Colon cancer model

Oxaliplatin (trans-L-diaminocyclohexane oxalate platinum II) was selected for development based on preclinical antitumor activity in murine leukemia lines and in colon cancer models (151,152). The clinical development of oxaliplatin has been primarily in colorectal cancer alone and in combination with 5-fluorouracil. 

Guda K., Cui H., Garg S., Dong M., Nambiar P. R., Achenie L. E. and Rosenberg D. (2003). Multistage gene expression profiling in a differentially susceptible mouse colon cancer model. Cancer Letters 191, pp 17-25. 

Chung YL et al. Magnetic resonance spectroscopic pharmacodynamic markers of the heat shock protein 90 inhibitor 17-allylamino,17-demethoxygeldanamycin (17AAG) in human colon cancer models. J Natl Cancer Inst 2003 95 1624-1633. 

Pouyet, L., Roisin-Bouffay, C., Clement, A., Millet, V., Garcia, S., Chasson, L., Issaly, N., Rostan, A., Hofman, P., Naquet, P., and Galland, F., 2010. Epithelial vanin-1 controls inflammation-driven carcinogenesis in the colitis-associated colon cancer model. Inflammatory Bowel Diseases. 16 96-104. 

There is accumulating evidence from animal studies that CLA has potential health benefits for humans (Sebedio et al., 1999 Roche et al., 2001). Potential anti-cancer properties of CLA have been reported using rodent mammary and colon cancer models (see Sebedio et al., 1999). Potential beneficial effects of CLA on body composition (i.e. reduced fat mass) have been reported in rodents, chickens and pigs (see Sebedio et al., 1999 Roche et al., 2001). Effects of CLA on plasma triacylglycerol concentration, on glucose homeostasis, on atherosclerosis, and on inunune function have also been reported in animal studies (see Sebedio et al., 1999 Roche et al., 2001). Many of these animal studies have used a mix of CLA isomers, but predominantly the cis 9, trans 11... 

The use of NO donors, which when released intracellularly can inhibit iNOS, has been reported to be successful in different malignancies. NO-releasing aspirin was able to improve the effects of a GM-CSF-based cancer vaccine in a murine colon cancer model, through inhibition of iNOS and other suppressive enzymes (De et al. 2005). 

The reports of successful immunotherapy eombined with inhibition of NO have in common that the immunotherapies have directly or indirectly been linked to release of IFN-y, the major trigger of NO release. This is also the case of the combined immunotherapy with IL-12- and IL-18-secreting tumor cells in an intra-hepatic rat colon cancer model. Due to the abundance of NO-producing myeloid cells in the liver immunotherapy per se did not have any affect but the combination of L-NAME and low doses of an anti-angiogenic compound, combretastatin, significantly prolonged the survival (Badn et al. 2006). 

Belley, A., Keller, K., Grove, J. and Chadee, K. (1996) Interaction of LS174T human colon cancer cell mucins with Entamoeba histolytica an in vitro model for colonic disease. Gastroenterology 111, 1484—1492. 

Experiments conducted in the early 1980s showed that lymphocytes incubated in vitro with IL-2 could subsequently kill a range of cultured cancer cell lines, including melanoma and colon cancer cells. These latter cancers do not respond well to conventional therapies. Subsequent investigations showed that cancer cell destruction was mediated by IL-2-stimulated NK cells (i.e. LAK cells). Similar responses were seen in animal models upon administration of LAK cells activated in vitro using IL-2. 

The two-hit model applies to a number of other inherited neoplasias, including familial breast cancer, familial colon cancer, familial melanoma, and neurofibromatosis. 

N. D. Nigro, N. Bhadrachari and C. Chomchai, A rat model for studying colonic cancer Effect of cholestyramine on induced tumours, Dis. Colon Rectum, 1973, 16, 438. 

Emenaker NJ, Calaf GM, Cox D, Basson MD, Qureshi N. (2001) Short-chain fatty acids inhibit invasive human colon cancer by modulating uPA, TIMP-1, TlMP-2, mntant p53, Bcl-2, BAX, p21 and PCNA protein expression in an in vitro cell cnltnre model. JNutr 131 3041S-3046S. 

Moved] Cranberry fruit of Early Black cultivar was fractionated chromatographically and fractions were analyzed for flavonoid content. The effects of the flavonoid fractions and ursolic acid, an abundant triterpenoid in cranberry peel, were assessed in two models of colon cancer and one model of breast cancer. Clonogenic soft agar assays were used to determine the effect of these compounds on tumor colony formation in HCT-116, HT-29 and MCF-7 cells. MTT and trypan blue assays were performed to assess their ability to inhibit tumor cell proliferation. TUNEL assays were performed to assess apop-totic response to the cranberry compounds. The proanthocyanidins inhibited tumor colony formation in HCT-116 and HT-29 cells in a dose-dependent manner, with greater effect on the HCT-116 cell line. Ursolic acid strongly inhibited tumor colony formation in both colon cell lines. These compounds also decreased proliferation in all three tumor cell lines with the HCT-116 cell line most strongly affected. (150 words)... 

Weiswald LB, Bichon S, VaHdire P et al (2009) Newly characterised ex vivo colo-spheres as a three-dimensional colon cancer cell model of tumom aggressiveness. Br J Cancer 101 473 82... 

Oh BY, Lee RA, Kim KH (2011) siRNA targeting Livin decreases tumor in a xenograft model for colon cancer. World J Gastroenterol 17 2563-2571... 

We tested the effect of LPS in a model of peritoneal carcinomatosis (solid tumor) induced by PROb colon cancer cells in syngeneic BDEX rats. We showed that i.p. injections of LPS from E. coli can cure 20 % of the rats [157], Comparing the effect of LPS from different strains in this model, we found that the efficacy depends on the bacterial strain and on the structure of the lipid A used. Whatever the lipid A used, we have shown a correlation with in vitro macrophage secretion of IL-ip but not with NO, TNF-a or IL-6 [83],... 

Although there are preliminary data supporting the antitumoral activity of quercetin, the most common flavonoid, in humans in the course of a Phase I clinical trial [189], direct evidence of the anticancer effect of flavonoids is derived almost exclusively from studies performed in animal models as well as studies performed on cultured cell lines, Fig. (2). Most animal studies on gastrointestinal cancer have focused on colon cancer using the azoxymethane (AOM) model in rats or mice [190-197]. There are also available reports on models of cancer of the stomach (induced by benzo[a]pyrene [198] or N-methyl-N-nitro-N-nitro so guanidine [199]), oesophagus (N-methyl-N-amylnitrosamine [200]), and the tongue/oral cavity (methyl-(acetoxymethyl)-nitrosamine [198], 7,12-dimethyl-... 

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