The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis
Open accessAbstract
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.
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Cited by
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Metadata
- Authors
- Popivanova, B. K., Kitamura, K., Wu, Y., Kondo, T., Kagaya, T., Kaneko, S., Oshima, M., Fujii, C., & Mukaida, N.
- Venue
- Journal of Clinical Investigation
- Published
- 2008-01-24
- Volume
- 118
- Issue
- 2
- Pages
- 560-70
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1988139137
- Cited by
- 832
- References
- 55
- FWCI
- 32.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Popivanova, B. K., Kitamura, K., Wu, Y., Kondo, T., Kagaya, T., Kaneko, S., Oshima, M., Fujii, C., & Mukaida, N. (2008). Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis. Journal of Clinical Investigation. https://doi.org/10.1172/jci32453
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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