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Induction of endogenous interferon by superinduction or gene transfection and its anti-tumor activity toward malignant glioma

Research Project

Project/Area Number 01570807
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionNagoya University

Principal Investigator

YOSHIDA Jun  Department of Neurosurgery, Nagoya University School of Medicine, 医学部, 講師 (40158449)

Co-Investigator(Kenkyū-buntansha) YAGI Kunio  Inst. Appl. Biochem., president, 所長 (00022749)
SEO Hisao  Inst. Envivon. Med., Professor, 環境医学研究所, 教授 (40135380)
WAKABAYSHI Toshihiko  Nagoya Univ., Neurosurg., Clinical Instructor, 医学部, 助手 (50220835)
SUGITA Kenichiro  Nagoya Univ., Neurosur. Professor, 医学部, 教授 (30023807)
井上 達  名古屋大学, 環境医学研究所, 助手 (80184737)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsInterferon / Brain Tumor / Monoclonal antibody / Liposome / Gene fransfection / Tumor necrosis factor / 超誘導法 / 殺細胞効果
Research Abstract

Human malignant gliona is one of the most formidable neoplases arising in the brain, and patients afflicted have an average survival time of less than two years. Since malignant gliona invades aggressively into normal brain tissue and tends to disseminate into the subarachnoid space via the cerebro-spinal fluid, surgical resection and/or radiation cannot be expected to be successful. To cure the patient with a malignant brain tumor requires targeting therapy which selectively kills the tumor cells without any damage to normal cells. For this purpose, we have been studying the targeting of cytotoxic agents to glioma cells by using liposomes and a monoclonal antibody(MCA). We entrapped the HuIFN-betza gene inserted in a eukaryotic expression vector (pSV2IFN-beta) into novel liposomes having positive charge on their surface, and found that our liposome-mediated transfer of the gene to cultured glioma cells brought about the production of HuIFN-beta in the cells followed by their growth inhibition. When the plasmid-containing liposomes were coupled with G-22, an MCA against a glioma-associated surface antigen, production of HuIFN-beta in the cells was increased and the growth inhibition of the glioma cells became complete. Furthermore, we found by in vitro experimentation that production of HuIFN-beta in the cells transfected with the gene could be increased by treatment of the cells with tumor necrosis factor-alpha (TNF-alpha) prior to the transfection and that the cells completely disappeared by 9 days after the transfection. Human glioma subcutaneously transplanted into nude mice could be killed completely if the mice were given TNF-alpha prior to the gene transfection. Thus the gate to gene therapy for brain tumors has been opened.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Masaaki Mizuno: "Growth inhibition of glioma cells transfected with the human β-interferon gene by liposomes caipled with a monoclonal antibody" Cancer Research. 50. 7826-7829 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masaaki Mizuno: "Growth inhibition of glioma cells of different cell lines by human interferon-β produced in the cells transfected with its gene by means of liposomes" J.Clin.Biochem.Nutr.9. 269-273 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Itaru Inoue: "Superinduction of cytotoxic interferon-β in glioma cells" Neurol.med-chirur.31. 485-489 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Jun Yoshida: "Secretion of human β-Interferon into the cystic fluid of glioma transfected with the interferon gene" J.Clin.Biochem.Nutr.11. 123-128 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masaaki Mizuno: "Growth inhibition of glioma cells transfected with the human beta-interferon gene by liposomes caipled with a monoclonal antibody" Cancer Research. 50. 7826-7829 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masaaki Mizuno: "Growth inhibition of glioma cells of different cell lines by human interferon-beta produced in the cells transfected with its gene by means of liposomes" J. Clin. biochem. Nutr.9. 269-273 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Itaru Inoue: "Superinduction of cytotoxic interferon-beta in glioma cells" Neuro. med-chirur.31. 485-489 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Jun Yoshida: "Secretion of human beta-Interferon into the cystic fluid of glioma transfected with interferon gene" J. Clin. Biochem. Nutr.11. 123-128 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Jun Yoshida: "Secretion of Human βーInterferon into Cystic Fuid of Glioma Transfected with the Interferon Gene." J.Clin.Biochem.Nutr. 11. 123-128 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Masaki Mizuno: "Growth inhibition of glioma cells transfected with the human βーinterferon gene by liposomes caipled with a monoclonal antibody" Cancer Research. 50. 7826-7829 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Masaaki Mizuno: "Growth inhibition of glioma cells of different cell lines by human interferonーβ produced in the cells transfected with its sehe by means of liposomes" J Clin.Biochem.Nutr.9. 269-273 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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