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Enhanced apoptosis and transforming growth factor-β1 expression in colorectal adenomas and carcinomas after sulindac therapy

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Diseases of the Colon & Rectum

Abstract

PURPOSE: We tried to elucidate the effects of sulindac on human colorectal carcinoma. METHODS: Sulindac (300 mg/day) was administered for two weeks before operation to 33 patients with sporadic colorectal carcinoma (Sulindac Group). Resected specimens were used to detect apoptosis by terminal dUTP nick end labeling and transforming growth factor (TGF)-β1 expression by immunohistochemistry. The results were compared with those from the historical Control Group. Twenty-nine available preoperative biopsies taken from carcinomas before sulindac prescription and 22 concurrent colorectal adenomas (9 and 13 in Sulindac and Control Groups, respectively) in the resected specimen were also examined regarding TGF-β1 expression. RESULTS: In the resected carcinomas and adenomas, more frequent apoptosis and higher TGF-β1 scores were observed in the Sulindac Group than in the Control Group. Overexpression of TGF-β1 and apoptosis occurred in the same region in adenomas but not in carcinomas. A positive correlation between TGF-β1 scores and apoptotic frequency was found in adenomas (P=0.01,ρ=0.91) but not in carcinomas (P=0.89,ρ=0.03). CONCLUSION: We conclude that sulindac induces apoptosis in human colorectal carcinomas as well as in adenomas. Also, one of the antineoplastic effects of sulindac might be mediated by upregulating TGF-β1 expression, particularly in colorectal adenomas.

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Authors and Affiliations

  1. Second Department of Surgery, Shimane Medical University, 693-8501, Izumo, Japan

    Reiko Masunaga M.D., Hitoshi Kohno M.D., Dipok Kumar Dhar M.D., Tsukasa Kotoh M.D., Hideki Tabara M.D., Mitsuo Tachibana M.D., Hirofumi Kubota M.D. & Naofumi Nagasue M.D.

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  1. Reiko Masunaga M.D.
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  2. Hitoshi Kohno M.D.
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  3. Dipok Kumar Dhar M.D.
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  4. Tsukasa Kotoh M.D.
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  5. Hideki Tabara M.D.
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  7. Hirofumi Kubota M.D.
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  8. Naofumi Nagasue M.D.
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Masunaga, R., Kohno, H., Dhar, D.K. et al. Enhanced apoptosis and transforming growth factor-β1 expression in colorectal adenomas and carcinomas after sulindac therapy. Dis Colon Rectum 44, 1008–1015 (2001). https://doi.org/10.1007/BF02235490

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