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|Title:||Obesity-induced increase in tumor necrosis factor-alpha leads to development of colon cancer in mice|
|Abstract:||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 individuals|
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|Citation:||Gastroenterology. W B Saunders Co-elsevier Inc, v. 143, n. 3, n. 741, n. +, 2012.|
|Appears in Collections:||FCM - Artigos e Outros Documentos|
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