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Dextran sulfate sodium-induced colitis-associated neoplasia:a promising model for the development of chemopreventive interventions

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Acta Pharmacologica Sinica 2007年第9期28卷 1450-1459页

作者： margie lee clapper Harry Stanley COOPER Wen-Chi lee CHANG Divisions of Population Science Medical Science Fox Chase Cancer CenterPhiladelphiaPA 19111USA

Individuals diagnosed with ulcerative colitis face a significantly increased risk ofdeveloping colorectal dysplasia and cancer during their *** date,littleattention has been given to the development of a chemopreventive interventionfor this high-risk *** mouse model of dextran sulfate sodium (DSS)-induced colitis represents an excellent preclinical system in which to both charac-terize the molecular events required for tumor formation in the presence of inflam-mation and assess the ability of select agents to inhibit this *** admin-istration of DSS in drinking water results in the establishment of chronic colitisand the development of colorectal dysplasias and cancers with pathological fea-tures that resemble those of human colitis-associated *** incidenceand multiplicity of lesions observed varies depending on the mouse strain used(ie,Swiss Webster,C57BL/6J,CBA,ICR) and the dose (0.7%-5.0%) and schedule(1-15 cycles with or without a subsequent recovery period) of *** incidenceof neoplasia can be increased and its progression to invasive cancer acceleratedsignificantly by administering DSS in combination with a known colon carcinogen(azoxymethane (AOM),2-amino-3-methylimidazo[4,5-f]quinoline (IQ),2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)) or *** recent induction ofcolitis-associated neoplasia in genetically defined mouse strains has providednew insight into the role of specific genes (ie,adenomatous polyposis coli (Apc),p53,inducible nitric oxide synthase (iNOS),Msh2) in the development of colitis-associated *** data from chemopreventive intervention studiesdocument the efficacy of several agents in inhibiting DSS-induced neoplasiaand provide great promise that colitis-associated colorectal neoplasia is a pre-ventable disease.

关键词： colorectal colitis chemoprevention dextran sulfate sodium mouse models

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