Noninvasive Detection of Inflammation-Associated Colon Cancer in a Mouse

Mar 11th, 2014 | By | Category: CMP in the News

by  Aaron C. Ericsson, Matthew Myles, Wade Davis,, Lixin Ma, Michael Lewis, Lillian Maggio-Price and Craig Franklin 

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, approxi- mately 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 reso- nance 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 iso- lated from feces at early time points were correlated to later histologic lesions. Fecal expression of interleukin 1β, macrophage inflammatory protein 1α, 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 develop- ment of MUC can be predicted based on the early expression of certain inflammatory mediators in feces.

Neoplasia (2010) 12, 1054–1065

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