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Cyclooxygenase-2 in development of colorectal neoplasia and effect of cyclooxyhgenase-2 inhbitor on colorectal neoplasia

Research Project

Project/Area Number 12470253
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SUGIHARA Kenichi  Tokyo Medical and Dental University, Graduate School Department of physiology, Professor, 大学院・歯学総合研究科, 教授 (10171167)

Co-Investigator(Kenkyū-buntansha) UETAKE Hiroyuki  Tokyo Medical and Dental University, Medical Hospital, Research Associate, 医学部附属病院, 助手 (60311651)
ENOMOTO Masayuki  Tokyo Medical and Dental University, Graduate School Department of physiology, Lecturer, 大学院・歯学総合研究科, 講師 (60301165)
樋口 哲郎  東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (90334416)
吉永 圭吾  東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (80240745)
Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsCyclooxygenase-2 / NSAIDs / COX-2 Inhibitor / colorectal adenoma / Colorectal cancer / familial nolyposis coli / 大腸腺腫 / 大腸腺腫症 / COX2 / 動物実験 / 癌 / 治療 / サイクロオキシゲナーゼ / COX-2 / 大腸腺種 / NSAID
Research Abstract

1 COX-2protein is induced in the polyp stroma near the intestinal luminal surface in the APC^<Δ716> and stimulate tumor angiogenesis. By immunohistochemical analysis, we showed that majority of COX-2 expressing cells in the intestinal polyps of mice are fibroblasts and endotherial cells. Can Res 2002;62:6846-6849.
2 COX-2 expression was evaluated by immunohistochemical staining in 95 colorectal adenomas. Expression was significantly related to grade of dysplasia and tumor size, but multivariate analysis showed COX-2 expression to be independently associated with grade of dysplasia. (Dis Colon Rectum 2003;46:786-792.
3 Immunohistochemical staining for Ki-67 antigen and COX-2 was performed on 95 colorectal adenomas. The Ki-67 labeling index was significantly higher in the high-COX-2 group than in the low-COX-2 and negative group in adenoma with sever and moderate dysplasia. Ther was no correlation between Ki-67 labeling index and COX-2 expression in mild dysplasia. (Jpn J Clin Oncol 2003;33:631-635.
4 A total of 48 T1 colorectal cancers were classified into polypoid or non-polypoid. COX-2 expression was determined immunohistochmically and PCR-RFLP was used to detecte a K-ras mutation. COX-2 expression was significantly higher in polypoid tha in non-polypoid. The K-ras mutation was associated higher levels of COX-2 expression. (Dis Colon Rectum 2004;47: in press)
5 A total of 21 patients with familial adenomatous polyposis coli were assigned randomly to receive either 25 mg of rofecoxib or placebo for '9 months. The number and size of the rectal polyps were evaluated by colonoscopy. The number and size of the polyps of patients who had rofecoxib were significantly decreased at 9 months. (Clin Can Res 2003:9:4756-4760)

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Sato T, Yoshinaga K, Okabe T, Okawa T, Enomoto M, Sugihara K: "Cyclooxygenase-2 expression in colorectal adenoma"Diseases of the Colon and Rectum. 46(6). 786-792 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato T, Yoshinaga K, Okabe T, OKawa T, Enomoto M, Sugihara K: "Cycloxygenase-2 expression and its relationship with proliferation of colorectal adenoma"Japanese Journal of Clinical Oncology. 33(12). 631-635 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higuchi T, Iwama T, Yoshinaga K, Toyooka M, Taketo MM, Sugihara K: "A randomized, double-blind, palacebo-controlled trial of the effects of Rogecoxib, and a selective cyclooxygenase-2 inhibitor, on rectal polyp"Clinical Cancer Research. 15(9). 4756-4760 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeda H, Sonoshita M, Oshima H, Sugihara K, Oshima N, Taketo MM: "Cooperation of cyclooxygenase 1 and cyclooxynase 2 in intestinal Polyposis."Cancer Research. 63. 4827-4877 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sonoshita M, Takaku K, Oshima M, Sugihara K, Taketo MM.: "Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps"Cancer Research. 62. 6846-6849 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okawa T, Yoshinaga K, Uetake H, Sato T, Higuchi T, Sugihara K: "Cyclooxygenase-2 overexpression is related to polypoid groeth and k-ras mutation in invasive submucosal colorectal carcinoma"Diseases if the Colon and Rectum. 47(in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato T, Yoshinaga K, Okabe S, Okawa T, Enomoto M, Takizawa T, Sugihara K.: "Cyclooxygenase-2 expression in colorectal adenomas"Dis Colon Rectum. 46(6). 786-792 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato T, Yoshinaga K, Okabe S, Okawa T, Higuchi T, Enomoto M, Takizawa T, Sugihata K: "Cyclooxygenase-2 expression and its relationship with proliferation of colorectal adenoma"Jpn J Olin Oncol. 33. 631-635 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higuchi T, Iwama T, Yoshinaga K, Toyooka M, Taketo MM, Sugihara K.: "A randomized, double-blind, placebo-controlled trial of the effects of Rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous polyposis patients."Olin Can Res. 9. 4756-4760 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeda H, Sonoshita M, Oshima H, Sugihara K, Chulada PC, Langenbach R, Oshima M, Taketo MM.: "Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal Polyposis."Cancer Res. 63. 4872-4877 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsunozaki H, Yoshinaga K, Kumagai J, Sugihara K: "Cyclooxygenase-2 overexpresion in colorectal cancer is associated with non-polypoid growth."Jpn J Clin Oncol. 32(5). 167-171 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sonoshita M, Takaku K, Oshima M, Sugihara K, Taketo MM.: "Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps."Cancer Res. 62. 6846-6849 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okawa T, Yoshinaga K, Uetake H, Sato T, Higuchi T, Nemoto T, Sugihara K: "Cyclooxygenase-2 overexpression is related to polypoid growth and k-ras gene mutation in Ti colorectal carcinomas"Dis Colon Rectum. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato T, Yoshinaga K, Okabe T, Okawa T, Enomoto M, Sugihara K: "Cyclooxygenase-2 expression in colorectal adenoma"Diseases of the Colon and Rectum. 46(6). 786-792 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato T, Yoshinaga K, Okabe T, Okawa T, Enomoto M, Sugihara K: "Cyclooxygenase-2 expression and its relationship with proliferation of colorectal adenoma"Japanese Journal of Clinical Oncology. 33(12). 631-635 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higuchi T, Iwama T, Yoshinaga K, Toyooka M, Taketo MM, Sugihara K: "A randomized, double-blind, placebo-controlled trial of the effects of Rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in amilial adenomatous polyposis patients"Clinical Cancer Research. 15(9). 4756-4760 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okawa T, Yoshinaga K, Uetake H, Sato T, Higuchi T, Sugihara K: "Cyclooxygenase-2 overexpression is related to polypoid growth and k-ras mutation in invasive submucosal colorectal carcinoma"Diseases of the Colon and Rectum. 47(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohno R, Sugihara K: "Depth of invasion parallels increased cyclooxgenase-2 levels patients with gastric carcinoma"Cancer. 91. 1876-1881 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hasegawa K, Sugihara K: "Expression of cyclooxgenase-2 (cox)-2, mRNA in human colorectal adenomas"Eur J Cancer. 37. 1469-1474 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato T., Sugihara K: "Cyclooxygenase (cox)-2 expression in colorectal adeuomg"Dis Colon Rectur. (accepted).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohno R, et al.: "Depth of invasion parallels increased cyclooxygenese-2 levels in patients with gastric carcinoma"Cancer. 91. 1876-1881 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hasegawa K, et al.: "Expression of cyclooxygenase-2(COX-2)mRNA in human cdorectal adenomas"European Journal of Cancer. 37. 1469-1474 (2001)

    • Related Report
      2001 Annual Research Report

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

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