Identification of host genes responsible for the treatment response of interferon therapy for the patients with chronic hepatitis C

慢性丙型肝炎患者干扰素治疗反应宿主基因的鉴定

• 批准号: 21390227
• 负责人: HONDA Masao
• 金额: $ 8.82万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390227/
• 关键词: IFN; 遺伝子発現; C型慢性肝炎; C型肝炎ウイルス; インターフェロン; 治療抵抗性; IL28B; 肝内遺伝子発現

This study demonstrated that the induction of interferon stimulated genes(ISGs) was closely related to the treatment response to IFN therapy. Up-regulated ISGs expression of in liver before treatment might impair the de novo ISGs induction in liver. Interestingly, up-regulated ISGs in liver before treatment were closely related to IL28 minor genotype. Therefore, Il28B genotype must be involved in different ISGs induction in liver. There was a significant correlation of ISGs expression between the liver and PBMC in patients with IL28B major genotype, while no correlation was found in patients with IL28B minor genotype. Detailed examination of liver biopsy specimen by laser capture micro dissection revealed the impaired infiltration of immune cells in liver lobules in patients with IL28B minor genotype. These immune regulatory imbalances of IL28B minor genotype might contribute to the poor response to IFN therapy

这项研究表明，干扰素刺激基因（ISGs）的诱导与IFN治疗的治疗反应密切相关。治疗前肝脏ISGs表达上调可能会损害肝脏ISGs的新生诱导。有趣的是，治疗前肝脏中上调的ISGs与IL 28次要基因型密切相关。因此，I128 B基因型可能参与了肝脏ISGs的诱导。IL 28 B主基因型患者肝脏和PBMC中ISGs表达存在显著相关性，而IL 28 B次基因型患者肝脏和PBMC中ISGs表达无相关性。通过激光捕获显微切割对肝活检标本进行详细检查，发现IL 28 B次要基因型患者肝小叶中免疫细胞浸润受损。IL-28 B基因型的免疫调节失衡可能导致IFN治疗的不良反应

项目成果

当院における肝硬変に合併した門脈血栓症に対する治療の現状

我院肝硬化门静脉血栓治疗现状

• 发表时间: 2010
• 作者: 林武弘;鷹取元;荒井邦明;柿木嘉平太;加賀谷尚史;山下太郎;酒井佳夫;山下竜也;水腰英四郎;酒井明人;中本安成;本多政夫;岡田俊英;金子周一
• 通讯作者: 金子周一

HVR1 quasispecies selection and neutralization by anti-HVR1 of HCV in cell culture are strongly influenced by mutations in the EIE2 region outside of HCR1.

细胞培养物中 HVR1 准种的选择和 HCV 抗 HVR1 的中和受到 HCR1 之外 EIE2 区域突变的强烈影响。

• 发表时间: 2010
• 作者: Kazunori Kawaguchi;Kristina N Faulk;Masao Honda;et al
• 通讯作者: et al

Osteopontine Released from Ischemic Myocardium Altered Hepatic Gene Expression Profiles in Mice.

缺血性心肌释放的骨桥蛋白改变了小鼠的肝脏基因表达谱。

• 发表时间: 2010
• 作者: Hiroshi Ootsuji;Masao Honda;et al
• 通讯作者: et al

Differentiation of Cancer Stem Cells

癌症干细胞的分化

• 发表时间: 2011
• 期刊: Chapter
• 作者: Yamashita T;Honda M;Kaneko S.
• 通讯作者: Kaneko S.

La protein required for IRES-directed translation is a potential thera peutic target for hepatitis C virus replication

IRES 定向翻译所需的 La 蛋白是丙型肝炎病毒复制的潜在治疗靶标

• 发表时间: 2010
• 期刊: Journal of Infectious Diseases (in press)
• 作者: Shirasaki T;Honda M;et al
• 通讯作者: et al