GNAI1 and GNAI3 Reduce Colitis-Associated Tumorigenesis in Mice by Blocking IL6 Signaling and Down-regulating Expression of GNAI2 (original) (raw)
Related papers
Involvement of NF-κB/IL-6 Pathway in the Processing of Colorectal Carcinogenesis in Colitis Mice
International journal of inflammation, 2014
Nuclear factor-kappaB (NF-κB)/interleukin (IL-6) pathway links chronic inflammation to colitis associated cancer (CAC). In this study, we examined the dynamic temporal changes of the NF-κB/IL-6 pathway during the procession of experimental CAC mouse model. Mice were sacrificed after induction for 14, 16, 18, and 22 weeks for the examination of tumor burden, inflammation degree, and protein level of NF-κB and IL-6 in bowel tissues. The results showed that tumor burden and inflammation severity in the bowels were gradually increased over the observed time-points. The expressions of IL-6 and NF-κB proteins were gradually increased after induction of dysplastic lesions over times. These data provide new information on the dynamic temporal changes of NF-κB/IL-6 pathway in relation to CAC development that may be relevant in the design of future investigations of therapeutic interventions to effectively target CAC processes.
Murine Model for Colitis-Associated Cancer of the Colon
Methods in molecular biology (Clifton, N.J.), 2016
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), significantly increases the risk for development of colorectal cancer. Specifically, dysplasia and cancer associated with IBD (colitis-associated cancer or CAC) develop as a result of repeated cycles of injury and healing in the intestinal epithelium. Animal models are utilized to examine the mechanisms of CAC, the role of epithelial and immune cells in this process, as well as the development of novel therapeutic targets. These models typically begin with the administration of a carcinogenic compound, and inflammation is caused by repeated cycles of colitis-inducing agents. This review describes a common CAC model that utilizes the pro-carcinogenic compound azoxymethane (AOM) followed by dextran sulfate sodium (DSS) which induces the inflammatory insult.
Ileal immune tonus is a prognosis marker of proximal colon cancer in mice and patients
Cell Death & Differentiation
Ileal epithelial cell apoptosis and the local microbiota modulate the effects of oxaliplatin against proximal colon cancer by modulating tumor immunosurveillance. Here, we identified an ileal immune profile associated with the prognosis of colon cancer and responses to chemotherapy. The whole immune ileal transcriptome was upregulated in poor-prognosis patients with proximal colon cancer, while the colonic immunity of healthy and neoplastic areas was downregulated (except for the Th17 fingerprint) in such patients. Similar observations were made across experimental models of implanted and spontaneous murine colon cancer, showing a relationship between carcinogenesis and ileal inflammation. Conversely, oxaliplatin-based chemotherapy could restore a favorable, attenuated ileal immune fingerprint in responders. These results suggest that chemotherapy inversely shapes the immune profile of the ileum–tumor axis, influencing clinical outcome.
Cancer research, 2007
Inflammatory bowel disease (IBD) is a gastrointestinal disorder of unknown etiology or cure. One complication of IBD is an increased risk for development of colon cancer. The aims of this study were to use a previously established rat model of colitis to develop a new model of colitis-associated colon cancer and ascertain the involvement of three cancer-related genes: K-ras, adenomatous polyposis coli (APC), and p53. Four groups of rats were used: reactivated 1,2-dimethylhydrazine [DMH; trinitrobenzene sulfonic acid (TNBS) was used to induce colitis followed by a weekly s.c. dose of DMH], prolonged reactivation (inflammation was induced with TNBS, then maintained twice a week), saline-DMH (animals received saline instead of TNBS followed by a weekly dose of DMH), and normal (received no treatment). Animals were sacrificed at 5, 10, or 15 weeks, and colon samples were taken for pathologic analysis and gene mutation detection. No dysplasia was found in the normal group. The highest in...