Source:http://linkedlifedata.com/resource/pubmed/id/10395330
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1999-7-29
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pubmed:abstractText |
Given the associations between chronic inflammation and epithelial cancer, we studied susceptibility to skin carcinogenesis in mice deficient for the pro-inflammatory cytokine TNF-alpha (refs. 5,6). TNF-alpha(-/-) mice were resistant to development of benign and malignant skin tumors, whether induced by initiation with DMBA and promotion with TPA or by repeated dosing with DMBA. TNF-alpha(-/-) mice developed 5-10% the number of tumors developed by wild-type mice during initiation/promotion and 25% of those in wild-type mice after repeated carcinogen treatment. TNF-alpha could influence tumor and stromal cells during tumor development. The early stages of TPA promotion are characterized by keratinocyte hyperproliferation and inflammation. These were diminished in TNF-alpha(-/-) mice. TNF-alpha was extensively induced in the epidermis, but not the dermis, in TPA-treated wild-type skin, indicating that dermal inflammation is controlled by keratinocyte TNF-alpha production. Deletion of a TNF-alpha inducible chemokine also conferred some resistance to skin tumor development. TNF-alpha has little influence on later stages of carcinogenesis, as tumors in wild-type and TNF-alpha(-/-) mice had similar rates of malignant progression. These data provide evidence that a pro-inflammatory cytokine is required for de novo carcinogenesis and that TNF-alpha is important to the early stages of tumor promotion. Strategies that neutralize TNF-alpha production may be useful in cancer treatment and prevention.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1078-8956
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
828-31
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10395330-9,10-Dimethyl-1,2-benzanthracene,
pubmed-meshheading:10395330-Animals,
pubmed-meshheading:10395330-Crosses, Genetic,
pubmed-meshheading:10395330-Female,
pubmed-meshheading:10395330-Immunity, Innate,
pubmed-meshheading:10395330-Male,
pubmed-meshheading:10395330-Mice,
pubmed-meshheading:10395330-Mice, Inbred BALB C,
pubmed-meshheading:10395330-Mice, Inbred C57BL,
pubmed-meshheading:10395330-Mice, Inbred Strains,
pubmed-meshheading:10395330-Mice, Knockout,
pubmed-meshheading:10395330-Neoplasm Invasiveness,
pubmed-meshheading:10395330-Neoplasm Staging,
pubmed-meshheading:10395330-Skin,
pubmed-meshheading:10395330-Skin Neoplasms,
pubmed-meshheading:10395330-Tetradecanoylphorbol Acetate,
pubmed-meshheading:10395330-Time Factors,
pubmed-meshheading:10395330-Tumor Necrosis Factor-alpha
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pubmed:year |
1999
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pubmed:articleTitle |
Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis.
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pubmed:affiliation |
Biological Therapy Laboratory, Imperial Cancer Research Fund, London, UK.
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pubmed:publicationType |
Journal Article
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