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STUDY ON MECHANISM OF TUMOR ANGIOGENESIS IN UROTHELIAL CANCERS AND SCREENING OF ANGIOGENIC INHIBITORS

Research Project

Project/Area Number 07671739
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionOITA MEDICAL UNIVERSITY

Principal Investigator

NAKAGAWA Masayuki  OITA MEDICAL UNIVERSITY,UROLOGY,ASSOCIATE PROFESSOR, 医学部泌尿器科, 助教授 (90164144)

Co-Investigator(Kenkyū-buntansha) TASAKI Yoshihisa  OITA MEDICAL UNIVERSITY,UROLOGY,ASSISTANT PROFESSOR, 医学部泌尿器科, 助手 (80244177)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsangiogenesis / bladder cancer / renal cancer / tubulogenesis
Research Abstract

Tumor angiogenesis is essential for tumor growth and metastasis. Solid tumors depend on angiogenesis to grow larger than a few millimeters in diameter. To investigate the role of several angiogenic factors, such as b-FGF,VEGF,PDGF-A and TGF-alpha in angiogenesis in urothelial cancers, we examined the expression and localization of these angiogenic factors in patients with bladder cancers and renal cell carcinomas. Furthermore, tubulogenesis by VEGF and b-FGF of microvascular endothelial cells co-cultured with renal cancer cells was also examined by a three dimensional co-culture assay system. RT-PCR analysis detected mRNAs of b-FGF,VEGF,PDGF-A and TGF-alpha in 96%, 77%, 69% and 50% in renal cancers and 77%, 62%, 62% and 0% in bladder cancers, respectively. Immunohistochemical analysis revealed that b-FGF and VEGF were primarily localized in the nucleus and cytosol, respectively. Exogenous addition of b-FGF and VEGF increased tube formation of microvascular endothelial cells in a dose dependent manner in the three dimensional co-culture assay system. However, specific antibodies against b-FGF (10mug/ml) and VEGF (10mug/ml) completely inhibited the tube formation in the system, suggesting that neutral antibodies against angiogenic factors, including b-FGF and VEGF may suppress tumor growth by the inhibition of tumor angiogenesis. Recently, we observed that the expression of TGF-alpha increased as a function of tumor size in nude mice bearing bladder tumors, although the expression of TGF-alpha in the original bladder tumor was weak. Furthermore, we observed that bladder tumors which highly express PD-ECGF showed high tumor microvascular density determined by von-Willebrand factor. Thses results suggest that several angiogenic factors were involved in the multi-steps of tumor angiogenesis of urothelial cancers. Specific antibodies against these angiogenic factors may be clinically applicable to the cancer treatment.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] 中川昌之 他2名: "尿路癌における血管新生関連遺伝子の発現" 西日本泌尿器科. 58. 322-326 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Emoto,A.et al.: "Induction by basic fibroblast growth factor of angiogenesis in renal cell carcinoma" Journal of Urology. 157. 699-703 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakagawa,M.et al.: "Tubulogenesis by microvascular endothelial cells is mediated by vascular endothelial growth factor(VEGF)in renal cell carcinoma" British Journal of Urology. 78(印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakagawa, M., Emoto, A.and Nomura, Y.: "The expression of angiogenic factors in urinary cancers." Nishinihon J.Urol.58. 322-326 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Emoto, A., Nakagawa, M., Wakabayashi, Y., Hanada, T., Naito, S.and Nomura, Y.: "Induction of tubulogenesis of microvascular endothelial cells by basic fibroblast growth factor from human SN12C renal cancer cells." J.Urol.157. 699-703 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakagawa, M., Emoto, A., Hanada.T., Nasu, N.and Nomura, Y.: "Tubulogenesis by vascular endothelial cells is mediated by vascular endothelial growth factor (VEGF) in renal cell carcinoma." Brit.J.Urol.78(in press.). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakagawa, M., Emoto, A., Nasu, N., Hanada, T., Kuwano, N., Cole, S.P.C.and Nomura, Y.: "Clinical significance of multi-drug resistance associated protein and Pglycoprotein in patients with bladder cancer." J.Urol.157. 1260-1265 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 中川昌之 他2名: "尿路癌における血管新生関連遺伝子の発現" 西日本必尿器科. 58. 322-326 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Emoto,A.et al.: "Induction by basic fibroblast growth factor of angiogenesis in renal cell carcinoma" Journal of Urology. 157. 699-703 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakagawa,M.et al.: "Tubulogenesis by mictovascular endothelial cells is mediated by vascular endothelial growth factor (VEGF) in renal cell carcinoma" British Journal of Urology. 78(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 中川昌之 他2名: "尿路癌における血管新生関連遺伝子の発現" 西日本泌尿器科. 58(予定). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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