HHSN2612012000151/HHSN2610006Base Contract Title: Preclinical Efficacy and Intermediate Biomarkers. Task Order Title: Modulation of miRNA Expression in Blood or Other Biological Fluids Compared wi

雾化雷克生的化学预防作用及其对急性淋巴细胞白血病的疗效 肺癌的亚型，将使用最先进的(科利森雾化器)气雾剂进行检查 肺部给药系统，避免口服阿司匹林的全身副作用 这位特工。贝沙罗汀已被临床用于治疗皮肤T细胞淋巴瘤患者 对任何其他药物都不起作用。贝沙罗汀在1/2期试验中也显示出疗效。 非小细胞肺癌(NSCLC)。到目前为止，它是唯一一种经过测试的高效药剂 在腺癌、鳞状细胞癌(SCC)和小细胞肺癌的小鼠模型中。在苯并[a]磷诱导的肺中 贝沙罗汀雾化给药对A/J小鼠肿瘤的抑制作用 与对照组相比，不增加血浆总胆固醇和甘油三酯水平。这个 拟议的项目将研究雾化贝沙罗汀在鳞状细胞癌和小细胞肺癌小鼠模型中的作用，以及 丹参对小鼠肺肿瘤(从良恶性)进展的影响 腺癌，同时密切监测副作用和毒性。该项目还将分析 细胞增殖标记物(细胞周期蛋白D1和Ki-67)、细胞凋亡活性和浸润性的变化 淋巴样细胞，以及肺肿瘤和肺癌组织中mRNA的变化 周围的肺组织。

The chemopreventive effect of an aerosolized rexinoid, bexarotene, and its efficacy in all subtypes of lung cancer, will be examined using a state-of-the-art (Collison atomizer) aerosol delivery system to lung to avoid the systematic side effects associated with oral administration of this agent. Bexarotene has been used clinically to treat cutaneous T cell lymphoma in patients who were refractory to any other medication. Bexarotene has also shown efficacy in a Phase 1/2 trial of non-small cell lung cancer (NSCLC). It is the only agent tested to date that is highly effective in mouse models of adenocarcinoma, squamous cell carcinoma (SCC), and SCLC. In B[a]P-induced lung tumors in A/J mice, aerosolized delivery of bexarotene retained lung tumor inhibitory effects without increasing plasma total cholesterol and triglyceride levels, compared with control. The proposed project will study aerosolized bexarotene in mouse models of both SCC and SCLC, as well as its effects on tumor progression (from benign to malignant tumors) in mouse models of lung adenocarcinoma, while closely monitoring side effects and toxicity. The project will also analyze changes in cell proliferation markers (cyclin D1 and Ki- 67), apoptotic activity, and infiltrating lymphoid cells, as well as mRNA changes in lung tumors and surrounding lung tissues.