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1999 Fiscal Year Final Research Report Summary

GENE THERAPY FOR EXPERIMENTAL GLIOMAS USING ADENOVIRUS VECTOR

Research Project

Project/Area Number 10671302
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

ONO Yasuhiro  OKAYAMA UNIVERSITY MEDICAL SCHOOL, ASSISTANT, 医学部, 助手 (40294409)

Co-Investigator(Kenkyū-buntansha) TAMIYA Takashi  OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL, LECTURE, 医学部・附属病院, 講師 (50252953)
MATSUMOTO Kengo  OKAYAMA UNIVERSITY MEDICAL SCHOOL, ASSISTANT PROFESSOR, 医学部, 助教授 (10190521)
Project Period (FY) 1998 – 1999
Keywordsadenovirus vector / gene therapy / brain tumors / cytosine deaminase / uracil phosphoribosyltransferase / 5-fluorocytosine / 5-fluorouracil
Research Abstract

One of the transduction methods, denovirus vector, has been shown to transduce exogenous genes successfully into tumor cells both in vitro and in vivo. We have investigated the feasibility of gene transduction for brain tumors using adenovirus vector. On the other hand, suicide gene therapy for brain tumors was the second concern of our research. Transduction of the cytosine deaminase (CD) gene into tumor cells followed by administration of 5-fluorocytosine (5-FC), called 5-FC/CD gene therapy, was created as a suicide gene therapy for various cancers. We also reported the usefulness of 5-FC/CD gene therapy for malignant gliomas in vivo and pointed out its toxicity for normal brain tussues. For the reduction of this toxicity, we combined two genes, that is, CD gene and uracil phosphoribosyltransferase (UPRT) gene, which directly converts 5-fluorouracil (5-FU) to 5-fluorouridine 5'- monophosphate. CD+UPRT-transduced cells were 6,000 times more sensitive to 5-FC than parent cells, indicating that the acquisition of CD and UPRT further increased the 5-FC sensitivity of 9L cells compared to that of CD alone. In a brain tumor model, a decreased amount of vectors of CD and UPRT were enough to prolong the survival of rats compared to high dose of CD gene alone and were less toxic for adjacent normal brains. Our data demonstrated that simultaneous CD and UPRT gene expression by adenovirus enhanced the antitumor effect of the 5-FC/CD gene therapy.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Tomotsugu Ichikawa: "In vivo efficacy and toxicity of 5-fluorocytosine/cytosine deaminase gene therapy for malignant gliomas mediated by adenovirus"Cancer Gene Therapy. 7 (1). 74-82 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshiaki Adachi: "Experimental gene therapy for brain tumors using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltrnsferase gene with 5-fluorocytosine"Human Gene Therapy. 11 (1). 77-89 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinichiro Mizumatsu: "Expression of cell-cycle regulator p27^<Kip1> correlates with survival in patients with astrocytoma"Clinical Cancer Research. 5 (3). 551-557 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takashi Tamiya: "Ganglioglioma in a patient with Turcot's syndrome : case report"Journal of Neurosurgery. 92 (1). 170-175 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ichikawa T, Tamiya T, Adachi Y, Ono Y, Matsumoto K, Furuta T, Ohmoto T :: "In vivo efficacy and toxicity of 5-fluorocytosine / cytosine deaminase gene therapy for malignant gliomas mediated by adenovirus"Cancer Gene Ther. 7(1). 74-82 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Adachi Y, Tamiya T, Ichikawa T, Terada K, Ono Y, Matsumoto K, Furuta T, Hamada H, Ohmoto T :: "Experimental gene therapy for brain tumors using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene with 5-fluorocytosine"Hum Gene Ther. 11(1). 77-89 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizumatsu S, Tamiya T, Ono Y, Abe T, Matsumoto K, Furuta T, Ohmoto T :: "Expression of cell-cycle regulator p27ィイD1Kip1ィエD1 correlates with survival in patients with astrocytoma"Clinical Cancer Research. 5(3). 551-557 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamiya T, Hamazaki S, Ono Y, Tokunaga K, Matsumoto K, Furuta T, Ohmoto T :: "Ganglioglioma in a patient with Turcot's syndrome : Case report"J Neurosurg. 92(1). 170-175 (2000)

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

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Published: 2001-10-23  

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