Impact of Smoking on Lung Cancer Chemoprevention

描述(由申请人提供) 肺癌是#年男性和女性癌症死亡的主要原因。 今天的美国，以及整个世界日益严重的公共卫生问题 世界。尽管我们已经看到使用组合模式的一些改进。 这些方法对生存几乎没有影响。 化学预防是一种非常有希望的新方法，已经表明 控制其他上皮性实体肿瘤的巨大潜力。然而， 许多肺癌化学预防的研究都没有显示出任何益处，而且 其中一些已经显示出对当前吸烟者的实际有害影响。看起来很清楚 以前未被怀疑的烟草与烟草之间的不良相互作用 致癌物质和化学防护剂。虽然对肺的进一步研究 癌症的化学预防是必要的，对这些进行彻底的调查 致癌物/化学预防相互作用是必要的 实施大规模随机试验。 这个翻译、多学科项目的总体目标是 阐明烟草致癌物质与化学预防的相互作用 药物，研究塞来昔布治疗肺癌的潜力 化学预防，并验证肺癌发生的中间标志物。至 为了实现我们的目标，我们建议进行一项临床化学预防试验 在人类身上，在进行遗传学、分子和药理学研究的同时 了解致癌过程和致癌物与 通过下列项目提供化学预防药物： 项目1：塞来昔布在肺癌化学预防中的临床试验 项目2：环氧合酶-2和5-脂氧合酶抑制剂、维甲酸、 以及它们的组合 项目3：肺癌发生过程中的分子变化 项目4：转录因子NF-kB在肺癌发生发展中的作用 和化学预防 核心组成部分(管理、生物统计和数据管理、组织学、 和药理学)也包括在内，以提供结构和专业知识 这是成功整合和执行这些研究所必需的。

DESCRIPTION (provided by applicant) Lung cancer is the leading cause of cancer death among both men and women in the United States today, and a rising public health problem throughout the world. Although we?ve seen some improvement using combined modality approaches, these have had little impact on survival. Chemoprevention is a highly promising new approach that has already shown enormous potential for the control of other epithelial solid tumors. However, numerous studies of lung cancer chemoprevention have shown no benefit, and some have shown actual harmful effects in current smokers. It seems clear that previously unsuspected adverse interactions exist between tobacco carcinogens and chemopreventive agents. Although further studies of lung cancer chemoprevention are warranted, a thorough investigation of these carcinogen/chemoprevention interactions is necessary before further large-scale randomized trials are implemented. The overall goals of this translational, multidisciplinary Program project are to elucidate the interactions between tobacco carcinogens and chemopreventive agents, investigate the potential of celecoxib for lung cancer chemoprevention, and validate intermediate markers of lung carcinogenesis. To accomplish our goals, we propose to carry out a clinical chemoprevention trial in humans, while performing genetic, molecular, and pharmacologic studies to understand the carcinogenic process and the interaction of carcinogens with chemopreventive agents through the following projects: Project 1: Clinical Trial of Celecoxib in Lung Cancer Chemoprevention Project 2: Lung Cancer Prevention by COX-2 and 5-LOX Inhibitors, Retinoids, and Their Combinations Project 3: Molecular Alterations in Lung Carcinogenesis Project 4: The Role of Transcription Factor NF-kB in Lung Cancer Development and Chemoprevention Core components (Administration, Biostatistics and Data Management, Histology, and Pharmacology) are also included to provide the structure and expertise required for the successful integration and execution of these studies.