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Mechanisms of preventive effects of nonsteroidal anti- inflammatory drugs on colon carcinogenesis

Research Project

Project/Area Number 10670499
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSaitama Medical School

Principal Investigator

OTA Shinichi  SAITAMA MEDICAL SCHOOL, MEDICAL DEPARTMENT, PROFESSOR, 医学部, 教授 (30185269)

Co-Investigator(Kenkyū-buntansha) BAMBA Hiromi  SAITAMA MEDICAL SCHOOL, MEDICAL DEPARTMENT, RESEARCH ASSISTANT, 医学部, 実験助手
KATO Akira  SAITAMA MEDICAL SCHOOL, MEDICAL DEPARTMENT, ASSISTANT, 医学部, 助手 (30204457)
伴場 裕巳  埼玉医科大学, 医学部, 研究助手
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsNSAIDs / PROSTAGLANDIN / COX-2 / COLON CARCINOGENESIS / COLON ADENOMA / VEGF / PROSTAGLANDIN RECEPTORS / MACROPHAGE / PPArγ / NSAID / COX
Research Abstract

We investigated the localization of cyclooxygenase (COX)-2, a possible target of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of colon carcinogenesis. Then effects of prostaglandins on vascular endothelial growth factor (VEGF), an essential factor in tumor angiogenesis, production was studied. Results are as follows;
a. High expression of COX-2 was detected in sub-epithelial interstitial cells, possibly macrophages, broadly present in the surface area of human adenomas.
b. Coz-2 was only partly and weekly expressed in human advanced colon cancer.
c. Prostaglandin (PG) E dramatically increased the production of VEGF by human macrophages but not by human colonic adenoma cells or cancer cells.
d. This action was mediated by the increase of cAMP through EPィイD22ィエD2 and EPィイD24ィエD2 PGE receptors
e. PGJ2, an agonist of nuclear receptor PPAR γ, also dramatically increased VEGF production by human macrophages.
These results suggest that PGs produced by macrophaged of human colonic adenomas may play important roles in human colon carcinogenesis through the induction of VEGF. NSAIDs possibly prevent human coloncarcinogenesis by the suppression of this step.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Ota S, Tanaka Y, Bamba H, et al: "MSAID may prevent colon cancer through suppression of HGF expression"Eur. J. Pharmacol.. 367. 131-138 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Bamba H, Ota S, Kato A et al: "High expression of cyclooxygeuose-2 in macrophages of human calorie adenoma"Int J. Cancer. 83. 470-475 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Bamba H, Ota S, Kato A et al: "Effects of prostaglandin E on VEGF production by human macrophage and color cancer cells"Journal of experimental & clinical Cancer Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ota S, Bamba H, Kato A, et al: "Roles of prostaglandins in the regulation of growth factor expression in the stomach."Preceedings of GI Forum. 24-27 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ota S. Bamba H, Kato A,: "Colorectel Cancer and Neusteroidal Anti-inflammatory drugs"Acta Pharmacologica Sirica. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 太田慎一、伴場裕己、加藤孝: "NSAIDsによる大腸発癌発生予防機構の検討"消化器の臨床. 1. 282-285 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinlchi Ota, Yasuhiro Tanaka, Hiromi Bamba, Akira Kato, Fukashi Matsuzaki: "NSAIDs may prevent colon cancer through suppression of hepatocyte growth factor expression."Eur J Pharmacol. 367. 131-138 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiromi Bamba, Shinichi Ota, Akira Kato, Fukashi Matsuzaki.: "High expression of cyclooxygenase-2 in macrophages of human colonic adenoma."Int J Cancer. 83. 470-475 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiromi Bamba, Shinichi Ota, Akira Kato, Fukashi Matsuzaki.: "Effect of prostaglandin E1 on vascular endothelial growth factor production by human macrophages and colon cancer cells."Journal of Experimental & Clinical Cancer Research. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ota S, Bamba H, Kato A.: "Colorectal Cancer and Nonsteroidal Anti-inflammatory drugs."Acta Pharmacolol Sinica. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinichi Ota, Hiromi Bamba, Akira Kato, Fukashi Matsuzaki, Kenji Fujiwara.: "Roles of prostaglandins In the regulation of growth factor expression in the stomach. Further Advances in Gastrointestinal Ulcer (Disease Proceedings of GI Forum 1999 Edited by Terano A and Szabo S"Yamanouchi Pharmaceutical Co., Ltd.. 24-27 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ota S, Tanaka Y, Bamba H, et al: "NSAID may prevent colon cancer through suppression of HGF expression"Eur. J. Pharmacol. 367. 131-138 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Bamba H, Ota S, Kato A, et al: "High expression of cyclooxygenase-2 in macro phages of human colonire adenoume"Int, J. Cancer. 83. 470-475 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Bamba H, Ota S, Kato A, et al: "Effect of Prostaglandin E1 on VEGF production by human macrophages and colon concer cells"Journal of experimental & clinical cancer Reseurd. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ota S, Bamba H, Kato A, et al: "Roles of prostaglandins in the regulation of growth factor expression in the stomach"Preceedings of GI Forum. 24-27 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ota S, Bamba H, Kato A,: "Colorectal cancer and Nonsteroidal Anti-inflammatory drugs"Acta Pharmacologica Sinica. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] 太田慎一,伴場裕己,加藤章: "NSAIDsによる大腸癌発癌予防機構の検討"消化器の臨床. 1. 282-285 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Ota, Y.Tanaka, H.Banaba, A.Kato, F.Matsuzaki: "Nonsteroidal anti-inllammatory druugs may prevent color cancer through suppression of hepatocyte growth factor" European Journal of Pharmacology. 367. 131-138 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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