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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病毒相关胃癌：对一株可移植于SCID小鼠的EB病毒相关胃癌株的全局m-RNA表达分析表明，与EB病毒阴性株相比，白细胞介素1-β(il - 1-β)在细胞因子相关基因中高表达。应用原位杂交技术特异性观察了EB病毒相关胃癌手术切除组织中il - 1-β mRNA的表达。接下来，我们对日本胃癌患者的il - 1-β多态性进行了评估。EB病毒阴性胃癌存在一定的多态性，EB病毒阳性胃癌不存在一定的多态性。因此，il - 1-β可能与EB病毒相关性胃癌的维持直接相关，也可能通过其多态性与EB病毒阴性胃癌的发生相关。通过甲基化特异性PCR评估各种癌症相关基因的启动子甲基化。结果表明，EB病毒相关性胃癌具有全局性和非随机性，癌组织中p16和E-cadherin的免疫组化表达随着各相应启动子的甲基化而降低或异常。当用亚硫酸酯测序评估p14启动子的甲基化谱时，在所有29个CpG位点都观察到高密度甲基化，而在EB病毒阴性的胃癌中则观察到低密度和罕见的甲基化。由于DNMT1、3a和3b的表达在感染EB病毒或未感染EB病毒的胃癌中没有差异，可能存在EB病毒感染胃上皮细胞特异性机制。脓胸相关淋巴瘤：脓胸相关淋巴瘤表现为EB病毒感染的潜伏期III，与艾滋病淋巴瘤相似。两例潜伏期III型淋巴瘤的DNA芯片分析显示，5个基因是脓胸相关淋巴瘤的特征基因，分别是PRAD、CEB1、GFOD、INSR（胰岛素受体，X02160）、MGC23980 （C9orf72）。