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1997 Fiscal Year Final Research Report Summary

Establishment of gene therapy for hepatocellular carcinoma by transfer of suicide genes

Research Project

Project/Area Number 07457141
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNara Medical University

Principal Investigator

KURIYAMA Shigeki  Nara Medical University, Medicine, Assistant, 医学部, 講師 (50244710)

Co-Investigator(Kenkyū-buntansha) TOMINAGA Kentaro  Nara Medical University, Medicine, Staff, 医学部, 医員
MASUI Kazuhiro  Nara Medical University, Medicine, Assistant, 医学部, 助手 (10295800)
YOSHIKAWA Masahide  Nara Medical University, Medicine, Assistant, 医学部, 助手 (50230701)
Project Period (FY) 1995 – 1997
Keywordsgene therapy / hepatoma / retrovirus / suicide gene / thymidine kinase / cytosine deaminase
Research Abstract

We have previously reported that a reporter gene directed by the albumin gene promoter in a retroviral vector is expressed solely in hepatoma cells but not in non-hepatoma cells. This year, we have got the following additional results.
1)Transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene under the control of albumin promoter can render hepatoma cells, but not non-hepatoma cells, susceptible to ganciclovir (GCV) toxicity.
2)Established subcutaneous tumors consisting of HSV-tk gene-transduced hepatoma cells were abrogated completely by GCV treatment in 11 of 14 mice. However, in the remaining 3 mice, tumors did not regress completely despite GCV treatment due to methylation of the HSV-tk gene.
3)Bacterial cytosine deaminase (CD) gene/5-fluorocytosine (5-FC) system can cause profound bystander killing on neighboring untransduced cells without direct cell-to-cell contact. This bystander killing effect was shown to be mediated by 5-fluorouracil (5-FU) produced from 5-FC by CD gene-transduced hepatoma cells.
4)CD-5-FC system can induce substantial bystander effect in vivo. This in vivo bystander effect was mainly caused by host's tumor immunity elicited by the CD/5-FC system but not by 5-FU produced by the CD/5-FC system.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Tadanori Yoshimatsu: "Improvement of retroviral packaging cell lines by introducing the polyomavirus early region" Human Gene Therapy. 9. 161-172 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shigeki Kuriyama: "Tissue-specific expression of HSV-tk gene can induce efficient antitumor effect and protective immunity to wild-type hepatocellular carcinoma" International Journal of Cancer. 71. 470-475 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 栗山 茂樹: "TNF-αを用いたin vivo遺伝子治療" 血液・腫瘍科. 35. 322-330 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 栗山 茂樹: "消化器癌遺伝子治療への試みTNFを用いた癌遺伝子治療" 肝胆膵. 34. 501-509 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 栗山 茂樹: "TNF-α遺伝子を用いた肝癌に対する遺伝子治療の検討" Minophagen Medical Review. 42. 149-152 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山崎 正晴: "蛍光染色細胞を用いた肝細胞癌の浸潤および肝内転移様式の検討" 肝臓. 38. 576-577 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshimatsu, T,et al.: "Improvement of retroviral packaging cell lines by introducing the polymavirus early region." Hum Gene Ther. 9. 161-172 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuriyama S,et al.: "Tissue-specific expression of HSV-tk gene can induce efficient antitumor effect and protective immunity to wild-type hepatocellular carcinoma." Int J Cancer. 71. 470-475 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuriyama S,et al.: "Gene therapy for cancer by a use of herpes simplex virus thymidine kinase gene." Hematology&Oncology. 28. 396-403 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuriyama S,et al.: "Gene therapy against cancer using TNF." KAN TAN SUI. 34. 501-509 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuriyama S,et al.: "Gene therapy for hepatoma using TNF-alpha gene." Minophagen Medical Review. 42. 149-152 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamazaki M,et al.: "Analysis of intrahepatic invasion and metastasis of hepatoma cells using fluorescent-labeled hepatoma cells." Acta Hepatologica Japonica. 38. 576-577 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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