Mouse Models of Gastrointestinal Cancer

描述(由申请人提供)： 在过去的四年里，辛辛那提大学医学院通过参与人类癌症小鼠模型联盟，对胃肠道癌小鼠模型的研究做出了重大承诺。我们之前的工作导致了溃疡性结肠炎相关性结肠癌、胰腺癌和侵袭性肠道肿瘤的小鼠模型的发展，以及通过研究一种新的具有染色体不稳定性的小鼠模型来鉴定人类结直肠癌的遗传危险因素。我们仍然专注于了解导致胃肠道和胰腺上皮细胞正常生长调节中断的机制。我们建议进一步研究这些小鼠模型，以了解更多关于基因-环境相互作用、化学预防、基因组不稳定在肿瘤易感性中的作用、与肿瘤进展和侵袭相关的基因组和基因表达变化，以及用于癌症基因组分析的系统生物学方法。我们的目标是促进基因发现，了解影响小鼠肿瘤形成的遗传和环境因素，以提高对人类癌症的症状前诊断、检测和治疗。

DESCRIPTION (provided by applicant): Over the last four years, The University of Cincinnati College of Medicine has made a major commitment to the study of mouse models of gastrointestinal cancer through its participation in the Mouse Models of Human Cancers Consortium. Our previous work has led to the development of mouse models of ulcerative-colitis-associated colon cancer, pancreatic adenocarcinoma, and invasive intestinal tumors, as well as the identification of a genetic risk factor for human colorectal cancer through study of a novel mouse model with chromosomal instability. We remain focused on understanding the mechanisms that lead to the disruption of normal growth regulation in the epithelium of the gastrointestinal tract and pancreas. We propose to examine these mouse models further in order to learn more about gene-environment interactions, chemoprevention, the role of genomic instability in tumor susceptibility, the genomic and gene expression changes associated with tumor progression and invasion, and systems biology approaches to cancer genomic analyses. Our goal is to facilitate gene discovery and understand the genetic and environmental factors that influence tumor formation in the mouse in order to improve presymptomatic diagnosis, detection and treatment of human cancer.