Abstract:
:Metastatic colorectal cancer is the second most common cause of cancer mortality. The liver is a common site of metastasis and only a minority of patients with liver metastases are candidates for potentially curative surgical resection. The treatment of patients with unresectable liver tumors is a major clinical problem and survival remains low. Many animal models of hepatic metastasis do not result in disease which resembles the advanced cancer setting. The purpose of this study was to establish a murine model for use in the evaluation of therapy for secondary liver cancer. Human colon cancer cells were injected directly into the portal vein of nude mice. Magnetic resonance imaging (MRI), performed weekly, was used to follow the time-course and characteristics of tumor growth. As expected, tumor size increased proportionately with time, following inoculation, and the MRI images correlated well with gross pathology findings at necropsy with respect to both tumor size and location. The tumors retained important morphology and biological characteristics of human colon cancer. Mice bearing liver metastasis were treated with irinotecan or drug vehicle. MRI evaluation pre/post-therapy gave an objective measure of therapeutic response. Irinotecan therapy was able to double the survival (median 76-93 days) compared to vehicle alone (median 43-46 days). This murine model is reproducible, rapid, inexpensive and has an excellent success rate for the development of liver metastasis (100%). When used in conjunction with small animal MRI, this model allows the efficient evaluation of the therapeutics of liver metastasis without the use of repeated laparotomy or splenectomy and without requiring large numbers of animals undergoing terminal experiments.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Cai SR,Garbow JR,Culverhouse R,Church RD,Zhang W,Shannon WD,McLeod HLkeywords:
subject
Has Abstractpub_date
2005-07-01 00:00:00pages
113-20issue
1eissn
1019-6439issn
1791-2423journal_volume
27pub_type
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