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Development of gene therapy for malignant brain tumor

Research Project

Project/Area Number 04454358
Research Category

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

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

Principal Investigator

YOSHIDA Jun  Nagoya University School of Medicine Assistant Prof., 医学部, 講師 (40158449)

Co-Investigator(Kenkyū-buntansha) YAGI Kunio  Institute of Applied Biochemistry President, 所長 (00022749)
SEO Hisao  Nagoya University Institute of Enviornmental Medicine Professor, 環境医学研究所, 教授 (40135380)
WAKABAYASHI Toshihiko  Nagoya University School of Medicine Instructor, 医学部, 助手 (50220835)
SUGITA Kenichiro  Nagoya University, School of Medicine Professor, 医学部, 教授 (30023807)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥4,700,000 (Direct Cost: ¥4,700,000)
Keywordsgene therapy / brain tumor / interferon / liposome / monoclonal antibody / モノクローナル抗体
Research Abstract

Our approach developing gene therapy to malignant glioma is selectively transfer of cytokine gene into the tumor cells by means of DNA/immunoliposomes (monoclonal antibody coupled cationic liposomes). We confim in the present research work, the anti-tumor effect of transfection-induced HuIFN-beta by the use of human glioma produced in the brain of nude mice. We injected humanglioma cells into the cerebral hemisphere. The human gliomas grew in the mouse brain and they all made a huge brain tumor. For the evaluation of anti-tumor effect, we injected liposomes with entrapped pSV2IFN-beta into the tumor growing tn the brain once every second day for six times. We started the treatment at different days after the transplantation and sacrified all animals at 31st day, and it has been demonstrated that the transplanted glioma disappasred completely when the liposomes with entrapped pSV2IFN-beta was injected repeatedly into the tumor. The complete disappearance of the transplanted glioma was seen in 100% of nude mice if the treatment was started until 3 days after transplantation and when it was started at 7 days or 9 days, the tumor-free ratio was 5/7 (71%) or 2/7 (29%) respectively. Futhermore, the anti-tumor effect of transfection-induced HuIFN-beta was noted to be increased by using DNA/immunoliposomes.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Yoshida J, et al.: "Antitumor effect of endogenous human β-interferon on malignant glioma and augmentation of the effect by tumor necrosis factor-α" J Clin Biochem Nutr. 77. 78-83 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshida J, et al.: "Cytotoxicity of human β-interferon produced in human glioma cells transfected with its gene by means of liposomes" Biochem Int. 28. 1055-1061 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yagi K,Hayashi Y,Ishida N,Ohdayashi M,ohishi N,Mizumo M,Yoshida J: "Interferon-β-endogenously produced by intratumoral injection of cationic liposome-encapsulated gene:Cytocidal effect on glioma transplanted into nude mouse brain" Biochem Mol Biol Int. 32. 167-172 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mizuno,M,,Yoshida J Takaoka T,Sugita K: "Lepsomal transfection of numan γ-interferon gene into glioma cells and adoptive immunotherapy using lymphokine-activated killer cells" J Neurosurg. 80. 510-514 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takaoka T,Yoshida J,Mizuno,M,Sugita K: "Transfection-induced tumor necrosis factor-α increases the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells;continuous expression of intercellular adhesion molecule-1 on the glioma cells" Jpn J Cancer Res. 85. 750-755 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mizuno,M,Yoshida J,Takaoka T,Sugita K: "Reinforced cytotoxixity of lymphokine-activated killer cells toward glioma cells by transfection of the killer cells with the γ-interferon gene" Jpn J Cancer Res. 86. 95-100 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshida, J., et al.: "Antitumor effect of endogenous human beta-interferon on malignant glioma and augmentation of the effect by tumor necrosis factor-alpha" J Clin Biochem Nutr. 12. 153-160 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshida, J., et al.: "Cytotoxicity of human b-interferon produced in human glioma cells transfected with its gene by means of liposomes" Biochem Int. 28. 1055-1061 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yagi K., Hayashi Y.Ishida N., Ohbayashi M., Ohishi N., Mizuno M., Yoshida J.: "Interferon-beta endogenously produced by intratumoral injection of cationic liposome-encapsulated gene : Cytocidal effect on glioma transplanted into nude mouse brain" Biochem Mol Biol Int. 32. 167-172 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mizuno M., Yoshida J., et al.: "Lipsomal transfection of human gamma-interferon gene into glioma cells and adoptive immunotherapy using lymphokine-activated killer cells" J Neurosurg. 80. 510-514 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takaoka T., Yoshida J., et al.: "Transfection-induced tumor necrosis factor-alpha increases the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells : Continuous expression of intercellular abhesion molecule-1 on the glioma cells" Jpn J Cancer Res. 85. 750-755 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mizuno M., Yoshida J., Takaoka T., Sugita K.: "Reinforced cytotoxixity of lymphokine-activated killer cells toward glioma cells by transfection ofthe killer cells with the gamma-interferon gene" Jpn J Cancer Res. 86. 95-100 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yagi K,Hayashi Y,Ishida N,Ohbayashi M,Ohishi N,Mizuno M,Yoshida J: "Interferon-β endogenously produced by intratumoral injection of cationic loposomeencapsulated gene:Cytocidal effect on glioma transdplanted into nude mouse brain" Biochem Mol Biol Int. 32. 167-172 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mizuno M,Yoshida J,et al.: "Lipsomal transfection of human γ-interferon gene into glioma cells and adoptive immunotherapy using Iymphokine-activated killer cells" J Neurosurg. 80. 510-514 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshida J,et al.: "Long-term follow-up results of 175 patients with malignant glioma;Importance of radical tumor resection and postoperative adjuvant therapy with interferon,ACNU and radiation" Acta Neurochir. 127. 55-59 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kato K.,Yoshida J.,et al.: "Retroviral transfeetion of herpes simplex thymidine kinase gene into glioma cells causes targeting of gancyclovir cytotoxic effect" Neurol Med Chirur. 34. 339-344 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takaoka T,Yoshida J,et al.: "Transfection-induced tumor necrosis factor-α increases the susceptibility of human,glioma cells to lysis by lymphokine-activated killer cells:continuous expression of intercellular adhesion molecule-l on the glioma cells" Jpn J Cancer Res. 85. 750-755 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Okada H,Yoshida J,et al.: "Anti-glioma antigen monoclonal antibody G-22 recognized overexpressed CD44 in glioma cells" Cancer Immun Immunother. 39. 313-317 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kunio Yagi,Jun Yoshida et al.: "Interferon-β endogenously producedby intratumoral injection of cationic liposome-encapsulated gene:Cytocidal effect on glioma transplanted into nude mouse brain" Biochem.Mol.Biol.Int.32. 167-172 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masaaki Mizuno,Jun Yoshida,et al.: "Liposonal transfection of human γ-interferon gene into glioma cells and adoptive immunotherapy using lymphokine-activated killer cells" J.Neurosurg.80(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jun Yoshida,Toshihiko Wakabayashi,et al.: "Simple method to prepare cationic multilamellar liposome for effecient transfection of human interferon-β gene to human glioma cells" J.Veuro-Onol.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jun Yoshida: "Gene transfer with liposomes:Cytokine gene therapy for brain tumor" Cancer Chemothrapy:Challenges for the futher. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jun Yoshida et al.: "Secretion of human β-interferon into the cystic fluid of glioma transfected with the interferon gene" J. Clin. Biochem. Nutr.11. 123-128 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Jun Yoshida, et al: "Cytotoxicity of human β-interferon produced in human glioma cells transfected with its gene by means of liposomes" J. Clin. Biochem Nutr.12. 153-160 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Masaaki Mizumo,Jun Yoshida, et al: "Growth inhibition of glioma cells by liposomesーmediated cell transfection with tumor necrosisーα gene Its enhancement by prio γ-interferon treatment." Neurologia medico-chirurgica. 32. 873-876 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takashi Tashiro,Jun Yoshida, et al: "Reinforced cytotoxicity of lymphokine-activated killer cells toward glioma cells by transfection with the tumor necrosis factor-α gene" J.Neurosurg.78. 252-256 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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