Impact of Smoking on Lung Cancer Chemoprevention

描述（由申请人提供） 肺癌是男性和女性癌症死亡的主要原因， 今天的美国，以及整个美国日益严重的公共卫生问题， 世界虽然我们？我已经看到了一些改善，使用联合模式 这些方法对生存几乎没有影响。 化学预防是一种非常有前途的新方法， 控制其他上皮性实体瘤的巨大潜力。然而，在这方面， 许多关于肺癌化学预防的研究显示没有益处， 有些已经在目前的吸烟者中显示出实际的有害影响。似乎很明显 烟草和烟草制品之间存在着以前未曾预料到的不良相互作用， 致癌物质和化学预防剂。尽管对肺的进一步研究 癌症化学预防是必要的，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， 进行大规模的随机试验。 这个翻译，多学科计划项目的总体目标是 阐明烟草致癌物和化学预防剂之间的相互作用， 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。到 为了实现我们的目标，我们建议进行临床化学预防试验， 在人类中，同时进行遗传、分子和药理学研究， 了解致癌过程和致癌物与 化学预防剂，通过以下项目： 项目一：塞来昔布预防肺癌的临床研究 项目2：通过考克斯-2和5-脂氧合酶抑制剂、类维生素A预防肺癌 及其组合 项目3：肺癌发生中的分子改变 项目4：转录因子NF-κ B在肺癌发生中的作用 和化学预防 核心组件（管理、生物统计学和数据管理、组织学， 和药理学），以提供结构和专业知识 这些研究的成功整合和执行所需的。

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.