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Experimental and Molecular Pathology

Samir M Amer, Kamlesh K Bhopale, Ramu D Kakumanu, Vsevolod L Popov, Bill A Rampy, Inas H El-Mehallawi, Magdy M Ashmawy, G A Shakeel Ansari, Bhupendra S Kaphalia
The single most common cause of chronic pancreatitis (CP, a serious inflammatory disease) is chronic alcohol abuse, which impairs hepatic alcohol dehydrogenase (ADH, a major ethanol oxidizing enzyme). Previously, we found ~5 fold greater fatty acid ethyl esters (FAEEs), and injury in the pancreas of hepatic ADH deficient (ADH-) vs. hepatic normal ADH (ADH+) deer mice fed 3.5g% ethanol via liquid diet daily for two months. Therefore, progression of ethanol-induced pancreatic injury was determined in ADH- deer mice fed ethanol for four months to delineate the mechanism and metabolic basis of alcoholic chronic pancreatitis (ACP)...
January 11, 2018: Experimental and Molecular Pathology
Farhadul Islam, Vinod Gopalan, Jelena Vider, Cu-Tai Lu, Alfred K-Y Lam
OBJECTIVES: miR-142-5p was noted aberrantly expressed and plays important roles in different pathophysiological conditions in human. The present study aims to examine the expression of miR-142-5p and its association with clinicopathological factors in a large cohort of patients with colorectal cancer. In addition, the cellular effects of miR-142-5p and its interacting targets in colon cancer cells were investigated. METHODS: Expression of miR-142-5p in colorectal cancer tissues (n=125) and colon cancer cell lines were analysed using real-time polymerase chain reaction...
January 11, 2018: Experimental and Molecular Pathology
Juliane Büttner, Korinna Jöhrens, Frederick Klauschen, Michael Hummel, Dido Lenze, Wolfgang Saeger, Annika Lehmann
Anti-EGFR-targeted therapy is used to treat metastatic colorectal cancers with RAS wild-type. However, resistance to targeted therapy is often observed and can be primary or acquired. One reason for primary resistance is the presence of mutations that are undetected due to genetic heterogeneity, which can be expressed by differences present in primary tumor and distant metastasis or recurrence or by an intratumoral heterogeneity (presence of different subclones in the investigated tumor sample). The aim of our study was to investigate if morphological heterogeneity can be an indicator of intratumoral heterogeneity...
January 11, 2018: Experimental and Molecular Pathology
Riajul Wahab, Vinod Gopalan, Farhadul Islam, Afraa Mamoori, Katherine Ting-Wei Lee, Cu-Tai Lu, Alfred King-Yin Lam
AIM: GAEC1 (Gene amplified in esophageal cancer 1) is an oncogene with key regulatory roles in the pathogenesis of oesophageal and colorectal carcinomas. The aim of this study was to investigate expression profiles and clinicopathological significance of GAEC1 mRNA and protein in patients with colorectal carcinomas. METHOD: Matched cancer and non-cancer fresh frozen tissues were prospectively collected from 80 patients diagnosed with colorectal adenocarcinoma (39 men and 41 women)...
January 11, 2018: Experimental and Molecular Pathology
Elena Larrieta-Carrasco, Yvonne N Flores, Luis R Macias-Kauffer, Paula Ramírez, Manuel Quiterio, Eric G Ramirez-Salazar, Paola León-Mimila, Berenice Rivera-Paredez, Guillermo Cabrera-Álvarez, Samuel Canizales-Quinteros, Zuo-Feng Zhang, Tania V López-Pérez, Jorge Salmerón, Rafael Velázquez-Cruz
Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and risk of elevated transaminase levels in an admixed Mexican-Mestizo sample of 178 cases of NAFLD and 454 healthy controls...
January 4, 2018: Experimental and Molecular Pathology
Luan Nguyen, Maryam Masouminia, Alejandro Mendoza, Sara Samadzadeh, Brittany Tillman, Timothy Morgan, Barbara French, Samuel French
Non-alcoholic steatohepatitis (NASH) is commonly associated with obesity, type 2 diabetes, and/or hypertriglyceridemia, while alcoholic steatohepatitis (ASH) is associated with alcohol abuse. Both NASH and ASH patients can develop cirrhosis and hepatocellular carcinoma (HCC) if left untreated. However, the rate of tumorigenesis in NASH and ASH appears to be different. Individuals with NASH progress to HCC at a rate of 0.5% annually (Lindenmeyer, 2018), when individuals with ASH progress to HCC at a rate of 3-10% annually (Schwartz and Reinus, 2012)...
January 4, 2018: Experimental and Molecular Pathology
Taurino Federica, Gnoni Antonio
This review summarizes recent studies on plasma-membrane ecto-ATP synthase from structural and functional standpoints to possible pathophysiological roles. This review discusses significant new contributions and perspectives in the area of ecto-ATP synthase since the topic was last reviewed in 2015. Following an extensive summary of the cell types in which the ecto-ATP synthase is present, its structural and functional mechanism are discussed and physiological and pathological roles of the ecto-ATP synthase are reviewed and evaluated...
January 2, 2018: Experimental and Molecular Pathology
Tamara Knific, Snježana Frković Grazio, Tea Lanišnik Rižner
OBJECTIVE: To examine the potential of ARX as a novel biomarker of ovarian endometriosis and other ovarian pathologies. METHODS: The mRNA level of ARX in ovarian endometriosis and normal endometrium samples was determined by real-time PCR, while the protein level was determined by Western blotting and immunohistochemical staining. Immunohistochemical analysis was performed on nearly 200 tissue samples of different ovarian pathologies. GraphPad Prism was used for statistical analysis...
December 21, 2017: Experimental and Molecular Pathology
Chun Mei Hou, Xue Mei Qu, Jian Zhang, Ting Ting Ding, Wei Han, Guang Chuan Ji, Zhao Hua Zhong, He Chen, Feng-Min Zhang
Fibroblast activation protein-α (FAPα) is a type-II cell-surface-bound integral transmembrane serine protease and selectively overexpressed by tumor-associated stromal fibroblasts (TAFs), which are the main components in the tumor microenvironment, in >90% of malignant epithelial carcinomas. FAPα regulates the immunosuppression of tumor cells in the tumor microenvironment. Regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are the major immunosuppressive cells in the tumor microenvironment...
December 19, 2017: Experimental and Molecular Pathology
Andrea M Olofson, Laura J Tafe
Mixed morphology lung tumors are rare; this is the second report of a combined NSCLC and atypical carcinoid tumor. Next generation sequencing was performed on both histologically distinct patterns which identified that both components harbored a BRAF p.V600E mutation. Molecular studies inform our knowledge of the biology and aid in treatment decisions for mixed morphology lung cancers.
December 14, 2017: Experimental and Molecular Pathology
Zheng Li, Yonghua Tang, Wujun Xing, Wei Dong, Zhichou Wang
Osteosarcoma is the most common bone malignancy in adolescence. Recently, the long non-coding RNAs (lncRNAs) were reported to play important roles in osteosarcoma progression. The present study examined the potential role of the lncRNA, Colorectal Neoplasia Differentially Expressed (CRNDE) and molecular mechanisms underlying osteosarcoma progression. In the present study, we identified that CRNDE was up-regulated in osteosarcoma tissues and cell lines, and CRNDE expression level was significantly higher in osteosarcoma tissues from patients with advanced stage and metastasis...
December 12, 2017: Experimental and Molecular Pathology
Yongli Zhao, Guohua Li, Yuchuan Wang, Zhengjuan Liu
It is accepted that alteration of connexin43 (Cx43) expression in glomeruli is a common pathological response in several forms of kidney diseases. To date, however the change of the Cx43 expression in obesity-related glomerulopathy (ORG) has not been reported. In this study, the alteration of Cx43 expression in the glomeruli of rat with ORG was defined. Five-week-old rats were fed with high-fat diet for 18weeks to establish the ORG model, then the histological change of glomeruli, the foot process effacement of podocyte, the markers for podocyte injury (nephrin,podocin and WT1) and Cx43 expression in glomeruli were examined respectively...
December 12, 2017: Experimental and Molecular Pathology
Maryam Masouminia, Hassan Abdul Ghani, Dingle Foote, Danielle Hari, Samuel French
No abstract text is available yet for this article.
December 5, 2017: Experimental and Molecular Pathology
Colin T Shearn, David J Orlicky, Dennis R Petersen
OBJECTIVE: Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver disease that is characterized by severe peri-biliary tract inflammation and fibrosis, elevated oxidative stress and hepatocellular injury. A hallmark of PSC patients is the concurrent diagnosis of Inflammatory Bowel Disease occurring in approximately 70%-80% of PSC patients (PSC/IBD). The objective of this study was to determine the impact of end stage PSC/IBD on cellular antioxidant responses and the formation of protein carbonylation...
November 24, 2017: Experimental and Molecular Pathology
Ariangela J Kozik, Cindy H Nakatsu, Hyonho Chun, Yava L Jones-Hall
Mouse models are often used to determine the interactions between the microbiota and inflammatory processes and overcome the confounding effect of the naturally high inter-individual variation of the gut microbiota in humans. However, the microbiomes of mice are also variable and data detailing the degree to which factors like mouse sex and age contribute to mouse gut microbiota variation is limited. Our objective was to determine the impact sex and age have on the mouse gut microbiota and the severity of acute 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) induced colitis...
November 22, 2017: Experimental and Molecular Pathology
Fabien Forest, Marie-Laure Stachowicz, François Casteillo, Georgia Karpathiou, Fabienne Gouzy-Grosjean, Colette Guilaubey, Michèle Cottier, Julie Beal, Alix Clemenson, Michel Péoc'h
Molecular testing on metastatic lung adenocarcinoma or on non-small cell non-squamous lung carcinoma often relies on small specimen. In this group of patient with poor specimen adequacy, we analyzed the rate of EGFR, KRAS, BRAF and HER2 mutations compared to their rate in optimal specimen. We analyzed discrepancies in molecular testing results in patients with iterative analysis on several samples. We performed a retrospective study of 1538 samples consecutively analyzed. 263/665 (39,5%) biopsies and 37/708 (5,2%) surgical specimens were considered as samples with poor specimen adequacy (p<0,0001)...
November 22, 2017: Experimental and Molecular Pathology
Fabiana Bettoni, Fernanda Christtanini Koyama, Paola de Avelar Carpinetti, Pedro Alexandre Favoretto Galante, Anamaria Aranha Camargo, Paula Fontes Asprino
Next generation sequencing (NGS) has become an informative tool to guide cancer treatment and conduce a personalized approach in oncology. The biopsy collected for pathologic analysis is usually stored as formalin-fixed paraffin-embedded (FFPE) blocks and then availed for molecular diagnostic, resulting in DNA molecules that are invariably fragmented and chemically modified. In an attempt to improve NGS based diagnostics in oncology we developed a straightforward DNA integrity assessment assay based on qPCR, defining clear parameters to whether NGS sequencing results is accurate or when it should be analyzed with caution...
November 21, 2017: Experimental and Molecular Pathology
Daniel R Matson, Heather Hardin, Darya Buehler, Ricardo V Lloyd
The PI3K/AKT/mTOR signaling pathway controls major cellular processes such as cell growth, proliferation and survival. Stimulation of this pathway leads to AKT phosphorylation and activation, resulting in phosphorylation of mTOR and myriad other targets. AKT upregulation has been implicated in thyroid cancer pathogenesis and is a candidate treatment target for patients with advanced disease that has not responded to traditional therapies. Here we evaluate a large series of benign and malignant thyroid tumors for AKT activity and intracellular distribution...
November 20, 2017: Experimental and Molecular Pathology
Amin A Hedayat, Konstantinos Linos, Hou-Sung Jung, Laura J Tafe, Shaofeng Yan, Robert E LeBlanc, Joel A Lefferts
Histopathology is the gold standard for diagnosing melanocytic lesions; however, distinguishing benign versus malignant is not always clear histologically. Single nucleotide polymorphism (SNP) microarray analysis may help in making a definitive diagnosis. Here, we share our experience with the Oncoscan FFPE Assay and demonstrate its diagnostic utility in the context of ambiguous melanocytic lesions. Eleven archival melanocytic lesions, including three benign nevi, four melanomas, three BAP1-deficient Spitzoid nevi and one nevoid melanoma were selected for validation...
November 20, 2017: Experimental and Molecular Pathology
Ashkaun Shaterian, Daniela Bota, Amber Leis
The pathogenesis of neurofibromas is poorly understood outside of neurofibromatosis (NF). The BRAF proto-oncogene has been implicated in malignant peripheral nerve sheath tumors (PNSTs), however its role in neurofibromas has not been described. In this study, we identify a BRAF mutation in a 61-year old non-NF patient with a history of sporadic and recurrent neurofibromas localized to the right upper extremity. Despite repeat resections to establish local control, he developed median nerve neuropathy secondary to a 13×4cm plexiform neurofibroma...
November 18, 2017: Experimental and Molecular Pathology
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