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Diagnostic and therapeutic study of angiogenesis in urogenital cancers

Research Project

Project/Area Number 12671541
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

ETO Masatoshi (2002-2003)  Department of Urology, Graduate School of Medical Sciences, Assist Prof, 医学部附属病院, 講師 (90315078)

徳田 倫章 (2000-2001)  九州大学, 医学部・附属病院, 講師 (20264038)

Co-Investigator(Kenkyū-buntansha) UENO Hikaru  University of Occupational and Environmental Health, Department of Biochemistry and Molecular Pathophysiology, School of Medicine Prof, 医学部, 教授 (50260378)
江藤 正俊  九州大学, 医学部・附属病院, 助手 (90315078)
尾本 和也  東京女子医科大学, 助手
Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsangiogenesis / VEGF / VEGF receptor / Flt-1 / gene therapy / microarray / angiogenesis inhibitor / 腎細胞癌 / 膀胱癌 / 腎尿路性器癌
Research Abstract

As-basic research, we constructed an adenovirus vector encoding a soluble VEGF receptor/flt-1 (Adflt-ExR). This soluble receptor is secreted from Adflt-ExR-transfected cells. Murine renal cell carcinoma cell line, Renca cells or murine bladder carcinoma cell line, MBT2 cells were infected with Adflt-ExR beforehand and injected subcutaneously into BALB/c or C3H/He mice, respectively. in vivo growth of AdVEGF-ExR-infected tumor cell lines was significantly suppressed in syngeneic mice. Although two of five mice rejected the AdVEGF-ExR infected RENCA, tumor-specific cytotoxic T lymphocytes were not generated from their spleen cells, suggesting no elicitation of cellular immune response. Our results indicate that adenovirus-mediated expression of a soluble VEGF receptor can be an effective therapy for cancer treatment, but that VEGF-targeted gene therapy is not necessarily accompanied with subsequent anti-tumor T cell immunity.
As clinical research, serum VEGF and FGF concentrations were me … More asured in 57 RCC patients using the sandwich enzyme immunoassay. Although these factors showed no significant correlation with tumor size, TNM stage, subsequent recurrence or disease progression, a significantly high VEGF level was observed in V(+) patients compared with V(-) patients. In addition, microarray analysis of renal cell carcinomas also demonstrates high expression of VEGF and ECGF1 genes compared with normal kidney tissues. We also performed combined immunotherapy with IFN-α, 5-FU, Leucovorin, cimetidine in 37 patients with advanced renal cell carcinoma, since IFN-α and 5-FU were recently reported to have antiangiogeneic effects against cancers. Response rate (CR + PR) was 16.2 % 12 weeks after the beginning of the treatment, and 56.8 % of patients showed 【greater than or equal】 NC (CR + PR + NC). In addition, 1 or 3 year survival of the patients with 【greater than or equal】 NC was 90.0 % or 56.4 %, respectively. These results demonstrate the efficacy of our combined immunotherapy for advanced renal cell carcinoma. Less

Report

(5 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Eto M et al.: "Antitumor activity of interleukin-12 against murine bladder cancer"Journal of Urology. 163. 1549-1552 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 徳田倫章ら: "腎癌術後の経過観察に血中血管新生因子測定を果たして有用か"腎癌研究会会報. 18. 15-16 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 徳田倫章ら: "腎癌の臨床における血管新生因子群の有用性とVEGF受容体を標的とした遺伝子治療"西日本泌尿器科. 63. 219-222 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okano S et al.: "Cyclophosphamide-induced tolerance in rat orthotopic liver transplantation."Transplantation. 71. 447-456 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Eto M et al.: "Promotion of skin allograft tolerance across MHC barriers by mobilization dendritic cells in donor hemopoietic cell"Journal of Immunology. 169. 2390-2396 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Eto M et al.: "C16 ceramide accumulates following androgen ablation in LNCaP prostate cancer cells"Prostate. 57. 66-79 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 江藤正俊ら: "進行腎癌に対するIFN-a,5-FU, Leucovorin, cimetidine併用療法"腎癌研究会会報. 24. 7-8 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Eto, et al.: "Antitumor activity of interleukin-12 against murine bladder cancer"Journal of Urology. 163. 1549-1552 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Tokuda, et al.: "Are pretreatment serum VEGF and FGF values useful in following up the patients with renal cell carcinoma?"Jingan Kenkyukai kaiho,. 18. 15-16 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Tokuda, et al.: "Usefulness of pretreatment serum VEGF and FGF values inpatients with renal cell carcinoma and gene therapy to target tumor angiogenesis."Nishinihon J. Urol.. 63. 219-222 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Okano, et al.: "Cyclophosphamide-induced tolerance in rat orthotopic liver transplantation."Transplantation. 71. 447-456 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Eto, et al.: "Promotion of skin allograft tolerance across MHG barriers by mobilization of dendritic cells in donor hemopoietic cell infusion."Journal of Immunology. 169. 2390-2396 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Eto, et al.: "C16 ceramide accumulates following androgen ablation in LNCaP prostate cancer cells."Prostate. 57. 66-79 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Eto, et al.: "Combined immunotherapy with IFN-α, 5-FU, Leucovorin, cimetidine for advance dl renal cell carcinoma"Jingan Kenkyukai kaiho. 24. 7-8 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Eto M et al.: "Antitumor activity of interleukin-12 against murine bladder cancer"Journal of Urology. 163. 1549-1552 (2000)

    • Related Report
      2003 Annual Research Report
  • [Publications] 徳田倫章: "腎癌術後の経過観察に血中血管新生因子測定は果たして有用か"腎癌研究会会報. 18. 15-16 (2000)

    • Related Report
      2003 Annual Research Report
  • [Publications] 徳田倫章: "腎癌の臨床における血管新生因子群の有用性とVEGF受容体を標的とした遺伝子治療"西日本泌尿器科. 63. 219-222 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Eto M et al.: "Promotion of skin allograft tolerance across MHC barriers by mobilization of dendritic cells in donor hemopoietic cell infusion"Journal of Immunology. 169. 2390-2396 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Eto M et al.: "C16 ceramide accumulates following androgen ablation in LNCaP prostate cancer cells"Prostate. 57. 66-79 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 江藤正俊: "進行腎癌に対するIFN-a,5-FU,Leucovorin,cimetidine併用療法"胃癌研究会会報. 24. 7-8 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 徳田倫章, 中村元信, 江藤正俊, 内藤誠二: "腎癌術後の経過観察に血中血管新生因子測定は果たして有用か"腎癌研究会会報. 19. 25-26 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中村元信, 徳田倫章: "進行腎細胞癌に対するIFNa,5-FU, Leucovorin, Cimetidine併用療法"腎癌研究会会報. 20. 28-29 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] 徳田倫章, 中村元信, 江藤正俊: "腎癌の臨床における血管新生因子群の有用性とVEGF受容体を標的とした遺伝子治療"西日泌尿. 63. 219-222 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 横溝 晃, 徳田倫章, 他: "腎癌と前立腺癌における血管新生"Molecular Medicine. 37. 330-337 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 徳田倫章, 他: "腎癌の臨床における血管新生因子群の有用性とVEGF受容体を標的とした遺伝子治療"西日本泌尿器科. 63・4. 219-222 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 徳田倫章 他: "腎癌術後の経過観察に血中血管新生因子測定は果たして有用か。"腎癌研究会会報. 18. 25-26 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 中村元信,徳田倫章 他: "進行腎細胞癌に対するIFNα、5-FU、Leucovorin、Cimetidine併用療法"腎癌研究会会報. 19. 28-29 (2000)

    • Related Report
      2000 Annual Research Report

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

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