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2000 Fiscal Year Final Research Report Summary

Bystander effect-mediated suicide gene therapy of experimental brain tumor by genetically engineered tumor cells in rat

Research Project

Project/Area Number 11671408
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

NAMBA Hiroki  Hamamatsu University School of Medicine, Department of Neurosurgery, Professor, 医学部, 教授 (60198405)

Co-Investigator(Kenkyū-buntansha) TAGAWA Masatoshi  Chiba Cancer Center Research Institute, Division of Pathology, Chief, 病理研究部, 部長 (20171572)
YOKOTA Naoki  Hamamatsu University School of Medicine, Department of Neurosurgery, Research Associate, 医学部・附属病院, 助手 (00273186)
NISHIZAWA Shigeru  Hamamatsu University School of Medicine, Department of Neurosurgery, Asssitant Professor, 医学部・附属病院, 講師 (40135257)
Project Period (FY) 1999 – 2000
Keywordsgene therapy / bystander effect / ganciclovir / brain tumor / herpes simplex virus-thymidine kinase
Research Abstract

Our previous study demonstrated that intracranial 9L glioma could be efficiently treated due to the bystander effect by injecting the 9L glioma cells transduced with herpes simplex virus-thymidine kinase(HSVtk)gene(9Ltk)in the vicinity of the preimplanted wild-type 9L glioma and then administerin ganciclovir(GCV)(TK cell therapy). For a possible clinical application of the bystander effect-mediated cell killing, we tested HSVtk gene trransduced allogeneic C6 glioma(C6tk)cells instead of 9Ltk(allogeneic TK cell therapy). Intracranial 9L glioma could also be efficiently treated by allogeneic TK cell therapy, though this bystander effect was weaker than syngeneic TK cell therapy. Since allogeneic tumor cells are finally rejected, the allogeneic TK cell therapy is a safe and feasible strategy for glioma treatment.
The bystander effect between different tumor cell lines(9L and C6 cells)was then studied using mixed populations of wild-type cells(9Lwt and C6wt)and respective TK cells(9Ltk and C6tk). A potent in vitro bystander effect was observed in 9Lwt/9Ltk and 9Lwt/C6tk combinations but not in C6wt/9Ltk and C6wt/C6tk combinations. In vivo bystander effect studied in a subcutaneous tumor model in athymic nude mice was also potent in 9Lwt/9Ltk and 9Lwt/C6tk combinations. Since the expression of connexin43, a major protein in the connexin family gene products, in 9L cells is much higher than that in C6 cells, the results suggest that the amount of connexin in target wild-type cells but not in effector TK cells is important for the generation of the bystander effect. This hypothesis was further confirmed by the observation that in vitro bystander effect in C6wt/C6tk combination was potentiated by transduction of the connexin43 gene to the target cells

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Namba H: "Efficacy of the bystander effect in the herpes simplex virus thymidine kinase-mediated gene therapy is influenced by the expression of connexin43 in the target cells"Cancer Gene Ther. 8(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Namba H: "Treatment of rat experimental brain tumor by herpes simplex virus thymidine kinase gene-transduced allogeneic tumor cells and ganciclovir"Cancer Gene Ther. 7(6). 947-953 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwadate Y: "Immunological responsiveness to interleukin-2-producing brain tumors can be restored by concurrent subcutaneous transplantation of the same tumors"Cancer Gene Ther. 7(9). 1263-1269 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawamura K: "Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with the level of intercellular communication"Int J Oncol. 18(1). 117-120 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawamura K: "Transduction of the human deoxycytidine kinase gene in rodent tumor cells induces in vivo growth retardation in syngeneic hosts"Cancer Lett. 156(2). 151-157 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Namba H: "Treatment of rat experimental brain tumor by herpes simplex virus thymidine kinase gene-transduced allogeneic tumor cells and ganciclovir"Cancer Gene Ther. 7(6). 947-953 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawamura K: "Transduction of the human deoxycytidine kinase gene in rodent tumor cells induces in viro growth retardation in syngeneic hosts"Cencer Lett. 156(2). 151-157 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwadate Y: "Immunological responsiveness to interleukin-2-producing brain tumors can be restored by concurrent subcutaneous transplantation of the same tumors"Cancer Gene Ther. 7(9). 1263-1269 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawamura K: "Bystander effect on uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is sorrelated with the level of intercellular communication"Int J Oncol. 18(1). 117-120 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Namba H: "Efficacy of the bystander effect in the herpes simplex virus thymidine kinase-mediated gene therapy is influenced by the expression of connexin43 in the target cells"Cancer Gene Ther. (in press). (2001)

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

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Published: 2002-03-26  

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