Longitudinal Assessment of Colonic Tumor Fate in Mice by Computed Tomography and Optical Colonoscopy

      Rationale and Objectives

      The purpose of this study was to evaluate the relative merits of micro-computed tomograph colonography (mCTC) and optical colonoscopy (OC) for longitudinal studies of colonic tumors in mice.

      Materials and Methods

      Colonic tumors in mice carrying the Min allele of Apc were followed over several weeks using mCTC and OC. A total of 146 colonic tumors were monitored: 62 in 32 untreated Min mice, 53 in 43 Min mice treated with 5-fluorouracil (5-FU), and 31 in 17 Min mice treated with piroxicam.


      Colonic tumors in Min mice had three different spontaneous fates: 29 grew, 24 remained static, and 9 regressed. Treating Min mice with 5-FU increased the percentage of regressing tumors from 15% to 58%. The response was dependent in part on the initial size of the tumor. By contrast, treating Min mice with piroxicam did not alter colonic tumor fate.


      mCTC and OC can be used to determine the spontaneous fates of colonic tumors in mice and to document their individual responses to treatment. The ability to follow individually annotated colonic tumors reduces the number of mice needed for testing.

      Key Words

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        • Moser A.R.
        • Pitot H.C.
        • Dove W.F.
        A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse.
        Science. 1990; 247: 322-324
        • Shoemaker A.R.
        • Gould K.A.
        • Luongo C.
        • et al.
        Studies of neoplasia in the Min mouse.
        Biochim Biophys Acta. 1997; 1332: F25-F48
        • Corpet D.E.
        • Pierre F.
        Point: from animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system.
        Cancer Epidemiol Biomarkers Prev. 2003; 12: 391-400
        • Jacoby R.F.
        • Cole C.E.
        • Tutsch K.
        • et al.
        Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos.
        Cancer Res. 2000; 60: 1864-1870
        • Ritland S.R.
        • Gendler S.J.
        Chemoprevention of intestinal adenomas in the ApcMin mouse by piroxicam: kinetics, strain effects and resistance to chemosuppression.
        Carcinogenesis. 1999; 20: 51-58
        • Jacoby R.F.
        • Marshall D.J.
        • Newton M.A.
        • et al.
        Chemoprevention of spontaneous intestinal adenomas in the Apc Min mouse model by the nonsteroidal anti-inflammatory drug piroxicam.
        Cancer Res. 1996; 56: 710-714
        • Jacoby R.F.
        • Seibert K.
        • Cole C.E.
        • et al.
        The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the Min mouse model of adenomatous polyposis.
        Cancer Res. 2000; 60: 5040-5044
        • Bruce W.R.
        Counterpoint: from animal models to prevention of colon cancer. Criteria for proceeding from preclinical studies and choice of models for prevention studies.
        Cancer Epidemiol Biomarkers Prev. 2003; 12: 401-404
        • Hensley H.H.
        • Chang W.C.
        • Clapper M.L.
        Detection and volume determination of colonic tumors in Min mice by magnetic resonance micro-imaging.
        Magn Reson Med. 2004; 52: 524-529
        • Hensley H.H.
        • Merkel C.E.
        • Chang W.C.
        • et al.
        Endoscopic imaging and size estimation of colorectal adenomas in the multiple intestinal neoplasia mouse.
        Gastrointest Endosc. 2009; 69: 742-749
        • Pickhardt P.J.
        • Halberg R.B.
        • Taylor A.J.
        • et al.
        Microcomputed tomography colonography for polyp detection in an in vivo mouse tumor model.
        Proc Natl Acad Sci U S A. 2005; 102: 3419-3422
        • Becker C.
        • Fantini M.C.
        • Neurath M.F.
        High resolution colonoscopy in live mice.
        Nature Protocols. 2006; 1: 2900-3904
        • Durkee B.Y.
        • Mudd S.R.
        • Roen C.N.
        • et al.
        Reproducibility of tumor volume measurement at microCT colonography in living mice.
        Acad Radiol. 2008; 15: 334-341
        • Becker C.
        • Fantini M.C.
        • Wirtz S.
        • et al.
        In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy.
        Gut. 2005; 54: 950-954
        • Cooper H.S.
        • Everley L.
        • Chang W.C.
        • et al.
        The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium-induced colitis.
        Gastroenterology. 2001; 121: 1407-1416
        • Akaike H.
        New look at statistical-model identification.
        IEEE Trans Automatic Control. 1974; AC19: 716-723
        • Efron B.
        • Tibshirani R.J.
        An introduction to the bootstrap.
        Chapman & Hall/CRC, Boca Raton, FL1993
        • Ware J.H.
        Linear models for the analysis of longitudinal studies.
        Am Statistician. 1985; 39: 95-101
        • Kim D.H.
        • Pickhardt P.J.
        • Taylor A.J.
        • et al.
        CT colonography versus colonoscopy for the detection of advanced neoplasia.
        N Engl J Med. 2007; 357: 1403-1412
        • Jackson-Thompson J.
        • Ahmed F.
        • German R.R.
        • et al.
        Descriptive epidemiology of colorectal cancer in the United States, 1998–2001.
        Cancer. 2006; 107: 1103-1111
        • Regula J.
        • Rupinski M.
        • Kraszewska E.
        • et al.
        Colonoscopy in colorectal-cancer screening for detection of advanced neoplasia.
        N Engl J Med. 2006; 355: 1863-1872
        • Rossouw J.E.
        • Anderson G.L.
        • Prentice R.L.
        • et al.
        Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.
        JAMA. 2002; 288: 321-333
        • Amos-Landgraf J.M.
        • Kwong L.N.
        • Kendziorski C.M.
        • et al.
        A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer.
        Proc Natl Acad Sci U S A. 2007; 104: 4036-4041
        • Thirion P.
        • Michiels S.
        • Pignon J.P.
        • et al.
        Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis.
        J Clin Oncol. 2004; 22: 3766-3775
        • Blijham G.H.
        Chemotherapy of colorectal cancer.
        Anticancer Drugs. 1991; 2: 233-245
        • Tucker J.M.
        • Davis C.
        • Kitchens M.E.
        • et al.
        Response to 5-fluorouracil chemotherapy is modified by dietary folic acid deficiency in ApcMin/+ mice.
        Cancer Lett. 2002; 187: 153-162
        • Uronis J.M.
        • Herfarth H.H.
        • Rubinas T.C.
        • et al.
        Flat colorectal cancers are genetically determined and progress to invasion without going through a polypoid stage.
        Cancer Res. 2007; 67: 11594-11600
        • Gambino J.J.
        • Lindberg R.G.
        Response of the pocket mouse to ionizing radiation.
        Radiat Res. 1964; 22: 586-597
        • Halberg R.B.
        • Waggoner J.
        • Rasmussen K.
        Long-lived Min mice develop advanced intestinal cancers through a genetically conservative pathway.
        Cancer Research. 2009; 69: 5768-5775