Production of interferon stimulated gene library and screening of new therapeutic drug for hepatitis viruses

干扰素刺激基因库的构建及肝炎病毒治疗新药的筛选

• 批准号: 18390218
• 负责人: CHAYAMA Kazuaki
• 金额: $ 9.35万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390218/
• 关键词: interferon; hepatitis C virus; interferon stimulated genes; expression profile; microarray; mRNA; human hepatocyte chimeric mouse; therapeutic drug; 肝炎ウイルス; ゲノム; キメラマウス; 免疫

We inflicted human hepatocyte chimerie mice with hepatitis B and hepatitis C viruses by injecting serum samples obtained from serum samples of chronic hepatitis B and hepatitis C virus carriers. After confirming the development of viremia in mice, we administered daily 7000 U/g of alpha interferon intramusculary. A rapid decrease in hepatitis C virus RNA levels was observed in all treated mice In contrast, only faint reduction of hepatitis B virus DNA was observed in mice infected with hepatitis B virus. We also administered the same amount of interferon to some human hepatocyte chimeric mice. We sacrificed and collected liver samples from each mice and extracted mRNA from each maim. Using them mRNA samples we performed microarray analysis. We obtained expression profiles from control, non-infected and non-interferon treated mice. We compared expression profiles of mice liver obtained from hepatitis B virus and hepatitis C virus infected mouse as well as interferon treated mice inflicted with hepatitis B and C viruses and treated with interferon. Up regulation of interferon stimulated genes ware observed in hepatitis C virus infected mice The up regulation of them genes was not so eminent in mice infected with hepatitis B virus. Interestingly, up regulation of some interferon stimulated genes were diminished in mice infected with hepatitis C virus compared with non-infected mouse. Further research is now in progress to analyze a mechanism underlining this suppression of interferon stimulated gene production.

我们通过注射从慢性B型肝炎和丙型肝炎病毒携带者的血清样品中获得的血清样品，使人肝细胞嵌合体小鼠感染B型肝炎和丙型肝炎病毒。在确认小鼠病毒血症的发展后，我们每天肌肉注射7000 U/g的α干扰素。在所有治疗的小鼠中观察到丙型肝炎病毒RNA水平的快速降低。相反，在感染B型肝炎病毒的小鼠中仅观察到B型肝炎病毒DNA的微弱降低。我们还给予相同数量的干扰素，一些人肝细胞嵌合小鼠。我们从每只小鼠中处死并收集肝脏样品，并从每只小鼠中提取mRNA。使用它们的mRNA样品，我们进行了微阵列分析。我们从对照、未感染和未干扰素处理的小鼠获得表达谱。我们比较了从B病毒和丙型肝炎病毒感染的小鼠以及用干扰素治疗的B和丙型肝炎病毒感染的小鼠和用干扰素治疗的小鼠获得的小鼠肝脏的表达谱。丙型肝炎病毒感染小鼠干扰素刺激基因表达上调，B肝炎病毒感染小鼠干扰素刺激基因表达上调不明显。有趣的是，与未感染的小鼠相比，感染丙型肝炎病毒的小鼠中一些干扰素刺激基因的上调减少。目前正在进行进一步的研究，以分析这种抑制干扰素刺激基因产生的机制。

项目成果

Balloon-occluded retrograde transvenous obliteration for portal-systemic encephalopathy due to superior mesenteric-caval shunt via the right gonadal vein

球囊闭塞逆行经静脉闭塞术治疗因右性腺静脉肠系膜上腔分流引起的门体性脑病

• 发表时间: 2007
• 期刊: Intern Med 46(17):
• 作者: Katamura Y;Aikata H;Azakami T;Chayama K.;et. al.
• 通讯作者: et. al.

Efficacy of Percutaneous Cementoplasty for Bone Metastasis from Hepatocellular Carcinoma

• DOI: 10.1159/000113040
• 发表时间: 2008-01
• 期刊: Oncology
• 影响因子: 3.5
• 作者: Hideaki Kodama;H. Aikata;K. Uka;S. Takaki;N. Mori;K. Waki;S. Jeong;Y. Kawakami;Hiroo Shirakawa-Hiroo-Shiraka

Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma

• DOI: 10.3748/wjg.v13.i3.414
• 发表时间: 2007-01-21
• 期刊: WORLD JOURNAL OF GASTROENTEROLOGY
• 影响因子: 4.3
• 作者: Uka, Kiminori;Aikata, Hiroshi;Chayama, Kazuaki
• 通讯作者: Chayama, Kazuaki

Successful treatment of an entecavir-resistant hepatitis B virus variant.

成功治疗恩替卡韦耐药乙型肝炎病毒变种。

• 发表时间: 2007
• 期刊: J Med Virol 79(12)
• 作者: Yatsuji H;Hiraga N;Kumada H;Chayama K.;et. al.
• 通讯作者: et. al.

Similar effects of recombinant interferon-alpha-2b and natural interferon-alpha when combined with intra-arterial 5-fluorouracil for the treatment of advanced hepatocellular carcinoma

重组干扰素-α-2b与天然干扰素-α联合动脉注射5-氟尿嘧啶治疗晚期肝细胞癌具有相似的效果

• 发表时间: 2007
• 期刊: Liver Int. 27(9)
• 作者: Uka K;Aikata H;Takaki S;Chayama K.;et. al.
• 通讯作者: et. al.