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Molecular pathology

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https://www.readbyqxmd.com/read/28319834/molecular-mechanisms-in-the-pathogenesis-of-arrhythmogenic-cardiomyopathy
#1
REVIEW
Jeffrey E Saffitz
The article is based on work presented in the Distinguished Achievement Award lecture at the Society for Cardiovascular Pathology meeting in Seattle, WA, in March 2016. It reviews our current understanding of mechanisms responsible for a highly arrhythmogenic, nonischemic cardiomyopathy. It highlights the armamentarium of powerful methods available to the experimental pathologist in efforts to define how complex cardiovascular diseases work. It concludes with acknowledgment of the need for a far more detailed approach as to how we categorize human disease, a task for which pathologists are especially well positioned...
February 27, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28319275/mrf-ann-a-machine-learning-approach-for-automated-er-scoring-of-breast-cancer-immunohistochemical-images
#2
T Mungle, S Tewary, D K DAS, I Arun, B Basak, S Agarwal, R Ahmed, S Chatterjee, C Chakraborty
Molecular pathology, especially immunohistochemistry, plays an important role in evaluating hormone receptor status along with diagnosis of breast cancer. Time-consumption and inter-/intraobserver variability are major hindrances for evaluating the receptor score. In view of this, the paper proposes an automated Allred Scoring methodology for estrogen receptor (ER). White balancing is used to normalize the colour image taking into consideration colour variation during staining in different labs. Markov random field model with expectation-maximization optimization is employed to segment the ER cells...
March 20, 2017: Journal of Microscopy
https://www.readbyqxmd.com/read/28319253/heat-shock-protein-expression-in-cerebral-x-linked-adrenoleukodystrophy-reveals-astrocyte-stress-prior-to-myelin-loss
#3
Anna Lena Görtz, Laura A N Peferoen, Wouter H Gerritsen, Johannes M van Noort, Marianna Bugiani, Sandra Amor
AIMS: X-linked adrenoleukodystrophy (X-ALD) is a genetic white matter disorder in which demyelination occurs due to accumulation of very long chain fatty acids. Inflammation in the brain white matter is a hallmark of the pathology of cerebral X-ALD, but the underlying pathogenic mechanisms are still largely unknown. In other inflammatory demyelinating disorders such as multiple sclerosis, the expression of heat shock proteins (HSPs) in combination with interferon-γ (IFN-γ) has been suggested to play a prominent role in the initiation of demyelination and inflammation...
March 20, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28318327/pathologic-diagnosis-of-breast-cancer-patients-evolution-of-the-traditional-clinical-pathologic-paradigm-toward-precision-cancer-therapy
#4
B M Turner, D G Hicks
We present an updated account of breast cancer treatment and of progress toward "precision" cancer therapy; we focus on new developments in diagnostic molecular pathology and breast cancer that have emerged during the past 2 years. Increasing awareness of new prognostic and predictive methodologies, and introduction of next generation sequencing has increased understanding of both tumor biology and clinical behavior, which offers the possibility of more appropriate therapeutic choices. It remains unclear which of these testing methodologies provides the most informative and cost-effective actionable results for predictive and prognostic pathology...
March 20, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28317889/mirnas-novel-regulators-of-autoimmunity-mediated-pancreatic-%C3%AE-cell-destruction-in-type-1-diabetes
#5
REVIEW
Ying Zheng, Zhen Wang, Zhiguang Zhou
MicroRNAs (miRNAs) are a series of conserved, short, non-coding RNAs that modulate gene expression in a posttranscriptional manner. miRNAs are involved in almost every physiological and pathological process. Type 1 diabetes (T1D) is an autoimmune disease that is the result of selective destruction of pancreatic β-cells driven by the immune system. miRNAs are also important participants in T1D pathogenesis. Herein, we review the most recent data on the potential involvement of miRNAs in T1D. Specifically, we focus on two aspects: the roles of miRNAs in maintaining immune homeostasis and regulating β-cell survival and/or functions in T1D...
March 20, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28316321/analyzing-esophageal-squamous-cell-papillomas-for-the-presence-of-human-papilloma-virus
#6
Arzu Tiftikçi, Eser Kutsal, Ender Altıok, Ümit İnce, Bahattin Çicek, Murat Saruç, Nurten Türkel, Özdal Ersoy, Güven Yenmiş, Nurdan Tözün
BACKGROUND/AIMS: Human Papilloma Virus (HPV) infection can be a predisposing condition for the development of squamous cell papilloma (SCP) of the esophagus, which can progress to dysplasia and to carcinoma as a result of chronic infection. The aim of the present study was to search for the presence of HPV in the esophageal SCP, and to genotype the detected HPV. MATERIALS AND METHODS: Data from patients with definite diagnosis of SCP of the esophagus were identified from pathology records for two years period at different Hospitals...
March 17, 2017: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
https://www.readbyqxmd.com/read/28316060/hotair-functions-as-a-competing-endogenous-rna-to-regulate-pten-expression-by-inhibiting-mir-19-in-cardiac-hypertrophy
#7
Yanjun Lai, Shuai He, Liming Ma, Hong Lin, Biyun Ren, Jing Ma, Xinyu Zhu, Shifang Zhuang
Sustained cardiac hypertrophy (CH) is related to a variety of physiological as well as pathological stimuli and eventually increases the risk of heart failure. HOTAIR has been identified as a competing endogenous RNA in multiple human biological processes. Whether lncRNA-HOTAIR is involved in the progress of CH and how it works still remain unknown. Herein, we found that HOTAIR was down-regulated, while miR-19 was up-regulated in both heart tissues from TAC-operated mice in vivo and cultural cardiomyocytes treated with Ang-II in vitro by real-time PCR...
March 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28315938/the-relationship-between-breast-cancer-molecular-subtypes-and-mast-cell-populations-in-tumor-microenvironment
#8
Anna Glajcar, Joanna Szpor, Agnieszka Pacek, Katarzyna Ewa Tyrak, Florence Chan, Joanna Streb, Diana Hodorowicz-Zaniewska, Krzysztof Okoń
Mast cells (MCs) are a part of the innate immune system. The MC functions toward cancer are partially based on the release of chymase and tryptase. However, the MC effect on breast cancer is controversial. The aim of our study was to investigate the presence of MCs in breast cancer tumors of different molecular subtypes and their relationships with other pathological prognostic factors. Tryptase- and chymase-positive mast cell densities were evaluated by immunohistochemistry in 108 primary invasive breast cancer tissue samples...
March 18, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28315789/involvement-of-epithelial-mesenchymal-transition-afforded-by-activation-of-lox-1-tgf-%C3%AE-1-klf6-signaling-pathway-in-diabetic-pulmonary-fibrosis
#9
Xiao-Zhou Zou, Zhi-Cheng Gong, Ting Liu, Fang He, Tian-Tian Zhu, Dai Li, Wei-Fang Zhang, Jun-Lin Jiang, Chang-Ping Hu
BACKGROUND AND OBJECTIVE: Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. METHODS: The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg)...
March 15, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315694/incorporation-of-autopsy-case-based-learning-into-phd-graduate-education-a-novel-approach-to-bridging-the-bench-to-bedside-gap
#10
Erin G Brooks, Joanne M Thornton, Erik A Ranheim, Zsuzsanna Fabry
Given the current rapid expansion of biological knowledge and the challenges of translating that knowledge into clinical practice, finding effective methods of teaching graduate students clinical medicine concepts has become even more critical. The utility of autopsy in medical student and resident education has been well-established. Multiple studies have reported it to be a helpful means of teaching anatomy, pathophysiology, clinical problem-solving skills, and medical diagnostic techniques. While various models of training Ph...
March 15, 2017: Human Pathology
https://www.readbyqxmd.com/read/28315674/dichotomy-between-receptor-interacting-protein-1-and-receptor-interacting-protein-3-mediated-necroptosis-in-experimental-pancreatitis
#11
Jianghong Wu, Tunike Mulatibieke, Jianbo Ni, Xiao Han, Bin Li, Yue Zeng, Rong Wan, Xingpeng Wang, Guoyong Hu
Pancreatic acinar cell necrosis and inflammatory responses are two key pathologic processes in acute pancreatitis (AP), which determines the severity and outcome of the disease. Recent studies suggest that necroptosis, a programed form of necrosis, is involved in the pathogenesis of AP, but the underlying mechanisms remain unknown. We investigated the expression of necrosome components, including receptor-interacting protein (RIP) 1, RIP3, and mixed lineage kinase domain-like (MLKL), and the molecular mechanisms in pancreatitis-associated necroptosis...
March 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28315269/sigma-1-receptors-and-neurodegenerative-diseases-towards-a-hypothesis-of-sigma-1-receptors-as-amplifiers-of-neurodegeneration-and-neuroprotection
#12
Linda Nguyen, Brandon P Lucke-Wold, Shona Mookerjee, Nidhi Kaushal, Rae R Matsumoto
Sigma-1 receptors are molecular chaperones that may act as pathological mediators and targets for novel therapeutic applications in neurodegenerative diseases. Accumulating evidence indicates that sigma-1 ligands can either directly or indirectly modulate multiple neurodegenerative processes, including excitotoxicity, calcium dysregulation, mitochondrial and endoplasmic reticulum dysfunction, inflammation, and astrogliosis. In addition, sigma-1 ligands may act as disease-modifying agents in the treatment for central nervous system (CNS) diseases by promoting the activity of neurotrophic factors and neural plasticity...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315264/the-evolution-of-the-sigma-2-%C3%AF-2-receptor-from-obscure-binding-site-to-bona-fide-therapeutic-target
#13
Chenbo Zeng, Robert H Mach
The sigma-2 (σ2) receptor represents one of the most poorly understood proteins in cell biology. Although this receptor was identified through in vitro binding studies over 25 years ago, the molecular identity of this protein is currently not unambiguously known, and the results from recent attempts to identify the σ2 receptor through protein purification and mass spectral analysis have been the subject of debate in the literature. However, there is overwhelming data demonstrating that the σ2 receptor is an important biomarker of tumor cell proliferation ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315110/impact-of-astrocytes-on-the-injury-induced-by-in-vitro-ischemia
#14
Cláudio Roque, Graça Baltazar
Cell cultures are characterized by their simplicity, controllability, and ability to provide detailed basic information on how a particular cell population responds to specific stimuli or insult. These characteristics led to their extensive application in the study of molecular interactions and represent a valuable tool in the study of different pathologies. However, due to the lack of interactions between the different components that form an in vivo system, the results obtained in pure cell cultures not always translate what occurs in vivo...
March 17, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28315031/feasibility-of-large-scale-identification-of-sessile-serrated-polyp-patients-using-electronic-records-a-utah-study
#15
Kajsa Affolter, Keith Gligorich, Niloy Jewel Samadder, Wade S Samowitz, Karen Curtin
BACKGROUND/AIMS: The serrated pathway accounts for 15-25% of sporadic colorectal cancer (CRC). In our study, we sought to accurately characterize sessile serrated polyps (SSP) in a population by electronically interrogating colonoscopy patients' endoscopy and pathology reports using a rules-based text search of pre-defined SSP-related terms. To this aim, we compared a sample of putative SSP and hyperplastic polyps (HP) using our algorithm to a determination of SSP or HP by pathologist and molecular examination to determine the feasibility of large-scale identification of SSP in electronic medical records...
March 17, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28314842/performance-of-mid-treatment-breast-ultrasound-and-axillary-ultrasound-in-predicting-response-to-neoadjuvant-chemotherapy-by-breast-cancer-subtype
#16
Rosalind P Candelaria, Roland L Bassett, William Fraser Symmans, Maheshwari Ramineni, Stacy L Moulder, Henry M Kuerer, Alastair M Thompson, Wei Tse Yang
BACKGROUND: The primary objective was to determine whether mid-treatment ultrasound measurements of index breast tumors and index axillary nodes of different cancer subtypes associate with residual cancer burden (RCB). METHODS: Patients with invasive breast cancer who underwent neoadjuvant chemotherapy and had pre-treatment and mid-treatment breast and axillary ultrasound were included in this single-institution, retrospective cohort study. Linear regression analysis assessed associations between RCB with (a) change in index breast tumor size, (b) change in index node size, and (c) absolute number of abnormal nodes at mid-treatment...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28314821/phases-of-hyper-and-hypo-connectivity-in-the-default-mode-and-salience-networks-track-with-amyloid-and-tau-in-clinically-normal-individuals
#17
Aaron P Schultz, Jasmeer P Chhatwal, Trey Hedden, Elizabeth C Mormino, Bernard J Hanseeuw, Jorge Sepulcre, Willem Huijbers, Molly LaPoint, Rachel F Buckley, Keith A Johnson, Reisa A Sperling
Alzheimer's disease (AD) is characterized by two hallmark molecular pathologies: amyloid aβ1-42, and Tau neurofibrillary tangles. To date, studies of functional connectivity MRI (fcMRI) in preclinical AD have relied on associations with in-vivo measures of amyloid pathology. With the recent advent of in-vivo Tau-PET tracers it is now possible to extend investigations on fcMRI in a sample of cognitively normal elderly humans to regional measures of Tau. We modeled fcMRI measures across four major cortical association networks (Default Mode (DMN), Salience, Dorsal Attention (DAN), and Frontoparietal Control (FPCN)) as a function of global cortical amyloid (PiB-PET) and regional Tau (AV1451-PET) in entorhinal, inferior temporal (IT), and inferior parietal (IP) cortex...
March 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28314771/high-density-lipoprotein-hdl-metabolism-and-bone-mass
#18
Nicholaos Papachristou, Harry Blair, Kyriakos E Kypreos, Dionysios Papachristou
It is well appreciated that high density lipoprotein (HDL) and bone physiology and pathology are tightly linked. Studies, primarily in mouse models have shown that dysfunctional and/or disturbed HDL can affect bone mass through many different ways. Specifically, reduced HDL levels have been associated with the development of an inflammatory microenvironment that affects the differentiation and function of osteoblasts. In addition, perturbation in HDL metabolic pathways favor adipoblastic and restrain osteoblastic differentiation through, among others, the modification of specific bone-related chemokines and signaling cascades...
March 17, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28314770/cribriform-morular-variant-of-papillary-thyroid-carcinoma-a-distinctive-type-of-thyroid-cancer
#19
REVIEW
Alfred King-Yin Lam, Nassim Saremi
The aim of this systematic review is to study the features of cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) by analysing the 129 documented cases in the English literature. The disease occurred almost exclusively in women. The median age of presentation for CMV-PTC was 24 years. Slightly over half of the patients with CMV-PTC had familial adenomatous polyposis (FAP). CMV-PTC presented before the colonic manifestations in approximately half of the patients with FAP. Patients with FAP often have multifocal tumours in the thyroid...
April 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28314589/fgfr2-mutations-are-associated-with-poor-outcomes-in-endometrioid-endometrial-cancer-an-nrg-oncology-gynecologic-oncology-group-study
#20
Yvette W Jeske, Shamshad Ali, Sara A Byron, Feng Gao, Robert S Mannel, Rahel G Ghebre, Paul A DiSilvestro, Shashikant B Lele, Michael L Pearl, Amy P Schmidt, Heather A Lankes, Nilsa C Ramirez, Golnar Rasty, Matthew Powell, Paul J Goodfellow, Pamela M Pollock
PURPOSE: Activating FGFR2 mutations have been identified in ~10% of endometrioid endometrial cancers (ECs). We have previously reported that mutations in FGFR2 are associated with shorter disease free survival (DFS) in stage I/II EC patients. Here we sought to validate the prognostic importance of FGFR2 mutations in a large, multi-institutional patient cohort. METHODS: Tumors were collected as part of the GOG 210 clinical trial "Molecular Staging of Endometrial Cancer" where samples underwent rigorous pathological review and had more than three years of detailed clinical follow-up...
March 14, 2017: Gynecologic Oncology
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