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DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein-Barr virus

World Journal of Gastroenterology 2014年第14期20卷 3916-3926页

作者： Keisuke Matsusaka Sayaka Funata masashi fukayama Atsushi Kaneda Department of Molecular Oncology Graduate School of MedicineChiba University Department of Pathology Graduate School of MedicineThe University of Tokyo CREST Japan Science and Technology Agency

Gastric cancer is a leading cause of cancer death worldwide,and significant effort has been focused on clarifying the pathology of gastric *** particular,the development of genome-wide analysis tools has enabled the detection of genetic and epigenetic alterations in gastric cancer;for example,aberrant DNA methylation in gene promoter regions is thought to play a crucial role in gastric *** etiological viewpoint is also essential for the study of gastric cancers,and two distinct pathogens,Helicobacter pylori(***)and Epstein-Barr virus(EBV),are known to participate in gastric *** inflammation of the gastric epithelium due to *** infection induces aberrant polyclonal methylation that may lead to an increased risk of gastric *** addition,EBV infection is known to cause extensive methylation,and EBV-positive gastric cancers display a high methylation epigenotype,in which aberrant methylation extends to not only Polycomb repressive complex(PRC)-target genes in embryonic stem cells but also non-PRC-target ***,we review aberrant DNA methylation in gastric cancer and the association between methylation and infection with *** and EBV.

关键词： Gastric cancer Epigenetics DNA methylation Epstein-Barr virus Helicobacter pylori

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Involvement of miR-214 and miR-375 in Malignant Features of Non-Small-Cell Lung Cancer by Down-Regulating CADM1

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Journal of Cancer Therapy 2012年第4期3卷 379-387页

作者： Megumi Ishimura Mika Sakurai-Yageta Tomoko Maruyama Tomoko Ando masashi fukayama Akiteru Goto Yoshinori Murakami Department of Pathology Graduate School of Medicine The University of Tokyo Tokyo Japan Division of Molecular Pathology The University of Tokyo Tokyo Japan Laboratory of Pathology Institute of Medical Science The University of Tokyo Tokyo Japan

A tumor suppressor gene, CADM1, encoding an immunoglobulin superfamily cell adhesion molecule, is inactivated in various cancers, including non-small-cell lung cancer (NSCLC). Although promoter methylation is one of the mechanisms to suppress CADM1 expression, about half of tumors lacking CADM1 expression do not show methylation of the gene promoter. We herein investigated the possible involvement of microRNA (miRNA) in the down-regulation of CADM1. Using computational algorithms, miR-214 and miR-375 were identified as candidate miRNAs targeting CADM1. A luciferase reporter assay demonstrated that miR-214 and miR-375 repressed the promoter activity through 3’-UTR of CADM1. Quantitative RT-PCR analysis demonstrated that miR-214 and miR-375 was highly expressed in 21 (62%) and 17 cases (50%) of 34 primary NSCLCs. Notably, increased expression of miR-214 was preferentially observed in tumors with advanced pathological stages and in those lacking CADM1 expression but were not associated with the promoter methylation, suggesting that miR-214-mediated silencing would be another mechanism to suppress CADM1 expression. On the other hand, introduction of miR-214 or miR-375 into NSCLC cells decreased CADM1 protein expression. Furthermore, overexpression of miR-214 enhanced anchorage-independent growth of NSCLC cells, A549, whereas transfection of miRNA inhibitor, miR-214 or miR-375, significantly suppressed the in vitro wound healing activity of HCC827 cells. These findings suggest that overexpression of miR-214 and miR-375 could participate in the malignant features of NSCLC through down-regulating CADM1 and would provide a potential target for the treatment of a subset of NSCLC.

关键词： CADM1 miR-214 miR-375 Non-Small-Cell Lung Cancer

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Sessile serrated adenoma detection rate is correlated with adenoma detection rate

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World Journal of Gastrointestinal Oncology 2018年第3期10卷 82-90页

作者： Daisuke Ohki Yosuke Tsuji Tomohiro Shinozaki Yoshiki Sakaguchi Chihiro Minatsuki Hiroto Kinoshita Keiko Niimi Satoshi Ono Yoku Hayakawa Shuntaro Yoshida Atsuo Yamada Shinya Kodashima Nobutake Yamamichi Yoshihiro Hirata Tetsuo Ushiku Mitsuhiro Fujishiro masashi fukayama Kazuhiko Koike Department of Gastroenterology Graduate School of Medicinethe University of Tokyo Department of Biostatistics School of Public Healththe University of Tokyo Center for Epidemiology and Preventive Medicine Graduate School of Medicinethe University of Tokyo Department of Endoscopy and Endoscopic Surgery Graduate School of Medicinethe University of Tokyo Department of Pathology Graduate School of Medicine the University of Tokyo

AIM To investigated the association between adenoma detection rate(ADR) and sessile serrated ADR(SSADR) and significant predictors for sessile serrated adenomas(SSA) *** This study is a retrospective, single-center analysis. Total colonoscopies performed by the gastroenterologists at the University of Tokyo Hospital between January and December 2014 were retrospectively identified. Polyps were classified as low-grade or high-grade adenoma, cancer, SSA, or SSA with cytological dysplasia, and the prevalence of each type of polyp was investigated. Predictors of adenoma and SSA detection were examined using logistic generalized estimating equation models. The association between ADR and SSADR for each gastroenterologist was investigated by calculating a correlation coefficient weighted by the number of each gastroenterologist's *** A total of 3691 colonoscopies performed by 35 gastroenterologists were assessed. Overall, 978 (26.5%) low-and 84 (2.2%) high-grade adenomas, 81 (2.2%) cancers, 66 (1.8%) SSAs, and 2 (0.1%) SSAs with cytological dysplasia were detected. Overall ADR was 29.5%(men 33.2%, women 23.8%) and overall SSADR was 1.8%(men 1.7%, women 2.1%). In addition, 672 low-grade adenomas (68.8% of all the detected lowgrade adenomas), 58 (69.9%) high-grade adenomas, 29 (34.5%) cancers, 52 (78.8%) SSAs, and 2 (100%) SSAs with cytological dysplasia were found in the proximal colon. Adenoma detection was the only significant predictor of SSA detection (adjusted OR: 2.53, 95%CI: 1.53-4.20; P < 0.001). The correlation coefficient between ADR and SSADR weighted by the number of each gastroenterologist's examinations was 0.606(P < 0.001).CONCLUSION Our results demonstrated that ADR is correlated to SSADR. In addition, patients with adenomas had a higher prevalence of SSAs than those without adenomas.

关键词： Sessile serrated adenoma Sessile serrated adenoma detection rate Adenoma detection rate Colonoscopy Interval colorectal cancer

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