Pathogenesis of EB virus-associated neoplasms

EB病毒相关肿瘤的发病机制

基本信息

批准号：
14207009
负责人：
FUKAYAMA Masashi
金额：
$ 32.45万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

EB virus-associated gastric carcinoma : Global m-RNA expression analysis of a strain of EB-virus associated gastric carcinoma, which is transplantable in SCID mice, has demonstrated that interleukin 1-β(IL1-β) was highly expressed among the cytokine-related genes, when compared to EB virus-negative strains. IL1-β mRNA signals were specifically observed by in situ hyridization in surgically resected cancer tissues of EB virus-associated gastric carcinoma. Next, IL1-β polymorphisms were evaluated in Japanese patients with gastric cancer. Certain polymorphism was at high risk for EB virus-negative gastric carcinoma, but not for EB virus-positive one. Thus, IL1-β may be directly associated with the maintenance of EB virus-associated gastric carcinoma, and it may be also related with the development of EB virus-negative gastric carcinoma through its polymorphism.Promoter methylation of various cancer-related genes was evaluated by methylation specific PCR. As a result, EB virus-associated gastric carcinoma showed global and non-random, and immunohistochemical expression of p16 and E-cadherin in cancer tissues was decreased or abnormal along with methylation of each corresponding promoter. When the methylation profile of p14 promoter was evaluated by the Bisulfite sequencing, high density methylation was observed in all of 29 CpG sites in contrast to low density and infrequent methylation in EB virus-negative gastric carcinoma. Since expression of DNMT1, 3a and 3b was not different between gastric carcinomas with or without infection of EB virus, there might be a mechanism specific to EB virus infection of stomach epithelial cells.Pyotherax associated lymphoma : Pyothorax-associated lymphoma shows Latency III of EB virus infection similar to AIDS lymphomas. The DNA chip analysis of both Latency III type lymphomas demonstrated that five genes were characteristic to pyothorax-associated lymphoma, that is, PRAD,CEB1,GFOD,INSR (insulin receptor, X02160), MGC23980 (C9orf72).

EB病毒相关的胃癌：与EB病毒 - 阴性菌株相比，EB病毒相关的EB病毒菌株的全球M-RNA表达分析表明了相关基因在日本的胃癌患者中，对EB病毒相关的胃癌进行了IL1-β多态性与维持EB病毒囊肿的胃癌有关，它可能与EB病毒阴性胃castric Carugh的发展有关。通过甲基化特异性PCR评估了各种癌症相关ES的促甲基化ES的多态性。由于胃癌的全球非随机表达在癌症组织中p16和e-钙粘着蛋白的表达降低或异常，而甲基开口启动子则通过Bisulfite测序密度和EB病毒性胃癌的不经常性评估具有或没有感染EB病毒的DNMT1 Cinomas可能是与EB病毒感染的一种机制。证明五个基因是具有Pyothorax相关淋巴瘤的特征，即Prad，CEB1，GFOD，GFOD，GFOD INSR（胰岛素受体，X02160），MGC23980（C9orf72）。