Modulation of miRNA Expression in Blood or Other Biological Fluids Compared with Tissue Levels in Mice Exposed to Cigarette Smoke and/or with NSAIDs

The chemopreventive effect of an aerosolized rexinoid, bexarotene, and its efficacy in all \nsubtypes of lung cancer, will be examined using a state-of-the-art (Collison atomizer) aerosol \ndelivery system to lung to avoid the systematic side effects associated with oral administration of \nthis agent. Bexarotene has been used clinically to treat cutaneous T cell lymphoma in patients who \nwere refractory to any other medication. Bexarotene has also shown efficacy in a Phase 1/2 trial of \nnon-small cell lung cancer (NSCLC). It is the only agent tested to date that is highly effective \nin mouse models of adenocarcinoma, squamous cell carcinoma (SCC), and SCLC. In B[a]P-induced lung \ntumors in A/J mice, aerosolized delivery of bexarotene retained lung tumor inhibitory effects \nwithout increasing plasma total cholesterol and triglyceride levels, compared with control. The \nproposed project will study aerosolized bexarotene in mouse models of both SCC and SCLC, as well as \nits effects on tumor progression (from benign to malignant tumors) in mouse models of lung \nadenocarcinoma, while closely monitoring side effects and toxicity. The project will also analyze \nchanges in cell proliferation markers (cyclin D1 and Ki- 67), apoptotic activity, and infiltrating \nlymphoid cells, as well as mRNA changes in lung tumors and \nsurrounding lung tissues.