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GENE THERAPY OF GLIOBLASTOMA BY ADEVOVIRUS VECTOR CARRYING ASTROCYTES SPECIFIC ENHANCER SEQUENCES

Research Project

Project/Area Number 07671529
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionSAGA MEDICAL SCHOOL

Principal Investigator

FUKUYAMA Kouzou  SAGA MEDICAL,SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (60238516)

Co-Investigator(Kenkyū-buntansha) HAGIHARA Naoshi  SAGA MEDICAL SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (90281203)
MINETA Toshihiro  SAGA MEDICAL SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (20264187)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsglioma / gene therapy / adenovirus / GFAP / p53 / p21 / レトロウィルスベクター / p16 / プロモーター / 神経膠腫
Research Abstract

We investigated the efficacy and the side effect of the gene therapy using adenovirus and retroviruses for the treatment of malignant gliomas. The recombinant adenovirus and retrovirus were injected into the brain of Wistar rats, and the efficiency of gene expression and the immune response of hosts were monitored with lac Z gene as a reporter gene. Adenoviruses could be concentrated at the titer of 1010 pfu/ml, and the expression of lac Z was extremely strong. It was observed that the lac Z expression was continued upto 6 weeks after injection. On the contrary the titer of retrovirus solution was only at 106 pfu/ml. The transferred gene expression was very localized at the injected area. In both vector system, there occurred only little infiltration of immune cells, nor allergic reactions. There was slight gliosis and the diminish of ependymal cells at 6 weeks after the injection. We considered adenovirus system was superior to retrovirus system for the purpose of the gene therapy of malignant gliomas, which requires high efficiency of gene transduction.
Adenovirus bearing lacz, p53, and p21 genes were infected into cultured glioma cells. In p53 wild type cells, the cell growth was inhibited by the induction of p21. On the other hand, in p53 mutant and deleted cells, the growth inhibition were induced by the up regulation of p53. In the subcutaneously transplanted glioma cells in nude mice, in infection of p21 bearing adenovirus resulted the tumor growth inhibition.
The astrocytes specific expression vector was constructed with the tandem ligation of enhancer sequences of GFAP gene into adenovirus. The lac Z gene and p53, p16, and p21 genes were inserted in the downstream of this enhancer unit. These viruses were only expressed the expected genes in the astrocytes. The astrocytes specific expression adenovirus can be a useful arms for the treatment of malignant gliomas.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Fukuyama K,et al: "Analysis of alial fibrillary acidic protein gene methylation in human malignant gliomas" Anticancer Research. 16. 1251-7 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuzawa K,Fukuyama K et al: "Expression of stomelysin 1 in human astrocytoma cell lives" Journal of Neuro-Oncology,. 30. 181-188 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toda K,Fukuyama K et al: "The cytocidal activity of OK-432 activated mononuclear cell against human glioma is partly mediated through Fas" J.J.of Cancer Research. 87. 972-976 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuzawa K,Fukuyama K et al: "Transfection of an invasire human astrocytoma cell line with a Timp 1 cDNA" J.of Neuropathology & Experimental Neurology.55. 88-96 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 田渕和雄、福山幸三: "グリオーマの遺伝子異常" 脳と神経. 49(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 田渕和雄、福山幸三: "神経膠腫の遺伝子治療概説" Neurosurgeons. 14. 148-158 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tabuchi, K., Fukuyama, K.: "An overview of gene therapy for glioma." Neurosurgeons. 14. 148-158 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuyama, K., et al.: "Analysis of glial fibrillary acidic protein gene methylation in human malignant gliomas." Anticancer Research. 16. 1251-1257 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuzawa, K., Fukuyama, K., et al.: "Transfection of an invasive human astrocytoma cell line with a TIMP-1 cDNA : modulation of astrocytoma invasive potential" Journal of Neuropathology, & Experimental Neurology. 55. 88-96 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuzawa, K., Fukuyama, K., et al: "Expression of stromelysin-1 in human astrocytoma cell lines" Journal of Neurooncology. 30. 181-188 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toda, K., Fukuyama, K., et al: "The cytocidal activity of OK-432 activated mononuclear cell against human glioma is partly mediated through FAS/FAS-L system" Japanese Journal of Cancer Research. 87. 972-976 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mineta, T., et al: "Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas" Nature Medicine. 1. 938-943 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tabuchi, K., Fukuyama, K.: "Genetic alterations of gliomas." Brain and Nerve. 49. 205-213 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuyama K,et al: "Analysis of glial fibrillary acidic protein gene methylation in human malignant gliomas" Anticancer Research.16. 1251-7 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuzawa K,Fukuyama K,rt al: "Expression of sbomehsin 1 in human astrocytowa cell lives" Jouemal of Neuro-Oucology.30. 181-188 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Toda K,Fukuyama K,rt al: "The cytocical activity of OK-432 octivated mononuclean cell against human alioma is sertly mediated through Fas" J.J.of Cancer Research. 87. 972-976 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuzawa K,Fukuyama K,rt al: "Transfection of invasire human astrocytowa cel line with a timp 1 cDNA" J.of Neuropatbology & Eperimental neurology. 55. 88-96 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 田渕和雄,福山幸三: "グリオーマの遺伝子異常" 脳と神経. 49(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 田渕和雄,福山幸三: "神経膠腫の遺伝子治療概説" Neurosurgeons. 14. 148-158 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 田渕和雄,福山幸三: "神経膠腫の遺伝子治療概説" Neurosurgeons. 13. 148-158 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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