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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-7-29
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.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1078-8956
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
828-31
pubmed:dateRevised
2008-11-21
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
pubmed:year
1999
pubmed:articleTitle
Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis.
pubmed:affiliation
Biological Therapy Laboratory, Imperial Cancer Research Fund, London, UK.
pubmed:publicationType
Journal Article