The development of gene therapy using HSV-TK gene for HCC by ultrasonic tomography guiding

超声断层引导下HSV-TK基因治疗肝癌的进展

• 批准号: 13671359
• 负责人: TAKEUCHI Masaharu
• 金额: $ 2.24万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671359/
• 关键词: hepatocellular carcinoma; gene therapy; HSV-TK; 超音波下遺伝子導入

To achieve gene therapy using HSV-TK gene for Hepatocellular carcinoma (HCC) by Ultrasonic tomography guiding, we established the HCC tumor bearing mice and assessed the efficacy of gene expression by direct injection to tumor nodule with laparotomy last year. As we reported last year, tumor nodules were observed in the liver eight weeks after inoculation via spleen. At this point, most of mice died after gene transduction mediated by Hemaggultinating Virus of Japan (HVJ)-liposome and the efficacy of gene transduction was not clarified. We next tried to deliver two kinds of genes (AFP/LacZ or CMV/LacZ) by direct injection six weeks after tumor cell inoculation. Although survival rate was improved compared to eight weeks, halh of mice were still died. LacZ expression driven by AFP promoter was much lower than CMV promoter in tumor that could obtain from survival mice.Ultrasonic tomography (UST) could faintly detect liver tumor in rats liver but it could not detected tumor in mice liver. Thus, UST guiding gene deliverly was not feasible by available UST in animal model.

为实现超声引导下HSV-TK基因治疗肝细胞癌（Hepatocellular carcinoma，HCC），我们于去年建立了HCC荷瘤小鼠模型，并通过剖腹手术直接注射到肿瘤结节中来评估基因表达的疗效。正如我们去年所报道的，通过脾脏接种后8周，在肝脏中观察到肿瘤结节。目前，日本血凝病毒（HVJ）-脂质体介导的基因转导后大部分小鼠死亡，基因转导的有效性尚不清楚。我们接下来尝试在肿瘤细胞接种后六周通过直接注射递送两种基因（AFP/LacZ或CMV/LacZ）。虽然存活率比8周时有所提高，但仍有半数小鼠死亡。AFP启动子驱动的LacZ表达在存活小鼠体内的肿瘤中明显低于CMV启动子驱动的LacZ表达，超声断层扫描（UST）在大鼠肝脏中能微弱地检测到肝肿瘤，而在小鼠肝脏中不能检测到肿瘤。因此，利用现有的UST在动物模型中进行UST引导基因的传递是不可行的。