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结肠炎相关癌症(CAC)的氧化偶氮甲烷/白细胞介素10模型

The Azoxymethane/Il10 Model of Colitis-Associated Cancer (CAC).

作者信息

Rothemich Aaron, Arthur Janelle C

机构信息

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

出版信息

Methods Mol Biol. 2019;1960:215-225. doi: 10.1007/978-1-4939-9167-9_19.

DOI:10.1007/978-1-4939-9167-9_19
PMID:30798535
Abstract

Mouse models have proved essential for generating a mechanistic understanding of human disease processes. The azoxymethane/interleukin-10 knockout (AOM/Il10) model is a powerful tool for assessing the effects of intestinal microbiota and inflammation on colon tumorigenesis. This model of colitis-associated colorectal cancer (CAC) is particularly relevant to inflammatory bowel disease (IBD)-associated colon cancer and recapitulates many of the molecular effects underlying inflammation's influence on human colorectal cancer. The model utilizes inflammation-susceptible Il10 mice injected intraperitoneally (i.p.) with the colon-specific carcinogen AOM. AOM and its metabolites cause mutagenesis and colorectal tumorigenesis in an inflammation-dependent manner, which in Il10 mice is driven by the presence and composition of the intestinal microbiota. Here we describe bacterial colonization with the pathobiont Escherichia coli strain NC101, cancer initiation with AOM, bacterial quantification, and histologic assessment of inflammation and cancer.

摘要

小鼠模型已被证明对于深入理解人类疾病进程的机制至关重要。偶氮甲烷/白细胞介素-10基因敲除(AOM/Il10)模型是评估肠道微生物群和炎症对结肠癌发生影响的有力工具。这种结肠炎相关结直肠癌(CAC)模型与炎症性肠病(IBD)相关结肠癌尤为相关,并概括了炎症对人类结直肠癌影响的许多分子效应。该模型利用对炎症敏感的Il10小鼠,通过腹腔注射(i.p.)结肠特异性致癌物AOM。AOM及其代谢产物以炎症依赖的方式导致诱变和结直肠癌发生,在Il10小鼠中,这是由肠道微生物群的存在和组成驱动的。在这里,我们描述了致病性大肠杆菌菌株NC101的细菌定植、AOM引发的癌症、细菌定量以及炎症和癌症的组织学评估。

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