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

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671359
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hyogo College of Medicine
• Principal Investigator: TAKEUCHI Masaharu Hyogo College of Medicine, Research Associate, 医学部, 助手 (00258162)
• Co-Investigator(Kenkyū-buntansha): UEKI Takahiro Hyogo College of Medicine, Research Associate, 医学部, 助手 (10309461) ; FUJIMOTO Jiro Hyogo College of Medicine, Professor, 医学部, 教授 (90199373)
• Project Period (FY): 2001 – 2002
• Keywords: hepatocellular carcinoma / gene therapy / HSV-TK / 超音波下遺伝子導入

Research Abstract

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.