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Gene therapy against ovarian cancers using hTERT promoter

Research Project

Project/Area Number 12470339
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKanazawa University

Principal Investigator

INOUE Masaki  Kanazawa University, Medical Science, Professor, 医学系研究科, 教授 (10127186)

Co-Investigator(Kenkyū-buntansha) KYO Satoru  Kanazawa University, Medical Science, Assistant professor, 医学系研究科, 講師 (50272969)
高倉 正博  金沢大学, 医学部・附属病院, 助手 (20313661)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥9,300,000 (Direct Cost: ¥9,300,000)
Keywordstelomere / telomerase / gene therapy / ovarian cancer / hTERT / Multidisciplinary treatment / 癌治療
Research Abstract

Telomerase activation has been observed in almost 90% of human cancers but not normal tissues of somatic origin. The recent research on the transcriptional regulation of hTERT promoter identified several factors, including c-Myc, SP1 and E2, which critically regulate promoter activity. The present study is based on the idea that the hTERT promoter can confer strong tumor-specific transgene expression, minimizing toxicity to normal cells, compared to the universal promoters. The following results were obtained from the present study.
1) In vitro and in vivo administration of chimeric vectors in which hTERT promoter is linked to apoptosis-inducing genes, such as Caspase, FADD or Bax successfully induce apoptosis in cancer cells with damaging normal cell.
2) The binary adenovirus system using two vectors, Ad/GT-BAX and Ad/hTERT-GV16 augmented the anti tumor-efficacy.
3) The transfection of the vector designed to drive MCP-1 gene by hTERT promoter induced the expression of MCP-1 more extensively, compare to CMV-promoter. The multidisciplinary treatment of therapeutic vectors with MCP-1 gene and cisplatin suppressed significantly tumor growth in vivo.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Kyo S, Inoue M: "How to inhibit telomerase activity for cancer therapy"Current Medical chemistry. 2. 613-626 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kyo S, Inoue M: "Complex regulatory mechanisms of telomerase activity"Oncogene. 21. 688-697 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komata T, Kondo Y, Inoue M, et al.: "Caspas-8 gene therapy using hTERT for malignet glicma cells"Human gene Therapy. 13. 1015-1025 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yatabe N, Kyo S, Inoue M, et al.: "2-5A antisenes therapy directed against h-telomerase RNA in bibits telomerase activits in cancer cells"Cancer Gene Therapy. 9. 624-630 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komata T, Kondo Y, Inoue M, et al.: "Treatment of maligant cells with transfeve of active caspase 6 using hTERT gene"Cancer Research. 61. 5796-5802 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koga S, Kyo S, Inoue M, et al.: "FAOD gene therapy using the human TERT gene promoter to restrict in duction of apoptosis to tumors"Anti-Cancer Research. 21. 1937-1943 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koga S., Hirohata S., Kondo Y., Komata T., Takakura M., Inoue M., Kyo S., Kondo S.: "FADD gene therapy using the human telomerase catalytic subunit (hTERT) gene promoter to restrict induction of apoptosis to tumors in vitro and in vivo"Anti Cancer Res. 21. 1937-1943 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komata T., Kondo Y., Kanzawa T., Hirohata S., Koga S., Sumiyoshi H., Srinivasula S.M., Barna B.P., Alnemri E.S., Germano I.M., Takakura M., Inoue M., Alnemri E.S., Shay J.W., Kyo S. and Kondo S.: "Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (hTERT) gene."Cancer Res. 61. 5796-5802 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takakura M., Kyo S., Sowa Y., Wang Z., Yatabe N., Maida Y., anaka M., Inoue M.: "Telomerase activation by histone deacetylase inhibitor in normal cells: induction of hTERT expression through Sp1 binding sites."Nucleic Acids Res. 29. 3006-3011 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komata T., Koga S., Hirohata S., Takakura M., Germano I.M., Inoue M., Kyo S., Kondo S.: "A novel treatment of human malignant gliomas in vitro and in vivo"Int J Oncol. 19. 1015-1020 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maida Y., Kyo S., Kanaya S., Zhuo Wang, Takakura M., Yatabe N., Tanaka M., Nakamura M., Ohmichi M., Gotoh M., and Inoue M.: "Direct activation of telomerase by EGF through Ets - mediated transactivation of TERT via MAP kinase signaling pathway"Oncogene. 21. 4071-4079 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wang Z., Kyo S., Maida Y., Takakura M., Tanaka M., Yatabe N., Koike K., Hayakawa J., Ohmichi M., Inoue M.: "Tamoxifen regulates human telomerase reverse transcriptase (hTERT) gene expression differently in breast and endometrial cancer cells"Oncogene. 21. 3517-3524 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yatabe N., Kyo S., Kondo S., Kanaya T., Wang Z., maida Y., Takakura M., Nakamura M., Tanaka M. and Inoue M.: "2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells."Cancer Gene Ther. 9. 624-630 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komata T., Kondo Y., Hirohata S., Koga S., Sumiyoshi H., Takakura M., Inoue M., Barna B.P., Germano I.M., Kyo S., Kondo S.: "Caspace-8 gene therapy using human telomerase reverse transcrptase promoter for malignant glioma cells."Human Gene Therapy. 13. 1015-1025 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kyo S., Inoue M.: "Review Article: Complex regulatory mechanisms of telomerase activity in normal and cancer cells."Oncogen. 21. 688-697 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kyo S., Inoue M.: "How to inhibit telomerase activity for cancer therapy. Current Medical Chemistry."Anti-cancer Agents. 2. 613-626 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanaya T, Kyo S, Maid Y, Yatabe N, Tanaka M, Nakamura M, Inoue M: "Frequent hypermethylation of RMLH, promoter in normal endometrium of patients with endometridl Cancers"Oncogene. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka M, Kyo S, Kanaya T, Nakamura M, Maida Y, Inoue M: "Evidence of the monoclonal composition of human endowetridl epithelial glands and masaic pattern of clonal distribution"Am J. Pathology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maida Y, Kyo S, Kanaya T, Wang Z, ・・・ Inoue M.: "Direct activation of telomerase by EGF through Ets-mediated Transactination of TERT via MAP Kinase signaling pathway"Oncogene. 21. 4071-4079 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wang Z, Kyo S, Maida Y, ・・・ Inoue M.: "Tamoxiten regulates hTERT expression differently in breast and endometral Cancer cells"Oncogene. 21. 3517-3524 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kyo S, Inoue M.: "Complex regulatory mechanisms of telomerase activation in normal and cancer cells"Oncogene. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kyo S, Inoue M.: "Antisense-based strategies that block telomerase activity for the trearment at cancers"Current Medical chem. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue, M.: "Current molecular aspects of the carcinogenesis of the uterine endometrium"Int J Gynecol Cancer. 11. 339-348 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takakura M, Kyo S, et al.: "Telomerase activition by histone deacetylase inhibition in normal cells"Nucleic Acids Res. 29. 3006-3011 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Komata T, Kyo S, et al.: "Treatment of malignat gliona cells with the transfen of constitufivery active casposeb using hTERT gene"Cancer Res. 61. 5796-5802 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Komata T,Kondoh Y,Hirohata S, et al.: "Treatment of malignant glioma cells with the transfer of constitutively acetine caspase-G using hTERT gene"Cancer Research. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wang Z,Kyo S,Takakura M, et al.: "Progesterone regulates human telome rase reverse transcriptase gene expression via activation of MAP kinase signaling pathway"Cancer Research. 60. 5376-5381 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kyo S,Takakura M,Kamaya T et al: "SP, cooperates with c-myc to activate transcription of human telome rase reverse transcrip tase gene"Mucleic Acids Research. 28. 669-677 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kanaya T,Kyo S,Hamada K et al.: "Adenoviral expression of p53 represses telomerase activity through down-regulation of hTERT transcription"Climical Cancer Research. 6. 1239-1247 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaya S,Hiroheta S,Kondo Y. et al.: "A novel telomerase-specific gene therapy"Human gene therapy. 10. 1397-1406 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Gu J,Kagawa S,Takakura H,kyo S,I.nocce M, et al: "Trencor-specific trans gene expression from hTERT promorterm enable targeting of the therapeutic effects to cancer"Carcer Research. 60. 5359-5364 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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