Pathogenesis of EB virus-associated neoplasms

EB病毒相关肿瘤的发病机制

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14207009/
• 关键词: EB virus; gastric carcinoma; pyothorax-associated lymphoma; interleukin 1-b; genetic polymorphism; methylation; promoter; AIDS lymphoma; EBウイルス関連腫瘍; EBウイルス関連胃癌; IL1-β; 胃癌細胞株; アポトーシス; DNAチップ; 遺伝子発現プロファイル; SCIDマウス移植株; プロモーター領域

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：对可移植到 SCID 小鼠的 EB 病毒相关胃癌株的整体 mRNA 表达分析表明，白细胞介素 1-β(IL1-β) 在细胞因子-中高表达。与 EB 病毒阴性菌株相比，通过原位杂交在 EB 病毒相关胃癌的癌组织中特异性观察到 IL1-β mRNA 信号。在日本胃癌患者中进行了评估，某些多态性对于 EB 病毒阴性胃癌具有高风险，但对于 EB 病毒阳性胃癌则不然，因此，IL1-β 可能与 EB 病毒相关胃癌的维持直接相关。其多态性可能与EB病毒阴性胃癌的发生有关。通过甲基化特异性PCR对多种癌症相关基因的启动子甲基化进行评估，结果发现EB病毒相关性胃癌。结果显示，癌组织中 p16 和 E-cadherin 的免疫组织化学表达呈整体性和非随机性，并且伴随着各个相应启动子的甲基化，当通过亚硫酸氢盐测序评估 p14 启动子的甲基化谱时，观察到高密度甲基化。与 EB 病毒阴性胃癌中低密度且不频繁的甲基化相比，DNMT1、3a 和 3b 的表达均在所有 29 个 CpG 位点中。感染或不感染EB病毒的胃癌之间没有区别，可能存在一种针对胃上皮细胞的EB病毒感染的特异性机制。 脓胸相关淋巴瘤：脓胸相关淋巴瘤表现出与艾滋病淋巴瘤相似的EB病毒感染潜伏期III。对两种潜伏期III型淋巴瘤的芯片分析表明，五个基因是脓胸相关淋巴瘤的特征，即PRAD、CEB1、GFOD、INSR （胰岛素受体，X02160），MGC23980（C9orf72）。

项目成果

Global and non-random CpG-island methlylation in gastric carcinoma associated with Epstein-Barr virus.

与 Epstein-Barr 病毒相关的胃癌中的整体和非随机 CpG 岛甲基化。

• 发表时间: 2003
• 作者: Chong JM; et al.
• 通讯作者: et al.

Cancer risk to the gastric corpus in Japanese, its correlation with Interleukin-1beta gene polymorphism (+3953^*T) and Epstein-Barr virus infection.

日本人胃体癌症风险及其与Interleukin-1beta基因多态性(3953^*T)和Epstein-Barr病毒感染的相关性。

• 发表时间: 2005
• 作者: Sakuma K et al.

Cancer risk to the gastric corpus in Japanese, its correlation with Interleukin-1beta gene polymorphism (+3953^*T) and Epstein-Barr virus infection.

日本人胃体癌症风险及其与Interleukin-1beta基因多态性(3953^*T)和Epstein-Barr病毒感染的相关性。

• 发表时间: 2005
• 作者: Sakuma K et al.

Interleukin-1β Expression in Human Gastric Carcinoma with Epstein-Barr Virus Infection

EB 病毒感染的人胃癌中白细胞介素 1β 的表达

• DOI: 10.1128/jvi.76.13.6825-6831.2002
• 发表时间: 2002-07-01
• 期刊: Journal of Virology
• 影响因子: 5.4
• 作者: J. Chong;Kazuya Sakuma;Makoto Sudo;Toshio Osawa;Etsuko Ohara;H. Uozaki;J. Shibahara;Kenji Kuroiwa;S. Tominaga;Y. Hippo;Hiroyuki Aburatani;N. Funata;Masashi Fukayama
• 通讯作者: Masashi Fukayama

P16 protein abnormality in Epstein-Barr virus-associated gastric carcinomas.

Epstein-Barr 病毒相关胃癌中的 P16 蛋白异常。

• 发表时间: 2006-03-01
• 期刊: Anticancer research
• 影响因子: 2
• 作者: H. Ojima;Kana Saito;H. Yamauchi;E. Yamaki;Akihito Idetu;Y. Hosouchi;Y. Nishida;K. Tukada;H. Kato
• 通讯作者: H. Kato