Chemoprevention of Carcinogen-Induced Lung Cancer

致癌物诱发肺癌的化学预防

• 批准号: 6872927
• 负责人: KAM-MENG TCHOU-WONG
• 金额: $ 42.25万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6872927
• 关键词: angiogenesis factor; biomarker; cancer prevention; chemical carcinogenesis; chemical related neoplasm /cancer; chemoprevention; dexamethasone; disease /disorder model; enzyme linked immunosorbent assay; genetically modified animals; immunocytochemistry; laboratory mouse; lung imaging /visualization /scanning; lung neoplasms; magnetic resonance imaging; microarray technology; model design /development; neoplasm /cancer blood supply; neoplastic growth; p53 gene /protein; selenium; smoking; tobacco abuse

DESCRIPTION (provided by applicant) p53 mutations are found in more than 50% of all human cancers, including lung cancer. These mutations strongly select for p53 proteins that fail to bind to DNA in a sequence-specific fashion. The p53 protein is a tetramer and requires zinc ions for its activity as DNA-binding transcription Lung cancer is the leading cause of cancer death in the United States and the poor lung cancer survival rates argue strongly for new approaches to control this devastating disease. Chemoprevention represents an approach to reverse, suppress, or prevent lung carcinogenesis. Over 80% of lung cancers are attributed to tobacco and carcinogens from cigarette smoke. Even after quitting smoking, former smokers remain at high risk and account for over 50% of current lung cancer cases. With the recent developments in microarray technology, increased insights in lung carcinogenesis will led to the development of targeted intervention and optimism for new chemopreventive approaches to prevent tobacco-related lung cancer, especially in former smokers. We have developed a transgenic mouse model for smoking-related lung cancer by exposure to tobacco carcinogen. The dominant-negative mutant p53 transgene is specifically expressed in the bronchial epithelium under the Clara Cell Specific Protein (CCSP) promoter which results in increased susceptibility to both spontaneous and BaP-induced lung cancer, hence offering a preclinical model for studying chemoprevention of tobacco-related lung cancer. The specific aims are as follows: (1) To establish a mouse model to mimic high risk former smokers and to identify surrogate biomarkers for lung cancer; (2) To determine the efficacy of chemopreventive agents and to validate the use of surrogate biomarkers as endpoints for chemoprevention; (3) To evaluate the use of magnetic resonance imaging (MRI) for assessing tumor growth and and efficacy of chemopreventive agents.

描述（由申请人提供）