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- W2321893272 abstract "Abstract Estrogen receptor β (ER-β) has been implicated in several neoplastic diseases. Previously we have shown that ER-β is up-regulated in human and rodent colonic tumors, suggesting ER-β as a potential target for colon cancer prevention (Naveena et al., CaPR 2009). Thus, ER-β modualtors, SERMs are useful for colon cancer prevention. Hence, we tested raloxifene, an ER antagonist in APCMin/+ mice treated with azoxymethane (AOM), to enhance the colonic tumors. Six-week-old male and female APCMin/+ (9/group) were injected s.c., with AOM at 5 mg/kg BW, once a week for three weeks. APCMin/+ mice were then fed diets containing 0, 1.5, and 3.0 ppm raloxifene for 12 weeks before intestinal tumors and various markers of toxicity, cell proliferation and apoptosis were evaluated. Results suggest that dietary administration of 1.5 and 3.0 ppm raloxifene in male mice suppressed small intestinal polyp formation by 24% (p<0.05) and 58% (p<0.0001), respectively. In female mice, 1.5 and 3.0 ppm raloxifene suppressed small intestinal polyps by 58% (0<0.0001) and 48% (p<0.0001), respectively. Also, significant inhibition of colonic tumor suppression was observed in female mice fed the 1.5 and 3.0 ppm of raloxifene, whereas in male mice, only high-dose inhibited colonic tumors. Mice fed with raloxifene had >70% less polyps with size of >1-mm suggesting suppression of tumor volume/size. Also, we find that raloxifene treatment in female APCMin/+ mice showed significantly reduced serum creatine phosphokinase and cholesterol levels, and an increased alkaline phosphatase levels when compared to untreated control mice. Also, a dose-dependent increase in serum calcium was observed with raloxifene administration. Dietary raloxifene showed no liver enzyme toxicities as measured by aspartate aminotransferase levels in serum. However, raloxifene administered mice showed a modest decrease in serum glucose levels. The mRNA and protein expression levels for p21cip/waf1 were significantly higher with decreased expression of Cyclin D1 and PCNA in raloxifene treated colonic tumors and SI polyps compared to control diet fed mice tissues, suggesting estrogen's function in crypt cell proliferation. Overall, our results clearly suggest that raloxifene significantly suppresses small intestinal and colonic polyps formation by up-regulating p21cip/waf1 and has potential usefulness for human colon cancer prevention. (Supported by CN53300 and R01-94962) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 831. doi:10.1158/1538-7445.AM2011-831" @default.
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- W2321893272 date "2011-04-01" @default.
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- W2321893272 title "Abstract 831: Chemopreventive effects of selective estrogen receptor modulator (SERM) raloxifene on intestinal neoplasia of APCMin/+mice" @default.
- W2321893272 doi "https://doi.org/10.1158/1538-7445.am2011-831" @default.
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