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Antiangiogenesis gene therapy for advanced hepatocellular carcinoma by transferrin-DNA conjugate.

Research Project

Project/Area Number 11670520
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSAPPORO MEDICAL UNIVERSITY

Principal Investigator

TAKAHASHI Minoru  SAPPORO MEDICAL UNIVERSITY, assistant professor, 医学部, 助手 (60291556)

Co-Investigator(Kenkyū-buntansha) KATO Junji  SAPPORO MEDICAL UNIVERSITY, assistant professor, 医学部, 講師 (20244345)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsgene therapy / transferrin-DNA conjugate / antiangenesis factor / hepatocellular carcinoma
Research Abstract

Advanced hepatocellular carcinoma (HCC) is one of poor prognostic malignancies. As an alternative therapy to overcome these malignancies, we have developped the novel gene therapy with systemic administaration of Transferrin-DNA conjugate for disseminated lesions. Here we extended this system to the anti-angiogenesis gene therapy because it is well known that advanced HCC is hypervascular tumor and the blood supply is definitely dependent on the arterial blood flow. Angiostatin (Ast) is one of the potent antiangeogenesis factor and induces the apoptosis in vascular endotherial cells (Endt). However the little of the mechanism of apoptosis is elucidated yet. The aim of this study is to examine whether caspase and reactive oxygene species (ROS) are involved in the apoptotic process of Endt by Ast. Anti-oxydant agent significantly inhibited apoptosis of CPAE cells induced by Ast. Caspase 3 inhibitor also inhibited apoptosis of CPAE cells induced by Ast. These results demonstrate that caspase 3 and ROS are involved in the process of apoptosis induced by Ast.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Lu Y,Takahashi M, et al: "Administration of sub tumor-regression dosage of TNF-α to mice with preexisting parental tumors augments the vaccination effect of TNF gene modified tumor through the induction of MHC class I molecule."Gene Ther.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiwara H,Takahashi M, et al: "Synergistic suppressive effect of double transfection of TNF-α and IL-12 genes on tumorigenicity of Meth-A cells."Jpn J Cancer Res.. 91. 1296-1302 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato Y,Takahashi M, et al.: "In vivo gene delivery to tumor cells by transferrin-streptavidin-DNA conjugate."FASEB J. 14:. 2108-2118 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Igarashi T,Takahashi M, et al: "A novel strategy of cell targeting based on tissue specific expression of the ecotropic retrovirus receptor gene."Hum.Gene Ther.. 9. 2691-2698 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamano S,Takahashi M, et al: "Induction of Transformation and p53-dependent-apoptosis by adenovirus type 5 early region4 ORF6/7 cDNA."J.Virology. 13. 721-730 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato T,Takahashi M, et al: "An apoptosis-inducing gene therapy for pancreatic cancer with a combination of 55-kDa tumor necrosis factor(TNF) receptor gene transfection and mutein TNF administration"Cancer Res.. 58. 1677-1683 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 高橋稔,佐藤勉 他: "癌治療の新たな試み 新編II:癌の遺伝子治療"医薬ジャーナル社. 414 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 高橋稔,新津洋司郎: "臨床家のための癌遺伝子/癌抑制遺伝子"新津洋司郎、横田淳. 198 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] O'Reilly MS., Boehm T., Shing Y., Fukai N., Vasios G., Lane WS., Flynn E., Birkhead JR., Olsen BR., Folkman J.: "Endostatin : an endogenous inhibitor of angiogenesis and tumor growth."Cell. 88. 277-85 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] O'Reilly MS., Holmgren L., Chen C., Folkman J.: "Angiostatin induces and sustains dormancy of human primary tumors in mice."Nature Med. 2. 689-92 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato Y, Yamauchi N, Takahashi M, et al.: "In vivo gene delivery to tumor cells by transferrin-streptavidin-DNA conjugate."FASEB J. 14. 2108-2118 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lu Y,Takahashi M, et al: "Administration of sub tumor-regression dosage of TNF-α to mice with preexisting parental tumors augments the vaccination effect of TNF gene modified tumor through the induction of MHC class I molecule."Gene Ther.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiwara H,Takahashi M, et al: "Synergistic suppressive effect of double transfection of TNF-α and IL-12 genes on tumorigenicity of Meth-A cells."Jpn J Cancer Res.. 91. 1296-1302 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sato Y,Takahashi M, et al.: "In vivo gene delivery to tumor cells by transferrin-streptavidin-DNA conjugate."FASEB J. 14:. 2108-2118 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Igarashi T,Takahashi M, et al: "A novel strategy of cell targeting based on tissue specific expression of the ecotropic retrovirus receptor gene."Hum. Gene Ther.. 9. 2691-2698 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] YamanoS,Takahashi M et al: "Induction of Transformation and p53-dependent-apoptosis by adenovirus type 5 early region4 ORF6/7 cDNA."J.Virology. 13. 721-730 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sate T,Takahashi M et al: "An apoptosis-inducing gene therapy for pancreatic cancer with a combination of 55-kDa tumor necrosis factor (TNF) receptor gene transfection and mutein TNF administration"Cancer Res.. 58. 1677-1683 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋稔,佐藤勉 他: "癌治療の新たな試み 新編II:癌の遺伝子治療"医薬ジャーナル社. 414 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋稔,新津洋司郎: "臨床家のための癌遺伝子/癌抑制遺伝子"新津洋司郎,横田淳. 198 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Igarashi T., Takahashi M., et al: "A novel strategy of cell targeting based on tissue specific expression of the ecotropic retrovirus gene."Hum. Gene Ther. 9. 2691-2698 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] YamanoS., Takahashi M. et al: "Induction of Transformation and p53-dependent-apoptosis by adenovirus type 5 early region4 ORF6/7 cDNA."J. Virology. 13. 721-730 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sato T., Takahashi M. et al: "An apoptpsis-inducing gene therapy for pancreatic cancer with a combination of 55-kDa tumor necrosis factor(TNF) receptor gene transfection and mutein TNF administration"Cancer Res. 58. 1677-1683 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi M., Ilan Y et al: "Long-term correction of bilirubin-UDP-glucuronosyltransferase deficiency in Gunn rats by administration of a recombinant adenovirus during the neonatal period"J. Biol. Chem. 271. 26536-26542 (1996)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ilan Y. ,Takahashi M. et al: "Induction of central tolerance by intrathymic inoculation of adenovirral agents into the host thymus permits Long-term gene therapy in Gunn rats"J.Clin.Invest. 98. 2640-2647 (1996)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lu Y. ,Takahashi M et al: "Upregulation of Class II and B7 on tumor cell surface in thymidine kinase gene therapy for animals with low immune response"Biotherpy. 13. 721-730 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 高橋 稔、新津洋司: "最新電器泳動実験法:癌の遺伝子治療"日本電気泳動学会編、第1版、. 470 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 高橋 稔、新津洋司郎: "臨床家のための癌遺伝子/癌抑制遺伝子"新津洋司郎、横田 淳. 198 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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