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：需要发展职业癌的研究方法 从工作场所暴露并设计的不良健康影响的早期标志 中断工作场所暴露与结果之间的路径的方法 癌症。 p53肿瘤抑制基因产物都是两者的潜在目标 这些方法。某些职业暴露会在 p53导致循环p53产生免疫反应 自动抗体，甚至在发生临床可检测到的癌症发生之前， 因此，这些抗体可以作为不良反应的有用早期标记。 另外，在 细胞培养以使突变体p53恢复到正常功能， 导致含有突变体p53的癌细胞死亡，但没有影响 在具有野生型P53的正常细胞上，这表明这可能是有用的 中断产生的工作场所暴露道路的方法 p53突变和结果癌。拟议研究的目的是 检查这两种方法是由石棉引起的职业癌症 在两个相关项目中曝光。对于第一个项目，储存的血清样品 将检查一大批具有石棉的工人 p53通过酶联免疫吸附测定和Ininiunobobotting通过p53自动抗体 确定抗体的存在是否与随后的 癌症的发展以及在p53突变中的存在 由此产生的肿瘤。对于第二个项目，p53细胞培养的影响 肽序列（作为肽或基于质粒的微型基因传递） 石棉相关的肺癌和间皮瘤细胞系，有或没有 p53突变和具有野生型p53的相应的非癌细胞系将 研究并确定肽的作用机理 用于诱导这些细胞的死亡。