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使用活体小鼠的连续内镜成像对肠道疾病新疗法的疗效进行非侵入性评估。

Non-invasive assessment of the efficacy of new therapeutics for intestinal pathologies using serial endoscopic imaging of live mice.

作者信息

Ernst Matthias, Preaudet Adele, Putoczki Tracy

机构信息

The Walter and Eliza Hall Institute for Medical Research; The Department of Medical Biology, University of Melbourne; Olivia Newton-John Cancer Research Institute.

The Walter and Eliza Hall Institute for Medical Research.

出版信息

J Vis Exp. 2015 Mar 10(97):52383. doi: 10.3791/52383.

Abstract

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic mechanisms that contribute to the onset and progression of intestinal diseases. The identification of new molecules that promote these pathologies has led to a flurry of activity focused on the development of potential new therapies to inhibit their function. As a result, various pre-clinical mouse models with an intact immune system and stromal microenvironment are now heavily used. Here we describe three experimental protocols to test the efficacy of new therapeutics in pre-clinical models of (1) acute mucosal damage, (2) chronic colitis and/or colitis-associated colon cancer, and (3) sporadic colorectal cancer. We also outline procedures for serial endoscopic examination that can be used to document the therapeutic response of an individual tumor and to monitor the health of individual mice. These protocols provide complementary experimental platforms to test the effectiveness of therapeutic compounds shown to be well tolerated by mice.

摘要

炎症性肠病(IBD)和结直肠癌(CRC)的动物模型为深入了解促成肠道疾病发生和发展的细胞内在和外在机制提供了重要见解。对促进这些病理过程的新分子的鉴定引发了一系列活动,重点是开发抑制其功能的潜在新疗法。因此,各种具有完整免疫系统和基质微环境的临床前小鼠模型现在被大量使用。在这里,我们描述了三种实验方案,以测试新疗法在以下临床前模型中的疗效:(1)急性粘膜损伤,(2)慢性结肠炎和/或结肠炎相关结肠癌,以及(3)散发性结直肠癌。我们还概述了连续内镜检查的程序,可用于记录单个肿瘤的治疗反应并监测单个小鼠的健康状况。这些方案提供了互补的实验平台,以测试已证明小鼠耐受性良好的治疗化合物的有效性。

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