Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis.

Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. Research Abstract Details 

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Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. Abstract Text:

Boryana K Popivanova,Kazuya Kitamura,Yu Wu,Toshikazu Kondo,Takashi Kagaya,Shiuchi Kaneko,Masanobu Oshima,Chifumi Fujii,Naofumi Mukaida,

The inflammatory bowel disease ulcerative colitis (UC) frequently progresses to colon cancer. To understand the mechanisms by which UC patients develop colon carcinomas, we used a mouse model of the disease whereby administration of azoxymethane (AOM) followed by repeated dextran sulfate sodium (DSS) ingestion causes severe colonic inflammation and the subsequent development of multiple tumors. We found that treating WT mice with AOM and DSS increased TNF-alpha expression and the number of infiltrating leukocytes expressing its major receptor, p55 (TNF-Rp55), in the lamina propria and submucosal regions of the colon. This was followed by the development of multiple colonic tumors. Mice lacking TNF-Rp55 and treated with AOM and DSS showed reduced mucosal damage, reduced infiltration of macrophages and neutrophils, and attenuated subsequent tumor formation. WT mice transplanted with TNF-Rp55-deficient bone marrow also developed significantly fewer tumors after AOM and DSS treatment than either WT mice or TNF-Rp55-deficient mice transplanted with WT bone marrow. Furthermore, administration of etanercept, a specific antagonist of TNF-alpha, to WT mice after treatment with AOM and DSS markedly reduced the number and size of tumors and reduced colonic infiltration by neutrophils and macrophages. These observations identify TNF-alpha as a crucial mediator of the initiation and progression of colitis-associated colon carcinogenesis and suggest that targeting TNF-alpha may be useful in treating colon cancer in individuals with UC.

Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. Publishing Authors By Initials

BK Popivanova,K Kitamura,Y Wu,T Kondo,T Kagaya,S Kaneko,M Oshima,C Fujii,N Mukaida,

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Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of clinical investigation

VOLUME: 118

Page Numbers: 560-70

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 4

MONTH: Feb

YEAR: 2008

Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. Information

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LANGUAGE: eng

NlmUniqueID: 7802877

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Grant and Affiliation Information for Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis.

AFFILIATION: Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.

Country: United States

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MEDLINETA: J Clin Invest

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