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dc.contributor.CRUESPUniversidade Estadual de Campinaspt_BR
dc.typeArtigo de periódicopt_BR
dc.titleObesity-Induced Increase in Tumor Necrosis Factor-alpha Leads to Development of Colon Cancer in Micept_BR
dc.contributor.authorFlores, MBSpt_BR
dc.contributor.authorRocha, GZpt_BR
dc.contributor.authorDamas-Souza, DMpt_BR
dc.contributor.authorOsorio-Costa, Fpt_BR
dc.contributor.authorDias, MMpt_BR
dc.contributor.authorRopelle, ERpt_BR
dc.contributor.authorCamargo, JApt_BR
dc.contributor.authorde Carvalho, RBpt_BR
dc.contributor.authorCarvalho, HFpt_BR
dc.contributor.authorSaad, MJApt_BR
dc.contributor.authorCarvalheira, JBCpt_BR
unicamp.authorFlores, Marcelo B. S. Rocha, Guilherme Z. Osorio-Costa, Felipe Dias, Marilia M. Ropelle, Eduardo R. Camargo, Juliana A. de Carvalho, Rita B. Saad, Mario J. A. Carvalheira, Jose B. C. Univ Estadual Campinas, Dept Internal Med, Fac Med Sci, BR-13083887 Campinas, SP, Brazilpt_BR
unicamp.authorDamas-Souza, Danilo M. Univ Estadual Campinas, Dept Anat Cell Biol Physiol & Biophys, BR-13083887 Campinas, SP, Brazilpt_BR
dc.subjectInsulin Resistancept_BR
dc.subjectMouse Modelpt_BR
dc.subject.wosColitis-associated Carcinogenesispt_BR
dc.subject.wosInsulin-receptor Substrate-1pt_BR
dc.subject.wosDextran Sulfate Sodiumpt_BR
dc.subject.wosSerine Phosphorylationpt_BR
dc.description.abstractBACKGROUND & AIMS: Epidemiology studies have shown that obesity increases risk for colorectal cancer (CRC). We investigated the contribution of obesity-induced increases in levels of tumor necrosis factor (TNF)-alpha and hyperinsulinemia to the development of CRC in mice. METHODS: Lean and obese mice (C57BL6/J and ob/ob) were given a combination of azoxymethane and dextran sulfate sodium, which led to the development of CRC; lean and obese severe combined immunodeficient mice were injected with HT-29 cells. We analyzed the roles of TNF-alpha and insulin in the development of obesity-mediated CRC using immunoblot, immunohistochemical, and apoptosis assays. RESULTS: Genetic-and diet-induced obesity increased the incidence and size of tumors that developed after administration of azoxymethane and dextran sulfate sodium, compared with lean mice. HT-29 xenograft tumors grew more rapidly in obese than lean mice. Neutralization of TNF-alpha reduced activation of c-Jun N-terminal kinase, I kappa B kinase, and the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin signaling pathway; it also reduced the growth and development of tumors in obese mice. Reducing levels of insulin levels had no effect on tumor growth in obese mice. CONCLUSIONS: TNF-alpha contributes to colon tumor growth in obese mice. Reagents that inhibit TNF-alpha might prevent the development or progression of CRC in obese
dc.publisherW B Saunders Co-elsevier Incpt_BR
dc.identifier.citationGastroenterology. W B Saunders Co-elsevier Inc, v. 143, n. 3, n. 741, n. +, 2012.pt_BR
dc.sourceWeb of Sciencept_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorship1Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorship1Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.provenanceMade available in DSpace on 2014-07-30T14:49:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2012en
dc.description.provenanceMade available in DSpace on 2015-11-26T16:46:16Z (GMT). No. of bitstreams: 2 WOS000308399300038.pdf: 7280308 bytes, checksum: 68b967951350a19109f127de0d09f771 (MD5) WOS000308399300038.pdf.txt: 49800 bytes, checksum: 4b1c05ba1afb01722abfdad44f3ed8c2 (MD5) Previous issue date: 2012en
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