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- W2534856699 abstract "A225 Lung cancer is the leading cause of cancer deaths in the United States, and prevention is required to reduce the significant mortality and poor prognosis of this disease. Because of the emerging link between inflammation and carcinogenesis, the triterpenoids were originally developed as anti-inflammatory agents, and CDDO (2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid) and its methyl ester (CDDO-ME) are currently in Phase I clinical trial for treatment of leukemia and solid tumors. We have shown that the rexinoid LG100268 (268) has anti-inflammatory properties and is effective for the prevention of estrogen receptor-positive and -negative breast cancer in rodent models of mammary tumorigenesis. CDDO-ME and the methyl amide (CDDO-MA) and ethyl amide (CDDO-EA) of CDDO potently (IC 50 = 1-2 nM) inhibit nitric oxide production in RAW264.7 macrophage-like cells stimulated with IFN-gamma and LPS. Low nanomolar concentrations of these triterpenoids also block the expression of inducible nitric oxide synthase and cyclooxygenase and induce the phase 2 cytoprotective enzymes NAD(P)H quinone oxidoreductase and heme oxygenase-1. The compounds also reduce constitutive pSTAT3 levels, inhibit proliferation, and induce apoptosis in human lung cancer cells. Thus, the triterpenoids and rexinoids are promising agents for lung cancer prevention and were tested for their ability to prevent lung tumors. Female A/J mice were injected i.p. with vinyl carbamate (16 mg/kg), once a week for two weeks. One week later, the mice were fed 268 (60 mg/kg diet) or CDDO-MA (800 mg/kg diet) for 20 weeks. CDDO-MA and 268 significantly (P 1 mm. Instead, 63% and 70% of the tumors in the CDDO-ME and CDDO-EA groups, respectively, were" @default.
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- W2534856699 date "2006-12-01" @default.
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- W2534856699 title "Triterpenoids and the rexinoid LG100268 prevent lung tumors induced by vinyl carbamate in strain A/J mice." @default.
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