P53 Biomaker and Intervention in Occupational Cancer

P53 Biomaker 与职业癌症干预

• 批准号: 6753496
• 负责人: Paul W Brandt-Rauf
• 金额: $ 20.93万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6753496
• 关键词: apoptosis; asbestos; autoantibody; biomarker; clinical research; comorbidity; diagnosis design /evaluation; drug screening /evaluation; early diagnosis; environment related neoplasm /cancer; enzyme linked immunosorbent assay; gene mutation; human tissue; neoplasm /cancer diagnosis; neoplasm /cancer epidemiology; neoplastic cell; occupational disease /disorder; p53 gene /protein; peptide chemical synthesis; pneumoconiosis; protein sequence; spectrometry; tissue /cell culture; transfection /expression vector; western blottings

DESCRIPTION: Research Methods for Occupational Cancer are needed to develop early markers of adverse health effects from workplace exposures and to devise ways for interrupting the pathways between workplace exposures and resultant cancers. The p53 tumor suppressor gene product is a potential target for both of these approaches. Certain occupational exposures can produce mutations in p53 which cause the generation of an immune response with circulating p53 auto-antibodies, even before the occurrence of clinically detectable cancers, so that these antibodies may serve as useful early markers of adverse effects. In addition, certain short peptide sequences from p53 have been demonstrated in cell culture to be able to cause mutant p53 to revert to normal function, resulting in the death of cancer cells containing mutant p53 but with no effect on normal cells with wild-type p53, suggesting that this may be a useful approach for interrupting the pathway between workplace exposures that produce p53 mutations and resultant cancers. The purpose of the proposed research is to examine both of these approaches for occupational cancers caused by asbestos exposure in two related projects. For the first project, banked serum samples from a cohort of workers with asbestosis will be examined for the presence of p53 auto-antibodies by enzyme-linked immunosorbent assay and ininiunoblotting to determine if the presence of the antibodies correlates with the subsequent development of cancer, as well as with the presence of p53 mutations in the resultant tumors. For the second project, the effects in cell culture of a p53 peptide sequence (delivered as the peptide or as a plasmid-based mini-gene) on asbestos-associated lung cancer and mesothelioma cell lines with and without p53 mutations and corresponding non-cancer cell lines with wild-type p53 will be investigated, as well as determining the mechanism of action of the peptide for inducing death in these cells.

描述：职业性癌症的研究方法有待发展