Proteomic Signatures of Cancer

癌症的蛋白质组学特征

• 批准号: 7681304
• 负责人: Jason Allan Bush
• 金额: $ 40.9万
• 依托单位: CALIFORNIA STATE UNIVERSITY FRESNO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7681304
• 关键词: Acute; Address; Age; Agriculture; Area; Biological; Biological Assay; Biological Testing; Breast; Breast Cancer Epidemiology; California; Carcinogens; Case-Control Studies; Cells; Chemicals; Chlorinated Hydrocarbons; Chronic; Class; Cooperative Human Tissue Network; Core Facility; DNA; Data; Data Analyses; Data Set; Databases; Epithelial; Epithelial Cells; Etiology; Exposure to; Gene Expression Profiling; Genes; Genomics; Genotype; Goals; Health; Hispanics; Human; Incidence; Individual; Investigation; Latina; Learning; Link; Malignant Neoplasms; Mammary gland; Methoxychlor; Molecular; Molecular Profiling; Normal Cell; Participant; Pesticides; Phase; Pilot Projects; Polymerase Chain Reaction; Populations at Risk; Proteomics; Questionnaires; Range; Rate; Recruitment Activity; Regression Analysis; Research Personnel; Resistance; Risk; Saliva; Specimen; Staging; Students; Techniques; Toxaphene; Work; anticancer research; base; cancer epidemiology; ethnic minority population; farm worker; health disparity; innovation; malignant breast neoplasm; neoplasm registry; organochlorine pesticide; pesticide exposure

Environmental substances seem to be involved in the etiology of breast cancers. Several studies have found an association between human cancer and exposure to agricultural pesticides such as the organochlorine (OC) pesticides; therefore, farmworkers may be at higher risk for acute and chronic health effects associated with pesticides. The objective of this project is two-fold, 1) obtain epidemiological data specific to breast cancer incidence rates in areas of high and low pesticide use, and 2) expose normal breast epithelial in culture with organochlorine chemicals to determine the biological effects. This is responsive to the health disparity of Hispanic farmworkers in the Central Valley. For Phase 1, student researchers will calculate age-adjusted breast cancer incidence rates for pesticide use and identify databases from which other variables pertinent to breast cancer epidemiology are useful. Upon promising results, individual breast cancer cases (and healthy "controls") will be approached and recruited for entry into a breast cancer case-control study in which both questionnaire-based information and biological specimens are collected. DNA will be extracted from saliva and genotyped by PCR techniques at Fresno State for several of the common carcinogenmetabolizing genes. For Phase 2, student researchers will test the biological effects of organochlorines on primary normal human mammary epithelial cells derived from Hispanic participants of the NCI/Cooperative Human Tissue Network. Cells maintained under long-term OC treatment will be compared by proteomic expression profiling by 2D-PAGE and LC-MS/MS in year 1 followed by gene expression profiling in year 2. Finally, OC-resistant cells will be screened in conjunction with the BIMR Chemical Genomics Core for reversion of the estrogenic effects. This innovative pilot project takes students through a range of cancer research aspects from identifying at-risk populations to molecular analyses of the problem.

环境物质似乎与乳腺癌的病因有关。几项研究 发现人类癌症与暴露于农业杀虫剂之间存在关联， 有机氯（OC）农药;因此，农场工人可能面临更高的急性和慢性健康风险 与农药有关的影响。该项目的目标有两个：1）获得流行病学数据 具体到在高和低农药使用地区的乳腺癌发病率，和2）暴露正常乳房 用有机氯化学品培养上皮细胞，以确定生物效应。这是响应于 中央谷西班牙裔农场工人的健康差异。对于第一阶段，学生研究人员将计算 使用杀虫剂的年龄调整乳腺癌发病率，并确定其他变量 与乳腺癌流行病学相关的信息是有用的。在有希望的结果，个别乳腺癌病例 (and健康的“对照组”）将被招募进入一项乳腺癌病例对照研究， 其中收集基于指纹的信息和生物样本。DNA将被提取 在弗雷斯诺州，通过PCR技术对几种常见的致癌物质代谢进行基因分型。 基因.对于第二阶段，学生研究人员将测试有机氯对 来源于NCI/Cooperative的西班牙裔参与者的原代正常人乳腺上皮细胞 人类组织网络.将通过蛋白质组学比较长期OC处理下维持的细胞 在第1年通过2D-PAGE和LC-MS/MS进行表达谱分析，随后在第2年进行基因表达谱分析。 最后，OC抗性细胞将与BIMR化学基因组学核心一起筛选， 雌激素作用的逆转。这个创新的试点项目需要学生通过一系列的癌症 研究方面，从确定风险人群到问题的分子分析。