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Experimental and Molecular Pathology

Yu-Chuan Chen, Matthew Baik, Joshua Byers, Kathryn T Chen, Samuel W French, Begoña Díaz
Invadopodia, cancer cell protrusions with proteolytic activity, are functionally associated with active remodeling of the extracellular matrix. Here, we show that the invadopodia-related protein TKS5 is expressed in human pancreatic adenocarcinoma lines, and demonstrate that pancreatic cancer cells depend on TKS5 for invadopodia formation and function. Immunofluorescence staining on human pancreatic cancer cells reveals that TKS5 is a marker of mature and immature invadopodia in these cells. We analyze the co-staining patterns of TKS5 and the commonly used invadopodia marker Cortactin, and find only partial co-localization of these two proteins at invadopodia, with a large fraction of TKS5-positive invadopodia lacking detectable levels of Cortactin...
November 12, 2018: Experimental and Molecular Pathology
Cameron M Scott, Ee Ming Wong, JiHoon Eric Joo, Pierre-Antoine Dugué, Chol-Hee Jung, Neil O'Callaghan, James Dowty, Graham G Giles, John L Hopper, Melissa C Southey
Breast cancers arising in women carrying a germline mutation in BRCA1 are typically high-grade, early-onset and have distinct morphological features (BRCA1-like). However, the majority of early-onset breast cancers of this morphological type are not associated with germline BRCA1 mutations or constitutional BRCA1 promoter methylation. We aimed to assess DNA methylation across the genome for associations with the "BRCA1-like" morphology. Genome-wide methylation in blood-derived DNA was measured using the Infinium HumanMethylation450K BeadChip assay for women under the age of 40 years participating in the Australian Breast Cancer Family Study (ABCFS) diagnosed with: i) BRCA1-like breast cancer (n = 30); and ii) breast cancer without BRCA1-like morphological features (non BRCA1-like; n = 30), and age-matched unaffected women (controls; n = 30)...
November 10, 2018: Experimental and Molecular Pathology
Christine M Longo, Paul J Higgins
Graves' ophthalmopathy (GO), a complication of Graves' disease (GD), is typified by orbital inflammation, ocular tissue expansion and remodeling and, ultimately, fibrosis. Orbital fibroblasts are key effectors of GO pathogenesis exhibiting exaggerated inflammatory and fibroproliferative responses to cytokines released by infiltrating immune cells. Activated orbital fibroblasts also produce inflammatory mediators that contribute to disease progression, facilitate the orbital trafficking of monocytes and macrophages, promote differentiation of matrix-producing myofibroblasts and stimulate accumulation of a hyaluronan-rich stroma, which leads to orbital tissue edema and fibrosis...
November 8, 2018: Experimental and Molecular Pathology
Firoz Ahmad, Richa Nathani, Janani Venkat, Anahita Bharda, Veena Vanere, Simi Bhatia, Bibhu Ranjan Das
BACKGROUND: Somatic mutation of the BRAF gene is one to be the most commonly known genetic change in thyroid tumors especially papillary thyroid cancers. The T1799A activating point mutation is detected in >98% of the thyroid tumors, and result in substitution of amino acid valine at position 600 to glutamic acid. METHOD: In this study, we evaluated BRAF mutation in 95 Indian thyroid tumors by pyrosequencing assay. RESULTS: Overall, 36 cases (38%) showed presence of BRAF V600E mutation, while none of the cases showed V600 K mutation...
November 8, 2018: Experimental and Molecular Pathology
Lisa Linck, Janika Liebig, Daniel Völler, Norbert Eichner, Gerhard Lehmann, Gunter Meister, Anja Bosserhoff
MicroRNAs (miRNAs) deregulated in melanoma are of growing importance in cancer research. We aimed to define the miRNAome of melanoma cell lines and primary melanocytes by RNA-Seq using identical cell lines as in a published miRNA expression study based on cDNA arrays. We identified 79 miRNAs, which are significantly deregulated during melanoma development. In addition, we could also determine 29 miRNAs being involved in melanoma progression. Interestingly, not all characterized miRNAs derived from cDNA array analyses of our and other groups could be found to be differentially expressed using RNA-Seq analyses, however, new miRNAs, formerly not associated with melanoma, were found to be strongly regulated...
November 8, 2018: Experimental and Molecular Pathology
Ufuk Senel, Ozlem Silan Coskun, Emre Can Tuysuz, Mesut Sahin, Omer Faruk Bayrak, Bulent Cakmak, Halil Ibrahim Tanriverdi, Aysegul Kuskucu
Amniotic fluid (AF) is the liquid layer that provides mechanical support and allows movement of the fetus during embryogenesis. Mesenchymal stem cells (MSCs), which have differentiation capacity, are also found in AF-derived cells at a low ratio. Smooth muscle cells (SMCs) play an important role in organ function and are frequently used in tissue engineering. We examined the differentiation of AF-derived MSCs (AMSCs) into SMCs. AMSCs were sorted from cultured amniotic cells and differentiated into SMCs using differentiation agents, including platelet-derived growth factor BB (PDGF-BB) and tumor growth factor B (TGF-B)...
November 8, 2018: Experimental and Molecular Pathology
Regina You Zhen Soh, Jia Pei Lim, Ramar Perumal Samy, Pei Jou Chua, Boon Huat Bay
A-kinase anchor protein 12 (AKAP12) also known as Gravin and SSeCKS, is a novel potent scaffold protein for many key signaling factors, such as protein kinase C (PKC), PKA, cyclins as well as F-actin. AKAP12 expression is known to be suppressed in several human malignancies including breast, prostate, gastric and colon cancers. In this study, we evaluated the role of AKAP12 in the migration of breast cancer cells, an important cellular process in cancer progression. AKAP12 gene expression was analyzed in human breast cancer tissues using the Gene expression-based Outcome for Breast cancer Online (GOBO) database and TissueScan array, followed by relapse free survival (RFS) analysis with the Kaplan Meier Plotter...
October 29, 2018: Experimental and Molecular Pathology
Fahad Mubariz, Joseph L Bryant, Vamshi K C Nimmagadda, Jayanta Ray, Tapas K Makar
No abstract text is available yet for this article.
October 22, 2018: Experimental and Molecular Pathology
A Pires-Luis, D Montezuma, J Vieira, J Ramalho-Carvalho, C Santos, M Teixeira, C Jerónimo, R Henrique
INTRODUCTION: Hybrid oncocytic/chromophobe tumor (HOCT) is a renal cell neoplasm displaying overlapping cellular and architectural features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC). It has been described in the context of oncocytosis, Birt-Hogg-Dubé syndrome, and also sporadically. Thus far, HOCT immunohischemical profile and cytogenetic alterations have been reported, but not epigenetic alterations. Herein, we characterize a HOCT case, including microRNA expression, comparing it to sporadic RO and chRCC...
October 18, 2018: Experimental and Molecular Pathology
Samantha N McNulty, Katherine Schwetye, Michael Goldstein, Jamal Carter, Robert E Schmidt, George Ansstas, Christina I Tsien, Albert H Kim, Sonika Dahiya
Meningiomas are among the most common tumors of the adult central nervous system (CNS). They are classified by the World Health Organization into three pathologic grades with increasing severity: grade I are benign with favorable treatment outcomes and low recurrence rates while grade III display malignant behavior and poor progression-free survival. Previous studies have shown that inactivation of NF-2 is the most common genetic event in high-grade meningioma; however, there is dearth of molecular data to distinguish grade II (AM-II) from the even more aggressive grade III (AM-III)...
October 11, 2018: Experimental and Molecular Pathology
Kenichi Watanabe, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Geetha Kandasamy, Meilei Harima, Ravichandiran Velayutham, Somasundaram Arumugam
Basidiomycetes-X (BDM-X) is a novel edible mushroom recently identified as a new fungi species and is effective against oxidative stress and anti-inflammation associated with immune response. However the effect of BDM-X on atopic dermatitis (AD) has not been elucidated. In this study, we have investigated the effect of BDM-X on AD skin lesions in NC/Nga mouse model. AD-like lesion was induced by the application of house dust mite extract (DfE) to the dorsal skin of NC/Nga mouse. After AD induction, BDM-X was administered once daily for 2 weeks...
October 9, 2018: Experimental and Molecular Pathology
Weiguo Wang, Ruisen Zhan, Jiahui Zhou, Jianlong Wang, Shijie Chen
The present study is aimed to investigate the molecular mechanism of miR-10 targeting NgR to regulate the proliferation and inflammatory cytokine secretion in microglia cells (MCs). The expression levels of NgR, IL-1β, and TNF-α in rat MCs were detected by QPCR and Immunoblotting assays. The proliferation of MC was detected by MTT and Soft agar clone formation assays. The target gene of miR-10 was verified by dual luciferase reporter gene assay. Overexpressed miR-10 downregulated the expression of NgR, promoted MC proliferation and inhibited inflammatory cytokine secretion...
October 9, 2018: Experimental and Molecular Pathology
Luisa F González Arbeláez, Alejandro Ciocci Pardo, Erik R Swenson, Bernardo V Álvarez, Susana M Mosca, Juliana C Fantinelli
BACKGROUND: Recent studies from our laboratory show the cardioprotective action of benzolamide (BZ, carbonic anhydrase inhibitor) against ischemia-reperfusion injury. However, the mechanisms involved have not been fully elucidated. OBJECTIVE: To examine the participation of the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) in the effects of BZ in a model of regional ischemia. METHODS: Isolated rat hearts perfused by Langendorff technique were submitted to 40 min of coronary artery occlusion followed by 60 min of reperfusion (IC)...
October 9, 2018: Experimental and Molecular Pathology
Yosra M Magdy, Omnyah A El-Kharashi, Dalia A A El-Waseef, Enas S Nabih, Abeer A Abd El Samad
OBJECTIVES: The repression of renal Farnesoid X Receptor (FXR) had been shown to result from lack of bile acid production from cirrhotic liver. We hypothesized that silymarin and rosuvastatin (Rvs) could have a hepatorenal therapeutic effects in hepatic nephropathy through induction of FXR. METHODS: Forty two male Wistar rats were used; naïve (n = 12); six of them were sacrificed after 4 weeks and six continued till the end of the experiment. Thirty rats were treated as follows: Rvs, silymarin, thioacetamide (TAA), TAA + Rvs and TAA + silymarin...
October 9, 2018: Experimental and Molecular Pathology
Xin Diao, Jing Zhou, Shengyu Wang, Xuan Ma
The role of microRNAs has been recently identified in chronic obstructive pulmonary disease (COPD). This study aimed to examine the role of miR-132 in the pathophysiology of COPD and to explore the underlying molecular mechanisms of miR-132 in COPD. MiR-132 and suppressor of cytokine signaling 5 (SOCS5) mRNA expression were detected by qRT-PCR. The number of CD4+ and CD8+ T cells was analyzed by flow cytometry. SOCS5 and epidermal growth factor receptor (EGFR) protein levels were determined by western blot...
October 4, 2018: Experimental and Molecular Pathology
Marwa Chaouali, Veronica Fernandes, Ezzedine Ghazouani, Luisa Pereira, Radhia Kochkar
The physiopathology of autoimmune hepatitis (AIH) is complex and still not fully elucidated. The genes localized outside the histocompatibility complex involved in regulation and signal transduction of the immune system SH2B3, TGFβ1, STAT4 and PTPN22 could be associated to the susceptibility and hepatocyte lysis mechanism of this lethal autoimmune disorder. PATIENTS AND METHODS: We investigated four polymorphic sites in SH2B3 (rs3184504), TGFβ1 (rs1800471), STAT4 (rs7574865) and PTPN22 (rs2476601) in 45 AIH patients and 150 healthy controls from Tunisia using real-time PCR...
October 3, 2018: Experimental and Molecular Pathology
Farhana Afroz, Alwyn Kist, Jin Hua, Yabin Zhou, Elke M Sokoya, Robert Padbury, Vincent Nieuwenhuijs, Greg Barritt
Rapamycin (sirolimus) is employed as an immunosuppressant following liver transplant, to inhibit the re-growth of cancer cells following liver resection for hepatocellular carcinoma (HCC), and for the treatment of advanced HCC. Rapamycin also induces the expression of antioxidant enzymes in the liver, suggesting that pretreatment with the drug could provide a potential strategy to reduce ischemia reperfusion injury following liver surgery. The aim of this study was to further investigate the actions of rapamycin in inducing expression of the antioxidant enzymes heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prx-1) in normal liver and in tumorigenic liver cells...
October 2, 2018: Experimental and Molecular Pathology
Yuan Qu, Xingchi Liang, Dan Liu, Huimin Jia, Weilin Wang
BACKGROUND: This study aimed to determine Msh homeobox 2 (MSX2) and B cell lymphoma-2 (BCL2) expression patterns during anorectal development in anorectal malformations (ARM) and normal rat embryos, with the goals of determining the role of MSX2 and BCL2 in ARM pathogenesis. METHODS: ARM was induced in rat embryos with ethylenethiourea administered to dams on gestational day 10 (GD10). Embryos were harvested by cesarean deliveries from GD14 to GD16. MSX2 and BCL2 expression was evaluated via immunohistochemical staining, immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR)...
September 28, 2018: Experimental and Molecular Pathology
Sara Ibrahim, Rania Dayoub, Michael Melter, Thomas S Weiss
Bile acids (BA) are signaling molecules that activate nuclear factors and g-protein coupled receptors signaling to maintain metabolic homeostasis. However, accumulation of toxic BA promotes liver injury by initiating inflammation, inducing apoptosis and causing oxidative stress leading to cirrhosis and liver failure. Augmenter of Liver Regeneration (ALR) is a hepatotrophic growth factor with anti-apoptotic and anti-oxidative properties that has been shown to improve mitochondrial and hepatic functions in rats after bile duct ligation...
September 20, 2018: Experimental and Molecular Pathology
Zhao-Bin Yang, Wen-Wen Chen, Hui-Ping Chen, Shu-Xian Cai, Jian-Dong Lin, Lu-Zhen Qiu
OBJECTIVE: Liver is uniquely vulnerable during sepsis. MicroRNA-155 (miR-155) is confirmed to play crucial roles in septic liver injury. The present study aims to investigate the mechanisms of miR-155 in septic liver injury. METHODS: The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) in mice. Mice were divided into four groups: Vehicle, miR-155 antagomir, LPS, LPS+ miR-155 antagomir. The survival rate and body weight were monitored...
September 12, 2018: Experimental and Molecular Pathology
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