Noninvasive Detection of Inflammation-Associated Colon Cancer in a Mouse Model
Noninvasive Detection of Inflammation-Associated Colon Cancer in a Mouse Model
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DOI：
10.1593/neo.10940
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发表时间：
2010-12-01
期刊：
影响因子：
4.8
通讯作者：
Franklin, Craig
中科院分区：
文献类型：
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作者：
Ericsson, Aaron C.;Myles, Matthew;Franklin, Craig
胆汁螺杆菌感染的Smad 3（-/-）小鼠是一种有吸引力的炎症相关结肠癌模型。大多数感染的小鼠在接种后6周（PI）发生粘液腺癌（MUC）;然而，约三分之一的小鼠没有进展为MUC。在治疗研究中使用的小鼠中预测MUC发展的能力将带来相当大的时间和金钱的节省。此外，无意中使用没有MUC的小鼠可能会混淆治疗研究，使治疗似乎虚假有效。我们评估了磁共振成像（MRI）和粪便生物标志物在螺旋杆菌和假接种的小鼠作为非侵入性检测MUC的方法预测发病前。非对比增强MRI能够检测到58%的组织学确诊MUC小鼠的病变;然而，连续成像会话产生不一致的结果。MRI也是一种需要麻醉的劳动和时间密集型技术。或者，在早期时间点从粪便中分离的炎性生物标志物与后来的组织学病变相关。感染后3周粪便中白细胞介素1 β、巨噬细胞炎性蛋白1 α的表达和活化调节、正常T细胞的表达和分泌与感染后9周的病变严重程度显著相关。对于每种生物标志物，还生成了受试者-操作者特征曲线，并且所有三种生物标志物在PI 1至3周时表现良好，表明可以基于粪便中某些炎症介质的早期表达来预测MUC的发展。
Helicobacter bilis-infected Smad3(-/-) mice represent an attractive model of inflammation-associated colon cancer. Most infected mice develop mucinous adenocarcinoma (MUC) by 6 weeks post inoculation (PI); however, approximately one third do not progress to MUC. The ability to predict the development of MUC in mice used in therapeutic studies would confer a considerable saving of time and money. In addition, the inadvertent use of mice without MUC may confound therapeutic studies by making treatments seem falsely efficacious. We assessed both magnetic resonance imaging (MRI) and fecal biomarkers in Helicobacter-and sham-inoculated mice as methods of noninvasively detecting MUC before the predicted onset of disease. Non-contrast-enhanced MRI was able to detect lesions in 58% of mice with histologically confirmed MUC; however, serial imaging sessions produced inconsistent results. MRI was also a labor- and time-intensive technique requiring anesthesia. Alternatively, inflammatory biomarkers isolated from feces at early time points were correlated to later histologic lesions. Fecal expression of interleukin 1 beta, macrophage inflammatory protein 1 alpha, and regulated on activation, normal T-cell expressed, and secreted at 3 weeks PI correlated significantly with lesion severity at 9 weeks PI. For each biomarker, receiver-operator characteristic curves were also generated, and all three biomarkers performed well at 1 to 3 weeks PI, indicating that the development of MUC can be predicted based on the early expression of certain inflammatory mediators in feces.