Comprehensive analyses of therapeutic strategy against chronic active Epstein-Barr virus(EBV) infection
Comprehensive analyses of therapeutic strategy against chronic active Epstein-Barr virus(EBV) infection
批准号:
18591190
负责人:
WAKIGUCHI Hiroshi
金额:
$2.44万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2006
资助国家:
日本
项目状态:
已结题
起止时间:
2006 至 2007
中文摘要
本研究的目的是利用显性阴性EBNA1 (DNE1; Mal. Ther.),在EBV阳性的T细胞、MC细胞和上皮肿瘤细胞中,鉴定与eb病毒(EBV)致癌相关或负责的细胞基因。生物工程学报,11(4):578- 90,2005),可以从细胞中根除EBV发作。我们通过DNE1转导制备ebv阳性和阴性NK和t细胞系等基因对,并比较它们的恶性分级。这些细胞对中伴随的细胞基因表达变化通过多细胞因子分析系统进行了全面评估,从而阐明了EBV在恶性转化中的作用。此外,我们使用ebv抗原BRLF1、BMLF1和EBNA3,通过四聚体分析ebv特异性细胞毒性t细胞(EBV-CTL)。得到的结果如下:1。腺病毒载体介导的DNE1在几天内成功地从大多数自然EBV阳性t细胞和nk细胞淋巴瘤和上皮性肿瘤细胞系中根除EBV发作。与亲代ebv阳性t细胞和nk细胞肿瘤相比,dne1诱导的ebv缺失t细胞和nk细胞表现出显著的恶性表型抑制,如加倍时间延长和锚定不依赖生长势的丧失。在部分丢失ebv的t细胞和nk细胞中,病毒基因组的丢失也导致细胞死亡。与亲代ebv阳性t细胞和nk细胞肿瘤相比,ebv缺失的t细胞和nk细胞的某些细胞因子如白细胞介素-9的产生明显减少。相反,另一种细胞因子的产生水平也被发现在ebv丢失的t细胞中上调。这些结果表明,在T细胞和nk细胞以及上皮细胞(如b细胞淋巴瘤)中,ebv依赖的恶性表型至少部分与某些细胞因子的上调(即自分泌机制)和/或下调相关。我们正计划精确地探索细胞因子基因在EBV肿瘤发生中的调控机制和特异性作用。少
英文摘要
The aim of this study was to identify the cellular genes associated with or responsible for the oncogenesisi of Epstein-Barr virus (EBV) in EBV-positive T, MC and epithelial tumor cells, by utilizing dominant-negative EBNA1 (DNE1; Mal. Ther., 11(4): 578-90, 2005)that can eradicate EBV episomes from cells. We prepared isogenic pairs of EBV-positive and -negative NK- and T-cell lines by DNE1 transduction and compared their malignant grade. Concomitantly alterations of cellular gene expression in those cell pairs were comprehensively assessed with the multi-cytokine assay system, thereby elucidating the role(s)of EBV in malignant conversion. Further, we analysed EBV-specific cytotoxic T-cells (EBV-CTL) by a tetramer assay using 3 EBV-antigens, i.e., BRLF1, BMLF1 and EBNA3. The results obtained are as follows.1. Adenovirus vector-mediated transduction of our DNE1 successfully eradicated EBV episomes from the majority of naturally EBV-positive T-cell and NK-cell lymphoma and epithelial tumo … More r cell lines in a few days.2. The DNE1-induced EBV-lost T-cells and NK-cells showed a striking suppression of their malignant phenotypes, such as prolongation of doubling time and loss of anchorage-independent growth potential, compared with parental EBV-positive T-cell and NK-cell tumors. In a part of the EBV-lost T-cells and NK-cells, loss of viral genome also brought about cell death.3. The EBV-lost T-cells and NK-cells showed significantly decreased production of some cytokines, such as interleukin-9, compared with the parental EBV-positive T-cell and NK-cell tumors. Conversely, the production levels of another cytokine was also found to be upregulated in the EBV-lost T-cells.These results indicate that the EBV-dependent malignant phenotypes in T- and NK-cells and perhaps also in epithelial cells, as in B-cell lymphomas, are associated, at least partly, with upregulation (i.e., the autocrine mechanism) and/or down regulation of certain cytokines. We are planning to explore precisely the mechanisms of cytokine gene control and specific effects on EBV oncogenesis. Less
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
登录
查看更多内容
小児腎移植におけるEBウイルス(EBV)モニタリング-EBV負荷量およびkillerT細胞の推移-
儿科肾移植中的 EB 病毒 (EBV) 监测 - EBV 载量和杀伤性 T 细胞的变化 -
DOI:
--
发表时间:
2008
期刊:
影响因子:
--
作者:
[佐藤, 哲也]
通讯作者:
哲也
小児腎移植におけるEBVモニタリング-EBV未感染レシピエントにおけるEBV負荷量とkillerT細胞推移の意義と限界
儿科肾移植中的 EBV 监测 - 未感染 EBV 的受者中 EBV 载量和杀伤性 T 细胞转变的意义和局限性
DOI:
--
发表时间:
2007
期刊:
影响因子:
--
作者:
[石原, 正行]
通讯作者:
正行
シンポジウム 3.EBウイルス感染症と皮膚 1)EBウイルス感染症-overview
研讨会 3. EB 病毒感染与皮肤 1) EB 病毒感染 - 概述
DOI:
--
发表时间:
2007
期刊:
影响因子:
--
作者:
[脇口, 宏, 脇口 宏]
通讯作者:
脇口 宏
がんのベーシックサイエンスThe Basic Science of Oncology日本語版第3版「第6章 ウイルスとがん」
肿瘤学基础科学日文版第3版《第6章病毒与癌症》
DOI:
--
发表时间:
2006
期刊:
影响因子:
--
作者:
[藤枝 幹也, 前田 明彦, 脇口 宏, 今井 章介(翻訳)]
通讯作者:
今井 章介(翻訳)
CD8+ T cells play disparate roles in the induction and the effector phases of murine experimental allergic conjunctivitis
CD8 T 细胞在小鼠实验性过敏性结膜炎的诱导期和效应期发挥不同的作用
DOI:
--
发表时间:
2006
期刊:
Microbiol Immunol 50(9)
影响因子:
--
作者:
[Fukushima A, Yamaguchi T, Imai S, et. al.]
通讯作者:
et. al.
共 47 条
Study of pathogenesis of chronic active EB virus infection and its treatment strategy.
-
批准号:22591182
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.83万
-
财政年份:2010
-
负责人:WAKIGUCHI Hiroshi
-
依托单位:
Studies on Pathogenesis of Chronic Active Epstein-Barr Virus Infection
-
批准号:14570750
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.56万
-
财政年份:2002
-
负责人:WAKIGUCHI Hiroshi
-
依托单位:
海外基金