERBB2 alterations, including 596 (10.6%) ERBB2 amplifications (ERBB2amp) and 138 (2.4%) ERBB2mut; 38 cases (0.7%) had co-occurring ERBB2amp and ERBB2mut. ERBB2mut predominantly affected the kinase (124 cases; 90%) or extracellular (15 cases; 11%) domains. Both primary BC (52 cases; 38%) and metastatic site biopsies (86 cases; 62%) were found to harbor ERBB2mut, which were distributed across carcinoma not otherwise specified (NOS) (69 cases; 50%), invasive ductal carcinoma (IDC) (40 cases; 29%), invasive lobular carcinoma (ILC) (27 cases; 20%), and mucinous mBC (2 cases; 1%). Genes commonly coaltered with ERBB2 were tumor protein 53 (TP53) (49%); phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (42%); cadherin 1, type 1 (CDH1) (37%); MYC (17%); and cyclin D1 protein (CCND1) (16%). CDH1 mutations were enriched in ERBB2mut mBC (P<0.0006) and associated with recurrent mBC. Selected patients with ERBB2mut, without ERBB2amp, who responded to anti-HER2 targeted therapies are presented herein.<br><br>CONCLUSIONS: Within this large series, 1.8% of cases harbored ERBB2mut, which are undetectable by standard-of-care IHC or FISH tests. Metastatic BC driven by ERBB2mut respond to anti-HER2 targeted therapies, and expanding clinical trials designed to detect ERBB2mut by CGP and optimize targeted treatments are warranted. Cancer 2016. &#xa9; 2016 American Cancer Society. Cancer 2016;122:2654-2662. &#xa9; 2016 American Cancer Society.},
}
@article {pmid27279334,
year = {2016},
author = {Shen, S and Wang, Y and Wang, C and Wu, YN and Xing, Y},
title = {SURVIV for survival analysis of mRNA isoform variation.},
journal = {Nature communications},
volume = {7},
number = {},
pages = {11548},
pmid = {27279334},
issn = {2041-1723},
support = {R01 GM088342/GM/NIGMS NIH HHS/United States ; R01 GM105431/GM/NIGMS NIH HHS/United States ; },
mesh = {*Alternative Splicing ; Breast Neoplasms/*etiology/mortality ; Carcinoma, Ductal, Breast/*etiology/mortality ; Humans ; Models, Statistical ; *RNA Isoforms ; *Survival Analysis ; },
abstract = {The rapid accumulation of clinical RNA-seq data sets has provided the opportunity to associate mRNA isoform variations to clinical outcomes. Here we report a statistical method SURVIV (Survival analysis of mRNA Isoform Variation), designed for identifying mRNA isoform variation associated with patient survival time. A unique feature and major strength of SURVIV is that it models the measurement uncertainty of mRNA isoform ratio in RNA-seq data. Simulation studies suggest that SURVIV outperforms the conventional Cox regression survival analysis, especially for data sets with modest sequencing depth. We applied SURVIV to TCGA RNA-seq data of invasive ductal carcinoma as well as five additional cancer types. Alternative splicing-based survival predictors consistently outperform gene expression-based survival predictors, and the integration of clinical, gene expression and alternative splicing profiles leads to the best survival prediction. We anticipate that SURVIV will have broad utilities for analysing diverse types of mRNA isoform variation in large-scale clinical RNA-seq projects.},
}
@article {pmid27267193,
year = {2016},
author = {Desmond, BL and Blattner, CM and Young Iii, J},
title = {Generalized morphea as the first sign of breast carcinoma: a case report.},
journal = {Dermatology online journal},
volume = {22},
number = {2},
pages = {},
pmid = {27267193},
issn = {1087-2108},
mesh = {Breast Neoplasms/*complications/diagnosis ; Carcinoma, Ductal, Breast/*complications/diagnosis ; Female ; Humans ; Middle Aged ; Paraneoplastic Syndromes/*complications/pathology ; Scleroderma, Localized/*complications/pathology ; },
abstract = {Generalized morphea is a rare idiopathic form of scleroderma that literally means "hard skin." Morphea is usually considered an isolated event that is not associated with malignancy. However, case reports of lung, hematologic, and breast cancer occurring simultaneously with large plaque morphea have caused dermatologists to question whether a work-up for malignancy is appropriate. We highlight a case of generalized morphea that preceded invasive ductal carcinoma of the breast and provide a discussion about the possible paraneoplastic origin of generalized morphea and systemic sclerosis (SSc).},
}
@article {pmid27258056,
year = {2016},
author = {Ahuja, S and Makkar, P and Gupta, S and Vigoda, I},
title = {Paraneoplastic syndrome and underlying breast cancer: a worsening rash despite initiation of chemotherapy.},
journal = {The Journal of community and supportive oncology},
volume = {14},
number = {5},
pages = {229-231},
doi = {10.12788/jcso.0186},
pmid = {27258056},
issn = {2330-7749},
abstract = {Skin may show the first clinical evidence of systemic disease and can be the first clue to malignancy in 1% of cases. Dermatomyositis is an immunologically mediated inflammatory myopathy characterized by proximal muscle weakness, muscle inflammation, and characteristic skin findings. It has an incidence of 1 in 100,000 patients. In 15%-30% cases of dermatomyositis, an underlying malignancy is the cause of paraneoplastic syndrome. Ovarian and breast cancer in women and lung cancer in men are the most common malignancies associated with dermatomyositis. Here we report the case of a 55-year-old postmenopausal woman who initially presented with a facial rash. She was treated for chemical dermatitis without resolution of symptoms and was subsequently found to have dermatomyositis associated with stage IV invasive ductal carcinoma of the breast. In most cases, the skin changes resolve after treatment for the underlying malignancy has been initiated, but in this case of paraneoplastic dermatomyositis, the rash worsened with initiation of treatment for underlying breast cancer.},
}
@article {pmid27255575,
year = {2017},
author = {Bond, SE and Boutlis, CS and Jansen, SG and Miyakis, S},
title = {Discontinuation of peri-operative gentamicin use for indwelling urinary catheter manipulation in orthopaedic surgery.},
journal = {ANZ journal of surgery},
volume = {87},
number = {11},
pages = {E199-E203},
doi = {10.1111/ans.13642},
pmid = {27255575},
issn = {1445-2197},
mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Antibiotic Prophylaxis/standards ; Arthroplasty/*adverse effects ; Australia/epidemiology ; Bacteremia/drug therapy/prevention &amp; control ; Bacteriuria/drug therapy/prevention &amp; control ; Catheters, Indwelling/adverse effects/microbiology/*standards ; Device Removal/adverse effects/standards ; Female ; Gentamicins/administration &amp; dosage/*therapeutic use ; Humans ; Male ; Middle Aged ; New South Wales/epidemiology ; Orthopedic Procedures/*adverse effects ; Perioperative Care/*standards ; Practice Patterns, Physicians'/standards ; Retrospective Studies ; Surgical Wound Infection/prevention &amp; control ; Urinary Catheters/*microbiology ; },
abstract = {BACKGROUND: Gentamicin has historically been used prior to insertion and removal of indwelling urinary catheters (IDCs) around elective joint replacement surgery to prevent infection; however, this indication is not recognized in the Australian Therapeutic Guidelines: Antibiotic and the paradigm for safe use of gentamicin has shifted.<br><br>METHODS: The antimicrobial stewardship team of a 500 bed tertiary regional hospital performed a retrospective clinical study of gentamicin IDC prophylaxis around total hip and knee arthroplasties. Results were presented to the orthopaedic surgeons. A literature review identified no guidelines to support gentamicin prophylaxis and only a very low risk of bacteraemia associated with IDC insertion/removal in patients with established bacteriuria. Consensus was reached with the surgeons to discontinue this practice. Subsequent prospective data collection was commenced to determine effectiveness, with weekly feedback to the Department Head of Orthopaedics.<br><br>RESULTS: Data from 137 operations pre-intervention (6 months) were compared with 205 operations post-intervention (12 months). The median patient age was 72 years in both groups. Following the intervention, reductions in gentamicin use were demonstrated for IDC insertion (59/137 (42%) to 4/205 (2%), P < 0.01) and removal (39/137 (28%) to 6/205 (3%), P < 0.01). No gentamicin use was observed during the final 40 weeks of the post-intervention period. There were no significant differences between the groups for pre-operative bacteriuria, surgical site infections or acute kidney injury.<br><br>CONCLUSION: A collaborative approach using quality improvement methodology can lead to an evidence-based reappraisal of established practice. Regular rolling audits and timely feedback were useful in sustaining change.},
}
@article {pmid27209064,
year = {2016},
author = {Roggenbuck, D and Borghi, MO and Somma, V and Büttner, T and Schierack, P and Hanack, K and Grossi, C and Bodio, C and Macor, P and von Landenberg, P and Boccellato, F and Mahler, M and Meroni, PL},
title = {Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers.},
journal = {Arthritis research &amp; therapy},
volume = {18},
number = {1},
pages = {111},
pmid = {27209064},
issn = {1478-6362},
mesh = {Adult ; Aged ; Antibodies, Antiphospholipid/*analysis ; Antiphospholipid Syndrome/*diagnosis/immunology ; Diagnosis, Differential ; Female ; Humans ; Immunoassay/*methods ; Infections/diagnosis/immunology ; Male ; Middle Aged ; Young Adult ; },
abstract = {BACKGROUND: Antiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)).<br><br>METHODS: Sixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (&#x3b2;2GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-&#x3b2;2GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human &#x3b2;2GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human &#x3b2;2GPI or after CL-micelle absorption.<br><br>RESULTS: Comparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM a&#xdf;2GPI and aCL. Anti-CL and anti-&#xdf;2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and &#xdf;2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL)&#x2009;+&#x2009;samples than in patients with APS. HumoAb against domain 1 recognized &#x3b2;2GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-&#x3b2;2GPI humoAbs.<br><br>CONCLUSIONS: The LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1.},
}
@article {pmid27208304,
year = {2016},
author = {Van Aken, O and De Clercq, I and Ivanova, A and Law, SR and Van Breusegem, F and Millar, AH and Whelan, J},
title = {Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases.},
journal = {Plant physiology},
volume = {171},
number = {3},
pages = {2150-2165},
pmid = {27208304},
issn = {1532-2548},
mesh = {Antimycin A/pharmacology ; Arabidopsis/drug effects/*physiology ; Arabidopsis Proteins/genetics/metabolism ; Chloroplasts/drug effects/*physiology ; Energy Metabolism/genetics ; Fluoroacetates/pharmacology ; Gene Expression Regulation, Plant/drug effects ; Mitochondria/drug effects/*physiology ; Mitochondrial Proteins/genetics ; Plants, Genetically Modified ; Signal Transduction/drug effects ; Stress, Physiological/*physiology ; Transcription Factors/genetics/metabolism ; },
abstract = {Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control.},
}
@article {pmid27184932,
year = {2016},
author = {Desai, K and Nair, MG and Prabhu, JS and Vinod, A and Korlimarla, A and Rajarajan, S and Aiyappa, R and Kaluve, RS and Alexander, A and Hari, PS and Mukherjee, G and Kumar, RV and Manjunath, S and Correa, M and Srinath, BS and Patil, S and Prasad, MS and Gopinath, KS and Rao, RN and Violette, SM and Weinreb, PH and Sridhar, TS},
title = {High expression of integrin β6 in association with the Rho-Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers.},
journal = {Cancer medicine},
volume = {5},
number = {8},
pages = {2000-2011},
pmid = {27184932},
issn = {2045-7634},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*metabolism/mortality/pathology ; Female ; Gene Amplification ; Gene Expression ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Integrin beta Chains/*genetics ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Receptor, ErbB-2/genetics/*metabolism ; *Signal Transduction ; rac GTP-Binding Proteins/*metabolism ; },
abstract = {Integrin αvβ6 is involved in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast. In addition, integrin β6 (ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin αvβ6 in clinical progression of invasive breast cancers need further elucidation. We have examined human breast cancer specimens (N = 460) for the expression of integrin β6 (ITGB6) mRNA by qPCR. In addition, we have examined a subset (N = 147) for the expression of αvβ6 integrin by immunohistochemistry (IHC). The expression levels of members of Rho-Rac pathway including downstream genes (ACTR2, ACTR3) and effector proteinases (MMP9, MMP15) were estimated by qPCR in the HER2+ subset (N = 59). There is a significant increase in the mean expression of ITGB6 in HER2+ tumors compared to HR+HER2- and triple negative (TNBC) subtypes (P = 0.00). HER2+ tumors with the highest levels (top quartile) of ITGB6 have significantly elevated levels of all the genes of the Rho-Rac pathway (P-values from 0.01 to 0.0001). Patients in this group have a significantly shorter disease-free survival compared to the group with lower ITGB6 levels (HR = 2.9 (0.9-8.9), P = 0.05). The mean level of ITGB6 expression is increased further in lymph node-positive tumors. The increased regional and distant metastasis observed in HER2+ tumors with high levels of ITGB6 might be mediated by the canonical Rho-Rac pathway through increased expression of MMP9 and MMP15.},
}
@article {pmid27173185,
year = {2016},
author = {Oliveira, NC and Gomig, TH and Milioli, HH and Cordeiro, F and Costa, GG and Urban, CA and Lima, RS and Cavalli, IJ and Ribeiro, EM},
title = {Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.},
journal = {Genetics and molecular research : GMR},
volume = {15},
number = {2},
pages = {},
doi = {10.4238/gmr.15027701},
pmid = {27173185},
issn = {1676-5680},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Proteome/*genetics/metabolism ; },
abstract = {Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy.},
}
@article {pmid27161340,
year = {2016},
author = {Zalsman, G and Shoval, G and Mansbach-Kleinfeld, I and Farbstein, I and Kanaaneh, R and Lubin, G and Apter, A},
title = {Maternal versus adolescent reports of suicidal behaviors: a nationwide survey in Israel.},
journal = {European child &amp; adolescent psychiatry},
volume = {25},
number = {12},
pages = {1349-1359},
pmid = {27161340},
issn = {1435-165X},
mesh = {Adolescent ; Adolescent Behavior/*psychology ; Depressive Disorder/psychology ; Female ; *Health Surveys/standards ; Humans ; Israel/epidemiology ; Male ; Mothers/*psychology ; Prevalence ; Residence Characteristics ; Risk Factors ; *Self Report/standards ; Stress Disorders, Post-Traumatic/epidemiology/psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; },
abstract = {Community and nationwide surveys on adolescent suicidal behaviors using clinical interviews are not abundant. Rates of self-reported suicide attempts in community samples vary greatly between 1 and 20 %. In general, adolescent and parental agreement in child psychiatry practice is low, and their agreement with regard to suicidal behavior is unknown. The current study assesses the rates of suicidal ideation and behaviors as well as the rate of agreement between adolescents and their mothers in a representative nationwide sample. The survey included a representative and randomized community sample of 14- to 17-year-old adolescents (n = 957), and their mothers who were interviewed using the Development and Well-Being Assessment Inventory (DAWBA). The prevalence of suicidal ideation and self-initiated behaviors was 4.9 and 1.9 %, respectively. The concordance between mothers' and adolescents' reporting on ideation was low (7.3 %). There was no concordance between mothers' and adolescents' reports of suicidal acts. Adolescents reported self-initiated behaviors nearly three times more frequently than their mothers. Paternal unemployment, care by welfare agencies and having a psychiatric disorder, specifically depression or post-traumatic stress disorder, was associated with a higher risk for both suicidal ideation and attempts. In this nationwide community study, by evaluating information gathered by clinical interviews, it was found that the lifetime rates of suicidal ideation were moderate. The rates of suicide attempts were lower than have been previously reported. The concordance between the reports of adolescents and their mothers was low for ideation and nonexistent for attempts. Thus, clinicians should interview adolescents separately from their mothers regarding their suicidality.},
}
@article {pmid27156133,
year = {2016},
author = {Santos, CS and Carvalho, SM and Leite, A and Moniz, T and Roriz, M and Rangel, AO and Rangel, M and Vasconcelos, MW},
title = {Effect of tris(3-hydroxy-4-pyridinonate) iron(III) complexes on iron uptake and storage in soybean (Glycine max L.).},
journal = {Plant physiology and biochemistry : PPB},
volume = {106},
number = {},
pages = {91-100},
doi = {10.1016/j.plaphy.2016.04.050},
pmid = {27156133},
issn = {1873-2690},
mesh = {Biomass ; Chlorophyll/metabolism ; FMN Reductase/metabolism ; Ferric Compounds/*pharmacology ; Gene Expression Regulation, Plant/drug effects ; Iron/*metabolism ; Iron Chelating Agents/chemistry/pharmacology ; Ligands ; Lipid Peroxidation/drug effects ; Malondialdehyde/metabolism ; Minerals/metabolism ; Plant Development/drug effects ; Plant Diseases ; Plant Leaves/drug effects/metabolism ; Plant Proteins/genetics/metabolism ; Plant Roots/metabolism ; Plant Shoots/drug effects/metabolism ; Pyridines/*pharmacology ; Glycine max/drug effects/genetics/*metabolism ; Spectrum Analysis ; },
abstract = {Iron deficiency chlorosis (IDC) is a serious environmental problem affecting the growth of several crops in the world. The application of synthetic Fe(III) chelates is still one of the most common measures to correct IDC and the search for more effective Fe chelates remains an important issue. Herein, we propose a tris(3-hydroxy-4-pyridinonate) iron(III) complex, Fe(mpp)3, as an IDC corrector. Different morphological, biochemical and molecular parameters were assessed as a first step towards understanding its mode of action, compared with that of the commercial fertilizer FeEDDHA. Plants treated with the pyridinone iron(III) complexes were significantly greener and had increased biomass. The total Fe content was measured using ICP-OES and plants treated with pyridinone complexes accumulated about 50% more Fe than those treated with the commercial chelate. In particular, plants supplied with compound Fe(mpp)3 were able to translocate iron from the roots to the shoots and did not elicit the expression of the Fe-stress related genes FRO2 and IRT1. These results suggest that 3,4-HPO iron(III) chelates could be a potential new class of plant fertilizing agents.},
}
@article {pmid27153443,
year = {2017},
author = {Chatterjee, D and Bal, A and Das, A and Kohli, PS and Singh, G and Mittal, BR},
title = {Invasive Duct Carcinoma of the Breast With Dominant Signet-Ring Cell Differentiation: A Microsatellite Stable Tumor With Aggressive Behavior.},
journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM},
volume = {25},
number = {10},
pages = {720-724},
doi = {10.1097/PAI.0000000000000366},
pmid = {27153443},
issn = {1533-4058},
mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Signet Ring Cell/*diagnosis/pathology ; DNA-Binding Proteins/genetics ; Female ; Humans ; Immunohistochemistry ; Microsatellite Repeats/genetics ; Middle Aged ; MutS Homolog 2 Protein/genetics ; Prognosis ; },
abstract = {AIMS: Invasive duct carcinoma, no special type (IDC, NST), of the breast with signet-ring cell differentiation is uncommon. This study was undertaken to describe the clinicopathologic characteristics of IDC, NST, with dominant signet-ring cell differentiation, and look for microsatellite instability in these tumors.<br><br>METHODS: Cases of IDC, NST, with dominant signet-ring cell differentiation, diagnosed over the past 2 years, were retrieved. Detailed clinical and pathologic analyses were performed. Immunohistochemistry was performed for estrogen receptor, progesterone receptors, Her-2 neu, Ki-67, E-cadherin, CK7, and CK20. Microsatellite instability was examined using immunohistochemistry for the 4 mismatch repair proteins: MLH1, MSH2, MSH6, and PMS2.<br><br>RESULTS: Of the total 1646 cases of IDC, NST, only 5 cases showed dominant signet-ring cells (ranging from 70% to 100%) and strong E-cadherin positivity and were diagnosed as IDC, NST, with dominant signet-ring cell differentiation. The age ranged from 32 to 65 years. Two cases were of histologic grade 3 and the remaining cases were grade 2 tumors. Four patients had T2 tumor and 1 had T3 tumor. All cases had axillary lymph node metastasis and distant metastasis was present in 1 case. All cases were microsatellite stable.<br><br>CONCLUSIONS: Signet-ring cell differentiation in IDC, NST, is rare and associated with a high histologic grade. Lymph node metastasis and distant metastasis are common, indicating an aggressive clinical behavior. Thus, they should be recognized separately as they may warrant aggressive management. However, these are microsatellite-stable tumors in contrast to signet-ring cell tumors of other organs.},
}
@article {pmid27146735,
year = {2016},
author = {Krishnamurthy, J and Kumar, PS},
title = {Significance of prognostic indicators in infiltrating duct carcinoma breast: Scenario in developing country.},
journal = {Indian journal of cancer},
volume = {53},
number = {1},
pages = {34-38},
doi = {10.4103/0019-509X.180834},
pmid = {27146735},
issn = {1998-4774},
mesh = {Adult ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Developing Countries ; Female ; Humans ; Middle Aged ; Prognosis ; },
abstract = {CONTEXT: Carcinoma of the breast is one of the most common malignant tumors and is the most common cause of death from cancers in females. Early diagnosis and assessing the prognosis for each patient is essential for a better therapeutic plan and management.<br><br>AIMS: To evaluate the significance of various prognostic indicators of breast carcinoma by correlating with Nottingham modification of Scarff Bloom-Richardson's grading system (NMBGS).<br><br>MATERIALS AND METHODS: Eighty four patients who underwent mastectomy for breast carcinoma at a tertiary care centre in South India over a period of 2 years have been evaluated to note the importance of the various prognostic factors correlating them with NMBGS.<br><br>STATISTICAL ANALYSIS: A Chi-square test was used to determine possible association between the various prognostic factors.<br><br>RESULTS: Eighty percent of the tumors were infiltrating ductal carcinoma (IDC), and it is seen that the larger tumor size, higher histopathological grade, increased lymphovascular invasion, lymphnode metastasis, tumor necrosis, microvessel density, estrogen and progesterone receptor negativity, and HER-2/neu positivity were associated with higher grade of tumor.<br><br>CONCLUSIONS: The traditional morphological factors including the histological type, grade, tumor size, lymphovascular invasion, lymph node status, presence of necrosis, stromal reaction, and microvascular density (MVD) count are relatively simple but robust prognostic factors to assess, while the hormonal and genetic status not only have prognostic value but are useful predictive marker for adjuvant chemotherapy. Hence, the status of these various prognostic factors should form the basis of all routine histopathological reports in cases of breast cancer for better management.},
}
@article {pmid27145402,
year = {2016},
author = {Tessitore, A and Giordano, A and De Micco, R and Caiazzo, G and Russo, A and Cirillo, M and Esposito, F and Tedeschi, G},
title = {Functional connectivity underpinnings of fatigue in "Drug-Naïve" patients with Parkinson's disease.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {31},
number = {10},
pages = {1497-1505},
doi = {10.1002/mds.26650},
pmid = {27145402},
issn = {1531-8257},
mesh = {Aged ; Cerebral Cortex/diagnostic imaging/*physiopathology ; Connectome/*methods ; Fatigue/diagnostic imaging/etiology/*physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parkinson Disease/complications/diagnostic imaging/*physiopathology ; },
abstract = {INTRODUCTION: Fatigue is a common problem in PD either in the early or later stage of the disease. Using resting-state functional MRI, we investigated the functional correlates of fatigue in a cohort of "drug-naïve" patients with PD.<br><br>METHODS: MRI at 3Tesla was collected in 40 patients with PD, 20 with and 20 without fatigue, and 20 matched healthy controls. Presence and the severity of fatigue were defined based on the 16-item Parkinson fatigue scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting state networks between patients subgroups and healthy controls. In addition, we used voxel-based morphometry to test whether between-group functional changes were related to structural differences.<br><br>RESULTS: Distressing fatigue was associated with a decreased connectivity in the supplementary motor area within the sensorimotor network and an increased connectivity in the prefrontal and posterior cingulate cortices within the default mode network (P < 0.05 corrected). Fatigue severity was correlated with both sensorimotor and default mode networks connectivity changes. Voxel-based morphometry analysis did not reveal any significant volume differences between all patients with PD and healthy controls and between patients with PD with and without fatigue (P < 0.05; family-wise error).<br><br>CONCLUSIONS: Our findings revealed that primary PD-related fatigue is associated with an altered default mode network and sensorimotor network connectivity in drug-na&#xef;ve patients. We hypothesize that these divergent motor and cognitive networks connectivity changes and their adaptive or maladaptive functional outcome may play a prominent role in the pathophysiology of fatigue in PD. &#xa9; 2016 International Parkinson and Movement Disorder Society.},
}
@article {pmid27125354,
year = {2016},
author = {Yao, M and Yu, E and Staggs, V and Fan, F and Cheng, N},
title = {Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {29},
number = {8},
pages = {810-823},
pmid = {27125354},
issn = {1530-0285},
mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology/therapy ; Calcium-Binding Proteins/analysis ; Carcinoma, Ductal, Breast/*chemistry/pathology/therapy ; Carcinoma, Lobular/*chemistry/pathology/therapy ; Chemokine CCL2/*analysis ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Risk Factors ; S100 Calcium-Binding Protein A4 ; Stromal Cells/*chemistry/pathology ; Time Factors ; Tissue Array Analysis ; Treatment Outcome ; Tumor Burden ; Tumor Microenvironment ; Up-Regulation ; },
abstract = {Despite advances in treatment, up to 30% of breast cancer patients experience disease recurrence accompanied by more aggressive disease and poorer prognosis. Treatment of breast cancer is complicated by the presence of multiple breast cancer subtypes, including: luminal, Her2 overexpressing, and aggressive basal-like breast cancers. Identifying new biomarkers specific to breast cancer subtypes could enhance the prediction of patient prognosis and contribute to improved treatment strategies. The microenvironment influences breast cancer progression through expression of growth factors, angiogenic factors and other soluble proteins. In particular, chemokine C-C ligand 2 (CCL2) regulates macrophage recruitment to primary tumors and signals to cancer cells to promote breast tumor progression. Here we employed a software-based approach to evaluate the prognostic significance of CCL2 protein expression in breast cancer subtypes in relation to its expression in the epithelium or stroma or in relation to fibroblast-specific protein 1 (Fsp1), a mesenchymal marker. Immunohistochemistry analysis of tissue microarrays revealed that CCL2 significantly correlated with Fsp1 expression in the stroma and tumor epithelium of invasive ductal carcinoma. In the overall cohort of invasive ductal carcinomas (n=427), CCL2 and Fsp1 expression in whole tissues, stroma and epithelium were inversely associated with cancer stage and tumor size. When factoring in molecular subtype, stromal CCL2 was observed to be most highly expressed in basal-like breast cancers. By Cox regression modeling, stromal CCL2, but not epithelial CCL2, expression was significantly associated with decreased recurrence-free survival. Furthermore, stromal CCL2 (HR=7.51 P=0.007) was associated with a greater hazard than cancer stage (HR=2.45, P=0.048) in multivariate analysis. These studies indicate that stromal CCL2 is associated with decreased recurrence-free survival in patients with basal-like breast cancer, with important implications on the use of stromal markers for predicting patient prognosis.},
}
@article {pmid27116366,
year = {2016},
author = {Dobbs, JL and Shin, D and Krishnamurthy, S and Kuerer, H and Yang, W and Richards-Kortum, R},
title = {Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.},
journal = {International journal of cancer},
volume = {139},
number = {5},
pages = {1140-1149},
doi = {10.1002/ijc.30160},
pmid = {27116366},
issn = {1097-0215},
mesh = {Adipocytes/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal/*pathology ; Carcinoma, Ductal, Breast/immunology/pathology ; Female ; Humans ; *Microscopy, Confocal/methods ; *Tumor Microenvironment ; },
abstract = {Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions.},
}
@article {pmid27097912,
year = {2016},
author = {Costello, LC and Zou, J and Franklin, RB},
title = {In situ clinical evidence that zinc levels are decreased in breast invasive ductal carcinoma.},
journal = {Cancer causes &amp; control : CCC},
volume = {27},
number = {6},
pages = {729-735},
pmid = {27097912},
issn = {1573-7225},
support = {R01 CA079903/CA/NCI NIH HHS/United States ; R01 CA093443/CA/NCI NIH HHS/United States ; R01 DK042839/DK/NIDDK NIH HHS/United States ; R01 DK076763/DK/NIDDK NIH HHS/United States ; },
mesh = {Breast/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Case-Control Studies ; Chelating Agents ; Dithizone ; Female ; Humans ; Zinc/*metabolism ; },
abstract = {PURPOSE: Altered zinc levels in malignant cells versus their normal cells have important implications in the development and progression of several cancers. Prostate, pancreatic, and hepatocellular carcinomas exhibit consistent marked zinc decrease in situ in the malignant cells, and other cancers (such as kidney, lung, and thyroid) also exhibit decreased tissue zinc levels. However, zinc levels are increased in breast cancer tissue compared to breast normal tissue, and the contemporary dominant view is that zinc is increased in invasive ductal carcinoma. This has important implications regarding the role and effects of zinc in breast malignancy compared to other cancers, which caused us to initiate this study to either confirm or challenge the contemporary view of an increased zinc level in the invasive ductal malignant cells.<br><br>METHODS: We employed dithizone staining of breast tissue sections and tissue cores to determine the relative in situ cellular zinc levels specifically in the invasive ductal malignant cells as compared to normal ductal epithelium. This approach had not been employed in any of the reported breast studies.<br><br>RESULTS: The results revealed that the zinc levels are consistently and markedly decreased in the ductal malignant cells as compared with higher prominent zinc levels in the normal ductal epithelium. Decreased zinc is evident in Grade 1 well-differentiated malignancy and in Grade 2 and Grade 3 carcinomas. Among the twenty-five cancer cases in this study, none exhibited increased zinc in the invasive ductal carcinoma compared to the zinc level in the normal ductal epithelium.<br><br>CONCLUSIONS: The decreased zinc levels in breast invasive ductal carcinoma is consistent with prostate, pancreatic, and liver carcinomas in which the decrease in zinc is a required event in the development of malignancy to prevent cytotoxicity that would result from the higher zinc levels in the normal cells. This new understanding requires a redirection in elucidating the mechanisms and factors regarding the regulation of zinc in breast cancer, its potential translational applications as possible biomarkers, and for treatment of breast invasive ductal carcinoma.},
}
@article {pmid27092808,
year = {2017},
author = {Giarenis, I and Zacchè, M and Robinson, D and Cardozo, L},
title = {Is there any association between urodynamic variables and severity of overactive bladder in women with idiopathic detrusor overactivity?.},
journal = {Neurourology and urodynamics},
volume = {36},
number = {3},
pages = {780-783},
doi = {10.1002/nau.23023},
pmid = {27092808},
issn = {1520-6777},
mesh = {Adult ; Aged ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Severity of Illness Index ; Urinary Bladder/*physiopathology ; Urinary Bladder, Neurogenic/complications/diagnosis/*physiopathology ; Urinary Bladder, Overactive/complications/diagnosis/*physiopathology ; Urinary Incontinence/diagnosis/etiology/*physiopathology ; Urodynamics/*physiology ; },
abstract = {AIMS: The lack of a validated detrusor overactivity (DO) severity tool limits the clinical value of urodynamics in the management of patients with overactive bladder syndrome (OAB). The aim of this study, was to identify urodynamic variables that correlate with validated OAB severity measures.<br><br>METHODS: This was a cross-sectional study enrolling consecutive women with idiopathic DO. The 24&#x2009;hr urgency episodes and the score of the Incontinence Impact (II) domain of the King's Health Questionnaire (KHQ) were used to assess the severity of OAB.<br><br>RESULTS: The study enrolled 299 women with idiopathic DO. The cystometric capacity, compliance, and the threshold volume for the first involuntary detrusor contraction (IDC) showed a statistically significant negative correlation with the II domain of the KHQ and the 24&#x2009;hr urgency episodes. There was a statistically significant positive correlation between the amplitude of first IDC and the OAB severity measures, but only borderline for the amplitude of the highest IDC. There were no statistically significant differences between women with and without leakage per urethram during a detrusor contraction.<br><br>CONCLUSIONS: Cystometric capacity, compliance (measured in ml/cm H2 O), threshold volume, and amplitude of the first IDC could be routinely documented in everyday clinical practice. The measures more commonly used for describing the severity of DO, such as leakage per urethram during a detrusor contraction and amplitude of the highest detrusor contraction, have a limited role confirming the complicated interaction between the detrusor muscle, the urethral sphincter, and the pelvic floor in women. Neurourol. Urodynam. 36:780-783, 2017. &#xa9; 2016 Wiley Periodicals, Inc.},
}
@article {pmid27080531,
year = {2016},
author = {Chabot, V and Martin, L and Meley, D and Sensebé, L and Baron, C and Lebranchu, Y and Dehaut, F and Velge-Roussel, F},
title = {Unexpected impairment of TNF-α-induced maturation of human dendritic cells in vitro by IL-4.},
journal = {Journal of translational medicine},
volume = {14},
number = {},
pages = {93},
pmid = {27080531},
issn = {1479-5876},
mesh = {Biomarkers/metabolism ; CD4-Positive T-Lymphocytes/drug effects ; Cell Differentiation/*drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Chemokines/pharmacology ; Dendritic Cells/*cytology/drug effects/metabolism ; Humans ; Interleukin-12/metabolism ; Interleukin-4/metabolism ; Lymphocyte Activation/drug effects ; RNA, Messenger/genetics/metabolism ; Receptors, CCR7/genetics/metabolism ; Th1 Cells/drug effects ; Tumor Necrosis Factor-alpha/*pharmacology ; },
abstract = {BACKGROUND: An efficient strategy for programming dendritic cells (DCs) for cancer immunotherapy is the optimization of their maturation so that they can efficiently stimulate cancer-specific T cell responses. Interleukin (IL)-4 has appeared as an essential cytokine, widely used in vitro with granulocyte macrophage-colony stimulating factor (GM-CSF) to differentiate monocytes into immature DCs (iDC) and to prevent macrophage formation. Conflicting data have been published regarding the effect of IL-4 on functional DC maturation. To further understand IL-4's effects on DC maturation and function in vitro, we choose the most commonly used maturation factor tumor necrosis factor (TNF)-α.<br><br>METHODS: Human monocyte-derived iDC were treated for 48 h with GM-CSF and TNF-&#x3b1; in the presence (IL-4(+)-DC) or absence (IL-4(-)-DC) of IL-4 and functions of both DC populations were compared.<br><br>RESULTS: On mixed lymphocyte reaction assay, IL-4(+)-DC were less potent than IL-4(-)-DC at inducing the proliferation of allogeneic CD4(+) T cells and the proportion of activated T cells expressing CD69 and/or CD25 was smaller. Interleukin-4 reduced the cell-surface expression of TNF-&#x3b1;-induced DC maturation markers CD83, CD86, HLA-DR and CD25 and generated a heterogeneous population of DCs. IL-4(+)-DC secreted less IL-12 and more IL-10 than IL-4(-)-DC following activation by soluble CD40L, and IL-4(+)-DC-activated T cells secreted lesser amounts of T helper (Th) 1 cytokines (IL-2 and interferon-&#x3b3;). Importantly, IL-4 impaired the in vitro migratory capacity of DCs in response to CCL21 and CCL19 chemokines. This effect was related to reduced expression of CCR7 at both mRNA and protein levels.<br><br>CONCLUSION: Interleukin-4 used with GM-CSF and TNF-&#x3b1; during the maturation of DCs in vitro impaired DC functions and disturbed the maturation effect of TNF-&#x3b1;. Finally, our study reinforces the view that the quality of the DC maturation stimulus, which regulates DC migration and cytokine production, may be a decisive feature of the immunogenicity of DCs.},
}
@article {pmid27067853,
year = {2016},
author = {Ooe, A and Suganuma, Y},
title = {[Breast Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine Monotherapy after Failure of Combination Therapy Comprising Bevacizumab and Paclitaxel].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {43},
number = {3},
pages = {349-351},
pmid = {27067853},
issn = {0385-0684},
mesh = {Aged ; Antimetabolites, Antineoplastic/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration &amp; dosage ; Breast Neoplasms/*drug therapy/*pathology ; Capecitabine/*therapeutic use ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Paclitaxel/administration &amp; dosage ; Salvage Therapy ; },
abstract = {We report a case of breast cancer with multiple liver metastases successfully treated with capecitabine monotherapy after failure of combination therapy comprising bevacizumab (Bev) and paclitaxel (PTX). In March 2012, a 67-year-old woman was diagnosed with Stage IV breast cancer with massive pleural effusion. Histological examination showed invasive ductal carcinoma (scirrhous carcinoma) that was positive for hormonal receptor but negative for HER2 expression, and the nuclear grade was 1. She first received chemotherapy to decrease the tumor volume followed by hormonal therapy. After progression, imaging studies showed increased multiple lung and liver metastases and pleural effusion. Subsequently, treatment with combination of Bev and PTX was started from July 2014. After 4 courses of the combination therapy, multiple liver metastases were unchanged, but her liver function was impaired. Hence, she received capecitabine monotherapy (1,800 mg bis in die [BID]; 2-week administration followed by a week of rest). Her liver function improved early, and a partial response (PR) in the multiple liver metastases was achieved 3 months after initiation of therapy. Furthermore, the metastatic lesions were well controlled 4 months later. These findings suggest that the sensitivity to an anticancer agent greatly varies among patients.},
}
@article {pmid27050973,
year = {2016},
author = {Zhao, L and Zhang, QY and Luan, X and Huang, X and Zhao, S and Zhao, H},
title = {Relationship between the expression of Notch1 and EZH2 and the prognosis of breast invasive ductal carcinoma.},
journal = {Genetics and molecular research : GMR},
volume = {15},
number = {1},
pages = {},
doi = {10.4238/gmr.15017464},
pmid = {27050973},
issn = {1676-5680},
mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Enhancer of Zeste Homolog 2 Protein/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Middle Aged ; Prognosis ; Receptor, Notch1/genetics/*metabolism ; },
abstract = {We determined whether the coexpression of Notch1 and EZH2 influences the progression and prognosis of breast invasive ductal carcinoma. Using the χ(2) test, a significant difference was found between high and low expression of Notch1 in terms of lymph node, hormone receptor, and p53 expression (P < 0.05). Moreover, a significant difference was found between high and low expression of EZH2 in terms of tumor size, histologic grade, hormone receptor, and expression of Ki67 (P < 0.05). Using Pearson correlation analysis, we found a significant positive correlation between Notch1 and EZH2 expression in the tissue samples of breast invasive ductal carcinoma (P = 0.038). High Notch1 and EZH2 expression was associated with poor progression-free survival compared with low expression (PNotch1 = 0.000, 40.3 vs 48.9 months; PEZH2 = 0.000, 40.2 vs 49.9 months). Moreover, we found that high Notch1 and EZH2 expression was associated with poor overall survival compared with low expression (PNotch1 = 0.000, 51.2 vs 56.2 months; PEZH2 = 0.002, 51.7 vs 56.4 months). In conclusion, Notch1 and EZH2 coexpression contributes to the progression and prognosis of breast invasive ductal carcinoma.},
}
@article {pmid27041335,
year = {2016},
author = {Lim, ST and Choi, JE and Kim, SJ and Kim, HA and Kim, JY and Park, HK and Suh, YJ},
title = {Prognostic implication of the tumor location according to molecular subtypes in axillary lymph node-positive invasive ductal cancer in a Korean population.},
journal = {Breast cancer research and treatment},
volume = {156},
number = {3},
pages = {473-483},
doi = {10.1007/s10549-016-3771-6},
pmid = {27041335},
issn = {1573-7217},
mesh = {Adult ; Axilla ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/genetics ; Registries ; Republic of Korea ; Retrospective Studies ; },
abstract = {Previous studies have not considered the axillary lymph node status when investigating the prognostic role of tumor location according to each molecular subtype. The present study aimed to investigate the prognostic implication of tumor location according to each molecular subtype in Korean invasive ductal carcinoma (IDC) patients with axillary lymph node metastasis. Data from 7856 Korean IDC women with axillary lymph node metastasis were retrospectively analyzed. According to tumor location, patients were divided into the following groups: upper-outer quadrant, lower-outer quadrant, upper-inner quadrant, lower-inner quadrant (LIQ), and central group. Overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated according to tumor location and molecular subtype. A subgroup analysis based on tumor size categorization was also performed. The patients' mean age was 47.97 ± 9.64 years, and the median follow-up time was 90 months. The LIQ group showed significantly worse prognosis in OS and BCSS (76.4 and 83.3 %, respectively) compared with the other groups, which was only significant in human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative (TN) subtypes. In the subgroup analysis according to tumor size, the LIQ group showed a significantly worse prognosis in OS and BCSS compared with the other groups, in HER2 and TN subtypes, and only in patients with more than T2 stage. In Korean IDC patients with axillary lymph node metastasis, LIQ tumor location was associated with poor prognosis among those with HER2 and TN molecular subtypes and especially in those with more than T2 stage.},
}
@article {pmid27039751,
year = {2016},
author = {Yadav, P and Mir, R and Nandi, K and Javid, J and Masroor, M and Ahmad, I and Zuberi, M and Kaza, R and Jain, S and Khurana, N and Ray, PC and Saxena, A},
title = {The C609T (Pro187Ser) Null Polymorphism of the NQO1 Gene Contributes Significantly to Breast Cancer Susceptibility in North Indian Populations: a Case Control Study.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {17},
number = {3},
pages = {1215-1219},
doi = {10.7314/apjcp.2016.17.3.1215},
pmid = {27039751},
issn = {2476-762X},
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/epidemiology/*genetics/pathology ; Carcinoma, Ductal, Breast/epidemiology/*genetics/pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; *Genetic Predisposition to Disease ; Genotype ; Humans ; India/epidemiology ; Middle Aged ; NAD(P)H Dehydrogenase (Quinone)/*genetics ; Neoplasm Grading ; Neoplasm Staging ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide/*genetics ; Prognosis ; Risk Factors ; },
abstract = {BACKGROUND: Worldwide, breast cancer is the most common cancer among women and is a leading cause of cancer death. In the present study, we investigated the NQO1 C609T genotypic and allelic distribution in north Indian breast cancer patients.<br><br>MATERIALS AND METHODS: The genotypic distribution of the NQ01 C609T polymorphism was assessed in 100 invasive ductal carcinoma (IDC) breast cancer patients and 100 healthy controls using allele specific PCR (AS-PCR).<br><br>RESULTS: A lower frequency of the CC genotype was found in breast cancer patients (24%) than in the controls. On the other hand, TT genotype frequency was also found to be higher in female healthy controls (32%) than the female breast cancer patients (20%). The frequencies of all three genotypes CC, CT, TT in patients were 24%, 56% and 20% and in healthy controls 50%, 22% and 32% respectively. We did not find any significant correlation between the NQO1 C609T polymorphism and age group, grading, menopausal status and distant metastasis. A less significant association was found between the NQ01 C609T polymorphism and the stage of breast cancer (X2=5.931, P=0.05).<br><br>CONCLUSIONS: The present study shows a strong association between NQO1 C609T polymorphism with the breast cancer risk in the north Indian breast cancer patients so that possible use as a risk factor should be further explored.},
}
@article {pmid27032379,
year = {2016},
author = {Wieczorek, E and Galicki, M and Tomasik, B and Krol, M and Jablonska, E and Fendler, W and Gromadzinska, J and Morawiec, Z and Wasowicz, W and Reszka, E},
title = {Expression of MMP and TIMP mRNA in peripheral blood leukocytes of patients with invasive ductal carcinoma of the breast.},
journal = {The International journal of biological markers},
volume = {31},
number = {3},
pages = {e309-16},
doi = {10.5301/jbm.5000203},
pmid = {27032379},
issn = {1724-6008},
mesh = {Breast Neoplasms/blood/*genetics/metabolism ; Carcinoma, Ductal, Breast/blood/*genetics/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leukocytes/cytology/*metabolism ; Matrix Metalloproteinases/biosynthesis/*genetics/metabolism ; Middle Aged ; RNA, Messenger/*biosynthesis/blood/genetics ; Tissue Inhibitor of Metalloproteinase-1/biosynthesis/*genetics/metabolism ; },
abstract = {PURPOSE: An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) appears critical for tumor progression and metastasis. This study aimed to determine whether gene expression of MMP1, MMP2, MMP9, TIMP1 and TIMP3 and the MMP/TIMP expression ratio in peripheral blood leukocytes (PBLs) and the MMP1 and TIMP1 contents or MMP1/TIMP1 ratio in plasma were associated with clinicopathological characteristics in invasive ductal carcinoma (IDC) of the breast.<br><br>MATERIALS AND METHODS: Blood samples were collected from women newly diagnosed with IDC who had not received prior treatment (n = 102). Gene expression in PBLs was analyzed by quantitative real-time polymerase chain reaction. Concentrations of MMP1 and TIMP1 in plasma were measured using ELISA.<br><br>RESULTS: In univariate analysis the expression levels of MMP2 and TIMP1 mRNA were significantly higher in premenopausal compared to postmenopausal patients (p<0.001 and p = 0.014, respectively). MMP2 mRNA expression negatively correlated with age (p<0.001, r = -0.43). We found that the MMP2/TIMP3 expression ratio was significantly higher in women after menopause (p = 0.007). The MMP2/TIMP1 expression ratio was higher in human epidermal growth factor receptor 2 (HER2)-positive patients (p = 0.022). Low-grade tumors had significantly lower MMP1/TIMP1 and MMP2/TIMP1 expression ratios (p = 0.047 and p = 0.048, respectively). TIMP1 plasma concentration was significantly higher in small tumors compared with T2-T3 tumors (p = 0.013).<br><br>CONCLUSIONS: These findings reveal an important association between tumor characteristics and expression ratios of MMP1/TIMP1 and MMP2/TIMP1 in PBLs and TIMP1 concentration in plasma. Menopausal status may influence the mRNA expression levels of MMP2 and TIMP1 as well as the MMP2/TIMP3 expression ratio in IDC of the breast.},
}
@article {pmid27022189,
year = {2016},
author = {Lau, SS and Cheung, PS and Wong, TT and Ma, MK and Kwan, WH},
title = {Comparison of clinical and pathological characteristics between screen-detected and self-detected breast cancers: a Hong Kong study.},
journal = {Hong Kong medical journal = Xianggang yi xue za zhi},
volume = {22},
number = {3},
pages = {202-209},
doi = {10.12809/hkmj154575},
pmid = {27022189},
issn = {1024-2708},
mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology/therapy ; *Breast Self-Examination ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/*pathology/therapy ; Early Detection of Cancer/statistics &amp; numerical data ; Female ; Hong Kong ; Humans ; Logistic Models ; Lymph Nodes/pathology ; Mammography ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Young Adult ; },
abstract = {INTRODUCTION: Breast cancer is the leading cause of death of Hong Kong women with increasing incidence. This study aimed to determine any prognostic differences between screen-detected and self-detected cases of breast cancer in a cohort of Hong Kong patients.<br><br>METHODS: This was a case series with internal comparison carried out in a private hospital in Hong Kong. Approximately 3000 cases of Chinese patients diagnosed with ductal carcinoma in situ or invasive breast cancer were reviewed.<br><br>RESULTS: The screen-detected group showed better pathological characteristics than the self-detected group. Number of lymph nodes involved, invasive tumour size, and tumour grade were more favourable in the screen-detected group. There was also a lower proportion of patients with pure invasive ductal carcinoma and mastectomy in the screen-detected group.<br><br>CONCLUSION: This study provides indirect evidence that women in the local population may gain clinical benefit from regular breast cancer screening. The findings need to be validated in a representative population of Hong Kong women.},
}
@article {pmid27014949,
year = {2016},
author = {Cenarro, A and Etxebarria, A and de Castro-Orós, I and Stef, M and Bea, AM and Palacios, L and Mateo-Gallego, R and Benito-Vicente, A and Ostolaza, H and Tejedor, T and Martín, C and Civeira, F},
title = {The p.Leu167del Mutation in APOE Gene Causes Autosomal Dominant Hypercholesterolemia by Down-regulation of LDL Receptor Expression in Hepatocytes.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {101},
number = {5},
pages = {2113-2121},
doi = {10.1210/jc.2015-3874},
pmid = {27014949},
issn = {1945-7197},
mesh = {Adult ; Apolipoproteins E/*genetics/metabolism ; Case-Control Studies ; DNA Mutational Analysis ; Down-Regulation/*genetics ; Female ; Hepatocytes/*metabolism ; Humans ; Hyperlipoproteinemia Type II/*genetics/metabolism ; Male ; Middle Aged ; *Mutation ; Receptors, LDL/*genetics/metabolism ; },
abstract = {CONTEXT: The p.Leu167del mutation in the APOE gene has been associated with hyperlipidemia.<br><br>OBJECTIVES: Our objective was to determine the frequency of p.Leu167del mutation in APOE gene in subjects with autosomal dominant hypercholesterolemia (ADH) in whom LDLR, APOB, and PCSK9 mutations had been excluded and to identify the mechanisms by which this mutant apo E causes hypercholesterolemia.<br><br>DESIGN: The APOE gene was analyzed in a case-control study.<br><br>SETTING: The study was conducted at a University Hospital Lipid Clinic.<br><br>Two groups (ADH, 288 patients; control, 220 normolipidemic subjects) were included.<br><br>INTERVENTION: We performed sequencing of APOE gene and proteomic and cellular experiments.<br><br>MAIN OUTCOME MEASURE: To determine the frequency of the p.Leu167del mutation and the mechanism by which it causes hypercholesterolemia.<br><br>RESULTS: In the ADH group, nine subjects (3.1%) were carriers of the APOE c.500_502delTCC, p.Leu167del mutation, cosegregating with hypercholesterolemia in studied families. Proteomic quantification of wild-type and mutant apo E in very low-density lipoprotein (VLDL) from carrier subjects revealed that apo E3 is almost a 5-fold increase compared to mutant apo E. Cultured cell studies revealed that VLDL from mutation carriers had a significantly higher uptake by HepG2 and THP-1 cells compared to VLDL from subjects with E3/E3 or E2/E2 genotypes. Transcriptional down-regulation of LDLR was also confirmed.<br><br>CONCLUSIONS: p.Leu167del mutation in APOE gene is the cause of hypercholesterolemia in the 3.1% of our ADH subjects without LDLR, APOB, and PCSK9 mutations. The mechanism by which this mutation is associated to ADH is that VLDL carrying the mutant apo E produces LDLR down-regulation, thereby raising plasma low-density lipoprotein cholesterol levels.},
}
@article {pmid27007655,
year = {2016},
author = {Jin, B and Wu, BW and Wen, ZC and Shi, HM and Zhu, J},
title = {HLA-DR3 antigen in the resistance to idiopathic dilated cardiomyopathy.},
journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica},
volume = {49},
number = {4},
pages = {e5131},
pmid = {27007655},
issn = {1414-431X},
mesh = {Biopsy ; Cardiomyopathy, Dilated/*genetics/pathology ; Case-Control Studies ; Genetic Predisposition to Disease ; HLA-DR3 Antigen/*genetics ; Humans ; Myocardium/pathology ; Polymorphism, Genetic ; Risk Factors ; },
abstract = {Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC.},
}
@article {pmid26980443,
year = {2016},
author = {Fujikawa, Y and Roma, LP and Sobotta, MC and Rose, AJ and Diaz, MB and Locatelli, G and Breckwoldt, MO and Misgeld, T and Kerschensteiner, M and Herzig, S and Müller-Decker, K and Dick, TP},
title = {Mouse redox histology using genetically encoded probes.},
journal = {Science signaling},
volume = {9},
number = {419},
pages = {rs1},
doi = {10.1126/scisignal.aad3895},
pmid = {26980443},
issn = {1937-9145},
mesh = {Animals ; HEK293 Cells ; Humans ; Mice ; Mice, Nude ; Molecular Imaging/*methods ; Molecular Probes/genetics/*metabolism ; Oxidation-Reduction ; *Transgenes ; },
abstract = {Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation.},
}
@article {pmid26975010,
year = {2016},
author = {Dong, A and Wang, Y and Lu, J and Zuo, C},
title = {Spectrum of the Breast Lesions With Increased 18F-FDG Uptake on PET/CT.},
journal = {Clinical nuclear medicine},
volume = {41},
number = {7},
pages = {543-557},
pmid = {26975010},
issn = {1536-0229},
mesh = {Breast/metabolism ; Breast Diseases/*diagnostic imaging/metabolism ; Breast Neoplasms/diagnostic imaging ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Male ; Positron Emission Tomography Computed Tomography/*methods ; Radiopharmaceuticals/*pharmacokinetics ; },
abstract = {Interpretation of F-FDG PET/CT studies in breast is challenging owing to nonspecific FDG uptake in various benign and malignant conditions. Benign conditions include breast changes in pregnancy and lactation, gynecomastia, mastitis, fat necrosis, fibroadenoma, intraductal papilloma, and atypical ductal hyperplasia. Among malignancies, invasive ductal carcinoma and invasive lobular carcinoma are common histological types of breast carcinoma. Rarely, other unusual histological types of breast carcinomas (eg, intraductal papillary carcinoma, invasive micropapillary carcinoma, medullary carcinoma, mucinous carcinoma, and metaplastic carcinoma), lymphoma, and metastasis can be the causes. Knowledge of a wide spectrum of hypermetabolic breast lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT. The purpose of this atlas article is to demonstrate features of various breast lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging.},
}
@article {pmid26972027,
year = {2016},
author = {Mata-Cantero, L and Azkargorta, M and Aillet, F and Xolalpa, W and LaFuente, MJ and Elortza, F and Carvalho, AS and Martin-Plaza, J and Matthiesen, R and Rodriguez, MS},
title = {New insights into host-parasite ubiquitin proteome dynamics in P. falciparum infected red blood cells using a TUBEs-MS approach.},
journal = {Journal of proteomics},
volume = {139},
number = {},
pages = {45-59},
doi = {10.1016/j.jprot.2016.03.004},
pmid = {26972027},
issn = {1876-7737},
mesh = {*Erythrocytes/metabolism/parasitology ; Host-Parasite Interactions/*physiology ; Humans ; Malaria, Falciparum/*metabolism ; Plasmodium falciparum/*physiology ; Proteome/*metabolism ; Protozoan Proteins/*metabolism ; Ubiquitin/*metabolism ; },
abstract = {UNLABELLED: Malaria, caused by Plasmodium falciparum (P. falciparum), ranks as one of the most baleful infectious diseases worldwide. New antimalarial treatments are needed to face existing or emerging drug resistant strains. Protein degradation appears to play a significant role during the asexual intraerythrocytic developmental cycle (IDC) of P. falciparum. Inhibition of the ubiquitin proteasome system (UPS), a major intracellular proteolytic pathway, effectively reduces infection and parasite replication. P. falciparum and erythrocyte UPS coexist during IDC but the nature of their relationship is largely unknown. We used an approach based on Tandem Ubiquitin-Binding Entities (TUBEs) and 1D gel electrophoresis followed by mass spectrometry to identify major components of the TUBEs-associated ubiquitin proteome of both host and parasite during ring, trophozoite and schizont stages. Ring-exported protein (REX1), a P. falciparum protein located in Maurer's clefts and important for parasite nutrient import, was found to reach a maximum level of ubiquitylation in trophozoites stage. The Homo sapiens (H. sapiens) TUBEs associated ubiquitin proteome decreased during the infection, whereas the equivalent P. falciparum TUBEs-associated ubiquitin proteome counterpart increased. Major cellular processes such as DNA repair, replication, stress response, vesicular transport and catabolic events appear to be regulated by ubiquitylation along the IDC P. falciparum infection.<br><br>BIOLOGICAL SIGNIFICANCE: In this work we analyze for the first time the interconnection between Plasmodium and human red blood cells ubiquitin-regulated proteins in the context of infection. We identified a number of human and Plasmodium proteins whose ubiquitylation pattern changes during the asexual infective stage. We demonstrate that ubiquitylation of REX1, a P. falciparum protein located in Maurer's clefts and important for parasite nutrient import, peaks in trophozoites stage. The ubiquitin-proteome from P. falciparum infected red blood cells (iRBCs) revealed a significant host-parasite crosstalk, underlining the importance of ubiquitin-regulated proteolytic activities during the intraerythrocytic developmental cycle (IDC) of P. falciparum. Major cellular processes defined from gene ontology such as DNA repair, replication, stress response, vesicular transport and catabolic events appear to be regulated by ubiquitylation along the IDC P. falciparum infection. Given the importance of ubiquitylation in the development of infectious diseases, this work provides a number of potential drug-target candidates that should be further explored.},
}
@article {pmid26971121,
year = {2016},
author = {Sun, H and Li, K and Shen, S},
title = {A study of the role of Notch1 and JAG1 gene methylation in development of breast cancer.},
journal = {Medical oncology (Northwood, London, England)},
volume = {33},
number = {4},
pages = {35},
pmid = {26971121},
issn = {1559-131X},
mesh = {Adolescent ; Adult ; Aged ; Breast Diseases/genetics/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; CpG Islands ; DNA Methylation ; Female ; Humans ; Hyperplasia/pathology ; Jagged-1 Protein/*genetics/metabolism ; Lymphatic Metastasis/pathology ; Middle Aged ; Receptor, Notch1/*genetics/metabolism ; Young Adult ; },
abstract = {This study is to explore the roles of gene methylation of Notch1 and JAG1 in development of invasive ductal carcinoma of breast. Quantitative analysis the DNA methylation levels of Notch1 and JAG1 gene by the MassARRAY method in invasive ductal carcinoma of breast (IDC; n = 89), atypical ductal hyperplasia of breast (ADH; n = 11), and ordinary ductal hyperplasia of breast (UDH; n = 20). The expressions of JAG1 and Notch1 protein in four breast tissues were detected by immunohistochemistry SP method. (1) Positive expression rates of Notch1 protein in IDC and DCIS were 88.7 % (79/89) and 70.0 % (14/20), respectively, which were significantly higher than the levels in ADH (36.0 %, 4/11) and UDH (25.0 %, 5/20; P < 0.05). Notch1 protein expression was significant positively correlated with lymph node metastasis, pathological grades, and TNM stages of IDC. (2) Positive expression rates of JAG1 protein in IDC and DCIS were 89.9 % (80/89) and 75.0 % (15/20), respectively, which were significantly higher than those of ADH (45.0 %, 5/11) and UDH (30.0 %, 6/20; P < 0.05). JAG1 protein expression was significant positive correlation with lymph node metastasis, pathological grades and TNM stages of IDC. There is an overall hypomethylation alteration of Notch1 and JAG gene in IDC, with corresponding over-expression of Notch1 and JAG1 protein. This inverse correlation shows that the alteration of protein expression results from hypomethylation oncogene Notch1 and JAG1, and this change may play an important role in occurrence and progression of breast cancer.},
}
@article {pmid26950599,
year = {2016},
author = {Stephen, HM and Khoury, RJ and Majmudar, PR and Blaylock, T and Hawkins, K and Salama, MS and Scott, MD and Cosminsky, B and Utreja, NK and Britt, J and Conway, RE},
title = {Epigenetic suppression of neprilysin regulates breast cancer invasion.},
journal = {Oncogenesis},
volume = {5},
number = {3},
pages = {e207},
pmid = {26950599},
issn = {2157-9024},
abstract = {In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer.},
}
@article {pmid26943913,
year = {2016},
author = {Takagi, M and Miki, Y and Miyashita, M and Hata, S and Yoda, T and Hirakawa, H and Sagara, Y and Rai, Y and Ohi, Y and Tamaki, K and Ishida, T and Suzuki, T and Ouchi, N and Sasano, H},
title = {Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.},
journal = {Breast cancer research and treatment},
volume = {156},
number = {1},
pages = {45-55},
doi = {10.1007/s10549-016-3739-6},
pmid = {26943913},
issn = {1573-7217},
mesh = {17-Hydroxysteroid Dehydrogenases/metabolism ; Adult ; Aged ; Aged, 80 and over ; Aromatase/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Lobular/genetics/*metabolism/pathology ; Estrogens/*biosynthesis ; Female ; Forkhead Transcription Factors/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Repressor Proteins/genetics ; Sulfatases/metabolism ; Sulfotransferases/metabolism ; },
abstract = {The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.},
}
@article {pmid26939875,
year = {2016},
author = {Kweldam, CF and Kümmerlin, IP and Nieboer, D and Verhoef, EI and Steyerberg, EW and van der Kwast, TH and Roobol, MJ and van Leenders, GJ},
title = {Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {29},
number = {6},
pages = {630-636},
pmid = {26939875},
issn = {1530-0285},
mesh = {Adenocarcinoma/mortality/*pathology/therapy ; Aged ; Biopsy ; Chi-Square Distribution ; Disease-Free Survival ; Europe ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Predictive Value of Tests ; Proportional Hazards Models ; Prostatic Neoplasms/mortality/*pathology/therapy ; Risk Factors ; Time Factors ; Treatment Outcome ; },
abstract = {Invasive cribriform and intraductal carcinoma in radical prostatectomy specimens have been associated with an adverse clinical outcome. Our objective was to determine the prognostic value of invasive cribriform and intraductal carcinoma in pre-treatment biopsies on time to disease-specific death. We pathologically revised the diagnostic biopsies of 1031 patients from the first screening round of the European Randomized Study of Screening for Prostate Cancer (1993-2000). Ninety percent of all patients (n=923) had received active treatment, whereas 10% (n=108) had been followed by watchful waiting. The median follow-up was 13 years. Patients who either had invasive cribriform growth pattern or intraductal carcinoma were categorized as CR/IDC+. The outcome was disease-specific survival. Relationships with outcome were analyzed using multivariable Cox regression and log-rank analysis. In total, 486 patients had Gleason score 6 (47%) and 545 had ≥7 (53%). The 15-year disease-specific-survival probabilities were 99% in Gleason score 6 (n=486), 94% in CR/IDC- Gleason score ≥7 (n=356) and 67% in CR/IDC+ Gleason score ≥7 (n=189). CR/IDC- Gleason score 3+4=7 patients did not have statistically different survival probabilities from those with Gleason score 6 (P=0.30), while CR/IDC+ Gleason score 3+4=7 patients did (P<0.001). In multivariable analysis, CR/IDC+ status was independently associated with a poorer disease-specific survival (HR 2.6, 95% CI 1.4-4.8, P=0.002). We conclude that CR/IDC+ status in prostate cancer biopsies is associated with a worse disease-specific survival. Our findings indicate that men with biopsy CR/IDC- Gleason score 3+4=7 prostate cancer could be candidates for active surveillance, as these patients have similar survival probabilities to those with Gleason score 6.},
}
@article {pmid26904685,
year = {2016},
author = {Wu, Y and Gu, Y and Guo, S and Dai, Q and Zhang, W},
title = {Expressing Status and Correlation of ARID1A and Histone H2B on Breast Cancer.},
journal = {BioMed research international},
volume = {2016},
number = {},
pages = {7593787},
pmid = {26904685},
issn = {2314-6141},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Chromatin/genetics ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Histones/*biosynthesis/genetics ; Humans ; Middle Aged ; Mutation ; Nuclear Proteins/*biosynthesis/genetics ; Prognosis ; Transcription Factors/*biosynthesis/genetics ; },
abstract = {ARID1A is one of the important cancer-related genes and regulates transcription of certain genes by altering chromatin structure. Inactivated mutations and decreased expression of ARID1A gene have been reported in several kinds of cancer. Histone H2B is a major component of chromatin and encoded by HIST1H2BE. The goal of the study is to evaluate expressing status of ARID1A and H2B as well as their correlation on breast cancer. Gene expression profiles of ARID1A and H2B on Oncomine database are analyzed. Tissue microarray of breast cancer was used for examination of ARID1A and H2B expression by immunohistochemistry. As a result, the disagreement of ARID1A expression was found, while HIST1H2BE expression is elevated in 4 out of 5 datasets on Oncomine database. There were 15 cases (20%) of breast cancers that were positive for ARID1A. Fifty-eight out of 75 cases of breast cancer (77.3%) were highly expressed for H2B protein and 17 cases (22.7%) were low expressed for H2B protein. All cases with ARID1A expression are overlapped with H2B high expression. Among 15 cases with ARID1A and H2B coexpression, 13 are invasive ductal carcinoma and 2 are mucinous carcinoma. Our results indicate that ARID1A gene may be involved in carcinogenesis of some subtypes of breast cancer.},
}
@article {pmid26897954,
year = {2015},
author = {Matsuoka, S and Ishii, T and Miyazawa, S and Mizutani, T and Ito, K and Kamimura, S and Matsumoto, N and Moriyama, M and Takayama, T},
title = {Utility of Partial Splenic Embolization for Hypersplenism using Guglielmi Detachable Coils.},
journal = {Hepato-gastroenterology},
volume = {62},
number = {139},
pages = {683-687},
pmid = {26897954},
issn = {0172-6390},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; C-Reactive Protein/metabolism ; Embolization, Therapeutic/adverse effects/*instrumentation ; Equipment Design ; Female ; Humans ; Hypersplenism/blood/diagnosis/etiology/*therapy ; Liver Cirrhosis/complications ; Male ; Middle Aged ; Platelet Count ; *Splenic Artery ; Time Factors ; Treatment Outcome ; },
abstract = {BACKGROUND/AIMS: We examined the utility of partial splenic embolization (PSE) using a Guglielmi Detachable Coil (GDC) comparing its safety and therapeutic efficacy with those of conventional metallic coils (IDC).<br><br>METHODOLOGY: The GDC group comprised 8 patients who were subjected to embolization using a GDC in combination with an IDC, and the IDC group comprised 13 patients. Treatment factors were evaluated by the total number of coils used. We assessed the mean C-reactive protein (CRP) and the increased rate of platelet counts, 2 weeks after treatment.<br><br>RESULTS: The rate of increase in platelet counts at 2 weeks after PSE was 2.47 in the GDC group and 3.18 in the IDC group (p = 0.076). The mean CRP levels were 3.0 in the GDC group and 5.9 in the IDC group (p = 0.14). The mean number of coils were 5.3 in the GDC group and 15.3 in the IDC group and this difference was statistically significant (p = 0.0008).<br><br>CONCLUSION: A GDC is excellent in terms of stability and allows the operator to conduct embolization of hypersplenism in an accurate and reliable manner. In summary, use of a GDC for hypersplenism reduced the total number of coils required for successful treatment.},
}
@article {pmid26886800,
year = {2016},
author = {Kuhlwilm, M and Gronau, I and Hubisz, MJ and de Filippo, C and Prado-Martinez, J and Kircher, M and Fu, Q and Burbano, HA and Lalueza-Fox, C and de la Rasilla, M and Rosas, A and Rudan, P and Brajkovic, D and Kucan, &#x17d; and Gušic, I and Marques-Bonet, T and Andrés, AM and Viola, B and Pääbo, S and Meyer, M and Siepel, A and Castellano, S},
title = {Ancient gene flow from early modern humans into Eastern Neanderthals.},
journal = {Nature},
volume = {530},
number = {7591},
pages = {429-433},
pmid = {26886800},
issn = {1476-4687},
support = {R01 GM102192/GM/NIGMS NIH HHS/United States ; GM102192/GM/NIGMS NIH HHS/United States ; U01 MH106874/MH/NIMH NIH HHS/United States ; },
mesh = {Altitude ; Animals ; Bayes Theorem ; Chromosomes, Human, Pair 21/genetics ; Croatia/ethnology ; Gene Flow/*genetics ; Genome, Human/genetics ; Genomics ; Haplotypes/genetics ; Heterozygote ; Humans ; Hybridization, Genetic/genetics ; Neanderthals/*genetics ; Phylogeny ; Population Density ; Siberia ; Spain/ethnology ; Time Factors ; },
abstract = {It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.},
}
@article {pmid26884359,
year = {2016},
author = {Petridis, C and Brook, MN and Shah, V and Kohut, K and Gorman, P and Caneppele, M and Levi, D and Papouli, E and Orr, N and Cox, A and Cross, SS and Dos-Santos-Silva, I and Peto, J and Swerdlow, A and Schoemaker, MJ and Bolla, MK and Wang, Q and Dennis, J and Michailidou, K and Benitez, J and González-Neira, A and Tessier, DC and Vincent, D and Li, J and Figueroa, J and Kristensen, V and Borresen-Dale, AL and Soucy, P and Simard, J and Milne, RL and Giles, GG and Margolin, S and Lindblom, A and Brüning, T and Brauch, H and Southey, MC and Hopper, JL and Dörk, T and Bogdanova, NV and Kabisch, M and Hamann, U and Schmutzler, RK and Meindl, A and Brenner, H and Arndt, V and Winqvist, R and Pylkäs, K and Fasching, PA and Beckmann, MW and Lubinski, J and Jakubowska, A and Mulligan, AM and Andrulis, IL and Tollenaar, RA and Devilee, P and Le Marchand, L and Haiman, CA and Mannermaa, A and Kosma, VM and Radice, P and Peterlongo, P and Marme, F and Burwinkel, B and van Deurzen, CH and Hollestelle, A and Miller, N and Kerin, MJ and Lambrechts, D and Floris, G and Wesseling, J and Flyger, H and Bojesen, SE and Yao, S and Ambrosone, CB and Chenevix-Trench, G and Truong, T and Guénel, P and Rudolph, A and Chang-Claude, J and Nevanlinna, H and Blomqvist, C and Czene, K and Brand, JS and Olson, JE and Couch, FJ and Dunning, AM and Hall, P and Easton, DF and Pharoah, PD and Pinder, SE and Schmidt, MK and Tomlinson, I and Roylance, R and García-Closas, M and Sawyer, EJ},
title = {Genetic predisposition to ductal carcinoma in situ of the breast.},
journal = {Breast cancer research : BCR},
volume = {18},
number = {1},
pages = {22},
pmid = {26884359},
issn = {1465-542X},
support = {CA54281/CA/NCI NIH HHS/United States ; CA128978/CA/NCI NIH HHS/United States ; R01 CA176785/CA/NCI NIH HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; UM1 CA164920/CA/NCI NIH HHS/United States ; 16565/CRUK_/Cancer Research UK/United Kingdom ; C12292/A11174/CRUK_/Cancer Research UK/United Kingdom ; C5047/A10692/CRUK_/Cancer Research UK/United Kingdom ; R01 CA128978/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; C5047/A15007/CRUK_/Cancer Research UK/United Kingdom ; R01 CA132839/CA/NCI NIH HHS/United States ; C1281/A12014/CRUK_/Cancer Research UK/United Kingdom ; CA098758/CA/NCI NIH HHS/United States ; C8197/A16565/CRUK_/Cancer Research UK/United Kingdom ; MC_PC_14105/MRC_/Medical Research Council/United Kingdom ; CA116201/CA/NCI NIH HHS/United States ; P30 CA016056-32/CA/NCI NIH HHS/United States ; /CAPMC/CIHR/Canada ; CA63464/CA/NCI NIH HHS/United States ; C490/A10124/CRUK_/Cancer Research UK/United Kingdom ; U01 CA116167/CA/NCI NIH HHS/United States ; C5047/A8384/CRUK_/Cancer Research UK/United Kingdom ; C1287/A 10710/CRUK_/Cancer Research UK/United Kingdom ; CA116167/CA/NCI NIH HHS/United States ; CA176785/CA/NCI NIH HHS/United States ; U19 CA148537/CA/NCI NIH HHS/United States ; R01 CA116167/CA/NCI NIH HHS/United States ; C1287/A12014/CRUK_/Cancer Research UK/United Kingdom ; R01 CA063464/CA/NCI NIH HHS/United States ; 16563/CRUK_/Cancer Research UK/United Kingdom ; R01 CA054281/CA/NCI NIH HHS/United States ; U01 CA063464/CA/NCI NIH HHS/United States ; 090532/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; U19 CA148112/CA/NCI NIH HHS/United States ; U01 CA098758/CA/NCI NIH HHS/United States ; CA132839/CA/NCI NIH HHS/United States ; U19 CA148065/CA/NCI NIH HHS/United States ; 10119/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; C1287/A10118/CRUK_/Cancer Research UK/United Kingdom ; U01 CA164973/CA/NCI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; 16561/CRUK_/Cancer Research UK/United Kingdom ; 10124/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cyclin D1/*genetics ; Female ; *Genetic Association Studies ; Genotype ; Humans ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Proteins/genetics ; Polymorphism, Single Nucleotide ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; },
abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci.<br><br>METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip.<br><br>RESULTS: Most (67&#xa0;%) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P&#x2009;<&#x2009;5.0x10(-8).<br><br>CONCLUSION: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.},
}
@article {pmid26876209,
year = {2016},
author = {Kim, DY and Helfman, DM},
title = {Loss of MLCK leads to disruption of cell-cell adhesion and invasive behavior of breast epithelial cells via increased expression of EGFR and ERK/JNK signaling.},
journal = {Oncogene},
volume = {35},
number = {34},
pages = {4495-4508},
pmid = {26876209},
issn = {1476-5594},
mesh = {Actin Cytoskeleton/metabolism ; Breast/*pathology ; Breast Neoplasms/enzymology/*pathology ; Cell Adhesion ; Cell Aggregation ; Cell Line, Tumor ; Cell Movement ; Cells, Cultured ; Epithelial Cells/pathology ; ErbB Receptors/*physiology ; Female ; Humans ; MAP Kinase Signaling System/*physiology ; Myosin-Light-Chain Kinase/*physiology ; Neoplasm Invasiveness ; RNA, Small Interfering/genetics ; },
abstract = {Myosin light chain kinase (MLCK) expression is downregulated in breast cancer, including invasive ductal carcinoma compared with ductal breast carcinoma in situ and metastatic breast tumors. However, little is known about how loss of MLCK expression contributes to tumor progression. MLCK is a component of the actin cytoskeleton and its known role is the phosphorylation of the regulatory light chain of myosin II. To gain insights into the role of MLCK in breast cancer, we perturbed its function using small interfering RNA (siRNA) or pharmacological inhibition in untransformed breast epithelial cells (MCF10A). Loss of MLCK by siRNAs led to increased cell migration and invasion, disruption of cell-cell adhesions and enhanced formation of focal adhesions at the leading edge of migratory cells. In addition, downregulation of MLCK cooperated with HER2 in MCF10A cells to promote cell migration and invasion and low levels of MLCK is associated with a poor prognosis in HER2-positive breast cancer patients. Associated with these altered migratory behaviors were increased expression of epidermal growth factor receptor and activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways in MLCK downregulated MCF10A cells. By contrast, inhibition of the kinase function of MLCK using pharmacological agents inhibited cell migration and invasion, and did not affect cellular adhesions. Our results show that loss of MLCK contributes to the migratory properties of epithelial cells resulting from changes in cell-cell and cell-matrix adhesions, and increased epidermal growth factor receptor signaling. These findings suggest that decreased expression of MLCK may have a critical role during tumor progression by facilitating the metastatic potential of tumor cells.},
}
@article {pmid26864079,
year = {2016},
author = {Gulvin, J and Aboulafia, DM},
title = {Squamous Cell Cancer of Unknown Primary and Primary Breast Cancer in an HIV-Infected Woman: The Importance of Cancer Screening for People Living with HIV/AIDS.},
journal = {Journal of the International Association of Providers of AIDS Care},
volume = {15},
number = {3},
pages = {194-200},
doi = {10.1177/2325957416629550},
pmid = {26864079},
issn = {2325-9574},
mesh = {*Breast Neoplasms/complications/diagnostic imaging ; *Carcinoma, Squamous Cell/complications/diagnostic imaging/secondary ; Early Detection of Cancer ; Female ; Groin/diagnostic imaging/pathology ; HIV Infections/*complications ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Middle Aged ; Papillomavirus Infections ; },
abstract = {People living with HIV/AIDS (PLWHA) are surviving longer, with an increased risk of cancer. Cancer screening strategies in PLWHA are lacking. We describe the case of a woman with a history of AIDS, who had a nondetectable viral load on treatment. She is an activist, promoting HIV care, but had not undergone routine screening for breast, cervical, or colonic neoplasia. She presented with a left groin mass, which on biopsy proved to be a p16 immuno-histochemical positive squamous cell carcinoma. Anal and cervicovaginal examinations did not show invasive cancer, although high-resolution anoscopy identified high-grade anal dysplasia. A mammogram followed by magnetic resonance imaging showed invasive ductal carcinoma. Her breast cancer was treated with lumpectomy, adjuvant brachytherapy and chemotherapy. The left groin tumor was treated with chemo-radiation. Herein, we also review medical literature concerning anal, cervical, breast, colorectal, and lung cancer screening for PLWHA, which is important for our aging population of PLWHA.},
}
@article {pmid26858037,
year = {2016},
author = {Zhu, L and Mok, S and Imwong, M and Jaidee, A and Russell, B and Nosten, F and Day, NP and White, NJ and Preiser, PR and Bozdech, Z},
title = {New insights into the Plasmodium vivax transcriptome using RNA-Seq.},
journal = {Scientific reports},
volume = {6},
number = {},
pages = {20498},
pmid = {26858037},
issn = {2045-2322},
support = {093956//Wellcome Trust/United Kingdom ; },
mesh = {Chromosomes/genetics/metabolism ; *High-Throughput Nucleotide Sequencing ; Humans ; Plasmodium vivax/*genetics/metabolism ; RNA, Protozoan/biosynthesis/*genetics ; Transcriptome/*physiology ; },
abstract = {Historically seen as a benign disease, it is now becoming clear that Plasmodium vivax can cause significant morbidity. Effective control strategies targeting P. vivax malaria is hindered by our limited understanding of vivax biology. Here we established the P. vivax transcriptome of the Intraerythrocytic Developmental Cycle (IDC) of two clinical isolates in high resolution by Illumina HiSeq platform. The detailed map of transcriptome generates new insights into regulatory mechanisms of individual genes and reveals their intimate relationship with specific biological functions. A transcriptional hotspot of vir genes observed on chromosome 2 suggests a potential active site modulating immune evasion of the Plasmodium parasite across patients. Compared to other eukaryotes, P. vivax genes tend to have unusually long 5' untranslated regions and also present multiple transcription start sites. In contrast, alternative splicing is rare in P. vivax but its association with the late schizont stage suggests some of its significance for gene function. The newly identified transcripts, including up to 179 vir like genes and 3018 noncoding RNAs suggest an important role of these gene/transcript classes in strain specific transcriptional regulation.},
}
@article {pmid26843058,
year = {2016},
author = {Pare, R and Shin, JS and Lee, CS},
title = {Increased expression of senescence markers p14(ARF) and p16(INK4a) in breast cancer is associated with an increased risk of disease recurrence and poor survival outcome.},
journal = {Histopathology},
volume = {69},
number = {3},
pages = {479-491},
doi = {10.1111/his.12948},
pmid = {26843058},
issn = {1365-2559},
mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; *Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p16/analysis/*biosynthesis ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local/mortality/pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Tissue Array Analysis ; Tumor Suppressor Protein p14ARF/analysis/*biosynthesis ; },
abstract = {AIMS: Breast cancer is a hormonally driven disease. Cellular senescence is an age-related irreversible cell cycle arrest at the G1 phase upon induction. The aim of this study was to characterize the expression patterns of the senescence markers p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) during breast cancer progression in a large patient cohort.<br><br>METHODS AND RESULTS: We conducted a retrospective study of 1080 patients with invasive ductal carcinoma, no special type, over an 11-year period. We performed immunohistochemical staining on tissue microarrays that included normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma tissue from each patient. Invasive ductal carcinomas showed higher expression of p14(ARF) and p16(INK4a) but lower expression of p21(WAF1/Cip1) than non-malignant tissues. There were significant correlations of normal, benign, preinvasive and malignant tissues with p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) expression (P < 0.05). Univariate comparison showed a correlation between high p16(INK4a) expression and poor survival (P = 0.000) and an increased risk of relapse (P = 0.000), whereas high p14(ARF) expression correlated only with an increased risk of relapse (P = 0.038). Multivariate analysis showed p16(INK4a) to be an important prognostic factor for overall survival (P = 0.011) and disease-free survival (P = 0.004), with p14(ARF) also being a significant prognostic factor for disease-free survival (P = 0.043). Moreover, patients showing both high p16(INK4a) expression and and high p14(ARF) expression had an adjusted three-fold increased risk of disease recurrence (P < 0.05) and a two-fold increased risk of all-cause-related death (P < 0.05).<br><br>CONCLUSIONS: These finding suggest p16(INK4a) expression and p14(ARF) expression may play an important role in the progression of proliferative breast tissue to invasive cancer, and may be useful as prognostic factors.},
}
@article {pmid26838218,
year = {2016},
author = {Moazzezy, N and Ebrahimi, F and Sisakht, MM and Yahyazadeh, H and Bouzari, S and Oloomi, M},
title = {Relationship between erb-B2 mRNA Expression in Blood and Tissue of Invasive Ductal Carcinoma Breast Cancer Patients and Clinicopathological Characteristics of the Tumors.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {17},
number = {1},
pages = {249-254},
doi = {10.7314/apjcp.2016.17.1.249},
pmid = {26838218},
issn = {2476-762X},
mesh = {Adult ; Aged ; Biomarkers, Tumor/blood/metabolism ; Breast Neoplasms/blood/*genetics/metabolism/*pathology ; Carcinoma, Ductal/blood/*genetics/metabolism/*pathology ; Cell Line, Tumor ; Female ; Humans ; Lymph Nodes/metabolism/pathology ; Middle Aged ; Prognosis ; RNA, Messenger/blood/*genetics/metabolism ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Young Adult ; },
abstract = {Molecular detection methods such as RT-PCR for detecting breast cancer-associated gene expression in the peripheral blood have the potential to modify breast cancer (BC) staging and therapy. In this regard, we evaluated the potential of erb-B2 molecular marker in BC detection and analyzed the expression of erb-B2 mRNA in the peripheral blood and fresh tissue samples of 50 pretreated female BC patients and 50 healthy females by reverse transcription-PCR (RT-PCR) method. We also assessed the correlation of erb-B2 mRNA marker positivity in peripheral blood and tumor tissue samples with clinical and pathological factors in BC patients in order to evaluate its prognostic value. It was shown that there is a significant difference between healthy females and BC patients with expression of the erb-B2 molecular marker (p<0.01). A significant difference between the expression of erb-B2 in the peripheral blood and tissue samples of BC patients (p<0.01) and the frequency of circulating erb-B2 mRNA expression in peripheral blood and in tissue was detected by RT-PCR. No correlation was found between erb-B2 mRNA expression in blood or tumor tissue samples and lymph node, tumor grade, tumor stage, tumor size, patient's age, ki67, estrogen receptor (ER), progesterone receptor (PGR), P53, and HER-2 status. However, in a small subset of 31 BC patients we found that expression of erb-B2 in peripheral blood or in both peripheral blood and tumor tissue was directly correlated with lympho-vascular invasion and perineural invasion as poor prognostic features. The highest rates of erb-B2 expression in peripheral blood or tumor tissue were in the ER and PR negative and HER-2 positive group. This study suggests that the application of the RT-PCR and immunohistochemical methods for erb-B2 molecular marker detection would provide a higher detection rate, especially in early stage BC.},
}
@article {pmid26829374,
year = {2016},
author = {Annacontini, L and Ciancio, F and Parisi, D and Innocenti, A and Portincasa, A},
title = {Management of nipple-areolar complex complications in skin-sparing mastectomy with prosthetic reconstruction A case report.},
journal = {Annali italiani di chirurgia},
volume = {87},
number = {ePub},
pages = {},
pmid = {26829374},
issn = {2239-253X},
mesh = {Breast Neoplasms/pathology/surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Female ; Humans ; Mammaplasty/*adverse effects/methods ; *Mastectomy, Subcutaneous/adverse effects/methods ; Middle Aged ; *Negative-Pressure Wound Therapy/methods ; Neoplasm Invasiveness ; Neoplasm Staging ; Nipples/*blood supply ; Prostheses and Implants ; Surgical Wound/*etiology/*therapy ; Treatment Outcome ; },
abstract = {INTRODUCTION AND OBJECCTIVES: Venous congestion of the NAC (Nipple-Areola Complex) is not an uncommon complication of Skin-Reducing Mastectomy (SRM). The correct and prompt evaluation of the NAC's vitality in the first hours after surgery is important for the survival of the same, in fact the possibility of early intervention allows avoiding the use of invasive and radicals techniques to the advantage of simpler rapid procedures.<br><br>MATERIALS AND METHODS: DM, 57yr, multiple invasive ductal carcinoma of the right breast, underwent a SRM and immediate reconstruction with implant in August 2014 In the immediate post-operative appeared a venous stasis of the NAC. Treatment started with Negative Pressure Wound Therapy (NWPT) through VAC-Systems to 75 mmHg.<br><br>RESULTS: The use of the VAC-Therapy was in total 12 days and allowed the partial rescue of the NAC (85%). the vacuum pump is put into a portable bag so the patient's mobility is not limited.<br><br>DISCUSSION: NWPT permitted a rapid resolution of NAC's complication in SRM in order to guarantee an optimal timing for the start of adjuvant chemotherapy. The VAC-Therapy is a cost effective and simple to use in cases of suffering venous NAC in patients undergoing breast surgery.<br><br>KEY WORDS: NAC, NWPT, Skin-Reducing Mastectomy, VAC-Therapy.},
}
@article {pmid26826418,
year = {2016},
author = {Mardekian, SK and Bombonati, A and Palazzo, JP},
title = {Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions.},
journal = {Human pathology},
volume = {49},
number = {},
pages = {114-123},
doi = {10.1016/j.humpath.2015.11.003},
pmid = {26826418},
issn = {1532-8392},
mesh = {Animals ; Biomarkers, Tumor/analysis/*genetics ; Biopsy ; Breast Neoplasms/chemistry/*genetics/pathology/therapy ; Carcinoma/chemistry/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*genetics/pathology/therapy ; Disease Progression ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Mastectomy ; Molecular Diagnostic Techniques ; Neoplasm Recurrence, Local ; Phenotype ; Predictive Value of Tests ; Reproducibility of Results ; Treatment Outcome ; },
abstract = {Ductal carcinoma in situ (DCIS) of the breast is a lesion characterized by significant heterogeneity, in terms of morphology, immunohistochemical staining, molecular signatures, and clinical expression. For some patients, surgical excision provides adequate treatment, but a subset of patients will experience recurrence of DCIS or progression to invasive ductal carcinoma (IDC). Recent years have seen extensive research aimed at identifying the molecular events that characterize the transition from normal epithelium to DCIS and IDC. Tumor epithelial cells, myoepithelial cells, and stromal cells undergo alterations in gene expression, which are most important in the early stages of breast carcinogenesis. Epigenetic modifications, such as DNA methylation, together with microRNA alterations, play a major role in these genetic events. In addition, tumor proliferation and invasion is facilitated by the lesional microenvironment, which includes stromal fibroblasts and macrophages that secrete growth factors and angiogenesis-promoting substances. Characterization of DCIS on a molecular level may better account for the heterogeneity of these lesions and how this manifests as differences in patient outcome and response to therapy. Molecular assays originally developed for assessing likelihood of recurrence in IDC are recently being applied to DCIS, with promising results. In the future, the classification of DCIS will likely incorporate molecular findings along with histologic and immunohistochemical features, allowing for personalized prognostic information and therapeutic options for patients with DCIS. This review summarizes current data regarding the molecular characterization of DCIS and discusses the potential clinical relevance.},
}
@article {pmid26823905,
year = {2015},
author = {Huo, Z and Gao, Y and Yu, Z and Zuo, W and Zhang, Y},
title = {Metastasis of breast cancer to renal cancer: report of a rare case.},
journal = {International journal of clinical and experimental pathology},
volume = {8},
number = {11},
pages = {15417-15421},
pmid = {26823905},
issn = {1936-2625},
mesh = {Adult ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*secondary/surgery ; Carcinoma, Renal Cell/chemistry/*pathology ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; Kidney Neoplasms/chemistry/*pathology/secondary ; Mastectomy, Modified Radical ; Neoplasms, Multiple Primary/chemistry/*pathology/surgery ; Nephrectomy ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome ; },
abstract = {Tumor-to-tumor metastasis (TTM) is a rare phenomenon. We present a case of an invasive ductal carcinoma (IDC) of the breast metastasizing to a clear cell renal cell carcinoma (RCC). Breast cancer (BC) metastasis to the RCC is rarely reported, especially in resected kidney tumor. In several cases reported, IDC was the exclusively histologic type of BC metastasized to RCC. It seems that the different molecular type of IDC doesn't affect the metastatic tendencies to RCC. TTM was an indicator of diffuse disease. For any patient with a history of breast cancer, especially with multi-organs metastasis, resection of kidney tumor should be carefully considered.},
}
@article {pmid26813772,
year = {2016},
author = {Saita, C and Goto, R and Aruga, T and Idera, N and Honda, Y and Horiguchi, K and Miyamoto, H and Horiguchi, S and Yamashita, T and Kuroi, K},
title = {Invasive papillary carcinoma treated with neoadjuvant endocrine therapy in which pathological complete response was achieved.},
journal = {BMC research notes},
volume = {9},
number = {},
pages = {46},
pmid = {26813772},
issn = {1756-0500},
mesh = {Aged, 80 and over ; Antineoplastic Agents, Hormonal/*therapeutic use ; Aromatase Inhibitors/*therapeutic use ; Breast Neoplasms/genetics/metabolism/pathology/*therapy ; Carcinoma, Papillary/genetics/metabolism/pathology/*therapy ; Female ; Gene Expression ; Humans ; Letrozole ; Neoadjuvant Therapy/methods ; Nitriles/*therapeutic use ; Postmenopause ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Treatment Outcome ; Triazoles/*therapeutic use ; },
abstract = {BACKGROUND: Invasive papillary carcinoma is a rare type of invasive ductal carcinoma. Neoadjuvant endocrine therapy is now considered as an optional therapy for postmenopausal women with hormone receptor-positive breast cancers, including invasive papillary carcinoma.<br><br>CASE PRESENTATION: We discuss the case of an 83-year-old postmenopausal Japanese female with hormone receptor-positive invasive papillary carcinoma who started treatment with an aromatase inhibitor and achieved pathological complete response after 12 months of endocrine treatment.<br><br>CONCLUSION: Appropriate drugs and durations of neoadjuvant endocrine treatment have yet to be established. Continuing therapy with an aromatase inhibitor until the best clinical response is achieved may represent one of the best strategies in neoadjuvant endocrine therapy.},
}
@article {pmid26807730,
year = {2016},
author = {Korsten, H and Ziel-van der Made, AC and van Weerden, WM and van der Kwast, T and Trapman, J and Van Duijn, PW},
title = {Characterization of Heterogeneous Prostate Tumors in Targeted Pten Knockout Mice.},
journal = {PloS one},
volume = {11},
number = {1},
pages = {e0147500},
pmid = {26807730},
issn = {1932-6203},
mesh = {Adenocarcinoma/chemistry/genetics/pathology ; Animals ; Apoptosis/genetics ; Biomarkers ; Biomarkers, Tumor ; Cadherins/analysis ; Carcinoma/chemistry/*genetics/pathology ; Carcinosarcoma/chemistry/genetics/pathology ; Cellular Senescence/genetics ; Disease Progression ; Epithelial Cells/chemistry ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Inflammation/genetics ; Keratins/analysis ; Male ; Mesoderm/chemistry ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Neoplasm Proteins/analysis ; Neovascularization, Pathologic/genetics/pathology ; PTEN Phosphohydrolase/*deficiency ; Prostatic Hyperplasia/genetics/pathology ; Prostatic Neoplasms/chemistry/classification/*genetics/pathology ; RNA, Messenger/biosynthesis/genetics ; RNA, Neoplasm/biosynthesis/genetics ; Stromal Cells/chemistry ; },
abstract = {Previously, we generated a preclinical mouse prostate tumor model based on PSA-Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m) developed at older age (>10m) into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model. The morphologies of the tumors that developed were very heterogeneous. Different histopathological growth patterns could be identified, including intraductal carcinoma (IDC), adenocarcinoma and undifferentiated carcinoma, all strongly positive for the epithelial cell marker Cytokeratin (CK), and carcinosarcomas, which were negative for CK. IDC pattern was already detected in prostates of 7-8 month old mice, indicating that it could be a precursor stage. At more than 10 months IDC and carcinosarcoma were most frequently observed. Gene expression profiling discriminated essentially two molecular subtypes, denoted tumor class 1 (TC1) and tumor class 2 (TC2). TC1 tumors were characterized by high expression of epithelial markers like Cytokeratin 8 and E-Cadherin whereas TC2 tumors showed high expression of mesenchyme/stroma markers such as Snail and Fibronectin. These molecular subtypes corresponded with histological growth patterns: where TC1 tumors mainly represented adenocarcinoma/intraductal carcinoma, in TC2 tumors carcinosarcoma was the dominant growth pattern. Further molecular characterization of the prostate tumors revealed an increased expression of genes associated with the inflammatory response. Moreover, functional markers for senescence, proliferation, angiogenesis and apoptosis were higher expressed in tumors compared to hyperplasia. The highest expression of proliferation and angiogenesis markers was detected in TC2 tumors. Our data clearly showed that in the genetically well-defined PSA-Cre;Pten-loxP/loxP prostate tumor model, histopathological, molecular and biological heterogeneity occurred during later stages of tumor development.},
}
@article {pmid26805359,
year = {2015},
author = {Noguchi, K and Tomimaru, Y and Eguchi, H and Ogawa, H and Yamada, D and Tomokuni, A and Noda, T and Asaoka, T and Wada, H and Kawamoto, K and Goto, K and Marubashi, S and Nagano, H and Mori, M and Doki, Y},
title = {[Three Resected Cases of Metachronous Pancreatic Cancer Successfully Treated with Repeated Pancreatectomy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {42},
number = {12},
pages = {2346-2348},
pmid = {26805359},
issn = {0385-0684},
mesh = {Aged ; Biopsy ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/drug therapy/secondary ; Male ; Middle Aged ; Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; Recurrence ; },
abstract = {Repeated pancreatectomy for metachronous pancreatic cancer has rarely been reported. We report 3 cases with metachronous pancreatic ductal carcinoma that developed after pancreatectomy for the first pancreatic cancer. They were successfully resected by removal of the remnant pancreas. In all 3 cases, the cancers in the remnant pancreas were treated with repeated pancreatectomy. The histological margin of the first pancreatic resection was cancer-free in all the cases. Furthermore, the second cancer tissue contained carcinoma lesions in situ adjacent to invasive ductal carcinoma. Based on these findings, the 3 patients were diagnosed with metachronous pancreatic cancers.},
}
@article {pmid26805179,
year = {2015},
author = {Kakimoto, M and Nakata, T and Imaizumi, K and Hirano, T and Murata, T and Okuno, K and Hoshino, M and Matsuyama, T and Goto, H and Koshiishi, H and Yoshimura, T and Osanai, T and Suzuki, K},
title = {[Subclavian Artery Hemorrhage Related to Everolimus in a Patient with Recurrent Breast Cancer--A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {42},
number = {12},
pages = {1806-1808},
pmid = {26805179},
issn = {0385-0684},
mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Everolimus/administration &amp; dosage/*adverse effects ; Fatal Outcome ; Female ; Hemorrhage/*chemically induced ; Humans ; Mastectomy, Segmental ; Middle Aged ; Recurrence ; *Subclavian Artery ; },
abstract = {A 53-year-old woman underwent breast-conserving surgery for right breast cancer (invasive ductal carcinoma, T1cN0M0, ly+, stage ⅠA, ER+, PR+, HER2-) 5 years previously. During treatment with tamoxifen, massive recurrence in the axillary lymph nodes was found. First- through fourth-line chemotherapy were tried, but they all failed. Everolimus and exemestane were administered, resulting in rapid shrinking of the tumor, but the patient developed sudden severe bleeding from the subclavian artery. Hemostasis was achieved with artery stenting. The patient also developed a thoracic duct-cutaneous fistula. The patient died from tumor regrowth 6.5 months after her first everolimus treatment. Treating tumors involving major vessels with everolimus can cause severe bleeding after rapid shrinking of the tumor.},
}
@article {pmid26805172,
year = {2015},
author = {Sato, Y and Okishiro, M and Ohneda, Y and Motoyama, Y and Ishida, T and Morimoto, Y and Kusama, H and Matsushita, K and Hashimoto, T and Kimura, K and Naito, A and Murakami, K and Katsura, Y and Nitta, K and Ohmura, Y and Kagawa, Y and Takeno, A and Sakisaka, H and Taniguchi, H and Egawa, C and Takeda, Y and Kato, T and Tamura, S and Takatsuka, Y and Goto, T and Nagano, T and Nakatsuka, S},
title = {[A Case of Peritoneal Metastasis of Breast Cancer Diagnosed by Laparoscopic-Assisted Right Hemicolectomy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {42},
number = {12},
pages = {1785-1787},
pmid = {26805172},
issn = {0385-0684},
mesh = {Adenocarcinoma/*surgery ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy/*pathology/*surgery ; Carcinoma, Ductal/drug therapy/*surgery ; Colectomy ; Female ; Humans ; Laparoscopy ; Peritoneal Neoplasms/*secondary/*surgery ; Recurrence ; Tamoxifen/therapeutic use ; Tegafur/therapeutic use ; Uracil/therapeutic use ; },
abstract = {The patient was an 86-year-old woman. She underwent right breast-conserving surgery and sentinel lymph node biopsy for breast cancer in August 2006. The pathological diagnosis was invasive ductal carcinoma, T1N0M0, Stage Ⅰ, ER (+), PgR (-), HER2 (-). She was treated with tamoxifen for 5 years as adjuvant therapy and showed no signs of recurrence. In November 2014, CA15-3 was elevated and an accumulation of FDG in the right paracolic sulcus was observed on PET-CT. Peritoneal metastasis of breast cancer was suspected, and an operation was performed for a definitive diagnosis. During the operation, the tumor was seen on the paracolic sulcus, and laparoscopic-assisted right hemicolectomy was performed. A poorly differentiated adenocarcinoma was diagnosed by pathological examination, and immunostaining results were as follows: CK7(+), CK20(-), mammaglobin (-), GCDFP-15 (-), ER (-), PgR (-), and HER2 (-). Because there was no original lesion other than the breast cancer, the tumor was diagnosed as a metastasis of breast cancer. The frequency of peritoneal metastasis of breast cancer is low. In this case, pathological diagnosis was necessary for a definitive diagnosis. A change of subtype was also confirmed, and the treatment strategy was decided appropriately. Surgical resection should be considered for peritoneal metastasis of breast cancer when the operation can be performed safely.},
}
@article {pmid26805170,
year = {2015},
author = {Takaoka, A and Nakagawa, T and Ogawa, N and Hayashi, M and Park, S and Iseki, H and Bei, Y},
title = {[HER2-Positive T1a Breast Cancer Metastatic to the Liver and Brain in a Patient Who Died Four Years and Three Months after Mastectomy--A Case Report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {42},
number = {12},
pages = {1779-1781},
pmid = {26805170},
issn = {0385-0684},
mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary/*therapy ; Breast Neoplasms/chemistry/pathology/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/secondary/*therapy ; Mastectomy ; Middle Aged ; Receptor, ErbB-2/analysis ; },
abstract = {The prognosis of patients with T1a breast cancer is generally good, with a 5-year overall survival rate of 95%. However, HER2 overexpression is a risk factor for recurrence. A 46-year-old woman with left breast cancer underwent a total breast resection. The resected specimen showed invasive ductal carcinoma (T1a, NX, MX, g, ly0, v0, ER [-], PgR [-], HER2 [3+], Ki-67 20%). The patient did not receive adjuvant chemotherapy based on treatment guidelines. Nine months after the mastectomy, multiple liver metastases and severe acute hepatic insufficiency were found. The patient received chemotherapy with trastuzumab and paclitaxel, and a complete response was observed with disappearance of the liver metastases. One year and 11 months after the mastectomy, multiple brain metastases appeared. The patient received whole brain radiation therapy, Gamma Knife radiosurgery, and Cyber Knife radiosurgery. However, the brain metastasis could not be controlled, and the patient died 4 years and 3 months after mastectomy. HER2 positive T1a breast cancer should be observed carefully, and treatment with trastuzumab should be considered.},
}
@article {pmid26805079,
year = {2015},
author = {Kanada, Y and Matsuzaki, H and Kobayashi, H and Suzuki, K and Sawada, H and Senba, Y and Yoshioka, T and Note, H and Sato, Y and Miyazaki, A and Natsume, T and Tanaka, H and Maruyama, T},
title = {[A Case of Locally-Advanced Breast Cancer with Liver Metastasis, Treated with Mastectomy of the Primary Tumor after Chemotherapy].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {42},
number = {12},
pages = {1509-1511},
pmid = {26805079},
issn = {0385-0684},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Combined Modality Therapy ; Cyclophosphamide/administration &amp; dosage ; Epirubicin/administration &amp; dosage ; Estrogen Replacement Therapy ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Mastectomy ; Neoplasm Staging ; Tamoxifen/therapeutic use ; },
abstract = {The patient was a 39-year-old woman who was referred to our hospital with suspicion of locally-advanced breast cancer. After several tests, she received a diagnosis of cT4bN1M1 (liver), Stage Ⅳbreast cancer. The liver metastasis was located in S4, and was 1 cm in size. Core needle biopsy was performed on the breast tumor; the pathological diagnosis was invasive ductal carcinoma (scirrhous carcinoma), nuclear Grade (NG) 3, and HER2-positive. She received epirubicin plus cyclophosphamide (EC) followed by docetaxel (DOC) plus pertuzumab (PER) plus trastuzumab (HER). After chemotherapy, the liver metastasis and axillary lymph node metastases had disappeared on imaging findings, showing a complete response (CR), but the primary breast tumor remained, showing a partial response (PR). She underwent mastectomy and axillary lymph node dissection for local control. After surgery, no metastases including liver metastases were seen on CT. The patient is currently receiving tamoxifen and anti-HER2 therapy.},
}
@article {pmid26804549,
year = {2016},
author = {Fardmanesh, H and Shekari, M and Movafagh, A and Alizadeh Shargh, S and Poursadegh Zonouzi, AA and Shakerizadeh, S and Poursadegh Zonouzi, A and Hosseinzadeh, A},
title = {Upregulation of the double-stranded RNA binding protein DGCR8 in invasive ductal breast carcinoma.},
journal = {Gene},
volume = {581},
number = {2},
pages = {146-151},
doi = {10.1016/j.gene.2016.01.033},
pmid = {26804549},
issn = {1879-0038},
mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; RNA-Binding Proteins/*genetics ; *Up-Regulation ; },
abstract = {High-throughput experimental studies have indicated that the miRNAome is globally downregulated in various types of malignancy, and dysregulation of miRNAs processing component(s) is one possible mechanism for this phenomenon. Despite the progression in identifying cellular functions of Digeorge Syndrome Critical Region 8 (DGCR8) in miRNAs biogenesis, the role of altered expression of DGCR8 in the pathogenesis of invasive ductal breast carcinoma (IDC) has not yet been fully investigated. The objective of the present study was to evaluate DGCR8 mRNA expression in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissues using quantitative real-time PCR and to assess the value of clinicopathological parameters on its expression. Our findings revealed that DGCR8 mRNA expression is upregulated in more than two-thirds of the cancerous specimens (68.66%) when compared to adjacent non-neoplastic tissue. This difference is statistically significant (P<0.05). We found that DGCR8 mRNA levels were increased in the high-grade and metastatic compared with those of both low-grade and non-metastatic. We demonstrated that there is not significant correlation between DGCR8 mRNA expression levels and clinicopathological parameters. In conclusion, our study suggested that upregulation of DGCR8 may be involved in tumorigenesis and aggressiveness of IDC and may serve as future therapeutic target.},
}
@article {pmid26775637,
year = {2016},
author = {Ghandour, RA and Giroud, M and Vegiopoulos, A and Herzig, S and Ailhaud, G and Amri, EZ and Pisani, DF},
title = {IP-receptor and PPARs trigger the conversion of human white to brite adipocyte induced by carbaprostacyclin.},
journal = {Biochimica et biophysica acta},
volume = {1861},
number = {4},
pages = {285-293},
doi = {10.1016/j.bbalip.2016.01.007},
pmid = {26775637},
issn = {0006-3002},
mesh = {Adipocytes, Brown/*drug effects/metabolism ; Adipocytes, White/*drug effects/metabolism ; Adipogenesis/*drug effects ; Anti-Obesity Agents/*pharmacology ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dose-Response Relationship, Drug ; Energy Metabolism/drug effects ; Enzyme Activation ; Epoprostenol/*analogs &amp; derivatives/pharmacology ; Humans ; Infant ; Ion Channels/genetics/metabolism ; Male ; Mitochondrial Proteins/genetics/metabolism ; PPAR alpha/*agonists/genetics/metabolism ; PPAR gamma/*agonists/metabolism ; Phenotype ; RNA Interference ; Receptors, Epoprostenol ; Receptors, Prostaglandin/*agonists/metabolism ; Signal Transduction/drug effects ; Thermogenesis/drug effects ; Time Factors ; Transfection ; Uncoupling Protein 1 ; },
abstract = {Brite adipocytes recently discovered in humans are of considerable importance in energy expenditure by converting energy excess into heat. This property could be useful in the treatment of obesity, and nutritional aspects are relevant to this important issue. Using hMADS cells as a human cell model which undergoes a white to a brite adipocyte conversion, we had shown previously that arachidonic acid, the major metabolite of the essential nutrient Ω6-linoleic acid, plays a major role in this process. Its metabolites PGE2 and PGF2 alpha inhibit this process via a calcium-dependent pathway, whereas in contrast carbaprostacyclin (cPGI2), a stable analog of prostacyclin, activates white to brite adipocyte conversion. Herein, we show that cPGI2 generates via its cognate cell-surface receptor IP-R, a cyclic AMP-signaling pathway involving PKA activity which in turn induces the expression of UCP1. In addition, cPGI2 activates the pathway of nuclear receptors of the PPAR family, i.e. PPARα and PPARγ, which act separately from IP-R to up-regulate the expression of key genes involved in the function of brite adipocytes. Thus dual pathways are playing in concert for the occurrence of a browning process of human white adipocytes. These results make prostacyclin analogs as a new class of interesting molecules to treat obesity and associated diseases.},
}
@article {pmid26775353,
year = {2015},
author = {Qin, XJ and Gao, ZG and Huan, JL and Pan, XF and Zhu, L},
title = {Protein kinase D1 inhibits breast cancer cell invasion via regulating matrix metalloproteinase expression.},
journal = {European journal of gynaecological oncology},
volume = {36},
number = {6},
pages = {690-693},
pmid = {26775353},
issn = {0392-2936},
mesh = {Breast Neoplasms/enzymology/*pathology ; Cell Line, Tumor ; Female ; Humans ; Matrix Metalloproteinase 2/analysis ; Matrix Metalloproteinase 9/analysis ; Neoplasm Invasiveness ; Protein Kinase C/genetics/*physiology ; },
abstract = {PURPOSE: This study aimed to explore the role of protein kinase D1 (PKD1) in breast cancer invasion.<br><br>MATERIALS AND METHODS: The relative expression of PKD1mRNA and protein in human invasive breast cancer tissue samples and normal samples, as well as breast cancer cell lines, were detected. Constitutively-active PKD1 and PKD1 specific shRNA were expressed in the MD-MB-231 and MCF-7 cells, respectively. The role of PKD1 in the invasive behavior of breast cancer cell line was evaluated by matrix metalloproteinase (MMP) expression.<br><br>RESULTS: The results showed that PKD1, as a serine/threonine kinase, is downregulated significantly in invasive ductal carcinoma and metastatic invasive ductal carcinoma tissue than the normal tissue and the low expression of PKD1 is also found in breast cancer cell line MD-MB-231. The MMP2 and MMP9 expression in PKD1 constitutively-active MD-MB-231 cells and MCF-7 knockdown cells were decreased and increased respectively.<br><br>CONCLUSION: The authors confirmed that PKD1 was downregulated in invasive breast cancer. PKD1 can negatively regulate the MMP expression and may serve as a potential therapeutic target.},
}
@article {pmid26774154,
year = {2016},
author = {Sobic Saranovic, D and Stojiljkovic, M and Susnjar, S and Odalovic, S and Artiko, V and Pavlovic, S and Grozdic-Milojevic, I and Obradovic, V},
title = {Metabolic activity of breast cancer metastatic lesions on positron emission tomography/computed tomography: comparison with histological and biological characteristics of primary tumor.},
journal = {Neoplasma},
volume = {63},
number = {2},
pages = {313-321},
doi = {10.4149/219_150813N440},
pmid = {26774154},
issn = {0028-2685},
mesh = {Bone Neoplasms/metabolism/secondary ; Breast Neoplasms/*diagnostic imaging/*pathology ; Energy Metabolism/*physiology ; Female ; Fluorodeoxyglucose F18/*metabolism ; Glucose/*metabolism ; Humans ; Ki-67 Antigen/metabolism ; Liver Neoplasms/metabolism/secondary ; Lymph Nodes/metabolism ; Lymphatic Metastasis/pathology ; Middle Aged ; Multimodal Imaging ; *Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals/*metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {Higher intensity of FDG uptake on PET/CT in primary tumor is seen in patients with IDC compared to ILC, also in high grade tumours, tumours with negative ER and higher Ki67 values, while data are inconsistent in case of relation between primary tumor's PgR and HER2 expression with its metabolic activity levels. On account of the lack of studies that include research of breast cancer metastatic lesion metabolism level and its relation to tumor histology and biology, our goal was to investigate the association of metastatic lesions' glucose metabolism level on PET/CT with different histological and biological characteristics of primary tumor. In a total number of N=100 patients, highest SUVmax values for each patient were used in testing difference between metastatic metabolic activity in patients with different tumor histology, grade, ER, PgR and HER2 status, subtype, as well in testing relation of Ki67 index to metastasis' metabolism level. In testing difference between histological types of breast cancer, SUVmax values were also compared separately for each specific anatomical site (regional and distant lymph nodes, bones and liver). No difference was found regarding metastatic SUVmax values in patients with primary IDC (n=55, median SUVmax 9.70) and ILC (n=34, median SUVmax 7.20) independently of anatomic site, and for each of analysed sites separately. No difference was found as well between SUVmax detected in metastasis in patients with different grade (grade II: n=58, median SUVmax 7.70; grade III: n=12, median SUVmax 10.20), ER (59 positive, median SUVmax 8.50; 22 negative, median SUVmax 8.05), PgR (55 positive, median SUVmax 8.50; 23 negative, median SUVmax 7.80), and HER2 (14 positive, median SUVmax 6.84; 51 negative, median SUVmax 8.63) expression in primary tumor, and between patients with different tumor subtype. Ki67 was also not associated with tumor metastatic SUVmax values (n=11, rs = -0.21, p=0.53). We conclude that there is no association of primary breast cancer histological type, grade, ER, PgR, HER2 and Ki67 expression with metabolic activity in metastasis detected on PET/CT.},
}
@article {pmid26769139,
year = {2016},
author = {Thompson, E and Taube, JM and Elwood, H and Sharma, R and Meeker, A and Warzecha, HN and Argani, P and Cimino-Mathews, A and Emens, LA},
title = {The immune microenvironment of breast ductal carcinoma in situ.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {29},
number = {3},
pages = {249-258},
pmid = {26769139},
issn = {1530-0285},
support = {P30 CA006973/CA/NCI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*immunology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*immunology/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Tissue Array Analysis ; Tumor Microenvironment/*immunology ; Young Adult ; },
abstract = {The host immune response has a key role in breast cancer progression and response to therapy. However, relative to primary invasive breast cancers, the immune milieu of breast ductal carcinoma in situ (DCIS) is less understood. Here, we profile tumor infiltrating lymphocytes and expression of the immune checkpoint ligand programmed death ligand 1 (PD-L1) in 27 cases of DCIS with known estrogen receptor (ER), progesterone receptor, and human epidermal growth factor 2 (HER-2) expression using tissue microarrays. Twenty-four cases were pure DCIS and three had associated invasive ductal carcinoma. Tumors were stained by immunohistochemistry for PD-L1, as well as the lymphocyte markers CD3, CD4, CD8, FoxP3, and CD20. The expression of PD-L1 by DCIS carcinoma cells and tumor infiltrating lymphocytes was determined, and the average tumor infiltrating lymphocytes per high power field were manually scored. None of the DCIS cells expressed PD-L1, but 81% of DCIS lesions contained PD-L1+ tumor infiltrating lymphocytes. DCIS with moderate-diffuse tumor infiltrating lymphocytes was more likely to have PD-L1+ tumor infiltrating lymphocytes (P=0.004). Tumor infiltrating lymphocytes with high levels of PD-L1 expression (>50% cells) were seen only in triple-negative DCIS (P=0.0008), and PD-L1-tumor infiltrating lymphocytes were seen only in ER+/HER-2-DCIS (P=0.12). The presence of PD-L1+ tumor infiltrating lymphocytes was associated with a younger mean patient age (P=0.01). Further characterization of the DCIS immune microenvironment may identify useful targets for immune-based therapy and breast cancer prevention.},
}
@article {pmid26744317,
year = {2016},
author = {Riku, M and Inaguma, S and Ito, H and Tsunoda, T and Ikeda, H and Kasai, K},
title = {Down-regulation of the zinc-finger homeobox protein TSHZ2 releases GLI1 from the nuclear repressor complex to restore its transcriptional activity during mammary tumorigenesis.},
journal = {Oncotarget},
volume = {7},
number = {5},
pages = {5690-5701},
pmid = {26744317},
issn = {1949-2553},
mesh = {Apoptosis ; Blotting, Western ; Breast/metabolism/*pathology ; Breast Neoplasms/genetics/metabolism/*pathology ; Carboxypeptidases/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; Case-Control Studies ; Cell Proliferation ; Cell Transformation, Neoplastic/*genetics/pathology ; Cells, Cultured ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Receptors, CXCR4/genetics/metabolism ; Repressor Proteins/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcriptional Activation ; Zinc Finger Protein GLI1/genetics/*metabolism ; },
abstract = {Although breast cancer is one of the most common malignancies, the molecular mechanisms underlying its development and progression are not fully understood. To identify key molecules involved, we screened publicly available microarray datasets for genes differentially expressed between breast cancers and normal mammary glands. We found that three of the genes predicted in this analysis were differentially expressed among human mammary tissues and cell lines. Of these genes, we focused on the role of the zinc-finger homeobox protein TSHZ2, which is down-regulated in breast cancer cells. We found that TSHZ2 is a nuclear protein harboring a bipartite nuclear localization signal, and we confirmed its function as a C-terminal binding protein (CtBP)-dependent transcriptional repressor. Through comprehensive screening, we identified TSHZ2-suppressing genes such as AEBP1 and CXCR4, which are conversely up-regulated by GLI1, the downstream transcription factor of Hedgehog signaling. We found that GLI1 forms a ternary complex with CtBP2 in the presence of TSHZ2 and that the transcriptional activity of GLI1 is suppressed by TSHZ2 in a CtBP-dependent manner. Indeed, knockdown of TSHZ2 increases the expression of AEBP1 and CXCR4 in TSHZ2-expressing immortalized mammary duct epithelium. Concordantly, immunohistochemical staining of mammary glands revealed that normal duct cells expresses GLI1 in the nucleus along with TSHZ2 and CtBP2, whereas invasive ductal carcinoma cells, which does not express TSHZ2, show the increase in the expression of AEBP1 and CXCR4 and in the cytoplasmic localization of GLI1. Thus, we propose that down-regulation of TSHZ2 is crucial for mammary tumorigenesis via the activation of GLI1.},
}
@article {pmid26740749,
year = {2015},
author = {Makki, J},
title = {Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance.},
journal = {Clinical medicine insights. Pathology},
volume = {8},
number = {},
pages = {23-31},
pmid = {26740749},
issn = {1179-5557},
abstract = {Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality, with an incidence of >1,000,000 cases occurring worldwide annually. It is one of the most common human neoplasms, accounting for approximately one-quarter of all cancers in females worldwide and 27% of cancers in developed countries with a Western lifestyle. They exhibit a wide scope of morphological features, different immunohistochemical profiles, and unique histopathological subtypes that have specific clinical course and outcome. Breast cancers can be classified into distinct subgroups based on similarities in the gene expression profiles and molecular classification.},
}
@article {pmid26729235,
year = {2016},
author = {Michaut, M and Chin, SF and Majewski, I and Severson, TM and Bismeijer, T and de Koning, L and Peeters, JK and Schouten, PC and Rueda, OM and Bosma, AJ and Tarrant, F and Fan, Y and He, B and Xue, Z and Mittempergher, L and Kluin, RJ and Heijmans, J and Snel, M and Pereira, B and Schlicker, A and Provenzano, E and Ali, HR and Gaber, A and O'Hurley, G and Lehn, S and Muris, JJ and Wesseling, J and Kay, E and Sammut, SJ and Bardwell, HA and Barbet, AS and Bard, F and Lecerf, C and O'Connor, DP and Vis, DJ and Benes, CH and McDermott, U and Garnett, MJ and Simon, IM and Jirström, K and Dubois, T and Linn, SC and Gallagher, WM and Wessels, LF and Caldas, C and Bernards, R},
title = {Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.},
journal = {Scientific reports},
volume = {6},
number = {},
pages = {18517},
pmid = {26729235},
issn = {2045-2322},
support = {102696/WT_/Wellcome Trust/United Kingdom ; 16942/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics/*metabolism/mortality ; Carcinoma, Lobular/diagnosis/*genetics/*metabolism ; Cluster Analysis ; DNA-Binding Proteins/genetics/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Profiling ; *Genomics/methods ; Humans ; Immunohistochemistry ; Mutation Rate ; Polymorphism, Single Nucleotide ; Prognosis ; *Proteome ; Proteomics ; Reproducibility of Results ; Transcription Factors/genetics/metabolism ; *Transcriptome ; },
abstract = {Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.},
}
@article {pmid26721716,
year = {2016},
author = {Wang, L and Lyu, S and Wang, S and Shen, H and Niu, F and Liu, X and Liu, J and Niu, Y},
title = {Loss of FAT1 during the progression from DCIS to IDC and predict poor clinical outcome in breast cancer.},
journal = {Experimental and molecular pathology},
volume = {100},
number = {1},
pages = {177-183},
doi = {10.1016/j.yexmp.2015.12.012},
pmid = {26721716},
issn = {1096-0945},
mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*genetics/metabolism/*pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology/therapy ; Disease Progression ; Female ; Humans ; Immunohistochemistry/methods ; Middle Aged ; Receptors, Estrogen/metabolism ; Treatment Outcome ; beta Catenin/metabolism ; },
abstract = {FAT1 and β-catenin are important tumor regulatory factors. The aim of this study was to detect the possible disparity in their expression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) and to explore its correlation with clinicopathological factors. We used immunohistochemistry to detect protein expression of FAT1 and β-catenin in breast cancer tissues from 113 cases of DCIS and 149 cases of IDC. As compared with DCIS, expression of FAT1 and β-catenin were significantly decreased in IDC (P<0.05). In addition, our study also revealed a correlation between their expression and some clinicopathological factors. We found that FAT1 expression was associated with nuclear grade and comedonecrosis (P<0.05) in DCIS, whereas FAT1 expression showed significant variation with histological grade and LN status (P<0.05) in IDC. Similar associations were observed in the β-catenin subgroup. Furthermore, expressions of FAT1 and β-catenin were correlated with each other in DCIS and IDC (P<0.05). FAT1(-), β-catenin(-), or FAT1(-)/β-catenin(-) may indicate worse DFS and OS in breast cancer (P<0.05). This study suggests that loss of FAT1 and β-catenin are associated with breast cancer progression, aggressive behavior, and poor prognosis. FAT1 alone or together with β-catenin might be a valuable biomarker in predicting the prognosis of patients with breast cancer.},
}
@article {pmid29787025,
year = {2016},
author = {Kasap, E and Gene, M and Sahin, N and Sivrikoz, ON},
title = {Mayer-Rokitansky-Kuster-Hauser syndrome accompanied by invasive ductal carcinoma: a case report.},
journal = {European journal of gynaecological oncology},
volume = {37},
number = {5},
pages = {744-746},
pmid = {29787025},
issn = {0392-2936},
mesh = {46, XX Disorders of Sex Development/*complications/pathology ; Adult ; Breast Neoplasms/*etiology/pathology ; Carcinoma, Ductal, Breast/*etiology/pathology ; Congenital Abnormalities/pathology ; Female ; Humans ; Mullerian Ducts/*abnormalities/pathology ; },
abstract = {Milllerian agenesis and the absence of organs of Millerian canal origin are referred to as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Invasive ductal carcinoma constitutes 47-75% of all breast carcinomas and is the most common type. The authors report the first case of invasive ductal carcinoma associated with MRKH syndrome in the literature to their knowledge. A 25-year-old woman with a palpable mass in her right breast for three months presented to the presented clinic. On physical examination a mobile, firm mass measuring 2x2 cm was detected in right breast, at a region close to axilla. A fine needle aspiration biopsy from the lesion revealed malignant cells and thus a segmental mastectomy operation was performed. All genital tract and endocrinological system should be thoroughly examined before administering hormone replacement therapy to patients presenting with primary amenorrhea.The co-occurrence MRKH syndrome of with invasive ductal carcinoma is regarded as coincidental. Confirming the absence of a common etiology, however, requires further genetic studies.},
}
@article {pmid28330128,
year = {2016},
author = {Paryan, M and Tavakoli, R and Rad, SMAH and Feizi, N and Kamani, F and Mostafavi, E and Mohammadi-Yeganeh, S},
title = {Over-expression of NOTCH1 as a biomarker for invasive breast ductal carcinoma.},
journal = {3 Biotech},
volume = {6},
number = {1},
pages = {58},
pmid = {28330128},
issn = {2190-572X},
abstract = {Breast cancer is the leading cause of cancer-related death in women worldwide. Invasive ductal carcinoma (IDC) is the most frequent invasive form of breast cancer followed by metastasis. There is no accepted marker for distinguishing this form from other less aggressive forms of breast cancer. Therefore, finding new markers especially molecularly detectable ones are noteworthy. It has been shown that NOTCH1 has been overexpressed in the patients with breast cancer, but no study has investigated the expression of NOTCH1 and its correlation with other molecular and hormonal markers of breast cancer so far. In the current study, 20 breast cancer tissues and 20 matched adjacent normal breast tissue from breast cancer patients were obtained and categorized in two groups: patients with IDC and patient with other types of breast cancer. Gene expression analysis using real-time PCR showed that the NOTCH1 gene was significantly overexpressed in patients with IDC. We also found a slight correlation between NOTCH1 overexpression and p53 accumulation in the cancerous cells confirmed by Immunohistochemistry (IHC). This results showed that it is possible to introduce NOTCH1 expression as a novel biomarker of IDC, alone or preferably accompanied by IHC of p53. We also can design new therapeutic agents targeting NOTCH1 expression for inhibition of metastasis in ductal breast carcinoma.},
}
@article {pmid26715212,
year = {2016},
author = {Nakagawa, S and Miki, Y and Miyashita, M and Hata, S and Takahashi, Y and Rai, Y and Sagara, Y and Ohi, Y and Hirakawa, H and Tamaki, K and Ishida, T and Watanabe, M and Suzuki, T and Ohuchi, N and Sasano, H},
title = {Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets.},
journal = {Breast cancer research and treatment},
volume = {155},
number = {1},
pages = {65-75},
doi = {10.1007/s10549-015-3668-9},
pmid = {26715212},
issn = {1573-7217},
mesh = {Actins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Angiogenesis Inducing Agents/metabolism ; Antigens, CD34/metabolism ; Biomarkers ; Breast Neoplasms/genetics/*metabolism/*pathology/therapy ; Carcinoma, Lobular/genetics/*metabolism/*pathology/therapy ; Cell Cycle Proteins/metabolism ; Female ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor I/genetics/metabolism ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic/genetics/metabolism ; Nestin/metabolism ; Receptor, IGF Type 1/genetics/metabolism ; Tumor Burden ; *Tumor Microenvironment/genetics ; },
abstract = {Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC.},
}
@article {pmid26688682,
year = {2015},
author = {Grebić, D and Tomašić, AM},
title = {Sporadic Case of Breast Angiosarcoma as a Complication of Radiotherapy Following Breast-Conserving Surgery for Invasive Ductal Breast Cancer.},
journal = {Breast care (Basel, Switzerland)},
volume = {10},
number = {5},
pages = {336-338},
pmid = {26688682},
issn = {1661-3791},
abstract = {BACKGROUND: Angiosarcomas are highly aggressive and malignant blood vessel tumors. Rarely, angiosarcomas develop in the breast following conservative therapy, namely radiotherapy.<br><br>CASE REPORT: A 70-year-old female patient presented with dark purple discoloration of the skin of the right breast. 6 years earlier, the patient had undergone conservative surgery for invasive ductal carcinoma of the right breast. According to the breast-conserving surgery protocol, the patient had been treated with radiotherapy to the residual breast tissue. The patient's annual mammograms and ultrasound findings were normal. The skin lesion was superficially localized mostly at the border between the upper and lower medial quadrants of the breast (between 2 and 4 o'clock) and above the areola. The borders were uneven; the dimensions were 7 cm &#xd7; 4 cm. The mammogram was classified as Breast Imaging Report and Data System (BI-RADS) 2. Ultrasound examination showed a well-vascularized structure, although the etiology was unclear. A tissue biopsy revealed angiosarcoma. The patient underwent radical simplex mastectomy. Following surgery, the patient underwent chemotherapy. Tests excluded metastases for a follow-up period of 5 years.<br><br>CONCLUSION: Angiosarcomas that develop after radiotherapy following breast-conserving surgery are sporadic, but it is important to take this possible incident into consideration during treatment.},
}
@article {pmid26684357,
year = {2016},
author = {Dai, K and Qin, F and Zhang, H and Liu, X and Guo, C and Zhang, M and Gu, F and Fu, L and Ma, Y},
title = {Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy.},
journal = {Oncotarget},
volume = {7},
number = {4},
pages = {4770-4784},
pmid = {26684357},
issn = {1949-2553},
support = {R03 AA020101/AA/NIAAA NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Anthracyclines/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*metabolism ; Bone Morphogenetic Protein Receptors, Type I/*metabolism ; Breast Neoplasms/drug therapy/metabolism/*pathology ; Bridged-Ring Compounds/administration &amp; dosage ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*secondary ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Taxoids/administration &amp; dosage ; },
abstract = {Bone morphogenetic protein receptor type IB (BMPRIB) is one osteogenesis factor, which function in breast cancer has been rarely explored until recently. In the clinical study presented here, involving a cohort of 368 invasive ductal carcinoma (IDC) patients, we identified that patients with low expression of BMPRIB exhibited poor prognosis, especially in the luminal B subtype. We also provided the first piece of evidence that low level of BMPRIB was a promoting factor for breast cancer patients to develop bone metastasis, but not lung, liver or brain. The first of its kind, we reported that patients with high expression of BMPRIB exhibited favorable prognosis by a retrospective analysis consisting of 168 patients treated with TE (taxane and anthracycline) regimens. And the patients with high expression of BMPRIB were more sensitive to TE regimens in the detection of 32 paired pre-neoadjuvant and post-neoadjuvant specimens. Overall, our study concluded that low expression of BMPRIB indicated poor prognosis of breast cancer and was insensitive to taxane-anthracycline chemotherapy. Our findings also lay a foundation to help clinicians improve identification of patients for TE regimens by BMPRIB in the era of precision medicine.},
}
@article {pmid26680994,
year = {2016},
author = {Fan, Z and Silva, P and Gronau, I and Wang, S and Armero, AS and Schweizer, RM and Ramirez, O and Pollinger, J and Galaverni, M and Ortega Del-Vecchyo, D and Du, L and Zhang, W and Zhang, Z and Xing, J and Vilà, C and Marques-Bonet, T and Godinho, R and Yue, B and Wayne, RK},
title = {Worldwide patterns of genomic variation and admixture in gray wolves.},
journal = {Genome research},
volume = {26},
number = {2},
pages = {163-173},
pmid = {26680994},
issn = {1549-5469},
support = {R00 HG005846/HG/NHGRI NIH HHS/United States ; R00HG005846/HG/NHGRI NIH HHS/United States ; },
mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Dogs/*genetics ; Female ; Genome ; Hybridization, Genetic ; Male ; Markov Chains ; Models, Genetic ; Phylogeny ; Polymorphism, Single Nucleotide ; Principal Component Analysis ; Sequence Analysis, DNA ; Wolves/*genetics ; },
abstract = {The gray wolf (Canis lupus) is a widely distributed top predator and ancestor of the domestic dog. To address questions about wolf relationships to each other and dogs, we assembled and analyzed a data set of 34 canine genomes. The divergence between New and Old World wolves is the earliest branching event and is followed by the divergence of Old World wolves and dogs, confirming that the dog was domesticated in the Old World. However, no single wolf population is more closely related to dogs, supporting the hypothesis that dogs were derived from an extinct wolf population. All extant wolves have a surprisingly recent common ancestry and experienced a dramatic population decline beginning at least ∼30 thousand years ago (kya). We suggest this crisis was related to the colonization of Eurasia by modern human hunter-gatherers, who competed with wolves for limited prey but also domesticated them, leading to a compensatory population expansion of dogs. We found extensive admixture between dogs and wolves, with up to 25% of Eurasian wolf genomes showing signs of dog ancestry. Dogs have influenced the recent history of wolves through admixture and vice versa, potentially enhancing adaptation. Simple scenarios of dog domestication are confounded by admixture, and studies that do not take admixture into account with specific demographic models are problematic.},
}
@article {pmid26679836,
year = {2016},
author = {Ben-David, BM and Durham, NA and van Lieshout, PH},
title = {The Linguistic Acoustic ThreaT Effect (LATTE): Screening tool for the impact of semantic threat in speech processing after a brain injury.},
journal = {Brain injury},
volume = {30},
number = {2},
pages = {237-239},
doi = {10.3109/02699052.2015.1091506},
pmid = {26679836},
issn = {1362-301X},
mesh = {Adolescent ; Brain Injuries/*complications ; Female ; Humans ; Linguistics ; Male ; Semantics ; Speech/*physiology ; Young Adult ; },
}
@article {pmid26670275,
year = {2015},
author = {Serina, P and Riley, I and Stewart, A and Flaxman, AD and Lozano, R and Mooney, MD and Luning, R and Hernandez, B and Black, R and Ahuja, R and Alam, N and Alam, SS and Ali, SM and Atkinson, C and Baqui, AH and Chowdhury, HR and Dandona, L and Dandona, R and Dantzer, E and Darmstadt, GL and Das, V and Dhingra, U and Dutta, A and Fawzi, W and Freeman, M and Gamage, S and Gomez, S and Hensman, D and James, SL and Joshi, R and Kalter, HD and Kumar, A and Kumar, V and Lucero, M and Mehta, S and Neal, B and Ohno, SL and Phillips, D and Pierce, K and Prasad, R and Praveen, D and Premji, Z and Ramirez-Villalobos, D and Rampatige, R and Remolador, H and Romero, M and Said, M and Sanvictores, D and Sazawal, S and Streatfield, PK and Tallo, V and Vadhatpour, A and Wijesekara, N and Murray, CJ and Lopez, AD},
title = {A shortened verbal autopsy instrument for use in routine mortality surveillance systems.},
journal = {BMC medicine},
volume = {13},
number = {},
pages = {302},
pmid = {26670275},
issn = {1741-7015},
mesh = {Adult ; Cause of Death ; Child, Preschool ; Developing Countries ; *Epidemiological Monitoring ; Humans ; Infant, Newborn ; Reproducibility of Results ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed. In this paper we describe a shortened version of the VAI developed for the Population Health Metrics Research Consortium (PHMRC) Gold Standard Verbal Autopsy Validation Study using a systematic approach.<br><br>METHODS: We used data from the PHMRC validation study. Using the Tariff 2.0 method, we first established a rank order of individual questions in the PHMRC VAI according to their importance in predicting causes of death. Second, we reduced the size of the instrument by dropping questions in reverse order of their importance. We assessed the predictive performance of the instrument as questions were removed at the individual level by calculating chance-corrected concordance and at the population level with cause-specific mortality fraction (CSMF) accuracy. Finally, the optimum size of the shortened instrument was determined using a first derivative analysis of the decline in performance as the size of the VA instrument decreased for adults, children, and neonates.<br><br>RESULTS: The full PHMRC VAI had 183, 127, and 149 questions for adult, child, and neonatal deaths, respectively. The shortened instrument developed had 109, 69, and 67 questions, respectively, representing a decrease in the total number of questions of 40-55%. The shortened instrument, with text, showed non-significant declines in CSMF accuracy from the full instrument with text of 0.4%, 0.0%, and 0.6% for the adult, child, and neonatal modules, respectively.<br><br>CONCLUSIONS: We developed a shortened VAI using a systematic approach, and assessed its performance when administered using hand-held electronic tablets and analyzed using Tariff 2.0. The length of a VA questionnaire was shortened by almost 50% without a significant drop in performance. The shortened VAI developed reduces the burden of time and resources required for data collection and analysis of cause of death data in civil registration systems.},
}
@article {pmid26652003,
year = {2015},
author = {Hein, AM and Rosenthal, SB and Hagstrom, GI and Berdahl, A and Torney, CJ and Couzin, ID},
title = {The evolution of distributed sensing and collective computation in animal populations.},
journal = {eLife},
volume = {4},
number = {},
pages = {e10955},
pmid = {26652003},
issn = {2050-084X},
mesh = {Animals ; *Behavior, Animal ; Biological Evolution ; Fishes/*physiology ; Models, Biological ; *Social Behavior ; },
abstract = {Many animal groups exhibit rapid, coordinated collective motion. Yet, the evolutionary forces that cause such collective responses to evolve are poorly understood. Here, we develop analytical methods and evolutionary simulations based on experimental data from schooling fish. We use these methods to investigate how populations evolve within unpredictable, time-varying resource environments. We show that populations evolve toward a distinctive regime in behavioral phenotype space, where small responses of individuals to local environmental cues cause spontaneous changes in the collective state of groups. These changes resemble phase transitions in physical systems. Through these transitions, individuals evolve the emergent capacity to sense and respond to resource gradients (i.e. individuals perceive gradients via social interactions, rather than sensing gradients directly), and to allocate themselves among distinct, distant resource patches. Our results yield new insight into how natural selection, acting on selfish individuals, results in the highly effective collective responses evident in nature.},
}
@article {pmid26644140,
year = {2015},
author = {Serina, P and Riley, I and Stewart, A and James, SL and Flaxman, AD and Lozano, R and Hernandez, B and Mooney, MD and Luning, R and Black, R and Ahuja, R and Alam, N and Alam, SS and Ali, SM and Atkinson, C and Baqui, AH and Chowdhury, HR and Dandona, L and Dandona, R and Dantzer, E and Darmstadt, GL and Das, V and Dhingra, U and Dutta, A and Fawzi, W and Freeman, M and Gomez, S and Gouda, HN and Joshi, R and Kalter, HD and Kumar, A and Kumar, V and Lucero, M and Maraga, S and Mehta, S and Neal, B and Ohno, SL and Phillips, D and Pierce, K and Prasad, R and Praveen, D and Premji, Z and Ramirez-Villalobos, D and Rarau, P and Remolador, H and Romero, M and Said, M and Sanvictores, D and Sazawal, S and Streatfield, PK and Tallo, V and Vadhatpour, A and Vano, M and Murray, CJ and Lopez, AD},
title = {Improving performance of the Tariff Method for assigning causes of death to verbal autopsies.},
journal = {BMC medicine},
volume = {13},
number = {},
pages = {291},
pmid = {26644140},
issn = {1741-7015},
mesh = {Autopsy/*methods ; *Cause of Death ; Female ; Humans ; Male ; },
abstract = {BACKGROUND: Reliable data on the distribution of causes of death (COD) in a population are fundamental to good public health practice. In the absence of comprehensive medical certification of deaths, the only feasible way to collect essential mortality data is verbal autopsy (VA). The Tariff Method was developed by the Population Health Metrics Research Consortium (PHMRC) to ascertain COD from VA information. Given its potential for improving information about COD, there is interest in refining the method. We describe the further development of the Tariff Method.<br><br>METHODS: This study uses data from the PHMRC and the National Health and Medical Research Council (NHMRC) of Australia studies. Gold standard clinical diagnostic criteria for hospital deaths were specified for a target cause list. VAs were collected from families using the PHMRC verbal autopsy instrument including health care experience (HCE). The original Tariff Method (Tariff 1.0) was trained using the validated PHMRC database for which VAs had been collected for deaths with hospital records fulfilling the gold standard criteria (validated VAs). In this study, the performance of Tariff 1.0 was tested using VAs from household surveys (community VAs) collected for the PHMRC and NHMRC studies. We then corrected the model to account for the previous observed biases of the model, and Tariff 2.0 was developed. The performance of Tariff 2.0 was measured at individual and population levels using the validated PHMRC database.<br><br>RESULTS: For median chance-corrected concordance (CCC) and mean cause-specific mortality fraction (CSMF) accuracy, and for each of three modules with and without HCE, Tariff 2.0 performs significantly better than the Tariff 1.0, especially in children and neonates. Improvement in CSMF accuracy with HCE was 2.5%, 7.4%, and 14.9% for adults, children, and neonates, respectively, and for median CCC with HCE it was 6.0%, 13.5%, and 21.2%, respectively. Similar levels of improvement are seen in analyses without HCE.<br><br>CONCLUSIONS: Tariff 2.0 addresses the main shortcomings of the application of the Tariff Method to analyze data from VAs in community settings. It provides an estimation of COD from VAs with better performance at the individual and population level than the previous version of this method, and it is publicly available for use.},
}
@article {pmid26643230,
year = {2015},
author = {Street, P and Thompson, J and Bailey, M},
title = {Management of urinary catheters following hip fracture.},
journal = {Australasian journal on ageing},
volume = {34},
number = {4},
pages = {241-246},
doi = {10.1111/ajag.12166},
pmid = {26643230},
issn = {1741-6612},
mesh = {Aged ; Aged, 80 and over ; *Catheters, Indwelling ; Chi-Square Distribution ; Dementia/complications ; Device Removal ; Female ; Guideline Adherence ; *Health Services for the Aged/standards ; Hip Fractures/complications/diagnosis/*therapy ; Humans ; Logistic Models ; Male ; Medical Audit ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Patient Discharge ; Practice Guidelines as Topic ; Prognosis ; Residential Facilities ; Retrospective Studies ; Risk Factors ; Urinary Catheterization/adverse effects/*instrumentation/standards ; *Urinary Catheters ; },
abstract = {AIM: To examine current practices and factors associated with outcomes of urinary catheter removal ('trial of void' or TOV) in patients following hip fracture.<br><br>METHOD: Retrospective file audit of patients discharged over a three-year period with a diagnosis of recent hip fracture.<br><br>RESULTS: There were 133 TOVs in 310 patients. Of the 78 TOVs occurring in the aged care rehabilitation hospital, 50% were successful. Adherence to the hospital's TOV guideline was documented infrequently. TOV outcome was not related to interval since catheter insertion, constipation or inability to mobilise. Multivariate analysis showed that dementia was independently associated with the presence of an in-dwelling catheter (IDC) on discharge and that patients discharged with an IDC had a higher probability of residential care placement.<br><br>CONCLUSIONS: Practices in managing TOVs are inconsistent. No potentially modifiable predictors of TOV success were identified. The presence of an IDC has implications for discharge destination.},
}
@article {pmid26628432,
year = {2016},
author = {Kim, YS and Chang, JM and Moon, HG and Lee, J and Shin, SU and Moon, WK},
title = {Residual Mammographic Microcalcifications and Enhancing Lesions on MRI After Neoadjuvant Systemic Chemotherapy for Locally Advanced Breast Cancer: Correlation with Histopathologic Residual Tumor Size.},
journal = {Annals of surgical oncology},
volume = {23},
number = {4},
pages = {1135-1142},
doi = {10.1245/s10434-015-4993-2},
pmid = {26628432},
issn = {1534-4681},
mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Calcinosis/chemically induced/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/metabolism/pathology ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Magnetic Resonance Imaging/*methods ; Mammography ; Middle Aged ; Neoadjuvant Therapy/*adverse effects ; Neoplasm Staging ; Neoplasm, Residual/chemically induced/*diagnosis/diagnostic imaging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Young Adult ; },
abstract = {PURPOSE: To evaluate the accuracy of residual microcalcifications on mammogram (MG) in predicting the extent of the residual tumor after neoadjuvant systemic treatment (NST) in patients with locally advanced breast cancer and to evaluate factors affecting the accuracy of MG microcalcifications using magnetic resonance imaging (MRI) as a reference.<br><br>METHODS: The patients who underwent NST and showed suspicious microcalcifications on MG comprised our study population. Clinicopathologic and imaging (MG, MRI) findings were investigated. Agreement between image findings and pathology was assessed and factors affecting the discrepancy were analyzed.<br><br>RESULTS: Among 207 patients, 196 had residual invasive ductal carcinoma or ductal carcinoma-in-situ (mean size, 3.78&#xa0;cm). The overall agreement of residual microcalcifications on MG predicting residual tumor extents was lower than MRI in all tumor subtypes (intraclass correlation coefficient [ICC]&#xa0;=&#xa0;0.368 and 0.723, p&#xa0;<&#xa0;0.0001). The agreement of residual MG microcalcifications and pathology was highest in HR(+)/HER2(+) tumors and lowest in the triple-negative tumors (ICC&#xa0;=&#xa0;0.417 and 0.205, respectively). Multivariate linear regression analysis revealed that a size discrepancy between microcalcifications and histopathology was correlated with molecular subtype (p&#xa0;=&#xa0;0.005). In HR(+)/HER2(-) and triple-negative subtypes, the mean extents of residual microcalcification were smaller than residual cancer, and overestimation of tumor extent was more frequent in HR(+)/HER2(+) and HR(-)/HER2(+) tumors.<br><br>CONCLUSIONS: The extent of microcalcifications on MG after NST showed an overall lower correlation with the extent of the pathologic residual tumor than enhancing lesions on MRI. The accuracy of residual tumor evaluation after NST with MG and MRI is affected by their molecular subtype.},
}
@article {pmid26621543,
year = {2016},
author = {Ruszczyk, M and Zirpoli, G and Kumar, S and Bandera, EV and Bovbjerg, DH and Jandorf, L and Khoury, T and Hwang, H and Ciupak, G and Pawlish, K and Schedin, P and Masso-Welch, P and Ambrosone, CB and Hong, CC},
title = {Breast cancer risk factor associations differ for pure versus invasive carcinoma with an in situ component in case-control and case-case analyses.},
journal = {Cancer causes &amp; control : CCC},
volume = {27},
number = {2},
pages = {183-198},
pmid = {26621543},
issn = {1573-7225},
support = {U58 DP003931/DP/NCCDPHP CDC HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; 5U58DP003931-02/DP/NCCDPHP CDC HHS/United States ; P30 CA072720/CA/NCI NIH HHS/United States ; R01 CA169175/CA/NCI NIH HHS/United States ; P01 CA151135/CA/NCI NIH HHS/United States ; K22 CA138563/CA/NCI NIH HHS/United States ; N01PC-2013-00021/PC/NCI NIH HHS/United States ; R03 CA17106/CA/NCI NIH HHS/United States ; R03 CA171061/CA/NCI NIH HHS/United States ; R01 CA185623/CA/NCI NIH HHS/United States ; R01 CA100598/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Breast Feeding/*statistics &amp; numerical data ; Breast Neoplasms/*epidemiology/pathology ; Carcinoma, Ductal, Breast/*epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology/pathology ; Case-Control Studies ; Female ; Humans ; Logistic Models ; Middle Aged ; Multivariate Analysis ; Obesity/*epidemiology ; Odds Ratio ; Overweight/epidemiology ; *Reproductive History ; Risk Factors ; },
abstract = {PURPOSE: Invasive ductal carcinoma (IDC) is diagnosed with or without a ductal carcinoma in situ (DCIS) component. Previous analyses have found significant differences in tumor characteristics between pure IDC lacking DCIS and mixed IDC with DCIS. We will test our hypothesis that pure IDC represents a form of breast cancer with etiology and risk factors distinct from mixed IDC/DCIS.<br><br>METHODS: We compared reproductive risk factors for breast cancer risk, as well as family and smoking history between 831 women with mixed IDC/DCIS (n = 650) or pure IDC (n = 181), and 1,620 controls, in the context of the Women's Circle of Health Study (WCHS), a case-control study of breast cancer in African-American and European-American women. Data on reproductive and lifestyle factors were collected during interviews, and tumor characteristics were abstracted from pathology reports. Case-control and case-case analyses were conducted using unconditional logistic regression.<br><br>RESULTS: Most risk factors were similarly associated with pure IDC and mixed IDC/DCIS. However, among postmenopausal women, risk of pure IDC was lower in women with body mass index (BMI) 25 to <30 [odds ratio (OR) 0.66; 95 % confidence interval (CI) 0.35-1.23] and BMI &#x2265; 30 (OR 0.33; 95 % CI 0.18-0.67) compared to women with BMI < 25, with no associations with mixed IDC/DCIS. In case-case analyses, women who breastfed up to 12 months (OR 0.55; 95 % CI 0.32-0.94) or longer (OR 0.47; 95 % CI 0.26-0.87) showed decreased odds of pure IDC than mixed IDC/DCIS compared to those who did not breastfeed.<br><br>CONCLUSIONS: Associations with some breast cancer risk factors differed between mixed IDC/DCIS and pure IDC, potentially suggesting differential developmental pathways. These findings, if confirmed in a larger study, will provide a better understanding of the developmental patterns of breast cancer and the influence of modifiable risk factors, which in turn could lead to better preventive measures for pure IDC, which have worse disease prognosis compared to mixed IDC/DCIS.},
}
@article {pmid26617852,
year = {2015},
author = {Chen, Y and Song, J and Jiang, Y and Yu, C and Ma, Z},
title = {Predictive value of CD44 and CD24 for prognosis and chemotherapy response in invasive breast ductal carcinoma.},
journal = {International journal of clinical and experimental pathology},
volume = {8},
number = {9},
pages = {11287-11295},
pmid = {26617852},
issn = {1936-2625},
mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy/immunology/pathology/surgery ; CD24 Antigen/*analysis ; Carcinoma, Ductal, Breast/*drug therapy/*immunology/secondary/surgery ; Chemotherapy, Adjuvant ; Child ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Hyaluronan Receptors/*analysis ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Phenotype ; Predictive Value of Tests ; Proportional Hazards Models ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult ; },
abstract = {OBJECTIVE: Cells with unique phenotypes and stem cell-like properties have been found to exist in breast cancer. The aim of the present study was to study the relationship of CD24, CD44, CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor phenotypes' with clinico-pathological features, chemotherapy response and with prognosis.<br><br>METHODS: The study included paraffin-embedded tissues of 140 primary and secondary invasive ductal carcinoma samples. All the patients received routine chemotherapy. Expression of CD24, CD44, ER, PR, and Her2 were assayed immunohistochemically. We applied double-staining immunohistochemistry for the detection of CD44(+)/CD24(-/low), CD44(+)/CD24 (+), CD44(-)/CD24(-) and CD44(-)/CD24(+) cells. The association between the proportions of CD44(+)/CD24(-/low) and CD44(-)/CD24(+) and clinicopathological features, chemotherapy response and with prognosis of these patients was evaluated.<br><br>RESULTS: CD24 expression was not significantly associated with tumor characteristics, but was significantly associated with poor prognostic variables including ER-, PR-, HER2(+) and triple negative (TN) phenotype; There was no association of CD44 with nodal status, age or HER2 expression. In the correlation analysis, CD24 expression was positively associated with chemotherapy response (P = 0.018), however, CD44 expression was not associated with pathological response to chemotherapy When both markers are considered, the CD44(+)/CD24(-) phenotype had the poor prognosis. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement, recurrent or metastatic tumors and ER/PR status. High CD44(+)/CD24(-) phenotype had poor response to chemotherapy. The median disease-free survival (DFS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 19.8 &#xb1; 2.6 months and 31.7 &#xb1; 4.2 months, and the median overall survival (OS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 33.5 &#xb1; 2.8 months and 51.4 &#xb1; 3.9 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44(+)/CD24(-/low) tumor cells was strongly correlated with DFS and OS. However, the CD44(-)/CD24(+), CD44(+)/CD24(+), CD44(-)/CD24 (-) phenotype had no relation with prognosis.<br><br>CONCLUSION: There was significant correlation between CD44(+)/CD24(-/low) tumor cell prevalence and tumor metastasis, prognosis and chemotherapy response. The CD44(+)/CD24(-) phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.},
}
@article {pmid26613509,
year = {2016},
author = {Skazik-Voogt, C and Kühler, K and Ott, H and Czaja, K and Zwadlo-Klarwasser, G and Merk, HF and Amann, PM and Baron, JM},
title = {Myeloid human cell lines lack functional regulation of aryl hydrocarbon receptor-dependent phase I genes.},
journal = {ALTEX},
volume = {33},
number = {1},
pages = {37-46},
doi = {10.14573/altex.1502041},
pmid = {26613509},
issn = {1868-8551},
mesh = {Aryl Hydrocarbon Receptor Nuclear Translocator/*metabolism ; Cell Line ; Cytochrome P-450 CYP1A1/*genetics/metabolism ; Cytochrome P-450 CYP1B1/metabolism ; Dendritic Cells ; Dermatitis, Contact ; *Gene Expression Regulation/drug effects ; Humans ; Langerhans Cells ; Monocytes ; *Myeloid Cells ; RNA, Messenger/metabolism ; Receptors, Aryl Hydrocarbon/genetics/*metabolism ; },
abstract = {Primary dendritic cells and myeloid cell lines are used to assess the skin sensitization hazard in in vitro approaches. The aryl hydrocarbon receptor (AhR) modulates expression of CYP enzymes which play a significant role in the bioactivation of various xenobiotics. These studies revealed a strong constitutive expression of the AhR in primary human monocytes, monocyte-derived immature dendritic cells (iDC) and cord blood-derived Langerhans cells (LC). In contrast, mRNA and protein expression of AhR was hardly detectable in the cell lines THP-1 and MUTZ-3. U937 cells and MUTZ-3-derived dendritic (MUTZ-DC) or Langerhans cells (MUTZ-LC) showed about half the expression of AhR compared to iDC. Incubation of cells with the specific AhR-inducer benzo[a]anthracene resulted in an upregulation of CYP and IL-1β mRNA expression in primary monocytes and iDC. CYP1A1 but not CYP1B1 and IL-1β expression was increased by benzo[a]anthracene in these cell lines except for U937 cells. AhR-independent CYP genes were not regulated by benzo[a]anthracene. Constitutive mRNA expression of other non AhR-dependent CYP enzymes was higher in some of the cell lines compared to the corresponding primary cells. This study demonstrates significant differences in expression and regulation of phase I genes in cell lines currently used for in vitro skin sensitization hazard assessment compared to primary cells. Additional studies are required regarding the combination of cutaneous xenobiotic metabolizing enzymes and APC-sensitization for the development of valid in vitro models for skin sensitization assessment.},
}
@article {pmid26612847,
year = {2016},
author = {Coyne, JD},
title = {Gynecomastia With Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ Associated With Invasive Breast Carcinoma in a Male Patient on Antiretroviral Therapy: A Case Report.},
journal = {International journal of surgical pathology},
volume = {24},
number = {2},
pages = {139-141},
doi = {10.1177/1066896915608437},
pmid = {26612847},
issn = {1940-2465},
mesh = {Adult ; Antiretroviral Therapy, Highly Active ; Breast Neoplasms, Male/complications/*pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*pathology ; Gynecomastia/*etiology ; *HIV Infections ; Humans ; Male ; },
abstract = {Breast carcinoma in males is rare although a 4-fold increased incidence is reported in HIV-infected men. Herein we report a case of invasive breast carcinoma in a HIV-positive man on antiretroviral therapy. The carcinoma was associated with features of florid gynecomastia, atypical ductal hyperplasia, ductal carcinoma in situ, and columnar cell change. This combination of morphological changes has not previously been reported in the context of male breast carcinoma and their etiopathological associations are discussed.},
}
@article {pmid26610382,
year = {2015},
author = {Swain, SM and Nunes, R and Yoshizawa, C and Rothney, M and Sing, AP},
title = {Quantitative Gene Expression by Recurrence Score in ER-Positive Breast Cancer, by Age.},
journal = {Advances in therapy},
volume = {32},
number = {12},
pages = {1222-1236},
pmid = {26610382},
issn = {1865-8652},
mesh = {Adult ; Age Factors ; Aged ; Breast Neoplasms/*genetics/mortality/*pathology ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/mortality/*pathology ; Neoplasm Staging ; Receptors, Estrogen/*metabolism ; },
abstract = {INTRODUCTION: Breast cancer in young women (<50 years) has been associated with an increased risk of recurrence and decreased survival compared with patients older than 50. The objective of this analysis was to determine, from a large database of patients with early-stage breast cancer, if the Recurrence Score(®) result (Oncotype DX(®), Genomic Health, Inc, Redwood City, CA, USA) provided clinically meaningful differences in predicted risk of recurrence in younger-compared with older-patients.<br><br>METHODS: Tumor samples from patients with estrogen receptor (ER)-positive breast cancers that were successfully processed in the Genomic Health central lab between June 2004 and December 2013 for Recurrence Score and quantitative gene expression of ER, progesterone receptor (PR), and Her/2neu, were included. Descriptive statistics were used to describe the distribution of scores by age group: <40, 40-49, 50-59, 60-69, and &#x2265;70 years, nodal status, and histologic subtype.<br><br>RESULTS: Specimens from 394,031 patients [3.3% (n = 13,029) aged <40 years; 15.6% (n = 61,643) aged &#x2265;70 years] were included; 81.6% of patients had invasive ductal carcinoma. Nodal status was specified for 362,001 patients (87.0% negative). Median Recurrence Score results were similar across risk groups. Low (<18)- and high (&#x2265;31)- risk Recurrence Score results were seen in 58.5% and 8.5% of patients, respectively. A greater proportion of patients aged <40 (14.1%) than &#x2265;70 (8.8%) years had a high-risk score. ER expression increased as a function of age and PR single-gene and invasion gene group expression were similar across age groups.<br><br>CONCLUSION: These data indicate that in patients with ER-positive breast cancer, age alone does not reflect the underlying individual tumor biology, suggesting that the Recurrence Score result may add potentially useful information for personalized treatment decisions.<br><br>FUNDING: Genomic Health, Inc.},
}
@article {pmid26599012,
year = {2015},
author = {Mu, QJ and Li, HL and Yao, Y and Liu, SC and Yin, CG and Ma, XZ},
title = {Chromodomain Helicase/ATPase DNA-Binding Protein 1-Like Gene (CHD1L) Expression and Implications for Invasion and Metastasis of Breast Cancer.},
journal = {PloS one},
volume = {10},
number = {11},
pages = {e0143030},
pmid = {26599012},
issn = {1932-6203},
mesh = {Adult ; Aged ; Animals ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Helicases/antagonists &amp; inhibitors/*biosynthesis/genetics ; DNA-Binding Proteins/antagonists &amp; inhibitors/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Mice ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Proteins/*biosynthesis ; RNA, Small Interfering ; Xenograft Model Antitumor Assays ; },
abstract = {BACKGROUND: Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L), also known as ALC1 (amplified in liver cancer 1 gene), is a new oncogene amplified in many solid tumors. Whether this gene plays a role in invasion and metastasis of breast cancer is unknown.<br><br>METHODS: Immunohistochemistry was performed to detect the expression of CHD1L in patients with invasive ductal carcinoma and normal mammary glands. Chemotaxis, wound healing, and Transwell invasion assays were also performed to examine cell migration and invasion. Western blot analysis was conducted to detect the expression of CHD1L, MMP-2, MMP-9, pAkt/Akt, pARK5/ARK5, and pmTOR/mTOR. Moreover, ELISA was carried out to detect the expression levels of MMP-2 and MMP-9. Nude mice xenograft model was used to detect the invasion and metastasis of breast cancer cell lines.<br><br>RESULTS: CHD1L overexpression was observed in 112 of 268 patients (41.8%). This overexpression was associated with lymph node metastasis (P = 0.008), tumor differentiation (P = 0.020), distant metastasis (P = 0.026), MMP-2 (P = 0.035), and MMP-9 expression (P = 0.022). In the cell experiment, reduction of CHD1L inhibited the invasion and metastasis of breast cancer cells by mediating MMP-2 and MMP-9 expression. CHD1L knockdown via siRNA suppressed EGF-induced pAkt, pARK5, and pmTOR. This knockdown inhibited the metastasis of breast cancer cells into the lungs of SCID mice.<br><br>CONCLUSIONS: CHD1L promoted the invasion and metastasis of breast cancer cells via the PI3K/Akt/ARK5/mTOR/MMP signaling pathway. This study identified CHD1L as a potential anti-metastasis target for therapeutic intervention in breast cancer.},
}
@article {pmid26597811,
year = {2015},
author = {Lappalainen, AK and Mäki, K and Laitinen-Vapaavuori, O},
title = {Estimate of heritability and genetic trend of intervertebral disc calcification in Dachshunds in Finland.},
journal = {Acta veterinaria Scandinavica},
volume = {57},
number = {},
pages = {78},
pmid = {26597811},
issn = {1751-0147},
mesh = {Animals ; Calcinosis/diagnostic imaging/genetics/prevention &amp; control/*veterinary ; Dog Diseases/diagnostic imaging/*genetics/pathology/prevention &amp; control ; Dogs ; Female ; Finland ; Intervertebral Disc/*pathology ; Intervertebral Disc Degeneration/diagnostic imaging/genetics/prevention &amp; control/*veterinary ; Male ; Mass Screening/*veterinary ; Radiography ; },
abstract = {BACKGROUND: Intervertebral disc disease (IDD) is a hereditary condition particularly common in Dachshunds. The breed is predisposed to early intervertebral disc degeneration and intervertebral disc calcification (IDC). When calcified, these severely degenerated discs are visible in spinal radiographs. Since the number of calcified discs (NCD) is associated with IDD, spinal radiography can be utilized in screening programmes in attempts to diminish the incidence of IDD in Dachshunds. Our aims were to estimate the heritability and genetic trend of NCD in Dachshunds in Finland and to explore the effect of age at the time of radiographic screening. Since the NCD has a highly skewed distribution, a log-transformed NCD (lnNCD) was also used as an analysed trait. The variance components for both traits were estimated, using the restricted maximum likelihood method. The fixed effects of breed variant, sex, as well as year of screening and the random effects of litter and animal were included in the model. The genetic trends in the NCD and lnNCD were assessed from the estimated breeding values (EBVs) of individual dogs by comparing the mean EBV of dogs born in different years. The breeding values were estimated, using the best linear unbiased prediction animal model. The pedigree in the genetic analyses included a total of 9027 dogs, of which 1567 showed results for NCDs.<br><br>RESULTS: The heritability estimates of the NCD and lnNCD in Dachshunds were high (0.53 and 0.45, respectively). Small genetic improvements were seen as the mean EBVs increased from 100 to 104 and 105 over a 15-year period. The gain in the entire Dachshund population in Finland may differ from that observed, since less than 10 % of the Dachshunds registered have a screening result for NCD. Age at the time of the screening did not significantly affect the NCD or lnNCD.<br><br>CONCLUSIONS: We recommend systematic radiographic screening for IDC in Dachshunds and adopting EBVs as a tool for selecting breeding dogs. Age at the time of the radiographic screening may not be as important as previously suggested.},
}
@article {pmid26588055,
year = {2016},
author = {Tan, X and Fu, Y and Chen, L and Lee, W and Lai, Y and Rezaei, K and Tabbara, S and Latham, P and Teal, CB and Man, YG and Siegel, RS and Brem, RF and Fu, SW},
title = {miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer.},
journal = {Oncotarget},
volume = {7},
number = {1},
pages = {293-307},
pmid = {26588055},
issn = {1949-2553},
support = {R21 CA159103/CA/NCI NIH HHS/United States ; 1R21 CA159103/CA/NCI NIH HHS/United States ; },
mesh = {Antineoplastic Agents/pharmacology ; Blotting, Western ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Cycle/drug effects/genetics ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Cisplatin/pharmacology ; *Down-Regulation ; Epirubicin/pharmacology ; Epithelial-Mesenchymal Transition/*genetics ; Fluorouracil/pharmacology ; Forkhead Box Protein M1 ; Forkhead Transcription Factors/*genetics/metabolism ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; MicroRNAs/*genetics ; Microscopy, Confocal ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; },
abstract = {MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis. We found that expression of miR-671-5p was decreased significantly in invasive ductal carcinoma (IDC) compared to normal in microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. cDNA microarray data revealed that differentially expressed genes when miR-671-5p was transfected are associated with cell proliferation, invasion, cell cycle, and EMT. These data indicate that miR-671-5p functions as a tumor suppressor miRNA in breast cancer by directly targeting FOXM1. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management.},
}
@article {pmid26581728,
year = {2015},
author = {Ayal, S and Gino, F and Barkan, R and Ariely, D},
title = {Three Principles to REVISE People's Unethical Behavior.},
journal = {Perspectives on psychological science : a journal of the Association for Psychological Science},
volume = {10},
number = {6},
pages = {738-741},
doi = {10.1177/1745691615598512},
pmid = {26581728},
issn = {1745-6924},
mesh = {Humans ; *Morals ; Motivation ; *Public Policy ; Self Concept ; *Social Behavior ; *Social Control, Informal ; United States ; },
abstract = {Dishonesty and unethical behavior are widespread in the public and private sectors and cause immense annual losses. For instance, estimates of U.S. annual losses indicate $1 trillion paid in bribes, $270 billion lost due to unreported income, and $42 billion lost in retail due to shoplifting and employee theft. In this article, we draw on insights from the growing fields of moral psychology and behavioral ethics to present a three-principle framework we call REVISE. This framework classifies forces that affect dishonesty into three main categories and then redirects those forces to encourage moral behavior. The first principle, reminding, emphasizes the effectiveness of subtle cues that increase the salience of morality and decrease people's ability to justify dishonesty. The second principle, visibility, aims to restrict anonymity, prompt peer monitoring, and elicit responsible norms. The third principle, self-engagement, increases people's motivation to maintain a positive self-perception as a moral person and helps bridge the gap between moral values and actual behavior. The REVISE framework can guide the design of policy interventions to defeat dishonesty.},
}
@article {pmid26576347,
year = {2015},
author = {Ataei-Kachouei, M and Nadaf, J and Akbari, MT and Atri, M and Majewski, J and Riazalhosseini, Y and Garshasbi, M},
title = {Double Heterozygosity of BRCA2 and STK11 in Familial Breast Cancer Detected by Exome Sequencing.},
journal = {Iranian journal of public health},
volume = {44},
number = {10},
pages = {1348-1352},
pmid = {26576347},
issn = {2251-6085},
abstract = {BACKGROUND: Germ-line mutations of BRCA1 and BRCA2 genes are responsible for approximately 25-30% of dominantly inherited familial breast cancers; still a big part of genetic component is unknown. The aim of this study was to investigate genetic causes of familial breast cancer in a pedigree with recessive pattern of inheritance.<br><br>METHODS: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer. Sanger sequencing was applied for validation and segregation analysis of mutations.<br><br>RESULTS: Here, we describe a family with three affected sisters of early-onset invasive ductal carcinoma due to heterozygous frame shift mutation rs80359352 in BRCA2 gene as the first report in Iranian patients in association with a novel missense SNP of STK11 (p.S422G). These mutations are inherited from their normal father.<br><br>CONCLUSION: Despite apparent recessive pattern of inheritance a dominant gene (here BRCA2) can be involved in pathogenesis of hereditary breast cancer which can be explained by incomplete penetrance of BRCA2 mutations.},
}
@article {pmid26566041,
year = {2015},
author = {Li, CZ and Li, CC and Lin, MC and Chih-Chuan, H and Chen, NF and Chen, CL and Tang, CT},
title = {A Clinical Pitfall: Optimal Management of Single Dural-based Metastatic Carcinoma of the Breast Mimicking Meningioma.},
journal = {The neurologist},
volume = {20},
number = {5},
pages = {93-95},
doi = {10.1097/NRL.0000000000000059},
pmid = {26566041},
issn = {2331-2637},
mesh = {Brain Neoplasms/diagnosis/*secondary/therapy ; Breast Neoplasms/*pathology/surgery ; Carcinoma/*pathology/surgery ; Female ; Fluorodeoxyglucose F18/metabolism ; Humans ; Magnetic Resonance Imaging ; Meningeal Neoplasms/*physiopathology ; Meningioma/*physiopathology ; Middle Aged ; Positron-Emission Tomography ; },
abstract = {Meningioma is the most common benign brain lesion in adults. Conservative treatment is suggested if there is no obvious neurological symptom or mass effect, but cerebral metastases require aggressive therapy. Single dural-based metastatic carcinoma mimicking meningioma is uncommon. Here is a case of clinical dilemma between meningioma and metastatic carcinoma mimicking meningioma. A woman with a history of invasive ductal carcinoma of the breast presented with headache and blurred vision. Brain computed tomography and magnetic resonance imaging (MRI) both gave the impression of meningioma. After surgical resection of the brain lesion, histopathology revealed that it was a metastatic lesion from the breast. This report discussed the optimal management of single dural-based metastatic carcinoma mimicking meningioma.},
}
@article {pmid26564123,
year = {2016},
author = {Moccia, M and Erro, R and Picillo, M and Santangelo, G and Spina, E and Allocca, R and Longo, K and Amboni, M and Palladino, R and Assante, R and Pappatà, S and Pellecchia, MT and Barone, P and Vitale, C},
title = {A Four-Year Longitudinal Study on Restless Legs Syndrome in Parkinson Disease.},
journal = {Sleep},
volume = {39},
number = {2},
pages = {405-412},
pmid = {26564123},
issn = {1550-9109},
mesh = {Adult ; Age of Onset ; Aged ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Female ; Humans ; Incidence ; Logistic Models ; Longitudinal Studies ; Male ; Middle Aged ; Parkinson Disease/*complications/diagnosis/drug therapy/*epidemiology ; Prevalence ; Random Allocation ; Restless Legs Syndrome/*complications/diagnosis/*epidemiology/physiopathology ; Sleep Wake Disorders/complications ; Surveys and Questionnaires ; Tomography, Emission-Computed, Single-Photon ; },
abstract = {STUDY OBJECTIVES: Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data.<br><br>METHODS: One hundred nine newly diagnosed, drug-na&#xef;ve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability.<br><br>RESULTS: RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88).<br><br>CONCLUSIONS: RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.},
}
@article {pmid26552553,
year = {2015},
author = {Sánchez-Borque, P and Rubio, JM and Benezet-Mazuecos, J and Quiñones, MA and Farré, J},
title = {Atrial fibrillation with Wolff-Parkinson-White syndrome in epilepsy: A potentially fatal combination.},
journal = {Seizure},
volume = {32},
number = {},
pages = {1-3},
doi = {10.1016/j.seizure.2015.08.002},
pmid = {26552553},
issn = {1532-2688},
mesh = {Adult ; Atrial Fibrillation/*complications/physiopathology ; Electrocardiography/methods ; Epilepsy/*complications/physiopathology ; Female ; Humans ; Seizures/complications/physiopathology ; Video Recording/methods ; Wolff-Parkinson-White Syndrome/*complications/physiopathology ; },
}
@article {pmid26546077,
year = {2016},
author = {Azagra, R and Zwart, M and Aguyé, A and Martín-Sánchez, JC and Casado, E and Díaz-Herrera, MA and Moriña, D and Cooper, C and Díez-Pérez, A and Dennison, EM and , },
title = {Fracture experience among participants from the FROCAT study: what thresholding is appropriate using the FRAX tool?.},
journal = {Maturitas},
volume = {83},
number = {},
pages = {65-71},
doi = {10.1016/j.maturitas.2015.10.002},
pmid = {26546077},
issn = {1873-4111},
support = {MC_U147585827/MRC_/Medical Research Council/United Kingdom ; MC_U147585819/MRC_/Medical Research Council/United Kingdom ; MC_UP_A620_1014/MRC_/Medical Research Council/United Kingdom ; 19583/VAC_/Versus Arthritis/United Kingdom ; MC_UU_12011/1/MRC_/Medical Research Council/United Kingdom ; G0400491/MRC_/Medical Research Council/United Kingdom ; MC_U147585824/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Aged ; *Algorithms ; Female ; Humans ; Middle Aged ; Osteoporotic Fractures/*epidemiology ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Spain/epidemiology ; },
abstract = {OBJECTIVE: To perform an external validation of FRAX algorithm thresholds for reporting level of risk of fracture in Spanish women (low < 5%; intermediate ≥ 5% and < 7.5%; high ≥ 7.5%) taken from a prospective cohort "FRIDEX".<br><br>METHODS: A retrospective study of 1090 women aged &#x2265; 40 and &#x2264; 90 years old obtained from the general population (FROCAT cohort). FRAX was calculated with data registered in 2002. All fractures were validated in 2012. Sensitivity analysis was performed.<br><br>RESULTS: When analyzing the cohort (884) excluding current or past anti osteoporotic medication (AOM), using our nominated thresholds, among the 621 (70.2%) women at low risk of fracture, 5.2% [CI95%: 3.4-7.6] sustained a fragility fracture; among the 99 at intermediate risk, 12.1% [6.4-20.2]; and among the 164 defined as high risk, 15.9% [10.6-24.2]. Sensitivity analysis against model risk stratification FRIDEX of FRAX Spain shows no significant difference. By including 206 women with AOM, the sensitivity analysis shows no difference in the group of intermediate and high risk and minimal differences in the low risk group.<br><br>CONCLUSIONS: Our findings support and validate the use of FRIDEX thresholds of FRAX when discussing the risk of fracture and the initiation of therapy with patients.},
}
@article {pmid26543228,
year = {2016},
author = {Hart, PC and Ratti, BA and Mao, M and Ansenberger-Fricano, K and Shajahan-Haq, AN and Tyner, AL and Minshall, RD and Bonini, MG},
title = {Caveolin-1 regulates cancer cell metabolism via scavenging Nrf2 and suppressing MnSOD-driven glycolysis.},
journal = {Oncotarget},
volume = {7},
number = {1},
pages = {308-322},
pmid = {26543228},
issn = {1949-2553},
support = {R01 DK044525/DK/NIDDK NIH HHS/United States ; R01 HL071626/HL/NHLBI NIH HHS/United States ; },
mesh = {Animals ; Blotting, Western ; Breast Neoplasms/genetics/*metabolism/pathology ; Caveolin 1/*genetics/metabolism ; Cell Line ; *Glycolysis ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Kelch-Like ECH-Associated Protein 1 ; MCF-7 Cells ; Mammary Neoplasms, Animal/genetics/metabolism ; Mice ; Microscopy, Confocal ; NF-E2-Related Factor 2/genetics/*metabolism ; Prognosis ; Protein Binding ; RNA Interference ; Superoxide Dismutase/genetics/*metabolism ; Survival Analysis ; },
abstract = {Aerobic glycolysis is an indispensable component of aggressive cancer cell metabolism. It also distinguishes cancer cells from most healthy cell types in the body. Particularly for this reason, targeting the metabolism to improve treatment outcomes has long been perceived as a potentially valuable strategy. In practice, however, our limited knowledge of why and how metabolic reprogramming occurs has prevented progress towards therapeutic interventions that exploit the metabolic peculiarities of tumors. We recently described that in breast cancer, MnSOD upregulation is both necessary and sufficient to activate glycolysis. Here, we focused on determining the molecular mechanisms of MnSOD upregulation. We found that Caveolin-1 (Cav-1) is a central component of this mechanism due to its suppressive effects of NF-E2-related factor 2 (Nrf2), a transcription factor upstream of MnSOD. In transformed MCF10A(Er/Src) cells, Cav-1 loss preceded the activation of Nrf2 and its induction of MnSOD expression. Consistently, with previous observations, MnSOD expression secondary to Nrf2 activation led to an increase in the glycolytic rate dependent on mtH2O2 production and the activation of AMPK. Moreover, rescue of Cav-1 expression in a breast cancer cell line (MCF7) suppressed Nrf2 and reduced MnSOD expression. Experimental data were reinforced by epidemiologic nested case-control studies showing that Cav-1 and MnSOD are inversely expressed in cases of invasive ductal carcinoma, with low Cav-1 and high MnSOD expression being associated with lower 5-year survival rates and molecular subtypes with poorest prognosis.},
}
@article {pmid26511818,
year = {2016},
author = {Chang, JS and Lee, J and Kim, HJ and Kim, KH and Yun, M and Kim, SI and Keum, KC and Suh, CO and Kim, YB},
title = {(18)F-FDG/PET May Help to Identify a Subgroup of Patients with T1-T2 Breast Cancer and 1-3 Positive Lymph Nodes Who Are at a High Risk of Recurrence after Mastectomy.},
journal = {Cancer research and treatment},
volume = {48},
number = {2},
pages = {508-517},
pmid = {26511818},
issn = {2005-9256},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology/radiotherapy ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnostic imaging/*pathology/radiotherapy ; *Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/prevention &amp; control ; *Positron-Emission Tomography ; Risk Assessment ; Risk Factors ; Tumor Burden ; },
abstract = {PURPOSE: The purpose of this study is to assess the utility of positron emission tomography (PET) for predicting recurrence among patients with T1-T2/N1 breast cancer who were treated with mastectomy.<br><br>MATERIALS AND METHODS: Of 712 consecutive patients with T1-T2/N1 breast cancer treated during 2003-2012, 109 had undergone preoperative (18)F-fluorodeoxyglucose/PET and were included. Metabolic (maximum standardized uptake value [SUVmax]), volumetric (metabolic tumor volume [MTV]), and combined (total lesion glycolysis [TLG]) indices were measured. The resulting values were analyzed and compared with clinical outcome.<br><br>RESULTS: At the median follow-up of 46.7 months, the 3-year relapse-free survival (RFS) rate was 95.2%. SUVmax (area under curve, 0.824) was more useful than MTV or TLG as a means of identifying patients at high risk for any recurrence. In multivariate analysis, SUVmax remained an independent risk factor for RFS (p=0.006). Using the method of Contal and O'Quigley, a SUVmax threshold of 5.36 showed the best predictive performance. The PET-based high-risk group (&#x2265; 5.36 in either breast or nodes) had more T1c-T2, high-grade, hormone-receptor negative, and invasive ductal carcinoma tumors than the low-risk group (< 5.36 in both breast and nodes). The prognosis was much worse when high SUVmax (&#x2265; 5.36) was detected in nodes (p < 0.001). In the no-radiotherapy cohort, the PET-based high-risk group had increased risk of locoregional recurrence when compared to the low-risk group (p=0.037).<br><br>CONCLUSION: High SUVmax on preoperative PET showed association with elevated risk of locoregional recurrence and any recurrence. Pre-treatment PET may improve assessments of recurrence risk and clarify indications for post-mastectomy radiotherapy in this subset of patients.},
}
@article {pmid26505860,
year = {2016},
author = {Ni, J and Tang, P},
title = {An Unusual Bone Metastasis Mimicking SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis) Syndrome on Bone Scintigraphy.},
journal = {Clinical nuclear medicine},
volume = {41},
number = {2},
pages = {173-175},
doi = {10.1097/RLU.0000000000001061},
pmid = {26505860},
issn = {1536-0229},
mesh = {Acquired Hyperostosis Syndrome/*diagnostic imaging ; Bone Neoplasms/*diagnostic imaging/secondary ; Breast Neoplasms/diagnostic imaging/*pathology ; Diagnostic Errors ; Female ; Humans ; Middle Aged ; Radionuclide Imaging ; },
abstract = {The costosternoclavicular region is not a common bone metastasis site, and symmetrical involvement is even rarer. Increased tracer uptake in the manubrium and sternoclavicular joints usually gives the typical "bull-horn" appearance seen in SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis). Herein, we report a case of a 47-year-old woman with a history of invasive ductal carcinoma who had undergone left radical mastectomy 3 years earlier and presented with typical increased tracer uptake in the bilateral sternocostoclavicular region resembling the so-called bull horn. The final diagnosis of metastasis from breast cancer was made histopathologically following biopsy.},
}
@article {pmid26503945,
year = {2016},
author = {Podo, F and Santoro, F and Di Leo, G and Manoukian, S and de Giacomi, C and Corcione, S and Cortesi, L and Carbonaro, LA and Trimboli, RM and Cilotti, A and Preda, L and Bonanni, B and Pensabene, M and Martincich, L and Savarese, A and Contegiacomo, A and Sardanelli, F},
title = {Triple-Negative versus Non-Triple-Negative Breast Cancers in High-Risk Women: Phenotype Features and Survival from the HIBCRIT-1 MRI-Including Screening Study.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {22},
number = {4},
pages = {895-904},
doi = {10.1158/1078-0432.CCR-15-0459},
pmid = {26503945},
issn = {1557-3265},
mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/*diagnosis/genetics/mortality/therapy ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Middle Aged ; Mutation ; Phenotype ; Risk ; Treatment Outcome ; Triple Negative Breast Neoplasms/*diagnosis/genetics/mortality/therapy ; },
abstract = {PURPOSE: To compare phenotype features and survival of triple-negative breast cancers (TNBC) versus non-TNBCs detected during a multimodal annual screening of high-risk women.<br><br>EXPERIMENTAL DESIGN: Analysis of data from asymptomatic high-risk women diagnosed with invasive breast cancer during the HIBCRIT-1 study with median 9.7-year follow-up.<br><br>RESULTS: Of 501 enrolled women with BRCA1/2 mutation or strong family history (SFH), 44 were diagnosed with invasive breast cancers: 20 BRCA1 (45%), 9 BRCA2 (21%), 15 SFH (34%). Magnetic resonance imaging (MRI) sensitivity (90%) outperformed that of mammography (43%, P < 0.001) and ultrasonography (61%, P = 0.004). The 44 cases (41 screen-detected; 3 BRCA1-associated interval TNBCs) comprised 14 TNBCs (32%) and 30 non-TNBCs (68%), without significant differences for age at diagnosis, menopausal status, prophylactic oophorectomy, or previous breast cancer. Of 14 TNBC patients, 11 (79%) were BRCA1; of the 20 BRCA1 patients, 11 (55%) had TNBC; and of 15 SFH patients, 14 (93%) had non-TNBCs (P = 0.007). Invasive ductal carcinomas (IDC) were 86% for TNBCs versus 43% for non-TNBCs (P = 0.010), G3 IDCs 71% versus 23% (P = 0.006), size 16 &#xb1; 5 mm versus 12 &#xb1; 6 mm (P = 0.007). TNBC patients had more frequent ipsilateral mastectomy (79% vs. 43% for non-TNBCs, P = 0.050), contralateral prophylactic mastectomy (43% vs. 10%, P = 0.019), and adjuvant chemotherapy (100% vs. 44%, P < 0.001). The 5-year overall survival was 86% &#xb1; 9% for TNBCs versus 93% &#xb1; 5% (P = 0.946) for non-TNBCs; 5-year disease-free survival was 77% &#xb1; 12% versus 76% &#xb1; 8% (P = 0.216).<br><br>CONCLUSIONS: In high-risk women, by combining an MRI-including annual screening with adequate treatment, the usual reported gap in outcome between TNBCs and non-TNBCs could be reduced.},
}
@article {pmid26491255,
year = {2015},
author = {Su, Y and Wang, X and Li, J and Xu, J and Xu, L},
title = {The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review.},
journal = {Drug design, development and therapy},
volume = {9},
number = {},
pages = {5439-5445},
pmid = {26491255},
issn = {1177-8881},
mesh = {Acid Anhydride Hydrolases/*genetics/metabolism ; Animals ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*drug therapy/enzymology/*genetics/pathology ; Carcinoma, Ductal, Breast/*drug therapy/enzymology/*genetics/pathology ; Chi-Square Distribution ; DNA Methylation/*drug effects ; Drug Discovery/*methods ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *Molecular Targeted Therapy ; Neoplasm Proteins/*genetics/metabolism ; Neoplasm Staging ; Odds Ratio ; Risk Factors ; Signal Transduction/drug effects ; },
abstract = {FHIT is a bona fide tumor-suppressor gene and its loss contributes to tumorigenesis of epithelial cancers including breast cancer (BC). However, the association and clinicopathological significance between FHIT promoter hypermethylation and BC remains unclear. The purpose of this study is to conduct a meta-analysis and literature review to investigate the clinicopathological significance of FHIT methylation in BC. A detailed literature search was performed in PubMed, EMBASE, Web of Science, and Google Scholar databases. The data were extracted and assessed by two reviewers independently. Odds ratios with 95% corresponding confidence intervals were calculated. A total of seven relevant articles were available for meta-analysis, which included 985 patients. The frequency of FHIT hypermethylation was significantly increased in invasive ductal carcinoma compared to benign breast disease, the pooled odds ratio was 8.43, P<0.00001. The rate of FHIT hypermethylation was not significantly different between stage I/II and stage III/IV, odds ratio was 2.98, P=0.06. In addition, FHIT hypermethylation was not significantly associated with ER and PR status. FHIT hypermethylation was not significantly correlated with premenopausal and postmenopausal patients with invasive ductal carcinoma. In summary, our meta-analysis indicated that the frequency of FHIT hypermethylation was significantly increased in BC compared to benign breast disease. The rate of FHIT hypermethylation in advanced stages of BC was higher than in earlier stages; however, the difference was not statistically significant. Our data suggested that FHIT methylation could be a diagnostic biomarker of BC carcinogenesis. FHIT is a potential drug target for development of demethylation treatment for patients with BC.},
}
@article {pmid26489549,
year = {2015},
author = {Takayanagi, H and Hayami, R and Tsuneizumi, M and Nakagami, K},
title = {[Thrombophlebitis in an Elderly Japanese Woman Treated with Tamoxifen for Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {42},
number = {10},
pages = {1203-1205},
pmid = {26489549},
issn = {0385-0684},
mesh = {Aged, 80 and over ; Antineoplastic Agents, Hormonal/*adverse effects/therapeutic use ; Biopsy ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy ; Female ; Humans ; Neoplasm Staging ; Tamoxifen/*adverse effects/therapeutic use ; Thrombophlebitis/*chemically induced/diagnostic imaging ; Tomography, X-Ray Computed ; Ultrasonography ; },
abstract = {In this study, we report the rare case of an elderly woman who developed thrombophlebitis after being treated with tamoxifen for breast cancer. She visited our department with a lump in her left breast. She underwent core needle biopsy, and she was diagnosed with breast cancer (invasive ductal carcinoma, ER- and PgR-positive, HER2-negative). We chose hormonal therapy because surgical treatment was deemed too invasive considering her general status. She was administered tamoxifen (20 mg/day) instead of an aromatase inhibitor in consideration of her osteoporosis. Six months after initiating tamoxifen therapy, she exhibited swelling in her left leg. Computed tomography and ultrasound revealed thrombophlebitis in her left femoral vein. She stopped taking tamoxifen and started warfarin potassium as thrombolytic therapy, after which thrombophlebitis was relieved. Advanced age may be a risk factor for thrombophlebitis associated with tamoxifen treatment; therefore, precautions should be taken accordingly.},
}
@article {pmid26481274,
year = {2015},
author = {Ballard, AJ},
title = {Epstein-Barr virus infection is equally distributed across the invasive ductal and invasive lobular forms of breast cancer.},
journal = {Pathology, research and practice},
volume = {211},
number = {12},
pages = {1003-1005},
doi = {10.1016/j.prp.2015.09.017},
pmid = {26481274},
issn = {1618-0631},
mesh = {Breast Neoplasms/*pathology/*virology ; Carcinoma, Ductal, Breast/pathology/*virology ; Carcinoma, Lobular/pathology/*virology ; Epstein-Barr Virus Infections/*complications ; Female ; Humans ; Immunohistochemistry ; Tissue Array Analysis ; },
abstract = {The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer is still unclear, although a growing body of evidence supports a link. The aim of this study was to investigate if EBV infection was more prevalent in invasive ductal carcinoma or invasive lobular carcinoma. An immunohistochemical marker for EBV (Epstein-Barr virus nuclear antigen 1 (EBNA1) clone E1-2.5) was applied to a tissue micro array section. The tissue micro array contained 80 cases of invasive ductal carcinoma, and 80 cases of invasive lobular carcinoma. Each case was scored as positive or negative for nuclear expression of EBNA1 in tumor cells using standard light microscopy. EBNA1 staining was evident in the tumor cells of 63 cases (39.4% of tumor cases). By tumor type (ductal/lobular) EBV infection was noted in 34 (42.5%) cases of invasive ductal carcinoma and 29 (36.2%) cases of invasive lobular carcinoma, this difference was not found to be significant (P=0.518). This study indicates that EBV infection is equally distributed across the ductal and lobular tumor types.},
}
@article {pmid26475094,
year = {2015},
author = {Di Oto, E and Monti, V and Cucchi, MC and Masetti, R and Varga, Z and Foschini, MP},
title = {X chromosome gain in male breast cancer.},
journal = {Human pathology},
volume = {46},
number = {12},
pages = {1908-1912},
doi = {10.1016/j.humpath.2015.08.008},
pmid = {26475094},
issn = {1532-8392},
mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Chromosomes, Human, X/*genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; },
abstract = {Male breast cancer (MBC) is an uncommon disease whose molecular profile is not well known. X chromosome gain has been described as a marker of aggressive behavior in female breast cancer. The aim of this study is to investigate the role of the X chromosome in male breast cancer. Twenty cases of male breast invasive ductal carcinoma were retrieved and compared with 10 cases of gynecomastia. Cases were tested by fluorescence in situ hybridization to assess a cytogenetic profile for the X chromosome. The X chromosome status was compared with histopathologic features and stage at presentation. All MBC cases harbored an X chromosome gain (100%) in a variable percentage of neoplastic cells, ranging from 31% to 85% (mean, 59%). On the contrary, all cases of gynecomastia showed wild X chromosome asset. The patients' age at surgery and tumor grading showed a statistically significant correlation (P = .0188-.04), with the percentages of neoplastic cells showing an X chromosome gain. These data suggest that this X chromosome gain plays a role in the neoplastic transformation of male breast epithelial cells.},
}
@article {pmid26474389,
year = {2015},
author = {Aswad, L and Yenamandra, SP and Ow, GS and Grinchuk, O and Ivshina, AV and Kuznetsov, VA},
title = {Genome and transcriptome delineation of two major oncogenic pathways governing invasive ductal breast cancer development.},
journal = {Oncotarget},
volume = {6},
number = {34},
pages = {36652-36674},
pmid = {26474389},
issn = {1949-2553},
mesh = {Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cohort Studies ; Female ; Genome, Human ; Humans ; Middle Aged ; Prognosis ; Transcriptome ; },
abstract = {Invasive ductal carcinoma (IDC) is a major histo-morphologic type of breast cancer. Histological grading (HG) of IDC is widely adopted by oncologists as a prognostic factor. However, HG evaluation is highly subjective with only 50%-85% inter-observer agreements. Specifically, the subjectivity in the assignment of the intermediate grade (histologic grade 2, HG2) breast cancers (comprising ~50% of IDC cases) results in uncertain disease outcome prediction and sub-optimal systemic therapy. Despite several attempts to identify the mechanisms underlying the HG classification, their molecular bases are poorly understood.We performed integrative bioinformatics analysis of TCGA and several other cohorts (total 1246 patients). We identified a 22-gene tumor aggressiveness grading classifier (22g-TAG) that reflects global bifurcation in the IDC transcriptomes and reclassified patients with HG2 tumors into two genetically and clinically distinct subclasses: histological grade 1-like (HG1-like) and histological grade 3-like (HG3-like). The expression profiles and clinical outcomes of these subclasses were similar to the HG1 and HG3 tumors, respectively. We further reclassified IDC into low genetic grade (LGG = HG1+HG1-like) and high genetic grade (HGG = HG3-like+HG3) subclasses. For the HG1-like and HG3-like IDCs we found subclass-specific DNA alterations, somatic mutations, oncogenic pathways, cell cycle/mitosis and stem cell-like expression signatures that discriminate between these tumors. We found similar molecular patterns in the LGG and HGG tumor classes respectively.Our results suggest the existence of two genetically-predefined IDC classes, LGG and HGG, driven by distinct oncogenic pathways. They provide novel prognostic and therapeutic biomarkers and could open unique opportunities for personalized systemic therapies of IDC patients.},
}
@article {pmid26472289,
year = {2015},
author = {Ressl, N and Oberndorfer, S},
title = {Multiple calcified brain metastases in a man with invasive ductal breast cancer.},
journal = {BMJ case reports},
volume = {2015},
number = {},
pages = {},
pmid = {26472289},
issn = {1757-790X},
mesh = {Brain Neoplasms/*pathology/*secondary ; Breast Neoplasms, Male/*pathology ; Calcinosis/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Humans ; Male ; Middle Aged ; },
abstract = {We report a case of a 52-year-old Caucasian man with invasive ductal carcinoma of the breast. One year after initial diagnosis, he developed a generalised epileptic seizure and neuroimaging showed multiple, calcified intracerebral lesions. Owing to these atypical cerebral imaging findings, comprehensive serological and cerebrospinal fluid analysis was conducted and a latent toxoplasmosis was suspected. In order to distinguish between metastases and an infectious disease, a cerebral biopsy was performed, which verified brain metastases. The patient received whole-brain radiotherapy. The last cerebral CT scan, 18 months later showed stable disease. Calcification of brain metastases in patients with breast cancer is very rare. Owing to their non-characteristic radiological appearance with a lack of contrast enhancement, diagnosis of metastases can be difficult. Infectious diseases should be considered within the diagnostic work up. Owing to possible pitfalls, we recommend a widespread differential diagnostic work up in similar cases, and even in cases with a confirmed primary tumour.},
}
@article {pmid26466985,
year = {2016},
author = {Di Rosa, M and Tibullo, D and Saccone, S and Distefano, G and Basile, MS and Di Raimondo, F and Malaguarnera, L},
title = {CHI3L1 nuclear localization in monocyte derived dendritic cells.},
journal = {Immunobiology},
volume = {221},
number = {2},
pages = {347-356},
doi = {10.1016/j.imbio.2015.09.023},
pmid = {26466985},
issn = {1878-3279},
mesh = {Adipokines/genetics/*immunology ; Amino Acid Sequence ; Cell Differentiation ; Cell Nucleus/drug effects/*metabolism ; Chitinase-3-Like Protein 1 ; Dendritic Cells/cytology/drug effects/*immunology ; Gene Expression Regulation ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-4/pharmacology ; Lectins/genetics/*immunology ; Macrophages/cytology/drug effects/*immunology ; Models, Molecular ; Molecular Sequence Data ; Monocytes/cytology/drug effects/*immunology ; Primary Cell Culture ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Signal Transduction ; },
abstract = {Chitinase-3-like-1 protein (CHI3L1) is a glycosyl hydrolase (GH) highly expressed in a variety of inflammatory diseases at infectious and non-infectious etiology. CHI3L1 is produced by a wide variety of cells including monocyte-derived macrophages cell lines such as polarized M1 and M2 type macrophages, osteoclasts and Kupffer cells. In this study we have examined the expression of CHI3L1 during the differentiation and maturation of dendritic cells. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) through a combination of factors and cytokines. Our result showed, for the first time, that CHI3L1 is expressed during the process of differentiation and maturation of dendritic cells in time dependent manner. Furthermore, the CHI3L1 is evenly distributed in cytoplasm and in the nucleus of both the iDCs and mDCs. These results suggest that CHI3L1 may play crucial role in the DCs immunoresponse.},
}
@article {pmid26463438,
year = {2016},
author = {Gayarre, J and Kamieniak, MM and Cazorla-Jiménez, A and Muñoz-Repeto, I and Borrego, S and García-Donas, J and Hernando, S and Robles-Díaz, L and García-Bueno, JM and Ramón Y Cajal, T and Hernández-Agudo, E and Heredia Soto, V and Márquez-Rodas, I and Echarri, MJ and Lacambra-Calvet, C and Sáez, R and Cusidó, M and Redondo, A and Paz-Ares, L and Hardisson, D and Mendiola, M and Palacios, J and Benítez, J and García, MJ},
title = {The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients.},
journal = {Journal of gynecologic oncology},
volume = {27},
number = {1},
pages = {e7},
pmid = {26463438},
issn = {2005-0399},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis/genetics ; Carcinoma, Ovarian Epithelial ; Cystadenocarcinoma, Serous/*genetics/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Proteins/biosynthesis/genetics ; Neoplasms, Glandular and Epithelial/*genetics/metabolism/pathology ; Ovarian Neoplasms/*genetics/metabolism/pathology ; Prognosis ; Transcription Factors/biosynthesis/*genetics ; Tumor Cells, Cultured ; },
abstract = {OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.<br><br>METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and &#x2264; median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays.<br><br>RESULTS: Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells.<br><br>CONCLUSION: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.},
}
@article {pmid26451490,
year = {2015},
author = {Ciriello, G and Gatza, ML and Beck, AH and Wilkerson, MD and Rhie, SK and Pastore, A and Zhang, H and McLellan, M and Yau, C and Kandoth, C and Bowlby, R and Shen, H and Hayat, S and Fieldhouse, R and Lester, SC and Tse, GM and Factor, RE and Collins, LC and Allison, KH and Chen, YY and Jensen, K and Johnson, NB and Oesterreich, S and Mills, GB and Cherniack, AD and Robertson, G and Benz, C and Sander, C and Laird, PW and Hoadley, KA and King, TA and , and Perou, CM},
title = {Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.},
journal = {Cell},
volume = {163},
number = {2},
pages = {506-519},
pmid = {26451490},
issn = {1097-4172},
support = {P50-CA58223-09A1/CA/NCI NIH HHS/United States ; R00 CA166228/CA/NCI NIH HHS/United States ; K22 LM011931/LM/NLM NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U24 CA143848/CA/NCI NIH HHS/United States ; F30 CA192725/CA/NCI NIH HHS/United States ; U24 CA143867/CA/NCI NIH HHS/United States ; K99 CA166228/CA/NCI NIH HHS/United States ; P50 CA058223/CA/NCI NIH HHS/United States ; R01 CA180006/CA/NCI NIH HHS/United States ; U24 CA143858/CA/NCI NIH HHS/United States ; },
mesh = {Antigens, CD ; Breast Neoplasms/*genetics/metabolism/*pathology ; Cadherins/chemistry/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Lobular/*genetics/metabolism/*pathology ; Female ; Hepatocyte Nuclear Factor 3-alpha/chemistry/genetics/metabolism ; Humans ; Models, Molecular ; Mutation ; Oligonucleotide Array Sequence Analysis ; Oncogene Protein v-akt/metabolism ; Transcriptome ; },
abstract = {Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.},
}
@article {pmid26440364,
year = {2015},
author = {Cheng, YS and Seibert, O and Klöting, N and Dietrich, A and Straßburger, K and Fernández-Veledo, S and Vendrell, JJ and Zorzano, A and Blüher, M and Herzig, S and Berriel Diaz, M and Teleman, AA},
title = {PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis.},
journal = {PLoS genetics},
volume = {11},
number = {10},
pages = {e1005561},
pmid = {26440364},
issn = {1553-7404},
mesh = {AMP-Activated Protein Kinases/genetics ; Animals ; Dietary Carbohydrates/metabolism ; Energy Metabolism/*genetics ; Glucose/metabolism ; Hepatocytes/metabolism ; Humans ; Insulin Resistance/genetics ; Lipid Metabolism/*genetics ; Lipogenesis/genetics ; Liver/metabolism ; Mice ; Obesity/*genetics/pathology ; Protein Phosphatase 2/*genetics ; Sterol Regulatory Element Binding Protein 1/genetics ; },
abstract = {In mammals, the liver plays a central role in maintaining carbohydrate and lipid homeostasis by acting both as a major source and a major sink of glucose and lipids. In particular, when dietary carbohydrates are in excess, the liver converts them to lipids via de novo lipogenesis. The molecular checkpoints regulating the balance between carbohydrate and lipid homeostasis, however, are not fully understood. Here we identify PPP2R5C, a regulatory subunit of PP2A, as a novel modulator of liver metabolism in postprandial physiology. Inactivation of PPP2R5C in isolated hepatocytes leads to increased glucose uptake and increased de novo lipogenesis. These phenotypes are reiterated in vivo, where hepatocyte specific PPP2R5C knockdown yields mice with improved systemic glucose tolerance and insulin sensitivity, but elevated circulating triglyceride levels. We show that modulation of PPP2R5C levels leads to alterations in AMPK and SREBP-1 activity. We find that hepatic levels of PPP2R5C are elevated in human diabetic patients, and correlate with obesity and insulin resistance in these subjects. In sum, our data suggest that hepatic PPP2R5C represents an important factor in the functional wiring of energy metabolism and the maintenance of a metabolically healthy state.},
}
@article {pmid26438270,
year = {2015},
author = {Kim, TS and Kang, YJ and Kim, JY and Lee, S and Lee, WJ and Sohn, Y and Lee, HW},
title = {Up-regulated S100 calcium binding protein A8 in Plasmodium-infected patients correlates with CD4(+)CD25(+)Foxp3 regulatory T cell generation.},
journal = {Malaria journal},
volume = {14},
number = {},
pages = {385},
pmid = {26438270},
issn = {1475-2875},
mesh = {Adult ; CD4 Antigens/analysis ; Calgranulin A/*blood ; Enzyme-Linked Immunosorbent Assay ; Forkhead Transcription Factors/analysis ; Humans ; Immune Evasion ; Interleukin-2 Receptor alpha Subunit/analysis ; Malaria, Vivax/*immunology ; Plasmodium vivax/*immunology/physiology ; Serum/chemistry ; T-Lymphocyte Subsets/chemistry/*immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Regulatory/chemistry/*immunology ; },
abstract = {BACKGROUND: The pro-inflammatory S100 calcium binding protein A8 (S100A8) is elevated in the serum of patients with Plasmodium falciparum malaria, but its function in Plasmodium vivax malaria is not yet clear. This function was investigated in P. vivax-infected patients in this study.<br><br>METHODS: The level of S100A8 in the serum was measured with ELISA. Full amino acids of S100A8 were synthesized to verify the functions for maturation of immature dendritic cell (iDC) and evaluation of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) generation by mature DC (mDC).<br><br>RESULTS: A higher amount of S100A8 was detected in vivax-infected patients (141.2 &#xb1; 61.849 ng/ml, n = 40) compared with normal control group (48.1 &#xb1; 27.384 ng/ml, n = 40). The level of S100A8 did not coincide with that of anti-malarial antibody measured by indirect fluorescent antibody test (IFAT) using parasite-infected red blood cells as antigen. Programmed death-ligand 1 (PD-L1) was up-regulated on the surface of iDCs following treatment with synthetic S100A8, not with synthetic MSP-1, AMA-1 and CSP, as compared to the expression seen for non-treated iDCs. The addition of red blood cells of infected patients to iDCs also elevated their surface expression of CD86. However, the serum levels of S100A8 decreased with increase in parasitaemia. DCs matured by sera containing S100A8 generated Treg cells from na&#xef;ve T cells. The ratio of Treg cells generated was inversely proportional to the concentration of S100A8 in sera.<br><br>CONCLUSIONS: Treg cells suppress the activity of cytotoxic T cells, which kill malaria parasites; therefore, the up-regulation of S100A8 in malaria patients may contribute to pathogen immune escape or tolerance.},
}
@article {pmid26437542,
year = {2015},
author = {Claimon, A and Chuthapisith, S and Samarnthai, N and Pusuwan, P},
title = {Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.},
journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet},
volume = {98},
number = {8},
pages = {828-832},
pmid = {26437542},
issn = {0125-2208},
mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnosis/*secondary ; Carcinoma, Neuroendocrine/*diagnosis/*secondary ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed ; },
abstract = {The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor},
}
@article {pmid26425077,
year = {2015},
author = {Huang, R and Ding, P and Yang, F},
title = {Clinicopathological significance and potential drug target of CDH1 in breast cancer: a meta-analysis and literature review.},
journal = {Drug design, development and therapy},
volume = {9},
number = {},
pages = {5277-5285},
pmid = {26425077},
issn = {1177-8881},
mesh = {Antigens, CD ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/drug therapy/*genetics/metabolism/mortality/pathology ; Cadherins/*genetics/metabolism ; Carcinoma, Ductal, Breast/drug therapy/*genetics/metabolism/mortality/pathology ; Chi-Square Distribution ; *DNA Methylation ; Drug Design ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Molecular Targeted Therapy ; Odds Ratio ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Risk Factors ; Treatment Outcome ; },
abstract = {CDH1, as a tumor suppressor gene, contributes sporadic breast cancer (BC) progression. However, the association between CDH1 hypermethylation and BC, and its clinicopathological significance remains unclear. We conducted a meta-analysis to investigate the relationship between the CDH1 methylation profile and the major clinicopathological features. A detailed literature was searched through the electronic databases PubMed, Web of Science™, and EMBASE™ for related research publications. The data were extracted and assessed by two reviewers independently. Odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated and summarized respectively. The frequency of CDH1 methylation was significantly higher in invasive ductal carcinoma than in normal breast tissues (OR =5.83, 95% CI 3.76-9.03, P<0.00001). CDH1 hypermethylation was significantly higher in estrogen receptor (ER)-negative BC than in ER-positive BC (OR =0.62, 95% CI 0.43-0.87, P=0.007). In addition, we found that the CDH1 was significantly methylated in HER2-negative BC than in HER2-positive BC (OR =0.26, 95% CI 0.15-0.44, P<0.00001). However, CDH1 methylation frequency was not associated with progesterone receptor (PR) status, or with grades, stages, or lymph node metastasis of BC patients. Our results indicate that CDH1 hypermethylation is a potential novel drug target for developing personalized therapy. CDH1 hypermethylation is strongly associated with ER-negative and HER2-negative BC, respectively, suggesting CDH1 methylation status could contribute to the development of novel therapeutic approaches for the treatment of ER-negative or HER2-negative BC with aggressive tumor biology.},
}
@article {pmid26410088,
year = {2015},
author = {Yang, JZ and Wang, ZX and Ma, LH and Shen, XB and Sun, Y and Hu, DW and Sun, LX},
title = {The organochlorine pesticides residues in the invasive ductal breast cancer patients.},
journal = {Environmental toxicology and pharmacology},
volume = {40},
number = {3},
pages = {698-703},
doi = {10.1016/j.etap.2015.07.007},
pmid = {26410088},
issn = {1872-7077},
mesh = {Adipose Tissue/*chemistry ; Adult ; Aged ; Breast Neoplasms/*blood/metabolism/pathology ; Carcinoma, Ductal, Breast/*blood/metabolism/pathology ; Chlorobenzenes/blood ; Dichlorodiphenyl Dichloroethylene/blood ; Female ; Hexachlorocyclohexane/blood ; Humans ; Hydrocarbons, Chlorinated/*toxicity ; Middle Aged ; Receptors, Estrogen/metabolism ; },
abstract = {Investigation of organochlorine pesticides residues (important environmental contamination causing malignant transformation) in breast cancer patients is valuable to understanding their roles in breast cancer. 75 invasive ductal carcinoma (IDC) patients were enrolled with control of 79 benign breast diseases patients and control of 80 healthy women. Morning fasting blood specimens and adipose tissue specimens beside the primary lesion were detected with gas chromatograph. In blood specimens, both levels of β-HCH and PCTA were higher in IDC than those in both controls (both p<0.05), and increasingly higher among the three IDC degrees. In adipose tissue specimens, all levels of β-HCH, PCTA and pp'-DDE were higher in IDC than those in control (all p<0.05) and increasingly higher among three IDC degrees. The levels of β-HCH, PCTA in both blood specimens and adipose tissue specimens were higher in estrogen receptor (ER) positive IDC than those in ER negative IDC (all p<0.05). The higher level of organochlorine pesticides residues in blood and adipose tissue specimens of IDC infers its association with IDC, but the details remains to reveal, and this study may helpful in this field.},
}
@article {pmid26408705,
year = {2015},
author = {Ozturk, T and Kucukhuseyin, O and Eronat, AP and Tuzuner, MB and Daglar-Aday, A and Saygili, N and Kisakesen, HI and Seyhan, F and Velidedeoğlu, M and Calay, Z and Ilvan, &#x15e; and Yilmaz-Aydoğan, H and Ozturk, O and Isbir, T},
title = {Preliminary Study: Prominent miRNAs of Breast Malignant Tissues Compared to Normal Tissues in Turkish Patients with Breast Cancer.},
journal = {Anticancer research},
volume = {35},
number = {10},
pages = {5425-5432},
pmid = {26408705},
issn = {1791-7530},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/*pathology ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; MicroRNAs/*genetics ; Middle Aged ; Turkey ; },
abstract = {miRNA involvement has been observed in almost every type of cancer, including breast cancer. The etiology of abnormal expression of miRNAs in cancer is still not clearly understood. In order to obtain insight into miRNA de-regulation in breast cancer, we analyzed expression levels of five breast cancer-related miRNAs, miRNA21, miRNA155, miRNA19a, miRNA17-5p and let7a miRNA, in both malignant and neighboring non-tumoral paraffin-embedded tissues of 47 patients with invasive ductal breast cancer. The targeted miRNAs, and a reference snRNA, U6, were analyzed by real-time polymerase chain reaction. let7a Levels were significantly lower in patients with lymphatic invasion than in those without (p=0.047). miR21 was down-regulated in 93.3% of patients with necrosis [p=0.017 (Fisher's exact test (FE))], while at least one oncogenic miRNA was up-regulated in 87.3% of the patients with invasive ductal carcinoma [p=0.009 (FE)]. In addition, tumor-suppressor miRNA was down-regulated or unaltered in 65.8% of the patients with tumor grade 2 or 3 and in all with grade 1 [p=0.047 (FE)]. Based on this preliminary study, we suggest that these miRNAs, especially let7a and miRNA21, might be useful markers in follow-up of breast cancer and in prognosis.},
}
@article {pmid26404623,
year = {2015},
author = {Nestal de Moraes, G and Delbue, D and Silva, KL and Robaina, MC and Khongkow, P and Gomes, AR and Zona, S and Crocamo, S and Mencalha, AL and Magalhães, LM and Lam, EW and Maia, RC},
title = {FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance.},
journal = {Cellular signalling},
volume = {27},
number = {12},
pages = {2496-2505},
doi = {10.1016/j.cellsig.2015.09.013},
pmid = {26404623},
issn = {1873-3913},
support = {A12011/CRUK_/Cancer Research UK/United Kingdom ; BBS/B/03785/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Antibiotics, Antineoplastic/pharmacology ; Base Sequence ; Binding Sites ; Breast Neoplasms/drug therapy/metabolism/mortality ; Cell Survival ; Docetaxel ; Doxorubicin/pharmacology ; *Drug Resistance, Neoplasm ; Female ; Forkhead Box Protein M1 ; Forkhead Transcription Factors/*physiology ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Inhibitor of Apoptosis Proteins/genetics/*metabolism ; Kaplan-Meier Estimate ; MCF-7 Cells ; Middle Aged ; Prognosis ; Promoter Regions, Genetic ; Protein Binding ; Survivin ; Taxoids/pharmacology ; X-Linked Inhibitor of Apoptosis Protein/genetics/*metabolism ; },
abstract = {Drug resistance is a major hurdle for successful treatment of breast cancer, the leading cause of deaths in women throughout the world. The FOXM1 transcription factor is a potent oncogene that transcriptionally regulates a wide range of target genes involved in DNA repair, metastasis, cell invasion, and migration. However, little is known about the role of FOXM1 in cell survival and the gene targets involved. Here, we show that FOXM1-overexpressing breast cancer cells display an apoptosis-resistant phenotype, which associates with the upregulation of expression of XIAP and Survivin antiapoptotic genes. Conversely, FOXM1 knockdown results in XIAP and Survivin downregulation as well as decreased binding of FOXM1 to the promoter regions of XIAP and Survivin. Consistently, FOXM1, XIAP, and Survivin expression levels were higher in taxane and anthracycline-resistant cell lines when compared to their sensitive counterparts and could not be downregulated in response to drug treatment. In agreement with our in vitro findings, we found that FOXM1 expression is significantly associated with Survivin and XIAP expression in samples from patients with IIIa stage breast invasive ductal carcinoma. Importantly, patients co-expressing FOXM1, Survivin, and nuclear XIAP had significantly worst overall survival, further confirming the physiological relevance of the regulation of Survivin and XIAP by FOXM1. Together, these findings suggest that the overexpression of FOXM1, XIAP, and Survivin contributes to the development of drug-resistance and is associated with poor clinical outcome in breast cancer patients.},
}
@article {pmid26401837,
year = {2015},
author = {Wolmer, L and Hamiel, D and Versano-Eisman, T and Slone, M and Margalit, N and Laor, N},
title = {Preschool Israeli Children Exposed to Rocket Attacks: Assessment, Risk, and Resilience.},
journal = {Journal of traumatic stress},
volume = {28},
number = {5},
pages = {441-447},
doi = {10.1002/jts.22040},
pmid = {26401837},
issn = {1573-6598},
mesh = {Child ; Child, Preschool ; Diagnostic and Statistical Manual of Mental Disorders ; Explosive Agents ; Female ; Humans ; Interviews as Topic ; Israel/epidemiology ; Life Change Events ; Male ; Mothers/*psychology ; Multivariate Analysis ; *Resilience, Psychological ; Stress Disorders, Post-Traumatic/diagnosis/etiology/*psychology ; Terrorism/*psychology ; },
abstract = {Preschool children are among the most vulnerable populations to adversity. This study described the effects of 4 weeks of daily exposure to rocket attacks on children living on Israel's southern border. Participants enrolled in this study were 122 preschool children (50% boys) between the ages 3 and 6 years from 10 kindergartens. We assessed mothers' report of children's symptoms according to the DSM-IV and alternative criteria resembling the DSM-5 criteria for posttraumatic stress disorder (PTSD), general adaptation, traumatic exposure, and stressful life events 3 months after the war. The prevalence of PTSD was lower when the diagnosis was derived from the DSM-IV (4%) than from the DSM-5 criteria (14%). Mothers of children with 4 or more stressful life events reported more functional impairment in social, occupational, and other important areas of functioning compared to children with 0 or 1 stressful life event. Children with more severe exposure showed more severe symptoms and mothers had more concerns about the child's functioning (η(p)(2) = .09-.25). Stressful life events and exposure to traumatic experiences accounted for 32% of the variance in PTSD and 19% of the variance in the adaptation scale. Results were explored in terms of risk and resilience factors.},
}
@article {pmid26400100,
year = {2015},
author = {Qin, F and Zhang, H and Ma, L and Liu, X and Dai, K and Li, W and Gu, F and Fu, L and Ma, Y},
title = {Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients.},
journal = {Scientific reports},
volume = {5},
number = {},
pages = {14430},
pmid = {26400100},
issn = {2045-2322},
support = {R03 AA020101/AA/NIAAA NIH HHS/United States ; },
mesh = {Adult ; Aged ; Brain Neoplasms/*metabolism/mortality/*secondary ; Breast Neoplasms/*metabolism/mortality/*pathology ; Carcinoma in Situ/genetics ; Carcinoma, Ductal, Breast/genetics/pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Middle Aged ; Nerve Tissue Proteins/genetics/*metabolism ; Prognosis ; Proportional Hazards Models ; Receptors, Immunologic/genetics/*metabolism ; Roundabout Proteins ; Slit Homolog 2 Protein ; },
abstract = {Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast cancer brain metastasis for the first time. Our results demonstrated that (1) Invasive ductal carcinoma patients with low expression of Slit2 or Robo1 exhibited worse prognosis and brain-specific metastasis, but not liver, bone or lung. (2) Lower expression of Slit2 and Robo1 were observed in patients with brain metastasis, especially in their brain metastasis tumors, compared with patients without brain metastasis. (3) The interval from diagnosis of breast cancer to brain metastasis and brain metastasis to death were both much shorter in patients with low expression of Slit2 or Robo1 compared with the high expression group. Overall, our findings indicated that Slit2/Robo1 axis possibly be regarded as a significant clinical parameter for predicting brain metastasis in breast cancer patients.},
}
@article {pmid26396924,
year = {2015},
author = {Usmani, A and Shoro, AA and Memon, Z and Hussain, M and Rehman, R},
title = {Diagnostic, prognostic and predictive value of MicroRNA-21 in breast cancer patients, their daughters and healthy individuals.},
journal = {American journal of cancer research},
volume = {5},
number = {8},
pages = {2484-2490},
pmid = {26396924},
issn = {2156-6976},
abstract = {MicroRNA-21 (miR-21) located on 17q23.1 expressed in breast cancer has anti-apoptotic ability and causes tumor cell growth. It is also involved in functions such as signal transduction pathways effecting normal cell growth and differentiation. The primary objective of the study was to identify presence of miR-21 in the serum levels of stage III invasive ductal carcinoma patients and compare its expression with age matched healthy individuals and daughters of index cases. The secondary objective was to evaluate the significance of serum miR-21 gene expression with histologically proven estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) proteins. A total of 132 subjects were recruited: 50 (cases) of stage III invasive ductal carcinoma patients who had not undergone any chemotherapy or surgery were randomly picked with exclusion of females with other types of breast carcinoma. Age-matched, 50 healthy individuals (control A) were selected by purposive sampling after confirmation of no palpable lump/s in their breasts together with 32 daughters of index cases (control B). Serum tests were run on Real Time quantitative Reverse Transcription PCR, threshold cycle was determined and fold change calculated.Normality of continuous variables was assessed by Shapiro-Wilk's test, groups compared by student t-test, Mann-Whitney test and Fisher exact test, P-value ≤ 0.05 was considered significant. We observed that miR-21 was significantly higher in cases as compared to control A and B (P = 0.001) however control B showed significant gene expression as compared to control A (P = 0.001). The cases were also divided as positive or negative for ER, PR and HER2. High expression of miR-21 in females with stage III invasive ductal carcinoma had been calculated as compared to its age matched healthy subjects. It was observed that triple negative cases showed a greater expression of gene as compared to other groups (P = 0.001). Expression of miR-21 in daughters of the cases was significantly higher as compared to healthy controls but lesser than females with invasive intraductal carcinoma. This result strengthens the concept of inheritability of disease with prediction of miR-21 as a potentially strong diagnostic and prognostic biomarker of breast cancer.},
}
@article {pmid26394603,
year = {2015},
author = {Padovese, V and Racalbuto, V and Barnabas, GA and Morrone, A},
title = {Operational research on the correlation between skin diseases and HIV infection in Tigray region, Ethiopia.},
journal = {International journal of dermatology},
volume = {54},
number = {10},
pages = {1169-1174},
doi = {10.1111/ijd.12809},
pmid = {26394603},
issn = {1365-4632},
mesh = {Adult ; Candidiasis, Oral/epidemiology ; Case-Control Studies ; Condylomata Acuminata/epidemiology ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; HIV Infections/diagnosis/*epidemiology ; Hair Diseases/epidemiology ; Herpes Zoster/epidemiology ; Humans ; Leukoplakia, Hairy/epidemiology ; Male ; Prevalence ; Prurigo/epidemiology ; Skin Diseases/*epidemiology ; Tongue Diseases/epidemiology ; },
abstract = {BACKGROUND: In Ethiopia, skin diseases are among the leading causes of outpatient attendance to primary health service. Correlation of skin diseases and HIV has long been recognized and used to guide medical management in resource-limited settings. Therefore, this study aims to assess the correlation of skin diseases and HIV infection, to estimate epidemiological distribution in the study area, and to provide health workers of skin indicators for HIV early detection.<br><br>METHODS: The operational research was designed as a case-control study and carried out in three intervention districts of Tigray region; baseline and final data on skin diseases and HIV were compared with those of three control districts matched for population size, density, and environmental characteristics. Health workers of intervention districts were trained on skin diseases/STIs diagnosis and treatment. Data were collected from study and control districts and then analyzed at the Italian Dermatological Centre (IDC) in Mekele.<br><br>RESULTS: In the research period, a total of 1044 HIV positive patients were detected. Disorders of skin and mucous membranes statistically related with HIV (P < 0.05) were tongue papillary atrophy (80%), oral hairy leukoplakia (69%), herpes zoster (66%), oral candidiasis (50%), pruritic papular eruption (43%), condylomata acuminata (38%), and telogen effluvium (27%).<br><br>CONCLUSIONS: The high frequency of oral disorders and telogen effluvium is not described in literature and may be indicative for case detection. Operational research offers significant gains on health service delivery and outcomes at relatively low cost and in a short timeframe.},
}
@article {pmid26392358,
year = {2015},
author = {Moelans, CB and Vlug, EJ and Ercan, C and Bult, P and Buerger, H and Cserni, G and van Diest, PJ and Derksen, PW},
title = {Methylation biomarkers for pleomorphic lobular breast cancer - a short report.},
journal = {Cellular oncology (Dordrecht, Netherlands)},
volume = {38},
number = {5},
pages = {397-405},
pmid = {26392358},
issn = {2211-3436},
mesh = {Adaptor Proteins, Signal Transducing/genetics ; Analysis of Variance ; BRCA1 Protein/genetics ; Biomarkers, Tumor/classification/*genetics ; Breast Neoplasms/diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Carcinoma, Lobular/diagnosis/*genetics ; Cluster Analysis ; *DNA Methylation ; DNA-Binding Proteins/genetics ; Diagnosis, Differential ; Female ; Humans ; Logistic Models ; Multiplex Polymerase Chain Reaction/methods ; MutL Protein Homolog 1 ; Nuclear Proteins/genetics ; Promoter Regions, Genetic/genetics ; ROC Curve ; Tumor Protein p73 ; Tumor Suppressor Proteins/classification/genetics ; },
abstract = {BACKGROUND: Pleomorphic invasive lobular cancer (pleomorphic ILC) is a rare variant of ILC that is characterized by a classic ILC-like growth pattern combined with an infiltrative ductal cancer (IDC)-like high nuclear atypicality. There is an ongoing discussion whether pleomorphic ILC is a dedifferentiated form of ILC or in origin an IDC with a secondary loss of cohesion. Since gene promoter hypermethylation is an early event in breast carcinogenesis and thus may provide information on tumor progression, we set out to compare the methylation patterns of pleomorphic ILC, classic ILC and IDC. In addition, we aimed at analyzing the methylation status of pleomorphic ILC.<br><br>METHODS: We performed promoter methylation profiling of 24 established and putative tumor suppressor genes by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis in 20 classical ILC, 16 pleomorphic ILC and 20 IDC cases.<br><br>RESULTS: We found that pleomorphic ILC showed relatively low TP73 and MLH1 methylation levels and relatively high RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different.<br><br>CONCLUSION: This is the first report to identify TP73, RASSF1A, MLH1 and BRCA1 as possible biomarkers to distinguish pleomorphic ILC from classic ILC and IDC.},
}
@article {pmid26384318,
year = {2015},
author = {Elsarraj, HS and Hong, Y and Valdez, KE and Michaels, W and Hook, M and Smith, WP and Chien, J and Herschkowitz, JI and Troester, MA and Beck, M and Inciardi, M and Gatewood, J and May, L and Cusick, T and McGinness, M and Ricci, L and Fan, F and Tawfik, O and Marks, JR and Knapp, JR and Yeh, HW and Thomas, P and Carrasco, DR and Fields, TA and Godwin, AK and Behbod, F},
title = {Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion.},
journal = {Breast cancer research : BCR},
volume = {17},
number = {},
pages = {128},
pmid = {26384318},
issn = {1465-542X},
support = {R01 CA207445/CA/NCI NIH HHS/United States ; P20 RR016475/RR/NCRR NIH HHS/United States ; HD02528/HD/NICHD NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM103326/GM/NIGMS NIH HHS/United States ; R21 CA185460/CA/NCI NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; P20 GM103418/GM/NIGMS NIH HHS/United States ; 1R21CA185460-01/CA/NCI NIH HHS/United States ; U01 CA084955/CA/NCI NIH HHS/United States ; U01CA113916/CA/NCI NIH HHS/United States ; U01 CA113916/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Disease Progression ; Epithelial-Mesenchymal Transition/genetics ; Female ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Proteins/*genetics ; Neoplasm Recurrence, Local/genetics/pathology ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Transcription Factors ; Transcription, Genetic/genetics ; Transcriptome/*genetics ; Up-Regulation/genetics ; Wnt Proteins/genetics ; beta Catenin/genetics ; },
abstract = {INTRODUCTION: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However BCL9 role in breast cancer had not been previously recognized.<br><br>METHODS: Microarray and RNA sequencing were utilized to characterize the sequential changes in mRNA expression during DCIS invasive transition. BCL9-shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, epithelial-mesenchymal transition (EMT) and canonical Wnt-signaling. Immunofluorescence of 28 patient samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. The cancer genome atlas data were analyzed to assess the status of BCL9 gene alterations in breast cancers.<br><br>RESULTS: Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) and progesterone receptor (PR) negative, high nuclear grade, and high human epidermal growth factor receptor2 (HER2). In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of EMT. Analysis of the TCGA data showed BCL9 to be altered in 26 % of breast cancers. This is a significant alteration when compared to HER2 (ERBB2) gene (19 %) and estrogen receptor (ESR1) gene (8 %). A significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification.<br><br>CONCLUSION: BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC.},
}
@article {pmid26381749,
year = {2015},
author = {Roque, M and Duarte, I and Fouto, O and Távora, I},
title = {Invasive Ductal Carcinoma of the Breast in a Complex Cyst.},
journal = {The breast journal},
volume = {21},
number = {6},
pages = {683-684},
doi = {10.1111/tbj.12505},
pmid = {26381749},
issn = {1524-4741},
mesh = {Adult ; Breast Cyst/complications/*diagnosis ; Breast Neoplasms/complications/*diagnosis ; Carcinoma, Ductal, Breast/complications/*diagnosis ; Female ; Humans ; Mammography ; Ultrasonography, Mammary ; },
}
@article {pmid26376021,
year = {2015},
author = {Wong, SM and Freedman, RA and Sagara, Y and Stamell, EF and Desantis, SD and Barry, WT and Golshan, M},
title = {The effect of Paget disease on axillary lymph node metastases and survival in invasive ductal carcinoma.},
journal = {Cancer},
volume = {121},
number = {24},
pages = {4333-4340},
doi = {10.1002/cncr.29687},
pmid = {26376021},
issn = {1097-0142},
mesh = {Axilla ; Breast Neoplasms/complications/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/complications/metabolism/*pathology/therapy ; Chemotherapy, Adjuvant ; Databases, Factual ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Paget's Disease, Mammary/complications/metabolism/*pathology/therapy ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; SEER Program ; Tumor Burden ; },
abstract = {BACKGROUND: The objective of this study was to examine the effect of Paget disease (PD) on axillary lymph node metastases and survival in patients who had concomitant invasive ductal carcinoma (PD-IDC).<br><br>METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women who were diagnosed with PD-IDC from 2000 to 2011, comparing baseline demographic and tumor characteristics with those who were diagnosed with IDC alone during the same period. Multivariable logistic regression was used to examine the association of PD-IDC with axillary lymph node metastasis, and breast cancer-specific survival and overall survival were compared between the PD-IDC and IDC groups using the Kaplan-Meier method and Cox proportional hazards regression.<br><br>RESULTS: The study cohort included 1102 patients with PD-IDC and 302,242 controls with IDC alone. PD-IDC tumors were more likely to be centrally located (26.9% vs 5.5%; P&#x2009;<&#x2009;.001), high grade (63.5% vs 40.3%; P&#x2009;<&#x2009;.001), >2 cm in greatest dimension (47.1% vs 35.7%; P&#x2009;<&#x2009;.001), and estrogen/progesterone receptor-negative (45.2% vs 22.1%; P&#x2009;<&#x2009;.001). In adjusted analyses, patients with PD-IDC had higher odds of axillary lymph node metastasis (odds ratio, 1.83; P&#x2009;<&#x2009;.001). The unadjusted 10-year breast cancer-specific and overall survival rates were lower for the PD-IDC group compared with the IDC-alone group, although, after adjusting for disease stage, tumor characteristics, and local therapy, no significant differences in mortality risk were observed between the 2 groups (hazard ratio, 0.91; P&#x2009;=&#x2009;.24).<br><br>CONCLUSIONS: PD-IDC is associated with an increased risk of axillary lymph node metastasis, but not with inferior survival, compared with IDC alone after adjustment for other disease factors.},
}
@article {pmid26373617,
year = {2016},
author = {Zheng, B and Ohuchida, K and Chijiiwa, Y and Zhao, M and Mizuuchi, Y and Cui, L and Horioka, K and Ohtsuka, T and Mizumoto, K and Oda, Y and Hashizume, M and Nakamura, M and Tanaka, M},
title = {CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression.},
journal = {Molecular carcinogenesis},
volume = {55},
number = {11},
pages = {1560-1572},
doi = {10.1002/mc.22409},
pmid = {26373617},
issn = {1098-2744},
mesh = {CD146 Antigen/genetics/metabolism ; Cancer-Associated Fibroblasts/cytology/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Coculture Techniques ; Disease Progression ; *Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; NF-kappa B/metabolism ; Neoplasm Invasiveness ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Tumor Cells, Cultured ; },
abstract = {Cancer-associated fibroblasts (CAFs) are heterogeneous cell populations that influence tumor initiation and progression. CD146 is a cell membrane protein whose expression has been implicated in multiple human cancers. CD146 expression is also detected in pancreatic cancer stroma; however, the role it plays in this context remains unclear. This study aimed to clarify the function and significance of CD146 expression in pancreatic cancer. We performed immunohistochemical staining to investigate the prevalence of CD146 expression in stromal fibroblasts in pancreatic cancer. We also examined the influence of CD146 on CAF-mediated tumor invasion and migration and CAF activation using CD146 small interfering RNA or overexpression plasmids in primary cultures of CAFs derived from pancreatic cancer tissues. CD146 expression in CAFs was associated with high-grade pancreatic intraepithelial neoplasia and low histological grade invasive ductal carcinoma of the pancreas, while patients with low CD146 expression had a poorer prognosis. Blocking CD146 expression in CAFs significantly enhanced tumor cell migration and invasion in a co-culture system. CD146 knockdown also promoted CAF activation, possibly by inducing the production of pro-tumorigenic factors through modulation of NF-κB activity. Consistently, overexpression of CD146 in CAFs inhibited migration and invasion of co-cultured cancer cells. Finally, CD146 expression in CAFs was reduced by interaction with cancer cells. Our findings suggest that decreased CD146 expression in CAFs promotes pancreatic cancer progression. © 2015 Wiley Periodicals, Inc.},
}
@article {pmid26359561,
year = {2016},
author = {Makis, W and Robinson, D and McEwan, AJ and Riauka, TA},
title = {Chest X-ray Artifact Caused by Bilateral 99mTc-Antimony Trisulfite Injection for Sentinel Node Imaging in a Patient With Breast Cancer.},
journal = {Clinical nuclear medicine},
volume = {41},
number = {4},
pages = {319-320},
doi = {10.1097/RLU.0000000000000967},
pmid = {26359561},
issn = {1536-0229},
mesh = {Antimony/administration &amp; dosage/*adverse effects ; Artifacts ; Breast Neoplasms/*diagnostic imaging ; Female ; Humans ; Lymph Nodes/*diagnostic imaging ; Middle Aged ; Radiopharmaceuticals/administration &amp; dosage/*adverse effects ; Technetium Compounds/administration &amp; dosage/*adverse effects ; },
abstract = {A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x-ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (∼2.96 μSv).},
}
@article {pmid26358115,
year = {2016},
author = {Chikman, B and Davidson, T and Kais, H and Jeroukhimov, I and Leshno, A and Sandbank, J and Halevy, A and Lavy, R},
title = {Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?.},
journal = {Familial cancer},
volume = {15},
number = {1},
pages = {41-47},
pmid = {26358115},
issn = {1573-7292},
mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/genetics ; Carcinoma, Ductal, Breast/epidemiology/genetics ; Carcinoma, Lobular/*epidemiology/genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Humans ; Incidence ; Middle Aged ; Pedigree ; Retrospective Studies ; Stomach Neoplasms/*epidemiology/genetics ; },
abstract = {CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, <50 and ≥50 years. One thousand one hundred and sixty-seven patients with IDC and ILC entered the study. A family history of malignancies was reported in 21.6 % of patients with IDC as opposed to 37.8 % of patients with ILC (P < 0.001). A history of gastric cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P < 0.008. A family history of breast cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.},
}
@article {pmid26353381,
year = {2016},
author = {Catanzaro, D and Shackney, SE and Schaffer, AA and Schwartz, R},
title = {Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.},
journal = {IEEE/ACM transactions on computational biology and bioinformatics},
volume = {13},
number = {4},
pages = {643-655},
pmid = {26353381},
issn = {1557-9964},
support = {R01 AI076318/AI/NIAID NIH HHS/United States ; R01 CA140214/CA/NCI NIH HHS/United States ; },
mesh = {Algorithms ; Breast Neoplasms/diagnosis/*genetics/*physiopathology ; Carcinoma, Ductal/diagnosis/*genetics/*physiopathology ; Clonal Evolution ; Cluster Analysis ; Computational Biology/*methods ; Female ; Humans ; Models, Genetic ; },
abstract = {Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.},
}
@article {pmid26349603,
year = {2015},
author = {Omran, OM and Al Sheeha, M},
title = {Cytoskeletal Focal Adhesion Proteins Fascin-1 and Paxillin Are Predictors of Malignant Progression and Poor Prognosis in Human Breast Cancer.},
journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer},
volume = {34},
number = {3},
pages = {201-212},
doi = {10.1615/jenvironpatholtoxicoloncol.2015013663},
pmid = {26349603},
issn = {2162-6537},
mesh = {Adult ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/*genetics/pathology ; Carrier Proteins/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Microfilament Proteins/*genetics/metabolism ; Middle Aged ; Paxillin/*genetics/metabolism ; Prognosis ; },
abstract = {Breast cancer is a major health problem in both developing and developed countries. The incremental motility of malignant cells is a critical step in their migration, invasion, and metastasis and is regulated by the reorganization of the actin cytoskeleton and regulation of focal adhesion. Fascin-1 and paxillin are essential components of these cellular structures. In cancer, the expression level of fascin-1 and paxillin can vary depending on cell type. However, its precise role in breast cancer of Saudi women has not been evaluated in any published study. We investigated fascin-1 and paxillin expression in breast carcinoma, and we have related these results to the established prognostic factors. We studied 100 breast carcinoma specimens. Immunohistochemical analyses for fascin-1 and paxillin were conducted on paraffin sections of breast tissues using the avidin-biotin peroxidase method. Fascin-1 and paxillin were expressed in 58% and 43% of infiltrating duct carcinoma (IDC) cases. There was a statistically significant correlation between fascin-1 and paxillin expression with each of the following: tumor grade, clinical stage, lymph-node metastasis grade, and HER2 expression. Furthermore, there was a significant correlation between fascin-1 expression with paxillin immunostaining but no such association with PR or ER status. Increased fascin-1 and paxillin expression in IDC cells and their correlation with poor prognostic factors support their strong correlation with tumor progression, invasion, and metastasis in human breast cancer, indicating that these markers can be used as a target for the development of novel therapies.},
}
@article {pmid26347357,
year = {2015},
author = {Harrison, K and Hoad, G and Scott, P and Simpson, L and Horgan, GW and Smyth, E and Heys, SD and Haggarty, P},
title = {Breast cancer risk and imprinting methylation in blood.},
journal = {Clinical epigenetics},
volume = {7},
number = {1},
pages = {92},
pmid = {26347357},
issn = {1868-7075},
abstract = {BACKGROUND: Altered DNA methylation of imprinted genes has been implicated in a range of cancers. Imprinting is established early in development, and some are maintained throughout the life course in multiple tissues, providing a plausible mechanism linking known early life factors to cancer risk. This study investigated methylation status of seven imprinted differentially methylated regions-PLAGL1/ZAC1, H19-ICR1, IGF2-DMR2, KvDMR-ICR2, RB1, SNRPN-DMR1 and PEG3-in blood samples from 189 women with the most common type of invasive breast cancer (invasive ductal carcinoma-IDC), 41 women with in situ breast cancer (ductal carcinoma in situ-DCIS) and 363 matched disease-free controls.<br><br>RESULTS: There was no evidence that imprinted gene methylation levels varied with age (between 25 and 87&#xa0;years old), weight or height. Higher PEG3 methylation was associated with an elevated risk of IDC (odds ratio (OR) 1.065; 95&#xa0;% confidence interval (CI) 1.002, 1.132; p&#x2009;=&#x2009;0.042) and DCIS (OR 1.139; 95&#xa0;% CI 1.027, 1.263; p&#x2009;=&#x2009;0.013). The effect was stronger when in situ and invasive breast cancer were combined (OR 1.079; 95&#xa0;% CI 1.020, 1.142; p&#x2009;=&#x2009;0.008). DCIS breast cancer risk increased with higher KvDMR-ICR2 methylation (OR 1.395; 95&#xa0;% CI 1.190, 1.635; p&#x2009;<&#x2009;0.001) and lower PLAGL1/ZAC1 methylation (OR 0.905; 95&#xa0;% CI 0.833, 0.982; p&#x2009;=&#x2009;0.017). In a combined model, only KvDMR-ICR2 methylation remained significantly&#xa0;associated.<br><br>CONCLUSIONS: These findings may help to improve our understanding of the aetiology of breast cancer and the importance of early life factors in particular. Imprinting methylation status also has the potential to contribute to the development of improved screening and treatment strategies for women with, or at risk of, breast cancer.},
}
@article {pmid26336132,
year = {2015},
author = {Döppler, H and Bastea, L and Borges, S and Geiger, X and Storz, P},
title = {The phosphorylation status of VASP at serine 322 can be predictive for aggressiveness of invasive ductal carcinoma.},
journal = {Oncotarget},
volume = {6},
number = {30},
pages = {29740-29752},
pmid = {26336132},
issn = {1949-2553},
support = {P50 CA116201/CA/NCI NIH HHS/United States ; R01 GM086435/GM/NIGMS NIH HHS/United States ; CA116201-03DR4/CA/NCI NIH HHS/United States ; GM086435/GM/NIGMS NIH HHS/United States ; },
mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal/genetics/*metabolism/pathology ; Cell Adhesion Molecules/genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; Cell Movement/genetics ; Disease Progression ; HeLa Cells ; Humans ; Immunoblotting ; Immunohistochemistry ; Kaplan-Meier Estimate ; Microfilament Proteins/genetics/*metabolism ; Microscopy, Confocal ; Mutation ; Neoplasm Invasiveness ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Prognosis ; Protein Kinase D2 ; Protein Kinases/genetics/metabolism ; Serine/genetics/*metabolism ; Tissue Array Analysis ; Vasodilator-Stimulated Phosphoprotein ; },
abstract = {Vasodilator-stimulated phosphoprotein (VASP) signaling is critical for dynamic actin reorganization processes that define the motile phenotype of cells. Here we show that VASP is generally highly expressed in normal breast tissue and breast cancer. We also show that the phosphorylation status of VASP at S322 can be predictive for breast cancer progression to an aggressive phenotype. Our data indicate that phosphorylation at S322 is gradually decreased from normal breast to DCIS, luminal/ER+, HER2+ and basal-like/TN phenotypes. Similarly, the expression levels of PKD2, the kinase that phosphorylates VASP at this site, are decreased in invasive ductal carcinoma samples of all three groups. Overall, the phosphorylation status of this residue may serve as an indicator of aggressiveness of breast tumors.},
}
@article {pmid26331372,
year = {2016},
author = {Haffner, MC and Weier, C and Xu, MM and Vaghasia, A and Gürel, B and Gümüşkaya, B and Esopi, DM and Fedor, H and Tan, HL and Kulac, I and Hicks, J and Isaacs, WB and Lotan, TL and Nelson, WG and Yegnasubramanian, S and De Marzo, AM},
title = {Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.},
journal = {The Journal of pathology},
volume = {238},
number = {1},
pages = {31-41},
pmid = {26331372},
issn = {1096-9896},
support = {P50 CA058236/CA/NCI NIH HHS/United States ; R01 CA183965/CA/NCI NIH HHS/United States ; P30CA006973/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; R01CA183965/CA/NCI NIH HHS/United States ; R01 CA070196/CA/NCI NIH HHS/United States ; P50CA58236/CA/NCI NIH HHS/United States ; P50CA058236/CA/NCI NIH HHS/United States ; R01CA070196/CA/NCI NIH HHS/United States ; T32 GM008752/GM/NIGMS NIH HHS/United States ; },
mesh = {Adenocarcinoma/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Cell Line, Tumor ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Neoplasm Invasiveness ; Oncogene Proteins, Fusion/genetics ; PTEN Phosphohydrolase/genetics ; Prostatic Intraepithelial Neoplasia/genetics/*pathology ; Prostatic Neoplasms/genetics/*pathology ; Trans-Activators/genetics ; Transcriptional Regulator ERG ; },
abstract = {Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenocarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2-ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and intraductal carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenocarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenocarcinoma. These data suggest that invasive adenocarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for intraductal carcinoma adjacent to invasive adenocarcinoma. These findings represent a potentially undervalued indicator of pre-existing invasive prostate cancer and have significant implications for prostate cancer diagnosis and risk stratification.},
}
@article {pmid26329827,
year = {2015},
author = {Webster, BL and Rabone, M and Pennance, T and Emery, AM and Allan, F and Gouvras, A and Knopp, S and Garba, A and Hamidou, AA and Mohammed, KA and Ame, SM and Rollinson, D and Webster, JP},
title = {Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium.},
journal = {Parasites &amp; vectors},
volume = {8},
number = {},
pages = {432},
pmid = {26329827},
issn = {1756-3305},
support = {104958/Z/14/Z//Wellcome Trust/United Kingdom ; },
mesh = {Animals ; Cost-Benefit Analysis ; *Genetic Variation ; Genetics, Population ; Humans ; Larva/classification/genetics ; *Microsatellite Repeats ; Multiplex Polymerase Chain Reaction/*methods ; Niger ; Schistosoma haematobium/*classification/*genetics/isolation &amp; purification ; Schistosomiasis haematobia/parasitology ; Tanzania ; Time Factors ; Urinary Tract Infections/parasitology ; },
abstract = {BACKGROUND: Human urogenital schistosomiasis caused by Schistosoma haematobium is widely distributed across Africa and is increasingly targeted for control and regional elimination. The development of new high-throughput, cost-effective molecular tools and approaches are needed to monitor and evaluate the impact of control programs on the parasite populations. Microsatellite loci are genetic markers that can be used to investigate how parasite populations change over time and in relation to external influences such as control interventions.<br><br>FINDINGS: Here, 18 existing S. haematobium microsatellite loci were optimised to enable simultaneous amplification across two novel multiplex microsatellite PCR's, each containing nine loci. Methods were developed for the cost effective and rapid processing and microsatellite analysis of S. haematobium larval stages stored on Whatman-FTA cards and proved robust on miracidia and cercariae collected from Zanzibar and Niger.<br><br>CONCLUSION: The development of these novel and robust multiplex microsatellite assays, in combination with an improved protocol to elute gDNA from Whatman-FTA fixed schistosome larval stages, enables the high-throughput population genetic analysis of S. haematobium. The molecular resources and protocols described here advance the way researchers can perform multi locus-based population genetic analyses of S. haematobium as part of the evaluation and monitoring of schistosomiasis control programmes.},
}
@article {pmid26329135,
year = {2016},
author = {Zhang, Z and Atwell, LL and Farris, PE and Ho, E and Shannon, J},
title = {Associations between cruciferous vegetable intake and selected biomarkers among women scheduled for breast biopsies.},
journal = {Public health nutrition},
volume = {19},
number = {7},
pages = {1288-1295},
pmid = {26329135},
issn = {1475-2727},
support = {P01 CA090890/CA/NCI NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; UL1TR000128/TR/NCATS NIH HHS/United States ; R21 CA132236/CA/NCI NIH HHS/United States ; R21 CA132236-01A2/CA/NCI NIH HHS/United States ; P30 ES000210/ES/NIEHS NIH HHS/United States ; },
mesh = {Adult ; Aged ; Biomarkers/blood/urine ; Biopsy ; Body Mass Index ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Cell Proliferation/physiology ; Creatinine/urine ; *Diet ; Double-Blind Method ; Female ; Histone Deacetylases/metabolism ; Humans ; Isothiocyanates/blood/urine ; Ki-67 Antigen/genetics/metabolism ; Life Style ; Linear Models ; Middle Aged ; Multivariate Analysis ; Nutrition Assessment ; Socioeconomic Factors ; Sulfoxides ; *Vegetables ; },
abstract = {OBJECTIVE: To examine the relationship between dietary cruciferous vegetable intake and selected tumour biomarkers for histone acetylation (H3K9ac, H3K18ac, HDAC3 and HDAC6), proliferation (Ki-67) and cell-cycle regulation (p21) from breast tissue.<br><br>DESIGN: The study used baseline data of women recruited to participate in a clinical trial of sulforaphane supplement. Dietary cruciferous vegetable intake was collected through a validated Arizona Cruciferous Vegetable Intake Questionnaire. Breast tissue was obtained from biopsy samples. Spearman correlations were calculated between intake of specific cruciferous vegetables and biomarkers. Tissue biomarkers were log2-transformed to obtain approximate normality. Linear regression analyses were conducted to examine associations between cruciferous vegetable intake and biomarkers adjusting for age and use of non-steroidal anti-inflammatory drugs. False discovery rate (FDR) was used to account for multiple comparisons.<br><br>SETTING: Clinical trial baseline.<br><br>SUBJECTS: Fifty-four women who had abnormal mammogram findings and were scheduled for breast biopsy.<br><br>RESULTS: Mean intake of total cruciferous vegetables from all food sources was 81&#xb7;7 (sd 57&#xb7;3) g/d. Mean urinary total sulforaphane metabolites was 0&#xb7;08 (sd 0&#xb7;07) &#xb5;m/mm creatinine. Total cruciferous vegetable intake was inversely associated with Ki-67 protein expression in breast ductal carcinoma in situ (DCIS) tissue (&#x3b2;=-0&#xb7;004; se=0&#xb7;001; FDR q value=0&#xb7;03), but not in benign or invasive ductal carcinoma (IDC) tissue. No association was found for other biomarkers measured (HDAC3, HDAC6, H3K9, H3K18 and p21) in all tissues examined (benign, DCIS and IDC).<br><br>CONCLUSIONS: The present study sought to provide additional evidence for the potential role of sulforaphane in histone acetylation and cell proliferation. Here, we report that total cruciferous vegetable intake is associated with decreased cell proliferation in breast DCIS tissue.},
}
@article {pmid26323933,
year = {2015},
author = {Zhu, MZ and Yu, XF and He, XM and Feng, WL and Fan, JH and Li, J and Xu, F and Tang, ZH and Zhang, BN and Qiao, YL and Zheng, S and Yang, HJ},
title = {Clinicopathological features of invasive lobular carcinoma of the breast: A nationwide multicenter study in China.},
journal = {Journal of cancer research and therapeutics},
volume = {11 Suppl 1},
number = {},
pages = {C89-94},
doi = {10.4103/0973-1482.163851},
pmid = {26323933},
issn = {1998-4138},
mesh = {Adult ; Biomarkers ; Breast Neoplasms/*epidemiology/metabolism/*pathology ; Carcinoma, Lobular/*epidemiology/metabolism/*pathology ; China/epidemiology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Risk Factors ; },
abstract = {OBJECTIVE: To analyze the clinicopathological features of invasive lobular carcinoma (ILC) and compare them with invasive ductal carcinoma (IDC), hoping to find the fact of ILC in China and assist the decision makers with proper individualized treatment.<br><br>MATERIALS AND METHODS: A nationwide multicenter retrospective study was performed. A total of 4211 primary breast cancer cases were randomly selected from 1999 to 2008 in seven regions of China. ILC cases were compared with IDC by clinicopathological features and molecular subtypes.<br><br>RESULTS: A total of 135 (3.2%) ILC and 3471 (82.4%) IDC cases were included for analysis. The age, tumor size, menopausal state, family history, nodal status, and stage of ILC were similar to that of IDC. ILC was more likely to be positive for estrogen receptor (65.5% vs. 57.7%) and progesterone receptor (64.7% vs. 58.5%), and less likely to overexpress human epidermal growth factor receptor-2 (17.3% vs. 23.6%). Even though, these differences are not significant, the proportion of luminal A type of ILC is significantly larger than that of IDC (54.8% vs. 42.7%; P < 0.05).<br><br>CONCLUSION: ILC has a larger proportion of luminal A type compared with IDC. Larger sample size study for better known of molecular subtypes of ILC is needed in future to individualize the treatment decision.},
}
@article {pmid26321244,
year = {2015},
author = {do Nascimento, JC and Ferreira, Sde A and Vasconcelos, JL and da Silva-Filho, JL and Barbosa, BT and Bezerra, MF and Rocha, CR and Beltrão, EI},
title = {Fut3 role in breast invasive ductal carcinoma: Investigating its gene promoter and protein expression.},
journal = {Experimental and molecular pathology},
volume = {99},
number = {3},
pages = {409-415},
doi = {10.1016/j.yexmp.2015.08.015},
pmid = {26321244},
issn = {1096-0945},
mesh = {Brazil ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Female ; Fucosyltransferases/*genetics/metabolism ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Immunohistochemistry/methods ; Lewis X Antigen/metabolism ; *Promoter Regions, Genetic ; },
abstract = {Fucosylated glycans synthesized by α1,3/4-fucosyltransferase (FUT3) enzyme play an important role in breast cancer prognosis and metastasis, being involved in the binding of circulating tumor cells to the endothelium and being related to tumor stage, metastatic potential and chemoresistance. Despite the pro-tumor action of this enzyme, studies have demonstrated its role in natural killer-induced cytotoxicity through the recognition of sialyl Lewis X by C-type lectin receptors and through extrinsic apoptosis pathway triggered by Apo2L-TRAIL. This study aimed to investigate the expression pattern of FUT3 in invasive breast carcinoma (IDC) from patients of Pernambuco state, Northeast of Brazil, and genotype FUT3 promoter region to identify possible SNPs that could be associated with variations in FUT3 expression. Immunohistochemistry assay was used to access the FUT3 expression in normal (n=11) and tumor tissues (n=85). DNA sequencing was performed to genotype the FUT3 promoter region in patients with IDC (n=109) and healthy controls (n=110). Our results demonstrated that the absence of FUT3 enzyme is related to breast's IDC. The non-expression of FUT3 was more frequent in larger lesions and also in HER2 negative IDC tumors. Genomic analysis showed that two variations localized in FUT3 promoter region are possibly associated with IDC. Our results suggest that minor allele T of SNP rs73920070 (-6933 C>T) confers protection whereas minor allele T of SNP rs2306969 (-6951 C>T) triggers to susceptibility to IDC in the population of Pernambuco state, Northeast of Brazil.},
}
@article {pmid26320758,
year = {2016},
author = {Ben-David, BM and Icht, M},
title = {Voice Changes in Real Speaking Situations During a Day, With and Without Vocal Loading: Assessing Call Center Operators.},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {30},
number = {2},
pages = {247.e1-11},
doi = {10.1016/j.jvoice.2015.04.002},
pmid = {26320758},
issn = {1873-4588},
mesh = {Acoustics ; Adolescent ; Adult ; Case-Control Studies ; Female ; Habits ; Humans ; Life Style ; Male ; Occupational Diseases/diagnosis/etiology/*physiopathology ; *Occupational Health ; *Occupations ; Risk Factors ; *Speech Acoustics ; Speech Production Measurement ; Surveys and Questionnaires ; *Telephone ; Time Factors ; Voice Disorders/diagnosis/etiology/*physiopathology ; *Voice Quality ; Workload ; Young Adult ; },
abstract = {OBJECTIVES: Occupational-related vocal load is an increasing global problem with adverse personal and economic implications. We examined voice changes in real speaking situations during a single day, with and without vocal loading, aiming to identify an objective acoustic index for vocal load over a day.<br><br>METHODS: Call center operators (CCOs, n&#xa0;=&#xa0;27) and age- and gender-matched students (n&#xa0;=&#xa0;25) were recorded at the beginning and at the end of a day, with (CCOs) and without (students) vocal load. Speaking and reading voice samples were analyzed for fundamental frequency (F0), sound pressure level (SPL), and their variance (F0 coefficient of variation [F0 CV], SPL CV). The impact of lifestyle habits on voice changes was also estimated.<br><br>RESULTS AND CONCLUSIONS: The main findings revealed an interaction, with F0 rise at the end of the day for the students but not for the CCOs. We suggest that F0 rise is a typical phenomenon of a day of normal vocal use, whereas vocal loading interferes with this mechanism. In addition, different lifestyle profiles of CCOs and controls were observed, as the CCOs reported higher incidence of dehydrating behaviors (eg, smoking, caffeine). Yet, this profile was not linked with voice changes. In sum, we suggest that F0 rise over a day can potentially serve as an index for typical voice use. Its lack thereof can hint on consequent voice symptoms and complaints.},
}
@article {pmid26319586,
year = {2016},
author = {Liu, W and Tang, C and Liu, L and Zhu, QS and Huang, LF},
title = {Cervical intervertebral disc calcification with extreme lateral herniation in a child: T2-weighted signal intensity of the involved disc can be restored to normal.},
journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery},
volume = {32},
number = {4},
pages = {749-752},
pmid = {26319586},
issn = {1433-0350},
mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Calcinosis/*complications/diagnostic imaging/drug therapy ; Child ; Female ; Humans ; Imaging, Three-Dimensional ; Intervertebral Disc Degeneration/*complications/diagnostic imaging/drug therapy ; Longitudinal Studies ; Magnetic Resonance Imaging ; Tomography Scanners, X-Ray Computed ; },
abstract = {PURPOSE: The purpose of this case report is to present a very atypical case of cervical intervertebral disc calcification (IDC) with extreme lateral herniated calcification in a child. This is the first ever reported case in which T2-weighted signal intensity of the involved disc was restored to normal after a 2-year follow-up.<br><br>METHODS: A 10-year-old girl presented with neck pain and right upper limb numbness for 2 months. The initial computed tomography (CT) images on admission showed calcified nucleus pulposus with extreme lateral herniated calcification at the C6-C7 level. Meanwhile, T2-weighted magnetic resonance imaging (MRI) revealed decreased signal intensity of the involved disc. The patient was treated conservatively with nonsteroidal anti-inflammatory drugs and jaw-occipital belt traction for 2 weeks. The cervical CT and MRI scans were repeated at 2-year follow-up.<br><br>RESULTS: Her clinical symptoms were completely resolved after 2 weeks. At 2-year follow-up, CT and MRI images demonstrated that calcification was completely absorbed and T2-weighted signal intensity of the C6-C7 disc was restored back to normal.<br><br>CONCLUSION: Cervical IDC combined with extreme lateral herniated calcification is extremely rare in children. The recovery of signal intensity of intervertebral disc on MRI may provide further support to the feasibility of conservative treatment of IDC.},
}
@article {pmid26319120,
year = {2015},
author = {Buas, MF and Rho, JH and Chai, X and Zhang, Y and Lampe, PD and Li, CI},
title = {Candidate early detection protein biomarkers for ER+/PR+ invasive ductal breast carcinoma identified using pre-clinical plasma from the WHI observational study.},
journal = {Breast cancer research and treatment},
volume = {153},
number = {2},
pages = {445-454},
pmid = {26319120},
issn = {1573-7217},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; U01CA152637/CA/NCI NIH HHS/United States ; HHSN268201100046C/HL/NHLBI NIH HHS/United States ; HHSN268201100003C/WH/WHI NIH HHS/United States ; T32 CA009168/CA/NCI NIH HHS/United States ; HHSN271201100004C/AG/NIA NIH HHS/United States ; HHSN268201100002C/WH/WHI NIH HHS/United States ; U01 CA152746/CA/NCI NIH HHS/United States ; U01 CA152637/CA/NCI NIH HHS/United States ; T32CA009168/CA/NCI NIH HHS/United States ; HHSN268201100001C/WH/WHI NIH HHS/United States ; HHSN268201100004C/WH/WHI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/*metabolism ; Breast Neoplasms/blood/*diagnosis/*metabolism ; Carcinoma, Ductal, Breast/blood/*diagnosis/*metabolism ; Case-Control Studies ; Computational Biology/methods ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Proteome ; Proteomics/methods ; ROC Curve ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Risk Factors ; },
abstract = {Estrogen receptor (ER)-positive/progesterone receptor (PR)-positive invasive ductal carcinoma accounts for ~45 % of invasive breast cancer (BC) diagnoses in the U.S. Despite reductions in BC mortality attributable to mammography screening and adjuvant hormonal therapy, an important challenge remains the development of clinically useful blood-based biomarkers for risk assessment and early detection. The objective of this study was to identify novel protein markers for ER+/PR+ ductal BC. A nested case-control study was conducted within the Women's Health Initiative observational study. Pre-clinical plasma specimens, collected up to 12.5 months before diagnosis from 121 cases and 121 matched controls, were equally divided into training and testing sets and interrogated using a customized antibody array targeting >2000 proteins. Statistically significant differences (P < 0.05) in matched case versus control signals were observed for 39 candidates in both training and testing sets, and four markers (CSF2, RYBP, TFRC, ITGB4) remained significant after Bonferroni correction (P < 2.03 × 10(-5)). A multivariate modeling procedure based on elastic net regression with Monte Carlo cross-validation achieved an estimated AUC of 0.75 (SD 0.06). Most candidates did not overlap with those described previously for triple-negative BC, suggesting sub-type specificity. Gene set enrichment analyses identified two GO gene sets as upregulated in cases-microtubule cytoskeleton and response to hormone stimulus (P < 0.05, q < 0.25). This study has identified a pool of novel candidate plasma protein biomarkers for ER+/PR+ ductal BC using pre-diagnostic biospecimens. Further validation studies are needed to confirm these candidates and assess their potential clinical utility for BC risk assessment/early detection.},
}
@article {pmid26316122,
year = {2015},
author = {Gordon, N and Skinner, AM and Pommier, RF and Schillace, RV and O'Neill, S and Peckham, JL and Muller, P and Condron, ME and Donovan, C and Naik, A and Hansen, J and Pommier, SJ},
title = {Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism.},
journal = {Stem cell research &amp; therapy},
volume = {6},
number = {1},
pages = {157},
pmid = {26316122},
issn = {1757-6512},
mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Cells, Cultured ; Female ; *Glycolysis ; Humans ; MCF-7 Cells ; Neoplastic Stem Cells/*metabolism ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; *Transcriptome ; },
abstract = {INTRODUCTION: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response.<br><br>METHODS: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test.<br><br>RESULTS: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression.<br><br>CONCLUSIONS: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.},
}
@article {pmid26285240,
year = {2015},
author = {Shih, J and Bashir, B and Gustafson, KS and Andrake, M and Dunbrack, RL and Goldstein, LJ and Boumber, Y},
title = {Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {13},
number = {8},
pages = {947-952},
pmid = {26285240},
issn = {1540-1413},
support = {R01 GM084453/GM/NIGMS NIH HHS/United States ; },
mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Brain Neoplasms/diagnosis/secondary/therapy ; Breast Neoplasms/diagnosis/drug therapy/*genetics ; Female ; *Gene Amplification ; Genetic Testing ; Humans ; Lung Neoplasms/diagnosis/therapy ; *Mutation ; Neoplasm Staging ; Neoplasms, Second Primary ; Radiography, Thoracic ; Radiosurgery ; Receptor, ErbB-2/*genetics ; Tomography, X-Ray Computed ; Treatment Outcome ; },
abstract = {Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions.},
}
@article {pmid26271144,
year = {2015},
author = {Wang, X and Hu, B and Shen, H and Zhou, H and Xue, X and Chen, Y and Chen, S and Han, Y and Yuan, B and Zhao, H and Zhi, Q and Kuang, Y},
title = {Clinical and prognostic relevance of EZH2 in breast cancer: A meta-analysis.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {75},
number = {},
pages = {218-225},
doi = {10.1016/j.biopha.2015.07.038},
pmid = {26271144},
issn = {1950-6007},
mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Disease Progression ; Enhancer of Zeste Homolog 2 Protein ; Female ; Humans ; Kaplan-Meier Estimate ; Neoplasm Staging ; Odds Ratio ; Polycomb Repressive Complex 2/*analysis ; Risk Factors ; Treatment Outcome ; Up-Regulation ; },
abstract = {The polycomb group protein enhancer of zeste homolog 2 (EZH2) is regarded as a tightly linking oncogene in many types of cancer. However, the prognostic role of EZH2 in breast cancer (BC) still remains controversial. Our study aimed to evaluate the clinical and prognostic relevance of EZH2 in BC patients based on published studies. 11 studies totally containing 2330 patients (1052 EZH2-positive and 1278 EZH2-negative) were included in our meta-analysis. Our data showed that EZH2 over-expression was significantly associated with estrogen receptor (ER) negativity [OR=0.227, 95% CI=0.174-0.297, P=0.000], progesterone receptor (PR) negativity [OR=0.454, 95% CI=0.300-0.687, P=0.000], human epidermal growth factor receptor type 2 (HER-2) positivity [OR=1.846, 95% CI=1.366-2.496, P=0.000], invasive ductal cancer (IDC) [OR=2.237, 95% CI=1.489-3.361, P=0.000], race (Caucasian) [OR=0.707, 95% CI=0.522-0.957, P=0.025], high histological grade [OR=3.177, 95% CI=2.012-5.014, P=0.000] and triple-negative status (TNBCs) [OR=5.380, 95% CI=1.065-27.187, P=0.042], which led to a poor OS rate in BC [RR=2.193, 95% CI=1.495-3.217, P=0.000]. In conclusion, EZH2 participated in the progression of BC as a putative factor, and over-expression of EZH2 was distinctly correlated with a poor patient survival. EZH2 may serve as a prognostic biomarker and target in BC patients.},
}
@article {pmid26268905,
year = {2016},
author = {Rominger, M and Berg, D and Frauenfelder, T and Ramaswamy, A and Timmesfeld, N},
title = {Which factors influence MRI-pathology concordance of tumour size measurements in breast cancer?.},
journal = {European radiology},
volume = {26},
number = {5},
pages = {1457-1465},
pmid = {26268905},
issn = {1432-1084},
mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Multivariate Analysis ; Retrospective Studies ; Tumor Burden ; },
abstract = {OBJECTIVES: To assess MRI-pathology concordance and factors influencing tumour size measurement in breast cancer.<br><br>MATERIALS AND METHODS: MRI tumour size (greatest diameter in anatomical planes (MRI-In-Plane) and greatest diameter along main tumour axis (MRI-MPR)) of 115 consecutive breast lesions (59 invasive lobular carcinoma, 46 invasive ductal carcinoma, and 10 ductal carcinoma in situ) was retrospectively compared to size measured at histopathology (pT size (Path-TNM) and greatest tumour diameter as relevant for excision (Path-Diameter; reference standard)). Histopathological tumour types, preoperative palpability, surgical management, additional high-risk lesions, and BI-RADS lesion type (mass versus non-mass enhancements) were assessed as possible influencing factors.<br><br>RESULTS: Systematic errors were most pronounced between MRI-MPR and Path-TNM (7.1 mm, limits of agreement (LoA) [-21.7; 35.9]), and were lowest between MRI-In-Plane and Path-Diameter (0.2 mm, LoA [-19.7; 20.1]). Concordance rate of MRI-In-Plane with Path-Diameter was 86% (97/113), overestimation 9% (10/113) and underestimation 5% (6/113); BI-RADS mass lesions were overestimated in 7% (6/81) versus 41% (13/32) for non-mass enhancements. On multivariate analysis only BI-RADS lesion type significantly influenced MRI-pathology concordance (p&#x2009;<&#x2009;0.001). 2/59 (3%) ILC did not enhance.<br><br>CONCLUSION: Concordance rate varies according to the execution of MRI and histopathological measurements. Beyond this only non-mass enhancement significantly predicted discordance.<br><br>KEY POINTS: &#x2022; Execution and scope of MRI and histopathological size measurements influence concordance rate. &#x2022; Non-mass like enhancement predicts discordance. &#x2022; Additional high-risk lesions in proximity of tumour do not cause measurement discordance. &#x2022; Low percentage of ILC do not enhance at all.},
}
@article {pmid26255059,
year = {2015},
author = {Rane, SU and Mirza, H and Grigoriadis, A and Pinder, SE},
title = {Selection and evolution in the genomic landscape of copy number alterations in ductal carcinoma in situ (DCIS) and its progression to invasive carcinoma of ductal/no special type: a meta-analysis.},
journal = {Breast cancer research and treatment},
volume = {153},
number = {1},
pages = {101-121},
doi = {10.1007/s10549-015-3509-x},
pmid = {26255059},
issn = {1573-7217},
mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Chromosome Aberrations ; Chromosome Mapping ; Computational Biology ; *DNA Copy Number Variations ; Disease Progression ; Female ; Humans ; Molecular Sequence Annotation ; Neoplasm Invasiveness ; Neurophysins/genetics ; Protein Precursors/genetics ; Signal Transduction ; Vasopressins/genetics ; },
abstract = {Ductal carcinoma in situ (DCIS) is a pre-invasive malignancy detected with an increasing frequency through screening mammography. One of the primary aims of therapy is to prevent local recurrence, as in situ or as invasive carcinoma, the latter arising in half of the recurrent cases. Reliable biomarkers predictive of its association with recurrence, particularly as invasive disease, are however lacking. In this study, we perform a meta-analysis of 26 studies which report somatic copy number aberrations (SCNAs) in 288 cases of 'pure' DCIS and 328 of DCIS associated with invasive carcinoma, along with additional unmatched cases of 145 invasive carcinoma of ductal/no special type (IDC) and 50 of atypical ductal hyperplasia (ADH). SCNA frequencies across the genome were calculated at cytoband resolution (UCSC genome build 19) to maximally utilize the available information in published literature. Fisher's exact test was used to identify significant differences in the gain-loss distribution in each cytoband in different group comparisons. We found synchronous DCIS to be at a more advanced stage of genetic aberrations than pure DCIS and was very similar to IDC. Differences in gains and losses in each disease process (i.e. invasive or in situ) at each cytoband were used to infer evidence of selection and conservation for each cytoband and to define an evolutionary conservation scale (ECS) as a tool to identify and distinguish driver SCNA from the passenger SCNA. Using ECS, we have identified aberrations that show evidence of selection from the early stages of neoplasia (i.e. in ADH and pure DCIS) and persist in IDC; we postulate these to be driver aberrations and that their presence may predict progression to invasive disease.},
}
@article {pmid26253945,
year = {2015},
author = {Tsai, KW and Li, GC and Chen, CH and Yeh, MH and Huang, JS and Tseng, HH and Fu, TY and Liou, HH and Pan, HW and Huang, SF and Chen, CC and Chang, HY and Ger, LP and Chang, HT},
title = {Reduction of global 5-hydroxymethylcytosine is a poor prognostic factor in breast cancer patients, especially for an ER/PR-negative subtype.},
journal = {Breast cancer research and treatment},
volume = {153},
number = {1},
pages = {219-234},
doi = {10.1007/s10549-015-3525-x},
pmid = {26253945},
issn = {1573-7217},
mesh = {5-Methylcytosine/analogs &amp; derivatives ; Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics/*mortality/pathology ; Cytosine/*analogs &amp; derivatives/metabolism ; *DNA Methylation ; DNA-Binding Proteins/genetics/metabolism ; Dioxygenases ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Mixed Function Oxygenases ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Protein Transport ; Proto-Oncogene Proteins/genetics/metabolism ; Receptors, Estrogen/deficiency ; Receptors, Progesterone/deficiency ; Risk Factors ; Survival Analysis ; Young Adult ; },
abstract = {DNA methylation at the 5 position of cytosine (5 mC) is an epigenetic hallmark in cancer. The 5 mC can be converted to 5-hydroxymethylcytosine (5 hmC) through a ten-eleven-translocation (TET). We investigated the impact of 5 mC, 5 hmC, TET1, and TET2 on tumorigenesis and prognosis of breast cancer. Immunohistochemistry was used to assess the levels of 5 mC, 5 hmC, TET1, and TET2 in the corresponding tumor adjacent normal (n = 309), ductal carcinoma in situ (DCIS, n = 120), and invasive ductal carcinoma (IDC, n = 309) tissues for 309 breast ductal carcinoma patients. 5 mC, 5 hmC, TET1-n, and TET2-n were significantly decreased during DCIS and IDC progression. In IDC, the decrease of 5 hmC was correlated with the cytoplasmic mislocalization of TET1 (p < 0.001) as well as poor disease-specific survival (DSS) (adjusted hazard ratio [AHR] 1.95, p = 0.003) and disease-free survival (DFS) (AHR 1.91, p = 0.006). The combined decrease of 5 mC and 5 hmC was correlated with worse DSS (AHR 2.19, p = 0.008) and DFS (AHR 1.99, p = 0.036). Stratification analysis revealed that the low level of 5 mC was associated with poor DSS (AHR 1.89, p = 0.044) and DFS (AHR 2.02, p = 0.035) for the ER/PR-positive subtype. Conversely, the low level of 5 hmC was associated with worse DSS (AHR 2.77, p = 0.002) and DFS (AHR 2.69, p = 0.006) for the ER/PR-negative subtype. The decreases of 5 mC, 5 hmC, TET1-n, and TET2-n were biomarkers of tumor development. The global reduction of 5 hmC was a poor prognostic factor for IDC, especially for ER/PR-negative subtype.},
}
@article {pmid26242364,
year = {2015},
author = {McEvoy, MP and Coopey, SB and Mazzola, E and Buckley, J and Belli, A and Polubriaginof, F and Merrill, AL and Tang, R and Garber, JE and Smith, BL and Gadd, MA and Specht, MC and Guidi, AJ and Roche, CA and Hughes, KS},
title = {Breast Cancer Risk and Follow-up Recommendations for Young Women Diagnosed with Atypical Hyperplasia and Lobular Carcinoma In Situ (LCIS).},
journal = {Annals of surgical oncology},
volume = {22},
number = {10},
pages = {3346-3349},
doi = {10.1245/s10434-015-4747-1},
pmid = {26242364},
issn = {1534-4681},
mesh = {Adult ; Breast/*pathology ; Breast Neoplasms/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; *Continuity of Patient Care ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/pathology ; Mammography ; Neoplasm Invasiveness ; Neoplasm Staging ; Precancerous Conditions/*pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Young Adult ; },
abstract = {BACKGROUND: The risk of breast cancer in young women diagnosed with atypical hyperplasia and (LCIS) is not well defined. The objectives were to evaluate outcomes and to help determine guidelines for follow-up in this population.<br><br>METHODS: A retrospective review of women under age 35 diagnosed with ADH, ALH, LCIS, and severe ADH from 1987 to 2010 was performed. Patient characteristics, pathology and follow-up were determined from chart review.<br><br>RESULTS: We identified 58 young women with atypical breast lesions. Median age at diagnosis was 31 years (range 19-34). 34 patients had ADH, 11 had ALH, 8 had LCIS, and 5 had severe ADH. 7 (12%) patients developed breast cancer. The median follow-up was 86 months (range 1-298). Median time to cancer diagnosis was 90 months (range 37-231). 4 cancers were on the same side, 3 were contralateral. 4 were IDC, 1 was ILC, and 2 were DCIS. Cancer was detected by screening mammogram in 4 patients, 2 by clinical exam, and 1 unknown. In the entire cohort, 26 (45%) patients had screening mammograms as part of their follow up, 12 patients had only clinical follow up, and 20 had no additional follow up. 13 patients required subsequent biopsies.<br><br>CONCLUSION: Young women with atypical breast lesions are at a markedly increased risk for developing breast cancer and should be followed closely. Based on our findings, we recommend close clinical follow-up, MRI starting at age 25 through age 29, and screening mammograms for those over 30 in this high-risk group of patients.},
}
@article {pmid26233575,
year = {2015},
author = {Broch, K and Murbræch, K and Andreassen, AK and Hopp, E and Aakhus, S and Gullestad, L},
title = {Contemporary Outcome in Patients With Idiopathic Dilated Cardiomyopathy.},
journal = {The American journal of cardiology},
volume = {116},
number = {6},
pages = {952-959},
doi = {10.1016/j.amjcard.2015.06.022},
pmid = {26233575},
issn = {1879-1913},
mesh = {Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiac Resynchronization Therapy ; Cardiomyopathy, Dilated/complications/*therapy ; Cardiotonic Agents/therapeutic use ; Cohort Studies ; Death, Sudden, Cardiac/etiology/*prevention &amp; control ; Defibrillators, Implantable ; Digitoxin/therapeutic use ; Digoxin/therapeutic use ; Diuretics/therapeutic use ; Exercise Test ; Female ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Oxygen Consumption ; Prospective Studies ; Stroke Volume ; Treatment Outcome ; Ventricular Dysfunction, Left/complications/*therapy ; },
abstract = {Outcome is better in patients with idiopathic dilated cardiomyopathy (IDC) than in ischemic heart failure (HF), but morbidity and mortality are nevertheless presumed to be substantial. Most data on the prognosis in IDC stem from research performed before the widespread use of current evidence-based treatment, including implantable devices. We report outcome data from a cohort of patients with IDC treated according to current HF guidelines and compare our results with previous figures: 102 consecutive patients referred to our tertiary care hospital with idiopathic IDC and a left ventricular ejection fraction <40% were included in a prospective cohort study. After extensive baseline work-up, follow-up was performed after 6 and 13 months. Vital status and heart transplantation were recorded. Over the first year of follow-up, the patients were on optimal pharmacological treatment, and 24 patients received implantable devices. Left ventricular ejection fraction increased from 26 ± 10% to 41 ± 11%, peak oxygen consumption increased from 19.5 ± 7.1 to 23.4 ± 7.8 ml/kg/min, and functional class improved substantially (all p values <0.001). After a median follow-up of 3.6 years, 4 patients were dead, and heart transplantation had been performed in 9 patients. According to our literature search, survival in patients with IDC has improved substantially over the last decades. In conclusion, patients with IDC have a better outcome than previously reported when treated according to current guidelines.},
}
@article {pmid26229954,
year = {2015},
author = {Panisello-Tafalla, A and Clua-Espuny, JL and Gil-Guillen, VF and González-Henares, A and Queralt-Tomas, ML and López-Pablo, C and Lucas-Noll, J and Lechuga-Duran, I and Ripolles-Vicente, R and Carot-Domenech, J and López, MG},
title = {Results from the Registry of Atrial Fibrillation (AFABE): Gap between Undiagnosed and Registered Atrial Fibrillation in Adults--Ineffectiveness of Oral Anticoagulation Treatment with VKA.},
journal = {BioMed research international},
volume = {2015},
number = {},
pages = {134756},
pmid = {26229954},
issn = {2314-6141},
mesh = {Administration, Oral ; Adult ; Aged ; Anticoagulants/administration &amp; dosage/*therapeutic use ; Atrial Fibrillation/*diagnosis/*drug therapy/epidemiology ; Female ; Humans ; Male ; Prevalence ; *Registries ; Risk Factors ; Spain/epidemiology ; Survival Analysis ; Vitamin K/*antagonists &amp; inhibitors ; },
abstract = {OBJECTIVE: This study aimed to examine the effectiveness of the use of oral anticoagulation (OAC) medication, recommended by national guidelines for stroke prevention but reportedly underused in AF patients with moderate to high stroke risk.<br><br>METHOD: A multicentre and cross-sectional study of undiagnosed AF among out-of-hospital patients over 60 years old was carried out, visiting 3,638 patients at primary health centres or at home for AF diagnosis using the IDC-10 classification. The main outcome measures were CHA&#x2082;DS&#x2082;VASC, HAS-BLED scores, cardiovascular comorbidity, pharmacological information, TTR, and SAMe-TT2R2 scores.<br><br>RESULTS: The main findings were undiagnosed AF in 26.44% of cases; 31.04% registered with AF but not using OAC despite 95.6% having a CHA&#x2082;DS&#x2082;VASC &#x2265; 2 score; a risk of bleeding in important subgroups using OAC without indication (37.50% CHA&#x2082;DS&#x2082;VASC < 2 score); the use of OAC with TTR < 60% (33.1%), of whom 47.6% had a HAS-BLED score &#x2265;3. Thus, 35.4% of the expected AF prevalence achieved an optimal time in the therapeutic range.<br><br>CONCLUSIONS: The expected AF prevalence was 10.9% (n 5267), but the registered prevalence was 7.5% (n 3638). Only 35.04% (CI = 95%, 33.7-36.3) of AF patients treated with vitamin K antagonists (VKAs) achieve the goal of TTR > 60%.},
}
@article {pmid26214623,
year = {2015},
author = {Abu Rabi, Z and Zoranovic, T and Milovanovic, J and Todorovic-Rakovic, N and Nikolic-Vukosavljevic, D},
title = {Breast cancer in postmenopausal patients: Impact of age.},
journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology},
volume = {20},
number = {3},
pages = {723-729},
pmid = {26214623},
issn = {1107-0625},
mesh = {Age Factors ; Aged ; *Aging ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/secondary/*therapy ; Chemotherapy, Adjuvant ; Disease Progression ; Disease-Free Survival ; Estrogen Antagonists/therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; *Postmenopause ; Receptors, Estrogen/analysis/drug effects ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; Tamoxifen/therapeutic use ; Time Factors ; Treatment Outcome ; },
abstract = {PURPOSE: We analyzed the significance of age together with other classic prognostic parameters on the course of breast cancer in postmenopausal patients.<br><br>METHODS: Our study included 151 postmenopausal patients with primary breast cancer, of which 55% received adjuvant tamoxifen therapy and 45% did not receive any kind of therapy. Probabilities of disease-free interval (DFI) were estimated using the Kaplan-Meier method and were compared by the log-rank test. A p value<0.05 was considered as statistically significant.<br><br>RESULTS: In the tamoxifen-treated subgroup, patients with estrogen receptor (ER) or progesterone receptor (PR) concentration&#x2265;5 fmol/mg had favorable course of disease (p<0.01, p<0.04), respectively. Patients&#x2265;66 years of age had a worse disease course compared to those<66 years. Also, patients&#x2265;66 years with pT1 tumors had a worse disease course compared to those<66 years and pT1 tumors. This result was repeated in other groups as well. In pT2 (&#x2265;2 cm), ER-positive, PR-positive and invasive ductal carcinoma (IDC) subgroups, patients&#x2265;66 years always had a worse disease course compared to patients<66 years. In the untreated subgroup, patients with ER&#x2265;52 fmol/mg (p<0.01), tumors&#x2265;2 cm (p<0.01), IDC (p<0.01) type or &#x2265;56 years (p<0.04) had statistically more recurrences. Among patients&#x2265;56 years, those with ER-positive or pT2 tumors had shorter DFI compared to ER-negative or pT1. Positive correlation between ER, PR and age of patients was also shown in this subgroup (p<0.03, p<0.02).<br><br>CONCLUSION: Age of patients, ER and PR are significant prognostic factors in the tamoxifen-treated subgroup. In the untreated subgroup relevant prognostic parameters are age, tumor size, histological type and ER. The above prognostic factors retained their value in the long-term follow up in both the investigated subgroups of patients.},
}
@article {pmid26208902,
year = {2015},
author = {Benevides, L and da Fonseca, DM and Donate, PB and Tiezzi, DG and De Carvalho, DD and de Andrade, JM and Martins, GA and Silva, JS},
title = {IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment.},
journal = {Cancer research},
volume = {75},
number = {18},
pages = {3788-3799},
pmid = {26208902},
issn = {1538-7445},
support = {R01 AI103542/AI/NIAID NIH HHS/United States ; R21 AI083948/AI/NIAID NIH HHS/United States ; I083948-01//PHS HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/chemistry/immunology/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/immunology/mortality/*secondary ; Chemotaxis, Leukocyte/*physiology ; Cytokines/biosynthesis/genetics/metabolism ; Disease Progression ; Disease-Free Survival ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-17/analysis/antagonists &amp; inhibitors/immunology/*physiology ; Lymphocytes, Tumor-Infiltrating/*immunology/metabolism ; Mammary Neoplasms, Experimental/immunology/pathology ; Mice ; Mice, Inbred BALB C ; Neoplasm Proteins/analysis/antagonists &amp; inhibitors/immunology/*physiology ; Neutrophils/*immunology/metabolism ; Prognosis ; Th17 Cells/immunology ; },
abstract = {The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF, and TNFα, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors.},
}
@article {pmid26204115,
year = {2015},
author = {Son, SH and Lee, SW and Jeong, SY and Song, BI and Chae, YS and Ahn, BC and Lee, J},
title = {Whole-Body Metabolic Tumor Volume, as Determined by (18)F-FDG PET/CT, as a Prognostic Factor of Outcome for Patients With Breast Cancer Who Have Distant Metastasis.},
journal = {AJR. American journal of roentgenology},
volume = {205},
number = {4},
pages = {878-885},
doi = {10.2214/AJR.14.13906},
pmid = {26204115},
issn = {1546-3141},
mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; *Multimodal Imaging ; Neoplasm Metastasis/*diagnostic imaging ; *Positron-Emission Tomography ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Risk Factors ; *Tomography, X-Ray Computed ; Tumor Burden ; },
abstract = {OBJECTIVE: This study was performed to evaluate the prognostic relevance of PET parameters measured by (18)F-FDG PET/CT in patients with invasive ductal carcinoma of the breast (IDC) who had distant metastasis at the time of initial diagnosis.<br><br>MATERIALS AND METHODS: Forty women with IDC who had distant metastasis at the time of initial diagnosis and who underwent FDG PET/CT before receiving treatment were enrolled in the study. Clinicopathologic parameters and metabolic PET parameters, including the maximum standardized uptake value (SUVmax) of the primary tumor (pSUVmax), the SUVmax of the axillary lymph node (nSUVmax), the highest SUVmax of whole malignant lesions (wSUVmax), the whole-body (WB) metabolic tumor volume (MTV), and WB total lesion glycolysis (TLG), were analyzed to determine their usefulness in predicting overall survival (OS). Univariate and multivariate analyses were performed with the use of Kaplan-Meier and Cox proportional hazards models.<br><br>RESULTS: Twenty-one of the 40 patients (52.5%) died during follow-up (mean follow-up, 36.4 months; range, 0.8-71.4 months). Nonsurvivors had a statistically significantly higher mean (&#xb1; SD) WB MTV than did survivors (424.0 &#xb1; 683.9 vs 92.1 &#xb1; 96.3 cm(3); p = 0.0430). T category, performance of palliative surgery, presence of visceral metastasis, wSUVmax, WB MTV, and WB TLG were identified by univariate analysis as prognostic factors for OS, whereas age, N category, hormone receptor status, status, triple-negative breast cancer status (defined as a tumor for which estrogen receptor, progesterone receptor, and ERBB2 statuses were all negative), pSUVmax, and nSUVmax were not. Multivariate analysis revealed that only WB MTV independently predicted OS (hazard ratio, 4.10; 95% CI, 1.17-14.31; p = 0.0280).<br><br>CONCLUSION: The WB MTV value, as determined by FDG PET/CT performed before treatment, was found to be an independent prognostic factor for OS in patients with IDC who had distant metastasis at the time of initial diagnosis.},
}
@article {pmid26195469,
year = {2015},
author = {Yoon, PD and Chalasani, V and Woo, HH},
title = {Systematic review and meta-analysis on management of acute urinary retention.},
journal = {Prostate cancer and prostatic diseases},
volume = {18},
number = {4},
pages = {297-302},
pmid = {26195469},
issn = {1476-5608},
mesh = {5-alpha Reductase Inhibitors/therapeutic use ; Acute Disease ; Adrenergic alpha-1 Receptor Antagonists/therapeutic use ; Disease Management ; Humans ; Male ; Odds Ratio ; Prostatectomy/methods ; Prostatic Hyperplasia/complications ; Treatment Outcome ; Urinary Catheterization/methods ; Urinary Retention/*diagnosis/etiology/*therapy ; },
abstract = {BACKGROUND: Acute urinary retention (AUR) is a common urological emergency. In this article, we review the current literature and present a structured summary in management of AUR.<br><br>METHODS: A systematic review was conducted using the keywords 'acute AND retention AND urin*' within the title in search engines including Medline, EMBASE and EBM Review. The obtained literature was manually reviewed by the primary author (PDY) and was further refined by confining the subject to management of AUR. Exclusion criteria included paediatric and female population studies, case reports, reviews, surveys, economical assessment and articles on AUR in prostate cancer and post-operative patients.<br><br>RESULTS: Total of 54 articles met our inclusion and exclusion criteria. The trial without catheter (TWOC) post-immediate catheterisation is widely practiced although there remains a significant variability in terms of type and duration of catheterisation required, use of concurrent medical therapy or post-catheterisation management. Our systematic review and subsequent meta-analysis has shown superiority of &#x3b1;1-adrenergic receptor blockers over placebo in achieving successful voiding in patients with AUR. Suprapubic catheter (SPC) is an alternative to urethral catheterisation (indwelling catheter (IDC)) and may provide several advantages. Clean intermittent self-catheterisation may be a safe and useful option for patients with AUR until their definitive management. The overall long-term outcome of in-and-out catheterisation remains promising in selected patients. Surgery is an end point in patients with unsuccessful TWOC as well as in those with significant lower urinary tract symptoms post-successful TWOC.<br><br>CONCLUSIONS: We recommend use of &#x3b1;1-adrenergic receptor blockers before TWOC and discourage emergency operative management. Use of SPC over IDC in AUR is debatable. Duration of catheterisation is controversial but <3 days is a safe option in avoiding catheterisation-related complications. Although TURP remains the current gold standard, there has been an emergence of newer operative management utilising laser techniques.},
}
@article {pmid26193775,
year = {2016},
author = {Aires, L and Silva, G and Martins, C and Marques, E and Lagoa, MJ and Ribeiro, JC and Rêgo, C and Nascimento, H and Pereira, PR and Santos-Silva, A and Belo, L and Mota, J},
title = {Exercise intervention and cardiovascular risk factors in obese children. Comparison between obese youngsters taking part in a physical activity school-based programme with and without individualised diet counselling: the ACORDA project.},
journal = {Annals of human biology},
volume = {43},
number = {3},
pages = {183-190},
doi = {10.3109/03014460.2015.1059889},
pmid = {26193775},
issn = {1464-5033},
mesh = {Adolescent ; Body Composition ; Body Height ; Body Weight ; Cardiovascular Diseases/*epidemiology/*etiology ; Child ; *Counseling ; *Diet ; Exercise/*physiology ; Female ; Humans ; Male ; Obesity/complications/*epidemiology ; Risk Factors ; *Schools ; },
abstract = {AIM: To determine the effects of a school-based exercise intervention programme on cardiovascular risk factors, including body fat (BF), metabolic profile and physical activity (PA) in children with and without individualised dietary counselling approach (IDC and WIDC).<br><br>SUBJECTS AND METHODS: Forty-six overweight children from 6-16 years old (25 girls, 54.3%; age&#x2009;=&#x2009;10.3&#x2009;&#xb1;&#x2009;2.8) of six schools took part in an 8-month interdisciplinary, school-based intervention programme. All children were engaged in PA classes, but only one group was exposed to individualised counselling. Blood pressure (BP), lipids and lipoproteins, accelerometer-based PA, percentage of body fat (%BF) and trunk fat (%TF) measures were taken before and after intervention. General Linear Model (Repeated Measures ANOVA) adjusted for age, maturation and height change was used to analyse the longitudinal effect of individualised counselling between two evaluations in each group.<br><br>RESULTS: Favourable changes were observed for %BF, %TF, systolic BP and total cholesterol in the IDC group. Subjects WIDC only increased light and moderate-vigorous PA. In IDC, significant effects for time * group interactions were found for systolic BP, total cholesterol and LDL-cholesterol, indicating that counselling might add favourable changes in these markers, beyond those explained by PA and growth.<br><br>CONCLUSION: School-based interventions can contribute to counteracting obesity in youth, particularly when individualised dietary counselling is provided. Therefore, the link between schools and professional counselling should be strengthened to ensure consolidated changes towards healthy behaviours.},
}
@article {pmid26179699,
year = {2016},
author = {Cui, M and Wang, Q and Chen, G},
title = {Serum metabolomics analysis reveals changes in signaling lipids in breast cancer patients.},
journal = {Biomedical chromatography : BMC},
volume = {30},
number = {1},
pages = {42-47},
doi = {10.1002/bmc.3556},
pmid = {26179699},
issn = {1099-0801},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Breast Neoplasms/*blood/pathology ; Chromatography, High Pressure Liquid ; Disease Progression ; Female ; Humans ; Lipids/*blood ; Mass Spectrometry ; Metabolomics/*methods ; Middle Aged ; Pilot Projects ; },
abstract = {Breast cancer is the most commonly diagnosed cancer and one of the leading causes of cancer death among women worldwide. It is a biologically variable disease with different molecular subtypes, risk factors, clinical behaviors and responses to treatment. Better understanding of the molecular changes associated with each subtype is essential for identifying new therapeutic targets and markers for the monitoring of treatment responses. In this pilot study, mass spectrometry-based metabolic profiling was performed to characterize the changes in serum profiles of patients with invasive ductal carcinoma (IDC) - the most common type of breast cancer. Serum samples from 20 IDC patients and 20 age- and gender-matched healthy subjects were analyzed and 15 differentially expressed metabolites were identified. These metabolites are involved in several metabolic pathways such as sphingolipid metabolism, phospholipid metabolism and fatty acid β-oxidation. Among these, two classes of signaling lipids, lysophosphatidylethanolamine and ceramide, may play an important role in IDC development and progression. This study demonstrates metabolic profiling as a promising tool for finding disease biomarkers and our findings provide new directions for further mechanistic studies on the pathology of IDC.},
}
@article {pmid26179530,
year = {2015},
author = {Morita, S and Onaya, H and Kishi, Y and Hiraoka, N and Arai, Y},
title = {Multiple Intraglandular Metastases in a Patient with Invasive Ductal Carcinoma of the Pancreas.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {54},
number = {14},
pages = {1753-1756},
doi = {10.2169/internalmedicine.54.3819},
pmid = {26179530},
issn = {1349-7235},
mesh = {Carcinoma, Pancreatic Ductal/complications/*diagnosis/pathology/surgery ; Cholangiopancreatography, Endoscopic Retrograde ; Flank Pain/etiology ; Humans ; Jaundice/etiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasms, Second Primary/complications/*diagnosis/pathology/surgery ; Pancreas/*pathology ; Pancreatectomy/methods ; Pancreatic Neoplasms/complications/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; },
abstract = {A 56-year-old man was admitted to our hospital for an evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the head of the pancreas, with three other tumors detected in the body and tail. Magnetic resonance imaging showed similar enhancement patterns and signal intensities in all four lesions. The patient underwent total pancreatectomy based on a preoperative diagnosis of multiple invasive ductal carcinomas. Histopathologically, the lesion in the pancreatic head was considered to be the primary lesion, while the others were diagnosed as metastases. This is a rare case of pancreatic cancer with intraglandular metastases. The possibility of this differential diagnosis should thus be considered when imaging shows multiple hypovascular lesions in the pancreas.},
}
@article {pmid26175196,
year = {2015},
author = {Campagna, L and Gronau, I and Silveira, LF and Siepel, A and Lovette, IJ},
title = {Distinguishing noise from signal in patterns of genomic divergence in a highly polymorphic avian radiation.},
journal = {Molecular ecology},
volume = {24},
number = {16},
pages = {4238-4251},
doi = {10.1111/mec.13314},
pmid = {26175196},
issn = {1365-294X},
mesh = {Animals ; Bayes Theorem ; Female ; Gene Flow ; Genetic Loci ; *Genetic Speciation ; Genetics, Population ; Genomics ; Male ; Models, Genetic ; Passeriformes/classification/*genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; South America ; *Sympatry ; },
abstract = {Recently diverged taxa provide the opportunity to search for the genetic basis of the phenotypes that distinguish them. Genomic scans aim to identify loci that are diverged with respect to an otherwise weakly differentiated genetic background. These loci are candidates for being past targets of selection because they behave differently from the rest of the genome that has either not yet differentiated or that may cross species barriers through introgressive hybridization. Here we use a reduced-representation genomic approach to explore divergence among six species of southern capuchino seedeaters, a group of recently radiated sympatric passerine birds in the genus Sporophila. For the first time in these taxa, we discovered a small proportion of markers that appeared differentiated among species. However, when assessing the significance of these signatures of divergence, we found that similar patterns can also be recovered from random grouping of individuals representing different species. A detailed demographic inference indicates that genetic differences among Sporophila species could be the consequence of neutral processes, which include a very large ancestral effective population size that accentuates the effects of incomplete lineage sorting. As these neutral phenomena can generate genomic scan patterns that mimic those of markers involved in speciation and phenotypic differentiation, they highlight the need for caution when ascertaining and interpreting differentiated markers between species, especially when large numbers of markers are surveyed. Our study provides new insights into the demography of the southern capuchino radiation and proposes controls to distinguish signal from noise in similar genomic scans.},
}
@article {pmid26165857,
year = {2015},
author = {Allen, MD and Jones, LJ},
title = {The role of inflammation in progression of breast cancer: Friend or foe? (Review).},
journal = {International journal of oncology},
volume = {47},
number = {3},
pages = {797-805},
doi = {10.3892/ijo.2015.3075},
pmid = {26165857},
issn = {1791-2423},
mesh = {Biomarkers, Tumor/*immunology ; Breast Neoplasms/*drug therapy/immunology/*pathology ; Disease Progression ; Female ; Humans ; Immunotherapy/methods ; Prognosis ; Tumor Microenvironment/drug effects ; },
abstract = {There is a growing interest in the role of the microenvironment in cancer, however, it has been known for over one hundred years that the immune system plays a prominent role in cancer. Recent decades have revealed more and more data on how our own host response to cancer cells can help or hinder progression of the disease. Despite all this work it is surprising how little is known about the role of the immune system in human breast cancer development, as compared to other cancers. Recent successes of PD-1 blockade in treating multiple cancers, and new developments with other immune targets such as CTLA-4 and CSF-1 inhibitors, highlight that it is becoming ever more important that we understand the complexity of the immune and inflammatory systems in the development and progression of breast cancer. With this knowledge it may be possible to not only target therapy but also more accurately predict those patients that truly need it. This review summarises some of the most significant findings for the role of the immune system and inflammatory response in breast cancer progression. Focusing on how the inflammatory microenvironment may be involved in the progression of pre-invasive ductal carcinoma in situ to invasive breast cancer. It will also discuss the use of immune markers as diagnostic and prognostic tools and summarise the state of the art of immune-therapeutics in breast cancer treatment.},
}
@article {pmid26163605,
year = {2015},
author = {Payandeh, M and Sadeghi, M and Sadeghi, E and Aeinfar, M},
title = {Clinicopathology Figures and Long-term Effects of Tamoxifen Plus Radiation on Survival of Women with Invasive Ductal Carcinoma and Triple Negative Breast Cancer.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {16},
number = {12},
pages = {4863-4867},
doi = {10.7314/apjcp.2015.16.12.4863},
pmid = {26163605},
issn = {2476-762X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Carcinoma, Ductal, Breast/*mortality/*secondary/therapy ; Chemoradiotherapy/*mortality ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; Survival Rate ; Tamoxifen/*therapeutic use ; Triple Negative Breast Neoplasms/*mortality/*pathology/therapy ; Young Adult ; },
abstract = {BACKGROUND: Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports.<br><br>MATERIALS AND METHODS: Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results.<br><br>RESULTS: The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively.<br><br>CONCLUSIONS: The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.},
}
@article {pmid26154605,
year = {2015},
author = {Walker, CG and Solis-Trapala, I and Holzapfel, C and Ambrosini, GL and Fuller, NR and Loos, RJ and Hauner, H and Caterson, ID and Jebb, SA},
title = {Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.},
journal = {PloS one},
volume = {10},
number = {7},
pages = {e0131681},
pmid = {26154605},
issn = {1932-6203},
support = {G0701642/MRC_/Medical Research Council/United Kingdom ; MC_U105960389/MRC_/Medical Research Council/United Kingdom ; P60 DK020541/DK/NIDDK NIH HHS/United States ; MC_EX_G0701642/2/MRC_/Medical Research Council/United Kingdom ; U105960389/MRC_/Medical Research Council/United Kingdom ; P30 DK020541/DK/NIDDK NIH HHS/United States ; },
mesh = {Biomarkers/*metabolism ; Diabetes Mellitus, Type 2/*genetics ; Diet ; Dietary Fats/pharmacology ; Female ; *Genetic Predisposition to Disease ; Humans ; *Life Style ; Male ; Markov Chains ; Middle Aged ; *Models, Biological ; Quantitative Trait, Heritable ; Regression Analysis ; Risk Factors ; Weight Loss ; },
abstract = {The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention.},
}
@article {pmid26153395,
year = {2015},
author = {Santangelo, G and Trojano, L and Barone, P and Vitale, C},
title = {Cortical thickness in Parkinsonians with impulse control disorders: A comment.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {30},
number = {9},
pages = {1293},
doi = {10.1002/mds.26262},
pmid = {26153395},
issn = {1531-8257},
mesh = {Cerebral Cortex/*pathology ; Disruptive, Impulse Control, and Conduct Disorders/*complications/*pathology ; Female ; Humans ; Male ; Parkinson Disease/*complications ; },
}
@article {pmid26152288,
year = {2015},
author = {Dallol, A and Buhmeida, A and Merdad, A and Al-Maghrabi, J and Gari, MA and Abu-Elmagd, MM and Elaimi, A and Assidi, M and Chaudhary, AG and Abuzenadah, AM and Nedjadi, T and Ermiah, E and Alkhayyat, SS and Al-Qahtani, MH},
title = {Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {36},
number = {12},
pages = {9677-9683},
pmid = {26152288},
issn = {1423-0380},
mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Line, Tumor ; CpG Islands ; DNA Methylation/genetics ; Epigenesis, Genetic ; Female ; Fibroblast Growth Factors/*biosynthesis/genetics ; Gene Expression Regulation, Neoplastic ; Glucuronidase/*genetics ; Humans ; Klotho Proteins ; Middle Aged ; Promoter Regions, Genetic ; Receptor, Fibroblast Growth Factor, Type 4/*biosynthesis/genetics ; },
abstract = {Invasive ductal carcinoma of the breast is the most common cancer affecting women worldwide. The marked heterogeneity of breast cancer is matched only with the heterogeneity in its associated or causative factors. Breast cancer in Saudi Arabia is apparently an early onset with many of the affected females diagnosed before they reach the age of 50 years. One possible rationale underlying this observation is that consanguinity, which is widely spread in the Saudi community, is causing the accumulation of yet undetermined cancer susceptibility mutations. Another factor could be the accumulation of epigenetic aberrations caused by the shift toward a Western-like lifestyle in the past two decades. In order to shed some light into the molecular mechanisms underlying breast cancer in the Saudi community, we identified KLOTHO (KL) as a tumor-specific methylated gene using genome-wide methylation analysis of primary breast tumors utilizing the MBD-seq approach. KL methylation was frequent as it was detected in 55.3 % of breast cancer cases from Saudi Arabia (n = 179) using MethyLight assay. Furthermore, KL is downregulated in breast tumors with its expression induced following treatment with 5-azacytidine. The involvement of KL in breast cancer led us to investigate its relationship in the context of breast cancer, with one of the protagonists of its function, fibroblast growth factor receptor 4 (FGFR4). Overexpression of FGFR4 in breast cancer is frequent in our cohort and this overexpression is associated with poor overall survival. Interestingly, FGFR4 expression is higher in the absence of KL methylation and lower when KL is methylated and presumably silenced, which is suggestive of an intricate relationship between the two factors. In conclusion, our findings further implicate "metabolic" genes or pathways in breast cancer that are disrupted by epigenetic mechanisms and could provide new avenues for understanding this disease in a new context.},
}
@article {pmid26125904,
year = {2015},
author = {Ramos, FS and Serino, LT and Carvalho, CM and Lima, RS and Urban, CA and Cavalli, IJ and Ribeiro, EM},
title = {PDIA3 and PDIA6 gene expression as an aggressiveness marker in primary ductal breast cancer.},
journal = {Genetics and molecular research : GMR},
volume = {14},
number = {2},
pages = {6960-6967},
doi = {10.4238/2015.June.26.4},
pmid = {26125904},
issn = {1676-5680},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Protein Disulfide-Isomerases/*genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; },
abstract = {Changes in the expression of the protein disulfide isomerase genes PDIA3 and PDIA6 may increase endoplasmic reticulum stress, leading to cellular instability and neoplasia. We evaluated the expression of PDIA3 and PDIA6 in invasive ductal carcinomas. Using reverse transcription-quantitative polymerase chain reaction, we compared the mRNA expression level in 45 samples of invasive ductal carcinoma with that in normal breast samples. Increased expression of the PDIA3 gene in carcinomas (P = 0.0009) was observed. In addition, PDIA3 expression was increased in tumors with lymph node metastasis (P = 0.009) and with grade III (P < 0.02). The PDIA6 gene showed higher expression levels in the presence of lymph node metastasis (U = 99.00, P = 0.0476) and lower expression for negative hormone receptors status (P = 0.0351). Our results suggest that alterations in PDIA3/6 expression levels may be involved in the breast carcinogenic process and should be further investigated as a marker of aggressiveness.},
}
@article {pmid26125737,
year = {2015},
author = {Zhao, LH and Liu, HG},
title = {Immunohistochemical detection and clinicopathological significance of JARID1B/KDM5B and P16 expression in invasive ductal carcinoma of the breast.},
journal = {Genetics and molecular research : GMR},
volume = {14},
number = {2},
pages = {5417-5426},
doi = {10.4238/2015.May.22.11},
pmid = {26125737},
issn = {1676-5680},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Cyclin-Dependent Kinase Inhibitor p16/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/*biosynthesis/genetics ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Staging ; Nuclear Proteins/*biosynthesis/genetics ; Repressor Proteins/*biosynthesis/genetics ; },
abstract = {The aims of this study were to investigate the expression of the H3K4 demethylase, jumonji AT-rich interactive domain 1B (JARID1B/KDM5B) and of p16 (multiple tumor suppressor gene MTS1) in breast cancer tissue and determine its clinicopathological significance. JARID1B/KDM5B and P16 protein expression in 176 resected breast cancer specimens and adjacent normal breast tissue was detected by the streptavidin-peroxidase (S-P) immunohistochemical method. The TNM staging grade was assigned according to the World Health Organization (2012) breast classification system. The positive staining rate of JARID1B/KDM5B and p16 protein in cancer tissue was 74.43 and 35.8%, respectively. JARID1B/KDM5B protein expression was positively associated with T grade, Bloom and Richardson (B&amp;R) score and axillary lymph node metastasis (P < 0.05). p16 protein expression was negatively associated with T grade, B&amp;R score, and axillary lymph node metastasis (P < 0.05). JARID1B/KDM5B and p16 protein expression in breast cancer and adjacent normal breast tissue were negatively correlated (r = -0.303, P < 0.001). The data demonstrated that protein expression of p16 and JARID1B/KDM5B is negatively correlated in invasive ductal carcinoma of the breast.},
}
@article {pmid26124343,
year = {2015},
author = {Grzegrzolka, J and Biala, M and Wojtyra, P and Kobierzycki, C and Olbromski, M and Gomulkiewicz, A and Piotrowska, A and Rys, J and Podhorska-Okolow, M and Dziegiel, P},
title = {Expression of EMT Markers SLUG and TWIST in Breast Cancer.},
journal = {Anticancer research},
volume = {35},
number = {7},
pages = {3961-3968},
pmid = {26124343},
issn = {1791-7530},
mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics ; Disease-Free Survival ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Gene Expression/genetics ; Humans ; Middle Aged ; Nuclear Proteins/*genetics ; RNA, Messenger/genetics ; Snail Family Transcription Factors ; Stromal Cells/metabolism ; Transcription Factors/*genetics ; Twist-Related Protein 1/*genetics ; },
abstract = {BACKGROUND: The epithelial-mesenchymal transition (EMT) has been observed in progression of in situ breast cancer to the invasive form and might be initiated by snail family zinc finger 2 (SLUG) and twist family bHLH transcription factor 1 (TWIST) protein overexpression. During this phenomenon, cells lose their epithelial phenotype and acquire mesenchymal features. The aim of the study was to examine the association of EMT markers SLUG and TWIST with clinicopathological data and the possibility of using these proteins as prognostic markers of breast cancer.<br><br>MATERIALS AND METHODS: Immunohistochemical analysis (IHC) of SLUG and TWIST expression was performed on archival paraffin samples of 19 cases with fibrocystic breast changes (control group), 148 cases of invasive ductal breast cancer (IDC) and 26 of invasive lobular breast cancer (ILC). Laser capture microdissection for isolation of cells from 17 frozen samples of IDC was employed and subsequently SLUG and TWIST mRNA expression in cancer and stromal cells was detected separately by real-time polymerase chain reaction.<br><br>RESULTS: SLUG and TWIST expression in IDC was significant higher in stromal cells regardless of the method of quantification used (p<0.001 for SLUG mRNA, and p<0.0001 for SLUG IHC, TWIST IHC and TWIST mRNA expression). Positive correlation of SLUG and TWIST protein and mRNA expression was observed in stromal cells of IDC (r=0.347; p<0.0001 and r=0.704; p<0.01, respectively). Expression of TWIST protein in IDC was higher in cancer cells of cases with shorter event-free survival period, as well as in stromal cells of cases with shorter overall survival period (p<0.05 for both).<br><br>CONCLUSION: Stromal cells could play a role in the regulation of EMT in breast cancer.},
}
@article {pmid26112049,
year = {2015},
author = {Romaniuk, A and Lуndіn, M},
title = {Immune microenvironment as a factor of breast cancer progression.},
journal = {Diagnostic pathology},
volume = {10},
number = {},
pages = {79},
pmid = {26112049},
issn = {1746-1596},
mesh = {B-Lymphocytes/*immunology/pathology ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/*immunology/pathology ; Carcinoma, Ductal, Breast/chemistry/*immunology/pathology ; Estrogen Receptor alpha/analysis ; Female ; HSP90 Heat-Shock Proteins/analysis ; Humans ; Immunohistochemistry ; Inflammation/*immunology/metabolism/pathology ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Progesterone/analysis ; Triple Negative Breast Neoplasms/chemistry/immunology/pathology ; Tumor Microenvironment/*immunology ; },
abstract = {BACKGROUND: The rate of progression of the disease depends on various factors and the tumor microenvironment takes not the last place among them. One part of researchers argues that the presence of tumor-infiltrating leukocytes serves as a favorable marker of the disease. There exists a completely different point of view on the matter. The investigation of the effects of the inflammatory infiltration on the course of breast cancer process.<br><br>METHODS: We found a pronounced inflammatory infiltration in the tumor microenvironment in 24 cases. Nineteen cases of IDC without inflammatory infiltration were used as a control group. Immunohistochemical reaction showed expression of ER&#x3b1;, PR, HER2/neu, E-cadherin, Hsp90&#x3b1;, Bcl-2, CD3, CD79&#x3b1;, S100 and Myeloperoxidase receptors. Mathematical calculations were done using Microsoft Excel 2010 with 12.0.5 Attestat option.<br><br>RESULTS: We have determined five variants of immune microenvironment: interstitial, trabecular, nodular, diffuse and mixed. We have established a direct correlation between the expression of ER&#x3b1; and PR and indirect correlation between the receptors of steroid hormones and HER2/neo in both groups of breast cancer. HER2/neo positive tumors in 100% of cases were accompanied by the presence of heat shock proteins. There was a combination of Bcl-2 presence with the steroid receptors expression in 90 % of cases. There was found the indirect correlation between the presence of B lymphocytes and expression of steroid receptors.<br><br>CONCLUSIONS: The presence of B lymphocytes in an inflammatory infiltrate leads to the disappearance of estrogen receptors and progesterone receptors. It provokes the accumulation of Hsp90 in a cell. It contributes to the stabilization of HER2/neu receptors and most proteins that promote tumor progression.<br><br>VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1362330168161694.},
}
@article {pmid26097589,
year = {2015},
author = {Lv, ZD and Zhang, L and Liu, XP and Jin, LY and Dong, Q and Li, FN and Wang, HB and Kong, B},
title = {NKD1 down-regulation is associated with poor prognosis in breast invasive ductal carcinoma.},
journal = {International journal of clinical and experimental pathology},
volume = {8},
number = {4},
pages = {4015-4021},
pmid = {26097589},
issn = {1936-2625},
support = {CDP 13-005/HX/HSRD VA/United States ; },
mesh = {Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology/therapy ; Calcium-Binding Proteins ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology/therapy ; Carrier Proteins/genetics/*metabolism ; Cell Line, Tumor ; *Cell Movement ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Receptors, Estrogen/metabolism ; Risk Factors ; Time Factors ; Transfection ; Treatment Outcome ; Young Adult ; },
abstract = {As a negative modulator of the canonical Wnt signaling pathway, Naked1 (NKD1) is widely expressed in many normal tissues. However, the expression and clinicopathological significance of NKD1 in patients with breast cancer is still unclear. The aim of this study was to evaluate NKD1 expression in breast cancer and to investigate the question of whether reduced expression of NKD1 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of NKD1 and relevance with clinicopathological factors in the breast invasive ductal carcinoma. Reduction of NKD1 was significantly correlated with lymph node metastasis, histological grade and ER expression in breast cancer. Patients with negative NKD1 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive NKD1 expression. This interpretation is in keeping with the results obtained from our in vitro experiments on MDA-MB-231 cells, we demonstrated that upregulation of NKD1 expression by infect with an adenovirus containing a NKD1 vector significantly reduced the migration of breast cancer cells. These data suggest that NKD1 plays an important role in invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.},
}
@article {pmid26080617,
year = {2015},
author = {Luo, Y and Tanabe, E and Kitayoshi, M and Nishiguchi, Y and Fujiwara, R and Matsushima, S and Sasaki, T and Sasahira, T and Chihara, Y and Nakae, D and Fujii, K and Ohmori, H and Kuniyasu, H},
title = {Expression of MAS1 in breast cancer.},
journal = {Cancer science},
volume = {106},
number = {9},
pages = {1240-1248},
pmid = {26080617},
issn = {1349-7006},
mesh = {Animals ; Apoptosis/genetics ; Carcinoma, Ductal, Breast/drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cisplatin/pharmacology ; ErbB Receptors/genetics ; Female ; Humans ; Immunohistochemistry/methods ; Lymphatic Metastasis/genetics/pathology ; MCF-7 Cells ; Mice ; Proto-Oncogene Mas ; Proto-Oncogene Proteins/*genetics ; Receptors, G-Protein-Coupled/*genetics ; Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology ; },
abstract = {MAS1 is a receptor for angiotensin 1-7 (A1-7), which is derived from angiotensin II (A-II) by the action of angiotensin converting enzyme (ACE) 2. MAS1 induces anti-A-II phenotypes, such as vessel dilation and depression of blood pressure. Using immunohistochemistry, we examined the role of MAS1 in 132 cases of invasive ductal carcinoma (IDC) of the breast. While benign mammary tissues expressed MAS1 at high levels, MAS1 expression was attenuated in all IDC, especially in scirrhous IDC. The decrease in MAS1 expression was associated with tumor growth, lymph node metastasis, and grade. MAS1 expression was inversely associated with the proliferation index and epidermal growth factor receptor and human epidermal growth factor receptor-2 expression. Of the 132 cases, 12 (9.1%) were triple-negative breast cancer (TNBC) cases. All TNBC cases (the 12 cases and the additional 36 cases using a tissue array) expressed MAS1. Using the TNBC cell lines 4T1 and MDA-MB-468, which expresses MAS1, we found that cell growth, anti-apoptotic survival and invasion were suppressed by MAS1 activation with A1-7 treatment and enhanced by MAS1 knockdown. In contrast, synergic effect was found between tamoxifen and A1-7 in a luminal A breast cancer cell line, MCF-7. Combination treatment with cisplatin, an ACE2 activator, and an A-II type 1 receptor blocker showed synergic effects on tumor growth inhibition of 4T1 tumors in a syngeneic mouse model. These findings suggest that MAS1 might act as an inhibitory regulator of breast cancer and may be a possible molecular target for this malignancy.},
}
@article {pmid26076803,
year = {2015},
author = {Poursadegh Zonouzi, AA and Nejatizadeh, A and Rahmati-Yamchi, M and Fardmanesh, H and Shakerizadeh, S and Poursadegh Zonouzi, A and Nejati-Koshki, K and Shekari, M},
title = {Dysregulated expression of Dicer in invasive ductal breast carcinoma.},
journal = {Medical oncology (Northwood, London, England)},
volume = {32},
number = {7},
pages = {203},
pmid = {26076803},
issn = {1559-131X},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma/*genetics/pathology ; DEAD-box RNA Helicases/*genetics ; Down-Regulation/*genetics ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; MicroRNAs/genetics ; Middle Aged ; Ribonuclease III/*genetics ; },
abstract = {Several lines of evidence suggest that the global down-regulation of the microRNAome (miRNAome) involved in pathogenesis of various malignancies. Impaired microRNAs processing pathway is one possible mechanism for global down-regulation of the miRNAome. Dicer is a key enzyme in miRNA processing pathway, and dysregulation of its expression has been suggested as a possible cause of miRNAome alterations observed in various cancers. However, Dicer mRNA expression in invasive ductal breast carcinoma (IDC) has not been investigated in depth. Therefore, this study aimed to evaluate the mRNA expression of Dicer in IDC and also to assess the correlation of its expression with clinicopathological parameters including age, histological grade, tumor size and lymph node metastasis. We investigated the expression of the Dicer in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissue by quantitative real-time PCR using validated reference genes. In addition, the possible impact of clinicopathological characteristics on Dicer expression levels was analyzed. Our results showed that Dicer mRNA expression is down-regulated in slightly more than half (51.43 %) of the tumor specimens when compared to adjacent non-neoplastic tissue. Comparison of the Dicer expression level between tumor and matched adjacent non-neoplastic tissue showed that there is no statistical significant differences between them (P = 0.425). We also found that Dicer mRNA expression in IDC samples was not correlated with clinicopathological features. In conclusion, our findings provide additional evidence to support the hypothesis that Dicer expression down-regulated in breast cancer. This study suggested that the decreased expression of Dicer may be potential underlying mechanism in pathogenesis of IDC.},
}
@article {pmid26076065,
year = {2015},
author = {Khani, F and Epstein, JI},
title = {Prostate Biopsy Specimens With Gleason 3+3=6 and Intraductal Carcinoma: Radical Prostatectomy Findings and Clinical Outcomes.},
journal = {The American journal of surgical pathology},
volume = {39},
number = {10},
pages = {1383-1389},
doi = {10.1097/PAS.0000000000000465},
pmid = {26076065},
issn = {1532-0979},
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology/secondary/*surgery ; Disease Progression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Predictive Value of Tests ; *Prostatectomy ; Prostatic Neoplasms/chemistry/*pathology/*surgery ; Retrospective Studies ; Time Factors ; Treatment Outcome ; },
abstract = {Although intraductal carcinoma of the prostate (IDC-P) is typically present on biopsies in which there is also invasive prostate carcinoma of Gleason pattern 4 or 5 and an associated unfavorable outcome, there are limited studies on IDC-P in needle core biopsies or transurethral resections (TURP) with only a concomitant low-grade invasive component. There are differing opinions on incorporating IDC-P into the Gleason score in such cases. The aim of this study was to investigate clinical outcomes and radical prostatectomy (RP) findings in patients with Gleason 3+3=6 and IDC-P on biopsy or TURP. We identified 73 patients in our consult files (2001 to 2014) who had IDC-P and Gleason score 6 carcinoma on biopsy or TURP with no invasive higher Gleason grade component. Clinical follow-up information was available in 62 patients. Treatment was RP in 14 patients, radiation therapy in 31 patients, androgen deprivation therapy in 1 patient, and cryotherapy in 1 patient. Four patients were found to have metastatic disease at the time of diagnosis and were treated with chemotherapy. Eleven patients underwent active surveillance after diagnosis, of which 6 were eventually treated for progressive disease. The 14 RP specimens were centrally reviewed, and 86% had extensive IDC-P present. The Gleason grades in these 14 RP cases were 3+3=6 in 21%, 3+4=7 in 36%, 4+3=7 in 29%, and 4+4=8 in 14%. Pathologic stage was pT2 in 36%, pT3a in 36%, and pT3b in 28%. After 3 years, there was a 20% actuarial rate of disease progression in men who underwent either RP or radiation therapy. In summary, most men with IDC-P on biopsy/TURP have aggressive tumors, even when the invasive tumor on biopsy is Gleason score 6. As a minority of men may only have Gleason 6 invasive cancer at RP and a favorable prognosis, we recommend that IDC-P on biopsy/TURP be reported separately and not assigned a Gleason score.},
}
@article {pmid26074415,
year = {2015},
author = {Dittmar, L and Mohr, E and Kleist, C and Ehser, S and Demirdizen, H and Sandra-Petrescu, F and Hundemer, M and Opelz, G and Terness, P},
title = {Immunosuppressive properties of mitomycin C-incubated human myeloid blood cells (MIC) in vitro.},
journal = {Human immunology},
volume = {76},
number = {7},
pages = {480-487},
doi = {10.1016/j.humimm.2015.06.008},
pmid = {26074415},
issn = {1879-1166},
mesh = {Apoptosis/drug effects ; Cells, Cultured ; Dendritic Cells/drug effects ; Humans ; Immunosuppressive Agents/*pharmacology ; Mitomycin/*pharmacology ; Monocytes/cytology/drug effects/radiation effects ; Myeloid Cells/*drug effects ; T-Lymphocytes/immunology ; },
abstract = {Previous animal studies showed that donor-derived blood cells treated with mitomycin C (MMC) prolong allograft survival when injected into recipients. This model was effective with whole blood, peripheral blood mononuclear cells (PBMC) (monocytes being the active cell subpopulation) or dendritic cells. In view of a potential clinical application, we study now the immunosuppressive properties of human myeloid cells in vitro. Mature dendritic cells (generated from naïve monocytes) or monocytes treated with mitomycin C do not or only weakly inhibit allogeneic T cells in vitro, whereas cells in an early differentiation state between monocytes and DC exert suppressive activity when treated with MMC. In contrast, DC generated from MMC-treated monocytes show the morphology and phenotype of early immature DC (iDC) and suppress T-cell responses. It is known that untreated monocytes injected into a recipient encounter a cytokine milieu which differentiates them to stimulatory DC. In our in vitro experiment MMC-treated monocytes cultured in a DC-maturing milieu transform themselves into suppressive early iDC. This reproduces a process which takes place when administering MMC-monocytes to a recipient. In conclusion, human MMC-DC or MMC-monocytes are not or only weakly suppressive in vitro. When MMC-monocytes are differentiated to DC the resulting cells become suppressive.},
}
@article {pmid26070712,
year = {2015},
author = {Stoy, C and Sundaram, A and Rios Garcia, M and Wang, X and Seibert, O and Zota, A and Wendler, S and Männle, D and Hinz, U and Sticht, C and Muciek, M and Gretz, N and Rose, AJ and Greiner, V and Hofmann, TG and Bauer, A and Hoheisel, J and Berriel Diaz, M and Gaida, MM and Werner, J and Schafmeier, T and Strobel, O and Herzig, S},
title = {Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy.},
journal = {EMBO molecular medicine},
volume = {7},
number = {8},
pages = {1048-1062},
pmid = {26070712},
issn = {1757-4684},
mesh = {Animals ; Carcinoma, Pancreatic Ductal/*pathology ; Gene Expression Profiling ; Humans ; Mice ; Pancreatic Neoplasms/*pathology ; Survival Analysis ; Transducin/deficiency/*metabolism ; },
abstract = {Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here, we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and invasiveness, correlating with diminished glucose uptake, glycolytic flux, and oncogenic PI3 kinase signaling which in turn could rescue TBL1 deficiency-dependent phenotypes. TBL1 deficiency both prevented and reversed pancreatic tumor growth, mediated transcriptional PI3 kinase inhibition, and increased chemosensitivity of PDAC cells in vivo. As TBL1 mRNA levels were also found to correlate with PI3 kinase levels and overall survival in a cohort of human PDAC patients, TBL1 was identified as a checkpoint in the malignant behavior of pancreatic cancer and its expression may serve as a novel molecular target in the treatment of human PDAC.},
}
@article {pmid26070507,
year = {2015},
author = {Jazayeri, SB and Saadat, S and Ramezani, R and Kaviani, A},
title = {Incidence of primary breast cancer in Iran: Ten-year national cancer registry data report.},
journal = {Cancer epidemiology},
volume = {39},
number = {4},
pages = {519-527},
doi = {10.1016/j.canep.2015.04.016},
pmid = {26070507},
issn = {1877-783X},
mesh = {Adult ; Breast Neoplasms/*epidemiology ; Breast Neoplasms, Male/*epidemiology ; Female ; Humans ; Incidence ; Iran/epidemiology ; Male ; Middle Aged ; Registries ; },
abstract = {Breast cancer is the leading type of malignancy and the leading cause of cancer-related deaths in women worldwide. The screening programs and advances in the treatment of patients with breast cancer have led to an increase in overall survival. Cancer registry systems play an important role in providing basic data for research and the monitoring of the cancer status. In this study, the results of the 10-year national cancer registry (NCR) of Iran in breast cancer are reviewed. NCR database records were searched for primary breast cancer records according to ICD-O-3 coding and the cases were reviewed. A total of 52,068 cases were found with the coding of primary breast cancer. Females constituted 97.1% of the cases. Breast cancer was the leading type of cancer in Iranian females, accounting for 24.6% of all cancers. The mean age of the women with breast cancer was 49.6 years (95%CI 49.5-49.6). Most of the cases (95.7%) were registered as having invasive pathologies (behavior code 3). The most common morphology of primary breast cancer was invasive ductal carcinoma (ICD-O 8500/3) followed by invasive lobular carcinoma (ICD-O 8520/3) with relative frequencies of 77.8% and 5.2%, respectively. The average annual crude incidence of primary breast cancer in females was 22.6 (95%CI 22.1-23.1) per 100,000 females, with an age-standardized rate (ASR) of 27.4 (95%CI 22.5-35.9). There were no data on survival, staging or immunohistochemical marker(s) of the breast-cancer-registered cases. The incidence of breast cancer in Iran is lower than in low-middle-income neighboring countries. The NCR data registry of breast cancer is not accurate in monitoring the effect of screening programs or determining the current status of breast cancer in Iran. Screening programs of breast cancer in Iran have failed to enhance the detection of the patients with in situ lesion detection. A quality breast cancer registry and a screening program for breast cancer are both needed.},
}
@article {pmid26039396,
year = {2014},
author = {Silva, FX and Katz, L and Souza, AS and Amorim, MM},
title = {Mammography in asymptomatic women aged 40-49 years.},
journal = {Revista de saude publica},
volume = {48},
number = {6},
pages = {931-939},
pmid = {26039396},
issn = {1518-8787},
mesh = {Adult ; Biopsy ; Brazil ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Cross-Sectional Studies ; Early Detection of Cancer ; Female ; Humans ; Mammography/*statistics &amp; numerical data ; Mass Screening/*methods ; Middle Aged ; Risk Factors ; },
abstract = {OBJECTIVE To assess findings of mammography of and interventions resulting from breast cancer screening in women aged 40-49 years with no increased risk (typical risk) of breast cancer. METHODS This cross-sectional study evaluated women aged 40-49 years who underwent mammography screening in a mastology reference center in Recife, PE, Northeastern Brazil, between January 2010 and October 2011. Women with breast-related complaints, positive findings in the physical examination, or high risk of breast cancer were excluded. RESULTS The 1,000 mammograms performed were classified into the following Breast Imaging-Reporting and Data System (BI-RADS) categories BI-RADS 0, 232; BI-RADS 1, 294; BI-RADS 2, 294; BI-RADS 3, 16; BI-RADS 4A, 2; BI-RADS 5, 1. There was one case of grade II invasive ductal carcinoma and various interventions, including 469 ultrasound scans, 53 referrals to mastologists, 11 cytological examinations, and 8 biopsies. CONCLUSIONS Mammography screening in women aged 40-49 years with typical risk of breast cancer led to the performance of other interventions. However, it also resulted in increased costs without demonstrable efficacy in decreasing mortality.},
}
@article {pmid26033922,
year = {2015},
author = {Bochicchio, GV and Hipszer, BR and Magee, MF and Bergenstal, RM and Furnary, AP and Gulino, AM and Higgins, MJ and Simpson, PC and Joseph, JI},
title = {Multicenter Observational Study of the First-Generation Intravenous Blood Glucose Monitoring System in Hospitalized Patients.},
journal = {Journal of diabetes science and technology},
volume = {9},
number = {4},
pages = {739-750},
pmid = {26033922},
issn = {1932-2968},
mesh = {Adult ; Aged ; Automation ; Blood Glucose/*analysis ; Calibration ; Catheterization ; Equipment Design ; Female ; Hospitalization ; Humans ; Infusion Pumps, Implantable ; Infusions, Intravenous/instrumentation/methods ; *Insulin Infusion Systems ; Male ; Middle Aged ; Monitoring, Physiologic/*instrumentation/*methods ; Patient Safety ; Prospective Studies ; Reproducibility of Results ; United States ; },
abstract = {BACKGROUND: Current methods of blood glucose (BG) monitoring and insulin delivery are labor intensive and commonly fail to achieve the desired level of BG control. There is great clinical need in the hospital for a user-friendly bedside device that can automatically monitor the concentration of BG safely, accurately, frequently, and reliably.<br><br>METHODS: A 100-patient observation study was conducted at 6 US hospitals to evaluate the first generation of the Intravenous Blood Glucose (IVBG) System (Edwards Lifesciences LLC &amp; Dexcom Inc). Device safety, accuracy, and reliability were assessed. A research nurse sampled blood from a vascular catheter every 4 hours for &#x2264; 72 hours and BG concentration was measured using the YSI 2300 STAT Plus Analyzer (YSI Life Sciences). The IVBG measurements were compared to YSI measurements to calculate point accuracy.<br><br>RESULTS: The IVBG systems logged more than 5500 hours of operation in 100 critical care patients without causing infection or inflammation of a vein. A total of 44135 IVBG measurements were performed in 100 patients with 30231 measurements from the subset of 75 patients used for accuracy analysis. In all, 996 IVBG measurements were time-matched with reference YSI measurements. These pairs had a mean absolute difference (MAD) of 11.61 mg/dl, a mean absolute relative difference (MARD) of 8.23%, 93% met 15/20% accuracy defined by International Organization for Standardization 15197:2003 standard, and 93.2% were in zone A of the Clarke error grid. The IVBG sensors were exposed to more than 200 different medications with no observable effect on accuracy.<br><br>CONCLUSIONS: The IVBG system is an automated and user-friendly glucose monitoring system that provides accurate and frequent BG measurements with great potential to improve the safety and efficacy of insulin therapy and BG control in the hospital, potentially leading to improved clinical outcomes.},
}
@article {pmid26026464,
year = {2015},
author = {Di Rosa, M and Tibullo, D and Cambria, D and Distefano, G and Saccone, S and Di Raimondo, F and Malaguarnera, L},
title = {Chitotriosidase Expression during Monocyte-Derived Dendritic Cells Differentiation and Maturation.},
journal = {Inflammation},
volume = {38},
number = {6},
pages = {2082-2091},
pmid = {26026464},
issn = {1573-2576},
mesh = {*Cell Differentiation ; Cells, Cultured ; Cytoplasm/enzymology ; Dendritic Cells/*enzymology/immunology ; Gene Expression Regulation, Enzymologic ; Hexosaminidases/genetics/*metabolism ; Humans ; Monocytes/*enzymology/immunology ; Phenotype ; RNA, Messenger/metabolism ; Signal Transduction ; Time Factors ; },
abstract = {The chitotriosidase (CHIT-1) is a glycosyl hydrolase (GH), which has been found highly expressed in activated macrophages and in different monocyte-derived cell lines such as Kupffer cells and osteoclasts, as well is differently produced in diverse stages of macrophage polarization (M1 and M2). Recent finding suggests that CHIT-1 plays a crucial role in innate and acquired immunity. Dendritic cells (DCs) are a complex group of cells that play a critical role in immune response. The aim of this study was to investigate the presence of CHIT-1 during the differentiation and maturation of DCs. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs). Our results showed, for the first time, that CHIT-1 is expressed during the process of differentiation and maturation of DCs in a time-dependent manner. We found that CHIT1 is evenly distributed in cytoplasm of both the iDCs and mDCs. Additionally, a significantly increased expression of CHIT1 mRNA and protein was observed in mature DCs. These results suggest that CHIT-1 play an important role in the DCs immunoresponse.},
}
@article {pmid26024935,
year = {2015},
author = {Hoefgen, HR and Merritt, DF},
title = {Invasive Ductal Carcinoma in a 46,XY Partial Androgen Insensitivity Syndrome Patient on Hormone Therapy.},
journal = {Journal of pediatric and adolescent gynecology},
volume = {28},
number = {4},
pages = {e95-7},
doi = {10.1016/j.jpag.2014.08.005},
pmid = {26024935},
issn = {1873-4332},
mesh = {Androgen-Insensitivity Syndrome/blood/*diagnosis/etiology ; Breast Neoplasms/blood/*complications/drug therapy ; Carcinoma, Ductal/blood/*complications/drug therapy ; Female ; Follow-Up Studies ; Hormone Replacement Therapy/*adverse effects ; Humans ; Infant, Newborn ; Male ; },
abstract = {BACKGROUND: The hormonal management of patients with androgen insensitivity can be challenging.<br><br>CASE: An illustrative case is presented of a newborn with ambiguous genitalia who was raised female. She was diagnosed as 46,XY Disorder of Sexual Development with partial androgen insensitivity. To induce puberty, conjugated equine estrogens were administered beginning at age 12. At age 13, she instead began taking combined oral contraceptives for maternal concerns about height and continued taking them for social reasons. Invasive ductal carcinoma was diagnosed at age 27, and the patient was treated with chemotherapy, radiation therapy, bilateral mastectomies, and endocrine therapy.<br><br>SUMMARY AND CONCLUSION: The current literature is reviewed, and hormonal management and other risks for breast cancer are discussed.},
}
@article {pmid26017877,
year = {2015},
author = {Fulga, V and Rudico, L and Balica, AR and Cimpean, AM and Saptefrati, L and Raica, M},
title = {Invasive ductal carcinoma of no special type and its corresponding lymph node metastasis: do they have the same immunophenotypic profile?.},
journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists},
volume = {66},
number = {1},
pages = {30-37},
doi = {10.5114/pjp.2015.51150},
pmid = {26017877},
issn = {1233-9687},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*chemistry/classification/*pathology ; Carcinoma, Ductal, Breast/*chemistry/classification/*secondary ; Cell Differentiation ; Female ; Humans ; Immunohistochemistry ; *Immunophenotyping ; Lymph Nodes/*chemistry/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Phenotype ; Retrospective Studies ; },
abstract = {In the present study we compared the immunophenotypic subtypes of breast ductal invasive carcinomas with their ipsilateral, axillary lymph node metastasis. The ER (estrogen receptor), PR (progesterone receptor), Her2 (human epidermal growth factor receptor 2), and CK5 (cytokeratin 5) status and the proliferation marker Ki-67 were determined by immunohistochemistry on specimens from 43 women. All selected cases were diagnosed as invasive breast carcinomas, of no special type (NST), G2 grade of differentiation. The most frequently encountered subtype at both sites was luminal B. We determined that tumor profile evaluated by surrogate markers is not stable during the metastatic process. The total rate of shifted cases was 23.26% (10 cases), and the highest rate of shifting (6.98%) was encountered from luminal B/Ki-67 to luminal A subtype. In five cases, the subtype shifted to a poorer one according to prognosis. These data support the hypothesis that breast cancer is a heterogeneous disease, with substantial variability of cellular components within each category, a statement applicable to invasive breast carcinomas of NST type too. The receptor profile of this carcinoma, indicated by surrogate markers, is not stable throughout the metastatic process.},
}
@article {pmid26004371,
year = {2015},
author = {Chung, YR and Kim, H and Park, SY and Park, IA and Jang, JJ and Choe, JY and Jung, YY and Im, SA and Moon, HG and Lee, KH and Suh, KJ and Kim, TY and Noh, DY and Han, W and Ryu, HS},
title = {Distinctive role of SIRT1 expression on tumor invasion and metastasis in breast cancer by molecular subtype.},
journal = {Human pathology},
volume = {46},
number = {7},
pages = {1027-1035},
doi = {10.1016/j.humpath.2015.03.015},
pmid = {26004371},
issn = {1532-8392},
mesh = {Adult ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*enzymology/genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/mortality/*secondary ; *Cell Movement ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; MCF-7 Cells ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Predictive Value of Tests ; Proportional Hazards Models ; RNA Interference ; Retrospective Studies ; Sirtuin 1/genetics/*metabolism ; Tissue Array Analysis ; Transfection ; Triple Negative Breast Neoplasms/enzymology/pathology ; },
abstract = {The aim of this study was to evaluate silent mating type information regulation 2 homolog 1 (SIRT1) expression levels by subtype and evaluate its predictive power of axillary lymph node metastasis (LNM) and its association with clinical outcome. A total of 427 patients diagnosed with invasive ductal carcinoma were chosen, immunohistochemical staining for SIRT1 expression was performed on tissue microarrays, and in vitro experiments with each intrinsic subtype of human breast cancer cell line were carried out. Increased expression of SIRT1 in hormone receptor-positive breast cancer and HER2 breast cancer subtype significantly correlated with lower risks of LNM. On the contrary, in triple-negative breast cancer, increased SIRT1 expression was more frequently observed in LNM-positive subgroup than LNM-negative subgroup. Combination of statistically significant, independent parameters including SIRT1 revealed predictive performance for LNM with area under the curve of 0.602, 0.587, and 0.726 for hormone receptor-positive breast cancer, HER2 breast cancer, and triple-negative breast cancer subtype, respectively. Inhibition of SIRT1 expression with small interfering RNA suppressed tumor invasion in MDA-MB-231, specifically. This is the first study to examine SIRT1 expression in breast cancer by subtype, and we have observed the potentially different role of SIRT1 gene having tumor-suppressive or tumor-promoting influence depending on the subtype; thus, different associations between SIRT1 expression and prognosis by subtype should be considered in its target therapy.},
}
@article {pmid25998492,
year = {2015},
author = {Ben-Zvi, S and Soroker, N and Levy, DA},
title = {Parietal lesion effects on cued recall following pair associate learning.},
journal = {Neuropsychologia},
volume = {73},
number = {},
pages = {176-194},
doi = {10.1016/j.neuropsychologia.2015.05.009},
pmid = {25998492},
issn = {1873-3514},
mesh = {Acoustic Stimulation ; Adult ; Aged ; Aged, 80 and over ; Association Learning/*physiology ; Auditory Perception/physiology ; Brain Mapping ; Cues ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Mental Recall/*physiology ; Middle Aged ; Neuropsychological Tests ; Parietal Lobe/pathology/physiology/*physiopathology ; Photic Stimulation ; Stroke/pathology/*physiopathology ; Tomography, X-Ray Computed ; Visual Perception/physiology ; Young Adult ; },
abstract = {We investigated the involvement of the posterior parietal cortex in episodic memory in a lesion-effects study of cued recall following pair-associate learning. Groups of patients who had experienced first-incident stroke, generally in middle cerebral artery territory, and exhibited damage that included lateral posterior parietal regions, were tested within an early post-stroke time window. In three experiments, patients and matched healthy comparison groups executed repeated study and cued recall test blocks of pairs of words (Experiment 1), pairs of object pictures (Experiment 2), or pairs of object pictures and environmental sounds (Experiment 3). Patients' brain CT scans were subjected to quantitative analysis of lesion volumes. Behavioral and lesion data were used to compute correlations between area lesion extent and memory deficits, and to conduct voxel-based lesion-symptom mapping. These analyses implicated lateral ventral parietal cortex, especially the angular gyrus, in cued recall deficits, most pronouncedly in the cross-modal picture-sound pairs task, though significant parietal lesion effects were also found in the unimodal word pairs and picture pairs tasks. In contrast to an earlier study in which comparable parietal lesions did not cause deficits in item recognition, these results indicate that lateral posterior parietal areas make a substantive contribution to demanding forms of recollective retrieval as represented by cued recall, especially for complex associative representations.},
}
@article {pmid25981591,
year = {2015},
author = {Lajus, TB and Sales, RM},
title = {CDH1 germ-line missense mutation identified by multigene sequencing in a family with no history of diffuse gastric cancer.},
journal = {Gene},
volume = {568},
number = {2},
pages = {215-219},
doi = {10.1016/j.gene.2015.05.035},
pmid = {25981591},
issn = {1879-0038},
mesh = {Adult ; Aged ; Antigens, CD ; Breast Neoplasms/*genetics ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics ; DNA Mutational Analysis ; Female ; Genetic Testing ; Germ-Line Mutation ; Humans ; Male ; Mutation, Missense ; Stomach Neoplasms/*genetics ; },
abstract = {Germ-line mutation in CDH1 gene is associated with high risk for Hereditary Diffuse Gastric Cancer (HDGC) and Infiltrative Lobular Carcinoma (ILC). Although somatic CDH1 mutations were also detected in ILC with a frequency ranging from 10 to 56%, CDH1 alterations in more frequent infiltrative ductal carcinoma (IDC) appear to be rare, and no association with germ-line CDH1 mutation and IDC has been established. Here we report the case of a woman diagnosed with IDC at 39years of age, presenting extensive familial history of cancer at multiple sites with early-age onset and with no case of HDGC. Deep sequencing have revealed CDH1 missense mutation c.1849G>A (p.Ala617Thr) in heterozygous and four BRCA2 single nucleotide polymorphism in homozygosis. In this family, the mutation c.1849G>A in the CDH1 gene is not related to HDGC nor ILC. Therefore, here we highlight that multigene analysis is important to detect germ-line mutations and genetic variants in patients with cancers at multiple sites in the family, even if inconclusive genetic counseling can be offered, since hereafter, medical awareness will be held.},
}
@article {pmid25980321,
year = {2016},
author = {Truin, W and Vugts, G and Roumen, RM and Maaskant-Braat, AJ and Nieuwenhuijzen, GA and van der Heiden-van der Loo, M and Tjan-Heijnen, VC and Voogd, AC},
title = {Differences in Response and Surgical Management with Neoadjuvant Chemotherapy in Invasive Lobular Versus Ductal Breast Cancer.},
journal = {Annals of surgical oncology},
volume = {23},
number = {1},
pages = {51-57},
pmid = {25980321},
issn = {1534-4681},
mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/pathology/*surgery ; Carcinoma, Ductal, Breast/drug therapy/metabolism/secondary/*surgery ; Carcinoma, Lobular/drug therapy/metabolism/secondary/*surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {BACKGROUND: This study was conducted to determine the impact of neoadjuvant chemotherapy (NAC) on the likelihood of breast-conserving surgery (BCS) performed for patients with invasive lobular breast carcinoma (ILC) and invasive ductal carcinoma (IDC).<br><br>METHODS: Female patients with a diagnosis of ILC or IDC in The Netherlands between July 2008 and December 2012 were identified through the population-based Netherlands Cancer Registry.<br><br>RESULTS: A total of 466 ILC patients received NAC compared with 3622 IDC patients. Downstaging by NAC was seen in 49.7&#xa0;% of the patients with ILC and in 69.6&#xa0;% of the patients with IDC, and a pathologic complete response (pCR) was observed in 4.9 and 20.2&#xa0;% of these patients, respectively (P&#xa0;<&#xa0;0.0001). Breast-conserving surgery was performed for 24.4&#xa0;% of the patients with ILC receiving NAC versus 39.4&#xa0;% of the patients with IDC. In the ILC group, 8.2&#xa0;% of the patients needed surgical reinterventions after BCS due to tumor-positive resection margins compared with 3.4&#xa0;% of the patients with IDC (P&#xa0;<&#xa0;0.0001). Lobular histology was independently associated with a higher mastectomy rate (odds ratio 1.91; 95&#xa0;% confidence interval 1.49-2.44). Among the patients with clinical T2 and T3 disease, BCS was achieved more often when NAC was administered in ILC as well as IDC.<br><br>CONCLUSION: The patients with ILC receiving NAC were less likely to experience a pCR and less likely to undergo BCS than the patients with IDC. With regard to BCS, the impact of NAC for ILC patients was lower than for patients receiving surgery without NAC. However, despite the high number to treating in order to achieve BCS, a small subset of ILC patients, especially cT2 and cT3 patients, still may benefit from NAC.},
}
@article {pmid25971426,
year = {2015},
author = {Dashevsky, BZ and Goldman, DA and Parsons, M and Gönen, M and Corben, AD and Jochelson, MS and Hudis, CA and Morrow, M and Ulaner, GA},
title = {Appearance of untreated bone metastases from breast cancer on FDG PET/CT: importance of histologic subtype.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {42},
number = {11},
pages = {1666-1673},
pmid = {25971426},
issn = {1619-7089},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*diagnosis/diagnostic imaging/*secondary ; Breast Neoplasms/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; *Multimodal Imaging ; Neoplasm Grading ; *Positron-Emission Tomography ; Retrospective Studies ; *Tomography, X-Ray Computed ; },
abstract = {PURPOSE: To determine if the histology of a breast malignancy influences the appearance of untreated osseous metastases on FDG PET/CT.<br><br>METHODS: This retrospective study was performed under IRB waiver. Our Hospital Information System was screened for breast cancer patients who presented with osseous metastases, who underwent FDG PET/CT prior to systemic therapy or radiotherapy from 2009 to 2012. Patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or mixed ductal/lobular (MDL) histology were included. Patients with a history of other malignancies were excluded. PET/CT was evaluated, blinded to histology, to classify osseous metastases on a per-patient basis as sclerotic, lytic, mixed lytic/sclerotic, or occult on CT, and to record SUVmax for osseous metastases on PET.<br><br>RESULTS: Following screening, 95 patients who met the inclusion criteria (74 IDC, 13 ILC, and 8 MDL) were included. ILC osseous metastases were more commonly sclerotic and demonstrated lower SUVmax than IDC metastases. In all IDC and MDL patients with osseous metastases, at least one was FDG-avid. For ILC, all patients with lytic or mixed osseous metastases demonstrated at least one FDG-avid metastasis; however, in only three of seven patients were sclerotic osseous metastases apparent on FDG PET.<br><br>CONCLUSION: The histologic subtype of breast cancer affects the appearance of untreated osseous metastases on FDG PET/CT. In particular, non-FDG-avid sclerotic osseous metastases were more common in patients with ILC than in patients with IDC. Breast cancer histology should be considered when interpreting non-FDG-avid sclerotic osseous lesions on PET/CT, which may be more suspicious for metastases (rather than benign lesions) in patients with ILC.},
}
@article {pmid25955408,
year = {2015},
author = {Morikawa, A and Takeuchi, T and Kito, Y and Saigo, C and Sakuratani, T and Futamura, M and Yoshida, K},
title = {Expression of beclin-1 in the microenvironment of invasive ductal carcinoma of the breast: correlation with prognosis and the cancer-stromal interaction.},
journal = {PloS one},
volume = {10},
number = {5},
pages = {e0125762},
pmid = {25955408},
issn = {1932-6203},
mesh = {Apoptosis Regulatory Proteins/antagonists &amp; inhibitors/genetics/*metabolism ; Beclin-1 ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cells, Cultured ; Coculture Techniques ; Cytokines/metabolism ; Discoidin Domain Receptors ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Interleukin-10 Receptor beta Subunit/metabolism ; Interleukin-1beta/genetics/metabolism ; Lymphatic Metastasis ; MCF-7 Cells ; Membrane Proteins/antagonists &amp; inhibitors/genetics/*metabolism ; Mesenchymal Stem Cells/cytology/metabolism ; Neoplasm Recurrence, Local ; Prognosis ; RNA Interference ; RNA, Small Interfering/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Receptors, Cytokine/metabolism ; Receptors, Mitogen/genetics/metabolism ; Tumor Microenvironment ; },
abstract = {We examined the pathobiological properties of beclin-1, which is a key regulator of autophagosome formation in invasive ductal carcinoma of the breast, with a particular focus on the cancer microenvironment. Immunohistochemistry demonstrated that cancer cells and stromal mesenchymal cells expressed beclin-1 in 68 and 38 of 115 invasive ductal cancers, respectively. Expression of beclin-1 in cancer or stromal cells alone did not correlate with patient prognosis. In contrast, loss of beclin-1 in cancer cells and overexpression in stromal mesenchymal cells was associated with local cancer recurrence, postoperative lymph node metastasis, and a poor disease-free survival rate. A comprehensive gene expression analysis was performed on a co-culture of breast cancer cells and mesenchymal stromal cells, that latter of which either expressed beclin-1 or was depleted of beclin-1 by siRNA. Notably, siRNA-mediated downregulation of beclin-1 in mesenchymal cells co-cultured with breast cancer cells decreased the levels of various pro-inflammatory cytokines, their receptors, and collagen receptors. Quantitative reverse transcription polymerase chain reaction analysis confirmed that reduction of stromal beclin-1 expression decreased the expression of IL-1β and collagen receptor discoidin domain receptor 2 (DDR2). Microenvironmental IL-1β is believed to play an important role in tumor invasion. Recent work has also indicated that overexpression of DDR2 contributes to breast cancer invasion and lymph node metastasis. Taken together, these findings indicate beclin-1 expression in the stroma might be important for shaping the breast cancer microenvironment and thus could be a potent molecular target in patients with invasive ductal carcinoma of the breast.},
}
@article {pmid25955205,
year = {2015},
author = {Gutierrez, DA and Muralidhar, S and Feyerabend, TB and Herzig, S and Rodewald, HR},
title = {Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from Obesity and Insulin Resistance.},
journal = {Cell metabolism},
volume = {21},
number = {5},
pages = {678-691},
doi = {10.1016/j.cmet.2015.04.013},
pmid = {25955205},
issn = {1932-7420},
mesh = {Animals ; Gene Deletion ; Hematopoiesis ; *Insulin Resistance ; Male ; Mast Cells/immunology/metabolism/*pathology ; Metabolic Syndrome/genetics ; Mice ; Mice, Inbred C57BL ; Obesity/*genetics/immunology/pathology ; Stem Cell Factor/*genetics/immunology ; Transcriptome ; },
abstract = {Obesity, insulin resistance, and related pathologies are associated with immune-mediated chronic inflammation. Kit mutant mice are protected from diet-induced obesity and associated co-morbidities, and this phenotype has previously been attributed to their lack of mast cells. We performed a comprehensive metabolic analysis of Kit-dependent Kit(W/Wv) and Kit-independent Cpa3(Cre/+) mast-cell-deficient mouse strains, employing diet-induced or genetic (Lep(Ob/Ob) background) models of obesity. Our results show that mast cell deficiency, in the absence of Kit mutations, plays no role in the regulation of weight gain or insulin resistance. Moreover, we provide evidence that the metabolic phenotype observed in Kit mutant mice, while independent of mast cells, is immune regulated. Our data underscore the value of definitive mast cell deficiency models to conclusively test the involvement of this enigmatic cell in immune-mediated pathologies and identify Kit as a key hematopoietic factor in the pathogenesis of metabolic syndrome.},
}
@article {pmid25953261,
year = {2015},
author = {Jiang, G and Zhang, X and Zhang, Y and Wang, L and Fan, C and Xu, H and Miao, Y and Wang, E},
title = {A novel biomarker C6orf106 promotes the malignant progression of breast cancer.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {36},
number = {10},
pages = {7881-7889},
pmid = {25953261},
issn = {1423-0380},
mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Biomarkers, Tumor/genetics/*metabolism ; Blotting, Western ; Breast/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism/*secondary ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Movement ; *Cell Proliferation ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/antagonists &amp; inhibitors/genetics/*metabolism ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Triple Negative Breast Neoplasms/genetics/metabolism/*pathology ; Tumor Cells, Cultured ; },
abstract = {C6orf106 (chromosome 6 open reading frame 106) is a recently discovered protein encoded by the 6th chromosome. Though many proteins encoded by chromosome 6 are reportedly related to cancer, schizophrenia, autoimmunity and many other diseases, the function of C6orf106 was not well demonstrated so far. As measured by immunohistochemical staining, C6orf106 was positive in normal breast duct myoepithelial cells (92.31 %, 72/78), but negative in normal breast duct glandular epithelial cells (3.85 %, 3/78). In breast ductal carcinoma in situ, C6orf106 showed weakly or moderately positive (77.97 %, 46/59), but it was significantly strongly positive in invasive ductal carcinoma (79.57 %, 148/186). The expression intensity of C6orf106 seemed increased significantly along with the malignancy of breast cancer (p < 0.001). Additionally, C6orf106 expression was significantly correlated with TNM stage (p = 0.001 and p = 0.004) and lymph node metastasis (p = 0.018 and p = 0.025) of the overall and the triple-negative breast cancer, respectively. Consistently, we found that the interference of C6orf106 was able to inhibit cell proliferation and invasion of two triple-negative breast cancer cell lines, MDA-MB-231 and BT-549, accompanied by the decrease of cyclin A2, cyclin B1, c-myc, and N-cadherin and the increase of E-cadherin. Collectively, these results indicate that C6orf106 may promote tumor progression in the invasive breast cancer, particularly in triple-negative breast cancer, and C6orf106 might serve as a novel therapeutic target of breast cancer, especially for triple-negative breast cancer.},
}
@article {pmid25948818,
year = {2015},
author = {Alissafi, T and Hatzioannou, A and Ioannou, M and Sparwasser, T and Grün, JR and Grützkau, A and Verginis, P},
title = {De novo-induced self-antigen-specific Foxp3+ regulatory T cells impair the accumulation of inflammatory dendritic cells in draining lymph nodes.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {194},
number = {12},
pages = {5812-5824},
doi = {10.4049/jimmunol.1500111},
pmid = {25948818},
issn = {1550-6606},
mesh = {Animals ; Autoantigens/*immunology ; Autoimmunity ; Chemotaxis/immunology ; Cluster Analysis ; Dendritic Cells/*immunology ; Disease Models, Animal ; Disease Progression ; Encephalomyelitis, Autoimmune, Experimental/genetics/immunology/metabolism ; Female ; Forkhead Transcription Factors/metabolism ; Gene Expression Profiling ; Immune Tolerance ; Inflammation/genetics/*immunology/metabolism ; Interleukin-10/metabolism ; Lymph Nodes/*immunology ; Lymphocyte Depletion ; Mice ; Mice, Knockout ; Myelin-Oligodendrocyte Glycoprotein/administration &amp; dosage/immunology ; Peptide Fragments/administration &amp; dosage/immunology ; Receptors, CCR7/genetics/metabolism ; Signal Transduction ; T-Cell Antigen Receptor Specificity/immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism ; },
abstract = {Foxp3(+) regulatory T cell (Treg)-based immunotherapy holds promise for autoimmune diseases. However, this effort has been hampered by major caveats, including the low frequency of autoantigen-specific Foxp3(+) Tregs and lack of understanding of their molecular and cellular targets, in an unmanipulated wild-type (WT) immune repertoire. In this study, we demonstrate that infusion of myelin in WT mice results in the de novo induction of myelin-specific Foxp3(+) Tregs in WT mice and amelioration of experimental autoimmune encephalomyelitis. Myelin-specific Foxp3(+) Tregs exerted their effect both by diminishing Ag-bearing inflammatory dendritic cell (iDC) recruitment to lymph nodes and by impairing their function. Transcriptome analysis of ex vivo-isolated Treg-exposed iDCs showed significant enrichment of transcripts involved in functional properties of iDCs, including chemotaxis-related genes. To this end, CCR7 expression by iDCs was significantly downregulated in tolerant mice and this was tightly regulated by the presence of IL-10. Collectively, our data demonstrate a novel model for deciphering the Ag-specific Foxp3(+) Treg-mediated mechanisms of tolerance and delineate iDCs as a Foxp3(+) Treg cellular target in unmanipulated mice.},
}
@article {pmid25940209,
year = {2015},
author = {Di Bonito, M and Cantile, M and Cerrone, M and Liguori, G and Botti, G},
title = {Synchronous Pleomorphic Adenoma and Invasive Ductal Carcinoma in Distinct Breasts.},
journal = {The breast journal},
volume = {21},
number = {4},
pages = {428-430},
doi = {10.1111/tbj.12426},
pmid = {25940209},
issn = {1524-4741},
mesh = {Adenoma, Pleomorphic/*pathology/surgery ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasms, Multiple Primary/*pathology ; Parotid Neoplasms/*pathology ; },
}
@article {pmid25931358,
year = {2015},
author = {Dopheide, JF and Zeller, GC and Kuhlmann, M and Girndt, M and Sester, M and Sester, U},
title = {Differentiation of Monocyte Derived Dendritic Cells in End Stage Renal Disease is Skewed Towards Accelerated Maturation.},
journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University},
volume = {24},
number = {2},
pages = {257-266},
doi = {10.17219/acem/40463},
pmid = {25931358},
issn = {1899-5276},
mesh = {Age Factors ; Aged ; Biomarkers/metabolism ; Case-Control Studies ; *Cell Differentiation/drug effects ; Cells, Cultured ; Dendritic Cells/drug effects/*immunology/metabolism ; Female ; GPI-Linked Proteins/immunology/metabolism ; Humans ; Kidney Failure, Chronic/*immunology/therapy ; Lipopolysaccharide Receptors/immunology/metabolism ; Lipopolysaccharides/pharmacology ; Male ; Middle Aged ; Monocytes/drug effects/*immunology/metabolism ; Phenotype ; Receptors, IgG/immunology/metabolism ; Renal Dialysis ; Time Factors ; },
abstract = {BACKGROUND: Dendritic cells (DC) play an important role in the induction of immune responses. Patients with end stage renal disease (ESRD) suffer from chronic inflammation, leading to a secondary, uremic immunodeficiency associated with alterations in monocyte subpopulations with increased proinflammatory capacities.<br><br>OBJECTIVES: The aim of this study was to examine, under isolated conditions, whether alterations in monocyte subpopulations may affect in vitro maturation of dendritic cells (DC) in patients with ESRD, thus allowing us to draw conclusions for the situation in vivo.<br><br>MATERIAL AND METHODS: Monocytes from 30 patients undergoing hemodialysis (HD) and 15 healthy volunteers were enriched from peripheral blood leukocytes, differentiated into immature DC (iDC) in medium containing IL-4 and GM-CSF, and were induced with LPS to differentiate into mature DC (mDC). Monocyte subpopulations and DC maturation stages were phenotypically characterized using flow-cytometry.<br><br>RESULTS: Although phenotypically indistinguishable, the number of both iDC and mDC that were generated from uremic monocytes was significantly higher compared to those from healthy controls (p=0.02 and p=0.03, respectively). This was associated with an increased number of CD14+ CD16+ monocytes (p=0.02) and by a higher maturation efficiency of mDC in patients (p=0.04).<br><br>CONCLUSIONS: A high percentage of CD14+ CD16+ monocytes in patients with ESRD is associated with an increased propensity to differentiate into DC. This indicates that chronic inflammation may substantiate the biased consistence of monocyte subpopulations leading to profound alteration in DC generation and maturation in ESRD.},
}
@article {pmid25928089,
year = {2015},
author = {Katanov, C and Lerrer, S and Liubomirski, Y and Leider-Trejo, L and Meshel, T and Bar, J and Feniger-Barish, R and Kamer, I and Soria-Artzi, G and Kahani, H and Banerjee, D and Ben-Baruch, A},
title = {Regulation of the inflammatory profile of stromal cells in human breast cancer: prominent roles for TNF-α and the NF-κB pathway.},
journal = {Stem cell research &amp; therapy},
volume = {6},
number = {1},
pages = {87},
pmid = {25928089},
issn = {1757-6512},
mesh = {Blotting, Western ; Bone Marrow Cells/cytology ; Breast Neoplasms/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/drug effects ; Chemokine CCL2/analysis ; Chemokine CCL5/analysis ; Culture Media, Conditioned/pharmacology ; Female ; Fibroblasts/cytology/*metabolism ; Humans ; Interleukin-1beta/pharmacology ; Interleukin-8/analysis ; JNK Mitogen-Activated Protein Kinases/antagonists &amp; inhibitors/genetics/metabolism ; MCF-7 Cells ; Mesenchymal Stem Cells/cytology/*drug effects/metabolism ; NF-kappa B/*metabolism ; RNA Interference ; Signal Transduction ; Transcription Factor RelA/antagonists &amp; inhibitors/genetics/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism/*pharmacology ; Up-Regulation/drug effects ; },
abstract = {INTRODUCTION: Breast cancer progression is promoted by stromal cells that populate the tumors, including cancer-associated fibroblasts (CAFs) and mesenchymal stem/stromal cells (MSCs). The activities of CAFs and MSCs in breast cancer are integrated within an intimate inflammatory tumor microenvironment (TME) that includes high levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Here, we identified the impact of TNF-α and IL-1β on the inflammatory phenotype of CAFs and MSCs by determining the expression of inflammatory chemokines that are well-characterized as pro-tumorigenic in breast cancer: CCL2 (MCP-1), CXCL8 (IL-8) and CCL5 (RANTES).<br><br>METHODS: Chemokine expression was determined in breast cancer patient-derived CAFs by ELISA and in patient biopsies by immunohistochemistry. Chemokine levels were determined by ELISA in (1) human bone marrow-derived MSCs stimulated by tumor conditioned media (Tumor CM) of breast tumor cells (MDA-MB-231 and MCF-7) at the end of MSC-to-CAF-conversion process; (2) Tumor CM-derived CAFs, patient CAFs and MSCs stimulated by TNF-&#x3b1; (and IL-1&#x3b2;). The roles of AP-1 and NF-&#x3ba;B in chemokine secretion were analyzed by Western blotting and by siRNAs to c-Jun and p65, respectively. Migration of monocytic cells was determined in modified Boyden chambers.<br><br>RESULTS: TNF-&#x3b1; (and IL-1&#x3b2;) induced the release of CCL2, CXCL8 and CCL5 by MSCs and CAFs generated by prolonged stimulation of MSCs with Tumor CM of MDA-MB-231 and MCF-7 cells. Patient-derived CAFs expressed CCL2 and CXCL8, and secreted CCL5 following TNF-&#x3b1; (and IL-1&#x3b2;) stimulation. CCL2 was expressed in CAFs residing in proximity to breast tumor cells in biopsies of patients diagnosed with invasive ductal carcinoma. CCL2 release by TNF-&#x3b1;-stimulated MSCs was mediated by TNF-RI and TNF-RII, through the NF-&#x3ba;B but not via the AP-1 pathway. Exposure of MSCs to TNF-&#x3b1; led to potent CCL2-induced migration of monocytic cells, a process that may yield pro-cancerous myeloid infiltrates in breast tumors.<br><br>CONCLUSIONS: Our novel results emphasize the important roles of inflammation-stroma interactions in breast cancer, and suggest that NF-&#x3ba;B may be a potential target for inhibition in tumor-adjacent stromal cells, enabling improved tumor control in inflammation-driven malignancies.},
}
@article {pmid25927974,
year = {2015},
author = {Shenker, NS and Flower, KJ and Wilhelm-Benartzi, CS and Dai, W and Bell, E and Gore, E and El Bahrawy, M and Weaver, G and Brown, R and Flanagan, JM},
title = {Transcriptional implications of intragenic DNA methylation in the oestrogen receptor alpha gene in breast cancer cells and tissues.},
journal = {BMC cancer},
volume = {15},
number = {},
pages = {337},
pmid = {25927974},
issn = {1471-2407},
support = {13086/CRUK_/Cancer Research UK/United Kingdom ; 15954/CRUK_/Cancer Research UK/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; A13086/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Cell Line, Tumor ; DNA Methylation ; Epigenesis, Genetic ; Estrogen Receptor alpha/*genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Glands, Human/metabolism ; Milk, Human/cytology ; *Promoter Regions, Genetic ; Sequence Analysis, DNA ; Transcription, Genetic ; },
abstract = {BACKGROUND: DNA methylation variability regions (MVRs) across the oestrogen receptor alpha (ESR1) gene have been identified in peripheral blood cells from breast cancer patients and healthy individuals. In contrast to promoter methylation, gene body methylation may be important in maintaining active transcription. This study aimed to assess MVRs in ESR1 in breast cancer cell lines, tumour biopsies and exfoliated epithelial cells from expressed breast milk (EBM), to determine their significance for ESR1 transcription.<br><br>METHODS: DNA methylation levels in eight MVRs across ESR1 were assessed by pyrosequencing bisulphite-converted DNA from three oestrogen receptor (ER)-positive and three ER-negative breast cancer cell lines. DNA methylation and expression were assessed following treatment with DAC (1 &#x3bc;M), or DMSO (controls). ESR1 methylation levels were also assayed in DNA from 155 invasive ductal carcinoma biopsies provided by the Breast Cancer Campaign Tissue Bank, and validated with DNA methylation profiles from the TCGA breast tumours (n = 356 ER-pos, n = 109 ER-neg). DNA methylation was profiled in exfoliated breast epithelial cells from EBM using the Illumina 450 K (n = 36) and pyrosequencing in a further 53 donor samples. ESR1 mRNA levels were measured by qRT-PCR.<br><br>RESULTS: We show that ER-positive cell lines had unmethylated ESR1 promoter regions and highly methylated intragenic regions (median, 80.45%) while ER-negative cells had methylated promoters and lower intragenic methylation levels (median, 38.62%). DAC treatment increased ESR1 expression in ER-negative cells, but significantly reduced methylation and expression of ESR1 in ER-positive cells. The ESR1 promoter was unmethylated in breast tumour biopsies with high levels of intragenic methylation, independent of ER status. However, ESR1 methylation in the strongly ER-positive EBM DNA samples were very similar to ER-positive tumour cell lines.<br><br>CONCLUSION: DAC treatment inhibited ESR1 transcription in cells with an unmethylated ESR1 promoter and reduced intragenic DNA methylation. Intragenic methylation levels correlated with ESR1 expression in homogenous cell populations (cell lines and exfoliated primary breast epithelial cells), but not in heterogeneous tumour biopsies, highlighting the significant differences between the in vivo tumour microenvironment and individual homogenous cell types. These findings emphasise the need for care when choosing material for epigenetic research and highlights the presence of aberrant intragenic methylation levels in tumour tissue.},
}
@article {pmid25921169,
year = {2015},
author = {Sushma, C and Prasad, S and Devi, R and Murthy, S and Rao, Ts and Naidu, C},
title = {High Frequency of Codon 12 but not Codon 13 and 61 K-ras Gene Mutations in Invasive Ductal Carcinoma of Breast in a South Indian Population.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {16},
number = {8},
pages = {3505-3508},
doi = {10.7314/apjcp.2015.16.8.3505},
pmid = {25921169},
issn = {2476-762X},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Codon ; Female ; Genetic Predisposition to Disease ; Humans ; India ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins p21(ras) ; Sequence Analysis, DNA ; White People/*genetics ; ras Proteins/*genetics ; },
abstract = {BACKGROUND: Ras genes are thought to play an important role in human cancer since they have been found to be activated frequently in several types of tumors including breast cancer, where the overall incidence of K-RAS oncogene activation is 0-10%. Evaluation of K-RAS gene not only for mutational frequency but also for mutation types in this downstream signaling gene pathway is necessary to determine the mechanisms of action. The present study was conducted to test the hypothesis that K-RAS activation is involved in breast cancer risk of south Indian population.<br><br>MATERIALS AND METHODS: A total of 70 paired pathologically confirmed tumor and non-tumor tissues from the same breast cancer patients were analysed for most common K-RAS mutations of codon 12,13 and 61 by polymerase chain reaction followed by restriction digestion and direct nucleotide sequencing method.<br><br>RESULTS: We found that a high rate of homozygous and heterozygous mutations of codon 12, but not codon 13 and 61, may influence the invasive ductal carcinoma of breast risk in this study.<br><br>CONCLUSIONS: Our study indicated that only codon 12 may be involved in initiating breast carcinogenesis in India.},
}
@article {pmid25916980,
year = {2015},
author = {Kamrava, M and Kuske, RR and Anderson, B and Chen, P and Hayes, J and Quiet, C and Wang, PC and Veruttipong, D and Snyder, M and Jeffrey Demanes, D},
title = {Outcomes of Breast Cancer Patients Treated with Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.},
journal = {Annals of surgical oncology},
volume = {22 Suppl 3},
number = {},
pages = {S404-11},
doi = {10.1245/s10434-015-4563-7},
pmid = {25916980},
issn = {1534-4681},
mesh = {Adult ; *Brachytherapy ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/pathology/*radiotherapy ; Carcinoma, Intraductal, Noninfiltrating/pathology/*radiotherapy ; Carcinoma, Lobular/pathology/*radiotherapy ; Catheterization/*methods ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Neoplasm Staging ; Prognosis ; Radiotherapy Dosage ; *Registries ; Retrospective Studies ; Survival Rate ; },
abstract = {PURPOSE: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation with interstitial multicatheter brachytherapy by a cooperative group of institutions.<br><br>METHODS: From 1992 to 2013, a total of 1356 patients were treated with breast-conserving surgery and adjuvant accelerated partial breast irradiation using interstitial multicatheter brachytherapy. A total of 1131 patients had >1 year of data available to assess oncologic and cosmesis outcomes. Median age was 59 years old (range 22-90 years). Histologies treated included 1005 (73 %) invasive ductal carcinoma and 240 (18 %) ductal carcinoma-in situ. T stages were 18 % Tis, 75 % T1, and 8 % &#x2265;T2. Nodal status was 73 % N0 and 6 % N1a. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was positive in 83, 70, and 6 %, respectively. Cox multivariate analysis for local control was performed using histology, age, estrogen receptor status, tumor size, grade, margin, and nodal status.<br><br>RESULTS: The mean (SD) follow-up was 6.9 years (4.3). The 10-year actuarial risk (95 % confidence interval) of an ipsilateral breast tumor recurrence was 7.6 % (5.6-10.1). Other 10-year actuarial risks (95 % confidence interval) were regional failure 2.3 % (1.4-3.7), distant metastasis 3.8 % (2.5-5.7), cause-specific survival 96.3 % (94.2-97.6), overall survival 86.5 (83.0-89.3), and new contralateral cancers 4.6 % (3.0-6.9). On multivariate analysis, high grade (hazard ratio 2.81) and positive margin status (hazard ratio 18.42) were the only two significant variables associated with an increased risk of local recurrence. Physician-reported cosmesis was excellent/good in 84 % (98 of 116) of patients with >5 years of follow-up.<br><br>CONCLUSIONS: This is the largest report of outcomes with interstitial breast brachytherapy. This treatment resulted in excellent long-term local control and cosmesis outcomes.},
}
@article {pmid25911756,
year = {2015},
author = {Miki, H and Nakahashi-Oda, C and Sumida, T and Shibuya, A},
title = {Involvement of CD300a Phosphatidylserine Immunoreceptor in Aluminum Salt Adjuvant-Induced Th2 Responses.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {194},
number = {11},
pages = {5069-5076},
doi = {10.4049/jimmunol.1402915},
pmid = {25911756},
issn = {1550-6606},
mesh = {Adjuvants, Immunologic/*pharmacology ; Alum Compounds/*pharmacology ; Animals ; Antibodies, Neutralizing/administration &amp; dosage/immunology ; Apoptosis/immunology ; Asthma/genetics/immunology/therapy ; Bronchoalveolar Lavage Fluid/cytology/immunology ; Dendritic Cells/immunology ; Eosinophils/immunology ; Immunoglobulin E/blood ; Inflammation/immunology ; Interleukin-4/biosynthesis ; Lymphocyte Activation/drug effects/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Ovalbumin/*pharmacology ; Phosphatidylserines/antagonists &amp; inhibitors ; Receptors, Immunologic/biosynthesis/genetics/*immunology ; Respiratory Hypersensitivity/genetics/*immunology/prevention &amp; control ; Th2 Cells/*immunology ; },
abstract = {Aluminum salt (alum) has been widely used for vaccinations as an adjuvant. Alum not only enhances immunogenicity but also induces Th2 cell immune responses. However, the mechanisms of how alum enhances Th2 cell immune responses have been controversial. In an experimental allergic airway inflammation model, in which alum in conjunction with OVA Ag was i.p. injected for immunization, we found that apoptotic cells and inflammatory dendritic cells (iDC) expressing CD300a, an inhibitory immunoreceptor for phosphatidylserine (PS), significantly increased in number in the peritoneal cavity after the immunization. In contrast, apoptotic cells and iDCs were scarcely observed in the peritoneal cavity after injection of OVA alone. In CD300a-deficient mice, eosinophil infiltration in bronchoalveolar lavage fluid, serum IgE levels, and airway hyperreactivity were significantly decreased after immunization with alum plus OVA compared with wild-type mice. In vitro, iDCs purified from CD300a-deficient mice after the immunization induced significantly less IL-4 production from OT-II naive CD4(+) T cells after coculture with OVA Ag. CD300a expressed on iDCs bound PS on apoptotic cells in the peritoneal cavity after injection of OVA plus alum. Blocking CD300a interaction with PS by injection of a neutralizing anti-CD300a Ab resulted in inhibition of the development of allergic airway inflammation. These results suggest that CD300a is involved in alum-induced Th2 skewing.},
}
@article {pmid25909142,
year = {2015},
author = {Popovska, S and Damianova, P and Tomov, S and Dineva, T and Ivanov, I},
title = {[Case of encapsulated solid papillary carcinoma with triple-negative and basal-like phenotype occurred in pregnant woman with review of the literature].},
journal = {Akusherstvo i ginekologiia},
volume = {54},
number = {2},
pages = {50-56},
pmid = {25909142},
issn = {0324-0959},
mesh = {Adult ; BRCA1 Protein/analysis/genetics ; BRCA2 Protein/analysis/genetics ; Breast/*pathology ; Breast Neoplasms/diagnosis/genetics/*pathology ; Carcinoma, Papillary/diagnosis/genetics/*pathology ; Female ; Humans ; Mutation ; Pregnancy ; Pregnancy Complications, Neoplastic/diagnosis/genetics/*pathology ; Tumor Suppressor Protein p53/analysis ; },
abstract = {The term breast cancer in pregnant women is used when the disease has been diagnosed during pregnancy or within first 12 months after delivery. The frequency of this type of breast cancer is about 7% of all cases in reproductive period. We present a case of breast cancer that occurred in pregnant 35 year old woman. We performed histological and immunohistochemical tests of excised tumor formation. We did not find sufficient evidence of both carcinoma in situ and invasive ductal carcinoma. The lesion was consisted with encapsulated/intracystic carcinoma, solid papillary variant with a low degree of differentiation-G3. Young age of patient, receptor status of the tumor the characteristic morphology of hereditary cancer, the presence of inflammatory infiltrates intratumorally, absence of reaction to IHC protein product of the tumor suppressor gene BRCA1 in combination with a positive p53 IHC makes this case suitable for genetic testing of BRCA1/BRCA2 susceptibility genes. The case is interesting because of the rarity of the histological variant, the young age of the patient, the combination with BC and pregnancy and the triple-negative phenotype.},
}
@article {pmid25908223,
year = {2015},
author = {del Molino, F and Gonzalez, I and Saperas, E},
title = {[Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].},
journal = {Gastroenterologia y hepatologia},
volume = {38},
number = {8},
pages = {501-510},
doi = {10.1016/j.gastrohep.2015.02.014},
pmid = {25908223},
issn = {0210-5705},
mesh = {Administration, Oral ; Antithrombins/administration &amp; dosage/*adverse effects/pharmacokinetics/therapeutic use ; Blood Coagulation Factors/therapeutic use ; Blood Transfusion ; *Endoscopy, Digestive System/adverse effects ; Factor Xa Inhibitors/administration &amp; dosage/adverse effects/pharmacokinetics/therapeutic use ; Gastrointestinal Hemorrhage/*chemically induced/drug therapy/etiology/therapy ; Hemostatics/therapeutic use ; Humans ; Plasma Substitutes/therapeutic use ; Practice Guidelines as Topic ; Renal Dialysis ; Thrombophilia/drug therapy ; },
abstract = {New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed.},
}
@article {pmid25900029,
year = {2015},
author = {Zhifu, Y and Mingli, J and Shuang, C and Fan, W and Zhenkun, F and Wangyang, C and Lin, Z and Guangxiao, L and Yashuang, Z and Dianjun, L},
title = {SNP-SNP interactions of immunity related genes involved in the CD28/B7 pathway with susceptibility to invasive ductal carcinoma of the breast.},
journal = {Gene},
volume = {566},
number = {2},
pages = {217-222},
doi = {10.1016/j.gene.2015.04.044},
pmid = {25900029},
issn = {1879-0038},
mesh = {Algorithms ; Breast Neoplasms/genetics/*immunology ; CD28 Antigens/*immunology ; Carcinoma, Ductal, Breast/genetics/*immunology ; Cross-Over Studies ; Female ; *Genetic Predisposition to Disease ; Haplotypes ; Humans ; Immunity/*genetics ; *Polymorphism, Single Nucleotide ; },
abstract = {To explore the interactions among immunity related genes and the risk of breast cancer (BC), 376 invasive ductal carcinoma (IDC) of the breast cases and 366 healthy controls were selected into our study. Twenty single nucleotide polymorphisms (SNPs) of five immunological genes in the CD28/B7 pathway were genotyped. Overall, five SNPs filtered by the Relief F algorithm were rs733618, rs11889031, rs4553808, rs4675374 and rs10754339. The best model of multifactor dimensionality reduction (MDR) contained rs733618 and rs11889031. The high risk genotype combination contributed to increasing risk of breast cancer (odds ratio (OR), 4.36; 95% confidence interval (CI); 3.15-6.02). The information gain (IG) value of these two SNPs was 8.07%, presented the strongest interaction effect. Five significant multiplicative interactions and seven significant combining effects were found among the filtered SNPs. Moreover, the filtered SNPs were still stable in the groups of ER(+), PR(+), CerbB2(-) and lymph node (LN) involvement positive with the best models including rs733618 and rs11889031. The most frequent haplotype was TACC which significantly increased breast cancer risk (OR, 1.80; 95% CI, 1.43-2.25). These results suggested that interactions among cytotoxic T lymphocyte antigen-4 (CTLA4), inducible co-stimulator (ICOS) and B7H4 might play critical roles on the risk of breast cancer.},
}
@article {pmid25899545,
year = {2015},
author = {Amboni, M and Stocchi, F and Abbruzzese, G and Morgante, L and Onofrj, M and Ruggieri, S and Tinazzi, M and Zappia, M and Attar, M and Colombo, D and Simoni, L and Ori, A and Barone, P and Antonini, A and , },
title = {Prevalence and associated features of self-reported freezing of gait in Parkinson disease: The DEEP FOG study.},
journal = {Parkinsonism &amp; related disorders},
volume = {21},
number = {6},
pages = {644-649},
doi = {10.1016/j.parkreldis.2015.03.028},
pmid = {25899545},
issn = {1873-5126},
mesh = {Aged ; Aged, 80 and over ; Antiparkinson Agents/administration &amp; dosage/therapeutic use ; Female ; *Freezing Reaction, Cataleptic ; *Gait ; Gait Disorders, Neurologic/classification/*epidemiology/physiopathology ; Humans ; Levodopa/administration &amp; dosage/therapeutic use ; Male ; Middle Aged ; Parkinson Disease/drug therapy/*physiopathology/psychology ; Prevalence ; Quality of Life/*psychology ; Risk Factors ; Self Report ; Severity of Illness Index ; Surveys and Questionnaires ; },
abstract = {Freezing of Gait (FOG) is a common and disabling symptom in patients with Parkinson disease (PD). The relationship between FOG and dopaminergic medication is complex. The aim of the present study was to estimate the prevalence of self-reported FOG, its associated clinical features, and its relationship with wearing-off in a wide PD population. This is an observational multicenter study of 634 consecutive non-demented PD patients. Patients were identified either as freezers or non-freezers based on item-3 of the Freezing of Gait-Questionnaire. FOG was then classified as on, off and onoff freezing based on its relationship with wearing-off. Patients were assessed with Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale, 8-item Parkinson's disease Questionnaire, Mini-Mental State Examination. Data from 593 patients were analyzed, 325 (54.3%) were freezers of whom 200 (61.6%) experienced FOG only during off state (off-freezers), 6 (1.8%) only during on state and 119 (36.6%) either in on and off states or independently of dopaminergic response-related symptoms (onoff-freezers). Overall, freezers vs non-freezers had longer disease duration, more advanced disease and greater disability. Moreover, freezers more frequently reported wearing-off and experienced worse quality of life. Onoff-freezers vs off-freezers were older, more severely disabled, less likely to experience wearing-off, treated with lower levodopa equivalent daily dose and with poorer cognitive performance. Self-reported FOG is mainly recognizable in advanced PD and is associated with more disability and worse quality of life. Onoff-FOG may represent the result of under-treatment or rather interpretable as a distinct clinical entity.},
}
@article {pmid25893606,
year = {2015},
author = {Zhou, X and Wang, S and Wang, Z and Feng, X and Liu, P and Lv, XB and Li, F and Yu, FX and Sun, Y and Yuan, H and Zhu, H and Xiong, Y and Lei, QY and Guan, KL},
title = {Estrogen regulates Hippo signaling via GPER in breast cancer.},
journal = {The Journal of clinical investigation},
volume = {125},
number = {5},
pages = {2123-2135},
pmid = {25893606},
issn = {1558-8238},
mesh = {Acyltransferases ; Adaptor Proteins, Signal Transducing/physiology ; Animals ; Breast Neoplasms/genetics/metabolism/*physiopathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*physiopathology ; Cell Division ; Cell Movement ; Cell Transformation, Neoplastic ; Estrogens/pharmacology/*physiology ; Female ; GTP-Binding Protein alpha Subunits, Gq-G11/antagonists &amp; inhibitors/genetics/physiology ; Gene Expression Regulation, Neoplastic ; Hippo Signaling Pathway ; Humans ; Intracellular Signaling Peptides and Proteins ; Mice ; Mice, Inbred BALB C ; Neoplasm Proteins/*physiology ; Neoplasms, Hormone-Dependent/genetics/metabolism/*physiopathology ; Phospholipase C beta/physiology ; Phosphoproteins/physiology ; Phosphorylation ; Protein Kinase C/physiology ; Protein Processing, Post-Translational ; Protein Serine-Threonine Kinases/analysis/antagonists &amp; inhibitors/metabolism/*physiology ; RNA Interference ; Receptors, Estrogen/drug effects/*physiology ; Receptors, G-Protein-Coupled/drug effects/*physiology ; Serine-Threonine Kinase 3 ; Signal Transduction/*physiology ; Transcription Factors/physiology ; Transcription, Genetic ; Tumor Suppressor Proteins/analysis/*physiology ; YAP-Signaling Proteins ; rho-Associated Kinases/physiology ; },
abstract = {The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis.},
}
@article {pmid25893590,
year = {2015},
author = {Zhang, H and Li, Y and Moran, MS and Haffty, BG and Yang, Q},
title = {Predictive factors of nipple involvement in breast cancer: a systematic review and meta-analysis.},
journal = {Breast cancer research and treatment},
volume = {151},
number = {2},
pages = {239-249},
doi = {10.1007/s10549-015-3385-4},
pmid = {25893590},
issn = {1573-7217},
mesh = {Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*mortality ; Female ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Nipples/*pathology ; Prognosis ; Risk Factors ; Tumor Burden ; },
abstract = {Nipple-sparing mastectomy (NSM) provides a cosmetic and psychological benefit for patients, but concerns on nipple involvement (NI) of tumor continue to persist. Several studies have reported factors for predicting NI, but the results were inconsistent and uncomprehensive, making patient selection difficult. The aim of the systematic review was to pool the published data to further discern factors associated with NI. A literature review was conducted of PubMed database, following the PRISMA guidelines. Relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effect or fix-effect model. Publication bias and Chi-square test were also calculated. From 1978 to 2014, 27 clinical studies with 7971 patients met the inclusion criteria. Predictive factors suggest higher rates of NI including the following: tumor-to-nipple distance (TND) ≤ 2.5 cm (3.65, 1.42-9.33); positive lymph node status (2.09, 1.71-2.57); stage III or IV disease (2.41, 1.93-3.00); tumor size > 5 cm (2.42, 1.95-3.02); estrogen receptor (ER)-negative status (1.19, 1.01-1.40); progesterone receptor (PR)-negative status (1.52, 1.25-1.84); HER-positive status (1.76, 1.46-2.12); patients with ductal carcinoma in situ (DCIS) compared with invasive ductal carcinoma (1.55, 1.16-2.08). Due to the statistical heterogeneity detected with certain parameters, further investigations to confirm their association with NI will be needed. Patients with one or more risk factors such as centrally located tumors; higher tumor stage; large tumors; ER-negative/PR-negative/HER-positive status and associated DCIS have higher risk of NI. Taking these factors into consideration comprehensively may help with decision-making process for NSM.},
}
@article {pmid25890786,
year = {2015},
author = {Sugiyama, M and Hasebe, T and Shimada, H and Takeuchi, H and Shimizu, K and Shimizu, M and Yasuda, M and Ueda, S and Shigekawa, T and Osaki, A and Saeki, T},
title = {Grading system for blood vessel tumor emboli of invasive ductal carcinoma of the breast.},
journal = {Human pathology},
volume = {46},
number = {6},
pages = {906-916},
doi = {10.1016/j.humpath.2015.03.001},
pmid = {25890786},
issn = {1532-8392},
mesh = {Adult ; Breast/pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/diagnosis ; Neoplasms, Vascular Tissue/*pathology/secondary ; Neoplastic Cells, Circulating/pathology ; Prognosis ; },
abstract = {We previously reported that the number of mitotic and apoptotic figures in tumor cells in blood vessel tumor emboli had the greatest significant power for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. The purpose of the present study was to devise a grading system for blood vessel tumor emboli based on the mitotic and apoptotic figures of tumor cells in blood vessel tumor emboli, enabling accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 263 invasive ductal carcinomas into the following 3 grades according to the numbers of mitotic and apoptotic figures in tumor cells located in blood vessels within 1 high-power field: grade 0, no blood vessel invasion; grade 1, absence of mitotic figures and presence of any number of apoptotic figures, or 1 mitotic figure and 0 to 2 apoptotic figures; and grade 2, 1 mitotic figure and 3 or more apoptotic figures, or 2 or more mitotic figures and 1 or more apoptotic figures. Multivariate analyses with well-known prognostic factors demonstrated that grade 2 blood vessel tumor emboli significantly increased the hazard ratios for tumor recurrence independent of the nodal status, pathological TNM stage, hormone receptor status, or HER2 status. The presently reported grading system for blood vessel tumor emboli is the strongest histologic factor for accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast.},
}
@article {pmid25890610,
year = {2015},
author = {Debi, U and Thulkar, S and Sharma, S and Sharma, MC and Seenu, V and Deo, SV and Agarwal, S and Hari, S},
title = {Role of directional vacuum assisted breast biopsy in previously equivocal biopsies for breast masses suspicious for malignancy.},
journal = {The Malaysian journal of pathology},
volume = {37},
number = {1},
pages = {25-33},
pmid = {25890610},
issn = {0126-8635},
mesh = {Biomarkers, Tumor/analysis ; Biopsy, Large-Core Needle/*methods ; Breast Neoplasms/chemistry/*pathology/secondary/surgery ; Breast Neoplasms, Male/chemistry/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Male ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Reproducibility of Results ; Vacuum ; },
abstract = {UNLABELLED: Among percutaneous biopsy techniques, the vacuum assisted breast biopsy (VAB) obtains large tissue samples to alleviate some of the limitations associated with conventional percutaneous biopsy techniques. We aimed to determine the efficacy of VAB in previous equivocal biopsies using the mammotome device.<br><br>MATERIALS AND METHODS: A prospective non-randomized efficacy study was planned and executed on 43 patients (42 women, 1 man) whose previous FNAC and/or CNB of breast masses yielded inconclusive results or were suspicious for cancer.<br><br>RESULTS: VAB revealed malignancy in 31 (72%) of the 43 patients. Among them, 23 were diagnosed as infiltrative ductal carcinoma (IDC) on VAB, 20 underwent surgery and the final histopathological diagnosis was the same in 19 of them. One patient showed ductal carcinoma-in-situ (DCIS) only in the surgical specimen. Other malignancies included infiltrating lobular carcinoma (ILC) in 5 patients and one each of DCIS, non- Hodgkin lymphoma (NHL) and metastasis from lung cancer. Benign lesions were detected in 12 (28%) patients. These included 8 fibroadenomas, 2 fibrocystic disease and 1 each of mastitis and breast abscess. Four patients with fibroadenoma underwent surgical excision.},
}
@article {pmid25889325,
year = {2015},
author = {Han, Z and Chen, Z and Zheng, R and Cheng, Z and Gong, X and Wang, D},
title = {Clinicopathological significance of CD133 and CD44 expression in infiltrating ductal carcinoma and their relationship to angiogenesis.},
journal = {World journal of surgical oncology},
volume = {13},
number = {},
pages = {56},
pmid = {25889325},
issn = {1477-7819},
mesh = {AC133 Antigen ; Adult ; Aged ; Antigens, CD ; Breast Neoplasms/blood supply/metabolism/*pathology ; Carcinoma, Ductal, Breast/blood supply/metabolism/*secondary ; Female ; Follow-Up Studies ; Glycoproteins ; Humans ; Hyaluronan Receptors ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplastic Stem Cells/metabolism/*pathology ; Neovascularization, Pathologic/metabolism/*pathology ; Peptides ; Prognosis ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer is the leading cause of cancer death in females worldwide, and the majority type is infiltrating ductal carcinoma (IDC). Most of IDC patients died of metastasis and recurrence. Cancer stem cells (CSCs) are defined with the ability to be self-renewal and potentially promote proliferation and formation of tumors. CSCs are related to angiogenesis and are important targets in new cancer treatment strategies. In this study, we purposed to investigate on expression and clinical significances of CSCs marked by CD133 and CD44 in IDC and their relationship to angiogenesis.<br><br>METHODS: The specimens of IDC from 325 Chinese patients with follow-up were analyzed for CD133, CD44, CD82, and CD34 protein expression by immunohistochemical staining. The Pearson chi-square test and t test were used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time in these patients with IDC was analyzed by univariate and multivariate analyses.<br><br>RESULTS: In IDC tissues, positive rates of 48.6%, 53.8%, and 42.2% were obtained for CD133, CD44, and CD82 protein, respectively; the mean score of microvessel density (MVD) was 20.5&#x2009;&#xb1;&#x2009;7.0 in IDC group. And there was a significant difference between the two groups. There was a positive relationship between the expression of CD133, CD44, and the score of MVD and the grades of tumor, lymph node metastasis, tumor-node-metastasis (TNM) stages (all P&#x2009;<&#x2009;0.05); and the expression of CD82 was negatively related to grades of tumor, lymph node metastasis, and TNM stages (all P&#x2009;<&#x2009;0.05). The overall mean survival time of the patients with CD133, CD44, and the score of MVD (&#x2265;21) positive expression was lower than that of patients with negative expression. The overall mean survival time of patients of CD82-positive expression was longer than that of patients of the negative expression group. The positive expression of CD133 and CD82, and TNM stages were independent prognostic factors of IDC (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: CSCs, angiogenesis, and aberrant expression of CD82 may be involved in the initiation, development, metastasis, and recurrence. It is suggested that CSCs, angiogenesis, and CD82 be possible as a therapeutic marker for anti-tumor therapy.},
}
@article {pmid25888835,
year = {2015},
author = {Nakahori, R and Takahashi, R and Akashi, M and Tsutsui, K and Harada, S and Matsubayashi, RN and Nakagawa, S and Momosaki, S and Akagi, Y},
title = {Breast carcinoma originating from a silicone granuloma: a case report.},
journal = {World journal of surgical oncology},
volume = {13},
number = {},
pages = {72},
pmid = {25888835},
issn = {1477-7819},
mesh = {Aged ; Breast Implants/*adverse effects ; Breast Neoplasms/*etiology/pathology ; Carcinoma, Ductal, Breast/*etiology/pathology ; Female ; Granuloma, Foreign-Body/*etiology ; Humans ; Prognosis ; Silicones/*adverse effects ; },
abstract = {Breast carcinoma rarely occurs in cases of foreign body granulomas following liquid silicone injection. Although the Food and Drug Administration (FDA) banned the use of all silicone injection products in 1992, liquid silicone injection for breast augmentation continues to be performed illegally. We herein report a case of breast carcinoma following liquid silicone injection in a 67-year-old female.A total of 45 years after liquid silicone injection, the patient had felt a breast mass in the right breast. Mammography showed a smooth mass that retracted the right nipple. Due to the presence of a marked acoustic shadow caused by the granulomas, evaluating the mass on ultrasonography was difficult. However, magnetic resonance imaging (MRI) showed a lobulated mass under the right nipple. The mass exhibited low signal intensity (SI) on T1-weighted images and intermingled high and low SI on T2-weighted images. Heterogeneous early enhancement with central low intensity was noted on dynamic contrast-enhanced MRI. Several oval-shaped low SI structures in the adipose tissue and disruption of the pectoralis major muscle were also observed. We diagnosed the patient with invasive ductal carcinoma based on a stereotactic-guided Mammotome® (a vacuum-assisted biopsy system manufactured by DEVICOR MEDICAL JAPAN, Tokyo, Japan) biopsy and subsequently performed mastectomy and axillary lymph node dissection (with a positive result for the sentinel node biopsy). Histologically, invasive ductal carcinoma was observed in the silicone granuloma.The development of foreign body granulomas following breast augmentation usually makes it difficult to detect breast cancer; thus, various devices are required to confirm the histological diagnosis of breast lesions. The stereotactic-guided Mammotome® biopsy system may be an effective device for diagnosing breast cancer developing in the augmented breast.},
}
@article {pmid25886372,
year = {2015},
author = {Liu, D and Zhang, L and Li, Z and Zhang, X and Wu, Y and Yang, H and Min, B and Zhang, X and Ma, D and Lu, Y},
title = {Thinner changes of the retinal nerve fiber layer in patients with mild cognitive impairment and Alzheimer's disease.},
journal = {BMC neurology},
volume = {15},
number = {},
pages = {14},
pmid = {25886372},
issn = {1471-2377},
mesh = {Aged ; Alzheimer Disease/*physiopathology ; Case-Control Studies ; Cognitive Dysfunction/*physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nerve Fibers/*pathology ; Retina/*pathology ; Tomography, Optical Coherence ; Vision Disorders/etiology ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and patients often have visual disorders. Mild cognitive impairment (MCI) is characterized by a memory deficit when compared with those of a similar age and education level which could indicate an earlier onset of AD. The aim of this study is to measure the changes of the retinal nerve fiber layer (RNFL) thickness of AD and MCI patients in comparison with the normal age controls.<br><br>METHODS: The RNFL thickness was assessed using optical coherence tomography (OCT) in patients with MCI, AD (mild, moderate and severe) and the age matched controls.<br><br>RESULTS: The thickness of RNFL in the superior quadrant and total mean values are gradually and significantly decreased from MCI to severe AD when compared to that in the controls. There is also a significant reduction of the retinal nerve fiber layer in the inferior quadrant in severe AD patients.<br><br>CONCLUSIONS: Our data indicate that the retinal nerve fiber layer degeneration is paralleled with dementia progression. Owing to its non-invasive and cost effective nature, monitoring RNFL thickness may have a value in assessing disease progression and the efficacy of any treatments.},
}
@article {pmid25881005,
year = {2015},
author = {Toyoshima, M and Iwahashi, H and Shima, T and Hayasaka, A and Kudo, T and Makino, H and Igeta, S and Matsuura, R and Ishigaki, N and Akagi, K and Sakurada, J and Suzuki, H and Yoshinaga, K},
title = {Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.},
journal = {Journal of medical case reports},
volume = {9},
number = {},
pages = {47},
pmid = {25881005},
issn = {1752-1947},
mesh = {Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology ; Carcinoma, Lobular/diagnosis/*secondary/therapy ; Carrier Proteins/analysis ; Combined Modality Therapy ; Female ; Glycoproteins/analysis ; Humans ; Leiomyoma/therapy ; Membrane Transport Proteins ; Middle Aged ; Nitriles/therapeutic use ; Triazoles/therapeutic use ; Uterine Neoplasms/*secondary/therapy ; },
abstract = {INTRODUCTION: Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma.<br><br>CASE PRESENTATION: A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue.<br><br>CONCLUSION: We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.},
}
@article {pmid25880415,
year = {2015},
author = {Tancioni, I and Miller, NL and Uryu, S and Lawson, C and Jean, C and Chen, XL and Kleinschmidt, EG and Schlaepfer, DD},
title = {FAK activity protects nucleostemin in facilitating breast cancer spheroid and tumor growth.},
journal = {Breast cancer research : BCR},
volume = {17},
number = {},
pages = {47},
pmid = {25880415},
issn = {1465-542X},
support = {R01 CA087038/CA/NCI NIH HHS/United States ; CA180769/CA/NCI NIH HHS/United States ; R01 CA102310/CA/NCI NIH HHS/United States ; CA102310/CA/NCI NIH HHS/United States ; R01 CA180769/CA/NCI NIH HHS/United States ; F32 CA159558/CA/NCI NIH HHS/United States ; 1F32CA159558/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Enzyme Activation ; Female ; Focal Adhesion Protein-Tyrosine Kinases/antagonists &amp; inhibitors/genetics/*metabolism ; GTP-Binding Proteins/*metabolism ; Humans ; Mice ; Nuclear Proteins/*metabolism ; Nucleophosmin ; Protein Kinase Inhibitors/pharmacology ; Protein Transport ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Sirolimus/pharmacology ; Spheroids, Cellular ; Tumor Burden/drug effects/genetics ; Tumor Cells, Cultured ; Tumor Stem Cell Assay ; },
abstract = {INTRODUCTION: Focal adhesion kinase (FAK) controls cell growth and survival downstream of integrin-matrix receptors. Upon adhesion loss or FAK inhibition, FAK can translocate to the nucleus. The nucleolus is a non-membrane nuclear structure that regulates ribosome biogenesis and cell proliferation. Nucleostemin (NS), a nucleolar-localized protein, modulates cell cycle progression, stemness, and three-dimensional tumor spheroid formation. The signaling pathways that regulate NS levels in tumors remain undefined.<br><br>METHODS: Human breast carcinoma cells were evaluated for growth in culture (adherent and anchorage-independent spheroid) and as orthotopic tumors. FAK signaling was evaluated by pharmacological FAK inhibitor addition (PF-271, IC50~0.1 &#x3bc;M) and by small hairpin RNA (shRNA) knockdown followed by re-expression of FAK wildtype (WT) or a kinase-dead (KD, K454R) FAK point mutant. Immunoblotting was used to evaluate FAK, NS, nucleolar phosphoprotein B23, and nucleolin levels. Total and phosphospecific antibody imunoblotting were used to detect changes in FAK, Akt kinase (Akt also known as protein kinase B), and 4E-binding protein 1 (4E-BP1) phosphorylation, a translation repressor protein and target of the mammalian target of rapamycin (mTOR) complex. Immunohistochemical, co-immunoprecipitation, and cellular fractionation analyses were used to evaluate FAK association with nucleoli.<br><br>RESULTS: Pharmacological (0.1 &#x3bc;M PF-271) or genetic inhibition of FAK activity prevents MDA-MB-231 and 4T1L breast carcinoma growth as spheroids and as orthotopic tumors. FAK inhibition triggers proteasome-mediated decreased NS levels but no changes in other nucleolar proteins such as B23 (nucleophosmin) or nucleolin. Active FAK was associated with purified nucleoli of anchorage-independent cells and present within nucleoli of human invasive ductal carcinoma tumor samples. FAK co-immunoprecipitated with B23 that binds NS and a complex between FAK, NS, Akt, and mTOR was detected. Constitutively-active Akt kinase promoted tumor spheroid growth, stabilized NS levels, and promoted pS65 4E-BP1 phosphorylation in the presence of inhibited FAK. Rapamycin lowered NS levels and inhibited pS65 4E-BP1 phosphorylation in cells with activated Akt-mTOR signaling.<br><br>CONCLUSIONS: FAK signaling occurs in the nucleolus, active FAK protects NS, and Akt-mTOR pathway regulates NS protein stability needed for breast carcinoma spheroid and tumor growth.},
}
@article {pmid25880352,
year = {2015},
author = {Benezet-Mazuecos, J and Iglesias, JA and Rubio, JM and Farré, J},
title = {Anodal Stimulation in Biventricular Pacing: Unrecognized and Misinterpreted Phenomenon.},
journal = {Pacing and clinical electrophysiology : PACE},
volume = {38},
number = {12},
pages = {1485-1488},
doi = {10.1111/pace.12650},
pmid = {25880352},
issn = {1540-8159},
mesh = {Aged, 80 and over ; Cardiac Resynchronization Therapy/*adverse effects/*methods ; Diagnosis, Differential ; Diagnostic Errors/*prevention &amp; control ; Electric Injuries/*diagnosis/*etiology/prevention &amp; control ; Heart Failure/complications/*prevention &amp; control ; Humans ; },
}
@article {pmid25880075,
year = {2015},
author = {Bae, SY and Kim, S and Lee, JH and Lee, HC and Lee, SK and Kil, WH and Kim, SW and Lee, JE and Nam, SJ},
title = {Poor prognosis of single hormone receptor- positive breast cancer: similar outcome as triple-negative breast cancer.},
journal = {BMC cancer},
volume = {15},
number = {},
pages = {138},
pmid = {25880075},
issn = {1471-2407},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/drug therapy/genetics/*metabolism/*mortality/pathology ; Female ; Follow-Up Studies ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Risk Factors ; Survival Analysis ; Triple Negative Breast Neoplasms/drug therapy/genetics/mortality ; Young Adult ; },
abstract = {BACKGROUND: Response to endocrine therapy in breast cancer correlates with estrogen receptor (ER) and progesterone receptor (PR) status. Generally, hormone receptor-positive (HR+) breast cancers have favorable prognosis. In order to understand the exact clinical characteristics and prognosis of single HR-positive breast cancer (ER + PR- tumors and ER-PR+ tumors), we compared these tumors to double HR+ tumors as well as HR- negative tumors (ER-PR-).<br><br>METHODS: We examined the clinical and biological features of 6,980 women with invasive ductal carcinoma, and these patients were stratified according to ER and PR expression as double HR+ (ER + PR+), single HR+ (ER + PR- and ER-PR+) and double HR-negative (HR-, ER-PR-) tumors.<br><br>RESULTS: In this study, 571 (8.2%) cases were single HR+ tumors, of which 90 (1.3%) were ER-PR+ tumors and 481 (6.9%) were ER + PR- tumors. Our multivariate analysis showed that in patients without HER2 overexpression ER + PR- tumors were associated with an increased risk of recurrence and death compared with ER + PR+ tumors, with a hazard ratio of 2.12 for disease-free survival (DFS) and 4.79 for overall survival (OS). In patients without HER2 overexpression ER-PR+ tumors had increased risk of recurrence and death compared with ER + PR+ tumor, with a hazard ratio of 4.19 for DFS and 7.22 for OS. In contrast, in patients with HER2 overexpression, the difference in survival between single HR+ tumors and double HR+ HR- tumors was not statistically significant. In patients without HER2 overexpression the DFS and OS of ER + PR- and ER-PR+ tumors were not significantly different from those of ER-PR- tumors.<br><br>CONCLUSION: We have identified clinically and biologically distinct features of single HR+ tumors (ER-PR+ and ER + PR-) through comparison with both ER + PR+ and ER-PR- tumors. These differences were only significant in HER2- tumors, not in HER2+ tumors. Single HR+ tumors without HER2 overexpression (ER + PR-HER2- or ER-PR + HER2-) were associated with poorer survival than ER + PR + HER2- tumors, and had comparable poor survival to ER-PR-HER2- tumors (triple-negative breast cancer).},
}
@article {pmid25852060,
year = {2015},
author = {Borges, S and Perez, EA and Thompson, EA and Radisky, DC and Geiger, XJ and Storz, P},
title = {Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101.},
journal = {Molecular cancer therapeutics},
volume = {14},
number = {6},
pages = {1306-1316},
pmid = {25852060},
issn = {1538-8514},
support = {CA116201/CA/NCI NIH HHS/United States ; GM086435/GM/NIGMS NIH HHS/United States ; R01 CA140182/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; CA140182/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; R01 GM086435/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Blotting, Western ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Cell Line, Tumor ; Cell Movement/drug effects/genetics ; Cell Proliferation/drug effects/genetics ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/metabolism/prevention &amp; control/secondary ; Lymphatic Metastasis ; MCF-7 Cells ; Mice, Inbred NOD ; Mice, SCID ; Microscopy, Confocal ; Neoplasm Invasiveness ; Protein Kinase C/*antagonists &amp; inhibitors/genetics/metabolism ; Protein Kinase Inhibitors/*pharmacology ; Pyrimidines/*pharmacology ; RNA Interference ; Receptors, Estrogen/metabolism ; Tumor Burden/drug effects/genetics ; Xenograft Model Antitumor Assays ; },
abstract = {Invasive ductal carcinomas (IDC) of the breast are associated with altered expression of hormone receptors (HR), amplification or overexpression of HER2, or a triple-negative phenotype. The most aggressive cases of IDC are characterized by a high proliferation rate, a great propensity to metastasize, and their ability to resist to standard chemotherapy, hormone therapy, or HER2-targeted therapy. Using progression tissue microarrays, we here demonstrate that the serine/threonine kinase protein kinase D3 (PKD3) is highly upregulated in estrogen receptor (ER)-negative (ER(-)) tumors. We identify direct binding of the ER to the PRKD3 gene promoter as a mechanism of inhibition of PKD3 expression. Loss of ER results in upregulation of PKD3, leading to all hallmarks of aggressive IDC, including increased cell proliferation, migration, and invasion. This identifies ER(-) breast cancers as ideal for treatment with the PKD inhibitor CRT0066101. We show that similar to a knockdown of PKD3, treatment with this inhibitor targets all tumorigenic processes in vitro and decreases growth of primary tumors and metastasis in vivo. Our data strongly support the development of PKD inhibitors for clinical use for ER(-) breast cancers, including the triple-negative phenotype.},
}
@article {pmid25850931,
year = {2015},
author = {Sutton, EJ and Oh, JH and Dashevsky, BZ and Veeraraghavan, H and Apte, AP and Thakur, SB and Deasy, JO and Morris, EA},
title = {Breast cancer subtype intertumor heterogeneity: MRI-based features predict results of a genomic assay.},
journal = {Journal of magnetic resonance imaging : JMRI},
volume = {42},
number = {5},
pages = {1398-1406},
pmid = {25850931},
issn = {1522-2586},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cohort Studies ; Contrast Media ; Female ; Gadolinium DTPA ; Gene Expression/genetics ; Genomics/*methods ; Humans ; Image Enhancement ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Retrospective Studies ; },
abstract = {PURPOSE: To investigate the association between a validated, gene-expression-based, aggressiveness assay, Oncotype Dx RS, and morphological and texture-based image features extracted from magnetic resonance imaging (MRI).<br><br>MATERIALS AND METHODS: This retrospective study received Internal Review Board approval and need for informed consent was waived. Between 2006-2012, we identified breast cancer patients with: 1) ER+, PR+, and HER2- invasive ductal carcinoma (IDC); 2) preoperative breast MRI; and 3) Oncotype Dx RS test results. Extracted features included morphological, histogram, and gray-scale correlation matrix (GLCM)-based texture features computed from tumors contoured on pre- and three postcontrast MR images. Linear regression analysis was performed to investigate the association between Oncotype Dx RS and different clinical, pathologic, and imaging features. P&#x2009;<&#x2009;0.05 was considered statistically significant.<br><br>RESULTS: Ninety-five patients with IDC were included with a median Oncotype Dx RS of 16 (range: 0-45). Using stepwise multiple linear regression modeling, two MR-derived image features, kurtosis in the first and third postcontrast images and histologic nuclear grade, were found to be significantly correlated with the Oncotype Dx RS with P&#x2009;=&#x2009;0.0056, 0.0005, and 0.0105, respectively. The overall model resulted in statistically significant correlation with Oncotype Dx RS with an R-squared value of 0.23 (adjusted R-squared&#x2009;=&#x2009;0.20; P&#x2009;=&#x2009;0.0002) and a Spearman's rank correlation coefficient of 0.49 (P&#x2009;<&#x2009;0.0001).<br><br>CONCLUSION: A model for IDC using imaging and pathology information correlates with Oncotype Dx RS scores, suggesting that image-based features could also predict the likelihood of recurrence and magnitude of chemotherapy benefit.},
}
@article {pmid25848941,
year = {2015},
author = {Dossus, L and Benusiglio, PR},
title = {Lobular breast cancer: incidence and genetic and non-genetic risk factors.},
journal = {Breast cancer research : BCR},
volume = {17},
number = {},
pages = {37},
pmid = {25848941},
issn = {1465-542X},
mesh = {Breast Neoplasms/*epidemiology/*etiology ; Carcinoma, Lobular/*epidemiology/*etiology ; Environment ; Female ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Humans ; Incidence ; Risk Factors ; },
abstract = {While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ with respect to risk factors. Invasive lobular carcinoma is more strongly associated with exposure to female hormones, and therefore its incidence is more subject to variation. This is illustrated by US figures during the 1987 to 2004 period: after 12 years of increases, breast cancer incidence declined steadily from 1999 to 2004, reflecting among other causes the decreasing use of menopausal hormone therapy, and these variations were stronger for invasive lobular than for invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly associated with early menarche, late menopause and late age at first birth. As for genetic risk factors, four high-penetrance genes are tested in clinical practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2, TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated with invasive ductal carcinoma, while BRCA2 mutations are associated with both ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion protein, is of special interest as mutations are associated with invasive lobular carcinoma, but never with ductal carcinoma. It was initially known as the main susceptibility gene for gastric cancer of the diffuse type, but the excess of breast cancers of the lobular type in CDH1 families led researchers to identify it also as a susceptibility gene for invasive lobular carcinoma. The risk of invasive lobular carcinoma is high in female mutation carriers, as about 50% are expected to develop the disease. Carriers must therefore undergo intensive breast cancer screening, with, for example, yearly magnetic resonance imaging and mammogram starting at age 30 years.},
}
@article {pmid25845386,
year = {2015},
author = {Lin, CS and Chang, SC and Ou, LH and Chen, CM and Hsieh, SS and Chung, YP and King, KL and Lin, SL and Wei, YH},
title = {Mitochondrial DNA alterations correlate with the pathological status and the immunological ER, PR, HER-2/neu, p53 and Ki-67 expression in breast invasive ductal carcinoma.},
journal = {Oncology reports},
volume = {33},
number = {6},
pages = {2924-2934},
doi = {10.3892/or.2015.3887},
pmid = {25845386},
issn = {1791-2431},
mesh = {Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Cell Proliferation ; DNA Copy Number Variations/genetics ; DNA, Mitochondrial/*genetics ; Estrogen Receptor alpha/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen/*biosynthesis/genetics ; Middle Aged ; Mutation ; Prognosis ; Receptor, ErbB-2/*biosynthesis/genetics ; Receptors, Progesterone/*biosynthesis/genetics ; Tumor Suppressor Protein p53/*biosynthesis/genetics ; },
abstract = {We analyzed the changes in mitochondrial DNA (mtDNA) copy numbers and the shifting of mtDNA D310 sequence variations (D310 mutation) with their relationships to pathological status and the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2/neu), tumor-suppressor protein p53 and cellular proliferation protein Ki-67 in breast invasive ductal carcinoma (BIDC), respectively. Fifty-one paraffin-embedded BIDCs and their paired non-cancerous breast tissues were dissected for DNA extraction. The mtDNA copy number and mtDNA D310 sequence variations were determined by quantitative real-time polymerase chain reaction (q-PCR) and PCR-based direct sequencing, respectively. The expression levels of ER, PR, HER-2/neu, p53 and Ki-67 were determined by immunohistochemical (IHC) staining. Compared to the paired non-cancerous breast tissues, 24 (47.1%) BIDCs had elevated mtDNA copy numbers and 29 (56.9%) harbored mtDNA D310 mutations. Advanced T-status (p=0.056), negative-ER (p=0.005), negative-PR (p=0.007), positive-p53 (p=0.050) and higher Ki-67 (p=0.004) expressions were related to a higher mtDNA copy ratio. In addition, advanced T-status (p=0.019) and negative-HER-2/neu expression (p=0.061) were associated with mtDNA D310 mutations. In conclusion, higher mtDNA copy ratio and D310 mutations may be relevant biomarkers correlated with pathological T-status and the expression levels of ER, PR, HER-2/neu, p53 and Ki-67 in BIDCs.},
}
@article {pmid25837163,
year = {2015},
author = {Cha, YJ and Jung, WH and Cho, NH and Koo, JS},
title = {Expression of sarcosine metabolism-related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma.},
journal = {Yonsei medical journal},
volume = {56},
number = {3},
pages = {598-607},
pmid = {25837163},
issn = {1976-2437},
mesh = {Adult ; Breast/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Phenotype ; Proportional Hazards Models ; Regression Analysis ; Retrospective Studies ; Sarcosine/genetics/*metabolism ; Tissue Array Analysis ; },
abstract = {PURPOSE: The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results.<br><br>MATERIALS AND METHODS: Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)].<br><br>RESULTS: The sarcosine metabolic phenotype differed between ILC and IDC (p<0.001). In IDC, sarcosine metabolic phenotype was distributed as null type (61.7%)>low sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC.<br><br>CONCLUSION: Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.},
}
@article {pmid25833969,
year = {2015},
author = {Fuller, NR and Caterson, ID and Sainsbury, A and Denyer, G and Fong, M and Gerofi, J and Baqleh, K and Williams, KH and Lau, NS and Markovic, TP},
title = {The effect of a high-egg diet on cardiovascular risk factors in people with type 2 diabetes: the Diabetes and Egg (DIABEGG) study-a 3-mo randomized controlled trial.},
journal = {The American journal of clinical nutrition},
volume = {101},
number = {4},
pages = {705-713},
doi = {10.3945/ajcn.114.096925},
pmid = {25833969},
issn = {1938-3207},
mesh = {Aged ; Blood Glucose/metabolism ; Body Mass Index ; Cardiovascular Diseases/*diet therapy/*prevention &amp; control ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Diabetes Mellitus, Type 2/*diet therapy ; *Diet ; *Eggs ; Fatty Acids, Monounsaturated/administration &amp; dosage/blood ; Fatty Acids, Unsaturated/administration &amp; dosage/blood ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Nutritional Status ; Obesity/blood/diet therapy ; Overweight/blood/diet therapy ; Prospective Studies ; Risk Factors ; Satiation ; Surveys and Questionnaires ; Treatment Outcome ; Triglycerides/blood ; },
abstract = {BACKGROUND: Previously published research that examined the effects of high egg consumption in people with type 2 diabetes (T2D) produced conflicting results leading to recommendations to limit egg intake. However, people with T2D may benefit from egg consumption because eggs are a nutritious and convenient way of improving protein and micronutrient contents of the diet, which have importance for satiety and weight management.<br><br>OBJECTIVE: In this randomized controlled study, we aimed to determine whether a high-egg diet (2 eggs/d for 6 d/wk) compared with a low-egg diet (<2 eggs/wk) affected circulating lipid profiles, in particular high-density lipoprotein (HDL) cholesterol, in overweight or obese people with prediabetes or T2D.<br><br>DESIGN: A total of 140 participants were randomly assigned to one of the 2 diets as part of a 3-mo weight maintenance study. Participants attended the clinic monthly and were instructed on the specific types of foods and quantities to be consumed.<br><br>RESULTS: There was no significant difference in the change in HDL cholesterol from screening to 3 mo between groups; the mean difference (95% CI) between high- and low-egg groups was +0.02 mmol/L (-0.03, 0.08 mmol/L; P = 0.38). No between-group differences were shown for total cholesterol, low-density lipoprotein cholesterol, triglycerides, or glycemic control. Both groups were matched for protein intake, but the high-egg group reported less hunger and greater satiety postbreakfast. Polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) intakes significantly increased from baseline in both groups.<br><br>CONCLUSIONS: High egg consumption did not have an adverse effect on the lipid profile of people with T2D in the context of increased MUFA and PUFA consumption. This study suggests that a high-egg diet can be included safely as part of the dietary management of T2D, and it may provide greater satiety. This trial was registered at the Australia New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12612001266853.},
}
@article {pmid25831047,
year = {2015},
author = {Kim, SY and Jung, SH and Kim, MS and Baek, IP and Lee, SH and Kim, TM and Chung, YJ and Lee, SH},
title = {Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer.},
journal = {Oncotarget},
volume = {6},
number = {10},
pages = {7597-7607},
pmid = {25831047},
issn = {1949-2553},
mesh = {Adult ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Female ; Gene Dosage/*genetics ; Genomics ; Humans ; Middle Aged ; Sequence Analysis, DNA/*methods ; },
abstract = {Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.g., TP53, PIK3CA and AKT1), copy number alterations (CNAs) and chromothripses, but had significantly fewer driver genes and co-occurrence of mutation/CNAs than synchronous DCIS-IDC. We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC. Of note, synchronous DCIS genomes were closer to IDC than pure DCIS. Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations. Our results indicate that although pure DCIS has already acquired some drivers, more changes are needed to progress to IDC. In addition, IDC-associated DCIS is more aggressive than pure DCIS at genomic level and should really be considered IDC. Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.},
}
@article {pmid25820821,
year = {2015},
author = {Asiaf, A and Ahmad, ST and Malik, AA and Aziz, SA and Rasool, Z and Masood, A and Zargar, MA},
title = {Protein expression and methylation of MGMT, a DNA repair gene and their correlation with clinicopathological parameters in invasive ductal carcinoma of the breast.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {36},
number = {8},
pages = {6485-6496},
pmid = {25820821},
issn = {1423-0380},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Methylation/*genetics ; DNA Modification Methylases/biosynthesis/*genetics ; DNA Repair Enzymes/biosynthesis/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Promoter Regions, Genetic ; Tumor Suppressor Proteins/biosynthesis/*genetics ; },
abstract = {Epigenetic mechanisms such as DNA methylation are being increasingly recognized to play an important role in cancer and may serve as a cancer biomarker. The aim of this study was to evaluate the promoter methylation status of MGMT (O6-methylguanine-DNA methyltransferase) and a possible correlation with the expression of MGMT and standard clinicopathological parameters in invasive ductal breast carcinoma patients (IDC) of Kashmir. Methylation-specific PCR was carried out to investigate the promoter methylation status of MGMT in breast tumors paired with the corresponding normal tissue samples from 128 breast cancer patients. The effect of promoter methylation on protein expression in the primary breast cancer and adjacent normal tissues was evaluated by immunohistochemistry (n = 128) and western blotting (n = 30). The frequency of tumor hypermethylation was 39.8 % and a significant difference in methylation frequency among breast tumors were found (p < 0.001) when compared with the corresponding normal tissue. Immunohistochemical analysis showed no detectable expression of MGMT in 68/128 (53.1 %) tumors. MGMT promoter methylation mediated gene silencing was associated with loss of its protein expression (rs = -0.285, p = 0.001, OR = 3.38, 95 % CI = 1.59-7.17). A significant correlation was seen between loss of MGMT and lymph node involvement (p = 0.030), tumor grade (p < 0.0001), loss of estrogen receptors (ER; p = 0.021) and progesterone receptors (PR) (p = 0.016). Also, MGMT methylation was found to be associated with tumor grade (p = 0.011), tumor stage (p = 0.009), and loss of ER (p = 0.003) and PR receptors (p = 0.009). To our knowledge, our findings, for the first time, in Kashmiri population, indicate that MGMT is aberrantly methylated in breast cancer and promoter hypermethylation could be attributed to silencing of MGMT gene expression in breast cancer. Our data suggests that MGMT promoter hypermethylation could have a potential function as molecular biomarker of breast oncogenesis. Also, based on their predictive value of response to therapy, the immunohistochemical evaluation and interpretation of MGMT may also help in future to establish therapeutic strategies for patients with breast cancer.},
}
@article {pmid25818033,
year = {2015},
author = {Oger, AS and Boukerrou, M and Cutuli, B and Campion, L and Rousseau, E and Bussières, E and Raro, P and Classe, JM},
title = {[Male breast cancer: prognostic factors, diagnosis and treatment: a multi-institutional survey of 95 cases].},
journal = {Gynecologie, obstetrique &amp; fertilite},
volume = {43},
number = {4},
pages = {290-296},
doi = {10.1016/j.gyobfe.2015.02.010},
pmid = {25818033},
issn = {1769-6682},
mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms, Male/*diagnosis/pathology/*therapy ; Carcinoma, Ductal, Breast/diagnosis/pathology/therapy ; Chemotherapy, Adjuvant ; Humans ; Lymphatic Metastasis/pathology ; Male ; Mastectomy ; Middle Aged ; Obesity/complications ; Prognosis ; Radiotherapy, Adjuvant ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Survival Rate ; },
abstract = {OBJECTIVES: The optimal treatment for male breast cancer is not known because male breast cancer is a rare disease. It represents as little as 0.6% of all breast cancers and less than 1% of human cancers. The aim was to analyze the clinical, histological and therapeutic characteristics of 95 men cared for breast cancer between 2000 and 2010 in four hospitals, and determine predictors of poor prognosis to improve care of male breast cancer.<br><br>METHODS: This study is a multi-institutional survey, retrospective, involving four French institutions: Cancer Institute of the West (ICO), Reunion Island South hospital group, the hospital group of Dax, and the Bergoni&#xe9; Institute. All carcinomas in situ or invasive breast occurred in male patients were included. An analysis of clinical, histological and therapeutic features was performed. Statistical analysis of our study focused on the overall survival of patients and specific method of Kaplan-Meier, enabling search for predictors of poor prognosis.<br><br>RESULTS: The mean age was 65 years. Thirty-seven percent of patients were overweight or obese. It was in 88% of cases of palpable tumor whose average size was 26.29mm. Ninety patients, none had a lesion palpable T0, 44% T1 tumors, 38% T2 tumors, 3% had a T3 tumors, and finally 10% T4 tumors. The histological type was the most common invasive ductal carcinoma (87%). He found a similar proportion of patients with or without lymph node involvement. N+ patients, capsular rupture was observed in 29% of cases. Receptor positivity was found, estrogen in 95% of cases and progesterone in 83% of cases. Additional irradiation was performed in 75% of patients and chemotherapy in 37% of patients. Overall survival was 79.2% at five years and 70.8% at ten years. Age, tumor size and histological capsular rupture are factors that significantly influence the overall survival and specific.<br><br>CONCLUSION: Male breast cancer is a different pathology of breast cancer in women. The majority of recommendations suggest treating men who are diagnosed with breast cancer, using the guidelines applied to postmenopausal women treatments. There is no study based on male population that has evaluated these treatment modalities in terms of impact on survival. The diagnosis is usually made at later stages, and tumor size is often greater. Histological characteristics also differ. However, the treatment is almost identical.},
}
@article {pmid25816287,
year = {2015},
author = {Rebollo, MP and Mohammed, KA and Thomas, B and Ame, S and Ali, SM and Cano, J and Escalada, AG and Bockarie, MJ},
title = {Cessation of mass drug administration for lymphatic filariasis in Zanzibar in 2006: was transmission interrupted?.},
journal = {PLoS neglected tropical diseases},
volume = {9},
number = {3},
pages = {e0003669},
pmid = {25816287},
issn = {1935-2735},
support = {G1001337/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Child ; Communicable Disease Control/*methods ; Disease Eradication/methods/*statistics &amp; numerical data ; Elephantiasis, Filarial/*drug therapy/*epidemiology/*transmission ; Humans ; Indian Ocean Islands/epidemiology ; Male ; Surveys and Questionnaires ; Tanzania/epidemiology ; },
abstract = {BACKGROUND: Lymphatic filariasis (LF) is targeted for elimination through annual mass drug administration (MDA) for 4-6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped.<br><br>In line with ongoing efforts to shrink the LF map, we performed the WHO recommended transmission assessment surveys (TAS) in January 2012 to verify the absence of LF transmission on the main Zanzibar islands of Unguja and Pemba. Altogether, 3275 children were tested on both islands and 89 were found to be CFA positive; 70 in Pemba and 19 in Unguja. The distribution of schools with positive children was heterogeneous with pronounced spatial variation on both islands. Based on the calculated TAS cut-offs of 18 and 20 CFA positive children for Pemba and Unguja respectively, we demonstrated that transmission was still ongoing in Pemba where the cut-off was exceeded.<br><br>CONCLUSIONS: Our findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013.},
}
@article {pmid25804795,
year = {2015},
author = {Wang, T and Ma, Y and Wang, L and Liu, H and Chen, M and Niu, R},
title = {Strong adverse effect of epidermal growth factor receptor 2 overexpression on prognosis of patients with invasive lobular breast cancer: a comparative study with invasive ductal breast cancer in Chinese population.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {36},
number = {8},
pages = {6113-6124},
pmid = {25804795},
issn = {1423-0380},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*biosynthesis/genetics ; },
abstract = {The data on the outcome of breast invasive lobular carcinoma (ILC) are conflicting. In addition, the prognostic effect of molecular subtypes on ILC remains unclear. In this study, the clinicopathological and prognostic data between 269 ILC and 816 invasive ductal carcinoma (IDC) cases in a Chinese population were extensively compared, with a median follow-up time of 7.8 years. Compared with the IDC group, ILC tumors had more lymph node invasion, hormonal receptor positivity, and human epidermal growth factor receptor 2 (HER2) negativity. ILC patients showed overall survival (OS) and recurrence/metastasis-free survival (RFS) rates similar to those of IDC patients but exhibited worse disease-free survival (DFS) rate because of the higher rate of contralateral breast cancer (BC). Further analysis showed that OS, RFS, and DFS were similar between ILC and IDC patients in the subgroups of luminal A and triple-negative BC with HER2 negativity but were worse in ILC patients than those in IDC patients in the subgroups of luminal B and HER2 overexpression with positive HER2 expression. Multivariate analysis indicated HER2 positivity as an independent risk factor for OS, RFS, and DFS of ILC patients, which increased the risk in the ILC group than that in IDC group. The interaction of HER2 and ILC was also defined as an independent risk factor for OS, RFS, and DFS of the entire population. In conclusion, overexpression of HER2 exhibited stronger negative effect on the prognosis of ILC patients than that in IDC patients, suggesting that treatment targeting HER2 is crucial for this BC subgroup.},
}
@article {pmid25791599,
year = {2015},
author = {Karbiener, M and Scheideler, M},
title = {Microarray analysis of small non-coding RNAs.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {1296},
number = {},
pages = {161-171},
doi = {10.1007/978-1-4939-2547-6_15},
pmid = {25791599},
issn = {1940-6029},
mesh = {Microarray Analysis/*methods ; Nucleic Acid Hybridization/methods ; Oligonucleotide Probes/genetics ; RNA, Small Untranslated/*genetics ; Transition Temperature ; },
abstract = {Microarray technology has evolved to efficiently profile the expression of RNAs. However, analysis of small non-coding RNAs (ncRNAs) is challenging due to their short length and highly divergent sequences with large variation in GC content leading to very different hybridization properties. To overcome these challenges, LNA-modified oligonucleotides have been used to enhance and normalize the melting temperature (Tm) of capture probes, which allows sensitive profiling of small ncRNAs regardless of their sequence. Here, we describe the isolation and labeling of small non-coding RNAs, as well as their hybridization to microarrays with LNA-modified oligonucleotide probes using a semi-automated hybridization device.},
}
@article {pmid25784697,
year = {2015},
author = {Leonhardt, I and Spielberg, S and Weber, M and Albrecht-Eckardt, D and Bläss, M and Claus, R and Barz, D and Scherlach, K and Hertweck, C and Löffler, J and Hünniger, K and Kurzai, O},
title = {The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity.},
journal = {mBio},
volume = {6},
number = {2},
pages = {e00143},
pmid = {25784697},
issn = {2150-7511},
mesh = {Adaptive Immunity/*drug effects ; Candida albicans/*physiology ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/drug effects/immunology ; Farnesol/*metabolism ; Gene Expression Profiling ; Humans ; Immunologic Factors/*metabolism ; Monocytes/drug effects/immunology ; Neutrophils/drug effects/immunology ; *Quorum Sensing ; Virulence Factors/*metabolism ; },
abstract = {UNLABELLED: Farnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of farnesol on innate immune cells known to be important for fungal clearance and protective immunity. Farnesol enhanced the expression of activation markers on monocytes (CD86 and HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and macrophage inflammatory protein 1 alpha [MIP-1α]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of farnesol. Furthermore, farnesol modulated migrational behavior and cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of interleukin 12 (IL-12) induction in iDC generated in the presence of farnesol. Transcriptome analyses revealed a farnesol-induced shift in effector molecule expression and a down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and mitigating the Th1 response, which is essential for fungal clearance.<br><br>IMPORTANCE: Farnesol is a quorum-sensing molecule which controls morphological plasticity of the pathogenic yeast Candida albicans. As such, it is a major mediator of intraspecies communication. Here, we investigated the impact of farnesol on human innate immune cells known to be important for fungal clearance and protective immunity. We show that farnesol is able to enhance inflammation by inducing activation of neutrophils and monocytes. At the same time, farnesol impairs differentiation of monocytes into immature dendritic cells (iDC) by modulating surface phenotype, cytokine release and migrational behavior. Consequently, iDC generated in the presence of farnesol are unable to induce proper T cell responses and fail to secrete Th1 promoting interleukin 12 (IL-12). As farnesol induced down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, desensitization to GM-CSF could potentially explain transcriptional reprofiling of iDC effector molecules. Taken together, our data show that farnesol can also mediate Candida-host communication and is able to act as a virulence factor.},
}
@article {pmid25783336,
year = {2015},
author = {Kushnir, J and Djerassi, R and Sofer, T and Kushnir, T},
title = {Threat perception, anxiety and noncompliance with preoperative fasting instructions among mothers of children attending elective same day surgery.},
journal = {Journal of pediatric surgery},
volume = {50},
number = {5},
pages = {869-874},
doi = {10.1016/j.jpedsurg.2014.08.018},
pmid = {25783336},
issn = {1531-5037},
mesh = {Adult ; *Ambulatory Surgical Procedures ; Anxiety/*epidemiology/etiology ; Child ; Child, Preschool ; *Elective Surgical Procedures ; *Fasting ; Female ; Humans ; Incidence ; Israel/epidemiology ; Male ; Mothers/*psychology ; *Patient Compliance ; Preoperative Care/*methods ; },
abstract = {PURPOSE: The current study examined possible links between threat perception, anxiety, conscientiousness and parental noncompliance with preoperative fasting instructions for their children.<br><br>METHODS: 100 mothers of children about to undergo an ambulatory elective surgery were divided to two equal groups based on compliance/noncompliance with pre surgery fasting requirements. Logistic regression analysis was preformed to predict compliance/noncompliance. In addition a logistic model estimating the effect of anxiety and conscientiousness levels, and their interaction, on the probability of fasting was performed.<br><br>RESULTS: Mothers who did not comply with fasting requirements perceived the procedure as more threatening, were more anxious and had lower conscientiousness levels. Additionally, mother's anxiety prior to surgery mediated the association between mothers' threat perception and compliance. Finally, conscientiousness moderated the anxiety and compliance association so that high conscientiousness levels reduced the effect of anxiety, elevating the likelihood of anxious mothers to comply with fasting guidelines.<br><br>CONCLUSIONS: Based on these findings we recommend medical staff to make significant efforts to identify highly anxious parents as early as possible during the preoperative process. Innovative assessment and intervention tools should be developed in order to conduct a smooth medical operation and reduce the chance of unnecessary and costly surgery cancelation.},
}
@article {pmid25771081,
year = {2015},
author = {Sorin, T and Fyad, JP and Delay, E and Rouanet, P and Rimareix, F and Houpeau, JL and Classe, JM and Garrido, I and Tunon De Lara, C and Dauplat, J and Bendavid, C and Houvenaeghel, G and Clough, KB and Sarfati, I and Leymarie, N and Trudel, M and Salleron, J and Guillemin, F and Oldrini, G and Brix, M and Dolivet, G and Simon, E and Verhaeghe, JL and Marchal, F},
title = {Occult cancer in specimens of reduction mammaplasty aimed at symmetrization. A multicentric study of 2718 patients.},
journal = {Breast (Edinburgh, Scotland)},
volume = {24},
number = {3},
pages = {272-277},
doi = {10.1016/j.breast.2015.02.033},
pmid = {25771081},
issn = {1532-3080},
mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology/secondary/surgery ; Carcinoma, Lobular/*epidemiology/secondary/surgery ; Female ; Humans ; Incidence ; Mammaplasty/*statistics &amp; numerical data ; Mastectomy, Segmental ; Middle Aged ; Neoplasms, Unknown Primary/*epidemiology ; Retrospective Studies ; },
abstract = {Women who have undergone surgical treatment for breast cancer often benefit from a contralateral reduction mammaplasty (CRM) aimed at symmetrization of the contralateral breast unaffected by the initial cancer. In our 7-year multicentric study (12 centers) of 2718 patients, incidence of CRM cancers (CRMc) was 1.47% (n = 40) [95% CI 1.05%-2.00%]. The CRMc group had significantly more initial mammary cancers of invasive lobular carcinoma (ILC, 22.5% vs 12.0%) and ductal carcinoma in situ (DCIS, 35.0% vs 21.6%) types than the healthy CRM group (p = 0.017). 35.0% (n = 14) of patients had en bloc resection; 25.0% (n = 10) of surgical specimens were correctly oriented. En bloc resection and orientation of surgical specimens enable precise pinpointing of the CRMc. A salvage lumpectomy may be proposed as an option when margins are invaded. The histological distribution of the 40 CRMc (mean size 12.7 mm) was carcinoma in situ (CIS) 70%, ILC 12.5%, invasive ductal carcinoma (IDC) 12.5% and tubular carcinoma (TC) 5.0%.},
}
@article {pmid25769963,
year = {2015},
author = {Cassinello, F and Prieto, I and del Olmo, M and Rivas, S and Strichartz, GR},
title = {Cancer surgery: how may anesthesia influence outcome?.},
journal = {Journal of clinical anesthesia},
volume = {27},
number = {3},
pages = {262-272},
doi = {10.1016/j.jclinane.2015.02.007},
pmid = {25769963},
issn = {1873-4529},
mesh = {Anesthesia/*methods ; Anesthetics, Local/pharmacology ; Apoptosis ; Cell Movement ; Cell Proliferation ; Disease Progression ; Humans ; Neoplasms/mortality/pathology/*surgery ; Substance P/physiology ; Voltage-Gated Sodium Channels/drug effects ; },
abstract = {OBJECTIVE: To review the published literature regarding the effects of anesthesia on cancer surgery to prevent tumor cell proliferation/migration or induce apoptosis.<br><br>BACKGROUND: Surgery is the main treatment for potentially curable solid tumors, but most cancer-related deaths in patients who have received previous surgical treatment are caused by metastatic disease. There is increasing evidence that anesthetic technique has the potential to affect long-term outcome after cancer surgery.<br><br>METHODS: This work reviews the English published literature that was obtained by performing a search of the PubMed database up to January 2014. We selected articles that provided evidence or reviewed the possible actions of anesthetics on cancer cells or the influence of anesthesia in recurrence/outcome.<br><br>RESULTS: Inhaled anesthetics induce immunosuppression and activate inflammatory cascade activation, whereas propofol has a protective action. Opioids might promote cancer recurrence and metastasis. In vitro and in vivo studies have demonstrated that local anesthetics inhibit proliferation and migration of cancer cells and induce apoptosis.<br><br>CONCLUSIONS: Anesthesiologists should follow current best clinical practice and include all strategies that effectively decrease pain and attenuate stress. Regional anesthesia and multimodal analgesia, adding anti-inflammatory drugs, play an unquestionable role in the control of perioperative pain and may improve recurrence-free survival.},
}
@article {pmid25759617,
year = {2014},
author = {Basaran, D and Turgal, M and Beksac, K and Ozyuncu, O and Aran, O and Beksac, MS},
title = {Pregnancy-associated breast cancer: clinicopathological characteristics of 20 cases with a focus on identifiable causes of diagnostic delay.},
journal = {Breast care (Basel, Switzerland)},
volume = {9},
number = {5},
pages = {355-359},
pmid = {25759617},
issn = {1661-3791},
abstract = {BACKGROUND: The primary objective of this study was to evaluate the clinicopathological characteristics of patients with pregnancy-associated breast cancer (PABC), with a special focus on diagnostic delays and the identifiable causes of diagnostic delays.<br><br>PATIENTS AND METHODS: Clinicopathological data of patients treated for PABC between 2003 and 2012 at Hacettepe University Hospital was retrospectively reviewed.<br><br>RESULTS: 20 patients with PABC were included. The pathological examination revealed predominance of invasive ductal carcinoma (80%), grade III tumors (65%) and advanced-stage (III-IV) disease (75%). In 8 patients (40%), there was a diagnostic delay between occurrence of the presenting symptoms and the initiation of breast mass workup. For these 8 patients, the main identifiable causes of diagnostic delay were the attribution of disease-related symptoms to pregnancy or lactation in 5 (63%) and negligence of symptoms in 2 (25%).<br><br>CONCLUSIONS: PABC mostly presents with advanced-stage disease, and there can be a substantial diagnostic delay before these patients receive treatment. Preconceptional, gestational and postpartum examination of women of reproductive age should include a thorough breast examination and should provide adequate information regarding the physiological changes in breast tissue and the possible pathological symptoms.},
}
@article {pmid25752197,
year = {2015},
author = {Simpson, K and Jones, RE and Grimstead, JW and Hills, R and Pepper, C and Baird, DM},
title = {Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.},
journal = {Molecular oncology},
volume = {9},
number = {6},
pages = {1186-1193},
pmid = {25752197},
issn = {1878-0261},
support = {C17199/A13490//Cancer Research UK/United Kingdom ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/genetics/*metabolism/*mortality/pathology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Survival Rate ; Telomere/genetics/*metabolism ; *Telomere Homeostasis ; },
abstract = {Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.},
}
@article {pmid25751500,
year = {2015},
author = {Son, CH and Bae, JH and Lee, HR and Shin, DY and Yang, K and Park, YS},
title = {Enhanced dendritic cell-based immunotherapy using low-dose cyclophosphamide and CD25-targeted antibody for transplanted Lewis lung carcinoma cells.},
journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)},
volume = {38},
number = {3},
pages = {107-115},
doi = {10.1097/CJI.0000000000000068},
pmid = {25751500},
issn = {1537-4513},
mesh = {Animals ; Antibodies, Monoclonal/*administration &amp; dosage ; Antineoplastic Agents/*administration &amp; dosage ; Apoptosis/drug effects/radiation effects ; Carcinoma, Lewis Lung/*immunology/mortality/pathology/therapy ; Cell Line, Tumor ; Combined Modality Therapy ; Cyclophosphamide/*administration &amp; dosage ; Cytotoxicity, Immunologic/drug effects/radiation effects ; Dendritic Cells/*immunology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Immunophenotyping ; Immunosuppressive Agents/administration &amp; dosage ; Immunotherapy ; Interleukin-2 Receptor alpha Subunit/*antagonists &amp; inhibitors ; Male ; Mice ; Phenotype ; Radiation ; Spleen/immunology ; T-Lymphocytes, Regulatory/drug effects/immunology/metabolism/radiation effects ; Th1 Cells/drug effects/immunology/metabolism/radiation effects ; Tumor Microenvironment/drug effects/immunology/radiation effects ; },
abstract = {Regulatory T cells (Tregs) is one of the main obstacles to the success of cancer immunotherapy. The effect of dendritic cell (DC)-based immunotherapy can be attenuated by immune suppressive functions of Tregs. We used a CD25-targeted antibody and low-dose cyclophosphamide (CTX) as immunomodulators to increase the antitumor effect of intratumoral injection of immature DCs into the irradiated tumor cells (IR/iDC). CTX or CD25-targeted antibody alone showed a significant reduction in the number of Tregs within the tumor microenvironment. When they are combined with IR/iDC, the number of Tregs was further reduced. Although IR/IDC showed strong antitumor effects such as reduction in tumor growth, increase in Th1 immune response, and improvement of survival, the therapeutic effect was further improved by combining treatments with immunomodulators. CTX and CD25-targeted antibody showed no significant difference in tumor growth when combined with IR/iDC, but CTX further increased the number of interferon (IFN)-γ-secreting T cells, cytotoxicity, and survival rate. Although irradiation induced depletion of T lymphocytes, administration of DCs recovered this depletion. Particularly, the lymphocytes were more significantly increased when CTX and IR/iDC were combined. Low-dose CTX has already been used as an immunomodulator in clinical trials, and it offers several advantages, including convenience, low-cost, and familiarity to clinicians. However, CD25-targeted antibody cannot only deplete Tregs, but also may affect IL-2-dependent effector T lymphocytes. Therefore, CTX is an effective means to inhibit Tregs, and an effective immunomodulatory agent for multimodality therapy such as combination treatment of conventional cancer therapy and immunotherapy.},
}
@article {pmid25750340,
year = {2015},
author = {Arfaoui, A and Douik, H and Kablouti, G and Chaaben, AB and Handiri, N and Zid, Z and Ouni, N and Zouiouch, F and Ayari, F and Mamoughli, T and Bouassida, J and Abazza, H and Harzallaha, L and Guemira, F},
title = {Role of p53 Codon72 SNP in breast cancer risk and anthracycline resistance.},
journal = {Anticancer research},
volume = {35},
number = {3},
pages = {1763-1769},
pmid = {25750340},
issn = {1791-7530},
mesh = {Adult ; Aged ; Aged, 80 and over ; Anthracyclines/*therapeutic use ; Breast Neoplasms/drug therapy/etiology/*genetics ; Case-Control Studies ; *Codon ; *Drug Resistance, Neoplasm ; Female ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; *Polymorphism, Single Nucleotide ; Risk ; Tumor Suppressor Protein p53/*genetics ; },
abstract = {BACKGROUND/AIM: We undertook a case-control and a case-case study to examine the possible association of p53 codon72 polymorphism with the breast cancer risk and resistance to anthracycline-based chemotherapy.<br><br>PATIENTS AND METHODS: Case-control study: This study enrolled 175 patients with breast cancer treated at the Salah Aziez Institute and 159 healthy Tunisian women (matched for age, ethnicity and origin), used as a control, with no clinical evidence of any neoplastic disorder. Case-Case study: 400 breast cancer patients, with invasive ductal carcinoma (IDC) treated with anthracycline based-chemotherapy. Genomic DNA was isolated from whole-blood leucocytes using the phenol-chloroform method. Anthracycline response was scored according to the World Health Organization (WHO) criteria. P53 codon72 polymorphism was genotyped using real-time polymerase chain reaction (RT-PCR) with the TaqMan method. Data were statistically analyzed using the Chi-square test.<br><br>RESULTS: Clinical data revealed that among the 400 patients, one quarter was resistant to chemotherapy treatment. Genetic data revealed that the p53 Arg72Pro genotype was found to be greatly associated with breast cancer risk (p<0.001), as well as tumor site (p=0.046). However, resistance to anthracycline-based chemotherapy does not seem to be correlated with p53 codon72 polymorphism in our population. Also, the distribution of tumor size, lymph node involvement and tumor grade was not significantly different among the polymorphic variants.<br><br>CONCLUSION: We conclude that p53 codon72 polymorphism is involved in susceptibility to developing breast cancer. It may be a factor of progression when breast sites are taken into account. However, there is no evidence indicating that Arg72Pro SNP may influence response to anthracycline-based chemotherapy.},
}
@article {pmid25736840,
year = {2015},
author = {Cherbal, F and Gaceb, H and Mehemmai, C and Saiah, I and Bakour, R and Rouis, AO and Boualga, K and Benbrahim, W and Mahfouf, H},
title = {Distribution of molecular breast cancer subtypes among Algerian women and correlation with clinical and tumor characteristics: a population-based study.},
journal = {Breast disease},
volume = {35},
number = {2},
pages = {95-102},
doi = {10.3233/BD-150398},
pmid = {25736840},
issn = {1558-1551},
mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Algeria ; Black People ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism/pathology ; Cohort Studies ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/*metabolism/pathology ; Young Adult ; },
abstract = {BACKGROUND: Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. Molecular classification of breast cancer is an important factor for prognosis and clinical outcome. There are limited data regarding molecular breast cancer subtypes among Algerian women. The objective of the present study was to analyze the proportion and distribution of molecular subtypes and to determine their associations with some clinical and tumor characteristics: age at diagnosis, menopausal status, histological type and histological grade.<br><br>MATERIALS AND METHODS: The study population included 3014 female breast cancers. We analyzed breast cancers from cancer registries of academic medical oncology service of public hospital of Rouiba, anticancer center of Blida, and anticancer center of Batna. Breast cancers were diagnosed between 2008 and 2013. Molecular subtype classification was done based on immunohistochemical surrogates for ER (Estrogen receptor), PR (Progesterone receptor) and HER2 (human epidermal growth factor receptor-2) status obtained from medical records for 3014 breast cancer patients. Breast cancer subtypes definitions were as follow: Luminal A (ER+ and/or PR+, HER2-), Luminal B (ER+ and/or PR+, HER2+), TNBC (ER-, PR - , HER2-), HER2+ (ER-, PR-, HER2+). Molecular subtypes were correlated with the clinicopathological characteristics of the tumors.<br><br>RESULTS: The mean age at diagnosis cancer was 48.5 years. Proportions of the luminal A, TNBC, luminal B and HER2+ breast cancer subtypes were 50.59%, 20.80%, 19.67% and 8.92%, respectively. We noted a significant difference in the distribution of age at diagnosis among the four cancer subtypes (P= 0.004). Luminal A, Luminal B, TNBC and HER2+ subtypes were significantly different by premenopausal and postmenopausal status (P= 0.01). Invasive Ductal Carcinoma was the most common histological type in all breast cancer subtypes. Tumors with histological grade 2 and 3 were more common in patients for the four breast cancer subtypes.<br><br>CONCLUSIONS: For the first time, we report the distribution of molecular breast cancer subtypes and their associations with some clinicopathological characteristics in a large cohort of Algerian women. In our current study, the median age of diagnosis for all breast cancer subtypes was younger than the average age in Europe and America. Luminal A was the most common sub- type in our patients followed by TNBC. The proportion of luminal A subtype was lesser than reported in white women with breast cancer in Europe and America. The proportion of TNBC subtype in Algerian women was higher compared with Caucasian women of European ancestry. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for Algerian breast cancer patients.},
}
@article {pmid25731466,
year = {2014},
author = {Miyazawa, K and Yoshioka, S and Shiobara, M and Wakatsuki, K and Kataoka, M and Arai, S and Yamazaki, K},
title = {[Long-term survival following postoperative combined modality therapy for pancreatic cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {41},
number = {12},
pages = {2190-2192},
pmid = {25731466},
issn = {0385-0684},
mesh = {Aged ; Carcinoma, Ductal/*therapy ; Catheter Ablation ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/secondary/therapy ; Pancreatectomy ; Pancreatic Neoplasms/pathology/*therapy ; Recurrence ; Time Factors ; },
abstract = {A 69-year-old woman with back pain underwent distal pancreatectomy with left adrenectomy for advanced pancreatic cancer pathologically diagnosed as poorly differentiated invasive ductal carcinoma with retroperitoneal and perineural invasion, pT3N0M0, Stage III. The patient received adjuvant chemotherapy with S-1 for 6 months. However, 3 years after surgery, computed tomography (CT) revealed para-aorticlymph node (LN) recurrence. Treatment with gemcitabine (GEM) was begun and continued for 3 years. Following progression of the LN recurrence 5 and half years after surgery, administration of radiotherapy reduced diarrhea and back pain. Supportive care combined with radio-frequency ablation(RFA)was provided for multiple liver metastasis 5 years 7 months after surgery. The patient died due to gastrointestinal hemorrhage 6 years after surgery. We report long-term postoperative survival of a patient with recurrent pancreatic cancer following combined modality therapy.},
}
@article {pmid25731396,
year = {2014},
author = {Hayashi, K and Oshida, S and Nemoto, K and Habiro, T and Sengoku, N and Tanino, H and Watanabe, M},
title = {[Determination of treatment strategies for a 43-year-old single woman with Stage IV breast cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {41},
number = {12},
pages = {1981-1984},
pmid = {25731396},
issn = {0385-0684},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/drug therapy/*secondary ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy ; Female ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; },
abstract = {The patient was a 43-year-old single woman. Her family history included schizophrenia in her mother and manic-depression in her father. Remicade® (infliximab) had been administered for 3 years to treat rheumatoid arthritis. The patient initially presented to our hospital with dyspnea. Computed tomography revealed left-sided breast cancer associated with multiple bone tumors and multiple pulmonary nodules. A poorly mobile mass with an ulcer was found in left breast. Core-needle biopsy and fluorescent in situ hybridization (FISH)revealed an invasive ductal carcinoma that was positive for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2, 2 +). The clinical diagnosis was Stage IV T4bN3M1 cancer (metastases to the lungs, liver, and bone). Because of the presence of bone metastasis, the patient was admitted and she received complete bed rest as supportive therapy. However, the patient decided to receive treatment on an outpatient basis after carefully discussing the following points: 1) treatment of pulmonary metastasis with dyspnea should receive priority; 2) anticancer agents not causing nausea were required; 3) the risk of bone fractures as a complication (spinal cord injury); 4) how she wanted to spend the limited time available with her family; and 5) how the patient wanted to.},
}
@article {pmid25731395,
year = {2014},
author = {Yabe, N and Murai, S and Kunugi, C and Nakadai, J and Oto, I and Yoshikawa, T and Kitasato, K and Shimizu, H and Nakamura, A and Masuda, A and Miyazaki, Y and Ohashi, M and Jinno, H and Kitagawa, Y},
title = {[Synchronous male bladder cancer and breast cancer - a case report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {41},
number = {12},
pages = {1978-1980},
pmid = {25731395},
issn = {0385-0684},
mesh = {*Adenocarcinoma, Scirrhous/drug therapy/secondary/surgery ; Aged ; *Breast Neoplasms/drug therapy/pathology/surgery ; *Breast Neoplasms, Male/drug therapy/pathology/surgery ; Humans ; Lymphatic Metastasis ; Male ; *Neoplasms, Multiple Primary/drug therapy/surgery ; Sentinel Lymph Node Biopsy ; *Urinary Bladder Neoplasms/drug therapy/pathology/surgery ; },
abstract = {A 74-year-old man complained of blood in his urine over a 1-week period beginning in early October 2013, and was examined in the urology department of our hospital. A thorough examination revealed bladder cancer, and surgery was planned after two cycles of preoperative gemcitabine plus cisplatin chemotherapy. A chest computed tomography (CT) performed to evaluate the response to chemotherapy revealed a mass in the right breast. The patient had previously complained about the same site, and mammography and ultrasonography had suggested the possibility of a malignant mammary gland tumor. The results of aspiration cytology were Class V, and based on that finding, a diagnosis of cancer of the right breast was made. In February 2014, we performed a mastectomy, while preserving the pectoral muscles, along with sentinel node biopsy, total cystectomy, urethrectomy, pelvic lymph node dissection, and ureteroileal anastomosis. The histopathological diagnosis of the right breast tumor was invasive ductal carcinoma[scirrhous carcinoma, ly (+), v (-), g (+), f (+), s (+), nuclear grade 1=atypia 2+mitosis 1, EIC (-), ICT (-), NCAT (-)]. A micrometastatic tumor measuring approximately 1mm was observed in the sentinel lymph node. The breast disease was classified as pT1N1mi(sn)M0, Stage IIA, and the tumor was ER (+), PgR (+), HER2/neu (2+), and FISH (-). The bladder cancer was diagnosed as urothelial carcinoma, non-papillary, invasive G2>G3, pT2a; no pelvic lymph node metastases were detected, and it was classified as pT2aN0M0, Stage II. Synchronous male breast cancer and bladder cancer is a very rare condition, and we report the case with a review of the literature.},
}
@article {pmid25731387,
year = {2014},
author = {Tsubota, Y and Sueoka, N and Yamamoto, D},
title = {[A complete response following treatment with Paclitaxel and bevacizumab for metastatic breast cancer].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {41},
number = {12},
pages = {1954-1956},
pmid = {25731387},
issn = {0385-0684},
mesh = {Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/secondary ; Combined Modality Therapy ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Paclitaxel/administration &amp; dosage ; Remission Induction ; },
abstract = {A 60-year-old woman with left breast cancer underwent partial mastectomy and sentinel lymph node biopsy. Pathological examination revealed an invasive ductal carcinoma that was ER (+), PgR (-), HER2 (-), and node positive (1/1). She received adjuvant chemotherapy with doxorubicin and cyclophosphamide (AC), followed by weekly paclitaxel (PTX). After receiving radiation therapy, she was administered an aromatase inhibitor for 5 years. Six months after completion of therapy, she found a hard lymph node in the left infraclavicular area. Fine needle aspiration cytology of the lymph node indicated metastatic breast cancer. Fulvestrant was administered but disease progression was observed after 3 months. Systemic chemotherapy with PTX and bevacizumab (Bev) was begun. After 3 cycles of chemotherapy, computed tomography (CT) scan revealed a complete response (CR). After 6 cycles of chemotherapy, the CR has been maintained.},
}
@article {pmid25731373,
year = {2014},
author = {Sakurai, K and Fujisaki, S and Nagashima, S and Maeda, T and Tomita, R and Suzuki, S and Hara, Y and Hirano, T and Enomoto, K and Amano, S},
title = {[Usefulness of reductive surgery for elderly advanced breast cancer with bone metastases - a case report].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {41},
number = {12},
pages = {1912-1914},
pmid = {25731373},
issn = {0385-0684},
mesh = {Adenocarcinoma, Mucinous/drug therapy/secondary/*surgery ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/*drug therapy/secondary ; Breast Neoplasms/drug therapy/pathology/*surgery ; Carcinoma, Ductal, Breast/drug therapy/secondary/*surgery ; Combined Modality Therapy ; Female ; Humans ; },
abstract = {We report the case of an elderly, advanced breast cancer patient with multiple bone metastases. Breast reduction surgery was useful for this patient. The patient was an 81-year-old woman who had a breast lump. A core needle biopsy for breast cancer led to a diagnosis of invasive ductal carcinoma. The mucinous carcinoma was estrogen receptor (ER) nd progesterone receptor (PgR) positive and HER2/neu negative. Due to patient complications, it was not possible to treat with chemotherapy. The patient was administrated aromatase inhibitors (AI) and zoledronic acid hydrate. However, the AI treatment was not effective, and so she was administered toremifene. Toremifene treatment was effective for 6 months, after which she received fulvestrant. Fulvestrant treatment maintained stable disease (SD)for 14 months. After 14 months of fulvestrant treatment, serum concentrations of the tumor markers CA15-3, CEA, and BCA225 increased. We therefore decided to perform surgical breast reduction surgery. The pathological diagnosis from the surgically resected specimen was mucinous carcinoma, positive for ER and HER2, and negative for PgR. After surgery, serum concentrations of the tumor markers decreased. Following surgery, the patient was administrated lapatinib plus denosumab plus fulvestrant. The patient remains well, without bone metastases, 2 years and 6 months after surgery.},
}
@article {pmid25731362,
year = {2014},
author = {Kakimoto, M and Nakata, T and Imaizumi, K and Hirano, T and Yamamoto, Y and Chikatani, K and Hoshino, M and Matsuyama, T and Motoyama, K and Goto, H and Yoshimura, T and Koshiishi, H and Tsuruta, K},
title = {[A case of locally recurrent breast cancer difficult to differentiate from nodular fasciitis].},
journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy},
volume = {41},
number = {12},
pages = {1881-1883},
pmid = {25731362},
issn = {0385-0684},
mesh = {Aged ; Breast Neoplasms/complications/pathology/*therapy ; Carcinoma, Ductal, Breast/complications/*therapy ; Combined Modality Therapy ; Fasciitis/*etiology ; Fatal Outcome ; Female ; Humans ; Neoplasm Recurrence, Local ; },
abstract = {Breast-conserving surgery was performed on a 78-year-old woman for left breast cancer 5 years previously (invasive ductal carcinoma, T1cN2M0, stage IIIA, ER[+], PR[-], HER2[-]). Chemotherapy, radiotherapy, and hormonal therapy were administered. A left subclavian tumor was detected, and an excisional biopsy was performed. Histological examination showed spindle cells, different from primary breast cancer histology, and nodular fasciitis was diagnosed negative cytokeratin and vimentin immunostaining results. After 12 months, a mass had developed in the same region, and reoperation was performed for resection. Similar spindle cells were observed, but they tested positive for cytokeratin. Carcinoma was diagnosed and thought to be locally recurrent breast cancer. Despite postoperative chemotherapy, the patient experienced bone and lung metastasis and a third local recurrence. She died 13 months following the last surgery. Recurrent breast cancer sometimes displays different histology from the initial cancer, and mimics stromal tumors in certain cases.},
}
@article {pmid25721482,
year = {2015},
author = {Stolfo, D and Merlo, M and Pinamonti, B and Poli, S and Gigli, M and Barbati, G and Fabris, E and Di Lenarda, A and Sinagra, G},
title = {Early improvement of functional mitral regurgitation in patients with idiopathic dilated cardiomyopathy.},
journal = {The American journal of cardiology},
volume = {115},
number = {8},
pages = {1137-1143},
doi = {10.1016/j.amjcard.2015.01.549},
pmid = {25721482},
issn = {1879-1913},
mesh = {Adult ; Cardiomyopathy, Dilated/complications/diagnosis/*physiopathology ; Echocardiography, Doppler, Color ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging, Cine ; Male ; Middle Aged ; Mitral Valve Insufficiency/diagnosis/etiology/*physiopathology ; Prognosis ; *Recovery of Function ; Retrospective Studies ; Time Factors ; Ventricular Function, Left/*physiology ; Ventricular Remodeling/*physiology ; },
abstract = {The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy (IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 ± 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate-free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval [CI] 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation.},
}
@article {pmid25714914,
year = {2015},
author = {Mbongue, JC and Nicholas, DA and Zhang, K and Kim, NS and Hamilton, BN and Larios, M and Zhang, G and Umezawa, K and Firek, AF and Langridge, WH},
title = {Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.},
journal = {PloS one},
volume = {10},
number = {2},
pages = {e0118562},
pmid = {25714914},
issn = {1932-6203},
support = {DK-99-013/DK/NIDDK NIH HHS/United States ; S10 RR027643/RR/NCRR NIH HHS/United States ; R25 GM060507/GM/NIGMS NIH HHS/United States ; 1S10RR027643/RR/NCRR NIH HHS/United States ; P20 MD006988/MD/NIMHD NIH HHS/United States ; 5P20MD006988/MD/NIMHD NIH HHS/United States ; },
mesh = {Cell Differentiation ; Cholera Toxin/genetics/*immunology ; Cluster Analysis ; Dendritic Cells/cytology/*immunology/*metabolism ; Gene Expression Profiling ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*biosynthesis/genetics ; Monocytes/cytology/metabolism ; NF-kappa B/metabolism ; Proinsulin/genetics/*immunology ; Proteome ; Proteomics ; Signal Transduction ; Vaccines, Subunit/genetics/*immunology ; },
abstract = {Dendritic cells (DC) interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1). Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines) showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention of type 1 diabetes autoimmunity.},
}
@article {pmid25714366,
year = {2015},
author = {Medrikova, D and Sijmonsma, TP and Sowodniok, K and Richards, DM and Delacher, M and Sticht, C and Gretz, N and Schafmeier, T and Feuerer, M and Herzig, S},
title = {Brown adipose tissue harbors a distinct sub-population of regulatory T cells.},
journal = {PloS one},
volume = {10},
number = {2},
pages = {e0118534},
pmid = {25714366},
issn = {1932-6203},
mesh = {Adipose Tissue, Brown/*immunology/metabolism/pathology ; Animals ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Inflammation/genetics/immunology/metabolism ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics/methods ; Mice ; Phenotype ; Spleen/cytology/immunology/metabolism ; T-Lymphocyte Subsets/*immunology/metabolism ; T-Lymphocytes, Regulatory/*immunology/metabolism ; },
abstract = {Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control. Here we show that systemic ablation of Treg cells compromised the adaptation of whole-body energy expenditure to cold exposure, correlating with impairment in thermogenic marker gene expression and massive invasion of pro-inflammatory macrophages in brown adipose tissue (BAT). Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature. As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress.},
}
@article {pmid25713171,
year = {2015},
author = {Cohen-Chen, S and Crisp, RJ and Halperin, E},
title = {Perceptions of a changing world induce hope and promote peace in intractable conflicts.},
journal = {Personality &amp; social psychology bulletin},
volume = {41},
number = {4},
pages = {498-512},
pmid = {25713171},
issn = {1552-7433},
mesh = {Adult ; *Conflict, Psychological ; Female ; *Hope ; Humans ; Male ; Negotiating/*psychology ; *Social Perception ; Young Adult ; },
abstract = {The importance of hope in promoting conciliatory attitudes has been asserted in the field of conflict resolution. However, little is known about conditions inducing hope, especially in intractable conflicts, where reference to the outgroup may backfire. In the current research, five studies yielded convergent support for the hypothesis that hope for peace stems from a general perception of the world as changing. In Study 1, coders observed associations between belief in a changing world, hope regarding peace, and support for concessions. Study 2 revealed the hypothesized relations using self-reported measures. Studies 3 and 4 established causality by instilling a perception of the world as changing (vs. unchanging) using narrative and drawing manipulations. Study 5 compared the changing world message with a control condition during conflict escalation. Across studies, although the specific context was not referred to, the belief in a changing world increased support for concessions through hope for peace.},
}
@article {pmid25708664,
year = {2015},
author = {Yıldız, N and Alkan, H and Sarsan, A and Alkan, S},
title = {The effects of repeated filling cystometries on cystometric variables in spinal cord-injured patients with overactive detrusor, who utilize different type of urine drainage methods.},
journal = {Spinal cord},
volume = {53},
number = {8},
pages = {625-629},
pmid = {25708664},
issn = {1476-5624},
mesh = {Adult ; Aged ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Spinal Cord Injuries/*complications ; Treatment Outcome ; Urinary Bladder, Overactive/*etiology/*therapy ; Urinary Catheterization/*methods ; Young Adult ; },
abstract = {STUDY DESIGN: Cross-sectional study.<br><br>OBJECTIVES: Our aim was to compare the effects of repeated cystometric measurements in spinal cord injury (SCI) patients with neurogenic detrusor overactivity (NDO) who use indwelling catheters (IDC) or intermittent catheterization (IC).<br><br>SETTING: Turkey.<br><br>METHODS: A total of 20 SCI patients with NDO, 9 patients on IC and 11 on IDC for at least two consecutive months were included. After emptying the bladder, first involuntary detrusor contraction volume (1stIDCV), cystometric bladder capacity (CC), bladder compliance and maximum detrusor pressure (MPdet) were assessed by filling it with sterile physiological saline at room temperature at a continuous rate of 30&#x2009;ml&#x2009;min(-1). The bladder was re-emptied after the process and a second filling cystometry was performed in the same way.<br><br>RESULTS: When all study population were taken into account, 1stIDCV and CC measures were significantly increased in the second cystometry compared with the first cystometry (P=0.001 and P=0.022, respectively), whereas there was no statistically significant difference on bladder compliance and MPdet measures between the first and the repeated cystometry. There was no statistically significant difference on 1stIDCV, CC and bladder compliance measures between the first and the repeated cystometries for IC group, whereas there was statistically significant increase on these measures in the IDC group (P=0.003, P=0.008 and P=0.022, respectively). In addition there was no statistically significant difference on MP(det) measures between the first and the repeated cystometries for both the urine drainage methods. When IC and IDC groups were compared according to mean values of differences in 1stIDCV, CC and bladder compliance measures between the two cystometries, the IDC group had a statistically significant increase in all parameters when compared with the IC group in the second cystometry performed (P=0.001, P=0.003 and P=0.048, respectively).<br><br>CONCLUSION: Repeated cystometric measurements in SCI patients with NDO lead to an increase in 1stIDCV and CC. However, when the type of urine drainage method is taken into account, although repeated filling cystometry leads to an increase in 1stIDCV, MCC and bladder compliance in patients with IDC, it does not cause a difference in patients on IC.},
}
@article {pmid25697711,
year = {2015},
author = {Moccia, M and Picillo, M and Erro, R and Allocca, R and Barone, P and Vitale, C},
title = {Diagnosis and treatment of restless legs syndrome in progressive supranuclear palsy.},
journal = {Journal of the neurological sciences},
volume = {350},
number = {1-2},
pages = {103-104},
doi = {10.1016/j.jns.2015.01.025},
pmid = {25697711},
issn = {1878-5883},
mesh = {Dopamine Agents/therapeutic use ; Humans ; Male ; Middle Aged ; Restless Legs Syndrome/complications/*diagnosis/*therapy ; Supranuclear Palsy, Progressive/complications/*diagnosis/*therapy ; Treatment Outcome ; },
abstract = {Restless legs syndrome (RLS) has only been recently investigated in a small cohort of progressive supranuclear palsy (PSP) patients and it has been reported to have variable prevalence (among 3.7-58%). However little is known about its management. Here, we report a case of severe RLS occurring during the course of PSP. Diagnostic issues and therapeutic approaches are discussed.},
}
@article {pmid25691085,
year = {2015},
author = {Abouharb, S and Moulder, S},
title = {Metaplastic breast cancer: clinical overview and molecular aberrations for potential targeted therapy.},
journal = {Current oncology reports},
volume = {17},
number = {3},
pages = {431},
pmid = {25691085},
issn = {1534-6269},
mesh = {Antineoplastic Agents/*therapeutic use ; *Breast Neoplasms/drug therapy/genetics/pathology/secondary ; *Carcinoma/drug therapy/genetics/pathology/secondary ; Diagnosis, Differential ; Female ; Humans ; Molecular Targeted Therapy/*methods ; Prognosis ; *Rare Diseases/drug therapy/genetics/pathology ; },
abstract = {Metaplastic breast cancer is a rare subtype of invasive mammary carcinoma, with an aggressive behavior and usually poor outcome. Responses to systemic chemotherapy are suboptimal compared to patients with standard invasive ductal carcinoma. Limited data are available in regards to best treatment modalities, including chemotherapy. This review gives an overview of metaplastic breast cancer and its clinical and pathologic characteristics, in addition to treatment strategies, clinical trials, and future directions.},
}
@article {pmid25658358,
year = {2015},
author = {Matsuda, Y and Ishiwata, T and Izumiyama-Shimomura, N and Hamayasu, H and Fujiwara, M and Tomita, K and Hiraishi, N and Nakamura, K and Ishikawa, N and Aida, J and Takubo, K and Arai, T},
title = {Gradual telomere shortening and increasing chromosomal instability among PanIN grades and normal ductal epithelia with and without cancer in the pancreas.},
journal = {PloS one},
volume = {10},
number = {2},
pages = {e0117575},
pmid = {25658358},
issn = {1932-6203},
mesh = {Carcinoma in Situ/genetics/metabolism/*pathology ; Chromosomal Instability/*genetics ; Epithelium/metabolism/*pathology ; Humans ; Pancreas/metabolism/*pathology ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Telomere/genetics/*pathology ; *Telomere Shortening ; },
abstract = {A large body of evidence supports a key role for telomere dysfunction in carcinogenesis due to the induction of chromosomal instability. To study telomere shortening in precancerous pancreatic lesions, we measured telomere lengths using quantitative fluorescence in situ hybridization in the normal pancreatic duct epithelium, pancreatic intraepithelial neoplasias (PanINs), and cancers. The materials employed included surgically resected pancreatic specimens without cancer (n = 33) and with invasive ductal carcinoma (n = 36), as well as control autopsy cases (n = 150). In comparison with normal ducts, telomere length was decreased in PanIN-1, -2 and -3 and cancer. Furthermore, telomeres were shorter in cancer than in PanIN-1 and -2. Telomere length in cancer was not associated with histological type, lesion location, or cancer stage. PanINs with or without cancer showed similar telomere lengths. The incidences of atypical mitosis and anaphase bridges, which are morphological characteristics of chromosomal instability, were negatively correlated with telomere length. The telomeres in normal duct epithelium became shorter with aging, and those in PanINs or cancers were shorter than in age-matched controls, suggesting that telomere shortening occurs even when histological changes are absent. Our data strongly suggest that telomere shortening occurs in the early stages of pancreatic carcinogenesis and progresses with precancerous development. Telomere shortening and chromosomal instability in the duct epithelium might be associated with carcinogenesis of the pancreas. Determination of telomere length in pancreatic ductal lesions may be valuable for accurate detection and risk assessment of pancreatic cancer.},
}
@article {pmid25648466,
year = {2015},
author = {Boland, MR and Prichard, RS and Daskalova, I and Lowery, AJ and Evoy, D and Geraghty, J and Rothwell, J and Quinn, CM and O'Doherty, A and McDermott, EW},
title = {Axillary nodal burden in primary breast cancer patients with positive pre-operative ultrasound guided fine needle aspiration cytology: management in the era of ACOSOG Z011.},
journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology},
volume = {41},
number = {4},
pages = {559-565},
doi = {10.1016/j.ejso.2015.01.011},
pmid = {25648466},
issn = {1532-2157},
mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology/surgery ; Breast Neoplasms, Male/pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Image-Guided Biopsy ; *Lymph Node Excision ; Lymph Nodes/diagnostic imaging/*pathology/*surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Preoperative Care ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Tumor Burden ; Ultrasonography, Interventional ; Young Adult ; },
abstract = {INTRODUCTION: Recent years have seen a dramatic shift to more conservative management of the axilla in patients with a positive sentinel lymph node biopsy (SLNB). Identification of nodal disease with positive pre-operative ultrasound guided axillary fine needle aspiration cytology (AUS/FNAC) may represent a higher axillary disease burden mandating an axillary clearance and thus an upfront SLNB may be avoided. The aims of this study were to quantify nodal burden in patients with positive pre-operative AUS/FNAC and identify patients who may have been able to avoid an axillary clearance (ALND) based on ACOSOG Z011 criteria.<br><br>METHODS: A retrospective review of a prospectively maintained database identified patients with positive pre-operative AUS/FNAC between 2007 and 2012. Core biopsies were excluded. Demographic and tumour characteristics were analysed. Eligibility for ACOSOG Z011 criteria was assessed and patients who may have avoided ALND were identified.<br><br>RESULTS: 432 patients were identified with positive AUS/FNAC. 85 patients were excluded leaving 347 for analysis. Median age was 56 years (22-87), median tumour size was 25 mm (1.5 mm-150 mm) and median tumour pathology was grade 3 (50%) and invasive ductal carcinoma (82%). Median number of nodes removed at ALND was 23 (1-55) with a median number of positive nodes being 4 (1-47). 134 (39%) patients had &#x2264;2 positive nodes identified on ALND making them eligible for the ACOSOG Z011 study. When other ACOSOG Z011 exclusion factors were applied only 27 (7.8%) patients may have avoided ALND.<br><br>CONCLUSIONS: Nodal positivity on AUS/FNAC is associated with higher axillary disease burden. Few patients would satisfy ACOSOG/Z011 criteria and avoid ALND making an upfront SLNB unnecessary.},
}
@article {pmid25645984,
year = {2015},
author = {Cao, YW and Wan, GX and Sun, JP and Cui, XB and Hu, JM and Liang, WH and Zheng, YQ and Li, WQ and Li, F},
title = {Implications of the Notch1-Snail/Slug-epithelial to mesenchymal transition axis for lymph node metastasis in infiltrating ductal carcinoma.},
journal = {The Kaohsiung journal of medical sciences},
volume = {31},
number = {2},
pages = {70-76},
pmid = {25645984},
issn = {2410-8650},
mesh = {Antigens, CD/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Receptor, Notch1/*metabolism ; Snail Family Transcription Factors ; Transcription Factors/*metabolism ; },
abstract = {Emerging evidence suggests that activation of the Notch1 signaling pathway inducing epithelial to mesenchymal transition (EMT) mediated by Snail/Slug promotes invasion and metastasis of breast cancer cells in vitro. However, the implication of the Notch1-Snail/Slug-EMT axis in breast cancer patients remains unclear. A total of 200 formalin-fixed paraffin-embedded samples of invasive ductal carcinoma (IDC), and 37 adjacent non-neoplastic tissue (ANNT) samples from patients who had not been treated with neoadjuvant therapy were examined. Expression of Notch1, Slug, Snail, E-cadherin, N-cadherin, and vimentin was determined by immunohistochemistry on tissue microarrays (TMAs). The correlation between protein expression and clinicopathological characteristics of breast cancer patients was also evaluated. Results showed that a significantly high percentage of cases with high expression of Notch1 (74%, 148/200), Slug (36%, 72/200), Snail (62%, 124/200), and N-cadherin (77%, 153/200) and a low percentage of cases with high expression of E-cadherin (27%, 54/200) were observed in IDC compared to those in ANNTs. High Notch1, Slug, Snail, and N-cadherin expression and low E-cadherin expression in patients with IDC were significantly correlated with lymph node metastasis. In addition, correlation analysis results revealed that high Notch1 expression was significantly associated with high Slug, Snail, and N-cadherin expression and low E-cadherin expression in IDC. Furthermore, a high Snail expression was significantly associated with low E-cadherin expression, and a high Slug expression was found to be significantly associated with increased N-cadherin expression in patients with IDC. Hence, our study suggested that the Notch1-Snail/Slug-EMT axis may be implicated in the lymph node metastasis affecting patients with IDC.},
}
@article {pmid25644728,
year = {2014},
author = {Moschetta, M and Telegrafo, M and Cornacchia, I and Vincenti, L and Ranieri, V and Cirili, A and Rella, L and Stabile Ianora, AA and Angelelli, G},
title = {PIP breast implants: rupture rate and correlation with breast cancer.},
journal = {Il Giornale di chirurgia},
volume = {35},
number = {11-12},
pages = {274-278},
pmid = {25644728},
issn = {0391-9005},
mesh = {Adult ; *Breast Implants ; Breast Neoplasms/*diagnosis/*epidemiology/etiology ; Female ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Prospective Studies ; *Prosthesis Failure ; },
abstract = {AIM: To evaluate the incidence of Poly Implant Prosthése (PIP) rupture as assessed by magnetic resonance imaging (MRI), the prevalence of the detected signs and the potential correlation with breast carcinoma.<br><br>PATIENTS AND METHODS: 67 patients with silicone breast implants and clinical indications for breast MRI were evaluated for a total of 125 implants: 40 (32%) PIP in 21 patients and 85 non-PIP in 46 patients (68%), the latest considered as control group. A 1.5-T MR imaging device was used in order to assess implant integrity with dedicated sequences and in 6 cases a dynamic study was performed for characterizing breast lesions. Two radiologists with more than 5 years' experience in the field of MRI evaluated in consensus all MR images searching for the presence of clear signs of intra or extra-capsular implant rupture.<br><br>RESULTS: 20/40 (50%) PIP implants presented signs of intra-capsular rupture: linguine sign in 20 cases (100%), tear-drop sign in 6 (30%). In 12/20 cases (60%), MRI signs of extra-capsular rupture were detected. In the control group, an intra-capsular rupture was diagnosed in 12/85 cases (14%) associated with extra-capsular one in 5/12 cases (42%). Among the six cases with suspected breast lesions, in 2/21 patients with PIP implants (10%) a breast carcinoma was diagnosed (mucinous carcinoma, n=1; invasive ductal carcinoma, n=1). In 4/46 patients (9%) with non-PIP implants, an invasive ductal carcinoma was diagnosed.<br><br>CONCLUSION: The rupture rate of PIP breast implants is significantly higher than non-PIP (50% vs 14%). MRI represents the most accurate imaging tool for evaluating breast prostheses and the linguine sign is the most common MRI sign to be searched. The incidence of breast carcinoma does not significantly differ between the PIP and non-PIP implants and a direct correlation with breast cancer can not been demonstrated.},
}
@article {pmid25640082,
year = {2015},
author = {Li, L and Wang, K and Sun, X and Wang, K and Sun, Y and Zhang, G and Shen, B},
title = {Parameters of dynamic contrast-enhanced MRI as imaging markers for angiogenesis and proliferation in human breast cancer.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {21},
number = {},
pages = {376-382},
pmid = {25640082},
issn = {1643-3750},
mesh = {Adult ; Aged ; Antigens, CD/metabolism ; Biomarkers/metabolism ; Breast Neoplasms/*diagnosis/metabolism/*pathology ; Cell Proliferation ; Contrast Media/*chemistry ; Endoglin ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neovascularization, Pathologic/*pathology ; Permeability ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Prognosis ; Receptors, Cell Surface/metabolism ; },
abstract = {BACKGROUND: Breast cancer is the most common malignancy and the leading cause of cancer death in women worldwide; however, early diagnosis has been difficult due to its complex pathological structure. This study evaluated the value of morphological examination in conjunction with dynamic contrast-enhanced MRI (DCE-MRI) for more precise diagnosis of breast cancer, as well as their correlation with angiogenesis and proliferation biomarkers.<br><br>MATERIAL/METHODS: DCE-MRI parameters (including Ktrans: volume transfer coefficient reflecting vascular permeability, Kep: flux rate constant, Ve: extracellular volume ratio reflecting vascular permeability, and ADC: apparent diffusion coefficient) were obtained from 124 patients with breast cancer (124 lesions). Microvessel density (MVD) was evaluated by the immunohistochemical analysis of tumor vessels for CD31 and CD105 expression. The proliferation was assessed by analyzing Ki67.<br><br>RESULTS: Ktrans values were in the order of: malignant lesions>benign lesions>normal glands. Similar results were observed for Kep. The opposite changes were seen with Ve. Ktrans and Kep values were significantly higher in invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) than in mammary ductal dysplasia (MDD; ANOVA followed by Dunnett's test). In sharp contrast, ADC values were lower in IDC and DCIS than in MDD, and Ve was not significantly different among the three groups. The data from MIP (maximum intensity projection) showed that benign breast lesions had no or only one blood vessel, whereas malignant lesions had two or more blood vessels. In addition, expression of CD105 and Ki67, the commonly recognized markers for angiogenesis and proliferation, respectively, were closely correlated with MRI parameters as revealed by Pearson analysis.<br><br>CONCLUSIONS: Determination of Ktrans, Kep and ADC values permits estimation of tumor angiogenesis and proliferation in breast cancer and DCE-MRI parameters can be used as imaging biomarkers to predict patient prognosis and the biologic aggressiveness of the tumor.},
}
@article {pmid29147419,
year = {2015},
author = {Budimir, I and Sabol Pusic, M and Nikolic, M and Dorosulic, Z and Ljubicic, N and Stajduhar, E and Mise, I and Vazdar, L and Sarcevic, B},
title = {Obstructive Jaundice as an Uncommon Manifestation of Metastatic Breast Cancer.},
journal = {World journal of oncology},
volume = {6},
number = {1},
pages = {297-300},
pmid = {29147419},
issn = {1920-454X},
abstract = {Invasive ductal carcinoma is the most common type of breast cancer and accounts for about 70-85% of all invasive breast carcinomas. It primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain. Most of breast cancer recurrence occurs within the first 5 years of diagnosis, particularly for ER negative disease. Gastrointestinal tract involvement is very rare and is detected in only 10% of all the cases, and it usually derives from lobular breast cancer rather than the much more common cell type of ductal breast cancer. Early diagnosis is very important because it enables prompt and adequate choice of treatment and improves patient's long-term prognosis. In this report we describe an unusual case of obstructive jaundice caused by metastases from invasive ductal breast cancer to the lymph nodes of the hepatoduodenal ligament with extramural compression of the distal common bile duct and tumor invasion to the lumen of the duct. Our goal is to emphasize possible diagnostic pitfalls and increase the clinical awareness and the importance of intensive follow-up in patients with breast cancer, even years after the initial diagnosis.},
}
@article {pmid25620480,
year = {2014},
author = {Hua, X and Huang, X and Liao, Z and Xian, Q and Yu, L},
title = {[Changes of fibroblast immunophenotype and their clinical significance in stromal remodeling of breast tumors].},
journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]},
volume = {36},
number = {11},
pages = {834-838},
pmid = {25620480},
issn = {0253-3766},
mesh = {Breast ; Breast Neoplasms/immunology/*pathology ; Carcinoma in Situ ; Carcinoma, Ductal, Breast ; Carcinoma, Intraductal, Noninfiltrating ; Endopeptidases ; Fibroblasts/*immunology ; Gelatinases/metabolism ; Humans ; Hyperplasia ; Immunohistochemistry ; Immunophenotyping ; Membrane Proteins/metabolism ; Serine Endopeptidases/metabolism ; },
abstract = {OBJECTIVE: To evaluate the immunophenotype conversion of fibroblasts and its clinical significance in the process of breast tumor stromal remodeling.<br><br>METHODS: CD34, FAP-&#x3b1;, p63 and a-SMA were detected by immunohistochemistry in 273 breast biopsies, including 60 normal breast tissues, 46 atypical ductal hyperplasia (ADH), 60 ductal carcinoma in situ (DCIS), 47 DCIS microinvasive carcinoma (DCIS-MI) and 60 invasive ductal carcinoma (IDC).<br><br>RESULTS: The positive expression rates of CD34, FAP-&#x3b1; and &#x3b1;-SMA in the stromal fibroblasts of normal breast tissues were 93.3%, 6.7% and 18.3%, respectively. Those in the stromal fibroblasts of ADH tissues were 95.7%, 4.3% and 10.9%, respectively. Those in the stromal fibroblasts of DCIS tissues were 95.0%, 8.3% and 15.0%, respectively. Those in the IDC tissues were 35.0%, 85.0% and 93.3%, respectively. The expressions of CD34, &#x3b1;-SMA and FAP-&#x3b1; in the stromal fibroblasts of normal, ASH and DCIS breast tissues did not show significant differences (&#x3c7;(2) = 1.142, P = 0.896). The main immunophenotype of stromal fibroblasts in the tumor-host interface at the invasive front of ADH and DCIS lesions was CD34(+)&#x3b1;-SMA(+)FAP-&#x3b1;(+). There were statistically significant differences in the expression of CD34, &#x3b1;-SMA and FAP-&#x3b1; between IDC and ADH, DCIS and normal breast tissues (&#x3c7;(2) = 8.351, P < 0.001). The immunophenotype of stromal fibroblasts in the IDC and DCIS-MI breast tissues was CD34(-) &#x3b1;-SMA(+) FAP-&#x3b1;(+).<br><br>CONCLUSIONS: Immunophenotype conversion from CD34(+) &#x3b1;-SMA(-) FAP-&#x3b1;(-) to CD34(-) &#x3b1;-SMA(+)FAP-&#x3b1;(+) may be a sensitive indicator to judge whether DCIS has microinvasion. Detection of the immunophenotype conversion of stromal fibroblasts may be helpful to determine the presence of microinvasion, and to improve the diagnostic accuracy rate of DCIS.},
}
@article {pmid25604797,
year = {2015},
author = {Braunstein, LZ and Brock, JE and Chen, YH and Truong, L and Russo, AL and Arvold, ND and Harris, JR},
title = {Invasive lobular carcinoma of the breast: local recurrence after breast-conserving therapy by subtype approximation and surgical margin.},
journal = {Breast cancer research and treatment},
volume = {149},
number = {2},
pages = {555-564},
doi = {10.1007/s10549-015-3273-y},
pmid = {25604797},
issn = {1573-7217},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma, Lobular/*pathology/radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retreatment ; Risk Factors ; Time Factors ; Tumor Burden ; Young Adult ; },
abstract = {Invasive lobular carcinoma (ILC) typically presents at a later stage than invasive ductal carcinoma (IDC) and poses unique radiographic and surgical challenges. However, current principles of breast-conserving therapy (BCT) do not distinguish between histologic subtypes, raising uncertainty about the optimal approach for patients with ILC. We studied 998 BCT patients from 1998-2007, comprised 74 % IDC, 8 % ILC, and 18 % with mixed ILC/IDC. In light of recent guidelines addressing surgical margins, specimens were assessed for margin width and biologic subtype. The Kaplan-Meier method and Cox proportional hazards models were used to analyze effects of patient and disease characteristics on local recurrence (LR). At a median of 119 months, 45 patients had an isolated LR. 10-year LR was 5.5 % for patients with IDC, 4.4 % for ILC, and 1.2 % for mixed histology (p = 0.08). The majority of ILC cases had luminal A biologic subtype (91.1 %), and analysis among all luminal A cases revealed 10-year LR of 2.6 % for IDC, 3.4 % for ILC, and 0 % for mixed tumors (p = 0.12). Patients with ILC were more likely to have initially positive surgical margins (45.0 vs 17.5 %; p < 0.001) resulting in more frequent re-excision (57.1 % vs 40.4 %; p = 0.02), though final margins were similar between ILC and IDC (p = 0.88). No LR was observed among ILC or mixed histology patients with margins <2 mm (n = 28). On multivariate analysis, histologic subtype was not associated with LR (p = 0.52). Modern approaches confer similarly favorable LR rates for ILC, IDC, and mixed histology breast cancers despite inherent histologic differences. Patients with ILC did not require more extensive surgical margins than those with IDC.},
}
@article {pmid25598690,
year = {2015},
author = {Choi, JW and Moon, WJ and Choi, N and Roh, HG and Kim, MY and Kim, NR and Moon, SG and Chung, HW and Lim, SD and Yang, JH},
title = {Charcoal-induced granuloma that mimicked a nodal metastasis on ultrasonography and FDG-PET/CT after neck dissection.},
journal = {Korean journal of radiology},
volume = {16},
number = {1},
pages = {196-200},
pmid = {25598690},
issn = {2005-8330},
mesh = {Breast Neoplasms/pathology/surgery/therapy ; Carcinoma/*pathology/surgery/therapy ; Cervix Uteri/diagnostic imaging/pathology ; Charcoal/toxicity ; Female ; Fluorodeoxyglucose F18 ; Granuloma/*diagnosis/pathology ; Humans ; Lymph Nodes/diagnostic imaging/*surgery ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Positron-Emission Tomography ; Radiopharmaceuticals ; Tomography, X-Ray Computed ; Ultrasonography ; },
abstract = {Charcoal can be used for preoperative localization of metastatic lymph nodes in the neck. Charcoal remains stable without causing foreign body reactions during as hort period. However, foreign body reactions may develop if charcoal is left in situ for more than 6 months. We reported a case of charcoal granuloma mimicking local recurrence on fluorodeoxyglucose-positron emission tomography/computed tomography and ultrasonography in a 47-year-old woman who had cervical lymph node dissection due to metastatic invasive ductal carcinoma of the breast.},
}
@article {pmid25585858,
year = {2015},
author = {Bas, R and Vallverdú, M and Valencia, JF and Voss, A and de Luna, AB and Caminal, P},
title = {Evaluation of acceleration and deceleration cardiac processes using phase-rectified signal averaging in healthy and idiopathic dilated cardiomyopathy subjects.},
journal = {Medical engineering &amp; physics},
volume = {37},
number = {2},
pages = {195-202},
doi = {10.1016/j.medengphy.2014.12.001},
pmid = {25585858},
issn = {1873-4030},
mesh = {Adult ; Cardiomyopathy, Dilated/complications/diagnosis/*physiopathology ; Case-Control Studies ; Death, Sudden, Cardiac ; *Deceleration ; Feasibility Studies ; Female ; Follow-Up Studies ; Heart/*physiology/*physiopathology ; Humans ; Male ; Middle Aged ; Risk Assessment ; *Signal Processing, Computer-Assisted ; Sleep ; Wakefulness ; },
abstract = {The aim of the present study was to investigate the suitability of the Phase-Rectified Signal Averaging (PRSA) method for improved risk prediction in cardiac patients. Moreover, this technique, which separately evaluates acceleration and deceleration processes of cardiac rhythm, allows the effect of sympathetic and vagal modulations of beat-to-beat intervals to be characterized. Holter recordings of idiopathic dilated cardiomyopathy (IDC) patients were analyzed: high-risk (HR), who suffered sudden cardiac death (SCD) during the follow-up; and low-risk (LR), without any kind of cardiac-related death. Moreover, a control group of healthy subjects was analyzed. PRSA indexes were analyzed, for different time scales T and wavelet scales s, from RR series of 24 h-ECG recordings, awake periods and sleep periods. Also, the behavior of these indexes from simulated data was analyzed and compared with real data results. Outcomes demonstrated the PRSA capacity to significantly discriminate healthy subjects from IDC patients and HR from LR patients on a higher level than traditional temporal and spectral measures. The behavior of PRSA indexes agrees with experimental evidences related to cardiac autonomic modulations. Also, these parameters reflect more regularity of the autonomic nervous system (ANS) in HR patients.},
}
@article {pmid25585381,
year = {2015},
author = {Yang, M and Tang, M and Ma, X and Yang, L and He, J and Peng, X and Guo, G and Zhou, L and Luo, N and Yuan, Z and Tong, A},
title = {AP-57/C10orf99 is a new type of multifunctional antimicrobial peptide.},
journal = {Biochemical and biophysical research communications},
volume = {457},
number = {3},
pages = {347-352},
doi = {10.1016/j.bbrc.2014.12.115},
pmid = {25585381},
issn = {1090-2104},
mesh = {Amino Acid Sequence ; Antimicrobial Cationic Peptides/chemistry/*genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; Colorectal Neoplasms/genetics/metabolism/pathology ; Conserved Sequence ; DNA, Neoplasm/metabolism ; DNA-Binding Proteins/chemistry/*genetics/*metabolism ; Humans ; Molecular Sequence Data ; Recombinant Proteins/genetics/metabolism ; Sequence Homology, Amino Acid ; Tissue Distribution ; Tumor Suppressor Proteins/chemistry/genetics/metabolism ; },
abstract = {Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune response that provides host defence at skin and mucosal surfaces. Here, we report the identification and characterization of a new type human AMPs, termed AP-57 (Antimicrobial Peptide with 57 amino acid residues), which is also known as C10orf99 (chromosome 10 open reading frame 99). AP-57 is a short basic amphiphilic peptide with four cysteines and a net charge +14 (MW = 6.52, PI = 11.28). The highest expression of AP-57 were detected in the mucosa of stomach and colon through immunohistochemical assay. Epithelium of skin and esophagus show obvious positive staining and strong positive staining were also observed in some tumor and/or their adjacent tissues, such as esophagus cancer, hepatocellular carcinoma, squamous cell carcinoma and invasive ductal carcinoma. AP-57 exhibited broad-spectrum antimicrobial activities against Gram-positive Staphylococcus aureus, Actinomyce, and Fungi Aspergillus niger as well as mycoplasma and lentivirus. AP-57 also exhibited DNA binding capacity and specific cytotoxic effects against human B-cell lymphoma Raji. Compared with other human AMPs, AP-57 has its distinct characteristics, including longer sequence length, four cysteines, highly cationic character, cell-specific toxicity, DNA binding and tissue-specific expressing patterns. Together, AP-57 is a new type of multifunctional AMPs worthy further investigation.},
}
@article {pmid25583208,
year = {2015},
author = {Bursle, EC and Dyer, J and Looke, DF and McDougall, DA and Paterson, DL and Playford, EG},
title = {Risk factors for urinary catheter associated bloodstream infection.},
journal = {The Journal of infection},
volume = {70},
number = {6},
pages = {585-591},
doi = {10.1016/j.jinf.2015.01.001},
pmid = {25583208},
issn = {1532-2742},
mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Australia/epidemiology ; Bacteremia ; Case-Control Studies ; Catheter-Related Infections/drug therapy/*epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Risk Factors ; Urinary Catheterization/*adverse effects ; Urinary Catheters/*adverse effects ; Urinary Tract Infections/drug therapy/*epidemiology ; },
abstract = {OBJECTIVES: Urinary catheter associated bloodstream infection (UCABSI) causes significant morbidity, mortality and healthcare costs. We aimed to define the risk factors for UCABSI.<br><br>METHODS: A case-control study was conducted at two Australian tertiary hospitals. Patients with urinary source bloodstream infection associated with an indwelling urinary catheter (IDC) were compared to controls with an IDC who did not develop urinary source bloodstream infection.<br><br>RESULTS: There were 491 controls and 67 cases included in the analysis. Independent statistically significant risk factors for the development of UCABSI included insertion of the catheter in operating theatre, chronic kidney disease, age-adjusted Charlson comorbidity index, accurate urinary measurements as reason for IDC insertion and dementia. IDCs were inserted for valid reasons in nearly all patients, however an appropriate indication at 48 h post-insertion was found in only 44% of patients. Initial empiric antibiotics were deemed inappropriate in 23 patients (34%).<br><br>CONCLUSION: To our knowledge, this is the first study to look specifically at the risk factors for bloodstream infection in urinary catheterised patients. Several risk factors were identified. IDC management and empiric management of UCABSI could be improved and is likely to result in a decreased incidence of infection and its complications.},
}
@article {pmid25574147,
year = {2014},
author = {Yano, H and Nakayama, N and Morimitsu, K and Futamura, M and Ohe, N and Miwa, K and Shinoda, J and Iwama, T},
title = {Changes in protein level in the cerebrospinal fluid of a patient with cerebral radiation necrosis treated with bevacizumab.},
journal = {Clinical Medicine Insights. Oncology},
volume = {8},
number = {},
pages = {153-157},
pmid = {25574147},
issn = {1179-5549},
abstract = {A 32-year-old woman underwent surgeries and radiation therapy for astrocytoma. She developed symptomatic radiation necrosis in the lesion, which caused hydrocephalus. She initially underwent ventricular drainage, because the protein level in the cerebrospinal fluid (CSF) was 787 mg/dL, which was too high for shunt surgery. Because she also had breast cancer, which was pathologically diagnosed as an invasive ductal carcinoma, standard bevacizumab therapy in combination with paclitaxel every 2 weeks was selected. Interestingly, after 2 days, the agents had dramatically reduced the CSF protein level. However, it returned to approximately the initial level within 2 weeks. After two courses of this regimen, a ventriculoperitoneal shunt was placed. After 10 courses of this regimen, the CSF protein level decreased to 338 mg/dL, which is less than half of the initial level. Long-term administration of bevacizumab might decrease leakage of protein from the vessels around the ventriculus.},
}
@article {pmid25571972,
year = {2015},
author = {Vogel, S and Börger, V and Peters, C and Förster, M and Liebfried, P and Metzger, K and Meisel, R and Däubener, W and Trapp, T and Fischer, JC and Gawaz, M and Sorg, RV},
title = {Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death.},
journal = {Cell death and differentiation},
volume = {22},
number = {7},
pages = {1219-1230},
pmid = {25571972},
issn = {1476-5403},
mesh = {Animals ; *Apoptosis ; Chemotaxis ; Dendritic Cells/*physiology ; HMGB1 Protein/*metabolism ; Hepatocyte Growth Factor/*metabolism ; Humans ; Inflammation ; Male ; Mesenchymal Stem Cells/*physiology ; Mice ; Monocytes/*physiology ; Myocytes, Cardiac/metabolism/physiology ; *Necrosis ; Neurons/metabolism/physiology ; Regeneration ; },
abstract = {Tissue damage due to apoptotic or necrotic cell death typically initiates distinct cellular responses, leading either directly to tissue repair and regeneration or to immunological processes first, to clear the site, for example, of potentially damage-inducing agents. Mesenchymal stem cells (MSC) as well as immature dendritic cells (iDC) and monocytes migrate to injured tissues. MSC have regenerative capacity, whereas monocytes and iDC have a critical role in inflammation and induction of immune responses, including autoimmunity after tissue damage. Here, we investigated the influence of apoptotic and necrotic cell death on recruitment of MSC, monocytes and iDC, and identified hepatocyte growth factor (HGF) and the alarmin high mobility group box 1 (HMGB1) as key factors differentially regulating these migratory responses. MSC, but not monocytes or iDC, were attracted by apoptotic cardiomyocytic and neuronal cells, whereas necrosis induced migration of monocytes and iDC, but not of MSC. Only apoptotic cell death resulted in HGF production and HGF-mediated migration of MSC towards the apoptotic targets. In contrast, HMGB1 was predominantly released by the necrotic cells and mediated recruitment of monocytes and iDC via the receptor of advanced glycation end products. Moreover, necrotic cardiomyocytic and neuronal cells caused an HMGB1/toll-like receptor-4-dependent inhibition of MSC migration towards apoptosis or HGF, while recruitment of monocytes and iDC by necrosis or HMGB1 was not affected by apoptotic cells or HGF. Thus, the type of cell death differentially regulates recruitment of either MSC or monocytes and iDC through HGF and HMGB1, respectively, with a dominant, HMGB1-mediated role of necrosis in determining tropism after tissue injury.},
}
@article {pmid27386035,
year = {2015},
author = {Adeniji-Sofoluwe, AT and Obajimi, GO and Obajimi, MO},
title = {Pregnancy related breast diseases in a developing African country: Initial Sonographic Evaluation.},
journal = {The Pan African medical journal},
volume = {20},
number = {},
pages = {239},
pmid = {27386035},
issn = {1937-8688},
mesh = {Adult ; Breast Diseases/diagnosis/*epidemiology/pathology ; Breast Feeding ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology ; Female ; Humans ; Lactation ; Nigeria/epidemiology ; Nipple Discharge ; Pregnancy ; Pregnancy Complications/diagnosis/*epidemiology/pathology ; Pregnancy Complications, Neoplastic/diagnosis/*epidemiology/pathology ; Retrospective Studies ; Risk Factors ; Ultrasonography, Mammary ; Young Adult ; },
abstract = {Benign diseases are more common than malignant diseases in pregnant and lactating women. Fibroadenomas are the most commonly identified benign breast tumour in pregnant and lactating women. Pregnancy related breast cancer is defined as breast cancer that occurs during pregnancy or within 1 year of delivery. Its incidence is estimated at 1 in 3000 to 1 in 10 000 pregnancies. Several reproductive factors like age at menarche, age at menopause, age at full-term pregnancy, parity, age at any birth and spacing of pregnancies, breast feeding, characteristics of the menstrual cycle, infertility, spontaneous and induced abortions, characteristics of the menstrual cycle and infertility are some of the factors that have been incriminated as risk factors for breast cancer. We sought to describe the predominant breast pattern, sonographic array of pregnancy related breast diseases in women referred to the breast imaging unit in the department of Radiology at the University College Hospital, Ibadan south west Nigeria. Socio-demographic characteristics in these women were also evaluated. Archived images were reviewed and documented and data was analysed with SPSS version 17 and presented with descriptives. In this descriptive study, we retrospectively retrieved the sonomammographic records of 21 women (pregnant or lactating) referred to and imaged in the department of radiology, University college hospital Ibadan, between 2006 and 2013. Diagnostic breast sonograms performed by MO and ATS; Consultant radiologists with 7-10 years' experience utilized a 7-10 MHz transducer of the General electric GE Logiq P5 machine for the scans. Twenty-one women with ages between 22-42 years (Mean 31.4 ± 5.4 SD) pregnant or lactating were referred to the radiology department for sonomammographic evaluation. Majority of the women were in the 3rd decade. Referral was mainly (11) by family Physicians from the general outpatient clinic, 5 were self-referred, 2 from radiotherapy department, 2 from obstetrics and gynaecology department and 1 from the surgical outpatient clinic. Nineteen (89.5%) were lactating and breastfeeding while 2 (10.5%) were pregnant. Nipple discharge (89.5%) was the predominant presenting complaint in the study. They were all married with the majority attaining menarche at age 14.6 ± 2.1 SD years. Most of the women were multi-parous 17(89.5%) and possessed higher level of Education 17 (81.0%). Twenty (96.0%) women had no previous breast disease while only 1 (4.0%) woman had a positive family history of breast cancer. They weighed between 44-102 kg (mean 69.84 kg ± 15.33 SD). Their mean height was 159.8 cm. Waist hip ratio was between 0.69-0.93 (Mean 0.83). The heterogeneous fibroglandular pattern was predominant in 15 (71.4%) women. Final BIRADS assessment of 2 was most frequent (11/21) 52.4% while 19.0% were assigned to BIRADS categories 0 and 1 (4/21). Histological diagnosis of Invasive ductal carcinoma was made in the 3 women with final BIRADS of 5 breast diseases found in most pregnant and lactating women were benign. It is important to note that malignant breast lesions can also occur in this group of women who may assume that the changes noted in their breast are due to lactation.},
}
@article {pmid25527452,
year = {2015},
author = {Huang, KT and Tan, D and Chen, KE and Walker, AM},
title = {Blockade of estrogen-stimulated proliferation by a constitutively-active prolactin receptor having lower expression in invasive ductal carcinoma.},
journal = {Cancer letters},
volume = {358},
number = {2},
pages = {152-160},
doi = {10.1016/j.canlet.2014.12.031},
pmid = {25527452},
issn = {1872-7980},
mesh = {Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Estradiol/metabolism/pharmacology ; Estrogens/*metabolism/pharmacology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Neoplasm Invasiveness ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Receptors, Prolactin/chemistry/genetics/*metabolism ; },
abstract = {A comprehensive understanding of prolactin's (PRL's) role in breast cancer is complicated by disparate roles for alternatively-spliced PRL receptors (PRLR) and crosstalk between PRL and estrogen signaling. Among PRLRs, the short form 1b (SF1b) inhibits PRL-stimulated cell proliferation. In addition to ligand-dependent PRLRs, constitutively-active varieties, missing the S2 region of the extracellular domain (ΔS2), naturally occur. Expression analysis of the ΔS2 version of SF1b (ΔS2SF1b) showed higher expression in histologically-normal contiguous tissue versus invasive ductal carcinoma. To determine the function of ΔS2SF1b, a T47D breast cancer line with inducible expression was produced. Induction of ΔS2SF1b blocked estrogen-stimulated cell proliferation. Unlike intact SF1b, induction of ΔS2SF1b had no effect on PRL-mediated activation of Stat5a. However induction inhibited estrogen's stimulatory effects on serine-118 phosphorylation of estrogen receptor α, serine-473 phosphorylation of Akt, serine-9 phosphorylation of GSK3β, and c-myc expression. In addition, induction of ΔS2SF1b increased expression of the cell cycle-inhibiting protein, p21. Thus, increased expression of ΔS2SF1b, such as we demonstrate occurs with the selective PRLR modulator, S179D PRL, would create a physiological state in which estrogen-stimulated proliferation was inhibited, but differentiative responses to PRL were maintained.},
}
@article {pmid25523328,
year = {2014},
author = {Lappalainen, AK and Vaittinen, E and Junnila, J and Laitinen-Vapaavuori, O},
title = {Intervertebral disc disease in Dachshunds radiographically screened for intervertebral disc calcifications.},
journal = {Acta veterinaria Scandinavica},
volume = {56},
number = {1},
pages = {89},
pmid = {25523328},
issn = {1751-0147},
mesh = {Animals ; Calcinosis/diagnostic imaging/epidemiology/etiology/*veterinary ; Dog Diseases/diagnostic imaging/*epidemiology/etiology ; Dogs ; Finland/epidemiology ; Intervertebral Disc Degeneration/diagnostic imaging/epidemiology/etiology/*veterinary ; Intervertebral Disc Displacement/diagnostic imaging/epidemiology/etiology/*veterinary ; Mass Screening/veterinary ; Radiography ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Intervertebral disc disease (IDD) is a very common neurological disease, Dachshunds being the breed most often affected. In this breed, IDD has a hereditary background and is associated with intervertebral disc calcification (IDC), an indicator of severe intervertebral disc degeneration. In Finland, spinal radiography is used, when screening for IDC before breeding Dachshunds. We evaluated the association between IDC and IDD in Finnish Dachshunds radiographically screened for IDC. A questionnaire was sent to owners of 193 radiographically screened Dachshunds aged at least ten years. Clinical signs indicative of IDD were compared with IDC grade (grade 0 = no calcifications, grade 1 = 1 - 2 calcifications, grade 2 = 3 - 4 calcifications and grade 3 = 5 or more calcifications) and with age at the time of the radiographic examination. The diagnosis of IDD was confirmed by a veterinarian.<br><br>RESULTS: IDD was common in the study population with 31% of dogs being affected. IDD and IDC were clearly connected (P&#x2009;<&#x2009;0.001); IDD was rare in dogs with no calcifications (grade 0) and common in dogs with severe IDC (grade 3). The IDC grade was strongly positively associated with frequency of back pain periods (P&#x2009;<&#x2009;0.001), and dogs with IDC grade 3 had frequent periods of pain. Reluctance to jump onto a sofa had a strong positive association with back pain. No association existed between age of the dog at the time of the radiographic examination and clinical signs indicative of IDD.<br><br>CONCLUSIONS: Radiographically detected IDC and IDD are common in Finnish Dachshunds and are strongly associated with one another. Spinal radiography is an appropriate screening tool for breeders attempting to diminish IDC and IDD in Dachshunds. A breeding program that screens dogs and selects against IDC can be expected to reduce the occurrence of IDD in future. Twenty-four to 48 months of age is a suitable age for screening.},
}
@article {pmid25518541,
year = {2014},
author = {Andjelić-Dekić, N and Božović-Spasojević, I and Milošević, S and Matijašević, M and Karadžić, K},
title = {A rare case of isolated adrenal metastasis of invasive ductal breast carcinoma.},
journal = {Srpski arhiv za celokupno lekarstvo},
volume = {142},
number = {9-10},
pages = {597-601},
doi = {10.2298/sarh1410597a},
pmid = {25518541},
issn = {0370-8179},
mesh = {Adrenal Gland Neoplasms/drug therapy/*secondary ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2 ; Trastuzumab/therapeutic use ; },
abstract = {INTRODUCTION: Isolated adrenal metastases of invasive ductal breast carcinoma are extremely rare. We report a case with isolated left adrenal metastases, verified three years after diagnosed breast carcinoma.<br><br>CASE OUTLINE: A 58-year-old female patient with a right breast tumor, clinically staged as IIIA (T2N2M0) started neoadjuvant anthracycline chemotherapy after biopsy which revealed invasive ductal breast carcinoma. Immunohistochemical findings of tumor biopsy showed hormonal steroid receptors for estrogen and progesterone negative, and human epidermal growth factor receptor 2 (HER2) positive. After 4 cycles of chemotherapy and partial tumor regression the patient underwent radical mastectomy. Definite histopathological analysis confirmed the diagnosis of invasive ductal carcinoma. The patient continued treatment with adjuvant chemotherapy to cumulative dose of anthracyclines, postoperative radiotherapy and adjuvant trastuzumab for one year. Three years later abdominal computerized tomography showed tumor in the left adrenal gland as the only metastatic site. Left adrenalectomy was performed and histopathological finding confirmed breast cancer metastases. Postoperatively, the patient received 6 cycles of docetaxel with trastuzumab and continued trastuzumab until disease progression. One year after left adrenalectomy control abdominal computerized tomography showed a right adrenal tumor with retroperitoneal lymphadenopathy. Treatment with capecitabine was continued for one year, but eventually she developed brain metastasis causing lethal outcome.<br><br>CONCLUSION: In order to better understand metastatic pathways of invasive ductal breast carcinoma, publications of individual patient cases diagnosed with rare metastatic sites should be encouraged. This might improve our understanding of metastatic behavior of breast cancer and stimulate further clinical research.},
}
@article {pmid25493218,
year = {2014},
author = {Wazir, U and Mokbel, K},
title = {Emerging gene-based prognostic tools in early breast cancer: First steps to personalised medicine.},
journal = {World journal of clinical oncology},
volume = {5},
number = {5},
pages = {795-799},
pmid = {25493218},
issn = {2218-4333},
abstract = {Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor (ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer.},
}
@article {pmid25486426,
year = {2015},
author = {Chen, C and Wang, X and Xiong, X and Liu, Q and Huang, Y and Xu, Q and Hu, J and Ge, G and Ling, K},
title = {Targeting type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis.},
journal = {Oncogene},
volume = {34},
number = {35},
pages = {4635-4646},
pmid = {25486426},
issn = {1476-5594},
support = {R01 CA149039/CA/NCI NIH HHS/United States ; R01 DK090038/DK/NIDDK NIH HHS/United States ; R01 DK099160/DK/NIDDK NIH HHS/United States ; 1R01CA149039-01A1/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; ErbB Receptors/metabolism ; Female ; Gene Knockdown Techniques ; Lung Neoplasms/*enzymology/secondary ; Mammary Neoplasms, Experimental/*enzymology/pathology ; Mice, Inbred BALB C ; Neoplasm Invasiveness ; Phosphotransferases (Alcohol Group Acceptor)/*genetics/metabolism ; Protein Processing, Post-Translational ; RNA, Small Interfering/genetics ; },
abstract = {Most deaths from breast cancer are caused by metastasis, a complex behavior of cancer cells involving migration, invasion, survival and microenvironment manipulation. Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) regulates focal adhesion assembly and its phosphorylation at Y639 is critical for cell migration induced by EGF. However, the role of this lipid kinase in tumor metastasis remains unclear. Here we report that PIPKIγ is vital for breast cancer metastasis. Y639 of PIPKIγ can be phosphorylated by stimulation of EGF and hepatocyte growth factor (HGF), two promoting factors for breast cancer progression. Histological analysis revealed elevated Y639 phosphorylation of PIPKIγ in invasive ductal carcinoma lesions and suggested a positive correlation with tumor grade. Orthotopically transplanted PIPKIγ-depleted breast cancer cells showed substantially reduced growth and metastasis, as well as suppressed expression of multiple genes related to cell migration and microenvironment manipulation. Re-expression of wild-type PIPKIγ in PIPKIγ-depleted cells restored tumor growth and metastasis, reinforcing the importance of PIPKIγ in breast cancer progression. Y639-to-F or a kinase-dead mutant of PIPKIγ could not recover the diminished metastasis in PIPKIγ-depleted cancer cells, suggesting that Y639 phosphorylation and lipid kinase activity are both required for development of metastasis. Further analysis with in vitro assays indicated that depleting PIPKIγ inhibited cell proliferation, MMP9 secretion and cell migration and invasion, lending molecular mechanisms for the eliminated cancer progression. These results suggest that PIPKIγ, downstream of EGF and/or HGF receptor, participates in breast cancer progression from multiple aspects and deserves further studies to explore its potential as a therapeutic target.},
}
@article {pmid25481753,
year = {2015},
author = {Yasaka, R and Ohba, K and Schwinghamer, MW and Fletcher, J and Ochoa-Corona, FM and Thomas, JE and Ho, SYW and Gibbs, AJ and Ohshima, K},
title = {Phylodynamic evidence of the migration of turnip mosaic potyvirus from Europe to Australia and New Zealand.},
journal = {The Journal of general virology},
volume = {96},
number = {Pt 3},
pages = {701-713},
doi = {10.1099/jgv.0.000007},
pmid = {25481753},
issn = {1465-2099},
mesh = {Australia ; Biological Evolution ; Brassicaceae/*virology ; Europe ; Genome, Viral ; Molecular Sequence Data ; Mosaic Viruses/genetics/*isolation &amp; purification ; New Zealand ; Phylogeny ; Phylogeography ; Plant Diseases/*virology ; Reassortant Viruses ; Time Factors ; },
abstract = {Turnip mosaic virus (TuMV) is a potyvirus that is transmitted by aphids and infects a wide range of plant species. We investigated the evolution of this pathogen by collecting 32 isolates of TuMV, mostly from Brassicaceae plants, in Australia and New Zealand. We performed a variety of sequence-based phylogenetic and population genetic analyses of the complete genomic sequences and of three non-recombinogenic regions of those sequences. The substitution rates, divergence times and phylogeographical patterns of the virus populations were estimated. Six inter- and seven intralineage recombination-type patterns were found in the genomes of the Australian and New Zealand isolates, and all were novel. Only one recombination-type pattern has been found in both countries. The Australian and New Zealand populations were genetically different, and were different from the European and Asian populations. Our Bayesian coalescent analyses, based on a combination of novel and published sequence data from three non-recombinogenic protein-encoding regions, showed that TuMV probably started to migrate from Europe to Australia and New Zealand more than 80 years ago, and that distinct populations arose as a result of evolutionary drivers such as recombination. The basal-B2 subpopulation in Australia and New Zealand seems to be older than those of the world-B2 and -B3 populations. To our knowledge, our study presents the first population genetic analysis of TuMV in Australia and New Zealand. We have shown that the time of migration of TuMV correlates well with the establishment of agriculture and migration of Europeans to these countries.},
}
@article {pmid25478233,
year = {2014},
author = {Mirmalek, SA and Hajilou, M and Salimi Tabatabaee, SA and Parsa, Y and Yadollah-Damavandi, S and Parsa, T},
title = {Prevalence of HER-2 and Hormone Receptors and P53 Mutations in the Pathologic Specimens of Breast Cancer Patients.},
journal = {International journal of breast cancer},
volume = {2014},
number = {},
pages = {564308},
pmid = {25478233},
issn = {2090-3170},
abstract = {Prognostic factors are in interest for breast cancer as the second cause of malignancy deaths. Some have predictive values as human epidermal growth factor receptor-2 (HER-2) and estrogen receptor (ER). To access the incidence of HER2 and its relations to other factors, like age, pathology, ER, progesterone receptor (PR), and P53, 2000 pathologic blocks from 2750 total samples have been selected from 2011 to 2013 in Cancer Institute of Tehran. Incidence of HER2, ER, PR, and P53 was; 58.5%, 33.4%, 43.3%, and 65.4%, respectively. Invasive ductal carcinoma was the most pathologic type (82.2%) and 60%-70% positive HER2 and P53 had negative ER and PR (poor prognosis). The peak age of incidence of breast cancer was perimenopausal age group (46-55 years). Our cases had more positive HER2 and P53 and less positive PR and ER compared to other studies. High perimenopausal incidence as another finding assures the importance of breast cancer screening in these age groups.},
}
@article {pmid25476558,
year = {2015},
author = {Singh, TP and Blume, ED and Alexander, PM and Gauvreau, K},
title = {Association of hemodynamic profiles with wait-list mortality in children listed for heart transplantation with idiopathic dilated cardiomyopathy.},
journal = {The American journal of cardiology},
volume = {115},
number = {2},
pages = {243-248},
doi = {10.1016/j.amjcard.2014.10.030},
pmid = {25476558},
issn = {1879-1913},
mesh = {Adolescent ; Cardiomyopathy, Dilated/mortality/physiopathology/*surgery ; Cause of Death/trends ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; *Heart Transplantation ; Humans ; Infant ; Male ; Pulmonary Wedge Pressure/physiology ; Retrospective Studies ; Risk Assessment/*methods ; Risk Factors ; Survival Rate/trends ; Time Factors ; United States/epidemiology ; Waiting Lists/*mortality ; },
abstract = {The prognostic significance of intracardiac hemodynamics in children with advanced heart failure is unknown. The purpose of this study was to describe hemodynamic profiles in children with idiopathic dilated cardiomyopathy (IDC) listed for heart transplant (HT) and to assess their association with wait-list mortality. We identified all US children <18 years with IDC listed for HT during 2000 to 2010 with available pulmonary capillary wedge pressure (PCWP) and cardiac index (CIx) data. We excluded children on ventilator or mechanical support at listing. CIx >2.2 L/min/m(2) (warm) and PCWP >18 mm Hg (wet) were used to define 4 hemodynamic profiles: warm-dry, warm-wet, cold-dry, and cold-wet. The primary end point was death on the wait-list or becoming too sick to transplant. Of 476 children analyzed, 248 (52%) children had PCWP >18 mm Hg and 300 (63%) had CIx >2.2 L/min/m(2). Overall, 36% children were warm-dry, 27% were warm-wet, 12% were cold-dry, and 25% were cold-wet; 32 (6.7%) children reached the primary end point. In adjusted analysis, cold-dry (hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.1, 11.5) and cold-wet (HR 3.2, 95% CI 1.2, 8.6) children were at higher risk of wait-list death versus warm-dry children, whereas warm-wet children were not (HR 2.3, 95% CI 0.8, 6.6). All groups were equally likely to receive HT and had similar 1-year post-transplant survival. In conclusion, in children with IDC listed for HT, those with low cardiac output at evaluation are at higher risk of wait-list mortality. Defining hemodynamic profiles may improve risk stratification of children with IDC listed for HT.},
}
@article {pmid25466398,
year = {2015},
author = {Alberti, N and Bechade, D and Dupuis, F and Crombe, A and Neuville, A and Debled, M and Palussiere, J and Buy, X and Perez, JT and Desjardin, M and Frulio, N and Kind, M},
title = {Hepar lobatum carcinomatosum associated with liver metastases from breast cancer: report of five cases.},
journal = {Diagnostic and interventional imaging},
volume = {96},
number = {1},
pages = {73-78},
doi = {10.1016/j.diii.2014.11.003},
pmid = {25466398},
issn = {2211-5684},
mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Liver Neoplasms/*pathology/*secondary ; Middle Aged ; },
abstract = {BACKGROUNDS AND AIMS: Hepar lobatum carcinomatosum (HLC) is an exceptional acquired hepatic distortion which consists in irregularly lobulated hepatic contours seen in patients with known liver metastases, usually from breast carcinoma. We aimed to describe and analyze five similar cases of HLC resulting from metastatic mammary carcinoma in the liver and associated with rapid hepatic failure.<br><br>METHODS: Five cases of HLC were investigated. Medical (including blood liver tests), radiological and histological data (2 cases) were collected and retrospectively analyzed. All patients were followed up for metastatic invasive ductal carcinoma of the breast and had a common pattern of treatment with combination of targeted therapies (bevacizumab, AVASTIN) and chemotherapy (paclitaxel, TAXOL).<br><br>RESULTS: All the patients showed rapid hepatic failure after a mean of 9 courses of bevacizumab/paclitaxel. In all cases, liver imaging revealed liver capsule retraction and an irregular lobular margin. An apparent tumor regression of all liver metastases was showed in two cases. Biopsies were consistent with sinusoidal obstruction syndrome (SOS) and, surprisingly, no tumoral cells were found.<br><br>CONCLUSION: Although rare, such an unusual pattern of liver metastasis may mimick acute cirrhosis and cause rapid hepatic failure in patients, despite possible apparent tumor regression on imaging. The etiology of this pathology is unclear, and may involve multiple pathogenic factors. Direct or indirect vascular injury plays an important role in the development of HLC.},
}
@article {pmid25459069,
year = {2015},
author = {Yu, JI and Choi, DH and Huh, SJ and Ahn, SJ and Lee, JS and Shin, KH and Kwon, Y and Kim, YB and Suh, CO and Kim, JH and Cho, J and Kim, IA and Lee, JH and Park, W},
title = {Unique characteristics and failure patterns of metaplastic breast cancer in contrast to invasive ductal carcinoma: a retrospective multicenter case-control study (KROG 13-07).},
journal = {Clinical breast cancer},
volume = {15},
number = {2},
pages = {e105-15},
doi = {10.1016/j.clbc.2014.10.002},
pmid = {25459069},
issn = {1938-0666},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local/*mortality ; Prognosis ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/mortality/*pathology ; Young Adult ; },
abstract = {BACKGROUND: This retrospective study was performed to investigate the need for management modification in MBC according to evaluation of characteristics and failure patterns compared with IDC.<br><br>PATIENTS AND METHODS: We performed this multicenter study taking MBC and randomly assigned IDC cases matched for age (&#xb1; 3 years), pathologic stage (T and N), locoregional treatment methods (surgery with or without radiation therapy), and period of treatment (&#xb1; 6 months) that occurred from January 1999 to November 2011 in the 6 institutions of the Korean Radiation Oncology Group.<br><br>RESULTS: A total of 144 female MBC patients were enrolled. The median follow-up was 51 months (range, 1-186 months). The rates of positivity for estrogen receptor (P < .001), progesterone receptor (P < .001), and HER2 (P = .007) were significantly lower in MBC patients. During follow-up, recurrence developed in 22 (15.3%) MBC and 6 (4.2%) IDC patients (P = .002). The median time to recurrence of MBC and IDC was 15 months and 24 months, respectively. Most instances of recurrence in MBC developed in the triple-negative (TN) subgroup (TN-MBC). In particular, locoregional recurrence developed exclusively in the TN-MBC subgroup. In the TN-MBC subgroup, the number of risk factors (pT2-3, N1-3) was related to significant differences in overall survival (P = .001) and recurrence-free survival (P < .001).<br><br>CONCLUSION: The MBC patients had a higher rate of TN, poorer differentiation, and a higher recurrence rate than did the IDC patients. Considering the unique characteristics and failure patterns, it is necessary to modify the current management guidelines for MBC.},
}
@article {pmid25457635,
year = {2014},
author = {Xia, HJ and He, BL and Wang, CY and Zhang, HL and Ge, GZ and Zhang, YX and Lv, LB and Jiao, JL and Chen, C},
title = {PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {50},
number = {18},
pages = {3230-3242},
doi = {10.1016/j.ejca.2014.10.012},
pmid = {25457635},
issn = {1879-0852},
mesh = {9,10-Dimethyl-1,2-benzanthracene ; Animals ; Carcinogens ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Papillary/genetics ; *Disease Models, Animal ; Estrogens/metabolism ; Female ; Mammary Glands, Animal/metabolism ; Mammary Neoplasms, Animal/chemically induced/*genetics ; Mammary Neoplasms, Experimental/chemically induced/*genetics ; Medroxyprogesterone Acetate ; Mutation/*genetics ; PTEN Phosphohydrolase/*genetics ; Papilloma, Intraductal/genetics ; Phosphatidylinositol 3-Kinase/*genetics ; Progesterone/metabolism ; Random Allocation ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tupaiidae ; },
abstract = {Tree shrew has increasingly become an attractive experimental animal model for human diseases, particularly for breast cancer due to spontaneous breast tumours and their close relationship to primates and by extension to humans. However, neither normal mammary glands nor breast tumours have been well characterised in the Chinese tree shrew (Tupaia belangeri chinensis). In this study, normal mammary glands from four different developmental stages and 18 spontaneous breast tumours were analysed. Haematoxylin and eosin (H&amp;E) staining and immunohistochemistry (IHC) showed that normal mammary gland morphology and structures of tree shrews were quite similar to those found in humans. Spontaneous breast tumours of tree shrews were identified as being intraductal papilloma, papillary carcinoma, and invasive ductal carcinoma with or without lung metastasis. To further analyse breast cancer tumours among tree shrews, 40 3-4 month-old female tree shrews were orally administrated 20 mg 7,12-dimethylbenz(a)anthracene (DMBA) or peanut oil thrice, and then, 15 of these DMBA administrated tree shrews were implanted with medroxyprogesterone acetate (MPA) pellets. DMBA was shown to induce breast tumours (12%) while the addition of MPA increased the tumour incidence (50%). Of these, three induced breast tumours were intraductal papillary carcinomas and one was invasive ductal carcinoma (IDC). The PTEN/PIK3CA (phosphatase and tensin homologue/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), but not TP53 and GATA3, genes are frequently mutated in breast tumours, and the PTEN/PIK3CA gene mutation status correlated with the expression of pAKT in tree shrew breast tumours. These results suggest that tree shrews may be a promising animal model for a subset of human breast cancers with PTEN/PIK3CA gene mutations.},
}
@article {pmid25455606,
year = {2014},
author = {Bozorgmehr, M and Moazzeni, SM and Salehnia, M and Sheikhian, A and Nikoo, S and Zarnani, AH},
title = {Menstrual blood-derived stromal stem cells inhibit optimal generation and maturation of human monocyte-derived dendritic cells.},
journal = {Immunology letters},
volume = {162},
number = {2 Pt B},
pages = {239-246},
doi = {10.1016/j.imlet.2014.10.005},
pmid = {25455606},
issn = {1879-0542},
mesh = {Adult ; Antigens, Differentiation/immunology ; Cell Differentiation/*immunology ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology/*immunology ; Female ; Humans ; Interleukin-10/immunology ; Interleukin-6/immunology ; *Menstruation ; Mesenchymal Stem Cells/cytology/*immunology ; Monocytes/cytology/*immunology ; },
abstract = {INTRODUCTION: Menstrual blood stromal stem Cells (MenSCs) have shown promising potential for future clinical settings. Nonetheless, data regarding their interaction with immune cells is still scarce. Here, we investigated whether MenSCs could affect the generation and/or maturation of human blood monocyte-derived dendritic cells (DCs).<br><br>MATERIALS AND METHODS: MenSCs were isolated from menstrual blood of normal women through culture of adherent mononuclear cells. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) in the presence or absence of MenSCs. Monocyte-derived cells were assessed for the percentage of monocyte-, iDC-, and mDC-specific markers as well as the expression of costimulatory molecules. IL-6 and IL-10 levels were also determined in supernatants of MenSC-monocytes cocultures.<br><br>RESULTS: Optimal phenotypic differentiation of monocytes into iDCs was inhibited upon coculture with MenSCs. Moreover, higher levels of IL-6 and IL-10 were detected in these settings. Even though addition of MenSCs to iDC cultures could not prevent iDC maturation, coculture of MenSCs with monocytes from the beginning of differentiation process could effectively hinder generation of fully mature DCs.<br><br>CONCLUSION: This is the first study to address the inhibitory impact of MenSCs on generation and maturation of DCs. IL-6 and IL-10 could be partly held responsible for this effect. Given the central roles of DCs in regulation of immune responses, these results highlight the importance of further research on the potential modulatory impacts of MenSCs, as rather easily accessible and expandable stem cells, on the immune system-related cells.},
}
@article {pmid25445919,
year = {2015},
author = {Wahler, J and So, JY and Cheng, LC and Maehr, H and Uskokovic, M and Suh, N},
title = {Vitamin D compounds reduce mammosphere formation and decrease expression of putative stem cell markers in breast cancer.},
journal = {The Journal of steroid biochemistry and molecular biology},
volume = {148},
number = {},
pages = {148-155},
pmid = {25445919},
issn = {1879-1220},
support = {P30 CA072720/CA/NCI NIH HHS/United States ; P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 CA127645/CA/NCI NIH HHS/United States ; R03CA172827/CA/NCI NIH HHS/United States ; K22CA133105/CA/NCI NIH HHS/United States ; },
mesh = {Apoptosis/drug effects ; Biomarkers, Tumor/genetics/*metabolism ; Blotting, Western ; Breast/*drug effects/metabolism/pathology ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Cell Proliferation/drug effects ; Female ; Flow Cytometry ; Humans ; Neoplastic Stem Cells/*drug effects/metabolism/pathology ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Spheroids, Cellular/drug effects ; Tumor Cells, Cultured ; Vitamin D/*pharmacology ; Vitamins/*pharmacology ; },
abstract = {Breast cancer stem cells (BCSCs) are a subset of tumor cells that are believed to be the cells responsible for the establishment and maintenance of tumors. Moreover, BCSCs are suggested to be the main cause of progression to metastasis and recurrence of cancer because of their tumor-initiating abilities and resistance to conventional therapies. Ductal carcinoma in situ (DCIS) is an early precursor in breast carcinogenesis which progresses to invasive ductal carcinoma (IDC). We have previously reported that a vitamin D compound, BXL0124, inhibits the progression of DCIS to IDC. In the present study we sought to determine whether this effect was mediated through an influence on BCSCs. In MCF10DCIS cells treated with vitamin D compounds (1α25(OH)2D3 or BXL0124), the breast cancer stem cell-like population, identified by the CD44(+)/CD24(-/low) and CD49f(+)/CD24(-/low) subpopulations, was reduced. To determine the effects of vitamin D compounds on cancer stem cell activity, the MCF10DCIS mammosphere cell culture system, which enriches for mammary progenitor cells and putative BCSCs, was utilized. Untreated MCF10DCIS mammospheres showed a disorganized and irregular shape. When MCF10DCIS cells were treated with 1α25(OH)2D3 or BXL0124, the mammospheres that formed exhibited a more organized, symmetrical and circular shape, similar to the appearance of spheres formed by the non-malignant, normal mammary epithelial cell line, MCF10A. The mammosphere forming efficiency (MFE) was significantly decreased upon treatment with 1α25(OH)2D3 or BXL0124, indicating that these compounds have an inhibitory effect on mammosphere development. Treatment with 1α25(OH)2D3 or BXL0124 repressed markers associated with the stem cell-like phenotype, such as CD44, CD49f, c-Notch1, and pNFκB. Furthermore, 1α25(OH)2D3 and BXL0124 reduced the expression of pluripotency markers, OCT4 and KLF-4 in mammospheres. This study suggests that vitamin D compounds repress the breast cancer stem cell-like population, potentially contributing to their inhibition of breast cancer. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.},
}
@article {pmid25435991,
year = {2015},
author = {Liu, L and Shi, J and Mao, F and Wei, J and Fu, D and Zhang, J},
title = {Synchronous primary cancers of the thyroid and breast: A case report and review of the literature.},
journal = {Oncology letters},
volume = {9},
number = {1},
pages = {351-354},
pmid = {25435991},
issn = {1792-1074},
abstract = {The current report presents the case of a 41-year-old female exhibiting synchronous primary cancers of the thyroid and breast. Pathological examination of a tissue sample following biopsy identified papillary carcinoma of the thyroid and invasive ductal carcinoma of the breast to provide a definitive diagnosis of synchronous primary tumors. The patient underwent a modified radical mastectomy and total thyroidectomy. Following regular adjuvant chemotherapy with cyclophosphamide (800 mg), doxorubicin (100 mg) and paclitaxel (120 mg), once every three weeks for 3.5 months, oral levothyroxine and endocrinotherapy was recommended. Two years after the initial diagnosis, the patient was healthy with no disease recurrence. To the best of our knowledge, no association has been identified between the etiology and diagnoses of the two synchronous primary tumors. Thus, the aim of the current report was to improve the understanding of synchronous primary tumors of the thyroid and breast by presenting a review of the associated literature regarding breast and thyroid cancer. The mechanisms of synchronous neoplasms have only recently been elucidated, however, misdiagnosis is common. Clinicians are, therefore, advised to carefully examine patients with thyroid or breast cancer to avoid an incorrect or misdiagnosis. Furthermore, the present report aims to provide a reference for the cancer database, since the majority of analyses of rare diseases are derived from case reports. To improve the understanding of synchronous primary cancers of the thyroid and breast, an analysis of recent studies regarding the underlying mechanisms of synchronous primary cancers was also undertaken.},
}
@article {pmid25433206,
year = {2015},
author = {Huang, B and Warner, M and Gustafsson, J&#xc5;},
title = {Estrogen receptors in breast carcinogenesis and endocrine therapy.},
journal = {Molecular and cellular endocrinology},
volume = {418 Pt 3},
number = {},
pages = {240-244},
doi = {10.1016/j.mce.2014.11.015},
pmid = {25433206},
issn = {1872-8057},
mesh = {Breast Neoplasms/*drug therapy/metabolism/pathology ; Drug Resistance, Neoplasm ; Estrogen Receptor alpha/*metabolism ; Estrogen Receptor beta/*metabolism ; Estrogens/*therapeutic use ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Recurrence, Local/drug therapy/metabolism ; Signal Transduction ; Tamoxifen/*therapeutic use ; },
abstract = {Excessive exposure to estrogen has long been associated with an increased risk for developing breast cancer and anti-estrogen therapy is the gold standard of care in the treatment of estrogen receptor (ER) α-positive breast cancers. However, there are several mysteries concerning both anti-estrogen, tamoxifen, and estrogen. The most important of these are: (1) some ERα-positive breast cancers do not respond to tamoxifen; (2) some ERα-negative breast cancers do respond to tamoxifen; (3) initial or acquired resistance to tamoxifen occurs with recurrent tumors; (4) estrogen can cause marked tumor regression in long-term tamoxifen-resistant ERα-positive breast cancer. These mysteries indicate that we do not know enough about estrogen signaling to understand the effects of targeting these receptors in cancer. The discovery of ERβ, the second estrogen receptor, has added another level of complexity to estrogen signaling. This review summarizes recent publications and makes an updated portrait of ERα and ERβ in breast carcinogenesis and endocrine cancer therapy.},
}
@article {pmid25424886,
year = {2015},
author = {Lacaze, I and Lalucque, H and Siegmund, U and Silar, P and Brun, S},
title = {Identification of NoxD/Pro41 as the homologue of the p22phox NADPH oxidase subunit in fungi.},
journal = {Molecular microbiology},
volume = {95},
number = {6},
pages = {1006-1024},
doi = {10.1111/mmi.12876},
pmid = {25424886},
issn = {1365-2958},
mesh = {Amino Acid Sequence ; Cytochrome b Group/metabolism ; Endoplasmic Reticulum/*enzymology ; Genome, Fungal ; Mutation ; Mycelium/ultrastructure ; NADPH Oxidases/chemistry/*genetics/*metabolism ; Phylogeny ; Podospora/*enzymology/genetics ; Sequence Analysis, DNA ; Superoxides/metabolism ; Vacuoles/*enzymology ; },
abstract = {NADPH oxidases (Nox) are membrane complexes that produce O2(-). Researches in mammals, plants and fungi highlight the involvement of Nox-generated ROS in cell proliferation, differentiation and defense. In mammals, the core enzyme gp91(phox)/Nox2 is associated with p22(phox) forming the flavocytochrome b558 ready for activation by a cytosolic complex. Intriguingly, no homologue of the p22(phox) gene has been found in fungal genomes, questioning how the flavoenzyme forms. Using whole genome sequencing combined with phylogenetic analysis and structural studies, we identify the fungal p22(phox) homologue as being mutated in the Podospora anserina mutant IDC(509). Functional studies show that the fungal p22(phox), PaNoxD, acts along PaNox1, but not PaNox2, a second fungal gp91(phox) homologue. Finally, cytological analysis of functional tagged versions of PaNox1, PaNoxD and PaNoxR shows clear co-localization of PaNoxD and PaNox1 and unravel a dynamic assembly of the complex in the endoplasmic reticulum and in the vacuolar system.},
}
@article {pmid25421310,
year = {2015},
author = {Buijs, JT and Matula, KM and Cheung, H and Kruithof-de Julio, M and van der Mark, MH and Snoeks, TJ and Cohen, R and Corver, WE and Mohammad, KS and Jonkers, J and Guise, TA and van der Pluijm, G},
title = {Spontaneous bone metastases in a preclinical orthotopic model of invasive lobular carcinoma; the effect of pharmacological targeting TGFβ receptor I kinase.},
journal = {The Journal of pathology},
volume = {235},
number = {5},
pages = {745-759},
pmid = {25421310},
issn = {1096-9896},
support = {U01 CA143057/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Apoptosis/drug effects ; Bone Neoplasms/enzymology/genetics/*secondary ; Breast Neoplasms/chemically induced/enzymology/genetics/*pathology ; Carcinoma, Lobular/chemically induced/enzymology/genetics/*secondary ; Cdh1 Proteins/deficiency/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Female ; Mammary Neoplasms, Experimental/chemically induced/enzymology/genetics/*pathology ; Mice, Knockout ; Neoplasm Micrometastasis ; Protein Kinase Inhibitors/*toxicity ; Protein Serine-Threonine Kinases/*antagonists &amp; inhibitors/metabolism ; Pteridines/*toxicity ; Receptor, Transforming Growth Factor-beta Type I ; Receptors, Transforming Growth Factor beta/*antagonists &amp; inhibitors/metabolism ; Signal Transduction/drug effects ; Time Factors ; Transfection ; Tumor Burden/drug effects ; Tumor Suppressor Protein p53/deficiency/genetics ; },
abstract = {Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most frequently occurring histological subtypes of breast cancer, accounting for 80-90% and 10-15% of the total cases, respectively. At the time of diagnosis and surgical resection of the primary tumour, most patients do not have clinical signs of metastases, but bone micrometastases may already be present. Our aim was to develop a novel preclinical ILC model of spontaneous bone micrometastasis. We used murine invasive lobular breast carcinoma cells (KEP) that were generated by targeted deletion of E-cadherin and p53 in a conditional K14cre;Cdh1((F/F));Trp53((F/F)) mouse model of de novo mammary tumour formation. After surgical resection of the growing orthotopically implanted KEP cells, distant metastases were formed. In contrast to other orthotopic breast cancer models, KEP cells readily formed skeletal metastases with minimal lung involvement. Continuous treatment with SD-208 (60 mg/kg per day), an orally available TGFβ receptor I kinase inhibitor, increased the tumour growth at the primary site and increased the number of distant metastases. Furthermore, when SD-208 treatment was started after surgical resection of the orthotopic tumour, increased bone colonisation was also observed (versus vehicle). Both our in vitro and in vivo data show that SD-208 treatment reduced TGFβ signalling, inhibited apoptosis, and increased proliferation. In conclusion, we have demonstrated that orthotopic implantation of murine ILC cells represent a new breast cancer model of minimal residual disease in vivo, which comprises key steps of the metastatic cascade. The cancer cells are sensitive to the anti-tumour effects of TGFβ. Our in vivo model is ideally suited for functional studies and evaluation of new pharmacological intervention strategies that may target one or more steps along the metastatic cascade of events.},
}
@article {pmid25418428,
year = {2015},
author = {Cavallo Marincola, B and Pediconi, F and Anzidei, M and Miglio, E and Di Mare, L and Telesca, M and Mancini, M and D'Amati, G and Monti, M and Catalano, C and Napoli, A},
title = {High-intensity focused ultrasound in breast pathology: non-invasive treatment of benign and malignant lesions.},
journal = {Expert review of medical devices},
volume = {12},
number = {2},
pages = {191-199},
doi = {10.1586/17434440.2015.986096},
pmid = {25418428},
issn = {1745-2422},
mesh = {Breast/*pathology ; Breast Neoplasms/*diagnostic imaging/pathology/*therapy ; Female ; High-Intensity Focused Ultrasound Ablation/*methods ; Humans ; Magnetic Resonance Spectroscopy ; Treatment Outcome ; Ultrasonography ; },
abstract = {Breast neoplasms are one of the leading causes of morbidity and mortality in women. Even if surgery is the treatment of choice, other forms of less invasive radical treatment are desirable. High-intensity focused ultrasound is already established as a valid non-invasive technique that ensures tumor ablation in various organs. The use of ultrasound or magnetic resonance guidance allows having some advantages such as the capability to treat tumors in moving organs or the possibility to have a real-time monitoring of the temperature increase. The aim of this paper is to report the use of high-intensity focused ultrasound technique with ultrasound and magnetic resonance guidance for the ablation of breast tumors, including both benign and malignant lesions.},
}
@article {pmid25415740,
year = {2014},
author = {Maglione, KD and Margolies, L and Jaffer, S and Szabo, J and Schmidt, H and Weltz, C and Sonnenblick, EB},
title = {Breast cancer in male-to-female transsexuals: use of breast imaging for detection.},
journal = {AJR. American journal of roentgenology},
volume = {203},
number = {6},
pages = {W735-40},
doi = {10.2214/AJR.14.12723},
pmid = {25415740},
issn = {1546-3141},
mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/*etiology ; Female ; Humans ; Male ; Mammography/*methods ; Middle Aged ; *Transgender Persons ; Transsexualism/*complications/*diagnostic imaging ; },
abstract = {OBJECTIVE: The purposes of this article are to describe two cases of breast cancer in male-to-female transsexuals and to review eight cases previously reported in the literature.<br><br>CONCLUSION: Breast cancer occurs in male-to-female transsexuals who receive high doses of exogenous estrogen and develop breast tissue histologically identical to that of a biologically female breast. This exposure to estrogen results in increased risk of breast cancer. The first patient described is a male-to-female transsexual with screening-detected ductal carcinoma in situ and a family history of breast cancer. The other patient is a male-to-female transsexual with invasive ductal carcinoma that was occult on diagnostic digital mammographic and ultrasound findings but visualized on digital breast tomosynthesis and breast MR images. The analysis of the eight previously reported cases showed that breast cancer in male-to-female transsexuals occurs at a younger age and is more frequently estrogen receptor negative than breast cancer in others born biologically male. Screening for breast cancer in male-to-female transsexuals should be undertaken for those with additional risk factors (e.g., family history, BRCA2 mutation, Klinefelter syndrome) and should be available to those who desire screening, preferably in a clinical trial.},
}
@article {pmid25410489,
year = {2015},
author = {Kim, HJ and Im, SA and Keam, B and Ham, HS and Lee, KH and Kim, TY and Kim, YJ and Oh, DY and Kim, JH and Han, W and Jang, IJ and Kim, TY and Park, IA and Noh, DY},
title = {ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy.},
journal = {Cancer science},
volume = {106},
number = {1},
pages = {86-93},
pmid = {25410489},
issn = {1349-7006},
mesh = {ATP Binding Cassette Transporter, Subfamily B/genetics ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/drug therapy/*genetics/mortality ; Carcinoma, Ductal, Breast/drug therapy/*genetics/mortality ; Chemotherapy, Adjuvant ; Cytochrome P-450 CYP3A/genetics ; Docetaxel ; Doxorubicin/administration &amp; dosage ; Female ; Gene Frequency ; Genetic Association Studies ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Neoadjuvant Therapy ; Polymorphism, Single Nucleotide ; Prognosis ; Proportional Hazards Models ; Taxoids/administration &amp; dosage ; },
abstract = {Expression of the adenosine triphosphate-binding cassette B1 (ABCB1) transporter and P-glycoprotein are associated with resistance to anticancer drugs. The purpose of this study was to investigate the role of single nucleotide polymorphism in the ABCB1 and CYP3A genes in breast cancer patients who were treated with neoadjuvant chemotherapy. Stage II/III breast cancer patients were treated with three cycles of neoadjuvant, after which the patients received curative surgery and adjuvant chemotherapy. The polymorphisms of ABCB1 and CYP3A were genotyped. The correlation of polymorphism of ABCB1, CYP3A, and clinical outcomes was analyzed. Among the 216 patients, ABCB1 3435TT genotype had a longer overall survival (OS). than CC/CT. Multivariate analyses demonstrated that good PS, invasive ductal carcinoma, non-triple negative phenotype and initial operable stage were significantly associated with a lower death risk. ABCB1 3435TT genotype had a higher AUC than CC/CT for docetaxel. These higher AUCs in the C3435TT was associated with increased toxicities of neutropenia and diarrhea. This study showed that the genetic polymorphism of ABCB1 C3435T might be associated with a longer OS. Our results also suggest that the prediction of docetaxel toxicity might be possible for C3435T polymorphism. This study results provides valuable information on individualized therapy according to genotypes.},
}
@article {pmid25404445,
year = {2014},
author = {Iqbal, J and Shafi, AA and Alharthi, BN},
title = {Neoadjuvant chemotherapy in locally advanced breast cancer.},
journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP},
volume = {24},
number = {11},
pages = {845-848},
pmid = {25404445},
issn = {1681-7168},
mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/mortality/pathology/*therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Hormones/therapeutic use ; Humans ; *Mastectomy ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Recurrence, Local/epidemiology/therapy ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Retrospective Studies ; Saudi Arabia/epidemiology ; Severity of Illness Index ; Survival Analysis ; Survival Rate ; Treatment Outcome ; },
abstract = {OBJECTIVE: To assess the response to Neoadjuvant Chemotherapy (NAC) in Locally Advanced Breast Cancer (LABC) in terms of pathological response, overall survival and feasibility of breast conservation surgery.<br><br>STUDY DESIGN: Case series.<br><br>PLACE AND DURATION OF STUDY: King Fahad Medical City (KFMC), Riyadh, from January 2009 to July 2012.<br><br>METHODOLOGY: All patients of LABC who received NAC and underwent surgery were included. All these patients received the GORG001 regimen (FEC+Docetaxal+Cisplatin+/-Herceptin). After chemotherapy patients were offered surgery either Modified Radical Mastectomy (MRM) or Breast Conservation Surgery (BCS) +Radiotherapy. Patients were then followed to exclude local or distant metastasis. RESULTS were described in percentage.<br><br>RESULTS: The median age at the time of diagnosis was 46.8 years. While complete response was achieved in 24 (44.4%) patients, 14 (25.9%) of the patients had partial response and 16 (29.6%) progressed clinically. Surgery was performed in these patients after NAC. Forty (74%) patients had MRM, 14 (25.9%) had BCS; all had axillary lymph node dissection. Invasive ductal carcinoma accounted for 92% of cases. Vascular invasion was present in 12 (22%) of the patients. Estrogen / progesterone receptor positivity was 61%. Thirty nine percent of the patients were Her2 positive. On an average, follow-up of 4 - 51 months in the MRM group, one patient had resection margin (deep) positive and was treated with adjuvant therapy. While in the BCS group after 3 - 26 months of follow-up, one patient had resection margin positive (medial margin) and underwent MRM, while no patient had local or distant metastasis in both the groups.<br><br>CONCLUSION: NAC caused down staging of disease in LABC making more conservative surgery feasible. BCC should be considered as an option for treatment of LABC, however, longer follow-up is recommended.},
}
@article {pmid25400746,
year = {2014},
author = {Lv, ZD and Kong, B and Liu, XP and Dong, Q and Niu, HT and Wang, YH and Li, FN and Wang, HB},
title = {CXCL12 chemokine expression suppresses human breast cancer growth and metastasis in vitro and in vivo.},
journal = {International journal of clinical and experimental pathology},
volume = {7},
number = {10},
pages = {6671-6678},
pmid = {25400746},
issn = {1936-2625},
mesh = {Animals ; Breast Neoplasms/genetics/immunology/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/genetics/immunology/*metabolism/mortality/secondary ; *Cell Proliferation ; Chemokine CXCL12/genetics/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; MCF-7 Cells ; Mice, Nude ; Middle Aged ; Neoplasm Invasiveness ; Signal Transduction ; Time Factors ; Transfection ; Tumor Burden ; },
abstract = {Chemokine receptors are now known to play an important role in cancer growth and metastasis. However, there is little information regarding chemokine expression in breast cancer. The aim of this study was to evaluate CXCL12 expression in breast cancer and to investigate the question of whether reduced expression of CXCL12 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of CXCL12 and relevance with clinicopathological factors in the invasive ductal carcinoma. Reduction of CXCL12 was significantly correlated with tumor size, lymph node metastasis, TNM stage and Her-2 expression in breast cancer. Patients with negative CXCL12 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive CXCL12 expression. In addition, we demonstrated that upregulation of CXCL12 expression by infection with an adenovirus containing a CXCL12 vector significantly inhibited cell growth and reduced the migration of breast cancer cells. Furthermore, animal studies revealed that nude mice injected with the Ad-CXCL12 cell lines featured a lighter weight than the control cell lines. These data suggest that CXCL12 plays an important role in cell growth and invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.},
}
@article {pmid25394563,
year = {2015},
author = {Liu, Y and Liu, T and Sun, Q and Niu, M and Jiang, Y and Pang, D},
title = {Downregulation of Ras GTPase‑activating protein 1 is associated with poor survival of breast invasive ductal carcinoma patients.},
journal = {Oncology reports},
volume = {33},
number = {1},
pages = {119-124},
doi = {10.3892/or.2014.3604},
pmid = {25394563},
issn = {1791-2431},
mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*metabolism/mortality ; Carcinoma, Ductal, Breast/*metabolism/mortality ; Disease-Free Survival ; Down-Regulation ; Female ; Gene Expression ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; p120 GTPase Activating Protein/genetics/*metabolism ; },
abstract = {Ras GTPase‑activating protein 1 (RASA1) functions to inactivate Ras‑GTPase and inhibit the mitogenic signal. Reduction or loss of RASA1 expression occurs during human cancer development and progression. This study investigated RASA1 expression in normal and breast cancer tissue specimens to determine the association with prognosis of breast cancer patients. Two sets of patient samples (45 fresh tissues and 373 paraffin‑embedded tissues) were analyzed for RASA1 expression using RT‑qPCR and immunohisto-chemistry. The results showed that the expression of RASA1 mRNA was lower in breast cancer tissues than in the corresponding normal tissues (P<0.001). Additionally, RASA1 expression was reduced in 60.6% (226/373) of breast cancer tissues. The reduced RASA1 expression was significantly associated with tumor lymph node metastasis (P=0.002), advanced TNM stages (P=0.017), estrogen receptor (ER) expression (P=0.002), Ki‑67 (P=0.009), higher histological grade (P<0.001), and triple‑negative breast cancer (P=0.041). Moreover, the reduced RASA1 expression was associated with shorter disease‑free survival (P=0.036) and overall survival (P<0.001) of breast cancer patients. RASA1 expression, together with tumor lymph‑node metastasis, TNM stage, Her‑2 expression, and triple‑negative breast cancer were independent factors in predicting survival of breast cancer patients. In conclusion, RASA1 expression is frequently reduced in breast cancer tissues, and the reduced RASA1 expression is associated with breast cancer progression and poor survival and disease‑free survival of patients.},
}
@article {pmid25391703,
year = {2014},
author = {Yanagihara, K and Takei, H and Iida, S and Yamashita, K and Kurita, T and Iwamoto, M and Saegusa, H and Uchida, E},
title = {Grade 4 epistaxis in a woman with metastatic breast cancer treated with bevacizumab: a case report.},
journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi},
volume = {81},
number = {5},
pages = {333-336},
doi = {10.1272/jnms.81.333},
pmid = {25391703},
issn = {1347-3409},
mesh = {Adult ; Angiogenesis Inhibitors/*adverse effects ; Antibodies, Monoclonal, Humanized/administration &amp; dosage/*adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use ; Bevacizumab ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*secondary ; Epistaxis/*chemically induced ; Female ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Paclitaxel/administration &amp; dosage ; Severity of Illness Index ; },
abstract = {We describe a 39-year-old woman with metastatic breast cancer who had grade 4 epistaxis induced by bevacizumab. The patient visited our outpatient clinic with complaints of a lump in her right breast, fatigue, dyspnea, abdominal distention, appetite loss, and weight loss of 10 kg over 1 year. Liver dysfunction was detected, with elevated levels of aspartate aminotransferase (271 IU/L), alanine aminotransferase (100 IU/L), alkaline phosphatase (4,205 IU/L), total bilirubin (2.7 mg/dL), and direct bilirubin (2.1 mg/dL). A secondary liver tumor that occupied most of the liver volume was found, and bone metastasis, ascites, and pleural effusion were also discovered. The Eastern Cooperative Oncology Group performance status was 2. A core needle biopsy of the right breast tumor revealed invasive ductal carcinoma of the breast (nuclear grade 1) that was positive for estrogen receptor and progesterone receptor and negative for human epidermal growth factor receptor 2 overexpression and had a high Ki-67 score. We chose combination chemotherapy with paclitaxel (80 mg/m(2) on days 1, 8, and 15) and bevacizumab (10 mg/kg on days 1 and 15) for 28 days (1 cycle). After completion of the first cycle of chemotherapy, the ascites and pleural effusion decreased, and the metastatic liver tumor shrank. The performance status improved from 2 to 1. On day 3 of the third cycle of chemotherapy, however, she began having persistent epistaxis. On day 6, she lost consciousness and was transported to the emergency room of our hospital. The hemoglobin level was 5.6 g/dL. Blood transfusion and endoscopic hemostasis were immediately started. Bevacizumab was discontinued, and paclitaxel alone was continued; after this change, epistaxis did not recur.},
}
@article {pmid25385074,
year = {2014},
author = {Wong, H and Lau, S and Cheung, P and Wong, TT and Parker, A and Yau, T and Epstein, RJ},
title = {Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy.},
journal = {BMC cancer},
volume = {14},
number = {},
pages = {826},
pmid = {25385074},
issn = {1471-2407},
mesh = {Adult ; Australia ; Breast Neoplasms/*chemistry/*pathology ; Carcinoma, Ductal, Breast/*chemistry/*secondary ; Carcinoma, Lobular/*chemistry/*secondary ; Cell Proliferation ; Chemotherapy, Adjuvant ; Female ; Hong Kong ; Humans ; Ki-67 Antigen/analysis ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Tumor Burden ; },
abstract = {BACKGROUND: Although invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity.<br><br>METHODS: The clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed.<br><br>RESULTS: Two hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p <0.001) and more often postmenopausal (p <0.03) than HK patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p <0.002); yet despite this, ILC tumors were as likely as IDC to present with nodal metastases (p >0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p <0.0005), ILC tumors failed to demonstrate any such inverse relationship (p >0.6).<br><br>CONCLUSION: These data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.},
}
@article {pmid25379017,
year = {2014},
author = {Scheiber, MN and Watson, PM and Rumboldt, T and Stanley, C and Wilson, RC and Findlay, VJ and Anderson, PE and Watson, DK},
title = {FLI1 expression is correlated with breast cancer cellular growth, migration, and invasion and altered gene expression.},
journal = {Neoplasia (New York, N.Y.)},
volume = {16},
number = {10},
pages = {801-813},
pmid = {25379017},
issn = {1476-5586},
support = {P01 CA078582/CA/NCI NIH HHS/United States ; P30 CA138313/CA/NCI NIH HHS/United States ; P01CA78582/CA/NCI NIH HHS/United States ; P30 CA 138313/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/*genetics/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Neoplasms, Experimental/genetics/pathology ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mice, Transgenic ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Protein c-fli-1/*genetics/metabolism ; Proto-Oncogene Proteins c-ets/genetics ; },
abstract = {ETS factors have been shown to be dysregulated in breast cancer. ETS factors control the expression of genes involved in many biological processes, such as cellular proliferation, differentiation, and apoptosis. FLI1 is an ETS protein aberrantly expressed in retrovirus-induced hematological tumors, but limited attention has been directed towards elucidating the role of FLI1 in epithelial-derived cancers. Using data mining, we show that loss of FLI1 expression is associated with shorter survival and more aggressive phenotypes of breast cancer. Gain and loss of function cellular studies indicate the inhibitory effect of FLI1 expression on cellular growth, migration, and invasion. Using Fli1 mutant mice and both a transgenic murine breast cancer model and an orthotopic injection of syngeneic tumor cells indicates that reduced Fli1 contributes to accelerated tumor growth. Global expression analysis and RNA-Seq data from an invasive human breast cancer cell line with over expression of either FLI1 and another ETS gene, PDEF, shows changes in several cellular pathways associated with cancer, such as the cytokine-cytokine receptor interaction and PI3K-Akt signaling pathways. This study demonstrates a novel role for FLI1 in epithelial cells. In addition, these results reveal that FLI1 down-regulation in breast cancer may promote tumor progression.},
}
@article {pmid25373614,
year = {2014},
author = {Rai, R and Zhu, L and Chen, H and Gupta, AP and Sze, SK and Zheng, J and Ruedl, C and Bozdech, Z and Featherstone, M},
title = {Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle.},
journal = {BMC genomics},
volume = {15},
number = {1},
pages = {959},
pmid = {25373614},
issn = {1471-2164},
mesh = {Antibodies, Monoclonal/pharmacology ; Binding Sites/genetics ; Chromatin Immunoprecipitation ; Cluster Analysis ; Computational Biology ; Erythrocytes/parasitology ; Gene Dosage ; *Genome, Protozoan ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; Malaria, Falciparum/*parasitology ; Molecular Sequence Annotation ; Phosphorylation ; Plasmodium falciparum/*genetics/*metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Subunits/antagonists &amp; inhibitors ; RNA Polymerase II/antagonists &amp; inhibitors/chemistry/*metabolism ; RNA, Messenger/genetics ; Transcription, Genetic ; Transcriptional Activation ; },
abstract = {BACKGROUND: Over the course of its intraerythrocytic developmental cycle (IDC), the malaria parasite Plasmodium falciparum tightly orchestrates the rise and fall of transcript levels for hundreds of genes. Considerable debate has focused on the relative importance of transcriptional versus post-transcriptional processes in the regulation of transcript levels. Enzymatically active forms of RNAPII in other organisms have been associated with phosphorylation on the serines at positions 2 and 5 of the heptad repeats within the C-terminal domain (CTD) of RNAPII. We reasoned that insight into the contribution of transcriptional mechanisms to gene expression in P. falciparum could be obtained by comparing the presence of enzymatically active forms of RNAPII at multiple genes with the abundance of their associated transcripts.<br><br>RESULTS: We exploited the phosphorylation state of the CTD to detect enzymatically active forms of RNAPII at most P. falciparum genes across the IDC. We raised highly specific monoclonal antibodies against three forms of the parasite CTD, namely unphosphorylated, Ser5-P and Ser2/5-P, and used these in ChIP-on-chip type experiments to map the genome-wide occupancy of RNAPII. Our data reveal that the IDC is divided into early and late phases of RNAPII occupancy evident from simple bi-phasic RNAPII binding profiles. By comparison to mRNA abundance, we identified sub-sets of genes with high occupancy by enzymatically active forms of RNAPII and relatively low transcript levels and vice versa. We further show that the presence of active and repressive histone modifications correlates with RNAPII occupancy over the IDC.<br><br>CONCLUSIONS: The simple early/late occupancy by RNAPII cannot account for the complex dynamics of mRNA accumulation over the IDC, suggesting a major role for mechanisms acting downstream of RNAPII occupancy in the control of gene expression in this parasite.},
}
@article {pmid25368291,
year = {2014},
author = {Klopfer, K and Delahunt, B and Adamson, M and Samaratunga, H},
title = {Value of uroplakin III in distinguishing variants of primary bladder urothelial carcinoma from malignancy metastatic to the urinary bladder.},
journal = {Anticancer research},
volume = {34},
number = {11},
pages = {6779-6784},
pmid = {25368291},
issn = {1791-7530},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Giant Cell/metabolism/*secondary ; Carcinoma, Large Cell/metabolism/*secondary ; Carcinoma, Papillary/metabolism/*secondary ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Urinary Bladder Neoplasms/metabolism/*pathology ; Uroplakin III/*metabolism ; },
abstract = {BACKGROUND: Urothelial carcinoma (UC) variants can be difficult to differentiate from carcinoma metastatic to the bladder.<br><br>MATERIALS AND METHODS: We examined immunostaining for uroplakin III in 43 cases of primary bladder UC variants including micropapillary UC (n=19), nested variant of UC (n=2), pleomorphic giant-cell carcinoma (n=8), plasmacytoid UC (n=4), lymphoepithelioma-like carcinoma (n=2), large cell undifferentiated carcinoma (n=2), UC with abundant myxoid stroma (n=3) and lipid cell variant (n=3) and in 11 tumors from other organs metastatic to the bladder. These tumors included invasive ductal carcinoma of the breast (n=2), colorectal adenocarcinoma (n=4), endometrioid adenocarcinoma (n=1) and serous papillary carcinoma of the uterus (n=1) melanoma (n=1), embryonal carcinoma of the testis (n=1), and renal clear cell carcinoma (n=1).<br><br>RESULTS: Out of the 43 UC variants, 35 (81%) were positive for uroplakin III, including micropapillary, lipid cell variant and UC with abundant myxoid stroma. Pleomorphic giant cell carcinoma, plasmacytoid UC and nested variant of UC were less commonly positive. Of the 11 metastatic tumors, six were found to be positive for uropIakin III: metastatic colorectal adenocarcinoma, clear cell carcinoma of the kidney and embryonal carcinoma of testis.<br><br>CONCLUSION: UP III Positivity for uroplakin III is not found only in primary bladder UC variants, but in some tumors that have metastatized to the bladder. Staining for uroplakin III alone should not be taken as evidence of UC.},
}
@article {pmid25360699,
year = {2014},
author = {Ma, FJ and Liu, ZB and Hu, X and Ling, H and Li, S and Wu, J and Shao, ZM},
title = {Prognostic value of myeloid differentiation primary response 88 and Toll-like receptor 4 in breast cancer patients.},
journal = {PloS one},
volume = {9},
number = {10},
pages = {e111639},
pmid = {25360699},
issn = {1932-6203},
mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Myeloid Differentiation Factor 88/*metabolism ; Prognosis ; Toll-Like Receptor 4/*metabolism ; },
abstract = {PURPOSE: Breast cancer remains a major cause of death in women worldwide, and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment. Chronic inflammation is often related to the occurrence and growth of various malignancies. This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response: myeloid differentiation primary response 88 (MyD88) and Toll-like receptor 4 (TLR4).<br><br>METHODS: We analyzed data from 205 breast invasive ductal carcinoma (IDC) patients who were treated at the Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, from 2002 to 2006. Overall survival (OS) and disease-free survival (DFS) were compared.<br><br>RESULTS: In total, 152 patients (74.15%) were disease-free without relapse or metastasis, whereas 53 (25.85%) patients developed recurrence or metastasis. A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001). Patients with high expression were more likely to experience death and recurrence/metastasis events (p<0.05). Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels (log-rank test: p<0.001). Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test: p<0.001). In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663-6.641; p&#x200a;=&#x200a;0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546-13.098; p&#x200a;=&#x200a;0.006).<br><br>CONCLUSIONS: TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer. Therefore, TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy.},
}
@article {pmid25357113,
year = {2014},
author = {Jorns, JM and Thomas, DG and Healy, PN and Daignault, S and Vickery, TL and Snider, JE and Mardis, ER and Davies, SR and Ellis, MJ and Visscher, DW},
title = {Estrogen receptor expression is high but is of lower intensity in tubular carcinoma than in well-differentiated invasive ductal carcinoma.},
journal = {Archives of pathology &amp; laboratory medicine},
volume = {138},
number = {11},
pages = {1507-1513},
pmid = {25357113},
issn = {1543-2165},
support = {P30 CA091842/CA/NCI NIH HHS/United States ; T32 CA083654/CA/NCI NIH HHS/United States ; P30 CA91842/CA/NCI NIH HHS/United States ; },
mesh = {Adenocarcinoma/genetics/*metabolism/*pathology ; Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cell Differentiation ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Middle Aged ; Molecular Typing ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {CONTEXT: Tubular carcinoma (TC) is a rare, luminal A subtype of breast carcinoma with excellent prognosis, for which adjuvant chemotherapy is usually contraindicated.<br><br>OBJECTIVE: To examine the levels of estrogen receptor (ER) and progesterone receptor expression in cases of TC and well-differentiated invasive ductal carcinoma as compared to normal breast glands and to determine if any significant differences could be detected via molecular testing.<br><br>DESIGN: We examined ER and progesterone receptor via immunohistochemistry in tubular (N = 27), mixed ductal/tubular (N = 16), and well-differentiated ductal (N = 27) carcinomas with comparison to surrounding normal breast tissue. We additionally performed molecular subtyping of 10 TCs and 10 ductal carcinomas via the PAM50 assay.<br><br>RESULTS: Although ER expression was high for all groups, TC had statistically significantly lower ER staining percentage (ER%) (P = .003) and difference in ER expression between tumor and accompanying normal tissue (P = .02) than well-differentiated ductal carcinomas, with mixed ductal/tubular carcinomas falling between these 2 groups. Mean ER% was 79%, 87%, and 94%, and mean tumor-normal ER% differences were 13.6%, 25.9%, and 32.6% in tubular, mixed, and ductal carcinomas, respectively. Most tumors that had molecular subtyping were luminal A (9 of 10 tubular and 8 of 10 ductal), and no significant differences in specific gene expression between the 2 groups were identified.<br><br>CONCLUSIONS: Tubular carcinoma exhibited decreased intensity in ER expression, closer to that of normal breast parenchyma, likely as a consequence of a high degree of differentiation. Lower ER% expression by TC may represent a potential pitfall when performing commercially available breast carcinoma prognostic assays that rely heavily on ER-related gene expression.},
}
@article {pmid25355267,
year = {2014},
author = {Qing, Z and Zou, W and Luo, J and Wen, Q and Fan, S},
title = {[p53 protein expression in HER2-negative breast invasive ductal carcinoma].},
journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences},
volume = {39},
number = {10},
pages = {1016-1022},
doi = {10.11817/j.issn.1672-7347.2014.10.005},
pmid = {25355267},
issn = {1672-7347},
mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Prognosis ; Receptor, ErbB-2 ; Tumor Suppressor Protein p53/genetics/*metabolism ; },
abstract = {OBJECTIVE: To determine the expression of p53 and its clinical significance in HER2-negative breast invasive ductal carcinoma (BIDC).<br><br>METHODS: The expression of p53, ER and PR in the HER2-negative BIDC was detected by immunohistochemistry and the results were analyzed by SPSS10.0 software packet, chi-square test, spearman's correlation analysis, Kaplan-Meier survival curves and Cox regression analysis.<br><br>RESULTS: The positive expression of p53 protein in BIDC with pathological grade III was significantly higher than that with grade I (P<0.05), but there was no significant correlation between the expression of p53 and age, clinical stage, or lymph node metastasis status in the BIDC. The positive expression of p53 protein in BIDC with ER-positive was significantly lower than that with ER-negative (P<0.01). The positive expression of p53 protein was significantly lower in BIDC with common expression of ER and PR than that with negative expression of ER or PR (P<0.05). The HER2-negative BIDC patients with p53-positive expression had a lower 5 year survival than those with p53-negative expression.<br><br>CONCLUSION: The positive expression of p53 protein might have significant prognostic value and is an independent prognostic marker in HER2 -negative BIDC.},
}
@article {pmid25344624,
year = {2014},
author = {Riobó Serván, P and Sierra Poyatos, R and Soldo Rodríguez, J},
title = {Low and no calorie sweeteners (LNCS); myths and realities.},
journal = {Nutricion hospitalaria},
volume = {30 Suppl 2e},
number = {},
pages = {49-55},
doi = {10.3305/nh.2014.30.sup2e.8288},
pmid = {25344624},
issn = {1699-5198},
mesh = {Diabetes Mellitus/prevention &amp; control ; *Energy Intake ; Humans ; Neoplasms/chemically induced ; Obesity/prevention &amp; control ; *Sweetening Agents/adverse effects ; },
abstract = {Since their introduction in the market, there has been much debate regarding the health effects of low and no calorie sweetners (LNCS). Therefore, through this review, we aim to establish scientific information about the most commonly used LNCS by the food industry. Key questions about uses, safety, and weight control are reviewed. Scientific evidence revised concludes that LNCS available on the market are safe and no epidemiological relationship has been established with the development of non-communicable diseases, including different kind of cancer in humans. Also, LCNS combined with physical activity and a healthy lifestyle can play a significant role in weight loss and the maintenance of a healthy weight. But non nutritive sweeteners will be helpful only as long as people don't eat additional calories later as compensation. Even more, LNCS represent an additional instrument in the dietary treatment of people with diabetes for metabolic control, without avoiding sweet taste.},
}
@article {pmid25343550,
year = {2014},
author = {Hu, A and Sun, M and Yan, D and Chen, K},
title = {Clinical significance of mTOR and eIF4E expression in invasive ductal carcinoma.},
journal = {Tumori},
volume = {100},
number = {5},
pages = {541-546},
doi = {10.1700/1660.18176},
pmid = {25343550},
issn = {2038-2529},
mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Adult ; Aged ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/secondary ; Carrier Proteins/metabolism ; Cell Cycle Proteins ; Eukaryotic Initiation Factor-4E/*metabolism ; Eukaryotic Initiation Factors/metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Molecular Targeted Therapy ; Phosphoproteins/metabolism ; Prognosis ; Protein Transport ; TOR Serine-Threonine Kinases/*metabolism ; },
abstract = {AIMS AND BACKGROUND: Mammalian target of rapamycin (mTOR) is one of the serine-threonine protein kinases and plays an important regulatory role in cell growth. Eukaryotic translation initiation factor 4E (eIF4E) and 4E binding protein (4EBP) are the downstream proteins of mTOR signaling pathway and are the most efficient speed regulator of eukaryotic mRNA translation. The aim of the study was to investigate the clinical significance of mTOR, eIF4E and 4EBPs expression in invasive ductal carcinoma.<br><br>METHODS: Fresh biopsy specimens of invasive ductal carcinoma tissues and normal breast tissues were collected from 45 patients with breast cancer. The expressions of mTOR, eIF4E and 4EBPs in specimens were detected by an immunohistochemical SP method, and the relationship of mTOR, eIF4E and 4EBPS expressions and of their expressions with tumor metastasis were analyzed.<br><br>RESULTS: Expressions of mTOR, eIF4E and 4EBPs in invasive ductal carcinoma were significantly higher than in normal breast tissue (P <0.05). mTOR expression was positively correlated with eIF4E and 4EBP expression in invasive ductal carcinoma (P <0.05). The positive rates of mTOR, eIF4E and 4EBPs in patients with lymph node metastasis were significantly higher than in patients without lymph node metastasis (P <0.05).<br><br>CONCLUSIONS: Increased expressions of mTOR and eIF4E in invasive ductal carcinoma may be correlated with the occurrence and metastasis of breast cancer.},
}
@article {pmid25339043,
year = {2014},
author = {Wan Abdul Rahman, WF and Fauzi, MH and Jaafar, H},
title = {Expression of DNA methylation marker of paired-like homeodomain transcription factor 2 and growth receptors in invasive ductal carcinoma of the breast.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {15},
number = {19},
pages = {8441-8445},
doi = {10.7314/apjcp.2014.15.19.8441},
pmid = {25339043},
issn = {2476-762X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Cross-Sectional Studies ; *DNA Methylation ; Female ; Follow-Up Studies ; Homeodomain Proteins/*metabolism ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Transcription Factors/*metabolism ; Homeobox Protein PITX2 ; },
abstract = {BACKGROUND: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2).<br><br>METHODS: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH).<br><br>RESULTS: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001).<br><br>CONCLUSION: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.},
}
@article {pmid25337201,
year = {2014},
author = {Ren, J and Chen, QC and Jin, F and Wu, HZ and He, M and Zhao, L and Yu, ZJ and Yao, WF and Mi, XY and Wang, EH and Wei, MJ},
title = {Overexpression of Rsf-1 correlates with pathological type, p53 status and survival in primary breast cancer.},
journal = {International journal of clinical and experimental pathology},
volume = {7},
number = {9},
pages = {5595-5608},
pmid = {25337201},
issn = {1936-2625},
mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/mortality/pathology/surgery ; Carcinoma/*chemistry/mortality/pathology/surgery ; Chi-Square Distribution ; Chromatin Assembly and Disassembly ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Nuclear Proteins/*analysis ; Predictive Value of Tests ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies ; Risk Factors ; Time Factors ; Trans-Activators/*analysis ; Treatment Outcome ; Tumor Burden ; Tumor Suppressor Protein p53/*analysis ; Up-Regulation ; Young Adult ; },
abstract = {AIM: The incidence of breast cancer in developing countries still increasing, to identify novel molecular markers associated with carcinogenesis and prognosis of breast cancer still being implemented. The largest subunit of Remodeling and spacing factor (RSF), Rsf-1, mediates ATPase-dependent chromatin remodeling. Its oncogenic properties have been demonstrated in certain carcinomas. The aim of this study was to examine the prognostic value of Rsf-1 in patients with primary breast carcinoma.<br><br>METHODS: A total of 537 patients with primary breast cancer, and 54 with benign breast hyperplasia, were performed resection surgery in the same period were enrolled. Rsf-1 immunoexpression was retrospectively assessed by immunohistochemistry (IHC). As well as, it relationship with clinicopathological factors and patient survival (LRFS, DFS and OS) was investigated.<br><br>RESULTS: Compared with benign breast hyperplasia tissues, higher percentage of Rsf-1 positive expression was detected in malignant breast carcinomas. Based on IHC staining extent &#xd7; intensity scores and ROC analysis, 278 of 526 cancers (52.9%) had high-expression (cut-off values 2.5) of Rsf-1, which correlated significantly to pathologic subtypes of breast cancer (DCIS vs. IDC, P < 0.001; ILC vs. IDC, P = 0.036), bigger tumor size (P = 0.030), higher TNM stage (P = 0.044), and p53-positive expression. In addition, there was a trend that high-expression of Rsf-1 associated with younger age (P = 0.053). We further prove that combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) was correlated with the bigger tumor size (P = 0.018), and higher TNM stage (P = 0.024). Kaplan-Meier survival analysis showed that Rsf-1 high-expression and combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) exhibited a significant correlation with poor overall survival of patients with primary breast cancer, and no association has been identified in relation to LRFS or DFS. Especially, Univariate and multivariate survival analysis demonstrated Rsf-1 expression is an independent prognostic parameter for the overall survival of patients with breast cancer.<br><br>CONCLUSIONS: High-expression of Rsf-1 is associated with pathologic subtypes of breast cancer, aggressive phenotype, p53 positive and poor clinical outcome, which confers tumor aggressiveness through chromatin remodeling, and targeting Rsf-1 gene and the pathway it related may provide new therapeutic avenues for treating breast cancer.},
}
@article {pmid25327792,
year = {2014},
author = {Wang, X and Zheng, X and Lin, X and Shi, Y and He, Y and Chen, G},
title = {[Methylation of Runx3 promoter in different breast lesions].},
journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology},
volume = {43},
number = {7},
pages = {447-450},
pmid = {25327792},
issn = {0529-5807},
mesh = {Breast/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/*metabolism ; Core Binding Factor Alpha 3 Subunit/genetics/*metabolism ; *DNA Methylation ; Female ; Fibroadenoma/*metabolism ; Humans ; Neoplasm Proteins/*metabolism ; Promoter Regions, Genetic ; },
abstract = {OBJECTIVE: To investigate the methylation status of Runx3 promoter and Runx3 expression in breast lesion tissues.<br><br>METHODS: One hundred and fourteen breast lesions, including 35 cases of fibroadenoma, 39 cases of intraductal carcinoma, 40 cases of invasive ductal carcinoma, and 33 cases of normal breast tissue from Fabruary 2010 to August 2012 were included in this study. Runx3 protein expression was assessed by immunohistochemical SP method; whereas methylation of Runx3 promoter was assessed by high resolution melting (HRM) analysis.<br><br>RESULTS: Runx3 protein was mainly expressed in the cytoplasm of ductal epithelial cells. The expression rates of Runx3 in normal breast tissue, fibroadenoma, ductal carcinoma in situ, invasive ductal carcinoma were 87.9% (29/33), 85.7% (30/35), 53.8% (21/39), and 40.0% (16/40) respectively. The methylation rates of Runx3 promoter were 12.1% (4/33), 20.0% (7/35), 46.2% (18/39), and 57.5% (23/40), respectively. Correlation analysis between promoter methylation and protein expression of Runx3 in different breast tissue showed the r value in normal breast tissue, fibroadenoma, ductal carcinoma in situ and invasive ductal carcinoma was -0.431 (P = 0.012), -0.408 (P = 0.015), -0.589 (P = 0.000) and -0.743 (P = 0.000) respectively.<br><br>CONCLUSIONS: Runx3 protein expression shows a downward trend in ductal carcinoma in situ and invasive ductal carcinoma, meanwhile its promoter methylation increases significantly. The methylation of Runx3 promoter may be one of the important factors in the occurrence and development of breast cancer.},
}
@article {pmid25307858,
year = {2015},
author = {Zhao, T and Liao, B and Yao, J and Liu, J and Huang, R and Shen, P and Peng, Z and Gui, H and Chen, X and Zhang, P and Zhu, Y and Li, X and Wei, Q and Zhou, Q and Zeng, H and Chen, N},
title = {Is there any prognostic impact of intraductal carcinoma of prostate in initial diagnosed aggressively metastatic prostate cancer?.},
journal = {The Prostate},
volume = {75},
number = {3},
pages = {225-232},
doi = {10.1002/pros.22906},
pmid = {25307858},
issn = {1097-0045},
mesh = {Adenocarcinoma/*secondary ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Carcinoma, Ductal/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/*pathology ; Prognosis ; Prostatic Neoplasms/*pathology ; },
abstract = {BACKGROUND: Intraductal carcinoma of prostate (IDC-P) was usually found to be co-exist with conventional aggressive prostate adenocarcinoma. The presence of IDC-P was considered as an adverse pathological factor, which was associated with high Gleason score, large prostate volume and accelerated disease progression. However, no any information is available on the presence of IDC-P diagnosed by needle biopsy in patients with metastatic prostate cancer. We investigated the incidence and prognostic value of intraductal carcinoma of prostate (IDC-P) in initial diagnosed metastatic prostate cancer.<br><br>METHODS: We included 278 patients with initial diagnosed metastatic prostate cancer treated between 2008 and 2011, all the pathological diagnosis were from ultrasonic-guided transperineal needle biopsy. IDC-P was strictly defined according to Epstein's criteria. Analyzed factors included age, Eastern Cooperative Oncology Group (ECOG) score, clinical T staging, Gleason scores, baseline prostate specific antigen (PSA), alkaline phosphatase (ALP), hemoglobin (HGB), PSA normalization, and the presence of IDC-P.<br><br>RESULTS: Totally, IDC-P was found in 57/278 (20.5%) cases. Univariate analysis showed that, compared with cases without IDC-P, cases with IDC-P was definitely associated with much shorter CRPC-free survival (CFS) time (46.05&#x2009;&#xb1;&#x2009;1.39 vs. 22.98&#x2009;&#xb1;&#x2009;1.80 months, P&#x2009;=&#x2009;0.000) and OS time (50.38&#x2009;&#xb1;&#x2009;1.18 vs. 36.43&#x2009;&#xb1;&#x2009;2.10 months, P&#x2009;=&#x2009;0.000). Multivariate analysis showed that the presence of IDC-P was the only independent prognostic factor associated with poor CFS (HR&#x2009;=&#x2009;4.886, P&#x2009;=&#x2009;0.011) and OS (HR&#x2009;=&#x2009;1.945, P&#x2009;=&#x2009;0.020). Further sub-analysis showed, even among patients with higher Gleason score (&#x2265;8) (n&#x2009;=&#x2009;158), IDC-P was still significantly and inversely associated with CFS and OS (the median CFS time: 40 versus 22 months; P&#x2009;=&#x2009;0.000; the median OS time: 54 vs. 36 months, P&#x2009;=&#x2009;0.000). Again, Cox's regression model confirmed that only the presence of IDC-P was still not only an independent prognostic factor predicting shorter time of CRPC (HR&#x2009;=&#x2009;4.031, P&#x2009;=&#x2009;0.035), but also for poorer OS (HR&#x2009;=&#x2009;2.499, P&#x2009;=&#x2009;0.006).<br><br>CONCLUSIONS: The presence of IDC-P in initial diagnosed metastatic prostate cancer, even among patients with more aggressive pattern, was firstly found to be significantly and independently associated with earlier occurrence of CRPC and poorer OS. We recommended the presence of IDC-P should be a routine record in pathological report of clinical diagnosis and other potential therapeutic regimen might be added to intervene in the integrated therapy as early as possible. Prostate 75:225-232, 2015. &#xa9; 2014 Wiley Periodicals, Inc.},
}
@article {pmid25306216,
year = {2014},
author = {Volinia, S and Nuovo, G and Drusco, A and Costinean, S and Abujarour, R and Desponts, C and Garofalo, M and Baffa, R and Aeqilan, R and Maharry, K and Sana, ME and Di Leva, G and Gasparini, P and Dama, P and Marchesini, J and Galasso, M and Manfrini, M and Zerbinati, C and Corrà, F and Wise, T and Wojcik, SE and Previati, M and Pichiorri, F and Zanesi, N and Alder, H and Palatini, J and Huebner, KF and Shapiro, CL and Negrini, M and Vecchione, A and Rosenberg, AL and Croce, CM and Garzon, R},
title = {Pluripotent stem cell miRNAs and metastasis in invasive breast cancer.},
journal = {Journal of the National Cancer Institute},
volume = {106},
number = {12},
pages = {},
pmid = {25306216},
issn = {1460-2105},
support = {U01 CA166905/CA/NCI NIH HHS/United States ; U01 CA154200/CA/NCI NIH HHS/United States ; U01 CA152758/CA/NCI NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; 19995/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*secondary ; Female ; Humans ; Lymphatic Metastasis ; MicroRNAs/*analysis ; *Neoplastic Stem Cells ; *Pluripotent Stem Cells ; },
abstract = {BACKGROUND: The purpose of this study is to determine whether microRNA for pluripotent stem cells are also expressed in breast cancer and are associated with metastasis and outcome.<br><br>METHODS: We studied global microRNA profiles during differentiation of human embryonic stem cells (n =26) and in breast cancer patients (n = 33) and human cell lines (n = 35). Using in situ hybridization, we then investigated MIR302 expression in 318 untreated breast cancer patients (test cohort, n = 22 and validation cohort, n = 296). In parallel, using next-generation sequencing data from breast cancer patients (n = 684), we assessed microRNA association with stem cell markers. All statistical tests were two-sided.<br><br>RESULTS: In healthy tissues, the MIR302 (high)/MIR203 (low) asymmetry was exclusive for pluripotent stem cells. MIR302 was expressed in a small population of cancer cells within invasive ductal carcinoma, but not in normal breast (P < .001). Furthermore, MIR302 was expressed in the tumor cells together with stem cell markers, such as CD44 and BMI1. Conversely, MIR203 expression in 684 breast tumors negatively correlated with CD44 (Spearman correlation, Rho = -0.08, P = .04) and BMI1 (Rho = -0.11, P = .004), but positively correlated with differentiation marker CD24 (Rho = 0.15, P < .001). Primary tumors with lymph node metastasis had cancer cells showing scattered expression of MIR302 and widespread repression of MIR203. Finally, overall survival was statistically significantly shorter in patients with MIR302-positive cancer cells (P = .03).<br><br>CONCLUSIONS: In healthy tissues the MIR302(high)/MIR203(low) asymmetry was characteristic of embryonic and induced pluripotency. In invasive ductal carcinoma, the MIR302/MIR203 asymmetry was associated with stem cell markers, metastasis, and shorter survival.},
}
@article {pmid25299107,
year = {2014},
author = {Huan, JL and Gao, X and Xing, L and Qin, XJ and Qian, HX and Zhou, Q and Zhu, L},
title = {Screening for key genes associated with invasive ductal carcinoma of the breast via microarray data analysis.},
journal = {Genetics and molecular research : GMR},
volume = {13},
number = {3},
pages = {7919-7925},
doi = {10.4238/2014.September.29.5},
pmid = {25299107},
issn = {1676-5680},
mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal/*genetics ; Female ; *Genes, Neoplasm ; *Genetic Predisposition to Disease ; Humans ; Oligonucleotide Array Sequence Analysis ; },
abstract = {The aim of this study was to identify key genes related to invasive ductal carcinoma (IDC) of the breast by analyzing gene expression data with bioinformatic tools. Microarray data set GSE31138 was downloaded from Gene Expression Omnibus, including 3 breast cancer tissue samples and 3 normal controls. Differentially expressed genes (DEGs) between breast cancer and normal control were screened out (FDR < 0.05 and |logFC| > 2). Coexpression between genes was examined with String, and a network was then constructed. Relevant pathways and diseases were retrieved with KOBAS. A total of 56 DEGs were obtained in the IDC of the breast compared with normal controls. A gene coexpression network including 27 pairs of genes was constructed and all the genes in the network were upregulated. Further study indicated that most of the genes in the coexpression network were enriched in ECM-receptor interaction (COL4A2, FN1, and HMMR) and nucleotide excision repair (CETN2 and PCNA) pathways, and that the most significantly related disease was autoimmune lymphoproliferative syndromes. A number of DEGs were acquired through comparative analysis of gene expression data. These findings are beneficial in promoting the understanding of the molecular mechanisms in breast cancer. More importantly, some key genes were revealed via gene coexpression network analysis, which could be potential biomarkers for IDC of the breast.},
}
@article {pmid25296604,
year = {2014},
author = {Ross, M and Hadzikadic Gusic, L and Dabbs, DJ and Kelley, J and Diego, E},
title = {Simultaneous breast and axillary recurrence in a patient with a history of breast cancer and ipsilateral upper extremity melanoma: challenges in diagnosis and management.},
journal = {Tumori},
volume = {100},
number = {4},
pages = {136e-9e},
doi = {10.1700/1636.17928},
pmid = {25296604},
issn = {2038-2529},
mesh = {Adult ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Arm ; Axilla ; Breast Neoplasms/diagnosis/*therapy ; Capecitabine ; Carcinoma, Ductal, Breast/*diagnosis/*therapy ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/therapy ; Chemotherapy, Adjuvant ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Female ; Fluorouracil/administration &amp; dosage/analogs &amp; derivatives ; Humans ; Interferons/administration &amp; dosage ; *Lymph Node Excision ; Mammaplasty ; *Mastectomy, Segmental/methods ; Mastectomy, Simple ; Melanoma/*secondary ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnosis/*therapy ; Neoplasms, Multiple Primary/*diagnosis/pathology/*therapy ; Patient Care Team ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/pathology/*therapy ; Skin Neoplasms/*pathology ; Trastuzumab ; },
abstract = {BACKGROUND: Nodal patterns of spread for breast cancer and melanoma have been extensively studied in the literature. The phenomenon of upper extremity melanoma and ipsilateral breast cancer has been previously reported. We describe a rare case of a simultaneous locoregional recurrence of both malignancies.<br><br>CASE REPORT: A patient with a previous diagnosis of stage 1A melanoma of the left upper extremity at age 29 developed left breast invasive ductal carcinoma 1 year later. The patient underwent a wide local excision with negative margins for the melanoma and a partial mastectomy with axillary dissection followed by chemotherapy and radiation therapy for her breast cancer. Five years later she was diagnosed with a dual recurrence while 36 weeks pregnant.<br><br>CONCLUSIONS: Regular follow-up according to the NCCN guidelines is critical in diagnosing a recurrence of malignancy. Pathologic analysis is paramount in dictating management strategies in rare cases of dual recurrence.},
}
@article {pmid25287760,
year = {2015},
author = {Abomaray, FM and Al Jumah, MA and Kalionis, B and AlAskar, AS and Al Harthy, S and Jawdat, D and Al Khaldi, A and Alkushi, A and Knawy, BA and Abumaree, MH},
title = {Human Chorionic Villous Mesenchymal Stem Cells Modify the Functions of Human Dendritic Cells, and Induce an Anti-Inflammatory Phenotype in CD1+ Dendritic Cells.},
journal = {Stem cell reviews and reports},
volume = {11},
number = {3},
pages = {423-441},
pmid = {25287760},
issn = {2629-3277},
mesh = {Antigens, CD1/metabolism ; Cell Differentiation/drug effects/*genetics ; Cell Proliferation/genetics ; Chorionic Villi/metabolism ; Coculture Techniques ; Dendritic Cells/*cytology/metabolism ; Female ; Gene Expression Regulation, Developmental ; Granulocyte-Macrophage Colony-Stimulating Factor/administration &amp; dosage ; Humans ; Interleukin-4/administration &amp; dosage ; Mesenchymal Stem Cells/*cytology/metabolism ; Monocytes/*cytology/metabolism ; Placenta/cytology/metabolism ; Pregnancy ; },
abstract = {BACKGROUND: Mesenchymal stem cells derived from the chorionic villi of human term placenta (pMSCs) have drawn considerable interest because of their multipotent differentiation potential and their immunomodulatory capacity. These properties are the foundation for their clinical application in the fields of stem cell transplantation and regenerative medicine. Previously, we showed that pMSCs induce an anti-inflammatory phenotype in human macrophages. In this study, we determined whether pMSCs modify the differentiation and maturation of human monocytes into dendritic cells (DCs). The consequences on dendritic function and on T cell proliferation were also investigated.<br><br>METHODS: Interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF) were used to stimulate the differentiation of monocytes into immature dendritic cells (iDCs), which were subsequently co-cultured with pMSCs. Lipopolysaccharide (LPS) was used to induce maturation of iDCs into mature dendritic cells (mDCs). Flow cytometry and enzyme-linked immunosorbent assays (ELISA) were used to quantify the effect pMSC co-culturing on DC differentiation using CD1a, a distinctive marker of DCs, as well as other molecules important in the immune functions of DCs. The phagocytic activity of iDCs co-cultured with pMSCs, and the effects of iDCs and mDC stimulation on T cell proliferation, were also investigated.<br><br>RESULTS: Monocyte differentiation into iDCs was inhibited when co-cultured with pMSCs and maturation of iDCs by LPS treatment was also prevented in the presence of pMSCs as demonstrated by reduced expression of CD1a and CD83, respectively. The inhibitory effect of pMSCs on iDC differentiation was dose dependent. In addition, pMSC co-culture with iDCs and mDCs resulted in both phenotypic and functional changes as shown by reduced expression of costimulatory molecules (CD40, CD80, CD83 and CD86) and reduced capacity to stimulate CD4(+) T cell proliferation. In addition, pMSC co-culture increased the surface expression of major histocompatibility complex (MHC-II) molecules on iDCs but decreased MHC-II expression on mDCs. Moreover, pMSC co-culture with iDCs or mDCs increased the expression of immunosuppressive molecules [B7H3, B7H4, CD273, CD274 and indoleamine-pyrrole 2,3-dioxygenase (IDO). Additionally, the secretion of IL-12 and IL-23 by iDCs and mDCs co-cultured with pMSCs was decreased. Furthermore, pMSC co-culture with mDCs decreased the secretion of IL-12 and INF-&#x3b3; whilst increasing the secretion of IL-10 in a T cell proliferation experiment. Finally, pMSC co-culture with iDCs induced the phagocytic activity of iDCs.<br><br>CONCLUSIONS: We have shown that pMSCs have an inhibitory effect on the differentiation, maturation and function of DCs, as well as on the proliferation of T cells, suggesting that pMSCs can control the immune responses at multiple levels.},
}
@article {pmid25287438,
year = {2015},
author = {Adrada, BE and Huo, L and Lane, DL and Arribas, EM and Resetkova, E and Yang, W},
title = {Histopathologic correlation of residual mammographic microcalcifications after neoadjuvant chemotherapy for locally advanced breast cancer.},
journal = {Annals of surgical oncology},
volume = {22},
number = {4},
pages = {1111-1117},
doi = {10.1245/s10434-014-4113-8},
pmid = {25287438},
issn = {1534-4681},
mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Breast Neoplasms/diagnostic imaging/drug therapy/*pathology ; Calcinosis/chemically induced/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/drug therapy/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/drug therapy/*pathology ; Carcinoma, Lobular/diagnostic imaging/drug therapy/*pathology ; Female ; Follow-Up Studies ; Humans ; Mammography ; Middle Aged ; Neoadjuvant Therapy/*adverse effects ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasm, Residual/chemically induced/diagnostic imaging/*pathology ; Prognosis ; Retrospective Studies ; Young Adult ; },
abstract = {OBJECTIVE: This study was designed to determine the histopathologic correlation at surgery of residual mammographic calcifications in patients after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (LABC).<br><br>METHODS: This single-institution, retrospective study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability act compliant. Women with LABC who underwent NAC between January 1, 2004 and December 31, 2008 and had mammography performed before and after NAC available for review were included in this study. The extent of microcalcifications associated with cancer before and after the completion of NAC was correlated with histopathology and biomarker status.<br><br>RESULTS: Of 494 patients who met the inclusion criteria, 106 demonstrated microcalcifications on pre-, post-chemotherapy, or both sets of mammograms and were included in this study. Of 106 women, 31 (29 %) had invasive ductal carcinoma (IDC) and 60 (57 %) had both IDC and ductal carcinoma in situ (DCIS). Microcalcifications decreased or remained stable in 76 (72 %) patients after completion of NAC. Correlation of microcalcifications with histopathology after NAC showed that 43 (40.6 %) patients had tumors associated with benign pathology. Of 32 patients with pathologic complete response, calcifications were associated with DCIS in 9 (9 %) and benign findings in 21 (22 %). The proportion of residual malignant calcifications was higher in ER+ versus ER- patients after NAC.<br><br>CONCLUSIONS: The extent of calcifications on mammography following NAC does not correlate with the extent of residual disease in up to 22 % of women; this information may impact surgical planning in subsets of women with breast cancer.},
}
@article {pmid25271877,
year = {2015},
author = {Barbosa, OV and Reiriz, AB and Boff, RA and Oliveira, WP and Rossi, L},
title = {Angiosarcoma in previously irradiated breast in patient with Li-Fraumeni syndrome. A case report.},
journal = {Sao Paulo medical journal = Revista paulista de medicina},
volume = {133},
number = {2},
pages = {151-153},
pmid = {25271877},
issn = {1806-9460},
mesh = {Adult ; Breast Neoplasms/etiology/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/*radiotherapy ; Female ; Genes, p53 ; Genetic Predisposition to Disease ; Hemangiosarcoma/*etiology/pathology ; Humans ; Li-Fraumeni Syndrome/*genetics/pathology ; *Neoplasms, Radiation-Induced/pathology ; Radiotherapy, Adjuvant/adverse effects ; },
abstract = {CONTEXT: Li-Fraumeni syndrome is a rare disease with an autosomal dominant inheritance pattern and high penetrance that defines a 50% chance of developing cancer before the age of 30 years, including cases of breast sarcoma. Patients with this syndrome who require radiotherapy have an increased risk of developing secondary malignancies including angiosarcomas.<br><br>CASE REPORT: This was a case report on a female patient with Li-Fraumeni syndrome. In October 2005, she was diagnosed with invasive ductal carcinoma of the right breast and underwent sectorectomy. She then received chemotherapy and adjuvant radiotherapy. Trastuzumab and tamoxifen were also part of the treatment. She recently sought care at our hospital, complaining of hyperemia and nodulation in the right breast, and underwent surgical resection that revealed epithelioid angiosarcoma.<br><br>CONCLUSIONS: When genetic predisposition due to Li-Fraumeni syndrome is documented, the therapy should be adapted so as to minimize the risk. Thus, conservative surgical treatments should be avoided and mastectomy without radiation should be prioritized. In cases in which use of radiotherapy is justified, patients should be followed up intensively.},
}
@article {pmid25270118,
year = {2014},
author = {Pacheco-Velázquez, SC and Gallardo-Pérez, JC and Aguilar-Ponce, JL and Villarreal, P and Ruiz-Godoy, L and Pérez-Sánchez, M and Marín-Hernández, A and Ruiz-García, E and Meneses-García, A and Moreno-Sánchez, R and Rodríguez-Enríquez, S},
title = {Identification of a metabolic and canonical biomarker signature in Mexican HR+/HER2-, triple positive and triple-negative breast cancer patients.},
journal = {International journal of oncology},
volume = {45},
number = {6},
pages = {2549-2559},
doi = {10.3892/ijo.2014.2676},
pmid = {25270118},
issn = {1791-2423},
mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Estrogen Receptor alpha/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis ; Mexico ; Middle Aged ; Prognosis ; *Proteomics ; Proto-Oncogene Proteins c-myc/biosynthesis ; Receptor, ErbB-2/*genetics ; Retrospective Studies ; Triple Negative Breast Neoplasms/diagnosis/*genetics/pathology ; },
abstract = {Infiltrating ductal breast cancer (IDC) is the principal tumor associated-malignancy in Mexican women. In IDC, the development of intermittent hypoxia leads to an adaptive response coordinated by the transcriptional factor HIF-1α. In the present pilot, retrospective/cross-sectional study, the HIF-1α expression was analyzed in 102 tru-cut biopsies from female patients (51 ± 12 years) without previous clinical treatment and compared to 31 normal breast biopsies. The 102 IDC samples corresponded to 56% of HER2-/HR+; 8% of HER2+/HR-; 22% of triple positive (HER2+/HR+); and 14% of triple negative (TN, HER2-/HR-) subtypes. To assess HIF-1α functionality, proteomic and kinetic analysis of glycolytic as well as mitochondrial enzymes, were determined. Validation of HIF-1α as cancer biomarker was assessed by determining the contents of the commonly used biomarkers c-MYC, Ki67, and H- and K-RAS, as well as metastatic and autophagy proteins. Proteomic analysis revealed that HIF-1α, c-MYC, HER2 and COXIV contents were significantly increased in all IDC subtypes vs. normal tissue. The contents and activities of glycolytic proteins were similar between normal and IDC samples, except for HER2-/HR+ where a substantial increase of HKII was observed. Significant increase in 2OGDH and E-cadherin was detected for TN samples vs. other IDC subtypes and for normal samples. These results clearly indicated that HIF-1α + COXIV + c-MYC (+ HER2 for HER2+ subtype) may be useful to depict a breast cancer metabolic marker pattern for diagnosis, whereas the contents of HIF-1α + c-MYC + 2OGDH + E-cadherin may be an alternative useful and reliable signature for TN subtype cancer prognosis.},
}
@article {pmid25261651,
year = {2014},
author = {Petekkaya, I and Aksoy, S and Roach, EC and Okoh, AK and Gecmez, G and Gezgen, G and Isler, DC and Dogan, E and Babacan, T and Sarici, F and Petekkaya, E and Altundag, K},
title = {Impact of inflammatory markers on the prognosis of patients with operable breast cancer.},
journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology},
volume = {19},
number = {3},
pages = {673-680},
pmid = {25261651},
issn = {1107-0625},
mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Sedimentation ; Breast Neoplasms/blood/*mortality ; C-Reactive Protein/analysis ; Female ; Ferritins/blood ; Humans ; Inflammation/*complications ; L-Lactate Dehydrogenase/blood ; Middle Aged ; Prognosis ; Serum Albumin/analysis ; beta 2-Microglobulin/blood ; },
abstract = {PURPOSE: To investigate the effect of inflammatory markers on the prognosis of patients with operable breast cancer.<br><br>METHODS: This study was conducted on breast cancer patients followed up between December 2009 and December 2012 at the Division of Medical Oncology, Department of Internal Medicine, Hacettepe University Medical School. A total of 704 patients with stages I to III disease whose inflammatory markers were assessed at the time of diagnosis were included the study. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, ferritin, &#x3b2;2 microglobulin (&#x3b2;2-M), and lactate dehydrogenase (LDH) levels were evaluated as inflammatory markers.<br><br>RESULTS: The median age at diagnosis was 50 years (range 25-92). Of the patients 42.8% were premenopausal and 48.2 % postmenopausal. Invasive ductal carcinoma was the most common histology (76.5 %). Serum ferritin, LDH, &#x3b2;2-M, ESR, and CRP were higher than the normal values in 1.0, 4.3, 9.5, 32.4 and 36.4 % of the patients, respectively. Serum albumin levels were lower than the normal values in 1.7 % of the patients. The median patient follow-up period was 22 months (range 3-227). During follow-up, metastatic disease developed in 31 patients (4.4%) and 11 patients (1.56%) died due to disease progression. Two-year overall survival (OS) and disease free survival (DFS) rates were not statistically different among patients with normal and abnormal values with respect to albumin, ferritin, LDH, &#x3b2;2-M, CRP, and ESR.<br><br>CONCLUSION: Our study is the first study to investigate the effect of inflammatory markers on the prognosis of operable breast cancer patients. We showed that inflammatory markers such as ESR, CRP, ferritin, &#x3b2;2-M, albumin and LDH have no effect on prognosis.},
}
@article {pmid25260852,
year = {2015},
author = {Moccia, M and Mosca, L and Erro, R and Cervasio, M and Allocca, R and Vitale, C and Leonardi, A and Caranci, F and Del Basso-De Caro, ML and Barone, P and Penco, S},
title = {Hypomorphic NOTCH3 mutation in an Italian family with CADASIL features.},
journal = {Neurobiology of aging},
volume = {36},
number = {1},
pages = {547.e5-11},
doi = {10.1016/j.neurobiolaging.2014.08.021},
pmid = {25260852},
issn = {1558-1497},
mesh = {Adult ; Aged ; Animals ; CADASIL/*genetics ; *Codon, Nonsense ; Exons/genetics ; Female ; Humans ; Italy ; Male ; Mice ; Middle Aged ; RNA, Messenger ; Receptor, Notch3 ; Receptors, Notch/*genetics ; Signal Transduction/genetics/physiology ; Young Adult ; },
abstract = {The cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is because of NOTCH3 mutations affecting the number of cysteine residues. In this view, the role of atypical NOTCH3 mutations is still debated. Therefore, we investigated a family carrying a NOTCH3 nonsense mutation, with dominantly inherited recurrent cerebrovascular disorders. Among 7 family members, 4 received a clinical diagnosis of CADASIL. A heterozygous truncating mutation in exon 3 (c.307C>T, p.Arg103X) was found in the 4 clinically affected subjects and in one 27-year old lady, only complaining of migraine with aura. Magnetic resonance imaging scans found typical signs of small-vessel disease in the 4 affected subjects, supporting the clinical diagnosis. Skin biopsies did not show the typical granular osmiophilic material, but only nonspecific signs of vascular damage, resembling those previously described in Notch3 knockout mice. Interestingly, messenger RNA (mRNA) analysis supports the hypothesis of an atypical NOTCH3 mutation, suggesting a nonsense-mediated mRNA decay. In conclusion, the present study broadens the spectrum of CADASIL mutations, and, therefore, opens new insights about Notch3 signaling.},
}
@article {pmid25257596,
year = {2015},
author = {Zhang, M and Zhou, J and Wang, J and Zhou, Q and Fang, J and Zhou, C and Chen, W},
title = {Superparamagnetic iron oxide labeling limits the efficacy of rabbit immature dendritic cell vaccination by decreasing their antigen uptake ability in a lysosome-dependent manner.},
journal = {Biotechnology letters},
volume = {37},
number = {2},
pages = {289-298},
doi = {10.1007/s10529-014-1681-4},
pmid = {25257596},
issn = {1573-6776},
mesh = {Animals ; Aspirin ; Autophagy/drug effects ; Cell Survival/drug effects ; Dendritic Cells/*drug effects/metabolism ; Lysosomes/*drug effects/metabolism ; Magnetite Nanoparticles/*chemistry/toxicity ; Rabbits ; Vaccination ; },
abstract = {Immature dendritic cells (iDCs) are for cell transplantation; however, no method has yet been developed for in vivo monitoring the transplanted iDCs. We have explored the feasibility of using superparamagnetic iron oxide (SPIO) labeling and magnetic resonance imaging for in vivo tracking of transplanted iDCs and determined the effects of SPIO labeling on iDC vaccination. With up to 50 μg Fe/ml, SPIO effectively labeled the iDCs without affecting their growth. At or above 100 μg Fe/ml, SPIO caused considerable damage to iDCs. SPIO labeling resulted in autophagosome formation and decreased the uptake of oxidized low density lipoprotein (ox-LDL), an exogenous antigen, by iDCs. SPIO and ox-LDL both localized to the lysosomes, and this competition for lysosomes could be partially responsible for the decreased ox-LDL phagocytic capacity of iDCs due to SPIO labeling.},
}
@article {pmid25252956,
year = {2014},
author = {Ellegård, R and Crisci, E and Burgener, A and Sjöwall, C and Birse, K and Westmacott, G and Hinkula, J and Lifson, JD and Larsson, M},
title = {Complement opsonization of HIV-1 results in decreased antiviral and inflammatory responses in immature dendritic cells via CR3.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {193},
number = {9},
pages = {4590-4601},
pmid = {25252956},
issn = {1550-6606},
support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; },
mesh = {Complement System Proteins/*immunology ; Dendritic Cells/*immunology/*metabolism/virology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Profiling ; HIV Infections/genetics/*immunology/metabolism ; HIV-1/*immunology ; Humans ; Immunity, Innate/genetics ; Inflammation/genetics/immunology/metabolism ; Interferon Regulatory Factor-1/metabolism ; Interferon Regulatory Factor-3/metabolism ; Macrophage-1 Antigen/*metabolism ; Models, Biological ; NF-kappa B/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Phosphorylation ; Protein Transport ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; Toll-Like Receptor 8/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; src-Family Kinases/metabolism ; },
abstract = {Immature dendritic cells (iDCs) in genital and rectal mucosa may be one of the first cells to come into contact with HIV-1 during sexual transmission of virus. HIV-1 activates the host complement system, which results in opsonization of virus by inactivated complement fragments, for example, iC3b. We investigated antiviral and inflammatory responses induced in human iDCs after exposure to free HIV-1 (F-HIV), complement-opsonized HIV-1 (C-HIV), and complement and Ab-opsonized HIV-1 (CI-HIV). F-HIV gave rise to a significantly higher expression of antiviral factors such as IFN-β, myxovirus resistance protein A, and IFN-stimulated genes, compared with C-HIV and CI-HIV. Additionally, F-HIV induced inflammatory factors such as IL-1β, IL-6, and TNF-α, whereas these responses were weakened or absent after C-HIV or CI-HIV exposure. The responses induced by F-HIV were TLR8-dependent with subsequent activation of IFN regulatory factor 1, p38, ERK, PI3K, and NF-κB pathways, whereas these responses were not induced by C-HIV, which instead induced activation of IFN regulatory factor 3 and Lyn. This modulation of TLR8 signaling was mediated by complement receptor 3 and led to enhanced infection. The impact that viral hijacking of the complement system has on iDC function could be an important immune evasion mechanism used by HIV-1 to establish infection in the host.},
}
@article {pmid25231588,
year = {2014},
author = {Gabanti, E and Bruno, F and Fornara, C and Bernuzzi, S and Lilleri, D and Gerna, G},
title = {Polyfunctional analysis of human cytomegalovirus (HCMV)-specific CD4(+) and CD8 (+) memory T-cells in HCMV-seropositive healthy subjects following different stimuli.},
journal = {Journal of clinical immunology},
volume = {34},
number = {8},
pages = {999-1008},
pmid = {25231588},
issn = {1573-2592},
mesh = {Adult ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*chemistry ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/*immunology ; Flow Cytometry ; Healthy Volunteers ; Humans ; Immunization ; *Immunologic Memory ; Middle Aged ; },
abstract = {PURPOSE: Following primary human cytomegalovirus (HCMV) infection, both humoral and T-cell-mediated immune responses develop in immunocompetent subjects. However, while antibodies may be measured by different methodologies, the T-cell-mediated response remains to be analyzed in its polyfunctional aspects, in view of defining (following different stimuli) the optimal assay to monitor the HCMV-specific T-cell response in HCMV-seropositive subjects.<br><br>METHODS: In a group of 30 HCMV-seropositive adults, T-cell response revealed by the HCMV-infected dendritic cell (iDC) stimulus was compared with those given by the HCMV-infected cell lysate (iCL), and by a 34-peptide pool (PP).<br><br>RESULTS: All HCMV-seropositive subjects showed presence of both HCMV-specific CD4(+) and CD8(+) T-cells in peripheral blood following iDC stimulation. One subject did not respond to PP. As compared to iDC, the number of HCMV-specific stimulated T-cells/&#x3bc;l blood was slightly lower for iCL (P&#x2009;=&#x2009;0.195) and significantly lower for PP (P&#x2009;=&#x2009;0.001). Polyfunctional analysis of the T-cell response indicated that the lower number of CD4(+) T-cells stimulated by iCL was due to the bifunctional (IFN-&#x3b3;(+) TNF-&#x3b1;(+)) and CD40L-negative T-cell reduction, while the reduction in specific PP-stimulated CD8(+) T-cells was attributable to the reduction in tri-(IFN-&#x3b3;(+) TNF-&#x3b1;(+) IL2(+)), bi-(IFN-&#x3b3;(+) TNF-&#x3b1;(+)) and mono-(IFN-&#x3b3;(+)) functional T-cells. In addition, 15/30 (50&#xa0;%) subjects showed a CD4(+) cross-response to PP, and 11/30 (37&#xa0;%) a CD8(+) cross-response to iCL.<br><br>CONCLUSIONS: HCMV-specific stimulus given by iDC is not significantly different from that of iCL on CD4(+) and is significantly superior to that of PP on CD8+ T-cells. However, iCL may contribute significantly to CD8(+), and PP to CD4(+) T-cell stimulation.},
}
@article {pmid25230850,
year = {2014},
author = {Zheng, L and Zhou, B and Meng, X and Zhu, W and Zuo, A and Wang, X and Jiang, R and Yu, S},
title = {A model of spontaneous mouse mammary tumor for human estrogen receptor- and progesterone receptor-negative breast cancer.},
journal = {International journal of oncology},
volume = {45},
number = {6},
pages = {2241-2249},
pmid = {25230850},
issn = {1791-2423},
mesh = {Animals ; Biomarkers, Tumor/biosynthesis ; Breast Neoplasms/*genetics/pathology ; Cyclin D1/biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Mammary Neoplasms, Animal/*genetics/pathology ; Mice ; Proto-Oncogene Proteins c-myc/biosynthesis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Vascular Endothelial Growth Factor A/biosynthesis ; },
abstract = {Breast cancer (BC) is the most frequently malignancy in women. Therefore, establishment of an animal model for the development of preventative measures and effective treatment for tumors is required. A novel heterogeneous spontaneous mammary tumor animal model of Kunming mice was generated. The purpose of this study was to characterize the spontaneous mammary tumor model. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and muscle tissue. Metastatic spread through blood vessel into liver and lungs was observed by hematoxylin eosin staining. No estrogen receptor (ER) or progesterone receptor (PR) immunoreactivity was detected in their associated malignant tumors, human epidermal growth factor receptor-2 (HER-2) protein weak expression was found by immunohistochemistry. High expression of vascular endothelial growth factor (VEGF), moderate or high expression of c-Myc and cyclin D1 were observed in tumor sections at different stages (2, 4, 6 and 8 weeks after cancer being found) when compared with that of the normal mammary glands. The result showed that the model is of an invasive ductal carcinoma. Remarkably in the mouse model, ER and PR-negative and HER2 weak positivity are observed. The high or moderate expressions of breast cancer markers (VEGF, c-Myc and cyclin D1) in mammary cancer tissue change at different stages. To our knowledge, this is the first report of a spontaneous mammary model displaying colony-strain, outbred mice. This model will be an attractive tool to understand the biology of anti-hormonal breast cancer in women.},
}
@article {pmid25230018,
year = {2014},
author = {Yoda, T and McNamara, KM and Miki, Y and Takagi, M and Rai, Y and Ohi, Y and Sagara, Y and Tamaki, K and Hirakawa, H and Ishida, T and Suzuki, T and Ohuchi, N and Sasano, H},
title = {Intratumoral androgen metabolism and actions in invasive lobular carcinoma of the breast.},
journal = {Cancer science},
volume = {105},
number = {11},
pages = {1503-1509},
pmid = {25230018},
issn = {1349-7006},
mesh = {3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics/metabolism ; Adult ; Aged ; Aged, 80 and over ; Androgens/*metabolism ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Lobular/genetics/*metabolism/*pathology ; Estradiol Dehydrogenases/genetics/metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Tumor Burden ; },
abstract = {Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast carcinomas and is characterized by higher levels of androgen receptor (AR) compared to invasive ductal carcinoma (IDC). Despite this potentially androgen-responsive environment, the combined importance of AR and androgen metabolism in non-neoplastic lobules and lobular carcinoma remains unknown. Therefore, in this study, we evaluated the status of pivotal androgen-producing enzymes 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) and 5α-reductase type 1 (5αRed1) in 178 cases of ILC and surrounding histologically non-neoplastic lobular tissue using immunohistochemistry. Androgen receptor prevalence was higher but androgenic enzymes lower in ILC than non-neoplastic lobules. In ILC cases the status of 5αRed1 and 17βHSD5 was inversely correlated with tumor size (P = 0.0053) and nuclear grade (P = 0.0290), and significantly associated with better overall survival of the patients (P = 0.0059). Based on these findings, we hypothesized that androgen signaling could act as a tumor suppressor. As previous studies suggested that androgens might partially act by increasing levels of the estrogen inactivating enzyme 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) in IDC tissues, this was reasonably considered a potential mechanism of androgen actions. Significantly positive correlation was detected between the status of androgenic enzymes and 17βHSD2 (P < 0.0001) and intratumoral 17βHSD2 was inversely correlated with tumor size in ILC (P = 0.0075). These correlations suggest one protective mode of androgen action could be through modulation of estrogen metabolism. Results of our present study indicated that androgen-producing enzymes could play pivotal protective roles in AR-enriched ILC cases.},
}
@article {pmid25228385,
year = {2014},
author = {Tan, X and Peng, J and Fu, Y and An, S and Rezaei, K and Tabbara, S and Teal, CB and Man, YG and Brem, RF and Fu, SW},
title = {miR-638 mediated regulation of BRCA1 affects DNA repair and sensitivity to UV and cisplatin in triple-negative breast cancer.},
journal = {Breast cancer research : BCR},
volume = {16},
number = {5},
pages = {435},
pmid = {25228385},
issn = {1465-542X},
support = {R21 CA159103/CA/NCI NIH HHS/United States ; 1R21 CA159103-01/CA/NCI NIH HHS/United States ; },
mesh = {Antineoplastic Agents/*pharmacology ; BRCA1 Protein/*genetics/metabolism ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin/*pharmacology ; DNA Repair ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*physiology ; Neoplasm Invasiveness ; RNA Interference ; Triple Negative Breast Neoplasms/drug therapy/*genetics/metabolism/pathology ; Ultraviolet Rays ; },
abstract = {INTRODUCTION: Triple-negative breast cancer (TNBC) represents 15 to 20% of all types of breast cancer; however, it accounts for a large number of metastatic cases and deaths, and there is still no effective treatment. The deregulation of microRNAs (miRNAs) in breast cancer has been widely reported. We previously identified that miR-638 was one of the most deregulated miRNAs in breast cancer progression. Bioinformatics analysis revealed that miR-638 directly targets BRCA1. The aim of this study was to investigate the role of miR-638 in breast cancer prognosis and treatment.<br><br>METHODS: Formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were microdissected into normal epithelial and invasive ductal carcinoma (IDC) cells, and total RNA was isolated. Several breast cancer cell lines were used for the functional analysis. miR-638 target genes were identified by TARGETSCAN-VERT 6.2 and miRanda. The expression of miR-638 and its target genes was analyzed by real-time qRT-PCR and Western blotting. Dual-luciferase reporter assay was employed to confirm the specificity of miR-638 target genes. The biological function of miR-638 was analyzed by MTT chemosensitivity, matrigel invasion and host cell reactivation assays.<br><br>RESULTS: The expression of miR-638 was decreased in IDC tissue samples compared to their adjacent normal controls. The decreased miR-638 expression was more prevalent in non-TNBC compared with TNBC cases. miR-638 expression was significantly downregulated in breast cancer cell lines compared to the immortalized MCF-10A epithelial cells. BRCA1 was predicted as one of the direct targets of miR-638, which was subsequently confirmed by dual-luciferase reporter assay. Forced expression of miR-638 resulted in a significantly reduced proliferation rate as well as decreased invasive ability in TNBC cells. Furthermore, miR-638 overexpression increased sensitivity to DNA-damaging agents, ultraviolet (UV) and cisplatin, but not to 5-fluorouracil (5-FU) and epirubicin exposure in TNBC cells. Host cell reactivation assays showed that miR-638 reduced DNA repair capability in post UV/cisplatin-exposed TNBC cells. The reduced proliferation, invasive ability, and DNA repair capabilities are associated with downregulated BRCA1 expression.<br><br>CONCLUSIONS: Our findings suggest that miR-638 plays an important role in TNBC progression via BRCA1 deregulation. Therefore, miR-638 might serve as a potential prognostic biomarker and therapeutic target for breast cancer.},
}
@article {pmid25227964,
year = {2014},
author = {Kryh, CG and Pietersen, CA and Rahr, HB and Christensen, RD and Wamberg, P and Lautrup, MD},
title = {Re-resection rates and risk characteristics following breast conserving surgery for breast cancer and carcinoma in situ: A single-centre study of 1575 consecutive cases.},
journal = {Breast (Edinburgh, Scotland)},
volume = {23},
number = {6},
pages = {784-789},
doi = {10.1016/j.breast.2014.08.011},
pmid = {25227964},
issn = {1532-3080},
mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms/pathology/*surgery ; Carcinoma in Situ/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Carcinoma, Lobular/pathology/*surgery ; Cohort Studies ; Denmark ; Female ; Humans ; *Mastectomy, Segmental ; Neoadjuvant Therapy ; Reoperation ; Risk Factors ; },
abstract = {OBJECTIVES: To examine the frequency of re-resections and describe risk characteristics: invasive carcinoma or carcinoma in situ (CIS), palpability of the lesion, and neoadjuvant chemotherapy.<br><br>RESULTS: 1703 breast conserving surgeries were performed: 1575 primary breast conserving surgeries (BCS), and 128 diagnostic excisions (DE). 176 BCS (11.2% [9.6; 12.7]) and 100 DE had inadequate margins indicating re-resection. The overall re-resection rate was 16.2% [14.5; 18.0]. 10.3% of invasive carcinoma BCS patients, and 28.6% CIS patients underwent re-resection (relative risk (RR) 2.8 [1.9; 4.1]). Invasive lobular carcinoma (ilc) had an RR of re-resection of 2.5 [1.7; 3.8], compared with invasive ductal carcinoma (idc).<br><br>CONCLUSION: Overall 11.2% of the BCS patients needed a re-resection. For isolated CIS (28.6%), RR of re-resection was almost three times as high compared to invasive carcinoma (10.3%). Ilc had an RR of re-resection of 2.5 compared to idc. Palpability and neoadjuvant chemotherapy did not significantly influence the risk of re-resection.},
}
@article {pmid25225893,
year = {2014},
author = {Mamidi, S and Lee, RK and Goos, JR and McClean, PE},
title = {Genome-wide association studies identifies seven major regions responsible for iron deficiency chlorosis in soybean (Glycine max).},
journal = {PloS one},
volume = {9},
number = {9},
pages = {e107469},
pmid = {25225893},
issn = {1932-6203},
mesh = {Alleles ; Chromosome Mapping ; Disease Resistance/genetics ; Epistasis, Genetic ; Genes, Plant ; Genetic Association Studies ; Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Genotype ; *Iron Deficiencies ; Linkage Disequilibrium ; Molecular Sequence Annotation ; Phenotype ; Plant Diseases/*genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Glycine max/*genetics/*metabolism ; },
abstract = {Iron deficiency chlorosis (IDC) is a yield limiting problem in soybean (Glycine max (L.) Merr) production regions with calcareous soils. Genome-wide association study (GWAS) was performed using a high density SNP map to discover significant markers, QTL and candidate genes associated with IDC trait variation. A stepwise regression model included eight markers after considering LD between markers, and identified seven major effect QTL on seven chromosomes. Twelve candidate genes known to be associated with iron metabolism mapped near these QTL supporting the polygenic nature of IDC. A non-synonymous substitution with the highest significance in a major QTL region suggests soybean orthologs of FRE1 on Gm03 is a major gene responsible for trait variation. NAS3, a gene that encodes the enzyme nicotianamine synthase which synthesizes the iron chelator nicotianamine also maps to the same QTL region. Disease resistant genes also map to the major QTL, supporting the hypothesis that pathogens compete with the plant for Fe and increase iron deficiency. The markers and the allelic combinations identified here can be further used for marker assisted selection.},
}
@article {pmid25224685,
year = {2015},
author = {Ganoth, A and Merimi, KC and Peer, D},
title = {Overcoming multidrug resistance with nanomedicines.},
journal = {Expert opinion on drug delivery},
volume = {12},
number = {2},
pages = {223-238},
doi = {10.1517/17425247.2015.960920},
pmid = {25224685},
issn = {1744-7593},
mesh = {Animals ; Antineoplastic Agents/*pharmacology ; *Drug Delivery Systems ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Nanomedicine ; Nanoparticles ; Neoplasms/*drug therapy/pathology ; },
abstract = {INTRODUCTION: Cancer remains the leading cause of death worldwide. Numerous therapeutic strategies that include smart biological treatments toward specific cellular pathways are being developed. Yet, inherent and acquired multidrug resistance (MDR) to chemotherapeutic drugs remains the major obstacle in effective cancer treatments.<br><br>AREAS COVERED: Herein, we focused on an implementation of nanoscale drug delivery strategies (nanomedicines) to treat tumors that resist MDR. Specifically, we briefly discuss the MDR phenomenon and provide structural and functional characterization of key proteins that account for MDR. We next describe the strategies to target tumors using nanoparticles and provide a mechanistic overview of how changes in the influx:efflux ratio result in overcoming MDR.<br><br>EXPERT OPINION: Various strategies have been applied in preclinical and clinical settings to overcome cancer MDR. Among them are the use of chemosensitizers that aim to sensitize the cancer cells to chemotherapeutic treatment and the use of nanomedicines as delivery vehicles that can increase the influx of drugs into cancer cells. These strategies can enhance the therapeutic response in resistant tumors by bypassing efflux pumps or by increasing the nominal amounts of therapeutic payloads into the cancer cells at a given time point.},
}
@article {pmid25224155,
year = {2014},
author = {Li, J and Zhang, Y and Zhang, W and Gao, Y and Jia, S and Guo, J},
title = {Contrast enhanced computed tomography is indicative for angiogenesis pattern and display prognostic significance in breast cancer.},
journal = {BMC cancer},
volume = {14},
number = {},
pages = {672},
pmid = {25224155},
issn = {1471-2407},
mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*diagnostic imaging/mortality/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Female ; Humans ; Immunohistochemistry ; Microvessels/pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Neovascularization, Pathologic/*diagnostic imaging ; Prognosis ; Risk Factors ; Survival Analysis ; *Tomography, X-Ray Computed/methods ; },
abstract = {BACKGROUND: The Prognostic value of microvessel density in cancer remains unclear. Recent studies have suggested that the uneven distribution of microvessels in tumours caused the variation in sample selection which led to different prognostic outcome. The enhancement pattern of Contrast-enhanced computed tomography (CECT) is determined in part by the microvessel distribution in solid tumors. Therefore, survival analysis of tumors grouping by the enhancement pattern and the pattern of microvessel distribution is important.<br><br>METHODS: Survival analysis grouped by the tumor enhancement pattern and the microvessel distribution was carried out in 255 patients with invasive ductal carcinoma.<br><br>RESULTS: There were significant differences in overall survival (OS) and disease-free survival (DFS) among the homogeneous, heterogeneous and peripheral enhancement groups. There were significant differences between OS and DFS groups with uniform and uneven distributions of microvessels.<br><br>CONCLUSIONS: The distribution of microvessels in a tumor is a potential prognostic indicator in patients with breast cancer, and can be assessed by CECT prior the operation.},
}
@article {pmid25209856,
year = {2014},
author = {Kondo, Y and Kikuchi, T and Esteban, JC and Kumaki, N and Ogura, G and Inomoto, C and Hirabayashi, K and Kajiwara, H and Sakai, A and Sugimoto, R and Otsuru, M and Okami, K and Tsukinoki, K and Nakamura, N},
title = {Intratumoral heterogeneity of HER2 protein and amplification of HER2 gene in salivary duct carcinoma.},
journal = {Pathology international},
volume = {64},
number = {9},
pages = {453-459},
doi = {10.1111/pin.12195},
pmid = {25209856},
issn = {1440-1827},
mesh = {Adenocarcinoma/genetics/*metabolism/pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Child ; Child, Preschool ; Gene Amplification ; *Gene Expression Regulation, Neoplastic ; Genetic Heterogeneity ; Humans ; Immunohistochemistry ; In Situ Hybridization/methods ; Male ; Middle Aged ; Receptor, ErbB-2/genetics/*metabolism ; Retrospective Studies ; Salivary Gland Neoplasms/genetics/*metabolism/pathology ; Young Adult ; },
abstract = {Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands, and accounts for 1-3% of all malignant salivary gland tumors, resembling morphologically invasive ductal carcinoma (IDC) of the breast. In contrast to IDC of the breast and gastric carcinoma (GC), the study of human epidermal growth factor receptor 2 (HER2) in SDC has not progressed. Therefore, we investigated the relationship between HER2 protein expression and amplification of the HER2 gene, and compared them in terms of intratumoral heterogeneity (ITH) in 13 cases of SDC using immunohistochemistry and dual color in situ hybridization. We found seven cases with protein overexpression (53.8%) and five cases with gene amplification (38.5%) in accordance with ASCO/CAP guidelines. ITH of HER2 protein expression was seen in seven cases (53.8%). Interestingly, the ratio of the HER2 gene showed homogenous distribution with or without the presence of ITH of HER2 protein expression. SDC tends to have more ITH of HER2 protein similarly to GC, in contrast to IDC of the breast. ITH of HER2 protein in SDC has no heterogeneity of the HER2 gene amplification. The mechanism of HER2 protein expression in SDC might proceed through a more complex pathway relative to that of IDC of the breast.},
}
@article {pmid25205656,
year = {2014},
author = {List, T and Casi, G and Neri, D},
title = {A chemically defined trifunctional antibody-cytokine-drug conjugate with potent antitumor activity.},
journal = {Molecular cancer therapeutics},
volume = {13},
number = {11},
pages = {2641-2652},
doi = {10.1158/1535-7163.MCT-14-0599},
pmid = {25205656},
issn = {1538-8514},
mesh = {Animals ; Antibodies/chemistry/immunology/*pharmacology ; CHO Cells ; Cell Line, Tumor ; Cricetinae ; Cricetulus ; Cytokines/chemistry/immunology/*pharmacology ; Disease Models, Animal ; Female ; Humans ; Immunotoxins/*chemistry/immunology/*pharmacology ; Male ; Mice ; Neoplasms/*drug therapy/immunology ; },
abstract = {The combination of immunostimulatory agents with cytotoxic drugs is emerging as a promising approach for potentially curative tumor therapy, but advances in this field are hindered by the requirement of testing individual combination partners as single agents in dedicated clinical studies, often with suboptimal efficacy. Here, we describe for the first time a novel multipayload class of targeted drugs, the immunocytokine-drug conjugates (IDC), which combine a tumor-homing antibody, a cytotoxic drug, and a proinflammatory cytokine in the same molecular entity. In particular, the IL2 cytokine and the disulfide-linked maytansinoid DM1 microtubular inhibitor could be coupled to the F8 antibody, directed against the alternatively spliced EDA domain of fibronectin, in a site-specific manner, yielding a chemically defined product with selective tumor-homing performance and potent anticancer activity in vivo, as tested in two different immunocompetent mouse models.},
}
@article {pmid25202063,
year = {2014},
author = {Pula, B and Olbromski, M and Owczarek, T and Ambicka, A and Witkiewicz, W and Ugorski, M and Rys, J and Zabel, M and Dziegiel, P and Podhorska-Okolow, M},
title = {Nogo-B receptor expression correlates negatively with malignancy grade and ki-67 antigen expression in invasive ductal breast carcinoma.},
journal = {Anticancer research},
volume = {34},
number = {9},
pages = {4819-4828},
pmid = {25202063},
issn = {1791-7530},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/mortality/*pathology ; Cell Line, Transformed ; Cell Line, Tumor ; Female ; Fibroblasts/metabolism ; Follow-Up Studies ; Gene Expression ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Prognosis ; Receptors, Cell Surface/genetics/*metabolism ; },
abstract = {BACKGROUND: Nogo-B receptor (NgBR) has been shown to be involved in endothelial cell chemotaxis and morphogenesis. However, few studies analyzing its expression in cancer cells have been performed.<br><br>MATERIALS AND METHODS: We examined NgBR expression in 233 patients with invasive ductal breast carcinoma (IDC) and corresponding non-malignant breast tissues (NMBT) on mRNA (real-time polymerase chain reaction) and protein levels (immunohistochemistry; IHC and western-blot analysis). NgBR expression was found also analyzed in breast cancer cell lines of varying invasiveness.<br><br>RESULTS: NgBR expression was increased in IDC compared to NMBT on the mRNA (p=0.0007) and protein level (p=0.018). NgBR expression decreased significantly with IDC malignancy grade and correlated negatively with the Ki-67 antigen expression (r=-0.18; p=0.0005). High NgBR mRNA expression was associated with estrogen receptor negativity (p=0.0023) and the triple-negative phenotype of the tumors (p=0.0129).<br><br>CONCLUSION: NgBR may be involved in IDC development, however, its role in its progression requires further research.},
}
@article {pmid25192983,
year = {2015},
author = {Chu, J and Wang, T and Pei, S and Yin, Z},
title = {Surgical treatment for idiopathic intervertebral disc calcification in a child: case report and review of the literature.},
journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery},
volume = {31},
number = {1},
pages = {123-127},
pmid = {25192983},
issn = {1433-0350},
mesh = {Adolescent ; Calcinosis/*complications/*surgery ; Decompression, Surgical/*methods ; Humans ; Intervertebral Disc/*surgery ; Intervertebral Disc Degeneration/*complications/*surgery ; Male ; },
abstract = {PURPOSE: Intervertebral disc calcification (IDC) is rare in children. Conservative treatment has been recommended for the majority of cases. We describe surgical treatment of a case of IDC with progressive neurological impairment and review the literature relevant to this rare entity and its management.<br><br>METHODS: A 16-year-old boy presented with sudden onset of severe neck pain, radiating into his left shoulder. Three months later, he developed neurological symptoms and signs with a progressive motor and sensory loss of his left upper limb.<br><br>RESULTS: Anterior cervical corpectomy with fusion and instrumentation was performed. Neurologic deficits completely resolved within 1 week. After 1-year follow-up, radiological images showed solid fusion and no further compression.<br><br>CONCLUSION: Surgical decompression should be recommended for cases with acutely progressive and severe neurological impairments in IDC and a good result can be obtained. When surgery is needed, anterior decompression is usually used in cervical lesion, while in thoracic and lumbar area, posterior approach is suggested.},
}
@article {pmid25192706,
year = {2014},
author = {Chen, L and Malone, KE and Li, CI},
title = {Bra wearing not associated with breast cancer risk: a population-based case-control study.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {23},
number = {10},
pages = {2181-2185},
pmid = {25192706},
issn = {1538-7755},
support = {R01 CA085913/CA/NCI NIH HHS/United States ; R01CA 85913/CA/NCI NIH HHS/United States ; },
mesh = {Aged ; Breast Neoplasms/*epidemiology ; Carcinoma/*epidemiology ; Case-Control Studies ; Clothing/*adverse effects ; Female ; Humans ; Middle Aged ; Risk Factors ; United States/epidemiology ; },
abstract = {Despite the widespread use of bras among U.S. women and concerns in the lay media that bra wearing may increase breast cancer risk, there is a scarcity of credible scientific studies addressing this issue. The goal of the study was to evaluate the relationship between various bra-wearing habits and breast cancer risk among postmenopausal women. We conducted a population-based case-control study of breast cancer in the Seattle-Puget Sound metropolitan area that compared 454 invasive ductal carcinoma (IDC) cases and 590 invasive lobular carcinoma (ILC) cases diagnosed between 2000 and 2004 with 469 control women between 55 to 74 years of age. Information on bra-wearing habits and other breast cancer risk factors was collected from study participants through in-person interviews. Multivariate adjusted odds ratios (OR) and their associated 95% confidence intervals (CI) were estimated using polytomous logistic regression. No aspect of bra wearing, including bra cup size, recency, average number of hours/day worn, wearing a bra with an underwire, or age first began regularly wearing a bra, was associated with risks of either IDC or ILC. Our results did not support an association between bra wearing and increased breast cancer risk among postmenopausal women.},
}
@article {pmid25176936,
year = {2014},
author = {De Castro-Orós, I and Cenarro, A and Tejedor, MT and Baila-Rueda, L and Mateo-Gallego, R and Lamiquiz-Moneo, I and Pocoví, M and Civeira, F},
title = {Common genetic variants contribute to primary hypertriglyceridemia without differences between familial combined hyperlipidemia and isolated hypertriglyceridemia.},
journal = {Circulation. Cardiovascular genetics},
volume = {7},
number = {6},
pages = {814-821},
doi = {10.1161/CIRCGENETICS.114.000522},
pmid = {25176936},
issn = {1942-3268},
mesh = {Adaptor Proteins, Signal Transducing/genetics ; Adult ; Age Factors ; Alleles ; Apolipoprotein A-V ; Apolipoproteins A/genetics ; Blood Glucose/analysis ; Body Mass Index ; Female ; Gene Frequency ; *Genetic Variation ; Genotype ; Humans ; Hyperlipidemia, Familial Combined/*genetics/pathology ; Hypertriglyceridemia/*genetics/pathology ; Lipoprotein Lipase/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Sex Factors ; Triglycerides/blood ; },
abstract = {BACKGROUND: The majority of hypertriglyceridemias are diagnosed as familial combined hyperlipidemia (FCHL) and primary isolated hypertriglyceridemias. The contribution of common genetic variants in primary hypertriglyceridemias and the genetic difference between FCHL and isolated hypertriglyceridemias have not been thoroughly examined.<br><br>METHODS AND RESULTS: This study involved 580 patients with hypertriglyceridemias and 403 controls. Of the 37 single nucleotide polymorphisms examined, 12 located in 10 genes showed allelic and genotype frequency differences between hypertriglyceridemias and controls. The minor alleles of APOE, APOA5, GALNTN2, and GCKR variants were positively correlated with plasma triglycerides, whereas minor alleles of ADIPOR2, ANGPTL3, LPL, and TRIB1 polymorphisms were inversely associated. Body mass index, glucose, sex, rs328 and rs7007797 in LPL, rs662799 and rs3135506 in APOA5, and rs1260326 in GCKR explained 36% of the variability in plasma triglycerides, 7.3% of which was attributable to the genetic variables. LPL, GCKR, and APOA5 polymorphisms fit dominant, recessive, and additive inheritance models, respectively. Variants more frequently identified in isolated hypertriglyceridemias were rs7412 in APOE and rs1800795 in IL6; rs2808607 in CYP7A1 and rs3812316 and rs17145738 in MLXIPL were more frequent in FCHL. The other 32 single nucleotide polymorphisms presented similar frequencies between isolated hypertriglyceridemias and FCHL.<br><br>CONCLUSIONS: Common genetic variants found in LPL, APOA5, and GCKR are associated with triglycerides levels in patients with primary hypertriglyceridemias. FCHL and isolated hypertriglyceridemias are probably trace to an accumulation of genetic variants predisposing to familial and sporadic hypertriglyceridemias or to hypertriglyceridemias and hypercholesterolemia in case of FCHL.},
}
@article {pmid25173099,
year = {2015},
author = {Zhao, B and Xu, B and Hu, W and Song, C and Wang, F and Liu, Z and Ye, M and Zou, H and Miao, QR},
title = {Comprehensive proteome quantification reveals NgBR as a new regulator for epithelial-mesenchymal transition of breast tumor cells.},
journal = {Journal of proteomics},
volume = {112},
number = {},
pages = {38-52},
pmid = {25173099},
issn = {1876-7737},
support = {R01 HL108938/HL/NHLBI NIH HHS/United States ; R01HL108938/HL/NHLBI NIH HHS/United States ; },
mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Cell Line, Tumor ; *Epithelial-Mesenchymal Transition ; Female ; Humans ; Neoplasm Proteins/genetics/*metabolism ; Proteome/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; },
abstract = {UNLABELLED: Nogo-B receptor (NgBR) is a type I receptor and specifically binds to ligand Nogo-B. Our previous work has shown that NgBR is highly expressed in human breast invasive ductal carcinoma. Here, comprehensive proteome quantification was performed to examine the alteration of protein expression profile in MDA-MB-231 breast tumor cells after knocking down NgBR using lentivirus-mediated shRNA approach. Among a total of 1771 proteins feasibly quantified, 994 proteins were quantified in two biological replicates with RSD <50%. There are 122 proteins significantly down-regulated in NgBR knockdown MDA-MB-231 breast tumor cells, such as vimentin and S100A4, well-known markers for mesenchymal cells, and CD44, a stemness indicator. The decrease of vimentin, S100A4 and CD44 protein expression levels was further confirmed by Western blot analysis. MDA-MB-231 cells are typical breast invasive ductal carcinoma cells showing mesenchymal phenotype. Cell morphology analysis demonstrates NgBR knockdown in MDA-MB-231 cells results in reversibility of epithelial-mesenchymal transition (EMT), which is one of the major mechanisms involved in breast cancer metastasis. Furthermore, we demonstrated that NgBR knockdown in MCF-7 cells significantly prevented the TGF-β-induced EMT process as determined by the morphology change, and staining of E-cadherin intercellular junction as well as the decreased expression of vimentin.<br><br>BIOLOGICAL SIGNIFICANCE: Our previous publication showed that NgBR is highly expressed in human breast invasive ductal carcinoma. However, the roles of NgBR and NgBR-mediated signaling pathway in breast tumor cells are still unclear. Here, we not only demonstrated that the quantitative proteomics analysis is a powerful tool to investigate the global biological function of NgBR, but also revealed that NgBR is involved in the transition of breast epithelial cells to mesenchymal stem cells, which is one of the major mechanisms involved in breast cancer metastasis. These findings provide new insights for understanding the roles of NgBR in regulating breast epithelial cell transform during the pathogenesis of breast cancer.},
}
@article {pmid25171226,
year = {2014},
author = {Samikkannu, T and Rao, KV and Ding, H and Agudelo, M and Raymond, AD and Yoo, C and Nair, MP},
title = {Immunopathogenesis of HIV infection in cocaine users: role of arachidonic acid.},
journal = {PloS one},
volume = {9},
number = {8},
pages = {e106348},
pmid = {25171226},
issn = {1932-6203},
support = {R25 MH080663/MH/NIMH NIH HHS/United States ; DA 025576/DA/NIDA NIH HHS/United States ; R01 DA034547/DA/NIDA NIH HHS/United States ; DA034547/DA/NIDA NIH HHS/United States ; R37 DA025576/DA/NIDA NIH HHS/United States ; },
mesh = {Adult ; Arachidonic Acid/*blood ; Cells, Cultured ; Cocaine/*adverse effects ; Cyclooxygenase 2/metabolism ; Dendritic Cells/*immunology ; Dinoprostone/blood ; Drug Users ; Female ; Gene Expression Regulation/drug effects ; HIV Infections/blood/*immunology/pathology ; Humans ; Intramolecular Oxidoreductases/blood ; Male ; Middle Aged ; Prostaglandin D2/*analogs &amp; derivatives/blood ; Prostaglandin-E Synthases ; },
abstract = {Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC) has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2), prostaglandin E2 synthetase (PGE2), thromboxane A2 receptor (TBXA2R), cyclopentenone prostaglandins (CyPG), such as 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), 14-3-3 ζ/δ and 5-lipoxygenase (5-LOX) mediated induction of IDC immune dysfunctions in cocaine using HIV positive patients. The plasma levels of AA, PGE2, 15d-PGJ2, 14-3-3 ζ/δ and IDC intracellular COX-2 and 5-LOX expression were assessed in cocaine users, HIV positive patients, HIV positive cocaine users and normal subjects. Results showed that plasma concentration levels of AA, PGE2 and COX-2, TBXA2R and 5-LOX in IDCs of HIV positive cocaine users were significantly higher whereas 15d-PGJ2 and 14-3-3 ζ/δ were significantly reduced compared to either HIV positive subjects or cocaine users alone. This report demonstrates that AA metabolites are capable of mediating the accelerative effects of cocaine on HIV infection and disease progression.},
}
@article {pmid25154392,
year = {2015},
author = {Risbridger, GP and Taylor, RA and Clouston, D and Sliwinski, A and Thorne, H and Hunter, S and Li, J and Mitchell, G and Murphy, D and Frydenberg, M and Pook, D and Pedersen, J and Toivanen, R and Wang, H and Papargiris, M and Lawrence, MG and Bolton, DM},
title = {Patient-derived xenografts reveal that intraductal carcinoma of the prostate is a prominent pathology in BRCA2 mutation carriers with prostate cancer and correlates with poor prognosis.},
journal = {European urology},
volume = {67},
number = {3},
pages = {496-503},
doi = {10.1016/j.eururo.2014.08.007},
pmid = {25154392},
issn = {1873-7560},
mesh = {Aged ; Animals ; BRCA2 Protein/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics/mortality/*pathology/surgery ; Genetic Predisposition to Disease ; Heredity ; Heterografts ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; *Mutation ; Neoplasm Transplantation ; Pedigree ; Phenotype ; Proportional Hazards Models ; Prostatectomy ; Prostatic Neoplasms/*genetics/mortality/*pathology/surgery ; Risk Factors ; Time Factors ; Treatment Outcome ; },
abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathologic entity associated with aggressive prostate cancer (PCa). PCa patients carrying a breast cancer 2, early onset (BRCA2) germline mutation exhibit highly aggressive tumours with poor prognosis.<br><br>OBJECTIVE: To investigate the presence and implications of IDC-P in men with a strong family history of PCa who either carry a BRCA2 pathogenic mutation or do not carry the mutation (BRCAX).<br><br>Patient-derived xenografts (PDXs) were generated from three germline BRCA2 mutation carriers and one BRCAX patient. Specimens were examined for histologic evidence of IDC-P. Whole-genome copy number analysis (WG-CNA) was performed on IDC-P from a primary and a matched PDX specimen.<br><br>The incidence of IDC-P and association with overall survival for BRCA2 and BRCAX patients were determined using Kaplan-Meier analysis.<br><br>RESULTS AND LIMITATIONS: PDXs from BRCA2 tumours showed increased incidence of IDC-P compared with sporadic PCa (p=0.015). WG-CNA confirmed that the genetic profile of IDC-P from a matched (primary and PDX) BRCA2 tumour was similar. The incidence of IDC-P was significantly increased in BRCA2 carriers (42%, n=33, p=0.004) but not in BRCAX patients (25.8%, n=62, p=0.102) when both groups were compared with sporadic cases (9%, n=32). BRCA2 carriers and BRCAX patients with IDC-P had significantly worse overall and PCa-specific survival compared with BRCA2 carriers and BRCAX patients without IDC-P (hazard ratio [HR]: 16.9, p=0.0064 and HR: 3.57, p=0.0086, respectively).<br><br>CONCLUSIONS: PDXs revealed IDC-P in patients with germline BRCA2 mutations or BRCAX classification, identifying aggressive tumours with poor survival even when the stage and grade of cancer at diagnosis were similar. Further studies of the prognostic significance of IDC-P in sporadic PCa are warranted.<br><br>PATIENT SUMMARY: Intraductal carcinoma of the prostate is common in patients with familial prostate cancer and is associated with poor outcomes. This finding affects genetic counselling and identifies patients in whom earlier multimodality treatment may be required.},
}
@article {pmid25149281,
year = {2014},
author = {Moran Lauter, AN and Peiffer, GA and Yin, T and Whitham, SA and Cook, D and Shoemaker, RC and Graham, MA},
title = {Identification of candidate genes involved in early iron deficiency chlorosis signaling in soybean (Glycine max) roots and leaves.},
journal = {BMC genomics},
volume = {15},
number = {},
pages = {702},
pmid = {25149281},
issn = {1471-2164},
mesh = {Binding Sites ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Homeostasis ; *Iron Deficiencies ; Multigene Family ; Plant Diseases/*genetics ; Plant Leaves/*genetics/metabolism ; Plant Roots/*genetics/metabolism ; Protein Binding ; *Signal Transduction ; Glycine max/*genetics/*metabolism ; Stress, Physiological ; Time Factors ; Transcription Factors/genetics/metabolism ; },
abstract = {BACKGROUND: Iron is an essential micronutrient for all living things, required in plants for photosynthesis, respiration and metabolism. A lack of bioavailable iron in soil leads to iron deficiency chlorosis (IDC), causing a reduction in photosynthesis and interveinal yellowing of leaves. Soybeans (Glycine max (L.) Merr.) grown in high pH soils often suffer from IDC, resulting in substantial yield losses. Iron efficient soybean cultivars maintain photosynthesis and have higher yields under IDC-promoting conditions than inefficient cultivars.<br><br>RESULTS: To capture signaling between roots and leaves and identify genes acting early in the iron efficient cultivar Clark, we conducted a RNA-Seq study at one and six hours after replacing iron sufficient hydroponic media (100&#xa0;&#x3bc;M iron(III) nitrate nonahydrate) with iron deficient media (50&#xa0;&#x3bc;M iron(III) nitrate nonahydrate). At one hour of iron stress, few genes were differentially expressed in leaves but many were already changing expression in roots. By six hours, more genes were differentially expressed in the leaves, and a massive shift was observed in the direction of gene expression in both roots and leaves. Further, there was little overlap in differentially expressed genes identified in each tissue and time point.<br><br>CONCLUSIONS: Genes involved in hormone signaling, regulation of DNA replication and iron uptake utilization are key aspects of the early iron-efficiency response. We observed dynamic gene expression differences between roots and leaves, suggesting the involvement of many transcription factors in eliciting rapid changes in gene expression. In roots, genes involved iron uptake and development of Casparian strips were induced one hour after iron stress. In leaves, genes involved in DNA replication and sugar signaling responded to iron deficiency. The differentially expressed genes (DEGs) and signaling components identified here represent new targets for soybean improvement.},
}
@article {pmid25147131,
year = {2014},
author = {Bhattacharya-Ghosh, B and Bozkurt, S and Rutten, MC and van de Vosse, FN and Díaz-Zuccarini, V},
title = {An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system.},
journal = {Computers in biology and medicine},
volume = {53},
number = {},
pages = {141-153},
doi = {10.1016/j.compbiomed.2014.06.013},
pmid = {25147131},
issn = {1879-0534},
mesh = {Calcium/metabolism ; Cardiomyopathy, Dilated/*physiopathology ; Computational Biology ; *Computer Simulation ; Heart/physiology ; Humans ; *Models, Cardiovascular ; Muscle Proteins/metabolism ; *Myocardium/chemistry/cytology/metabolism ; Ventricular Pressure/physiology ; },
abstract = {Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view.},
}
@article {pmid25124574,
year = {2014},
author = {Chim-ong, A and Thawornkuno, C and Chavalitshewinkoon-Petmitr, P and Punyarit, P and Petmitr, S},
title = {SLC35B2 expression is associated with a poor prognosis of invasive ductal breast carcinoma.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {15},
number = {15},
pages = {6065-6070},
doi = {10.7314/apjcp.2014.15.15.6065},
pmid = {25124574},
issn = {2476-762X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast/metabolism ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/secondary ; Carcinoma, Lobular/genetics/secondary ; DNA-Binding Proteins/*genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Membrane Transport Proteins/*genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasms/*drug therapy/pathology ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfate Transporters ; },
abstract = {BACKGROUND: Breast cancer is the most common malignancy in women worldwide, including Thailand, and is a major cause of mortality and morbidity, despite advances in diagnosis and treatment. Novel gene expression in breast cancer is a focus in searches for prognostic biomarkers and new therapeutic targets.<br><br>MATERIALS AND METHODS: The mRNA expression of novel B4GALT4, SLC35B2, and WDHD1 genes in breast cancer were examined in invasive ductal breast carcinoma (IDC) patients using quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR).<br><br>RESULTS: Among these genes, increased expression of SLC35B2 mRNA was significantly associated with TNM stage III+IV of IDC (p<0.001). Hence, up-regulation of SLC35B2 may serve as a prognostic biomarker for poor prognosis, and is also a potential therapeutic target in breast cancer.},
}
@article {pmid25120811,
year = {2014},
author = {Cao, YW and Wan, GX and Zhao, CX and Hu, JM and Li, L and Liang, WH and Li, WQ and Li, YC and Li, YX and Du, XM and Yu, SY and Li, F},
title = {Notch1 single nucleotide polymorphism rs3124591 is associated with the risk of development of invasive ductal breast carcinoma in a Chinese population.},
journal = {International journal of clinical and experimental pathology},
volume = {7},
number = {7},
pages = {4286-4294},
pmid = {25120811},
issn = {1936-2625},
mesh = {Adult ; Aged ; Aged, 80 and over ; Asian People/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Female ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Immunohistochemistry ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Receptor, Notch1/*genetics ; Risk Factors ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; },
abstract = {Accumulated evidence has revealed the presence of Notch receptor polymorphisms in non-tumorous diseases; however, few studies have investigated the association of Notch polymorphisms with breast cancer risk. A total of 100 invasive ductal carcinoma (IDC) and 50 ductal carcinoma in situ (DCIS) patients and 100 usual ductal hyperplasia (UDH) controls were genotyped for the following Notch receptor single nucleotide polymorphisms (SNPs) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: Notch1, rs3124591; Notch2, rs11249433; Notch3, rs3815188, and rs1043994; and Notch4, rs367398, and rs520692. Immunohistochemistry was used to determine the effect of Notch polymorphisms on corresponding Notch protein expression in successfully genotyped patients. The frequency of rs3124591 TC genotype was significantly higher in IDC (24.7%, 20/81) and DCIS (30%, 12/40) patients than in UDH controls (8%, 8/97) (P = 0.002 and P = 0.011, respectively). However, the distribution of other SNP genotypes was not significantly different between IDC and DCIS patients and UDH controls. The frequency of TC genotype was significantly higher in poorly differentiated tumors than in well-differentiated and moderately differentiated tumors (P = 0.022). Importantly, a positive correlation between the rs3124591 TC genotype and high Notch1 protein expression was observed in DCIS patients (P = 0.043) but not in IDC patients. This is the first study to suggest an increased risk of IDC and DCIS of the breast for the Notch1 rs3124591 variant. Furthermore, given the inconsistent associations between the rs3124591 variant and Notch1 expression in IDC and DCIS, this variant may affect breast cancer risk through mechanisms in the latter stage other than alterations in Notch1 protein expression.},
}
@article {pmid25119012,
year = {2014},
author = {Colović, M and Todorović, M and Colović, N and Terzic, T and Karadzic, K and Jurišić, V},
title = {Appearance of estrogen positive bilateral breast carcinoma with HER2 gene amplification in a patient with aplastic anemia.},
journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists},
volume = {65},
number = {1},
pages = {66-69},
doi = {10.5114/pjp.2014.42672},
pmid = {25119012},
issn = {1233-9687},
mesh = {*Adenocarcinoma/complications/genetics/metabolism ; Anemia, Aplastic/*complications ; *Breast Neoplasms/complications/genetics/metabolism ; *Carcinoma, Ductal, Breast/complications/genetics/metabolism ; Estrogens/*metabolism ; Female ; Gene Amplification ; Humans ; Middle Aged ; Receptor, ErbB-2/*genetics ; },
abstract = {Immunosuppressive therapy is one of the standard therapy protocols for aplastic anemia (AA). However, immunosuppressive therapy and androgenic steroids can promote development of solid tumors such as squamous carcinoma, head and neck tumors, adenocarcinoma of the stomach, hepatocarcinoma and breast carcinoma in long surviving patients with aplastic anemia. We present here a rare case of a 56-year-old woman in whom bilateral adenocarcinoma of the breast developed 11 years after the start of immunosuppressive and androgenic steroid therapy for aplastic anemia. Histological examination showed invasive ductal carcinoma with intense nuclear staining for estrogen receptors. Her2 immunohistochemistry was positive for 80% of stained cells, and chromogenic in situ hybridization showed a high level of HER2 gene amplification. This case indicated that a new therapy option is needed for estimation and evaluation to avoid the consequence of cancer occurrence.},
}
@article {pmid25118162,
year = {2014},
author = {Reyna, C and Lee, MC and Frelick, A and Khakpour, N and Laronga, C and Kiluk, JV},
title = {Axillary burden of disease following false-negative preoperative axillary evaluation.},
journal = {American journal of surgery},
volume = {208},
number = {4},
pages = {577-581},
doi = {10.1016/j.amjsurg.2014.05.015},
pmid = {25118162},
issn = {1879-1883},
mesh = {Axilla ; Biopsy, Fine-Needle/*methods ; Breast Neoplasms/diagnosis/*secondary/surgery ; Diagnosis, Differential ; False Negative Reactions ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes/*diagnostic imaging/*pathology ; Lymphatic Metastasis ; Neoplasm Staging/methods ; Predictive Value of Tests ; Preoperative Period ; Retrospective Studies ; Sentinel Lymph Node Biopsy/*methods ; Ultrasonography ; },
abstract = {BACKGROUND: Preoperative axillary ultrasound (AUS) and fine-needle aspiration (FNA) are sensitive and specific for breast cancer nodal metastases. We hypothesize that false-negative result predicts minimal axillary disease (≤2 +nodes).<br><br>METHODS: A retrospective review of breast cancer patients receiving AUS identified T1/T2 tumors and positive sentinel node with axillary dissection. Chi-square analysis was performed using Fisher's exact test.<br><br>RESULTS: Of 903 AUS cases, 384 had T1/T2 tumors. False-negative rate of AUS &#xb1; FNA was 48% and 45%, respectively. Of 384 cases, 73 were sentinel node positive and had axillary dissection; 55 (75.3%) were invasive ductal carcinoma (IDC). Negative predictive value for greater than or equal to 2 nodes was 71% in IDC versus 44% for in non-IDC patients. Sixteen (29.0%) IDC patients had greater than or equal to 3 positive nodes versus 10 (55.5%) non-IDC (P = .05) patients.<br><br>CONCLUSION: The high negative predictive value for AUS with FNA for IDC suggests that the AUS plus FNA interpretation may be better limited to the ipsilateral nodes of IDC.},
}
@article {pmid25112791,
year = {2015},
author = {Klomek, AB and Lev-Wiesel, R and Shellac, E and Hadas, A and Berger, U and Horwitz, M and Fennig, S},
title = {The relationship between self-injurious behavior and self-disclosure in adolescents with eating disorders.},
journal = {Eating and weight disorders : EWD},
volume = {20},
number = {1},
pages = {43-48},
pmid = {25112791},
issn = {1590-1262},
mesh = {Adolescent ; Child ; Feeding and Eating Disorders/complications/*psychology ; Female ; Humans ; *Self Disclosure ; Self-Injurious Behavior/complications/*psychology ; Young Adult ; },
abstract = {PURPOSE: The aim of the current study is to examine the association between self disclosure and self-injurious behaviors among adolescent patients diagnosed with an eating disorder.<br><br>METHODS: Sixty three female patients who fulfilled the DSM-IV diagnostic criteria of eating disorders were included (i.e. anorexia, bulimia, binge eating disorder and eating disorders not otherwise specified). Participants' age ranged from 11.5 to 20 years (M = 15.42, SD = 1.82). Participants completed self- report questionnaires about eating disorders, self-disclosure, self-injurious behaviors (FASM) and depression (BDI-II) RESULTS: 82.5% of the sample endorsed severe self-injurious behaviors. A moderate negative relationship was found between general disclosure to parents and self-injurious behaviors indicating that patients who generally self-disclose to their parents (on different topics, apart from suicidal ideation) engage less frequently in self-injurious behaviors. In addition, the more patients self-disclose their suicidal ideation to others, the more they tend to self-injure.<br><br>CONCLUSION: Self-disclosure to parents on any topic may buffer against self-injurious behaviors and therefore it is important to work with adolescents suffering from eating disorders on effective self disclosure. In addition, self-disclosure about suicidal ideation to others by adolescents suffering from eating disorders should always be taken seriously, since it may be related to self-injurious behaviors.},
}
@article {pmid25109497,
year = {2014},
author = {Tanaka, N and Yoshida, H and Suzuki, Y and Harigaya, K},
title = {Relative expression of hMena11a and hMenaINV splice isoforms is a useful biomarker in development and progression of human breast carcinoma.},
journal = {International journal of oncology},
volume = {45},
number = {5},
pages = {1921-1928},
doi = {10.3892/ijo.2014.2591},
pmid = {25109497},
issn = {1791-2423},
mesh = {Alternative Splicing/genetics ; Biomarkers ; Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Microfilament Proteins/*biosynthesis/genetics ; Neoplasm Staging ; Protein Isoforms/*biosynthesis ; RNA, Messenger/*biosynthesis ; },
abstract = {Alternative splicing provides additional genomic complexity by producing multiple mRNAs and protein variants from any given gene. Splice variants have been identified in a large variety of cancer genes, suggesting that widespread aberrant and alternative splicing may be a consequence or even a cause of cancer. Human ortholog of mammalian enabled (hMena), a family of enabled/vasodilator-stimulated phosphoproteins (Ena/VASP), is an actin regulatory protein involved in the regulation of cell motility. hMena has been shown to have several splice variants, including the hMena(INV) isoform, expressed in invasive cancer cells, and the epithelial-specific isoform, hMena(11a). We assessed the relative mRNA expression of hMena splice variants in 50 cases of invasive ductal breast carcinoma of no special type (IDC-NST) and 45 cases of ductal breast carcinoma in situ (DCIS) with special reference to non-neoplastic breast epithelial tissues. The samples were dissected from their respective regions by laser microdissection. Our results confirmed previous reports that hMena(INV) expression is augmented during tumor progression, while hMena(11a) is downregulated. Furthermore, simultaneous expression of hMena(11a) and hMena(INV) was found only in malignant lesions, while their expression was hardly detected in normal breast tissue and benign proliferative breast lesions. These results indicate that the higher relative expression of hMena(11a) compared with hMena(INV) may predict malignant transformation in breast epithelial cells, and, furthermore, a reversal of expression of hMena(11a) and hMena(INV) may dictate the state of cancer progression. Here, we demonstrate that determination of hMena(11a) and hMena(INV) expression could be a useful biomarker for predicting malignant behavior in breast epithelial lesions, and show that their relative expression is linked to adverse prognostic factors. Although the biological activity of the majority of alternatively spliced isoforms and their contribution to cancer biology has yet to be determined, their elucidation will have a large impact on therapeutic strategies for cancer.},
}
@article {pmid25100562,
year = {2014},
author = {Arthur, LM and Turnbull, AK and Webber, VL and Larionov, AA and Renshaw, L and Kay, C and Thomas, JS and Dixon, JM and Sims, AH},
title = {Molecular changes in lobular breast cancers in response to endocrine therapy.},
journal = {Cancer research},
volume = {74},
number = {19},
pages = {5371-5376},
doi = {10.1158/0008-5472.CAN-14-0620},
pmid = {25100562},
issn = {1538-7445},
mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/*drug therapy/genetics ; Carcinoma, Lobular/*drug therapy/genetics ; Cohort Studies ; Female ; Humans ; Letrozole ; Nitriles/*therapeutic use ; Postmenopause ; Triazoles/*therapeutic use ; },
abstract = {Invasive lobular carcinoma (ILC) accounts for approximately 10% to 15% of breast carcinomas, and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 postmenopausal women with estrogen receptor-positive (ER(+)) histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding invasive ductal carcinomas (IDC) matched on clinicopathologic features. RNA was extracted and processed for whole human genome expression microarray. Dynamic clinical response was assessed using periodic three-dimensional ultrasound measurements performed during treatment and defined as a reduction of >70% in tumor volume by 3 months. Pretreatment profiles of ILC and IDC tumors showed distinctive expression of genes associated with E-cadherin signaling, epithelial adhesion, and stromal rearrangement. The changes in gene expression in response to letrozole were highly similar between responding ILC and IDC tumors; genes involved in proliferation were downregulated and those involved with immune function and extracellular matrix remodeling were upregulated. However, molecular differences between the histologic subtypes were maintained upon treatment. This is the first study of molecular changes in ILC in response to endocrine therapy to date. The genes that change on letrozole are highly consistent between ILC and IDC. Differences in gene expression between ILC and IDC at diagnosis are maintained at each time point on treatment.},
}
@article {pmid25097518,
year = {2014},
author = {Hong, L and Tang, S},
title = {Does HPV 16/18 infection affect p53 expression in invasive ductal carcinoma? An experimental study.},
journal = {Pakistan journal of medical sciences},
volume = {30},
number = {4},
pages = {789-792},
pmid = {25097518},
issn = {1682-024X},
abstract = {Objective : To determine the relations between human papilloma viruses type 16 and type 18 infection and the expression of p53 protein in invasive ductal carcinoma. Methods : We detected the expression of HPV 16/18 DNA and p53 protein in invasive ductal carcinoma in 45 cases, breast fibroadenoma in 20 cases and normal breast tissues in 20 cases. HPV detection was performed on paraffin sections using biotin-labeled probes by in situ hybridization and p53 protein expression was evaluated by immunohistochemistry. Results : The expression rate of HPV 16/18 DNA and p53 protein in invasive ductal carcinoma is significantly higher than those in breast fibroadenoma and normal breast tissues (p<0.05); the expression in cases with axillary lymph node metastasis is dramatically higher than those without (p<0.05); the expression of p53 protein increases with TMN staging advance. The expression of HPV16/18 DNA was significantly correlated with the expression of p53 protein (p<0.05). Conclusion : Both HPV16/18 infection and p53 mutation participate the occurrence and progress of invasive ductal carcinoma, and HPV 16/18 infection may be the major factor to cause p53 mutation.},
}
@article {pmid25081092,
year = {2014},
author = {Picillo, M and Barone, P and Amboni, M and Moccia, M and Pellecchia, MT},
title = {Comment on Szewczyk-Krolikowski et al.: the influence of age and gender on motor and non-motor features of early Parkinson's disease: initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort.},
journal = {Parkinsonism &amp; related disorders},
volume = {20},
number = {11},
pages = {1319-1320},
doi = {10.1016/j.parkreldis.2014.03.014},
pmid = {25081092},
issn = {1873-5126},
mesh = {Female ; Humans ; Male ; Parkinson Disease/*complications/*epidemiology ; },
}
@article {pmid25076063,
year = {2015},
author = {Türker, K and Albayrak, M and Öksüzoğlu, B and Balc, E and Oğan, MC and Iskender, G and Altuntaş, F},
title = {Entecavir as a first-line treatment for hepatitis B virus reactivation following polychemotherapy for chronic lymphocytic leukemia and invasive ductal carcinoma: a report of two cases and review of the literature.},
journal = {European journal of gastroenterology &amp; hepatology},
volume = {27},
number = {1},
pages = {39-45},
doi = {10.1097/MEG.0000000000000115},
pmid = {25076063},
issn = {1473-5687},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antiviral Agents/*therapeutic use ; Breast Neoplasms/complications/*drug therapy ; Carcinoma, Ductal, Breast/complications/*drug therapy ; Female ; Guanine/*analogs &amp; derivatives/therapeutic use ; Hepatitis B Antibodies/blood ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/*physiology ; Hepatitis B, Chronic/blood/complications/*drug therapy ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/complications/*drug therapy ; Male ; Middle Aged ; Recurrence ; Virus Activation ; },
abstract = {OBJECTIVE: Hepatitis B reactivation has been reported in chronic carriers of hepatitis B [hepatitis B surface antigen (HBsAg)] or in patients with prior hepatitis B virus (HBV) infection who are HBsAg-negative and have antibodies against hepatitis B core antigen (anti-HBc) with or without antibodies to HBsAg (anti-HBs). Lamivudine has been the first and commonly used nucleoside analog to inhibit HBV replication; however, prolonged therapy has been associated with an increased risk for drug-resistant mutations and mortality rates. Entecavir, a deoxyguanosine analog, offers several advantages over lamivudine for the treatment of HBV reactivation following chemotherapy while exhibiting more potent antiviral activity and a lower resistance rate.<br><br>METHODS: Herein, we report rapid and sustained suppression of polychemotherapy-related HBV reactivation by entecavir administered as a prompt antiviral therapy in the cases of two patients with chronic lymphocytic leukemia and invasive ductal carcinoma. A review of the literature is discussed.<br><br>RESULTS: Entecavir produced a rapid and sustained suppression of polychemotherapy-related HBV reactivation as a prompt antiviral therapy in the cases of two patients with chronic lymphocytic leukemia and invasive ductal carcinoma.<br><br>CONCLUSION: Allowing a rapid and sustained control of HBV replication, entecavir seems to be a promising drug for first-line prompt treatment of HBV reactivation in patients undergoing chemotherapy for hematological as well as solid organ malignancies, with safe long-term use enabling maintenance of resolved hepatitis.},
}
@article {pmid25074542,
year = {2014},
author = {Xiang, DB and Wei, B and Abraham, SC and Huo, L and Albarracin, CT and Zhang, H and Babiera, G and Caudle, AS and Akay, CL and Rao, P and Zhao, YJ and Lu, X and Wu, Y},
title = {Molecular cytogenetic characterization of mammary neuroendocrine carcinoma.},
journal = {Human pathology},
volume = {45},
number = {9},
pages = {1951-1956},
doi = {10.1016/j.humpath.2014.06.002},
pmid = {25074542},
issn = {1532-8392},
mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Neuroendocrine/*genetics/pathology ; *Chromosome Aberrations ; Chromosome Banding/methods ; Chromosomes, Human, Pair 12/*genetics ; Chromosomes, Human, Pair 7/*genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping/methods ; Middle Aged ; Trisomy ; },
abstract = {Primary mammary neuroendocrine carcinoma (NEC) is an uncommon entity that accounts for 2% to 5% of breast carcinomas. Recent reports have shown that NEC of the breast is an aggressive subtype of mammary carcinoma that is distinct from invasive ductal carcinoma, not otherwise specified, and have suggested that these tumors have a poorer prognosis than invasive ductal carcinoma, not otherwise specified. In this study, we provide the first cytogenetic characterization of mammary NEC using both conventional G-banding and spectral karyotype on a group of 7 tumors. We identified clonal chromosomal aberrations in 5 (71.4%) cases, with 4 of them showing complex karyotypes. Of these, recurrent numerical aberrations included gain of chromosome 7 (n = 2) and loss of chromosome 15 (n = 2). Recurrent clonal structural chromosomal aberrations involved chromosomes 1 (n = 3), 3 (n = 2), 6q (n = 3), and 17q (n = 3). Of the 4 (57.1%) cases with complex karyotypes, 2 showed evidence of chromothripsis, a phenomenon in which tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. One of these had evidence of chromothripsis involving chromosomes 1, 6, 8, and 15. The other also had evidence of chromosome 8 chromothripsis, making this a recurrent finding shared by both cases. We also found that mammary NEC shared some cytogenetic abnormalities--such as trisomy 7 and 12--with other neuroendocrine tumors in the lung and gastrointestinal tract, suggesting trisomy 7 and 12 as potential common molecular aberrations in neuroendocrine tumors. To our knowledge, this is the first report on molecular cytogenetic characterization of mammary NEC.},
}
@article {pmid25064063,
year = {2014},
author = {Tong, LC and Silar, P and Lalucque, H},
title = {Genetic control of anastomosis in Podospora anserina.},
journal = {Fungal genetics and biology : FG &amp; B},
volume = {70},
number = {},
pages = {94-103},
doi = {10.1016/j.fgb.2014.07.006},
pmid = {25064063},
issn = {1096-0937},
mesh = {Fungal Proteins/genetics/*metabolism ; *Gene Expression Regulation, Fungal ; Hyphae/genetics/*physiology ; Microscopy/methods ; Mutation ; Podospora/genetics/*physiology ; Signal Transduction ; },
abstract = {We developed a new microscopy procedure to study anastomoses in the model ascomycete Podospora anserina and compared it with the previous method involving the formation of balanced heterokaryons. Both methods showed a good correlation. Heterokaryon formation was less quantifiable, but enabled to observe very rare events. Microscopic analysis evidenced that anastomoses were greatly influence by growth conditions and were severely impaired in the IDC mutants of the PaMpk1, PaMpk2, IDC1 and PaNox1 pathways. Yet some mutants readily formed heterokaryons, albeit with a delay when compared to the wild type. We also identified IDC(821), a new mutant presenting a phenotype similar to the other IDC mutants, including lack of anastomosis. Complete genome sequencing revealed that IDC(821) was affected in the orthologue of the Neurospora crassa So gene known to control anastomosis in several other ascomycetes.},
}
@article {pmid25063898,
year = {2013},
author = {Villalón-López, JS and Souto-del Bosque, R and Alonso-Briones, MV and Trujillo-de Anda, AP},
title = {[Carcinosarcoma of the breast a rare entity with fatal prognosis. One case report].},
journal = {Cirugia y cirujanos},
volume = {81},
number = {4},
pages = {328-332},
pmid = {25063898},
issn = {2444-054X},
mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology/therapy ; Capecitabine ; Carcinosarcoma/*pathology/secondary/therapy ; Combined Modality Therapy ; Deoxycytidine/administration &amp; dosage/analogs &amp; derivatives ; Docetaxel ; Fatal Outcome ; Female ; Fluorouracil/administration &amp; dosage/analogs &amp; derivatives ; Humans ; Lung Neoplasms/secondary/therapy ; Lymphatic Metastasis ; Mastectomy ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local ; Paclitaxel/administration &amp; dosage ; Palliative Care ; Taxoids/administration &amp; dosage ; Gemcitabine ; },
abstract = {BACKGROUND: breast metaplastic carcinomas are a heterogeneous group of neoplasms that exhibit a poor prognosis compared with invasive ductal carcinoma. Correspond less than 1% of all malignant neoplasms of the mammary gland. They usually present as high-grade tumors with a lower rate of lymph node metastases and decreased expression of estrogen and progesterone receptors and Her2 and increased expression of Her1 and Ki-67.<br><br>CLINICAL CASE: we report a 52 year old woman with a breast carcinosarcoma presented with a left breast tumor fungated, ulcerated, polypoid and 18 cm in major diameter with lymph node metastases at diagnosis. She received multimodal management with neoadjuvant chemotherapy, followed by mastectomy and adjuvant chemotherapy; she presented progression of the disease with lung metastases and local massive recurrence, eventually died from complications associated to the disease.<br><br>CONCLUSIONS: metaplastic carcinomas of the breast are extremely rare entities. Due the nature of disease and presentation, the prognosis is poor in these patients. There are several histologic subtypes based on studies of hematoxylin and eosin and immunohistochemical stains. It requires multimodal therapy (surgery, radiotherapy and chemotherapy) for best results.},
}
@article {pmid25059790,
year = {2015},
author = {Yajima, R and Fujii, T and Yanagita, Y and Fujisawa, T and Miyamoto, T and Hirakata, T and Tsutsumi, S and Iijima, M and Kuwano, H},
title = {Prognostic value of extracapsular invasion of axillary lymph nodes combined with peritumoral vascular invasion in patients with breast cancer.},
journal = {Annals of surgical oncology},
volume = {22},
number = {1},
pages = {52-58},
doi = {10.1245/s10434-014-3941-x},
pmid = {25059790},
issn = {1534-4681},
mesh = {Adenocarcinoma/mortality/*secondary/therapy ; Adenocarcinoma, Scirrhous/mortality/*secondary/therapy ; Axilla ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Carcinoma, Papillary/mortality/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/mortality/*pathology/therapy ; Neoplasm Staging ; Prognosis ; Survival Rate ; },
abstract = {BACKGROUND: Extracapsular invasion (ECI) of metastatic axillary lymph nodes has been associated with aggressive nodal disease but its prognostic role in breast cancer is unclear. The present study evaluated nodal ECI as a predictor of breast cancer recurrence.<br><br>METHODS: We evaluated 154 women with histologically proven node-positive breast cancer who were diagnosed with invasive ductal carcinoma, and investigated the relationships between ECI and recurrences and other clinicopathological factors, particularly vascular invasion and the number of lymph node metastases.<br><br>RESULTS: The presence of ECI at positive nodes was significantly associated with the number of positive nodes, and with disease recurrence and survival in univariate (but not multivariate) analysis. Interestingly, all ECI(+) patients with distant metastases in our series had peritumoral vascular invasion (PVI), which may have reflected systemic disease; ECI with PVI of the primary tumor strongly predicted recurrent disease and shorter survival.<br><br>CONCLUSION: ECI of axillary metastases combined with PVI indicates high tumor aggressiveness. Patients with ECI and PVI may be considered for stronger adjuvant therapies because of their high risk for distant recurrences.},
}
@article {pmid25083433,
year = {2012},
author = {Niu, L and Zhou, L and Xu, K},
title = {Cryosurgery of breast cancer.},
journal = {Gland surgery},
volume = {1},
number = {2},
pages = {111-118},
pmid = {25083433},
issn = {2227-684X},
abstract = {With recent improvements in breast imaging, the ability to identify small breast tumors is markedly improved, prompting significant interest in the use of cryoablation without surgical excision to treat early-stage breast cancer. The cryoablation is often performed using ultrasound-guided tabletop argon-gas-based cryoablation system with a double freeze/thaw cycle. Recent studies have demonstrated that, as a primary therapy for small breast cancer, cryoablation is safe and effective with durable results, and can successfully destroy all cancers <1.0 cm and tumors between 1.0 and 1.5 cm without a significant ductal carcinoma-in-situ (DCIS) component. Presence of noncalcified DCIS is the cause of most cryoablation failures. At this time, cryoablation should be limited to patients with invasive ductal carcinoma <1.5 cm and with <25% DCIS in the core biopsy. For unresectable advanced breast cancer, cryoablation is a palliation modality and may be used as complementary for subsequent resection or other therapies.},
}
@article {pmid26141267,
year = {2001},
author = {Hanson, EL and Hershberger, RE},
title = {Genetic Counseling and Screening Issues in Familial Dilated Cardiomyopathy.},
journal = {Journal of genetic counseling},
volume = {10},
number = {5},
pages = {397-415},
pmid = {26141267},
issn = {1573-3599},
abstract = {Idiopathic dilated cardiomyopathy (IDC), a treatable condition characterized by left ventricular dilatation and systolic dysfunction of unknown cause, has only recently been recognized to have genetic etiologies. Although familial dilated cardiomyopathy (FDC) was thought to be infrequent, it is now believed that 30-50% of cases of IDC may be familial. Echocardiographic and electrocardiographic (ECG) screening of first-degree relatives of individuals with IDC and FDC is indicated because detection and treatment are possible prior to the onset of advanced, symptomatic disease. However, such screening often creates uncertainty and anxiety surrounding the significance of the results. Furthermore, FDC demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making genetic counseling complex. The provision of genetic counseling for IDC and FDC will require collaboration between cardiologists and genetics professionals, and may also improve the recognition of FDC, the availability of support services, and overall outcomes for patients and families.},
}
@article {pmid31159098,
year = {1996},
author = {Yu, FY and Chu, FS},
title = {Production and Characterization of Antibodies against Fumonisin B1.},
journal = {Journal of food protection},
volume = {59},
number = {9},
pages = {992-997},
doi = {10.4315/0362-028X-59.9.992},
pmid = {31159098},
issn = {1944-9097},
abstract = {Polyclonal antibodies against fumonisin B1 (FmB1) were produced in rabbits after immunizing the animals with either FmBl-keyhole limpet hemocyanin (KLH) or FmB1 bovine serum albumin (BSA). A direct competitive enzyme-linked immunosorbent assay (dc-ELISA) and an indirect competitive ELISA (idc-ELISA) were used for the characterization of the antibodies and for analysis of the toxin in corn samples. The antibody titers in the serum of rabbits immunized with FmBl-KLH were considerably higher than in those immunized with FmBl-BSA. The antibodies from the rabbits immunized with FmBl-KLH were further characterized. The concentrations causing 50% inhibition of binding of FmB1-horseradish peroxidase (HRP) to the antibodies by FmB1, FmB2 and FmB3 in the ELISA were found to be 0.45, 0.72, and 25 ng/ml, respectively. The detection limit of FmBl, based on 95% confidence at 5% of inhibition of binding of FmBl-HRP conjugate, in buffer of the dc-ELISA was found to be 0.05 ng/ml. In the presence of a matrix such as corn, the detection limit was less than 50 ppb. The overall analytical recoveries of FmBl (50 to 1,000 ng/g) added to the ground corn and then extracted with CH3CN/H2O (1/1, vol/vol) with cleanup and without cleanup in the dc ELISA were found to be 70.5 and 85.9%, respectively. A good correlation was found between the FmBl levels in 2 starch and 10 naturally contaminated corn samples analyzed by the dc-ELISA and the high-pressure liquid chromatography (HPLC) method. The correlation coefficients between ELISA and HPLC were found to be 0.955 (y [ELISA] = 1.3 1x [HPLC] + 77 ppb; P < 0.001) and 0.811 (y = 1.13x + 34 ppb; P < 0.01) for the sample without and with cleanup treatment, respectively.},
}
@article {pmid25049275,
year = {2014},
author = {Frittoli, E and Palamidessi, A and Marighetti, P and Confalonieri, S and Bianchi, F and Malinverno, C and Mazzarol, G and Viale, G and Martin-Padura, I and Garré, M and Parazzoli, D and Mattei, V and Cortellino, S and Bertalot, G and Di Fiore, PP and Scita, G},
title = {A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination.},
journal = {The Journal of cell biology},
volume = {206},
number = {2},
pages = {307-328},
pmid = {25049275},
issn = {1540-8140},
mesh = {Animals ; Breast Neoplasms/*genetics/pathology ; Cell Line, Tumor ; Disease Progression ; Extracellular Matrix/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Neoplasm Invasiveness/genetics ; Neoplasm Recurrence, Local/genetics/pathology ; Proteolysis ; Transplantation, Heterologous ; rab5 GTP-Binding Proteins/*genetics/metabolism/*physiology ; },
abstract = {The mechanisms by which tumor cells metastasize and the role of endocytic proteins in this process are not well understood. We report that overexpression of the GTPase RAB5A, a master regulator of endocytosis, is predictive of aggressive behavior and metastatic ability in human breast cancers. RAB5A is necessary and sufficient to promote local invasion and distant dissemination of various mammary and nonmammary tumor cell lines, and this prometastatic behavior is associated with increased intratumoral cell motility. Specifically, RAB5A is necessary for the formation of invadosomes, membrane protrusions specialized in extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5-dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix metalloprotease [MT1-MMP] and β3 integrin) required for invadosome formation in response to motogenic stimuli. This trafficking circuitry is necessary for spatially localized hepatocyte growth factor (HGF)/MET signaling that drives invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs promote tumor dissemination by controlling a proteolytic, mesenchymal invasive program.},
}
@article {pmid25047051,
year = {2014},
author = {Hadiji, N and Previnaire, JG and Benbouzid, R and Robain, G and Leblond, C and Mieusset, R and Enjalbert, M and Soler, JM},
title = {Are oxybutynin and trospium efficacious in the treatment of detrusor overactivity in spinal cord injury patients?.},
journal = {Spinal cord},
volume = {52},
number = {9},
pages = {701-705},
doi = {10.1038/sc.2014.113},
pmid = {25047051},
issn = {1476-5624},
mesh = {Adult ; Benzilates/*therapeutic use ; Female ; Humans ; Male ; Mandelic Acids/*therapeutic use ; Nortropanes/*therapeutic use ; Retrospective Studies ; Spinal Cord Injuries/*complications ; Time Factors ; Treatment Outcome ; Urinary Bladder, Overactive/*drug therapy/*etiology ; Urodynamics ; Urological Agents/*therapeutic use ; },
abstract = {OBJECTIVES: To evaluate the efficacy of anticholinergic agents in the treatment of neurogenic overactive bladder (NOAB) and neurogenic detrusor overactivity (NDO) in spinal cord injury (SCI) patients on clean intermittent catheterisation (CIC).<br><br>METHODS: Chronic suprasacral SCI patients on CIC presenting with at least one urinary leakage a day were included. Urodynamics and voiding diaries were performed at baseline and 1 month follow-up. In case of NDO at baseline, an anticholinergic drug was prescribed.<br><br>RESULTS: The 231 SCI patients presented with one to five urinary leakages per day (mean 2.1). Urodynamics showed NDO in all patients. A new anticholinergic treatment was started in all, either in monotherapy (134 patients) or in association with the existing anticholinergic drug (oxybutynin+trospium bitherapy, 97 patients). The mean maximum bladder capacity significantly increased from 225 to 441&#x2009;ml, and the mean involuntary detrusor contractions (IDC) significantly decreased from 67 to 41&#x2009;cm H2O. Only 75 SCI patients (32%) were fully continent. However, 25 out of these 75 patients showed persistent NDO, with amplitudes of IDC above 40&#x2009;cm H2O in 12 patients. Incontinence was still found in 156 SCI patients (67%), with an average of 1,2 leakages a day. In 100 patients, amplitudes of IDC remained above 40&#x2009;cm H2O. There was no statistical difference between patients on anticholinergic monotherapy or bitherapy at follow-up.<br><br>CONCLUSION: Anticholinergic treatment is not always satisfactory in terms of control of NDO and rarely allows full continence. Urodynamic follow-up is mandatory in all patients, even in those showing clinical continence.},
}
@article {pmid25041824,
year = {2014},
author = {Piscuoglio, S and Ng, CK and Martelotto, LG and Eberle, CA and Cowell, CF and Natrajan, R and Bidard, FC and De Mattos-Arruda, L and Wilkerson, PM and Mariani, O and Vincent-Salomon, A and Weigelt, B and Reis-Filho, JS},
title = {Integrative genomic and transcriptomic characterization of papillary carcinomas of the breast.},
journal = {Molecular oncology},
volume = {8},
number = {8},
pages = {1588-1602},
pmid = {25041824},
issn = {1878-0261},
mesh = {Breast Neoplasms/*genetics/*metabolism ; Carcinoma, Papillary/*genetics/*metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/genetics/physiology ; Genomics/*methods ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Polymorphism, Single Nucleotide/genetics ; },
abstract = {Papillary carcinoma (PC) is a rare type of breast cancer, which comprises three histologic subtypes: encapsulated PC (EPC), solid PC (SPC) and invasive PC (IPC). Microarray-based gene expression and Affymetrix SNP 6.0 gene copy number profiling, and RNA-sequencing revealed that PCs are luminal breast cancers that display transcriptomic profiles distinct from those of grade- and estrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs), and that the papillary histologic pattern is unlikely to be underpinned by a highly recurrent expressed fusion gene or a highly recurrent expressed mutation. Despite displaying similar patterns of gene copy number alterations, significant differences in the transcriptomic profiles of EPCs, SPCs and IPCs were found, and may account for their different histologic features.},
}
@article {pmid25036908,
year = {2015},
author = {Kitahashi, T and Takahashi, M and Imai, T},
title = {Biphasic Alterations in Expression and Subcellular Localization of MUC1 in Pancreatic Ductal Carcinogenesis in Syrian Hamsters.},
journal = {Pancreas},
volume = {44},
number = {1},
pages = {76-86},
doi = {10.1097/MPA.0000000000000178},
pmid = {25036908},
issn = {1536-4828},
mesh = {Animals ; Biomarkers, Tumor/genetics/*metabolism ; Carcinoma, Pancreatic Ductal/chemically induced/genetics/*metabolism/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/metabolism/pathology ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Mesocricetus ; Mucin-1/genetics/*metabolism ; Neoplasms, Experimental/chemically induced/genetics/*metabolism/pathology ; Nitrosamines ; Oligonucleotide Array Sequence Analysis ; RNA Interference ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; Transfection ; },
abstract = {OBJECTIVES: The aim of the present study was to characterize molecular targets for the prevention/diagnosis of pancreatic cancer using a chemically induced hamster pancreatic carcinogenesis model, in which background injuries to the parenchyma, for example, chronic pancreatitis or acinar atrophy, are limited.<br><br>METHODS: Gene expression profiles in atypical hyperplasias were first investigated using a microarray technique. Immunohistochemical analyses of early lesions and invasive ductal carcinoma (IDC) were then conducted for MUC1, of which mRNA levels were prominent among the up-regulated genes, in contrast with the coexpression of epithelial-mesenchymal transition (EMT)-related proteins.<br><br>RESULTS: Immunohistochemistry for MUC1 cytoplasmic domain (MUC1-CD), which was not detected in normal-like pancreatic ducts, was positive in the apical surfaces of the epithelia of hyperplasias with and without atypia and IDC areas with distinct tubular patterns. In contrast, cytoplasmic/nuclear positivity for MUC1-CD was observed in the invasive front of IDCs. The coexpression of EMT-related proteins, such as slug and vimentin, with cytoplasmic/nuclear MUC1-CD was also detected.<br><br>CONCLUSIONS: Alterations in the expression and subcellular localization of MUC1 represent a biphasic phenomenon, and the latter may be associated with EMT in pancreatic carcinogenesis in hamsters, which indicates that changes in MUC1 are important targets for pancreatic cancer prevention and chemotherapy.},
}
@article {pmid25034035,
year = {2014},
author = {Akabori, H and Shiomi, H and Naka, S and Murakami, K and Murata, S and Ishida, M and Kurumi, Y and Tani, T},
title = {Resectable carcinoma developing in the remnant pancreas 7 years and 10 months after distal pancreatectomy for invasive ductal carcinoma of the pancreas: report of a case.},
journal = {World journal of surgical oncology},
volume = {12},
number = {},
pages = {224},
pmid = {25034035},
issn = {1477-7819},
mesh = {Carcinoma, Pancreatic Ductal/*etiology/secondary/*surgery ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Second Primary/*etiology ; *Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; Prognosis ; Reoperation ; },
abstract = {BACKGROUND: Pancreatic ductal adenocarcinoma, which represents 90% of pancreatic cancers, is one of the most lethal and aggressive malignancies. Operative resection remains the only treatment providing prolonged survival, however, recurrence of pancreatic ductal adenocarcinoma occurs in up to 80% of patients with pancreatic cancer within 2 years of a potential curative resection. There are few reports of pancreatic carcinoma recurrence (primary second cancer) in the remnant pancreas after pancreatectomy.<br><br>CASE PRESENTATION: A 52-year-old woman underwent a distal pancreatectomy for pancreatic cancer in September 2004. Adjuvant chemotherapy was started after surgery and continued for 4&#xa0;years. In March 2012, marked elevation of DUPAN-II was observed, followed by an irregular stenotic finding in the main duct. We performed an en bloc resection of the remnant pancreas in July 2012. Histologically, the tumor contained a second primary pancreatic carcinoma with lymph node metastasis. At follow-up 20&#xa0;months after the second operation, the patient was alive without recurrence. Fourteen cases of resectable cancer developing in the remnant pancreas after a pancreatectomy for cancer have been reported; a minority of these was identified as second primary tumors. Therefore, our patient's primary second cancer is a rare event.<br><br>CONCLUSION: The patient is considered to have shown a rare, unique pancreatic cancer recurrence. Persistent elevation of a tumor marker and extensive imaging led to proper diagnosis and treatment.},
}
@article {pmid25031282,
year = {2014},
author = {Croall, ID and Cowie, CJ and He, J and Peel, A and Wood, J and Aribisala, BS and Mitchell, P and Mendelow, AD and Smith, FE and Millar, D and Kelly, T and Blamire, AM},
title = {White matter correlates of cognitive dysfunction after mild traumatic brain injury.},
journal = {Neurology},
volume = {83},
number = {6},
pages = {494-501},
pmid = {25031282},
issn = {1526-632X},
mesh = {Adolescent ; Adult ; Aged ; Brain Injuries/*complications/*diagnosis ; Cognition Disorders/*diagnosis/*etiology ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Nerve Fibers, Myelinated/*pathology ; Young Adult ; },
abstract = {OBJECTIVE: To relate neurophysiologic changes after mild/moderate traumatic brain injury to cognitive deficit in a longitudinal diffusion tensor imaging investigation.<br><br>METHODS: Fifty-three patients were scanned an average of 6 days postinjury (range = 1-14 days). Twenty-three patients were rescanned 1 year later. Thirty-three matched control subjects were recruited. At the time of scanning, participants completed cognitive testing. Tract-Based Spatial Statistics was used to conduct voxel-wise analysis on diffusion changes and to explore regressions between diffusion metrics and cognitive performance.<br><br>RESULTS: Acutely, increased axial diffusivity drove a fractional anisotropy (FA) increase, while decreased radial diffusivity drove a negative regression between FA and Verbal Letter Fluency across widespread white matter regions, but particularly in the ascending fibers of the corpus callosum. Raised FA is hypothesized to be caused by astrogliosis and compaction of axonal neurofilament, which would also affect cognitive functioning. Chronically, FA was decreased, suggesting myelin sheath disintegration, but still regressed negatively with Verbal Letter Fluency in the anterior forceps.<br><br>CONCLUSIONS: Acute mild/moderate traumatic brain injury is characterized by increased tissue FA, which represents a clear neurobiological link between cognitive dysfunction and white matter injury after mild/moderate injury.},
}
@article {pmid25029110,
year = {2014},
author = {Rizwani, W and Schaal, C and Kunigal, S and Coppola, D and Chellappan, S},
title = {Mammalian lysine histone demethylase KDM2A regulates E2F1-mediated gene transcription in breast cancer cells.},
journal = {PloS one},
volume = {9},
number = {7},
pages = {e100888},
pmid = {25029110},
issn = {1932-6203},
support = {P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA077301/CA/NCI NIH HHS/United States ; CA77301/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; E2F1 Transcription Factor/*genetics ; Epithelial Cells/metabolism/pathology ; F-Box Proteins/genetics/*metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism ; Matrix Metalloproteinases/metabolism ; Neoplasm Invasiveness ; Neovascularization, Pathologic/metabolism ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Retinoblastoma Protein/metabolism ; *Transcription, Genetic ; Up-Regulation ; Vascular Endothelial Growth Factor Receptor-1/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; },
abstract = {It is established that histone modifications like acetylation, methylation, phosphorylation and ubiquitination affect chromatin structure and modulate gene expression. Lysine methylation/demethylation on Histone H3 and H4 is known to affect transcription and is mediated by histone methyl transferases and histone demethylases. KDM2A/JHDM1A/FBXL11 is a JmjC-containing histone demethylase that targets mono- and dimethylated Lys36 residues of Histone H3; its function in breast cancer is not fully understood. Here we show that KDM2A is strongly expressed in myoepithelial cells (MEPC) in breast cancer tissues by immunohistochemistry. Ductal cells from ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) show positive staining for KDM2A, the expression decreases with disease progression to metastasis. Since breast MEPCs have tumor-suppressive and anti-angiogenic properties, we hypothesized that KDM2A could be contributing to some of these functions. Silencing KDM2A with small interfering RNAs demonstrated increased invasion and migration of breast cancer cells by suppressing a subset of matrix metalloproteinases (MMP-2, -9, -14 and -15), as seen by real-time PCR. HUVEC cells showed increased angiogenic tubule formation ability in the absence of KDM2A, with a concomitant increase in the expression of VEGF receptors, FLT-1 and KDR. KDM2A physically bound to both Rb and E2F1 in a cell cycle dependent manner and repressed E2F1 transcriptional activity. Chromatin immunoprecipitation (ChIP) assays revealed that KDM2A associates with E2F1-regulated proliferative promoters CDC25A and TS in early G-phase and dissociates in S-phase. Further, KDM2A could also be detected on MMP9, 14 and 15 promoters, as well as promoters of FLT1 and KDR. KDM2A could suppress E2F1-mediated induction of these promoters in transient transfection experiments. These results suggest a regulatory role for KDM2A in breast cancer cell invasion and migration, through the regulation of E2F1 function.},
}
@article {pmid25027758,
year = {2014},
author = {Rask, L and Balslev, E and Søkilde, R and Høgdall, E and Flyger, H and Eriksen, J and Litman, T},
title = {Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status.},
journal = {Cellular oncology (Dordrecht, Netherlands)},
volume = {37},
number = {3},
pages = {215-227},
pmid = {25027758},
issn = {2211-3436},
mesh = {Aged ; Blotting, Western ; Breast Neoplasms/classification/diagnosis/*genetics ; Down-Regulation ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; MicroRNAs/*genetics ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; PTEN Phosphohydrolase/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Up-Regulation ; },
abstract = {PURPOSE: Therapeutic decisions in breast cancer are increasingly guided by prognostic and predictive biomarkers. Non-protein-coding microRNAs (miRNAs) have recently been found to be deregulated in breast cancers and, in addition, to be correlated with several clinico-pathological features. One of the most consistently up-regulated miRNAs is miR-21. Here, we specifically searched for differentially expressed miRNAs in high-risk breast cancer patients as compared to low-risk breast cancer patients. In the same patients, we also compared miR-21 expression with the expression of its presumed target PTEN.<br><br>METHODS: Both microarray and RT-qPCR techniques were used to assess miRNA expression levels in lymph node-positive and -negative human invasive ductal carcinoma tissues. Simultaneously, PTEN protein expression levels were assessed using immunohistochemistry.<br><br>RESULTS: miR-486-5p and miR-139-5p were found to be down-regulated in patients with lymph node metastases, whereas miR-21 was found to be up-regulated in patients with a positive lymph node status. miR-21 expression levels were found to significantly correlate with tumour size (r&#x2009;=&#x2009;0.403, p&#x2009;=&#x2009;0.009; Spearman's rank), whereas no relation was found between miR-21 and PTEN expression levels (Kruskal-Wallis test).<br><br>CONCLUSION: Down-regulation of miR-486-5p and miR-139-5p, in conjunction with up-regulation of miR-21, may represent a useful signature for the identification of high-risk breast cancer patients.},
}
@article {pmid25027116,
year = {2014},
author = {Ramalho, EA and Silva-Filho, JL and Cartaxo, MF and Cavalcanti, CB and Rêgo, MJ and Oliveira, MB and Beltrão, EI},
title = {Assessment of changes in the BRCA2 and P53 genes in breast invasive ductal carcinoma in northeast Brazil.},
journal = {Biological research},
volume = {47},
number = {1},
pages = {3},
pmid = {25027116},
issn = {0717-6287},
mesh = {Alleles ; Brazil ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; CpG Islands/genetics ; DNA Methylation/*genetics ; Female ; *Genes, BRCA2 ; *Genes, p53 ; Genotype ; Humans ; Mutation ; Polymerase Chain Reaction/methods ; Polymorphism, Genetic ; Promoter Regions, Genetic/genetics ; Risk Factors ; Statistics as Topic ; },
abstract = {BACKGROUND: BRCA protein interacts with at least 13 different proteins that have been implicated with cancer susceptibility and loss of BRCA function is correlated to sensitivity to DNA crosslinking agents in preclinical models.<br><br>RESULTS: BRCA2 methylation frequency was 44%, p53 Pro22 allele frequency was 32% and heterozygous frequency of Arg/Pro72 genotype was 60% which could be associated as risk factor for metastasis (p = 0.046 OR = 4.190). Regarding to polymorphism of codon 249 the frequency of Arg249 allele presented 82% which was considered not statistically significant.<br><br>CONCLUSIONS: There was not statistical significance to BRCA2 promoter methylation with any parameters chosen. However, our findings suggest that patients who present heterozygous genotype at codon 72 of p53 gene may have a major susceptibility to any type of metastasis and this could serve as potential auxiliary biomarker for poor prognosis.},
}
@article {pmid25009006,
year = {2014},
author = {Fujihira, A and Suzuki, T and Chang, MO and Moriyama, T and Kitajima, M and Takaku, H},
title = {Antitumor effects of baculovirus-infected dendritic cells against human pancreatic carcinoma.},
journal = {Gene therapy},
volume = {21},
number = {9},
pages = {849-854},
doi = {10.1038/gt.2014.59},
pmid = {25009006},
issn = {1476-5462},
mesh = {Animals ; Baculoviridae/physiology ; CD8-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Dendritic Cells/immunology/*virology ; Female ; Humans ; Immunotherapy ; Killer Cells, Natural/*immunology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Pancreatic Neoplasms/*immunology/pathology/*therapy ; Survival Analysis ; },
abstract = {Recently, we showed that baculovirus (BV)-infected dendritic cells (DCs) (BV-DCs) induced antitumor immunity against established tumors in mice. These antitumor effects were CD8(+) T-cell and natural killer (NK) cell dependent but CD4(+) T-cell independent. In the current study, we examined the antitumor effect of BV-DCs on human pancreatic cancer cells (AsPC-1). After treatment with BV-infected bone marrow-derived dendritic cells (BMDCs), human pancreatic tumors caused by AsPC-1 cells in a nude mouse model were significantly reduced in size, and the survival of the mice was improved compared with that of non-immature BMDC (iDC)- and BV-DC-immunized mice. We also found that wild-type BV could activate human DCs (HDCs) and that NK cells were activated by BV-infected HDCs (BHDCs). Our findings show that BV-DCs can induce antitumor immunity, which paves the way for the use of this technique as an effective tool for DC immunotherapy against malignancies.},
}
@article {pmid25007177,
year = {2014},
author = {Rêgo, MJ and da Silva Filho, AF and Cordeiro, MF and Santos, PB and Beltrão, EI},
title = {The glycomic profile of invasive ductal carcinoma of the breast is altered in patients with hypoxic regions: implications for tumor behavior.},
journal = {Folia histochemica et cytobiologica},
volume = {52},
number = {2},
pages = {96-103},
doi = {10.5603/FHC.2014.0017},
pmid = {25007177},
issn = {1897-5631},
mesh = {Adult ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism ; Carbonic Anhydrases/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Case-Control Studies ; Cell Hypoxia ; Female ; Galectin 1/*genetics/metabolism ; Galectin 3/*genetics/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Oxygen/*metabolism ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; },
abstract = {Hypoxic areas in solid tumors are often associated with poor prognosis and resistance to chemotherapy. The aim of the study was to analyze the expression of galectin-1 (Gal-1), galectin-3 (Gal-3), sialic acid and b1-6 branched glycan structures in hypoxic environment of invasive ductal carcinoma (IDC) of the breast. We performed lectin histochemistry with phytohemag glutinin-L (L-PHA) and Sambucus nigra lectin (SNA); and immunohistochemistry for Gal-1, Gal-3, carbonic anhydrase IX, hypoxia-inducible factor, estrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor type-2 for 86 IDC samples. Patients with markers positive for hypoxia were mostly ER-negative (p = 0.003) and presented with more nodal invasion than the non-hypoxic group (p = 0.0439). Concerning the glycobiological aspects, the hypoxic group expressed more of Gal-3 (p = 0.0021) and SNA ligands (p = 0.0498), however, there was no association between lectin- and galectin-staining and clinical and histopathological data. Our results suggest a change in the glycomic profile of patients within hypoxic regions of IDC. However, further studies are needed to evaluate the role of lectin- and galectin-ligands in tumor's hypoxic environment, as well as their potential to be used as therapeutic targets.},
}
@article {pmid25001103,
year = {2014},
author = {Fang, X and Reifman, J and Wallqvist, A},
title = {Modeling metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle.},
journal = {Molecular bioSystems},
volume = {10},
number = {10},
pages = {2526-2537},
doi = {10.1039/c4mb00115j},
pmid = {25001103},
issn = {1742-2051},
mesh = {Animals ; Biomass ; Energy Metabolism ; Erythrocytes/*parasitology ; Host-Parasite Interactions ; Humans ; *Life Cycle Stages ; Malaria, Falciparum/*metabolism/*parasitology ; *Metabolic Networks and Pathways ; *Models, Biological ; Plasmodium falciparum/*growth &amp; development/*metabolism ; Time Factors ; },
abstract = {The human malaria parasite Plasmodium falciparum goes through a complex life cycle, including a roughly 48-hour-long intraerythrocytic developmental cycle (IDC) in human red blood cells. A better understanding of the metabolic processes required during the asexual blood-stage reproduction will enhance our basic knowledge of P. falciparum and help identify critical metabolic reactions and pathways associated with blood-stage malaria. We developed a metabolic network model that mechanistically links time-dependent gene expression, metabolism, and stage-specific growth, allowing us to predict the metabolic fluxes, the biomass production rates, and the timing of production of the different biomass components during the IDC. We predicted time- and stage-specific production of precursors and macromolecules for P. falciparum (strain HB3), allowing us to link specific metabolites to specific physiological functions. For example, we hypothesized that coenzyme A might be involved in late-IDC DNA replication and cell division. Moreover, the predicted ATP metabolism indicated that energy was mainly produced from glycolysis and utilized for non-metabolic processes. Finally, we used the model to classify the entire tricarboxylic acid cycle into segments, each with a distinct function, such as superoxide detoxification, glutamate/glutamine processing, and metabolism of fumarate as a byproduct of purine biosynthesis. By capturing the normal metabolic and growth progression in P. falciparum during the IDC, our model provides a starting point for further elucidation of strain-specific metabolic activity, host-parasite interactions, stress-induced metabolic responses, and metabolic responses to antimalarial drugs and drug candidates.},
}
@article {pmid24997789,
year = {2014},
author = {Kim, JY and Kim, YJ and Kim, SH and Kang, BJ and Song, BJ},
title = {Invasive ductal carcinoma of the breast in a 14-year-old girl.},
journal = {Pediatric radiology},
volume = {44},
number = {11},
pages = {1446-1449},
pmid = {24997789},
issn = {1432-1998},
mesh = {Adolescent ; Breast Neoplasms/genetics/*pathology/*therapy ; Carcinoma, Ductal, Breast/genetics/*pathology/*therapy ; *Chemoradiotherapy, Adjuvant ; Female ; Genetic Predisposition to Disease/genetics ; Humans ; Magnetic Resonance Imaging ; *Mastectomy, Segmental ; Neoplasm Staging ; Rare Diseases/diagnosis/genetics/therapy ; Ultrasonography, Mammary ; },
abstract = {Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer.},
}
@article {pmid24996432,
year = {2014},
author = {Asch-Kendrick, RJ and Samols, MA and Lilo, MT and Subhawong, AP and Sharma, R and Illei, PB and Argani, P and Cimino-Mathews, A},
title = {NKX3.1 is expressed in ER-positive and AR-positive primary breast carcinomas.},
journal = {Journal of clinical pathology},
volume = {67},
number = {9},
pages = {768-771},
pmid = {24996432},
issn = {1472-4146},
support = {P30 CA006973/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Carcinoma, Lobular/*chemistry/secondary ; Female ; Homeodomain Proteins/*analysis ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/analysis ; Receptors, Androgen/*analysis ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/analysis ; Tissue Array Analysis ; Transcription Factors/*analysis ; Tumor Burden ; },
abstract = {AIMS: NKX3.1 is an androgen-regulated tumour suppressor gene that is downregulated in prostate carcinoma. Immunohistochemistry for NKX3.1 is primarily specific for prostatic-derived tumours and tissue but is reported in a small number of breast carcinomas. NKX3.1 is also shown to inhibit estrogen receptor (ER) signalling in breast carcinoma models. Here, we investigate labelling of NKX3.1 in invasive ductal (IDC) and lobular (ILC) carcinomas of the breast with full characterisation of ER, progesterone receptor (PR), androgen receptor (AR) and Her2 status.<br><br>METHODS: Tissue microarrays of 86 primary IDC and 37 ILC were labelled for NKX3.1. The IDC consisted of 20 luminal A, 7 luminal B, 14 Her2, and 45 triple negative carcinomas. The ILC consisted of 34 luminal A and 3 luminal B cases. NKX3.1 expression was scored as percentage nuclear labelling and labelling intensity.<br><br>RESULTS: Nuclear NKX3.1 labelling was seen in 2 IDC (2%) and 10 ILCs (27%). labelling intensity was weak in all cases (1&#x2013;100% nuclear positivity). Positive NKX3.1 labelling was significantly associated with ILC (p<0.0001). NKX3.1 labelling was seen only in ER and AR-positive carcinomas, which showed a significant correlation (p=0.0003 and p=0.0079, respectively). Expression was not correlated with tumour stage, size, Her2 expression, presence of lymph node metastases or age.<br><br>CONCLUSIONS: This is the first study to evaluate NKX3.1 expression in breast carcinomas with known ER, PR, AR and Her2 status. Further studies are needed to evaluate what potential role NKX3.1 plays in ER and AR signalling and hormonal treatment response in breast carcinomas.},
}
@article {pmid24989617,
year = {2014},
author = {Saunderson, RB and Gouliouris, T and Cartwright, EJ and Nickerson, EJ and Aliyu, SH and O'Donnell, DR and Kelsall, W and Limmathurotsakul, D and Peacock, SJ and Török, ME},
title = {Impact of infectious diseases consultation on the management of Staphylococcus aureus bacteraemia in children.},
journal = {BMJ open},
volume = {4},
number = {7},
pages = {e004659},
pmid = {24989617},
issn = {2044-6055},
support = {G1000803/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Adolescent ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/microbiology/*therapy ; Child ; Child, Preschool ; Dimethoate ; *Disease Management ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Prognosis ; *Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/microbiology/*therapy ; Staphylococcus aureus/*isolation &amp; purification ; },
abstract = {OBJECTIVES: Infectious diseases consultation (IDC) in adults with Staphylococcus aureus bacteraemia (SAB) has been shown to improve management and outcome. The aim of this study was to evaluate the impact of IDC on the management of SAB in children.<br><br>STUDY DESIGN: Observational cohort study of children with SAB.<br><br>SETTING: Cambridge University Hospitals National Health Service (NHS) Foundation Trust, a large acute NHS Trust in the UK.<br><br>PARTICIPANTS: All children with SAB admitted to the Cambridge University Hospitals NHS Foundation Trust between 16 July 2006 and 31 December 2012.<br><br>METHODS: Children with SAB between 2006 and 31 October 2009 were managed by routine clinical care (pre-IDC group) and data were collected retrospectively by case notes review. An IDC service for SAB was introduced in November 2009. All children with SAB were reviewed regularly and data were collected prospectively (IDC group) until 31 December 2012. Baseline characteristics, quality metrics and outcome were compared between the pre-IDC group and IDC group.<br><br>RESULTS: There were 66 episodes of SAB in 63 children-28 patients (30 episodes) in the pre-IDC group, and 35 patients (36 episodes) in the IDC group. The median age was 3.4&#x2005;years (IQR 0.2-10.7&#x2005;years). Patients in the IDC group were more likely to have echocardiography performed, a removable focus of infection identified and to receive a longer course of intravenous antimicrobial therapy. There were no differences in total duration of antibiotic therapy, duration of hospital admission or outcome at 30 or 90&#x2005;days following onset of SAB.<br><br>CONCLUSIONS: IDC resulted in improvements in the investigation and management of SAB in children.},
}
@article {pmid24989112,
year = {2016},
author = {Kotani, H and Yoshimura, A and Adachi, Y and Ishiguro, J and Hisada, T and Ichikawa, M and Gondou, N and Hattori, M and Kondou, N and Sawaki, M and Fujita, T and Iwata, H},
title = {Sentinel lymph node biopsy is not necessary in patients diagnosed with ductal carcinoma in situ of the breast by stereotactic vacuum-assisted biopsy.},
journal = {Breast cancer (Tokyo, Japan)},
volume = {23},
number = {2},
pages = {190-194},
doi = {10.1007/s12282-014-0546-y},
pmid = {24989112},
issn = {1880-4233},
mesh = {Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Image-Guided Biopsy/*methods ; Lymph Nodes/diagnostic imaging/*pathology/surgery ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Sentinel Lymph Node Biopsy/*statistics &amp; numerical data ; Vacuum ; },
abstract = {BACKGROUND: This study evaluated the role and need of a sentinel lymph node biopsy (SLNB) in patients with an initial diagnosis of ductal carcinoma in situ (DCIS) made by stereotactic vacuum-assisted biopsy (VAB).<br><br>MATERIALS AND METHODS: A retrospective analysis was performed of 1,458 patients who underwent stereotactic VAB between January 1999 and December 2012 at Aichi Cancer Center Hospital. The rates of axillary node metastasis and the underestimation of invasive ductal carcinoma (IDC) were examined.<br><br>RESULTS: Of the 1,458 patients who underwent stereotactic VAB, 199 had a preoperative diagnosis of DCIS and underwent surgery. In these patients, 20 % (39/199) were upstaged to IDC or at least microinvasion in final pathology. Axillary lymph node status was investigated in 81 % (161/199) of initially diagnosed DCIS patients, and resulted in finding lymph node metastasis in 0.62 % (1/161) patients. To assess the potential preoperative predictors of invasiveness, the value of DCIS histological grade on biopsy samples, the distribution of calcifications on mammograms, and the combination of these factors were studied. The underestimation rate was higher (30 %) in the combination of high DCIS histological grade and extensive calcification although there was no significant association (p = 0.23).<br><br>CONCLUSION: The rate of lymph node metastasis was extremely low (0.62 %), even when invasive carcinoma was identified on excision in patients initially diagnosed with DCIS by stereotactic VAB. Because of the low prevalence of metastatic involvement, the cessation of SLNB is a reasonable consideration in patients initially diagnosed with DCIS by stereotactic VAB.},
}
@article {pmid24978026,
year = {2014},
author = {Pape-Zambito, D and Jiang, Z and Wu, H and Devarajan, K and Slater, CM and Cai, KQ and Patchefsky, A and Daly, MB and Chen, X},
title = {Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients.},
journal = {PloS one},
volume = {9},
number = {6},
pages = {e100488},
pmid = {24978026},
issn = {1932-6203},
support = {P30 CA006927/CA/NCI NIH HHS/United States ; R01 CA138819/CA/NCI NIH HHS/United States ; R21 CA186853/CA/NCI NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/complications/*diagnosis/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*diagnosis/genetics/pathology ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Female ; Formaldehyde ; Gene Expression ; *Genetic Heterogeneity ; Humans ; Immunohistochemistry ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tissue Embedding ; Tissue Fixation ; Tumor Suppressor Protein p53/genetics ; },
abstract = {The heterogeneity among multiple ductal carcinoma in situ (DCIS) lesions within the same patient also diagnosed with invasive ductal carcinoma (IDC) has not been well evaluated, leaving research implications of intra-individual DCIS heterogeneity yet to be explored. In this study formalin-fixed paraffin embedded sections from 36 patients concurrently diagnosed with DCIS and IDC were evaluated by immunohistochemistry. Ten DCIS lesions from each patient were then randomly selected and scored. Our results showed that expression of PR, HER2, Ki-67, and p16 varied significantly within DCIS lesions from a single patient (P<0.05 for PR; P<1×10(-8) for HER2, Ki-67 and p16). In addition, seventy-two percent of the individuals had heterogeneous expression of at least 2/6 markers. Importantly, by evaluating the expression of promising DCIS risk biomarkers (Ki-67, p53 and p16) among different DCIS subgroups classified by comparing DCIS molecular subtypes with those of adjacent normal terminal duct lobular units (TDLU) and IDC, our results suggest the existence of a highly-aggressive DCIS subgroup, which had the same molecular subtype as the adjacent IDC but not the same subtype as the adjacent normal TDLU. By using a systematic approach, our results clearly demonstrate that intra-individual heterogeneity in DCIS is very common in patients concurrently diagnosed with IDC. Our novel findings of a DCIS subpopulation with aggressive characteristics will provide a new paradigm for mechanistic studies of breast tumor progression and also have broad implications for prevention research as heterogeneous pre-invasive lesions are present in many other cancer types.},
}
@article {pmid24969877,
year = {2014},
author = {Sharma, M and Sharma, JD and Sarma, A and Ahmed, S and Kataki, AC and Saxena, R and Sharma, D},
title = {Triple negative breast cancer in people of North East India: critical insights gained at a regional cancer centre.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {15},
number = {11},
pages = {4507-4511},
doi = {10.7314/apjcp.2014.15.11.4507},
pmid = {24969877},
issn = {2476-762X},
mesh = {Adult ; Biomarkers, Tumor/genetics ; Female ; Humans ; India ; Lymph Nodes/pathology ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Retrospective Studies ; Triple Negative Breast Neoplasms/genetics/*pathology ; },
abstract = {BACKGROUND: Breast cancer is a heterogeneous disease comprising of distinct biological subtypes with many targeted prognostic biomarkers having therapeutic implications. However, no specific targeted therapy for triple negative breast cancer has been discovered to date and hence further research is needed.<br><br>AIM: The aim and objectives of the present study were to examine the prevalence of triple negative breast cancer (TNBC) in North-East India and to compare the clinicopathological parameters in two study groups defined by immunohistochemistry (IHC) -"TNBC" and "Others".<br><br>MATERIALS AND METHODS: We carried out a retrospective study in a cohort of 972 patients diagnosed with invasive breast carcinoma in the Department of Pathology, Dr. B. Borooah Cancer Institute, a Regional Cancer Centre for treatment and research, Guwahati, for a period of 3 years and 10 months from January 2010 to October 2013. Based on IHC findings, patients were divided into two groups - "TNBC" and "Others". All relevant clinicopathological parameters were compared in both. TNBC were defined as those that were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while those positive for any of these markers were defined as "Others".<br><br>RESULTS: In this study, out of total 972 cases 31.9% (310 cases) were defined as TNBC and 662 cases (68.1%) as "Others" based on IHC markers. Compared to the "Others" category, TNBC presented at an early age (mean 40 years), were associated with high grade large tumours and high rate of node positivity, IDC NOS being the most common histological subtype in TNBC.<br><br>CONCLUSIONS: TNBC accounts for a significant portion of breast cancers in this part of India and commonly present at younger age and tend to be large high grade tumours.},
}
@article {pmid24966964,
year = {2014},
author = {Miyai, K and Divatia, MK and Shen, SS and Miles, BJ and Ayala, AG and Ro, JY},
title = {Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between "precursor-like" and "regular type" lesions.},
journal = {International journal of clinical and experimental pathology},
volume = {7},
number = {5},
pages = {2518-2526},
pmid = {24966964},
issn = {1936-2625},
mesh = {Aged ; Biopsy ; Carcinoma, Ductal/blood/chemistry/mortality/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/blood/chemistry/mortality/*secondary/surgery ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Kallikreins/blood ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Predictive Value of Tests ; Proportional Hazards Models ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/blood/chemistry/mortality/*secondary/surgery ; Prostatic Neoplasms/blood/chemistry/mortality/*pathology/surgery ; Risk Factors ; Time Factors ; Treatment Outcome ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically "regular type" IDC-P and "precursor-like" IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.},
}
@article {pmid24966944,
year = {2014},
author = {dos-Santos, PB and Zanetti, JS and Vieira-de-Mello, GS and Rêgo, MB and Ribeiro-Silva A, A and Beltrão, EI},
title = {Lectin histochemistry reveals SNA as a prognostic carbohydrate-dependent probe for invasive ductal carcinoma of the breast: a clinicopathological and immunohistochemical auxiliary tool.},
journal = {International journal of clinical and experimental pathology},
volume = {7},
number = {5},
pages = {2337-2349},
pmid = {24966944},
issn = {1936-2625},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*enzymology/genetics/mortality/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/genetics/mortality/pathology ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; *Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; N-Acetylglucosaminyltransferases/*analysis ; Neoplasm Invasiveness ; *Plant Lectins ; Predictive Value of Tests ; Proportional Hazards Models ; *Ribosome Inactivating Proteins ; Risk Factors ; Time Factors ; Tissue Array Analysis ; },
abstract = {Increased sialylation and β1,6-branched oligosaccharides has been associated with a variety of structural changes in cell surface carbohydrates, most notably in tumorigenesis. Lectins are defined as proteins that preferentially recognize and bind carbohydrate complexes protruding from glycolipids and glycoproteins. This interaction with carbohydrates can be as specific as the interaction between antigen and antibody. Due to this type of interaction lectins have been used as experimental auxiliary tools in histopathological diagnosis of cancer. This study was designed to evaluate the differential expression of sialic acids and β1,6-N-acetylglucosaminyltransferase V (MGAT5) in invasive (IDC) and in situ (DCIS) ductal carcinoma of the breast and its possible application as prognostic biomarkers. A possible transition between pre-malign and malign lesions was evaluated using DCIS samples. Biopsies were analyzed regarding the expression of MUC1, p53, Ki-67, estrogen receptor, progesterone receptor, HER-2 and MGAT5. α2,6-linked sialic acids residues recognized by SNA lectin was overexpressed in 33.3% of IDC samples and it was related with Ki-67 (p=0.042), PR (p=0.029), lymphnodes status (p=0.017) and death (p=0.011). Regarding survival analysis SNA was the only lectin able to correlate with specific-disease survival and disease-free survival (p=0.024 and p=0.041, respectively), besides, it presents itself as an independent variable by Cox Regression analysis (p= 0.004). Comparing IDC and DCIS cases, only SNA showed different staining pattern (p=0.034). The presence of sialic acids on tumor cell surface can be an indicative of poor prognosis and our study provides further evidence that SNA lectin can be used as a prognostic probe in IDC and DCIS patients.},
}
@article {pmid24950714,
year = {2014},
author = {Aggarwal, A and Al-Rohil, RN and Batra, A and Feustel, PJ and Jones, DM and DiPersio, CM},
title = {Expression of integrin α3β1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer.},
journal = {BMC cancer},
volume = {14},
number = {},
pages = {459},
pmid = {24950714},
issn = {1471-2407},
support = {R01CA129637/CA/NCI NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cyclooxygenase 2/genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Integrin alpha3beta1/genetics/*metabolism ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; },
abstract = {BACKGROUND: Expression of integrin α3β1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin α3β1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin α3β1 and COX2 by testing for their correlated expression among various forms of human breast cancer.<br><br>METHODS: Immunohistochemistry was performed to assess co-expression of &#x3b1;3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n = 59 samples) or obtained from Albany Medical Center archives (n = 68 samples). Immunostaining intensity for the integrin &#x3b1;3 subunit or COX2 was scored, and Spearman's rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria.<br><br>RESULTS: Although expression of integrin &#x3b1;3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between &#x3b1;3 and COX2 in both tissue microarrays (r(s) = 0.49, p < 0.001, n = 59) and archived samples (r(s) = 0.59, p < 0.0001, n = 68). In both sample sets, this correlation was independent of hormone receptor status, histological grade, or disease stage.<br><br>CONCLUSIONS: COX2 and &#x3b1;3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin &#x3b1;3&#x3b2;1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of &#x3b1;3&#x3b2;1-dependent COX2 gene expression that we reported previously in breast cancer cells. The findings also suggest that COX2-positive breast carcinomas of various subtypes might be vulnerable to therapeutic strategies that target &#x3b1;3&#x3b2;1, and that &#x3b1;3 expression might serve as an independent prognostic biomarker.},
}
@article {pmid24937677,
year = {2014},
author = {Engels, CC and Fontein, DB and Kuppen, PJ and de Kruijf, EM and Smit, VT and Nortier, JW and Liefers, GJ and van de Velde, CJ and Bastiaannet, E},
title = {Immunological subtypes in breast cancer are prognostic for invasive ductal but not for invasive lobular breast carcinoma.},
journal = {British journal of cancer},
volume = {111},
number = {3},
pages = {532-538},
pmid = {24937677},
issn = {1532-1827},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Carcinoma, Lobular/*immunology/pathology ; Caspase 3/metabolism ; Disease-Free Survival ; Female ; Humans ; Ki-67 Antigen/metabolism ; Middle Aged ; Prognosis ; Young Adult ; },
abstract = {BACKGROUND: Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential.<br><br>METHODS: Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery.<br><br>RESULTS: No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC.<br><br>CONCLUSIONS: Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.},
}
@article {pmid24937604,
year = {2014},
author = {Chatfield, KC and Sparagna, GC and Sucharov, CC and Miyamoto, SD and Grudis, JE and Sobus, RD and Hijmans, J and Stauffer, BL},
title = {Dysregulation of cardiolipin biosynthesis in pediatric heart failure.},
journal = {Journal of molecular and cellular cardiology},
volume = {74},
number = {},
pages = {251-259},
pmid = {24937604},
issn = {1095-8584},
support = {R01 HL107715/HL/NHLBI NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01HL107715/HL/NHLBI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Cardiolipins/*biosynthesis/chemistry ; Cardiomyopathy, Dilated/*metabolism/pathology/surgery ; Child ; Child, Preschool ; Female ; Gene Expression ; Heart Failure/*metabolism/pathology/surgery ; Heart Transplantation ; Heart Ventricles/*metabolism/pathology ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Mitochondria, Heart/*metabolism/pathology ; Mitochondrial Proteins/genetics/metabolism ; Myocardium/*metabolism/pathology ; },
abstract = {Cardiolipin, a unique phospholipid in the inner mitochondrial membrane, is critical for optimal mitochondrial function. CL abnormalities have been demonstrated in the failing rodent and adult human heart. The aim of this study was to determine whether abnormalities in CL content and the CL biosynthesis and remodeling pathways are present in pediatric idiopathic dilated cardiomyopathy (IDC). A cross-sectional analysis of myocardial tissue from 119 IDC and non-failing (NF) control samples was performed. Electrospray ionizing mass spectrometry was used to measure total CL and CL species content in LV tissue. RT-PCR was employed to measure gene expression of the enzymes in the CL biosynthesis and remodeling pathways in both the adult and pediatric heart. Significantly lower total and (18:2)4CL (the beneficial species) content was demonstrated in myocardium from pediatric patients with IDC compared to NF controls. Analysis of mitochondrial gene transcripts was used to demonstrate that there is no decrease in mitochondrial content. Expression of two biosynthesis enzymes and one remodeling enzyme was significantly lower in pediatric IDC compared to NF controls. Expression of two phospholipases involved in CL degradation were also altered, one up- and one down-regulated. Except for one remodeling enzyme, these changes are unique from those in the failing adult heart. Similar to what has been seen in adults and in a rat model of IDC, total and (18:2)4CL are lower in pediatric IDC. Unique CL species profiles are seen in heart tissue from children with IDC compared to adults. Differences in CL biosynthesis and remodeling enzyme expression likely explain the differences in CL profiles observed in IDC and implicate unique age-related mechanisms of disease.},
}
@article {pmid24931343,
year = {2014},
author = {Oda, Y and Aishima, S and Morimatsu, K and Shindo, K and Fujino, M and Mizuuchi, Y and Hattori, M and Miyazaki, T and Tanaka, M and Oda, Y},
title = {Pancreatic intraepithelial neoplasia in the background of invasive ductal carcinoma of the pancreas as a prognostic factor.},
journal = {Histopathology},
volume = {65},
number = {3},
pages = {389-397},
doi = {10.1111/his.12397},
pmid = {24931343},
issn = {1365-2559},
mesh = {Aged ; Atrophy ; Carcinoma in Situ/*pathology ; Carcinoma, Pancreatic Ductal/*pathology/secondary ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Pancreatic Neoplasms/*pathology ; Prognosis ; },
abstract = {AIMS: Of the recognized precursor lesions of pancreatic adenocarcinoma, pancreatic intraepithelial neoplasia (PanIN) is the most common form. However, little is known about the relationship between the grade of PanIN and prognosis for patients with invasive ductal carcinoma.<br><br>METHODS AND RESULTS: In 124 patients with invasive ductal carcinoma, we examined the grade and number of PanIN lesions in all slides of resected pancreas. The prevalence rates of PanIN-1A, PanIN-1B, PanIN-2 and PanIN-3 were 86%, 84%, 57% and 30%, respectively. We allocated PanIN-2 and PanIN-3 cases into a PanIN-high group, and cases showing PanIN-1A, PanIN-1B or absence of PanIN into a PanIN-low group. In clinicopathological analysis, PanIN-high status was significantly correlated with the number of PanIN lesions (P < 0.0001). Disease-free and overall survival were statistically better in the PanIN-high group than in the PanIN-low group (P = 0.0005 and P = 0.0003). Univariate and multivariate analyses revealed that tumour size and PanIN-low status were statistically significant factors for a poorer prognosis (P = 0.042 and P = 0.007).<br><br>CONCLUSIONS: In a pathological examination, it is important to evaluate the grade and number of PanINs in assessing the prognosis of pancreatic cancer.},
}
@article {pmid24919244,
year = {2014},
author = {So, K and Habashy, D and Doyle, B and Chan, L},
title = {Indwelling urinary catheters: pattern of use in a public tertiary-level Australian hospital.},
journal = {Urologic nursing},
volume = {34},
number = {2},
pages = {69-73},
pmid = {24919244},
issn = {1053-816X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Australia ; Catheter-Related Infections/*etiology/nursing ; Female ; Hospitals, Public ; Humans ; Male ; Middle Aged ; Nursing Audit ; Tertiary Care Centers ; Urinary Catheterization/*adverse effects/nursing/*statistics &amp; numerical data ; Urinary Catheters/*adverse effects ; },
abstract = {An audit of charts from patients identified as having an indwelling urinary catheter (IDC) was conducted in a 450-bed, tertiary level hospital (Concord Repatriation General Hospital) in Australia. Documentation of relevant information regarding IDC in the medical record included indication for catheterization, insertion and removal dates, use of antibiotics, place of insertion, designation of inserter, catheter type, availability of IDC kits, and use of catheter fixation devices.},
}
@article {pmid24909183,
year = {2014},
author = {Min, KW and Kim, DH and Do, SI and Kim, K and Lee, HJ and Chae, SW and Sohn, JH and Pyo, JS and Oh, YH and Kim, WS and Lee, SY and Oh, S and Choi, SH and Park, YL and Park, CH},
title = {Expression patterns of stromal MMP-2 and tumoural MMP-2 and -9 are significant prognostic factors in invasive ductal carcinoma of the breast.},
journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica},
volume = {122},
number = {12},
pages = {1196-1206},
doi = {10.1111/apm.12285},
pmid = {24909183},
issn = {1600-0463},
mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/*genetics/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 2/genetics/*metabolism ; Matrix Metalloproteinase 9/genetics/*metabolism ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; },
abstract = {Matrix metalloproteinases (MMPs) are matrix-degrading enzymes that play a pivotal role in aggressive behaviours, such as rapid tumour growth, invasion, and metastasis, of several types of solid tumours. In particular, stromal MMP-2 plays important roles in the progression of malignant tumours, but most clinical studies have focused on tumoural MMP-2 and -9 expression, and not stromal MMP-2 expression. One hundred and seventy-seven cases diagnosed as invasive ductal carcinoma of the breast between 2000 and 2005 were included in this study. Expressions of tumoural MMP-2 and -9 and stromal MMP-2 were analysed by immunostaining on a tissue microarray. Subsequently, the associations between those results and various clinicopathological parameters were evaluated. Stromal MMP-2 expression correlated significantly with clinicopathological parameters such as advanced T category, larger tumour size, high histological grade, tumour necrosis, ER- and PR-negative, and HER-2-positive (all p < 0.05). In univariate and multivariate analyses, overall survival was linked with stromal MMP-2 expression as well as dual expression of stromal MMP-2 and tumoural MMP-2 and -9 (all p < 0.05). Stromal MMP-2 expression may play a crucial role in predicting aggressive clinical behaviour in breast cancer patients.},
}
@article {pmid24894013,
year = {2014},
author = {Das, U and Lakshmaiah, KC and Govind Babu, K and Suresh, TM and Lokanatha, D and Jacob, L and Babu, S},
title = {The actual scenario of neoadjuvant chemotherapy of breast cancer in developing country: a report of 80 cases of breast cancer from a tertiary cancer center in India.},
journal = {Journal of cancer research and clinical oncology},
volume = {140},
number = {10},
pages = {1777-1782},
pmid = {24894013},
issn = {1432-1335},
mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/economics/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/*drug therapy/secondary/surgery ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration &amp; dosage ; Epirubicin/administration &amp; dosage ; Female ; Fluorouracil/administration &amp; dosage ; Humans ; India/epidemiology ; Induction Chemotherapy ; Lymphatic Metastasis ; Medical Records ; Middle Aged ; Molecular Targeted Therapy/*economics ; Neoadjuvant Therapy/*methods ; Neoplasm Staging ; Postmenopause ; Premenopause ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Rural Population/statistics &amp; numerical data ; Tertiary Care Centers ; Treatment Outcome ; },
abstract = {BACKGROUND: Preoperative or neoadjuvant chemotherapy is an option in patients with large operable breast cancer to facilitate the breast conservation and to downstage the disease to make inoperable breast cancer to operable one. It is also called the window of opportunity; it provides a unique opportunity to derive biological information related to tumor response. Neoadjuvant chemotherapy has been compared with standard, postoperative adjuvant chemotherapy with goals of improving survival and facilitating local therapies. Unfortunately, neoadjuvant chemotherapy does not seem to improve overall survival. There is a lack of data from India regarding the neoadjuvant chemotherapy. The present study was carried out to assess the response to neoadjuvant chemotherapy in breast cancer.<br><br>MATERIALS AND METHODS: We retrospectively analyzed the records of patients who were started on neoadjuvant chemotherapy (NACT) at our center for 1 year (August 2012 to July 2013). Case files were thoroughly reviewed, and patient's characteristics (age, pre-/postmenopausal status, family history of breast/ovarian/other cancer), mode of detection, treatment, and histological features were analyzed.<br><br>RESULTS: Out of 322 patients with breast cancer registered in our institute, 80 patients received neoadjuvant chemotherapy. Median age was 45 years. The most common presentation was left-sided breast lump (Lt > Rt) with a median duration of symptoms was 4 months. Postmenopausal patients (53.75 %) were more than premenopausal (46.25 %). Seventy-two patients were stage III and 8 were stage II disease. Bilateral breast cancer was seen in 8 patients. Most common histological type was invasive ductal carcinoma (95 %). Estrogen receptor (ER) and/or progesterone (PR) positive were seen in 47 (58.75 %) patients. Ten patients were HER2 positive and ER/PR negative, and 5 patients were triple positive. Triple-negative patients were 22 (27.5 %). The most common neoadjuvant chemotherapy protocol used was FEC. Clinical response before surgery was CR 13 %, PR 68.68 %, stable disease 11.62 %, and progressive disease 4.65 %. Pathological CR was seen in 6.9 % of tumors. Nodal status at surgery was ypN0-40 %, ypN1-28. 5 %. ypN2-27 %, and ypN3-4.28 %.<br><br>CONCLUSION: In a population of predominantly locally advanced patients, NACT with anthracyclines yielded pCR rates comparable to published studies. There were a high proportion of HER2-positive patients, most of whom could not receive anti-HER2 therapy due to financial reasons.},
}
@article {pmid24888777,
year = {2014},
author = {Tajiri, R and Inokuchi, M and Sawada-Kitamura, S and Kawashima, H and Nakamura, R and Oyama, T and Dobashi, Y and Ooi, A},
title = {Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.},
journal = {Pathology international},
volume = {64},
number = {5},
pages = {231-236},
doi = {10.1111/pin.12158},
pmid = {24888777},
issn = {1440-1827},
mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/genetics/metabolism ; Biopsy, Needle ; Breast/metabolism/pathology ; Breast Neoplasms/*genetics/metabolism/therapy ; Carcinoma, Ductal, Breast/*genetics/metabolism/therapy ; Carcinoma, Lobular/*genetics/metabolism/therapy ; Cyclin D1/genetics/metabolism ; DNA Fingerprinting/*methods ; DNA, Neoplasm/*genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Mastectomy ; Multiplex Polymerase Chain Reaction/*methods ; Receptor, ErbB-2/genetics/metabolism ; Treatment Outcome ; },
abstract = {A needle biopsy of a mass in the right breast of a 36-year-old woman revealed invasive ductal carcinoma (IDC), and approximately 20% of cancer cells showed unequivocal membranous staining with the HercepTest. After systemic therapy with trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin + cyclophosphamide), a right mastectomy was performed. By histological and immunohistochemical examinations, the resected tumor consisted mainly of E-cadherin-negative invasive lobular carcinoma (ILC), and the rest was ERBB2-positive IDC; thus, the diagnosis was mixed ductal and lobular carcinoma. Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization (FISH) analyses revealed that ILC and IDC shared high-level amplification of CCND1 in homogeneously staining regions (HSR) and that IDC had an additional HSR-type amplicon of ERBB2. These findings strongly indicate that IDC and ILC had a common precursor cell with CCND1 amplification. Review of the biopsy specimen with FISH showed IDC with gene amplifications of CCND1 and ERBB2 as a minor component, IDC without amplification of CCND1 or ERBB2 as a major component, and a minute portion of ILC with CCND1 amplification. We speculate that chemotherapy and trastuzumab caused a marked reduction in IDC; however, ILC with CCND1 amplification was resistant to chemotherapy and grew.},
}
@article {pmid24887297,
year = {2014},
author = {Gruel, N and Benhamo, V and Bhalshankar, J and Popova, T and Fréneaux, P and Arnould, L and Mariani, O and Stern, MH and Raynal, V and Sastre-Garau, X and Rouzier, R and Delattre, O and Vincent-Salomon, A},
title = {Polarity gene alterations in pure invasive micropapillary carcinomas of the breast.},
journal = {Breast cancer research : BCR},
volume = {16},
number = {3},
pages = {R46},
pmid = {24887297},
issn = {1465-542X},
mesh = {Axonemal Dyneins/genetics ; Base Sequence ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Calmodulin-Binding Proteins/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Polarity/*genetics ; Chaperonins ; Class I Phosphatidylinositol 3-Kinases ; Cytoskeletal Proteins/genetics ; DNA Copy Number Variations ; Exome/genetics ; Female ; Forkhead Box Protein O3 ; Forkhead Transcription Factors/biosynthesis/genetics ; Formins ; Gene Amplification/genetics ; Group II Chaperonins/genetics ; Humans ; Membrane Glycoproteins/genetics ; Membrane Proteins/biosynthesis/genetics ; Microfilament Proteins/biosynthesis ; Molecular Chaperones ; Mutation, Missense ; Neoplasm Invasiveness/*genetics ; Neoplasm Proteins/genetics ; Nuclear Proteins/biosynthesis ; Phosphatidylinositol 3-Kinases/genetics ; Protein Tyrosine Phosphatases, Non-Receptor/genetics ; RNA-Binding Proteins ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Retrospective Studies ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Sequence Deletion/genetics ; Serine C-Palmitoyltransferase/genetics ; Tumor Suppressor Protein p53/genetics ; Ubiquitin-Protein Ligases ; },
abstract = {INTRODUCTION: Pure invasive micropapillary carcinoma (IMPC) is a special type of breast carcinoma characterised by clusters of cells presenting polarity abnormalities. The biological alterations underlying this pattern remain unknown.<br><br>METHODS: Pangenomic analysis (n=39), TP53 (n=43) and PIK3CA (n=41) sequencing in a series of IMPCs were performed. A subset of cases was also analysed with whole-exome sequencing (n=4) and RNA sequencing (n=6). Copy number variation profiles were compared with those of oestrogen receptors and grade-matched invasive ductal carcinomas (IDCs) of no special type.<br><br>RESULTS: Unsupervised analysis of genomic data distinguished two IMPC subsets: one (Sawtooth/8/16) exhibited a significant increase in 16p gains (71%), and the other (Firestorm/Amplifier) was characterised by a high frequency of 8q (35%), 17q (20% to 46%) and 20q (23% to 30%) amplifications and 17p loss (74%). TP53 mutations (10%) were more frequently identified in the amplifier subset, and PIK3CA mutations (4%) were detected in both subsets. Compared to IDC, IMPC exhibited specific loss of the 6q16-q22 region (45%), which is associated with downregulation of FOXO3 and SEC63 gene expression. SEC63 and FOXO3 missense mutations were identified in one case each (2%). Whole-exome sequencing combined with RNA sequencing of IMPC allowed us to identify somatic mutations in genes involved in polarity, DNAH9 and FMN2 (8% and 2%, respectively) or ciliogenesis, BBS12 and BBS9 (2% each) or genes coding for endoplasmic reticulum protein, HSP90B1 and SPTLC3 (2% each) and cytoskeleton, UBR4 and PTPN21 (2% each), regardless of the genomic subset. The intracellular biological function of the mutated genes identified by gene ontology analysis suggests a driving role in the clinicopathological characteristics of IMPC.<br><br>CONCLUSION: In our comprehensive molecular analysis of IMPC, we identified numerous genomic alterations without any recurrent fusion genes. Recurrent somatic mutations of genes participating in cellular polarity and shape suggest that they, together with other biological alterations (such as epigenetic modifications and stromal alterations), could contribute to the morphological pattern of IMPC. Though none of the individual abnormalities demonstrated specificity for IMPC, whether their combination in IMPC may have a cumulative effect that drives the abnormal polarity of IMPC needs to be examined further with in vitro experiments.},
}
@article {pmid24886617,
year = {2014},
author = {Wani, N and Nasser, MW and Ahirwar, DK and Zhao, H and Miao, Z and Shilo, K and Ganju, RK},
title = {C-X-C motif chemokine 12/C-X-C chemokine receptor type 7 signaling regulates breast cancer growth and metastasis by modulating the tumor microenvironment.},
journal = {Breast cancer research : BCR},
volume = {16},
number = {3},
pages = {R54},
pmid = {24886617},
issn = {1465-542X},
support = {P30 CA016058/CA/NCI NIH HHS/United States ; R01 CA109527/CA/NCI NIH HHS/United States ; R01 CA153490/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Chemokine CXCL12/*metabolism ; Female ; Humans ; Lung Neoplasms/genetics/mortality/*secondary ; Macrophage Activation/genetics ; Macrophage Colony-Stimulating Factor/biosynthesis ; Macrophages/immunology ; Matrix Metalloproteinase 2/biosynthesis ; Matrix Metalloproteinase 9/biosynthesis ; Mice ; Mice, Inbred BALB C ; Neoplasm Invasiveness/genetics ; Neoplasm Transplantation ; Protein Binding ; RNA Interference ; RNA, Small Interfering ; Receptor, Macrophage Colony-Stimulating Factor/biosynthesis ; Receptors, CXCR/antagonists &amp; inhibitors/biosynthesis/genetics/*metabolism ; STAT3 Transcription Factor/antagonists &amp; inhibitors/genetics/*metabolism ; Tumor Microenvironment ; Vascular Cell Adhesion Molecule-1/biosynthesis ; },
abstract = {INTRODUCTION: Although C-X-C motif chemokine 12 (CXCL12) has been shown to bind to C-X-C chemokine receptor type 7 (CXCR7), the exact molecular mechanism regulations by CXCL12/CXCR7 axis in breast tumor growth and metastasis are not well understood. CXCR7 expression has been shown to be upregulated during pathological processes such as inflammation and cancer.<br><br>METHODS: Breast cancer cell lines were genetically silenced or pharmacologically inhibited for CXCR7 and/or its downstream target signal transducer and activator of transcription 3 (STAT3). 4T1 or 4T1 downregulated for CXCR7 and 4T1.2 breast cancer cell lines were injected in mammary gland of BALB/c mice to form tumors, and the molecular pathways regulating tumor growth and metastasis were assessed.<br><br>RESULTS: In this study, we observed that CXCL12 enhances CXCR7-mediated breast cancer migration. Furthermore, genetic silencing or pharmacologic inhibition of CXCR7 reduced breast tumor growth and metastasis. Further elucidation of mechanisms revealed that CXCR7 mediates tumor growth and metastasis by activating proinflammatory STAT3 signaling and angiogenic markers. Furthermore, enhanced breast tumorigenicity and invasiveness were associated with macrophage infiltration. CXCR7 recruits tumor-promoting macrophages (M2) to the tumor site through regulation of the macrophage colony-stimulating factor (M-CSF)/macrophage colony-stimulating factor receptor (MCSF-R) signaling pathway. In addition, CXCR7 regulated breast cancer metastasis by enhancing expression of metalloproteinases (MMP-9, MMP-2) and vascular cell-adhesion molecule-1 (VCAM-1). We also observed that CXCR7 is highly expressed in invasive ductal carcinoma (IDC) and metastatic breast tissue in human patient samples. In addition, high CXCR7 expression in tumors correlates with worse prognosis for both overall survival and lung metastasis-free survival in IDC patients.<br><br>CONCLUSION: These observations reveal that CXCR7 enhances breast cancer growth and metastasis via a novel pathway by modulating the tumor microenvironment. These findings identify CXCR7-mediated STAT3 activation and modulation of the tumor microenvironment as novel regulation of breast cancer growth and metastasis. These studies indicate that new strategies using CXCR7 inhibitors could be developed for antimetastatic therapy.},
}
@article {pmid24885919,
year = {2014},
author = {Xie, R and Wang, Y and Nie, W and Huang, W and Song, W and Wang, Z and Guan, X},
title = {Lin28B expression correlates with aggressive clinicopathological characteristics in breast invasive ductal carcinoma.},
journal = {Cancer biotherapy &amp; radiopharmaceuticals},
volume = {29},
number = {5},
pages = {215-220},
pmid = {24885919},
issn = {1557-8852},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Female ; Humans ; Middle Aged ; RNA-Binding Proteins/*biosynthesis/genetics ; },
abstract = {Lin28B is a RNA-binding protein that inhibits the let-7 microRNA family and acts as an oncogene in various human malignant diseases. Conversely, the members of let-7 family function as tumor suppressers and are often inactivated in cancers. The interaction of Lin28B/let-7 plays a crucial part of tumorigenesis. In this study, the authors examined the Lin28B expression using immunohistochemistry in 190 breast cancers and analyzed the correlation of Lin28B immunostaining and clinicopathological characteristics. Breast cancer patients previously diagnosed with invasive ductal carcinomas were enrolled in this study. All cases went through surgical procedures as the initial treatment. The characteristics of every case were collected, including tumor size, pathologic grade, metastatic lymphoid nodes, and estrogen receptor α (ERα), progesterone receptor (PR), and HER2 status. The immunostaining was scored by two independent investigators. Eighty-three (43.7%) of 190 cases showed positive expression of Lin28B. Lin28B immunostaining was increased in tumors compared with the adjacent tissues. Overexpression of Lin28B was linked to poor differentiation, advanced-stage disease, and Ki67-positive status (all p<0.05). Besides, Lin28B expression was significantly different among breast cancer subtypes. This study addresses the role of Lin28B in breast cancers and provides insight of its predictive effects in disease development.},
}
@article {pmid24870789,
year = {2014},
author = {Rathore, AS and Goel, MM and Makker, A and Kumar, S and Srivastava, AN},
title = {Is the tumor infiltrating natural killer cell (NK-TILs) count in infiltrating ductal carcinoma of breast prognostically significant?.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {15},
number = {8},
pages = {3757-3761},
doi = {10.7314/apjcp.2014.15.8.3757},
pmid = {24870789},
issn = {2476-762X},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*immunology/pathology ; CD56 Antigen/immunology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Cell Count ; Female ; Humans ; Immunohistochemistry ; Killer Cells, Natural/*immunology ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; },
abstract = {PURPOSE: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast.<br><br>MATERIAL AND METHODS: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively.<br><br>RESULTS: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (&#x3c7;2=4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (&#x3c7;2=1.60, p>0.05).<br><br>CONCLUSION: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs.},
}
@article {pmid24868030,
year = {2014},
author = {Muss, HB},
title = {Adjuvant chemotherapy in older women with breast cancer: who and what?.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {32},
number = {19},
pages = {1996-2000},
doi = {10.1200/JCO.2013.54.8586},
pmid = {24868030},
issn = {1527-7755},
mesh = {Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/diagnosis/*drug therapy/*surgery ; Carcinoma, Ductal, Breast/drug therapy/surgery ; Chemotherapy, Adjuvant ; Clinical Trials as Topic ; Comorbidity ; Female ; Filgrastim ; Granulocyte Colony-Stimulating Factor/administration &amp; dosage ; Humans ; *Life Expectancy ; Lymphatic Metastasis ; Polyethylene Glycols ; *Quality of Life ; Receptor, ErbB-2/analysis ; Recombinant Proteins/administration &amp; dosage ; Referral and Consultation ; Risk Assessment ; Risk Factors ; Taxoids/administration &amp; dosage ; },
abstract = {A 73-year-old woman has been diagnosed with a mammographically detected grade 3, 2.2-cm invasive ductal carcinoma that is sentinel lymph node negative, estrogen receptor positive (80%), progesterone receptor negative, and human epidermal growth factor receptor 2 negative (0 by immunohistochemistry). A gene expression assay (Oncotype DX, Genomic Health, Redwood City, CA) showed a recurrence score of 28. Except for well-controlled hypertension and some aches and pains in her hands and knees, she has no other major illnesses. Her medications include an antihypertensive, vitamin D, and calcium. She discontinued cigarette smoking 20 years ago and has an occasional glass of wine. She describes her health as good, is fully functional, drives, has had no falls, and provides the majority of care for her sick husband. Her blood pressure is 146/88, her body mass index is 29.7, and her physical examination is normal. She is aware of the benefits and risks of adjuvant endocrine therapy and has been referred to discuss the role of chemotherapy.},
}
@article {pmid24866608,
year = {2014},
author = {Sohn, YM and Hong, IK and Han, K},
title = {Role of [18F]fluorodeoxyglucose positron emission tomography-computed tomography, sonography, and sonographically guided fine-needle aspiration biopsy in the diagnosis of axillary lymph nodes in patients with breast cancer: comparison of diagnostic performance.},
journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine},
volume = {33},
number = {6},
pages = {1013-1021},
doi = {10.7863/ultra.33.6.1013},
pmid = {24866608},
issn = {1550-9613},
mesh = {Adult ; Aged ; Axilla/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology/*secondary ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; False Negative Reactions ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Middle Aged ; Positron-Emission Tomography/methods ; Radiopharmaceuticals ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy/*methods ; Tomography, X-Ray Computed/methods ; Ultrasonography, Mammary/*methods ; },
abstract = {OBJECTIVES: The aim of this study was to compare the diagnostic performance of [(18)F]fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) with that of sonography and sonographically guided fine-needle aspiration (FNA) for determining the preoperative axillary lymph node (ALN) status and to evaluate the factors related to false-negative PET-CT, sonographic, and FNA results in ALN staging of invasive ductal carcinoma.<br><br>METHODS: From March 2009 to July 2012, 226 patients had a diagnosis of primary breast cancer. Among these patients, 107 constituted the study population after exclusion of transferred patients and patients with breast cancer other than invasive ductal carcinoma. The diagnostic performance of the modalities was compared with pathologic reports. Univariate and multivariate analyses were used to evaluate the relationship between clinicopathologic factors (symptoms, T stage, hormone receptors, and histologic grade), false-negative results, and true-negative results on PET-CT, sonography, and FNA.<br><br>RESULTS: Of the 107 patients, 45 (42.1%) had positive results on final pathologic analysis of ALNs. Sonographically guided FNA had a significantly higher specificity, positive predictive value, accuracy, and area under the receiver operating characteristic curve than sonography and PET-CT (P < .01). When sonography and PET-CT were combined, the sensitivity was significantly improved (P = .019) compared with sonography alone. When FNA and PET-CT were combined, the sensitivity and negative predictive value were significantly increased compared with each modality (P < .01).<br><br>CONCLUSIONS: Sonographically guided FNA was found to be an excellent diagnostic tool for preoperative evaluation of the ALN status. To obviate the step of sentinel lymph node biopsy for determining the ALN status, combined evaluation of ALNs by these modalities may be more complementary than the use of a single modality.},
}
@article {pmid24865535,
year = {2014},
author = {Hirota, M and Ogawa, M},
title = {No-touch pancreatectomy for invasive ductal carcinoma of the pancreas.},
journal = {JOP : Journal of the pancreas},
volume = {15},
number = {3},
pages = {243-249},
doi = {10.6092/1590-8577/2502},
pmid = {24865535},
issn = {1590-8577},
mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/mortality/secondary/*surgery ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness/pathology/prevention &amp; control ; Neoplasm Recurrence, Local/pathology/prevention &amp; control ; Neoplastic Cells, Circulating/*pathology ; Pancreatectomy/adverse effects/*methods/mortality ; Pancreatic Neoplasms/mortality/pathology/*surgery ; Prognosis ; Retroperitoneal Space/surgery ; Surgical Instruments ; Touch ; },
abstract = {BACKGROUND: Pancreatectomy is the only effective treatment for cancers of the pancreas. Surgeons usually grasp tumors during pancreatectomy; however, this procedure may increase the risk of squeezing and shedding of the cancer cells into the portal vein, retroperitoneum, and/or peritoneal cavity. In an effort to overcome these problems, we have developed surgical techniques for no-touch pancreatectomy.<br><br>METHODS: From April 2008 through September 2013, 52 patients have been operated on no-touch pancreatectomy for invasive ductal carcinoma of the pancreas by a single operator (M.H.). Among them, 40 received pancreatoduodenectomy (PD), and 12 did distal pancreatectomy (DP). Twenty two cases (42%) required SMV-PV resection. This is a study to see if pancreatectomy can be technically done using a no-touch surgical technique without deteriorating the post-operative prognosis. During the procedure, the pancreatic tumor is neither grasped nor squeezed by the surgeon. Furthermore, for improved dissection of the retroperitoneal tissue (leftward and posterior margins for PD and rightward and posterior margins for DP), we use a hanging and clamping maneuver and dissection behind Gerota fascia.<br><br>RESULTS: Overall 2- and 5-year survival rates were 64 and 42% with mean follow-up periods of 34.4 months (range: 6-68 months). Recurrence free 2- and 5-year survival rates were 49 and 31%, respectively. The 5-year survival rates of patients with JPS-stage III and those with JPS-stage IV were 57 and 20%, respectively. The 5-year survival rates of patients with UICC-stage IIA and those with UICC- stage IIB were 49 and 39%, respectively. Patients with UICC-stage III or IV did not survive for more than 2 years.<br><br>CONCLUSIONS: No-touch pancreatectomy has many theoretic advantages that merit further investigation in future randomized controlled trials.},
}
@article {pmid24862985,
year = {2014},
author = {Takagi, K and Moriguchi, T and Miki, Y and Nakamura, Y and Watanabe, M and Ishida, T and Yamamoto, M and Sasano, H and Suzuki, T},
title = {GATA4 immunolocalization in breast carcinoma as a potent prognostic predictor.},
journal = {Cancer science},
volume = {105},
number = {5},
pages = {600-607},
pmid = {24862985},
issn = {1349-7006},
mesh = {Adult ; Aged ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Disease-Free Survival ; Female ; GATA4 Transcription Factor/genetics/*metabolism ; Gene Expression ; Humans ; Immunohistochemistry ; Laser Capture Microdissection ; Middle Aged ; Neoplasm Recurrence, Local/genetics/*pathology ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; },
abstract = {Transcriptional GATA factors are known lineage selector genes and regulate a variety of biological processes including specification and differentiation of tissues. In the present study, we examined expression profiles of six GATA factor genes in invasive ductal carcinomas (IDC) of the breast using microarray analysis (n = 20) and found that GATA4 expression was closely correlated with recurrence in patients. Because the significance of GATA4 has remained largely unknown in breast carcinoma, we further immunolocalized GATA4 in ductal carcinoma in situ (DCIS) of the breast (n = 48) and IDC (n = 163). GATA4 immunoreactivity was detected in the nuclei of carcinoma cells and was positive in 27% of DCIS and 31% of IDC cases. GATA4 status was significantly associated with nuclear grade and van Nuys classification in DCIS and was positively associated with distant metastasis, histological grade and HER2 status, but negatively correlated with progesterone receptor labeling index in IDC. Subsequent multivariate analysis demonstrated that GATA4 status was an independent prognostic factor for both disease-free and breast cancer-specific survival of IDC patients. All of these results indicate that GATA4 plays important roles in the progression of breast carcinoma from an early stage and that immunohistochemical GATA4 status is considered a potent prognostic factor in human breast cancer patients.},
}
@article {pmid24848193,
year = {2015},
author = {Santangelo, G and Vitale, C and Trojano, L and Picillo, M and Moccia, M and Pisano, G and Pezzella, D and Cuoco, S and Erro, R and Longo, K and Pellecchia, MT and Amboni, M and De Rosa, A and De Michele, G and Barone, P},
title = {Relationship between apathy and cognitive dysfunctions in de novo untreated Parkinson's disease: a prospective longitudinal study.},
journal = {European journal of neurology},
volume = {22},
number = {2},
pages = {253-260},
doi = {10.1111/ene.12467},
pmid = {24848193},
issn = {1468-1331},
mesh = {Aged ; Apathy/*physiology ; Cognition Disorders/*etiology/physiopathology ; Disease Progression ; Executive Function/*physiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications/physiopathology ; },
abstract = {BACKGROUND AND PURPOSE: Apathy may be either a symptom of major depression or a behavioral disturbance occurring in concomitance with depression or alone in Parkinson's disease (PD). The aim of the present study was to determine the progression of cognitive impairment in drug-naïve untreated PD patients with or without clinically significant apathy.<br><br>METHODS: Sixty-two PD patients with a disease duration <2 years and without history of present or past therapy with pro-dopaminergic agents were included and underwent the Apathy Evaluation Scale (S-AES), a clinical interview based on diagnostic criteria for apathy and a comprehensive neuropsychological battery to assess memory, frontal functions and visuospatial functions. Two years after the first assessment, all patients were re-evaluated on the S-AES, a clinical interview and neuropsychological tests.<br><br>RESULTS: According to the cut-off value of the S-AES and diagnostic criteria for apathy, eight patients experienced apathy at both baseline and follow-up (A+A+), nine patients had apathy only at follow-up (A-A+), 37 patients never experienced apathy (A-A-) and eight patients showed apathy at the baseline only (A+A-). Cognitive performance significantly declined in all four groups. At both baseline and follow-up A+A+ performed worse than A-A- on visuospatial and frontal tests; A-A+ had lower scores than A-A- on the interference task of the Stroop test (IT-ST). Regression analysis showed that poor performance on the IT-ST at baseline was the only independent predictor of onset of apathy at follow-up.<br><br>CONCLUSIONS: The results indicated a relationship between apathy and dysexecutive syndrome in early PD. Reduced scores on the IT-ST may predict development of apathy in PD patients.},
}
@article {pmid24842702,
year = {2014},
author = {Picillo, M and Erro, R and Amboni, M and Longo, K and Vitale, C and Moccia, M and Pierro, A and Scannapieco, S and Santangelo, G and Spina, E and Orefice, G and Barone, P and Pellecchia, MT},
title = {Gender differences in non-motor symptoms in early Parkinson's disease: a 2-years follow-up study on previously untreated patients.},
journal = {Parkinsonism &amp; related disorders},
volume = {20},
number = {8},
pages = {850-854},
doi = {10.1016/j.parkreldis.2014.04.023},
pmid = {24842702},
issn = {1873-5126},
mesh = {Aged ; Antiparkinson Agents/*adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications/*drug therapy ; Sex Characteristics ; },
abstract = {BACKGROUND: We recently showed specific sex-related patterns of non motor symptoms (NMS) in early, drug-naïve PD patients. However, to date studies investigating gender-related effects of dopaminergic treatment on NMS in early PD are lacking.<br><br>METHODS: In the present study, we first report a prospective assessment of gender-related differences in the spectrum of NMS before (baseline) and after starting dopaminergic therapy (2-year follow-up) in a large cohort of newly diagnosed PD patients. Differences in NMS frequency between baseline and follow-up were evaluated by McNemar test. Spearman's rank test was employed to explore interactions between NMS and drug treatment.<br><br>RESULTS: One-hundred and thirty four PD patients (86M and 48W) were included in the present study. At 2-year follow-up, Sadness/blues presented a significant percentage reduction as compared to baseline in both sexes, while Urgency, Daytime sleepiness, Weight change and Sex drive presented a significant percentage increase only in men. At follow up men complained of a greater number of NMS as compared to women. Occurrence of Weight change was related to therapy in both sexes. Male gender was found to be a risk factor for developing Dribbling and Nocturia, irrespective of therapy and clinical features.<br><br>CONCLUSIONS: In conclusion, our study showed that mood symptoms improved after the introduction of therapy in both sexes, while men appeared to be more prone to develop some NMS possibly linked to dopaminergic treatment.},
}
@article {pmid24842355,
year = {2014},
author = {Vázquez Vicente, D and Di Fiore, HA and Garcia-Foncillas, J and Plaza Arranz, J},
title = {Endometrial adenocarcinoma in one horn of a didelphic uterus with vaginal duplication.},
journal = {BMJ case reports},
volume = {2014},
number = {},
pages = {},
pmid = {24842355},
issn = {1757-790X},
mesh = {Abnormalities, Multiple/diagnosis ; Adenocarcinoma/complications/*diagnosis/surgery ; Endometrial Neoplasms/complications/*diagnosis/surgery ; Endosonography/methods ; Female ; Follow-Up Studies ; Humans ; Hysterectomy/methods ; Hysteroscopy/methods ; Laparoscopy/methods ; Magnetic Resonance Imaging/methods ; Middle Aged ; Ovariectomy/methods ; Postmenopause ; Risk Assessment ; Treatment Outcome ; Urogenital Abnormalities/*diagnosis/surgery ; Uterine Hemorrhage/diagnosis/etiology ; Uterus/*abnormalities/surgery ; Vagina/*abnormalities/surgery ; },
abstract = {A 59-year-old female patient presented with vaginal bleeding. A didelphic uterus with vaginal duplication was diagnosed on the basis of physical examination and radiology tests. Biopsy revealed an endometrial cancer in the left horn, while the right was atrophic. Laparoscopic hysterectomy, bilateral salphingo-oophorectomy, pelvic and para-aortic lymphadenectomy were performed. According to Federation International of Gynecology and Obstetrics (FIGO) staging the tumour was classified Ib. The adjuvant therapy was vaginal cuff brachytherapy. After 6 months, she has no evidence of the disease.},
}
@article {pmid24841533,
year = {2014},
author = {Engstrom, LM and Brinkmeyer, MK and Ha, Y and Raetz, AG and Hedman, B and Hodgson, KO and Solomon, EI and David, SS},
title = {A zinc linchpin motif in the MUTYH glycosylase interdomain connector is required for efficient repair of DNA damage.},
journal = {Journal of the American Chemical Society},
volume = {136},
number = {22},
pages = {7829-7832},
pmid = {24841533},
issn = {1520-5126},
support = {T32 ES007058/ES/NIEHS NIH HHS/United States ; R01 CA067985/CA/NCI NIH HHS/United States ; T32 ES007059/ES/NIEHS NIH HHS/United States ; P41GM103393/GM/NIGMS NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; CA069785/CA/NCI NIH HHS/United States ; },
mesh = {Amino Acid Sequence ; Animals ; Cysteine/chemistry/genetics ; DNA Damage ; DNA Glycosylases/*chemistry/genetics ; DNA Repair Enzymes/*chemistry ; Humans ; Kinetics ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis ; Protein Conformation ; Serine/chemistry/genetics ; Zinc Compounds/*chemistry ; },
abstract = {Mammalian MutY glycosylases have a unique architecture that features an interdomain connector (IDC) that joins the catalytic N-terminal domain and 8-oxoguanine (OG) recognition C-terminal domain. The IDC has been shown to be a hub for interactions with protein partners involved in coordinating downstream repair events and signaling apoptosis. Herein, a previously unidentified zinc ion and its coordination by three Cys residues of the IDC region of eukaryotic MutY organisms were characterized by mutagenesis, ICP-MS, and EXAFS. In vitro kinetics and cellular assays on WT and Cys to Ser mutants have revealed an important function for zinc coordination on overall protein stability, iron-sulfur cluster insertion, and ability to mediate DNA damage repair. We propose that this "zinc linchpin" motif serves to structurally organize the IDC and coordinate the damage recognition and base excision functions of the C- and N-terminal domains.},
}
@article {pmid24833443,
year = {2015},
author = {Matsuda, H and Takahashi, Y and Nakata, K and Kitamura, A and Kakizaki, H},
title = {No Intense 18F-Fluorodeoxyglucose Uptake in Positron Emission Tomography of a Metastatic Orbital Tumor From Breast Carcinoma.},
journal = {Ophthalmic plastic and reconstructive surgery},
volume = {31},
number = {4},
pages = {e95-8},
doi = {10.1097/IOP.0000000000000115},
pmid = {24833443},
issn = {1537-2677},
mesh = {Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/secondary ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Magnetic Resonance Imaging ; Mastectomy, Radical ; Medroxyprogesterone/therapeutic use ; Middle Aged ; Muscle Neoplasms/diagnostic imaging/secondary ; Oculomotor Muscles/diagnostic imaging ; Orbital Neoplasms/*diagnostic imaging/secondary ; Paclitaxel/therapeutic use ; *Positron-Emission Tomography ; Radiopharmaceuticals/*metabolism ; Vision Disorders/diagnosis ; },
abstract = {A 47-year-old woman with a history of invasive ductal carcinoma in the right breast reported decreased vision in the OD for the past 3 months. Her best corrected visual acuity was 0.1 OD and 1.0 OS. T1-weighted MRI revealed enlargement of the right lateral rectus muscle with a faint tumor outline and no contrast enhancement in the lesion. F-fluorodeoxyglucose positron emission tomography did not demonstrate intense uptake at the lesion. Because the patient demonstrated optic neuropathy due to compression by the enlarged muscle, balanced orbital decompression (of the deep lateral and medial orbital walls) was performed simultaneously with a tumor biopsy. Visual acuity of the OD was dramatically improved to 1.0. The histopathological examination demonstrated similar findings to her breast carcinoma. F-fluorodeoxyglucose positron emission tomography does not always show a positive result for an orbital tumor that has metastasized from the breast.},
}
@article {pmid24810926,
year = {2014},
author = {Calvano Filho, CM and Calvano-Mendes, DC and Carvalho, KC and Maciel, GA and Ricci, MD and Torres, AP and Filassi, JR and Baracat, EC},
title = {Triple-negative and luminal A breast tumors: differential expression of miR-18a-5p, miR-17-5p, and miR-20a-5p.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {35},
number = {8},
pages = {7733-7741},
pmid = {24810926},
issn = {1423-0380},
mesh = {Breast/metabolism ; Carcinoma, Ductal, Breast/genetics ; Female ; Forkhead Box Protein O1 ; Forkhead Transcription Factors/genetics ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*analysis ; Triple Negative Breast Neoplasms/*genetics ; },
abstract = {New concepts in epigenetics, microRNAs, and gene expression analysis have significantly enhanced knowledge of cancer pathogenesis over the last decade. MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate gene expression by base pairing with target messenger RNAs (mRNAs), resulting in the repression of translation or the degradation of mRNA. To compare the carcinogenic process in tumors with different prognoses, we used real-time RT-PCR to evaluate the miRNA expression profiles of 24 triple-negative breast invasive ductal carcinoma, 20 luminal A breast invasive ductal carcinoma, and 13 normal breast parenchyma controls. We extracted total RNA from tissues fixed in formol and embedded in paraffin (FFPE). Results revealed the upregulation of miR-96-5p (9.35-fold; p = 0.000115), miR-182-5p (7.75-fold; p = 0.000033), miR-7-5p (6.71-fold; p = 0.015626), and miR-21-5p (6.10-fold; p = 0.000000) in tumors group. In addition, the expression of miR-125b-5p (4.49-fold; p = 0.000000) and miR-205-5p (4.36-fold; p = 0.006098) was downregulated. When the expression profiles of triple-negative and luminal A tumors were compared, there was enhanced expression of miR-17-5p (4.27-fold; p = 0.000664), miR-18a-5p (9.68-fold; p = 0.000545), and miR-20a-5 (4.07-fold; p = 0.001487) in the triple-negative tumors compared with luminal A. These data suggest that there is a similar regulation of certain miRNAs in triple-negative and luminal A tumors. However, it is possible that differences in the expression of miR-17-92 cluster will explain the phenotypic differences between these molecular tumor subtypes.},
}
@article {pmid24799764,
year = {2014},
author = {Stumpfova, Z and Hezova, R and Meli, AC and Slaby, O and Michalek, J},
title = {MicroRNA profiling of activated and tolerogenic human dendritic cells.},
journal = {Mediators of inflammation},
volume = {2014},
number = {},
pages = {259689},
pmid = {24799764},
issn = {1466-1861},
mesh = {Cells, Cultured ; Dendritic Cells/drug effects/*metabolism ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-10/pharmacology ; Interleukin-4/pharmacology ; Lipopolysaccharides/pharmacology ; MicroRNAs/*genetics ; Transforming Growth Factor beta/pharmacology ; },
abstract = {Dendritic cells (DCs) belong to the immune system and are particularly studied for their potential to direct either an activated or tolerogenic immune response. The roles of microRNAs (miRNAs) in posttranscriptional gene expression regulation are being increasingly investigated. This study's aim is to evaluate the miRNAs' expression changes in prepared human immature (iDCs), activated (aDCs), and tolerogenic dendritic cells (tDCs). The dendritic cells were prepared using GM-CSF and IL-4 (iDC) and subsequently maturated by adding LPS and IFN-γ (aDC) or IL-10 and TGF-β (tDC). Surface markers, cytokine profiles, and miRNA profiles were evaluated in iDC, tDC, and aDC at 6 h and 24 h of maturation. We identified 4 miRNAs (miR-7, miR-9, miR-155 and miR-182), which were consistently overexpressed in aDC after 6 h and 24 h of maturation and 3 miRNAs (miR-17, miR-133b, and miR-203) and miR-23b cluster solely expressed in tDC. We found 5 miRNAs (miR-10a, miR-203, miR-210, miR-30a, and miR-449b) upregulated and 3 miRNAs downregulated (miR-134, miR-145, and miR-149) in both tDC and aDC. These results indicate that miRNAs are specifically modulated in human DC types. This work may contribute to identifying specific modulating miRNAs for aDC and tDC, which could in the future serve as therapeutic targets in the treatment of cancer and autoimmune diseases.},
}
@article {pmid24795533,
year = {2014},
author = {Zahir, MN and Minhas, K and Shabbir-Moosajee, M},
title = {Pleomorphic lobular carcinoma of the male breast with axillary lymph node involvement: a case report and review of literature.},
journal = {BMC clinical pathology},
volume = {14},
number = {},
pages = {16},
pmid = {24795533},
issn = {1472-6890},
abstract = {BACKGROUND: Carcinoma of the male breast is responsible for less than 1% of all malignancies in men but the incidence is rising. Invasive ductal carcinoma is the most common histological subtype while invasive lobular carcinoma is responsible for only 1.5% of the total cases of which pleomorpic lobular carcinoma is an extremely rare variant. We report the case of a gentleman with node positive, pleomorphic lobular carcinoma of the breast.<br><br>CASE PRESENTATION: An elderly gentleman with a past history of type 2 diabetes and long term ethanol use presented to us with a self-discovered palpable lump in the left breast. Physical examination revealed bilateral gynaecomastia along with a well circumscribed subareolar mass and palpable lymphadenopathy in the ipsilateral axilla. The breast nodule revealed atypical cells on fine needle aspiration biopsy and the patient underwent a modified radical mastectomy after systemic surveillance was negative for metastatic disease. The lesion was reported as grade III pleomorphic lobular carcinoma with a lack of E-cadherin expression on immunohistochemistry and the neoplastic cells exhibited strong positivity for estrogen receptor in the absence of Her2 gene amplification. Six out of the eleven dissected regional lymph nodes showed evidence of disease. The patient completed 4&#xa0;cycles of adjuvant chemotherapy without evidence of recurrent disease and was subsequently lost to follow up.<br><br>CONCLUSIONS: Although invasive lobular carcinomas comprise 12% of all female breast cancers, they are very rare in males due to lack of acini and lobules in the normal male breast. Pleomorphic lobular carcinoma, an aggressive variant of ILC is even rarer in males. Chronic consumption of ethanol by our patient may have resulted in some degree of hepatic impairment with resultant hyperestrogenism. This in theory may have been the cause of his gynaecomastia, resultant breast cancer and is a plausible explanation for development of the invasive lobular subtype in a male. The prognosis and clinicopatholocial features of pleomorphic lobular carcinoma in men are less clearly defined due to its rarity. Additional studies are hence necessary to improve our understanding of this disease in males.},
}
@article {pmid24794782,
year = {2014},
author = {Li, X and Luo, R and Jiang, R and Kong, H and Tang, Y and Shu, Y and Hua, W},
title = {The prognostic use of serum concentrations of cardiac troponin-I, CK-MB and myoglobin in patients with idiopathic dilated cardiomyopathy.},
journal = {Heart &amp; lung : the journal of critical care},
volume = {43},
number = {3},
pages = {219-224},
doi = {10.1016/j.hrtlng.2014.03.001},
pmid = {24794782},
issn = {1527-3288},
mesh = {Adult ; Aged ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/diagnostic imaging/mortality ; Cohort Studies ; Creatine Kinase, MB Form/*blood ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Myoglobin/*blood ; Prognosis ; Proportional Hazards Models ; Troponin I/*blood ; },
abstract = {OBJECTIVE: To examine the association between survival and serum concentrations of cTnI, CK-MB, and myoglobin in patients with idiopathic dilated cardiomyopathy (IDC).<br><br>BACKGROUND: It has been suggested that elevated circulating biomarkers of myocardial damage such as cardiac troponin-I (cTnI), creatine kinase MB (CK-MB) and myoglobin are independent risk factors for mortality in patients with heart failure, and recent studies, although limited, showed that there was a potential association between cTnI and the prognosis of patients with dilated cardiomyopathy (DCM).<br><br>METHODS: A cohort study was undertaken in 310 patients with IDC. Standard demographic information, transthoracic echocardiography, and routine blood tests were obtained shortly after hospital admission. Outcome was assessed with all-cause mortality.<br><br>RESULTS: Among the 310 patients studied, 61 (19.7%) died during a mean follow-up of 2.2 years. There was a significant difference in the all-cause mortality rate between patients with serum cTnI >0.05 ng/mL and with cTnI &#x2264; 0.05 ng/mL (37.5% vs 15%, log-rank &#x3c7;(2) = 18.423, P < 0.001). After adjustment for other factors associated with prognosis at baseline, serum cTnI >0.05 ng/mL, QRS duration, NYHA functional class and systolic blood pressure predicted all-cause mortality in patients with IDC. There was no association between circulating CK-MB and myoglobin levels and all-cause mortality in the studied IDC patients.<br><br>CONCLUSION: Serum concentrations of cTnI but not CK-MB or myoglobin are an independent predictor of all-cause mortality in patients with IDC.},
}
@article {pmid24790704,
year = {2014},
author = {Mohamed, MM and Sabet, S and Peng, DF and Nouh, MA and El-Shinawi, M and El-Rifai, W},
title = {Promoter hypermethylation and suppression of glutathione peroxidase 3 are associated with inflammatory breast carcinogenesis.},
journal = {Oxidative medicine and cellular longevity},
volume = {2014},
number = {},
pages = {787195},
pmid = {24790704},
issn = {1942-0994},
mesh = {Breast/pathology ; Breast Neoplasms/enzymology/*pathology ; *DNA Methylation ; Down-Regulation ; Female ; Glutathione Peroxidase/*genetics/metabolism ; Humans ; Middle Aged ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; },
abstract = {Reactive oxygen species (ROS) play a crucial role in breast cancer initiation, promotion, and progression. Inhibition of antioxidant enzymes that remove ROS was found to accelerate cancer growth. Studies showed that inhibition of glutathione peroxidase-3 (GPX3) was associated with cancer progression. Although the role of GPX3 has been studied in different cancer types, its role in breast cancer and its epigenetic regulation have not yet been investigated. The aim of the present study was to investigate GPX3 expression and epigenetic regulation in carcinoma tissues of breast cancer patients' in comparison to normal breast tissues. Furthermore, we compared GPX3 level of expression and methylation status in aggressive phenotype inflammatory breast cancer (IBC) versus non-IBC invasive ductal carcinoma (IDC). We found that GPX3 mRNA and protein expression levels were downregulated in the carcinoma tissues of IBC compared to non-IBC. However, we did not detect significant correlation between GPX3 and patients' clinical-pathological prosperities. Promoter hypermethylation of GPX3 gene was detected in carcinoma tissues not normal breast tissues. In addition, IBC carcinoma tissues showed a significant increase in the promoter hypermethylation of GPX3 gene compared to non-IBC. Our results propose that downregulation of GPX3 in IBC may play a role in the disease progression.},
}
@article {pmid24789732,
year = {2014},
author = {Erro, R and Santangelo, G and Barone, P and Picillo, M and Amboni, M and Longo, K and Giordano, F and Moccia, M and Allocca, R and Pellecchia, MT and Vitale, C},
title = {Do subjective memory complaints herald the onset of mild cognitive impairment in Parkinson disease?.},
journal = {Journal of geriatric psychiatry and neurology},
volume = {27},
number = {4},
pages = {276-281},
doi = {10.1177/0891988714532015},
pmid = {24789732},
issn = {1552-5708},
mesh = {Aged ; Cognitive Dysfunction/complications/diagnosis/*psychology ; Disease Progression ; Educational Status ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Male ; Memory ; Memory Disorders/*diagnosis/psychology ; Middle Aged ; Neuropsychological Tests/statistics &amp; numerical data ; Parkinson Disease/complications/diagnosis/*psychology ; Predictive Value of Tests ; Prospective Studies ; Psychiatric Status Rating Scales/statistics &amp; numerical data ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Longitudinal studies on healthy participants have shown that subjective memory impairment (defined as subjective cognitive complaints with normal cognitive objective performance) might be a strong predictor of mild cognitive impairment (MCI). Parkinson disease (PD) also manifests cognitive disturbances, but whether subjective memory complaints may predict the development of MCI in PD has not yet been explored.<br><br>METHODS: We prospectively screened newly diagnosed, untreated patients with PD in order to evaluate whether subjective memory complaints may predict development of MCI over a 2-year follow-up evaluation.<br><br>RESULTS: We enrolled 76 de novo untreated patients with PD. Of the 76 patients, 23 (30.3%) complained memory issues. Among the patients cognitively unimpaired at baseline, those with subjective complaints were more likely to develop MCI at follow-up. The regression model confirmed that presence of subjective memory complaints at baseline was an independent predictor of development of MCI at follow-up.<br><br>DISCUSSION: This is the first prospective study to explore the relationship between subjective and objective cognitive deficits in newly diagnosed, untreated patients. Our results provide preliminary evidence that subjective memory complaints might predict future development of MCI.},
}
@article {pmid24786829,
year = {2014},
author = {Paul, A and Gunewardena, S and Stecklein, SR and Saha, B and Parelkar, N and Danley, M and Rajendran, G and Home, P and Ray, S and Jokar, I and Vielhauer, GA and Jensen, RA and Tawfik, O and Paul, S},
title = {PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis.},
journal = {Cell death and differentiation},
volume = {21},
number = {9},
pages = {1469-1481},
pmid = {24786829},
issn = {1476-5403},
support = {HL094892/HL/NHLBI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R01 HD062546/HD/NICHD NIH HHS/United States ; R21 HL094892/HL/NHLBI NIH HHS/United States ; HD075233/HD/NICHD NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; R21 HD075233/HD/NICHD NIH HHS/United States ; R21 HL104322/HL/NHLBI NIH HHS/United States ; HD062546/HD/NICHD NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; },
mesh = {Animals ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Isoenzymes/genetics/*metabolism ; Lung Neoplasms/metabolism/pathology/*secondary ; Mice ; Mice, Inbred NOD ; Mice, Nude ; Mice, SCID ; Neoplasm Transplantation ; Protein Kinase C/genetics/*metabolism ; *Signal Transduction ; Triple Negative Breast Neoplasms/*metabolism/*pathology ; },
abstract = {Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), and the patients with TNBC are often diagnosed with higher rates of recurrence and metastasis. Because of the absence of ER, PR and HER2/neu expressions, TNBC patients are insensitive to HER2-directed and endocrine therapies available for breast cancer treatment. Here, we report that expression of atypical protein kinase C isoform, PKCλ/ι, significantly increased and activated in all invasive breast cancer (invasive ductal carcinoma or IDC) subtypes including the TNBC subtype. Because of the lack of targeted therapies for TNBC, we choose to study PKCλ/ι signaling as a potential therapeutic target for TNBC. Our observations indicated that PKCλ/ι signaling is highly active during breast cancer invasive progression, and metastatic breast cancers, the advanced stages of breast cancer disease that developed more frequently in TNBC patients, are also characterized with high levels of PKCλ/ι expression and activation. Functional analysis in experimental mouse models revealed that depletion of PKCλ/ι significantly reduces TNBC growth as well as lung metastatic colonization. Furthermore, we have identified a PKCλ/ι-regulated gene signature consisting of 110 genes, which are significantly associated with indolent to invasive progression of human breast cancer and poor prognosis. Mechanistically, cytokines such as TGFβ and IL1β could activate PKCλ/ι signaling in TNBC cells and depletion of PKCλ/ι impairs NF-κB p65 (RelA) nuclear localization. We observed that cytokine-PKCλ/ι-RelA signaling axis, at least in part, involved in modulating gene expression to regulate invasion of TNBC cells. Overall, our results indicate that induction and activation of PKCλ/ι promote TNBC growth, invasion and metastasis. Thus, targeting PKCλ/ι signaling could be a therapeutic option for breast cancer, including the TNBC subtype.},
}
@article {pmid24781343,
year = {2016},
author = {Madden, NA and Macdonald, OK and Call, JA and Schomas, DA and Lee, CM and Patel, S},
title = {Radiotherapy and Male Breast Cancer: A Population-based Registry Analysis.},
journal = {American journal of clinical oncology},
volume = {39},
number = {5},
pages = {458-462},
doi = {10.1097/COC.0000000000000078},
pmid = {24781343},
issn = {1537-453X},
mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*mortality/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*mortality/*radiotherapy/secondary/surgery ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Mastectomy/methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; SEER Program ; Survival Rate ; Tumor Burden ; United States/epidemiology ; },
abstract = {BACKGROUND: The local-regional management of female breast cancer has been extensively investigated worldwide. The optimal approach for males diagnosed with breast cancer is less clear. We have analyzed the treatment of male breast cancer using a population-based national registry to determine the impact of surgery and radiation therapy on survival.<br><br>MATERIALS AND METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried to identify males with invasive ductal carcinoma of the breast who underwent primary surgical resection (radical mastectomy, modified radical mastectomy, total mastectomy, or segmental) for the years 1983 to 2002. Demographic, clinical, and pathologic data were culled and analyzed to determine the impact of radiation therapy (RT) following resection. Survival rates were estimated using the Kaplan-Meier method and significance was determined using the log-rank test (P<0.05). Multivariate analysis with the Cox proportional hazards model was performed to determine factors significant for overall (OS) and cause-specific survival (CSS).<br><br>RESULTS: A total of 1337 patients met the eligibility criteria and were analyzed. Median follow-up was 7.3 years (range, 1 mo to 25 y). Most men underwent modified radical mastectomy (n=1062) with a minority undergoing segmental (n=113). About 329 men received postoperative external beam RT. The median rates of OS and CSS for all men were 10.5 years and not yet reached, respectively. The surgical procedure did not significantly associate with OS or CSS. By stage, RT was associated with improved OS for stage I (P=0.03). There was a trend for improved survival with stage II (P=0.21) and III (P=0.15). RT was not associated with improved CSS by stage. RT improved rates of OS and CSS in N2 patients without reaching statistical significance (P=0.10 and 0.22). On multivariate analysis, advancing age, stage and grade, and no postoperative RT predicted for worse OS. However, when controlled for those with known hormone receptor status (n=978), only the factors of advancing age, stage, grade, and hormone receptor negativity predicted for worse OS. Advancing age, stage, and grade were the only predictors of CSS irrespective of the cohort analyzed.<br><br>CONCLUSIONS: The primary surgical procedure did not ultimately influence OS or CSS in this population-based registry of males with breast cancer. A statistically nonsignificant improvement with postoperative RT was observed in men with lymph node involvement, larger tumor size, or higher stage. When controlled for age, stage, and grade in multivariate analysis, postoperative RT predicted for improved OS but not CSS. These data suggest a beneficial effect of RT in the postoperative setting. A prospective study is necessary to further elucidate appropriate treatment strategies for men with breast cancer.},
}
@article {pmid24781337,
year = {2014},
author = {Petrović, N and Mandušić, V and Dimitrijević, B and Roganović, J and Lukić, S and Todorović, L and Stanojević, B},
title = {Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia.},
journal = {Medical oncology (Northwood, London, England)},
volume = {31},
number = {6},
pages = {977},
pmid = {24781337},
issn = {1559-131X},
mesh = {Aged ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; Female ; Humans ; MicroRNAs/*genetics/metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Reference Values ; Serbia ; },
abstract = {MicroRNAs play essential role in breast carcinoma progression and invasion. Our principal goals were to assess clinicopathological and prognostic correlations of microRNA-21 (miR-21) expression levels in a group of 39 Serbian breast cancer patients with invasive lobular (ILC), ductal (IDC), or mixed (ILC-IDC) breast carcinomas and in order to discover the role of miR-21 in potential novel form of stratification of the patients with different estrogen receptor (ER) and progesterone receptor (PR) status. MiR-21 expression levels were measured by stem-loop real-time RT-PCR using TaqMan technology. ER, PR, human epidermal growth factor 2 receptor (Her-2), and proliferative index (Ki-67) were evaluated by immunohistochemistry. MiR-21 levels do not vary among ILC, IDC, and ILC-IDC subgroups. MiR-21 expression levels varied significantly in the age, tumor size, Ki-67, and different grade (p = 0.030, p = 0.036, p = 0.027 and p = 0.032, respectively) subgroups. ER+ and PR+ showed higher miR-21 levels than their negative receptor status paired groups ER- and PR- with p = 0.012 and p = 0.018, respectively. MiR-21 positively correlated with ER and PR status (p = 0.018, ρ = 0.379 and p = 0.034, ρ = 0.345, respectively). Our findings suggest that miR-21 emulates transitional form of expression and that the levels of expression might be useful for stratification of the patients with different receptor status with the purpose to seek for new therapy approaches especially for the patients with the lack of response to conventional endocrine therapy.},
}
@article {pmid24768572,
year = {2014},
author = {Purushotham, A and Shamil, E and Cariati, M and Agbaje, O and Muhidin, A and Gillett, C and Mera, A and Sivanadiyan, K and Harries, M and Sullivan, R and Pinder, SE and Garmo, H and Holmberg, L},
title = {Age at diagnosis and distant metastasis in breast cancer--a surprising inverse relationship.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {50},
number = {10},
pages = {1697-1705},
doi = {10.1016/j.ejca.2014.04.002},
pmid = {24768572},
issn = {1879-0852},
mesh = {Adult ; Age Factors ; Aged ; Biomarkers, Tumor/analysis ; Bone Neoplasms/chemistry/mortality/*secondary/therapy ; Breast Neoplasms/chemistry/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary/therapy ; Carcinoma, Lobular/chemistry/mortality/*secondary/therapy ; Disease-Free Survival ; ErbB Receptors/analysis ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Proportional Hazards Models ; Prospective Studies ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Registries ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Burden ; },
abstract = {INTRODUCTION: Predictors for site of distant metastasis and impact on survival in breast cancer are incompletely understood.<br><br>METHODS: Clinico-pathological risk factors for site of distant metastasis and survival were analysed in patients with invasive breast cancer treated between 1986 and 2006.<br><br>RESULTS: Of 3553 patients, with median follow-up 6.32years, 825 (23%) developed distant metastasis. The site of metastasis was bone in 196/825 (24%), viscera in 540/825 (65%) and unknown in 89 (11%). Larger primary invasive tumour size, higher tumour grade and axillary nodal positivity increased risk of metastasis to all sites. Lobular carcinoma was more likely to first metastasise to bone compared to invasive ductal carcinoma (NST). Oestrogen receptor (ER) negative, progesterone receptor (PgR) negative and/or Human epidermal growth factor (HER2) positive tumours were more likely to metastasise to viscera. A striking relationship between increasing age at diagnosis and a reduction in risk of distant metastasis to bone and viscera was observed. Median time to death from onset of metastatic disease was 1.52 (Interquartile range (IQR) 0.7-2.9)years for patients with bone metastasis and 0.7 (IQR 0.2-1.5)years for visceral metastasis. On multivariate analysis, despite the decrease in risk of distant metastasis with increasing age, there was an elevated hazard for death in patients >50years at diagnosis of metastasis if they developed bone metastasis, with a similar trend observed in the >70years age group if they developed visceral metastasis.<br><br>CONCLUSION: These findings indicate that there are biological mechanisms underlying the impact of age on the development of distant metastasis and subsequent death. This may have important implications in the treatment of breast cancer.},
}
@article {pmid24762482,
year = {2014},
author = {Singh, R and Gupta, S and Pawar, SB and Pawar, RS and Gandham, SV and Prabhudesai, S},
title = {Evaluation of ER, PR and HER-2 receptor expression in breast cancer patients presenting to a semi urban cancer centre in Western India.},
journal = {Journal of cancer research and therapeutics},
volume = {10},
number = {1},
pages = {26-28},
doi = {10.4103/0973-1482.131348},
pmid = {24762482},
issn = {1998-4138},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/*metabolism ; Cancer Care Facilities ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; India ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Retrospective Studies ; Risk Factors ; Urban Health Services ; Young Adult ; },
abstract = {BACKGROUND: Hormone receptor expression has been reported to be low in breast cancer patients from developing countries. The pattern of receptor expression from urban and rural areas is not well studied.<br><br>MATERIALS AND METHODS: This is a retrospective analysis of 206 consecutive breast cancer patients presenting to a semi urban cancer centre from 2009-2010. The demographic and clinical variables included age, residential area (rural, semi urban, or urban), menopausal status, and clinical stage. The pathological variables included tumor type, the presence of ductal carcinoma in situ, lymphovascular invasion, and expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) receptors by immunohistochemical (IHC) analysis.<br><br>RESULTS: The majority of patients were postmenopausal with the median age of 50 years. Invasive ductal carcinoma was the most common subtype (94%). The ER status was available in 101 (49.3%), PR in 99 (48.0%), and HER2 in 82 (39.8%) cases. In patients in whom this data were available, ER was positive in 44.6%, PR in 40.4%, and HER2 in 34.2%. Out of the 82 patients in whom data on all three receptors were available, 34.1% patients had triple negative tumors. Analysis of our data showed a trend toward increasing ER and PR expression with age but this was not statistically significant. The average age of menopause was between 40-50 years of age.<br><br>CONCLUSION: This report is an important documentation of the pathological characteristics in a predominantly rural/semi urban population of Indian breast cancer patients. Further studies from other centers with a similar background are required to confirm these results.},
}
@article {pmid24759678,
year = {2014},
author = {Ramos, CS and Gonçalves, AS and Marinho, LC and Gomes Avelino, MA and Saddi, VA and Lopes, AC and Simões, RT and Wastowski, IJ},
title = {Analysis of HLA-G gene polymorphism and protein expression in invasive breast ductal carcinoma.},
journal = {Human immunology},
volume = {75},
number = {7},
pages = {667-672},
doi = {10.1016/j.humimm.2014.04.005},
pmid = {24759678},
issn = {1879-1166},
mesh = {Alleles ; Breast Neoplasms/*genetics/immunology/mortality/pathology ; Carcinoma, Ductal, Breast/*genetics/immunology/mortality/pathology ; Case-Control Studies ; Female ; Gene Expression ; Gene Frequency ; HLA-G Antigens/*genetics/immunology ; Humans ; *INDEL Mutation ; Lymph Nodes/immunology/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Survival Analysis ; },
abstract = {The human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule predominantly expressed in trophoblastic placental cells to protect the fetus during pregnancy. However, evidence has shown that this molecule may be implicated in the immune escape mechanism of tumor cells. Thus, the aim of this study was to evaluate the frequency of 14-bp insertion/deletion HLA-G polymorphism, as well as the expression of this molecule in patients with invasive breast ductal carcinoma (IDC). A significant association between the expression of HLA-G and the presence of metastasis in lymph nodes (p=0.01) was observed and the expression of HLA-G was significantly higher in patients with shorter survival time (p=0.03). The analysis suggests that the polymorphism observed in patients with IDC may be inducing a higher expression of the HLA-G molecule, which may possibly contribute to shorter survival time and a worse clinical prognosis for such patients.},
}
@article {pmid24756760,
year = {2014},
author = {Do, SI and Ko, E and Kang, SY and Lee, JE and Nam, SJ and Cho, EY and Kim, DH},
title = {Aberrant DNA methylation of integrin α4 in human breast cancer.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {35},
number = {7},
pages = {7079-7084},
pmid = {24756760},
issn = {1423-0380},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; CpG Islands/*genetics ; DNA Methylation/*genetics ; Female ; Humans ; Integrin alpha4/*genetics ; Lymphatic Metastasis ; MCF-7 Cells ; Middle Aged ; Neoplasm Staging ; Prognosis ; Promoter Regions, Genetic ; Receptor, ErbB-2/metabolism ; Signal Transduction ; },
abstract = {Integrins are cell surface receptors that mediate cell-cell/extracellular interactions and have shown an association with metastasis or transformation in several cancers. However, the correlation between the clinicopathological status of breast cancer and the altered integrin α4 status is not clear. In this study, we investigated DNA methylation of integrin α4 in breast cancer. We retrieved 351 cases of surgically resected breast cancer (290 invasive carcinoma and 61 intraductal carcinoma). Methylation-specific polymerase chain reaction was performed to determine integrin α4 methylation status. Integrin α4 methylation was frequently observed in breast cancer specimens (145/351 cases, 41.3 %). In addition, DNA methylation of integrin α4 showed statistical correlation with HER2 positivity and higher histologic grade (p = 0.001, 0.008 in ductal carcinoma in situ and 0.003 in invasive ductal carcinoma). However, other clinicopathological data such as estrogen receptor, progesterone receptor, metastasis, and TNM status showed no statistical correlation. Moreover, we found that the downregulated expression of integrin α4 in a heavily methylated breast cancer cell line (ZR-75) was restored by treatment with 5-aza-2'deoxycytidine, a DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. We observed that integrin α4 methylation is associated with the histologic grade of tumors and lymph node metastasis. Also, this data supports a previous study that suggested integrin α4 and HER2 are involved in the same signaling pathway. DNA methylation of integrin α4 may be a poor prognostic factor which affects undifferentiated histologic change of breast cancer.},
}
@article {pmid24748104,
year = {2014},
author = {Ruan, X and Liu, H and Boardman, L and Kocher, JP},
title = {Genome-wide analysis of loss of heterozygosity in breast infiltrating ductal carcinoma distant normal tissue highlights arm specific enrichment and expansion across tumor stages.},
journal = {PloS one},
volume = {9},
number = {4},
pages = {e95783},
pmid = {24748104},
issn = {1932-6203},
support = {P30 CA015083/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Chromosome Fragile Sites ; Chromosome Mapping ; *Chromosomes, Human ; Female ; *Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; *Loss of Heterozygosity ; Neoplasm Staging ; },
abstract = {Studies have shown concurrent loss of heterozygosity (LOH) in breast infiltrating ductal carcinoma (IDC) and adjacent or distant normal tissue. However, the overall extent of LOH in normal tissue and their significance to tumorigenesis remain unknown, as existing studies are largely based on selected microsatellite markers. Here we present the first autosome-wide study of LOH in IDC and distant normal tissue using informative loci deduced from SNP array-based and sequencing-based techniques. We show a consistently high LOH concurrence rate in IDC (mean = 24%) and distant normal tissue (m = 54%), suggesting for most patients (31/33) histologically normal tissue contains genomic instability that can be a potential marker of increased IDC risk. Concurrent LOH is more frequent in fragile site related genes like WWOX (9/31), NTRK2 (10/31), and FHIT (7/31) than traditional genetic markers like BRCA1 (0/23), BRCA2 (2/29) and TP53 (1/13). Analysis at arm level shows distant normal tissue has low level but non-random enrichment of LOH (topped by 8p and 16q) significantly correlated with matched IDC (Pearson r = 0.66, p = 3.5E-6) (topped by 8p, 11q, 13q, 16q, 17p, and 17q). The arm-specific LOH enrichment was independently observed in tumor samples from 548 IDC patients when stratified by tumor size based T stages. Fine LOH structure from sequencing data indicates LOH in low order tissues non-randomly overlap (∼67%) with LOH that usually has longer tract length (the length of genomic region affected by LOH) in high order tissues. The consistent observations from multiple datasets suggest progressive LOH in the development of IDC potentially through arm-specific pile up effect with discernible signature in normal tissue. Our finding also suggests that LOH detected in IDC by comparing to paired adjacent or distant normal tissue are more likely underestimated.},
}
@article {pmid24744949,
year = {2014},
author = {Santivasi, WL and Routt, MM and Terando, AM},
title = {Idiopathic thrombocytopenic purpura after mastectomy and axillary lymph node dissection.},
journal = {Case reports in surgery},
volume = {2014},
number = {},
pages = {316064},
pmid = {24744949},
issn = {2090-6900},
abstract = {First described in 1916, idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease resulting in the destruction of platelets. Here, we present a case of an 85-year-old patient diagnosed with invasive ductal carcinoma of the breast whose surgical treatment was complicated postoperatively by acute-onset thrombocytopenia with a resultant hematoma at the operative site. Diagnostic Workup revealed no clear etiology for the thrombocytopenia; therefore, a presumptive diagnosis of idiopathic thrombocytopenic purpura was made. Previous literature has associated the development of idiopathic thrombocytopenic purpura with breast cancer. However, to the authors' knowledge, there are no reported cases of ITP presenting immediately following surgical intervention for breast cancer in the absence of other etiologic factors.},
}
@article {pmid24743323,
year = {2014},
author = {Sawyer, E and Roylance, R and Petridis, C and Brook, MN and Nowinski, S and Papouli, E and Fletcher, O and Pinder, S and Hanby, A and Kohut, K and Gorman, P and Caneppele, M and Peto, J and Dos Santos Silva, I and Johnson, N and Swann, R and Dwek, M and Perkins, KA and Gillett, C and Houlston, R and Ross, G and De Ieso, P and Southey, MC and Hopper, JL and Provenzano, E and Apicella, C and Wesseling, J and Cornelissen, S and Keeman, R and Fasching, PA and Jud, SM and Ekici, AB and Beckmann, MW and Kerin, MJ and Marme, F and Schneeweiss, A and Sohn, C and Burwinkel, B and Guénel, P and Truong, T and Laurent-Puig, P and Kerbrat, P and Bojesen, SE and Nordestgaard, BG and Nielsen, SF and Flyger, H and Milne, RL and Perez, JI and Menéndez, P and Benitez, J and Brenner, H and Dieffenbach, AK and Arndt, V and Stegmaier, C and Meindl, A and Lichtner, P and Schmutzler, RK and Lochmann, M and Brauch, H and Fischer, HP and Ko, YD and , and Nevanlinna, H and Muranen, TA and Aittomäki, K and Blomqvist, C and Bogdanova, NV and Dörk, T and Lindblom, A and Margolin, S and Mannermaa, A and Kataja, V and Kosma, VM and Hartikainen, JM and Chenevix-Trench, G and , and Lambrechts, D and Weltens, C and Van Limbergen, E and Hatse, S and Chang-Claude, J and Rudolph, A and Seibold, P and Flesch-Janys, D and Radice, P and Peterlongo, P and Bonanni, B and Volorio, S and Giles, GG and Severi, G and Baglietto, L and McLean, CA and Haiman, CA and Henderson, BE and Schumacher, F and Le Marchand, L and Simard, J and Goldberg, MS and Labrèche, F and Dumont, M and Kristensen, V and Winqvist, R and Pylkäs, K and Jukkola-Vuorinen, A and Kauppila, S and Andrulis, IL and Knight, JA and Glendon, G and Mulligan, AM and Devillee, P and Tollenaar, RA and Seynaeve, CM and Kriege, M and Figueroa, J and Chanock, SJ and Sherman, ME and Hooning, MJ and Hollestelle, A and van den Ouweland, AM and van Deurzen, CH and Li, J and Czene, K and Humphreys, K and Cox, A and Cross, SS and Reed, MW and Shah, M and Jakubowska, A and Lubinski, J and Jaworska-Bieniek, K and Durda, K and Swerdlow, A and Ashworth, A and Orr, N and Schoemaker, M and Couch, FJ and Hallberg, E and González-Neira, A and Pita, G and Alonso, MR and Tessier, DC and Vincent, D and Bacot, F and Bolla, MK and Wang, Q and Dennis, J and Michailidou, K and Dunning, AM and Hall, P and Easton, D and Pharoah, P and Schmidt, MK and Tomlinson, I and Garcia-Closas, M},
title = {Genetic predisposition to in situ and invasive lobular carcinoma of the breast.},
journal = {PLoS genetics},
volume = {10},
number = {4},
pages = {e1004285},
pmid = {24743323},
issn = {1553-7404},
support = {U01 CA069638/CA/NCI NIH HHS/United States ; U01 CA69417/CA/NCI NIH HHS/United States ; UM1 CA164920/CA/NCI NIH HHS/United States ; U01 CA069467/CA/NCI NIH HHS/United States ; 16565/CRUK_/Cancer Research UK/United Kingdom ; 16459/CRUK_/Cancer Research UK/United Kingdom ; 2010NOVPR61/BBC_/Breast Cancer Now/United Kingdom ; R01 CA128978/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; 090532/WT_/Wellcome Trust/United Kingdom ; R01 CA132839/CA/NCI NIH HHS/United States ; 090532/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; CA098758/CA/NCI NIH HHS/United States ; U01 CA069417/CA/NCI NIH HHS/United States ; CA54281/CA/NCI NIH HHS/United States ; CA63464/CA/NCI NIH HHS/United States ; C490/A10124/CRUK_/Cancer Research UK/United Kingdom ; C1287/A12014/CRUK_/Cancer Research UK/United Kingdom ; R01 CA063464/CA/NCI NIH HHS/United States ; 16563/CRUK_/Cancer Research UK/United Kingdom ; R01 CA054281/CA/NCI NIH HHS/United States ; U01 CA69638/CA/NCI NIH HHS/United States ; U01 CA063464/CA/NCI NIH HHS/United States ; U01 CA098758/CA/NCI NIH HHS/United States ; CA132839/CA/NCI NIH HHS/United States ; C1287/A10118/CRUK_/Cancer Research UK/United Kingdom ; U01 CA69467/CA/NCI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; 16561/CRUK_/Cancer Research UK/United Kingdom ; 10124/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Breast Neoplasms/*genetics ; Carcinoma in Situ/*genetics ; Carcinoma, Lobular/*genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Genotype ; Humans ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; },
abstract = {Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.},
}
@article {pmid24743129,
year = {2014},
author = {Gudadze, M and Kankava, Q and Mariamidze, A and Burkadze, G},
title = {Features of CD44+/CD24-low phenotypic cell distribution in relation to predictive markers and molecular subtypes of invasive ductal carcinoma of the breast.},
journal = {Georgian medical news},
volume = {},
number = {228},
pages = {81-87},
pmid = {24743129},
issn = {1512-0112},
mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/*pathology ; CD24 Antigen/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*pathology ; Female ; Humans ; Hyaluronan Receptors/*metabolism ; Middle Aged ; Neoplastic Stem Cells/metabolism/pathology ; Phenotype ; Prognosis ; Young Adult ; },
abstract = {Breast cancer is the most widespread pathology among women. Despite the current progresses in research and treatment of metastatic breast cancer, mortality caused by this disease is still high, because above mentioned therapy is limited due to existence of cells resistant to therapy . Cancer stem cells are the only cells with ability of unlimited proliferative activity and cancerous potential, thus, they participate in the growth, progression and dissemination of cancer. Cancer stem cells are resistant to various forms of therapy, including chemotherapy and radiotherapy . Results of examination showed that 50% of all cases are positive on so called markers of stem cells, thus 45% of cases are negative. CD44+/CD24-low cases (cases that reveal stem cell-phenotype) in the group of invasive ductal carcinoma of Luminal A molecular subtype are almost as many as CD44+/CD24+ and CD44-/CD24+ phenotype cancers. In this group non-stem phenotype cases are 65%, so 5 times more than stem cell phenotype cancers. 1324 postoperative breast materials studied through 2008-2012 at the laboratory of "Pathgeo-Union of Pathologists" LTD and Academician N. Kipshidze Central University Clinic were used as test materials and specimens from 393 patients with invasive ductal carcinoma were selected. CD44/CD24 markers' expression in phenotypically different cancers and clinic-pathologic parameters as well as various biological features was conducted by the Pearson's correlation analysis and using X2 test. Statistical analysis of obtained numeral data was held using SPSS V.19.0 program. Confidence interval of 95% was considered statistically significant. Stem cell phenotype positive cases are with the highest percentage represented in Luminal B and basal-like molecular subgroup that to our minds is associated with their aggressive behavior and resistance to chemotherapy. Relatively good prognosis and response to chemotherapy of Luminal A molecular subtype cancers are to be stipulated by lower percentage of cases with stem cells phenotype. With regard to the dimension of cancer the analysis of stem cell phenotype cancers showed that frequency of stem cell phenotype (CD44+/CD24-low) dramatically increases from T1 to T4 cancers. High density of stem cell phenotype cancers in cancers with metastatic lymphatic nodes proves that presence of mentioned phenotype plays a role in progression and dissemination. On the one hand, little amount of stem cells phenotype cancers (CD44+/CD24-low), on the other hand absence of negative cases for markers of stem cell in Her2 subtype makes us consider that come phenotype, close to stem-cell phenotype, plays the leading role in Her2 positive cases.},
}
@article {pmid24725754,
year = {2014},
author = {Moccia, M and Picillo, M and Erro, R and Vitale, C and Longo, K and Amboni, M and Santangelo, G and Spina, E and De Rosa, A and De Michele, G and Santoro, L and Barone, P and Pellecchia, MT},
title = {Is serum uric acid related to non-motor symptoms in de-novo Parkinson's disease patients?.},
journal = {Parkinsonism &amp; related disorders},
volume = {20},
number = {7},
pages = {772-775},
doi = {10.1016/j.parkreldis.2014.03.016},
pmid = {24725754},
issn = {1873-5126},
mesh = {Adult ; Aged ; Biomarkers/blood ; Cardiovascular Diseases/blood/complications/diagnosis ; Cross-Sectional Studies ; Female ; Humans ; Male ; Mental Disorders/blood/complications/diagnosis ; Middle Aged ; Parkinson Disease/*blood/complications/*diagnosis ; Pilot Projects ; Uric Acid/*blood ; },
abstract = {BACKGROUND: Low serum uric acid (UA) has been consistently shown to be associated with increased risk of Parkinson's disease (PD), and to predict faster motor and cognitive decline in established PD. The aim of the present study is to evaluate the relationship between serum UA and non-motor symptoms (NMS) in de novo PD.<br><br>METHODS: Serum UA was measured in consecutively recruited, early drug-na&#xef;ve PD patients. Exclusion criteria were: treatment with UA modifying drugs; current smoking status; metabolic or cardiac morbidity. All patients completed the NMS Questionnaire (NMSQuest). The relationship between UA levels and NMSQuest domains was explored by logistic regression, subsequently adjusted for age, gender, disease duration (months since reported motor onset) UPDRS part III, H&amp;Y scale, and MMSE. Regression analysis studied the overall relationship between UA levels and total NMS score, and was subsequently adjusted for age, gender, disease duration UPDRS part III, H&amp;Y scale and MMSE.<br><br>RESULTS: Eighty PD patients were recruited. At logistic regression, higher UA levels were related to lower involvement of Attention/Memory (p = 0.004), Cardiovascular (0.009) and Sleep (p = 0.028) domains of NMSQuest. UA levels showed a significant negative correlation with total NMSQuest score at regression analysis (p = 0.001; Adjusted R-squared = 0.319).<br><br>DISCUSSION: The present study investigated, for the first time, the relationship between NMSQuest and UA in de novo PD. Lower UA was related to higher NMSQuest total score and in particular to Attention/Memory, Cardiovascular and Sleep domains. Thus, UA seems to be a major candidate to be a valuable biomarker of such early features of PD as NMS.},
}
@article {pmid24715382,
year = {2014},
author = {McNamara, KM and Yoda, T and Nurani, AM and Shibahara, Y and Miki, Y and Wang, L and Nakamura, Y and Suzuki, K and Yang, Y and Abe, E and Hirakawa, H and Suzuki, T and Nemoto, N and Miyashita, M and Tamaki, K and Ishida, T and Brown, KA and Ohuchi, N and Sasano, H},
title = {Androgenic pathways in the progression of triple-negative breast carcinoma: a comparison between aggressive and non-aggressive subtypes.},
journal = {Breast cancer research and treatment},
volume = {145},
number = {2},
pages = {281-293},
doi = {10.1007/s10549-014-2942-6},
pmid = {24715382},
issn = {1573-7217},
mesh = {3-Hydroxysteroid Dehydrogenases/genetics/metabolism ; Aldo-Keto Reductase Family 1 Member C3 ; Androgens/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cholestenone 5 alpha-Reductase/genetics/metabolism ; Dihydrotestosterone/pharmacology ; ErbB Receptors/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hydroxyprostaglandin Dehydrogenases/genetics/metabolism ; Keratin-5/metabolism ; Keratin-6/metabolism ; Receptors, Androgen/metabolism ; Triple Negative Breast Neoplasms/drug therapy/*metabolism/*pathology ; },
abstract = {One of the active intracellular pathways/networks in triple-negative breast carcinoma (TNBC) is that of the androgen receptor (AR). In this study, we examined AR and androgen-metabolising enzyme immunoreactivity in subcategories of TNBC to further elucidate the roles of androgenic pathways in TNBC. We utilised formalin-fixed paraffin-embedded breast cancer samples from ductal carcinoma in situ (DCIS) and invasive ductal carcinoma patient cohorts. We then used immunohistochemistry to classify these samples into basal-like and non-basal samples and to assess interactions between AR, androgen-metabolising enzymes and proliferation. To further substantiate our hypothesis and provide mechanistic insights, we also looked at the expression and regulation of these factors in publically available microarray data and in a panel of TNBC AR-positive cell lines. DCIS was associated with higher levels of AR and enzymes (p < 0.02), although a similar difference was not noticed in basal and non-basal samples. AR and enzymes were correlated in all states. In TNBC cell lines (MDA-MD-453, MFM-223 and SUM185-PE), we found that DHT treatment up-regulated 5αR1 and 17βHSD5 suggesting a mechanistic explanation for the correlations observed in the histological samples. Publicly available microarray data in TNBC cases suggested similar patterns to those observed in histological samples. In the majority of settings, including publically available microarray data, an inverse association between AR and proliferation was detected. These findings suggest that decreases in AR and androgen-metabolising enzymes may be involved in the increased biological aggressiveness in TNBC development.},
}
@article {pmid24713490,
year = {2014},
author = {Ruiz Santiago, F and Pozuelo Calvo, R and Almansa López, J and Guzmán Álvarez, L and Castellano García, MDM},
title = {T2 mapping in patellar chondromalacia.},
journal = {European journal of radiology},
volume = {83},
number = {6},
pages = {984-988},
doi = {10.1016/j.ejrad.2014.03.007},
pmid = {24713490},
issn = {1872-7727},
mesh = {Adolescent ; Adult ; *Algorithms ; Arthralgia/*diagnosis/*etiology ; Chondromalacia Patellae/*complications/*pathology ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Young Adult ; },
abstract = {OBJECTIVE: To study the correlation between the T2 relaxation times of the patellar cartilage and morphological MRI findings of chondromalacia.<br><br>METHODS: This prospective study comprises 50 patients, 27 men and 23 women suffering of anterior knee pain (mean age: 29.7, SD 8.3 years; range: 16-45 years). MRI of 97 knees were performed in these patients at 1.5T magnet including sagittal T1, coronal intermediate, axial intermediate fat sat and T2 mapping. Chondromalacia was assessed using a modified version of Noyes classification. The relaxation time, T2, was studied segmenting the full thickness of the patellar cartilage in 12 areas: 4 proximal (external facet-proximal-lateral (EPL), external facet-proximal-central (EPC), internal facet-proximal-central (IPC), internal facet-proximal-medial (IPM), 4 in the middle section (external facet-middle-lateral (EML), external facet-middle-central (EMC), internal facet-middle-central (IMC), internal facet-middle-medial (IMM) and 4 distal (external facet-distal-lateral (EDL), external facet-distal-central (EDC), internal facet-distal-central (IDC), internal facet-distal-medial (IDM).<br><br>RESULTS: T2 values showed a significant increase in mild chondromalacia regarding normal cartilage in most of the cartilage areas (p<0.05), except in the internal distal facet (IDC and IDM), EPC, EDL, and IMM. Severe chondromalacia was characterized by a fall of T2 relaxation times with loss of statistical significant differences in comparison with normal cartilage, except in EMC and IMC, where similar values as mild chondromalacia were maintained (p<0.05).<br><br>CONCLUSIONS: Steepest increase in T2 values of patellar cartilage occurs in early stages of patellar cartilage degeneration. Progression of morphologic changes of chondromalacia to more severe degrees is associated to a new drop of T2 relaxation times approaching basal values in most of the areas of the patellar cartilage, except in the central area of the middle section, where T2 values remain increased.},
}
@article {pmid24708527,
year = {2014},
author = {Schoellhammer, HF and Hsu, F and Vito, C and Chu, P and Park, J and Waisman, J and Kim, J},
title = {Complete pathologic response of HER2-positive breast cancer liver metastasis with dual anti-HER2 antagonism.},
journal = {BMC cancer},
volume = {14},
number = {},
pages = {242},
pmid = {24708527},
issn = {1471-2407},
mesh = {Antibodies, Monoclonal, Humanized/*administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage ; Breast Neoplasms/*drug therapy/genetics/pathology ; Clinical Trials as Topic ; Female ; Humans ; Liver Neoplasms/*drug therapy/pathology/secondary ; Middle Aged ; Molecular Targeted Therapy ; Receptor, ErbB-2/antagonists &amp; inhibitors/*genetics ; Trastuzumab ; },
abstract = {BACKGROUND: Although breast cancer frequently metastasizes to the bones and brain, rarely breast cancer patients may develop isolated liver metastasis. There is increasing data that anti-HER2 targeted therapy in conjunction with systemic chemotherapy may lead to increased rates of pathologic complete response in the primary breast cancer. However, little is known about its effects on metastatic liver disease.<br><br>CASE PRESENTATION: We report the treatment of a 54-year-old female who was diagnosed with HER2-positive invasive ductal carcinoma and synchronous breast cancer liver metastasis (BCLM). The patient underwent eight cycles of standard docetaxel with two anti-HER2 targeted agents, trastuzumab and pertuzumab. Subsequent radiographic imaging demonstrated complete radiographic response in the primary lesion with an approximate 75% decrease in the liver metastasis. After informed consent the patient underwent modified radical mastectomy that revealed pathologic complete response. Re-staging demonstrated no new disease outside the liver and a left hepatectomy was performed for resection of BCLM. Final pathologic examination revealed no residual malignant cells in the liver specimen, indicating pathologic complete response. Herein, we discuss the anti-HER2 targeted agents trastuzumab and pertuzumab and review the data on dual HER2 antagonism for HER2-positive breast cancer and the role of surgical resection of BCLM.<br><br>CONCLUSIONS: The role of targeted agents for metastatic HER2-positive breast cancer is under active clinical trial investigation and we await the maturation of trial results and long-term survival data. Our results suggest that these agents may also be effective for producing considerable pathologic response in patients with BCLM.},
}
@article {pmid24687377,
year = {2014},
author = {Yang, F and Zhou, X and Miao, X and Zhang, T and Hang, X and Tie, R and Liu, N and Tian, F and Wang, F and Yuan, J},
title = {MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast cancer metastasis.},
journal = {Breast cancer research and treatment},
volume = {145},
number = {1},
pages = {23-32},
pmid = {24687377},
issn = {1573-7217},
mesh = {Adult ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/analysis ; Blotting, Western ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Epithelial-Mesenchymal Transition/physiology ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Metastasis ; Neoplasm Proteins/*metabolism ; Prognosis ; Risk Factors ; Tissue Array Analysis ; },
abstract = {MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.},
}
@article {pmid24655736,
year = {2014},
author = {Moccia, M and Picillo, M and Erro, R and Vitale, C and Amboni, M and Palladino, R and Cioffi, DL and Barone, P and Pellecchia, MT},
title = {How does smoking affect olfaction in Parkinson's disease?.},
journal = {Journal of the neurological sciences},
volume = {340},
number = {1-2},
pages = {215-217},
doi = {10.1016/j.jns.2014.02.018},
pmid = {24655736},
issn = {1878-5883},
mesh = {Aged ; Analysis of Variance ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Olfaction Disorders/*etiology ; Parkinson Disease/*complications ; Severity of Illness Index ; *Smoking ; },
abstract = {Smoke-induced upper airway damage and Parkinson's disease (PD) can be considered independent risk factors for smell impairment. Interestingly, cigarette smoking has been strongly associated with reduced risk of PD and, therefore, has been suggested to have neuroprotective effects. Our pilot study aimed to evaluate the relationship between smoking and olfaction in PD patients and matched controls. Sixty-eight PD patients and 61 healthy controls were categorized in relation to PD diagnosis and current smoking status, and evaluated by means of the Italian version of the University of Pennsylvania 40-item Smell Identification Test (UPSIT-40). ANOVA analysis with post-hoc Bonferroni correction showed that non-smoker controls presented a higher UPSIT-40 total score than smoker controls (p<0.001), non-smoker PD patients (p<0.001) and smoker PD patients (p<0.001). In this view, smoking seems to affect olfaction in controls but not in PD patients, and no significant differences were found when comparing smoker controls, smoker PD patients and non-smoker PD patients. Several epidemiological studies showed a negative effect of smoking on olfaction in the general population. Otherwise the sense of smell is similar in smoker and non-smoker PD patients. These results suggest that PD and smoking are not independent risk factors for impairment of sense of smell, but they might variably interact.},
}
@article {pmid24654594,
year = {2014},
author = {Son, CH and Bae, JH and Shin, DY and Lee, HR and Yang, K and Park, YS},
title = {Antitumor effect of dendritic cell loaded ex vivo and in vivo with tumor-associated antigens in lung cancer model.},
journal = {Immunological investigations},
volume = {43},
number = {5},
pages = {447-462},
doi = {10.3109/08820139.2014.884576},
pmid = {24654594},
issn = {1532-4311},
mesh = {Animals ; Antigens, Neoplasm/*immunology ; Cancer Vaccines/administration &amp; dosage/*immunology ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Dendritic Cells/*immunology ; Injections, Intralesional ; Injections, Subcutaneous ; Interferon-gamma/biosynthesis ; Lung Neoplasms/*immunology/mortality/therapy ; Male ; Mice ; T-Cell Antigen Receptor Specificity/immunology ; T-Lymphocyte Subsets/immunology/metabolism ; },
abstract = {Various ex vivo or in vivo loading protocols have been developed or evaluated for the delivery of tumor antigens to dendritic cells (DCs). We compared the antitumor effect of mature DCs electroporation-pulsed (EP/mDC) ex vivo with tumor cell lysate and immature DCs (iDCs) injected into the tumor apoptosed by ionizing radiation (IR/iDC) in lung cancer model. DCs were generated from bone marrow of C57BL/6 mice. Ionizing radiation (IR) was applied at a dose of 10 Gy to the tumor on the right thigh. iDCs were intratumorally injected into the irradiated tumor and EP/mDC was injected subcutaneously in the right flank. DC injection induced strong tumor-specific immunity against Lewis lung carcinoma, as compared with the tumor-bearing control and IR only treated mice. The growth of a distant tumor on the right and left flank was inhibited by IR/iDC and EP/mDC. Particularly, IR/iDC resulted in a more significant inhibition of tumor growth and prolonged survival time. It was related to increase of tumor-specific interferon-gamma, cytotoxicity, and decrease of regulatory T-cells. The results indicate that DCs electroporation-pulsed with tumor cell lysate induce a potent antitumor effect, but that iDCs intratumoral injected into the irradiated tumor induce a more potent antitumor effect.},
}
@article {pmid24652232,
year = {2014},
author = {Yoon, HJ and Kang, KW and Chun, IK and Cho, N and Im, SA and Jeong, S and Lee, S and Jung, KC and Lee, YS and Jeong, JM and Lee, DS and Chung, JK and Moon, WK},
title = {Correlation of breast cancer subtypes, based on estrogen receptor, progesterone receptor, and HER2, with functional imaging parameters from [68]Ga-RGD PET/CT and [18]F-FDG PET/CT.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {41},
number = {8},
pages = {1534-1543},
pmid = {24652232},
issn = {1619-7089},
mesh = {Adult ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*diagnosis/diagnostic imaging/genetics ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/genetics ; Coordination Complexes ; Female ; Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; Multimodal Imaging ; Oligopeptides ; *Positron-Emission Tomography ; Radiopharmaceuticals ; Receptor, ErbB-2/*genetics/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Receptors, Progesterone/*genetics/metabolism ; Tomography, X-Ray Computed ; },
abstract = {PURPOSE: Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes.<br><br>METHODS: In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6&#x2009;&#xb1;&#x2009;7.5&#xa0;years old). (68)Ga-Labeled arginine-glycine-aspartic acid (RGD) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUVmax and SUVavg) from RGD PET/CT and SUVmax and SUVavg from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2-, ER/PR+,Her2+, ER/PR-,Her2+, and ER/PR-,Her2-), were considered.<br><br>RESULTS: Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88&#x2009;&#xb1;&#x2009;8.73 vs 10.48&#x2009;&#xb1;&#x2009;6.01, p&#x2009;=&#x2009;0.02 for SUVmax; 9.40&#x2009;&#xb1;&#x2009;5.19 vs 5.92&#x2009;&#xb1;&#x2009;4.09, p&#x2009;=&#x2009;0.02 for SUVavg) and the PR-negative group (8.37&#x2009;&#xb1;&#x2009;4.94 vs 4.79&#x2009;&#xb1;&#x2009;3.93, p&#x2009;=&#x2009;0.03 for SUVavg). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42&#x2009;&#xb1;&#x2009;0.59 vs 2.90&#x2009;&#xb1;&#x2009;0.75, p&#x2009;=&#x2009;0.04 for SUVmax; 1.60&#x2009;&#xb1;&#x2009;0.38 vs 1.95&#x2009;&#xb1;&#x2009;0.53, p&#x2009;=&#x2009;0.04 for SUVavg) and showed a significant positive correlation with the HER2/CEP17 ratio (r&#x2009;=&#x2009;0.38, p&#x2009;=&#x2009;0.03 for SUVmax and r&#x2009;=&#x2009;0.46, p&#x2009;<&#x2009;0.01 for SUVavg). FDG PET parameters showed significantly higher values in the ER/PR-,Her2- subgroup versus the ER/PR+,Her2- or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER/PR-,Her2- subgroup versus the other subgroups. There was no correlation between FDG and RGD PET parameters in the overall group. Only the ER/PR-,Her2- subgroup showed a significant positive correlation between FDG and RGD PET parameters (r&#x2009;=&#x2009;0.59, p&#x2009;=&#x2009;0.03 for SUVmax).<br><br>CONCLUSION: (68)Ga-RGD and (18)F-FDG PET/CT are promising functional imaging modalities for predicting biomarkers and molecular phenotypes in breast cancer patients.},
}
@article {pmid24648320,
year = {2015},
author = {Nakiwogga-Muwanga, A and Musaazi, J and Katabira, E and Worodria, W and Talisuna, SA and Colebunders, R},
title = {Patients who return to care after tracking remain at high risk of attrition: experience from a large HIV clinic, Uganda.},
journal = {International journal of STD &amp; AIDS},
volume = {26},
number = {1},
pages = {42-47},
doi = {10.1177/0956462414529098},
pmid = {24648320},
issn = {1758-1052},
mesh = {Adult ; Ambulatory Care Facilities ; Anti-HIV Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active ; Appointments and Schedules ; CD4 Lymphocyte Count ; Continuity of Patient Care/*organization &amp; administration ; Female ; Follow-Up Studies ; HIV Infections/*drug therapy/psychology ; Humans ; *Lost to Follow-Up ; Male ; Middle Aged ; Patient Compliance/psychology/*statistics &amp; numerical data ; Patient Dropouts/psychology/*statistics &amp; numerical data ; Socioeconomic Factors ; Time Factors ; Treatment Outcome ; Treatment Refusal ; },
abstract = {We determined the retention rate of patients infected with HIV who resumed care after being tracked at the Infectious Diseases Clinic (IDC) in Kampala, Uganda. Between April 2011 and September 2013, patients who missed their clinic appointment for 8-90 days were tracked, and those who returned to the clinic within 120 days were followed up. The proportion of patients retained among tracked patients, and those who resumed care before tracking started was compared. At 18 months of follow up, 33 (39%) of the tracked patients and 72 (61%) of those who had resumed care before tracking started were retained in care. The most important cause of attrition among the traceable was self-transfer to another clinic (38 [73%] patients), whereas among those who resumed care before tracking was loss to follow up (LTFU) (32 [71%] patients). Tracked patients who resume care following a missed appointment are at high risk of attrition. To increase retention, antiretroviral therapy clinics need to adopt a chronic care model which takes into consideration patients' changing needs and their preference for self-management.},
}
@article {pmid24628533,
year = {2014},
author = {Aiad, HA and Wahed, MM and Asaad, NY and El-Tahmody, M and Elhosary, E},
title = {Immunohistochemical expression of GPR30 in breast carcinoma of Egyptian patients: an association with immunohistochemical subtypes.},
journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica},
volume = {122},
number = {10},
pages = {976-984},
doi = {10.1111/apm.12241},
pmid = {24628533},
issn = {1600-0463},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/*pathology ; Egypt ; Female ; Humans ; Immunohistochemistry/methods ; Lymph Nodes/pathology ; Middle Aged ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/*genetics ; Receptors, G-Protein-Coupled/*genetics ; Retrospective Studies ; },
abstract = {Breast carcinoma in Egyptian women is a biologically more aggressive disease than those diagnosed in Western women, although a substantial number of cases are hormone responsive. G protein-coupled receptor-30 (GPR30), a seven transmembrane domain protein, is currently recognized as an estrogen receptor. This study aimed at evaluating the expression of GPR30 in breast carcinomas of Egyptian patients and its association with clinicopathologic parameters and immunohistochemical subtypes of breast carcinoma. Immunohistochemical staining for GPR30 was applied on 51 archival formalin-fixed paraffin-embedded cases of invasive ductal carcinoma. Staining was assessed using a semiquantitative scoring system taking staining intensity and extent into consideration. GPR30 was observed in 33/51 (65%) of invasive ductal carcinoma cases. GPR30 was significantly associated with larger tumor size (p = 0.009), increased number of positive lymph nodes (p = 0.04), definite lymph-vascular invasion (LVI) (p = 0.002), peri-nodal invasion (p = 0.02), and the presence of coagulative tumor cell necrosis (p = 0.02). Moreover, a significant association between positive GPR30 expression and ER positivity (p = 0.02), as well as HER2/neu positivity (p = 0.03), were also observed. Most of the luminal A and B subtypes were GPR30 positive; however, all the triple negative cases were GPR30 negative (p = 0.010). GPR30 might contribute to the aggressive behavior of Egyptian breast carcinoma. Therefore, it could be useful in the therapeutic decision making in breast cancer patients.},
}
@article {pmid24623017,
year = {2014},
author = {Feldman, AM and Begay, RL and Knezevic, T and Myers, VD and Slavov, DB and Zhu, W and Gowan, K and Graw, SL and Jones, KL and Tilley, DG and Coleman, RC and Walinsky, P and Cheung, JY and Mestroni, L and Khalili, K and Taylor, MR},
title = {Decreased levels of BAG3 in a family with a rare variant and in idiopathic dilated cardiomyopathy.},
journal = {Journal of cellular physiology},
volume = {229},
number = {11},
pages = {1697-1702},
pmid = {24623017},
issn = {1097-4652},
support = {R01 HL147064/HL/NHLBI NIH HHS/United States ; R01 HL109209/HL/NHLBI NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; 1R01HL109209-01A1/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01 HL116906/HL/NHLBI NIH HHS/United States ; P01 HL091799/HL/NHLBI NIH HHS/United States ; R01 HL123093/HL/NHLBI NIH HHS/United States ; },
mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Apoptosis Regulatory Proteins/*genetics/metabolism ; Base Sequence ; Cardiomyopathy, Dilated/*genetics ; Family ; Female ; Heart Failure/genetics ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation/*genetics ; Pedigree ; Phenotype ; RNA, Messenger/genetics/metabolism ; Sequence Deletion ; },
abstract = {The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole-exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10-nucleotide deletion in the BCL2-associated athanogene 3 (BAG3) gene (Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C-terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end-stage HF undergoing cardiac transplantation when compared with non-failing controls. Diminished levels of BAG3 protein may be associated with both familial and non-familial forms of dilated cardiomyopathy.},
}
@article {pmid24621503,
year = {2014},
author = {Mercier, I and Gonzales, DM and Quann, K and Pestell, TG and Molchansky, A and Sotgia, F and Hulit, J and Gandara, R and Wang, C and Pestell, RG and Lisanti, MP and Jasmin, JF},
title = {CAPER, a novel regulator of human breast cancer progression.},
journal = {Cell cycle (Georgetown, Tex.)},
volume = {13},
number = {8},
pages = {1256-1264},
pmid = {24621503},
issn = {1551-4005},
mesh = {Animals ; Breast Neoplasms/*metabolism/pathology ; Cell Cycle Checkpoints ; Cell Proliferation ; Disease Progression ; Female ; Gene Knockdown Techniques ; Humans ; MCF-7 Cells ; Mice, Nude ; Neoplasm Transplantation ; Nuclear Proteins/genetics/*metabolism ; Phosphorylation ; Proliferating Cell Nuclear Antigen/metabolism ; Protein Biosynthesis ; Proto-Oncogene Proteins c-jun/metabolism ; RNA, Small Interfering/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; },
abstract = {CAPER is an estrogen receptor (ER) co-activator that was recently shown to be involved in human breast cancer pathogenesis. Indeed, we reported increased expression of CAPER in human breast cancer specimens. We demonstrated that CAPER was undetectable or expressed at relatively low levels in normal breast tissue and assumed a cytoplasmic distribution. In contrast, CAPER was expressed at higher levels in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specimens, where it assumed a predominantly nuclear distribution. However, the functional role of CAPER in human breast cancer initiation and progression remained unknown. Here, we used a lentiviral-mediated gene silencing approach to reduce the expression of CAPER in the ER-positive human breast cancer cell line MCF-7. The proliferation and tumorigenicity of MCF-7 cells stably expressing control or human CAPER shRNAs was then determined via both in vitro and in vivo experiments. Knockdown of CAPER expression significantly reduced the proliferation of MCF-7 cells in vitro. Importantly, nude mice injected with MCF-7 cells harboring CAPER shRNAs developed smaller tumors than mice injected with MCF-7 cells harboring control shRNAs. Mechanistically, tumors derived from mice injected with MCF-7 cells harboring CAPER shRNAs displayed reduced expression of the cell cycle regulators PCNA, MCM7, and cyclin D1, and the protein synthesis marker 4EBP1. In conclusion, knockdown of CAPER expression markedly reduced human breast cancer cell proliferation in both in vitro and in vivo settings. Mechanistically, knockdown of CAPER abrogated the activity of proliferative and protein synthesis pathways.},
}
@article {pmid24621330,
year = {2014},
author = {Lim, ST and Yu, JH and Park, HK and Moon, BI and Ko, BK and Suh, YJ},
title = {A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population.},
journal = {World journal of surgical oncology},
volume = {12},
number = {},
pages = {56},
pmid = {24621330},
issn = {1477-7819},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/mortality/*secondary/therapy ; Carcinoma, Lobular/epidemiology/mortality/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Republic of Korea/epidemiology ; Survival Rate ; Young Adult ; },
abstract = {BACKGROUND: To investigate the clinicopathological characteristics and the survival outcomes of invasive lobular carcinoma (ILC) patients compared to invasive ductal carcinoma (IDC) patients according to their molecular subtype.<br><br>METHODS: We compared the clinicopathological characteristics, breast cancer-specific survival (BCSS) and overall survival (OS) between patients with IDC (n&#x2009;=&#x2009;14,547) and ILC (n&#x2009;=&#x2009;528).<br><br>RESULTS: The ILC presented with a larger tumor size, more advanced cancer stage, increased rate of hormonal receptor positivity, human epidermal growth factor 2 (HER2) negativity and mastectomy than the IDC. The ILC patients more frequently presented with the luminal A subtype, whereas the IDC patients more frequently presented with the luminal B, HER2-overexpression, or triple negative subtype. The BCSS and OS were not significantly different between the IDC and ILC for each molecular subtype.<br><br>CONCLUSIONS: Similar to IDC patients, molecular subtype should be considered when determining the prognosis and treatment regimen for ILC patients.},
}
@article {pmid24609797,
year = {2015},
author = {Caliskan, M and Gullu, H and Erdogan, D and Ozulku, M and Kulaksızoglu, S and Ciftci, O and Muderrisoglu, H},
title = {Association between serum total antioxidant status and coronary microvascular function in idiopathic dilated cardiomyopathy.},
journal = {Herz},
volume = {40},
number = {3},
pages = {487-494},
pmid = {24609797},
issn = {1615-6692},
mesh = {Adolescent ; Adult ; Aged ; Antioxidants/*analysis ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/*complications/diagnosis ; Coronary Artery Disease/*blood/*complications/diagnosis ; Cytokines/*blood ; Female ; Humans ; Male ; Microvessels/diagnostic imaging ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Ultrasonography ; Young Adult ; },
abstract = {BACKGROUND: Coronary microvascular impairment may cause myocardial ischemia and systolic dysfunction in patients with idiopathic dilated cardiomyopathy (IDC).<br><br>PATIENTS AND METHODS: The study included 41 patients with IDC and 33 healthy control subjects. Serum total antioxidant status (TAS), serum interleukin (IL)-6 levels, and tumor necrosis factor (TNF)-&#x3b1; levels were assayed and coronary flow reserve (CFR) was measured in all subjects via echocardiography.<br><br>RESULTS: High-sensitivity C-reactive protein (hsCRP) levels were significantly higher in patients with IDC than in the control group (3.42&#x2009;&#xb1;&#x2009;2.14 vs. 1.91&#xb1;&#x2009;1.40, p&#x2009;=&#x2009;0.001). Serum TAS was statistically lower in patients with IDC than in controls (1.23&#x2009;&#xb1;&#x2009;0.16 vs. 1.77&#x2009;&#xb1;&#x2009;0.12, p&#x2009;<&#x2009;0.001). CFR was statistically and significantly lower in the IDC group (2.10&#x2009;&#xb1;&#x2009;0.39 vs. 3.09&#x2009;&#xb1;&#x2009;0.49, p&#x2009;<&#x2009;0.001). The IDC group was subsequently subdivided into two groups according to CFR values, as CFR &#x2265;&#x2009;2 and CFR <&#x2009;2. HsCRP (4.30&#x2009;&#xb1;&#x2009;2.42 vs. 2.58&#x2009;&#xb1;&#x2009;1.42, p&#x2009;=&#x2009;0.01), TNF-&#x3b1; (16.67&#x2009;&#xb1;&#x2009;8.08 vs. 10.97&#x2009;&#xb1;&#x2009;1.63, p&#x2009;=&#x2009;0.01), and IL-6 (7.54&#x2009;&#xb1;&#x2009;6.16 vs. 3.14&#x2009;&#xb1;&#x2009;1.10, p&#x2009;=&#x2009;0.05) values were significantly higher in the CFR <&#x2009;2 group compared with the higher CFR group. TAS (1.3&#x2009;&#xb1;&#x2009;0.16 vs. 1.14&#x2009;&#xb1;&#x2009;0.10, p&#x2009;<&#x2009;0.001) was significantly lower in the CFR <&#x2009;2 group. CFR correlated significantly with hsCRP, TAS, red cell distribution width (RDW), IL-6, and TNF-&#x3b1;.<br><br>CONCLUSION: Plasma proinflammatory cytokine levels are increased in patients with IDC. CFR was impaired as a reflection of impaired coronary microvascular dysfunction in association with increasing plasma proinflammatory cytokine levels and hsCRP levels.},
}
@article {pmid24605219,
year = {2014},
author = {Demirhan, O and Ordu, C and Toker, A},
title = {Prolonged pleural catheters in the management of pleural effusions due to breast cancer.},
journal = {Journal of thoracic disease},
volume = {6},
number = {2},
pages = {74-78},
pmid = {24605219},
issn = {2072-1439},
abstract = {BACKGROUND: Breast cancer is the second most common etiologic cause in malignant pleural effusions (MPE). The aim of this study was to investigate the efficacy of long term pleural catheters in inducing self sclerosis in pleural effusions of breast cancer patients.<br><br>METHODS: In this study, 26 patients with breast cancer relapleural effusions that occurred between January 2011 and July 2013, who were considered not to undergo any other treatments and managed with prolonged pleural catheters (Jackson-Pratt silicone flat drain), were retrospectively analyzed. Thirty pleural catheters were inserted in 26 patients. All patients were female, mean age was 52 (range, 37-66) years old. Drainage over 1,500 mL per day was not allowed in order to avoid a lung edema. The catheters were removed in patients who had restoration of lung expansion and drainage under 50 mL/day.<br><br>RESULTS: The histologic subtypes in pleural effusions were invasive ductal carcinoma in 18 patients, ductal carcinoma in situ in 4, invasive lobular carcinoma in 2, tubular carcinoma in 1, and medullary carcinoma in 1. Three of the 26 patients underwent bilateral catheter insertion, and one patient underwent a reinsertion of the catheter into the same hemithorax due to a recurrence. The catheters were retained for a mean period of 18 days (range, 11-38 days). In one patient with invasive ductal carcinoma and paramalignant pleural effusion (PMPE) (3.8%), a recurrent pleural effusion was seen 34 days after removal of the catheter. There were no complications. One patient died while the catheter was in place.<br><br>CONCLUSIONS: Prolonged catheters for the management of pleural effusions in selected patients have become more popular than other treatment alternatives due to a shorter length of stay and lower costs. We recommend the use of Jackson Pratt (JP) silicone flat drains which in our opinion provide effective pleurodesis in addition to easy application in recurrent effusions caused by breast cancer.},
}
@article {pmid24603690,
year = {2014},
author = {Yin, J and Liu, Z and Li, H and Sun, J and Chang, X and Liu, J and He, S and Li, B},
title = {Association of PKCζ expression with clinicopathological characteristics of breast cancer.},
journal = {PloS one},
volume = {9},
number = {6},
pages = {e90811},
pmid = {24603690},
issn = {1932-6203},
mesh = {Adult ; Breast Neoplasms/*enzymology/mortality/pathology ; Carcinoma, Ductal, Breast/*enzymology/mortality/secondary ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Isoenzymes/*metabolism ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Protein Kinase C/*metabolism ; Receptor, ErbB-2/metabolism ; },
abstract = {The protein kinase C (PKC) family has been functionally linked to cancer. It has been suggested that atypical PKCs contribute to cell proliferation and cancer progression. With respect to breast cancer, PKCζ has been found to play a key role in intracellular transduction of mitogenic and apoptotic signals using mammary cell lines. However, little is known about its function in vivo. Here we examined the correlation between PKCζ protein levels and important clinicopathologic factors in breast cancer using patient samples. To conduct the study, 30 invasive ductal carcinoma cases and their paired normal tissues were used for tissue microarray analysis (TMA) and 16 were used for western blot analysis. In addition, the correlation between PKCζ expression levels and clinicopathologic characteristics was determined in 176 cases with relevant clinical data. Finally, the correlation between PKCζ and epithelial growth factor receptor 2 (HER2) expressions was determined using three breast cancer cell lines by western blot analysis. Both TMA and western blot results showed that PKCζ protein was highly expressed in primary tumors but not in paired normal tissue. The correlation study indicated that high PKCζ levels were associated with premenopausal patients (p = 0.019) and worse prognostic factors, such as advanced clinical stage, more lymph node involvement and larger tumor size. Both disease-free survival and overall survival rates were lower in the high PKCζ group than those in the low PKCζ group. No correlation was observed between PKCζ levels and age, histological grade, or estrogen or progesterone receptor expression status. A positive correlation between PKCζ and HER2 levels was observed in both tumor samples and cell lines. Our observations link PKCζ expression with factors pointing to worse prognosis, higher HER2 levels and a lower survival rate. This suggests that PKCζ protein levels may serve as a prognostic marker of breast cancer.},
}
@article {pmid24596383,
year = {2014},
author = {Merdad, A and Karim, S and Schulten, HJ and Dallol, A and Buhmeida, A and Al-Thubaity, F and Gari, MA and Chaudhary, AG and Abuzenadah, AM and Al-Qahtani, MH},
title = {Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis.},
journal = {Anticancer research},
volume = {34},
number = {3},
pages = {1355-1366},
pmid = {24596383},
issn = {1791-7530},
mesh = {Animals ; Apoptosis/*drug effects ; Biomarkers, Tumor/*genetics/metabolism ; Blotting, Western ; Breast Neoplasms/drug therapy/*enzymology/pathology ; Cell Proliferation/drug effects ; Female ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Immunoenzyme Techniques ; Matrix Metalloproteinases/*metabolism ; Mitochondria/drug effects/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Oligonucleotide Array Sequence Analysis ; Quinuclidines/pharmacology ; RNA, Messenger/genetics ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; beta Catenin/genetics/metabolism ; },
abstract = {BACKGROUND/AIM: Breast cancer (BC) is the most common type of cancer in Saudi women. Matrix metalloproteinases (MMPs) are endopeptidases with the ability to degrade extracellular matrix proteins. In healthy individual tissue disruption is prevented by precised regulation of MMPs; however, in cancer a number of MMPs are overexpressed causing tissue disruption and making tumor cells capable of invasion and metastasis. Invasive ductal carcinoma (IDC) of BCs are classified into grade 1 (G1), grade 2 (G2) and grade 3 (G3) tumors.<br><br>MATERIALS AND METHODS: We performed a transcriptomic profiling of 38 surgically-resected breast tumors (4 G1, 17 G2 and 17 G3) using Affymetrix Gene 1.0 ST microarrays. Differentially expressed genes for each grade were identified by the Partek Genomic Suite 6.4 and expression analysis results were validated by immunohistochemistry at the protein level. Pathway analyses and establishment of clinical significance of findings were performed using the appropriate software.<br><br>RESULTS: We identified 1,593 differentially expressed genes in BC grades in comparison to normal samples using a cut-off of p<0.05 and fold change >2. Out of these genes 429 were expressed throughout in all grades along with tumor progression while many others associated with specific grades (440 genes in G1, 203 in G2 and 394 in G3 only) were exclusively. Microarray results indicate that mRNA expression of MMP-1, -9,-11,-12, and -13 were up-regulated in higher BC grades when compared to normal breast tissues. MMP-9 was expressed in most IDC (97.5%) samples and was highly expressed in 55% of the tumors. Differential expression of MMP-9 significantly correlated with histological BC grades of (p=0.03) and strongly correlated with overall survival (p=0.08).<br><br>CONCLUSION: Gene expression signatures are unique for specific grades. Overexpression of MMPs in higher grades might be associated with BC tumor invasion and metastasis. Therefore, MMPs, and MMP-9 in particular, are reliable candidates for diagnostic biomarker and drug target and further functional analyses have to be performed in order to confirm their role in BC. Our results also suggest the incidence of MMP-9 expression is high in IDC, but it is of limited prognostic value.},
}
@article {pmid24586742,
year = {2014},
author = {Hung, MH and Liu, CY and Shiau, CY and Hsu, CY and Tsai, YF and Wang, YL and Tai, LC and King, KL and Chao, TC and Chiu, JH and Su, CH and Lo, SS and Tzeng, CH and Shyr, YM and Tseng, LM},
title = {Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.},
journal = {PloS one},
volume = {9},
number = {2},
pages = {e89389},
pmid = {24586742},
issn = {1932-6203},
mesh = {Adult ; Age Factors ; Brain/pathology ; Brain Neoplasms/metabolism/*pathology/*secondary ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk ; Triple Negative Breast Neoplasms/metabolism/*pathology ; },
abstract = {BACKGROUND: Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.<br><br>PATIENTS AND METHODS: We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis.<br><br>RESULTS: Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P&#x200a;=&#x200a;0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years.<br><br>CONCLUSIONS: Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.},
}
@article {pmid24585434,
year = {2014},
author = {Endo, M and Yamamoto, Y and Nakano, M and Masuda, T and Odagiri, H and Horiguchi, H and Miyata, K and Kadomatsu, T and Motokawa, I and Okada, S and Iwase, H and Oike, Y},
title = {Serum ANGPTL2 levels reflect clinical features of breast cancer patients: implications for the pathogenesis of breast cancer metastasis.},
journal = {The International journal of biological markers},
volume = {29},
number = {3},
pages = {e239-45},
doi = {10.5301/jbm.5000080},
pmid = {24585434},
issn = {1724-6008},
mesh = {Adult ; Aged ; Aged, 80 and over ; Angiopoietin-Like Protein 2 ; Angiopoietin-like Proteins ; Angiopoietins/*blood ; Animals ; Breast Neoplasms/*blood/*pathology ; Carcinoma, Ductal, Breast/*blood/*pathology ; Case-Control Studies ; Cell Line, Tumor ; Cell Proliferation/physiology ; Disease Progression ; Female ; Heterografts ; Humans ; MCF-7 Cells ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplasm Metastasis ; Triple Negative Breast Neoplasms/*blood/*pathology ; Young Adult ; },
abstract = {INTRODUCTION: Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression.<br><br>METHODS: We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients.<br><br>RESULTS: Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades.<br><br>CONCLUSIONS: These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.},
}
@article {pmid24581736,
year = {2014},
author = {Wei, S and Bleiweiss, IJ and Nagi, C and Jaffer, S},
title = {Characteristics of breast carcinoma cases with false-negative sentinel lymph nodes.},
journal = {Clinical breast cancer},
volume = {14},
number = {4},
pages = {280-284},
doi = {10.1016/j.clbc.2013.12.009},
pmid = {24581736},
issn = {1938-0666},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Carcinoma, Lobular/*secondary/surgery ; False Negative Reactions ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; *Sentinel Lymph Node Biopsy ; },
abstract = {BACKGROUND: In the past decade, sentinel lymph node biopsy (SLNB) has become standard for patients with early-stage clinically node-negative breast carcinoma (BC). Despite high overall surgical identification success rates with introduction of the dual-tracer techniques (dye and radiolabeled probe), false-negative rates remained unchanged in most recent meta-analyses.<br><br>PATIENTS AND METHODS: We analyzed cases with false-negative SLN biopsy results over a 12-year period in a single institution to evaluate their clinicopathologic characteristics. Sixty-three false-negative cases (3.1%) were found in 2043 successful SLN mapping procedures, all of which were followed by varying amounts of additional axillary sampling.<br><br>RESULTS: There was a higher proportion of invasive lobular carcinomas (ILCs; 23 cases [37%]) when compared with this lesion's overall reported frequency (5%-15%). The majority of invasive ductal carcinoma (IDC) cases (31 of 40) were poorly differentiated. In 80% of the ductal-type cases, 1 or more nonsentinel nodes (NSLNs) were completely or partially replaced by tumor, as opposed to less than half of such cases of the lobular type. Twenty-two cases had multiple positive NSLN metastases, which were significantly associated with larger tumor size (&#x2265; 1.0 cm) and tumor replacement of NSLNs. Eighty-two percent of the cases with known hormone receptor status were positive for estrogen or progesterone receptors, or both.<br><br>CONCLUSION: False-negative SLN biopsy results were more often associated with a primary BC characterized by a lobular or poorly differentiated ductal histologic type or partial to complete replacement of NSLNs with tumor, or both.},
}
@article {pmid24574467,
year = {2014},
author = {Starmer, HM and Liu, Z and Akst, LM and Gourin, C},
title = {Attendance in voice therapy: can an interdisciplinary care model have an impact?.},
journal = {The Annals of otology, rhinology, and laryngology},
volume = {123},
number = {2},
pages = {117-123},
doi = {10.1177/0003489414523708},
pmid = {24574467},
issn = {0003-4894},
mesh = {Adult ; Aged ; Dysphonia/etiology/*rehabilitation ; Female ; Humans ; Male ; Middle Aged ; Otolaryngology/*statistics &amp; numerical data ; Patient Compliance/*statistics &amp; numerical data ; Referral and Consultation/*statistics &amp; numerical data ; Retrospective Studies ; Speech-Language Pathology/*statistics &amp; numerical data ; Treatment Outcome ; *Voice Training ; Young Adult ; },
abstract = {OBJECTIVES: We sought to determine the effect of referral patterns on attendance in voice therapy.<br><br>METHODS: Patients who were seen by a laryngologist for vocal concerns and referred for voice therapy comprised the study population. Outcomes were compared between those who were initially evaluated through the interdisciplinary voice clinic (IDC), which combined speech-language pathology and laryngology care, and those who were evaluated by a laryngologist alone. Adherence was measured by completion of the plan of care.<br><br>RESULTS: There were 79 patients evaluated through the IDC and 100 patients evaluated initially by a laryngologist. Patients evaluated through the IDC had more visits with the speech-language pathologist (mean, 3.1 versus 1.24; p < 0.0001). Those initially evaluated through the IDC were more likely to complete their plan of care (p = 0.02). Completion of voice therapy was significantly more likely for individuals coded as being of "other" race (odds ratio, 7.98; p = 0.002) and for patients who participated in the IDC (odds ratio, 2.56; p = 0.018). The cause of dysphonia, sex, marital status, insurance status, days from laryngology referral to the initial speech-language pathologist consultation, the initial Voice-Related Quality of Life score, and distance to the clinic were not associated with patient attendance.<br><br>CONCLUSIONS: Patients evaluated in a coordinated IDC should be more likely to attend voice therapy and complete their plan of care, regardless of other factors.},
}
@article {pmid24574065,
year = {2014},
author = {Kwon, SY and Lee, JH and Kim, B and Park, JW and Kwon, TK and Kang, SH and Kim, S},
title = {Complexity in regulation of microRNA machinery components in invasive breast carcinoma.},
journal = {Pathology oncology research : POR},
volume = {20},
number = {3},
pages = {697-705},
pmid = {24574065},
issn = {1532-2807},
mesh = {Argonaute Proteins/*genetics/metabolism ; Breast/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; DEAD-box RNA Helicases/*genetics/metabolism ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proteins/*genetics/metabolism ; RNA, Messenger/genetics ; RNA-Binding Proteins ; Real-Time Polymerase Chain Reaction ; Ribonuclease III/*genetics/metabolism ; },
abstract = {Altered expression of microRNA (miRNA) machinery components may play an important role in breast cancer progression. The objective of the current study was to evaluate Drosha, the DiGeorge syndrome critical region gene 8 (DGCR8), Dicer, and Argonaute 2 (AGO2) mRNA expression in invasive breast carcinoma (IBC) and to assess the value of clinical parameters on their expression. By using quantitative real-time PCR, we examined the expression of the four miRNA machinery components in 52 breast tumor tissues which are diagnosed as invasive ductal carcinoma and adjacent non-neoplastic tissues. In the present study, decreased mRNA expression levels of major miRNA machinery components were observed in IBC. The altered mRNA expression levels of DGCR8 and AGO2 are positively correlated with to each other. This study revealed for the first time that expression alterations of DGCR8 are significantly associated with estrogen receptor and Ki-67 status in IBC. Moreover, AGO2 mRNA expression level was significantly correlated with N stage. These results provided evidences that down-regulated the four miRNA machinery components may play an important role in breast pathobiology and that DGCR8 and AGO2 might be associated with important clinical factors.},
}
@article {pmid24571647,
year = {2014},
author = {Rodrigues Dos Santos, C and Fonseca, I and Dias, S and Mendes de Almeida, JC},
title = {Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression.},
journal = {BMC cancer},
volume = {14},
number = {},
pages = {132},
pmid = {24571647},
issn = {1471-2407},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood/mortality/*pathology ; Cholesterol, LDL/*blood ; Disease Progression ; Female ; Humans ; Lipids/blood ; Lipoproteins/blood ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Risk Factors ; },
abstract = {BACKGROUND: Among women, breast cancer (BC) is the leading cancer and the most common cause of cancer-related death between 30 and 69 years. Although lifestyle and diet are considered to have a role in global BC incidence pattern, the specific influence of dyslipidemia in BC onset and progression is not yet completely understood.<br><br>METHODS: Fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) was prospectively assessed in 244 women with BC who were enrolled according to pre-set inclusion criteria: diagnosis of non-hereditary invasive ductal carcinoma; selection for surgery as first treatment, and no history of treatment with lipid-lowering or anti-diabetic drugs in the previous year. Pathological and clinical follow-up data were recorded for further inclusion in the statistical analysis.<br><br>RESULTS: Univariate associations show that BC patients with higher levels of LDL-C at diagnosis have tumors that are larger, with higher differentiation grade, higher proliferative rate (assessed by Ki67 immunostaining), are more frequently Her2-neu positive and are diagnosed in more advanced stages. Cox regression model for disease-free survival (DFS), adjusted to tumor T and N stages of TNM classification, and immunohistochemical subtypes, revealed that high LDL-C at diagnosis is associated with poor DFS. At 25 months of follow up, DFS is 12% higher in BC patients within the third LDL-C tertile compared to those in the first tertile.<br><br>CONCLUSIONS: This is a prospective study where LDL-C levels, at diagnosis, emerge as a prognostic factor; and this parameter can be useful in the identification and follow-up of high-risk groups. Our results further support a possible role for systemic cholesterol in BC progression and show that cholesterol metabolism may be an important therapeutic target in BC patients.},
}
@article {pmid24559473,
year = {2014},
author = {Siegel, TN and Hon, CC and Zhang, Q and Lopez-Rubio, JJ and Scheidig-Benatar, C and Martins, RM and Sismeiro, O and Coppée, JY and Scherf, A},
title = {Strand-specific RNA-Seq reveals widespread and developmentally regulated transcription of natural antisense transcripts in Plasmodium falciparum.},
journal = {BMC genomics},
volume = {15},
number = {1},
pages = {150},
pmid = {24559473},
issn = {1471-2164},
support = {250320/ERC_/European Research Council/International ; },
mesh = {3' Untranslated Regions ; Cell Nucleus/metabolism ; Cluster Analysis ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Library ; High-Throughput Nucleotide Sequencing ; Plasmodium falciparum/*genetics ; Polyadenylation ; RNA Splicing ; *RNA, Antisense ; RNA, Messenger/genetics/metabolism ; *RNA, Protozoan ; *Transcription, Genetic ; },
abstract = {BACKGROUND: Advances in high-throughput sequencing have led to the discovery of widespread transcription of natural antisense transcripts (NATs) in a large number of organisms, where these transcripts have been shown to play important roles in the regulation of gene expression. Likewise, the existence of NATs has been observed in Plasmodium but our understanding towards their genome-wide distribution remains incomplete due to the limited depth and uncertainties in the level of strand specificity of previous datasets.<br><br>RESULTS: To gain insights into the genome-wide distribution of NATs in P. falciparum, we performed RNA-ligation based strand-specific RNA sequencing at unprecedented depth. Our data indicate that 78.3% of the genome is transcribed during blood-stage development. Moreover, our analysis reveals significant levels of antisense transcription from at least 24% of protein-coding genes and that while expression levels of NATs change during the intraerythrocytic developmental cycle (IDC), they do not correlate with the corresponding mRNA levels. Interestingly, antisense transcription is not evenly distributed across coding regions (CDSs) but strongly clustered towards the 3'-end of CDSs. Furthermore, for a significant subset of NATs, transcript levels correlate with mRNA levels of neighboring genes.Finally, we were able to identify the polyadenylation sites (PASs) for a subset of NATs, demonstrating that at least some NATs are polyadenylated. We also mapped the PASs of 3443 coding genes, yielding an average 3' untranslated region length of 523 bp.<br><br>CONCLUSIONS: Our strand-specific analysis of the P. falciparum transcriptome expands and strengthens the existing body of evidence that antisense transcription is a substantial phenomenon in P. falciparum. For a subset of neighboring genes we find that sense and antisense transcript levels are intricately linked while other NATs appear to be regulated independently of mRNA transcription. Our deep strand-specific dataset will provide a valuable resource for the precise determination of expression levels as it separates sense from antisense transcript levels, which we find to often significantly differ. In addition, the extensive novel data on 3' UTR length will allow others to perform searches for regulatory motifs in the UTRs and help understand post-translational regulation in P. falciparum.},
}
@article {pmid24551675,
year = {2013},
author = {M, Y and Ahmadi M R, H and J, K and H, P and K H, A and M R, Y and K, H},
title = {An 8 years retrospective study of breast cancer incidence in ilam province, Western iran.},
journal = {Journal of clinical and diagnostic research : JCDR},
volume = {7},
number = {12},
pages = {2923-2925},
pmid = {24551675},
issn = {2249-782X},
abstract = {INTRODUCTION: Breast cancer is the most common cancer (27% of all cancers) and common cause of death (16%) which occurs due to cancers among women, either in develo