Proteomic Studiy of Androgen Independent Prostate Cancer

雄激素非依赖性前列腺癌的蛋白质组学研究

• 批准号: 6832075
• 负责人: DAVID K ORNSTEIN
• 金额: $ 15.15万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832075
• 关键词: androgens; biomarker; gel electrophoresis; gene expression; hormone regulation /control mechanism; hormone related neoplasm /cancer; human tissue; mass spectrometry; neoplasm /cancer genetics; neoplastic process; oncoproteins; prostate neoplasms; proteomics

DESCRIPTION (provided by applicant): Prostate cancer is the second leading cause of cancer deaths among men in the United States, and the vast majority of these deaths are the result of androgen-independent disease. Currently there are no effective means to prevent the development of androgen-independent prostate cancer or to treat patients once they have developed this deadly disease. This proposal aims to: 1) identify differentially expressed proteins associated with androgen-independent prostate cancer and, 2) validate clinical significance of differential expression of these proteins by examining a large series of human surgical specimens. The CWR22 xenografi and human surgical specimens will be used in this study. Laser capture microdissection will be used to procure pure populations of specific cancerous cells. Protein expression patterns will be compared by 2D-PAGE and the identity of differentially expressed proteins will be determined by mass spectrometry sequencing. The frequency of altered protein expression and the relationship to cellular proliferation and clinical evidence of progression to androgen independence will be assessed by immunohistochemical studies of the complete CWR22 xenograft series as well as serial biopsies obtained from advanced prostate cancer patients prior to and at intervals following castration. The long-term goal of this proposal is to find new biomarkers that can be used to identify men with androgen-independent prostate cancer clones prior to the onset of clinical androgen independence. This will facilitate development of therapies that prevent progression to androgen-independent disease and will enable clinicians to identify those men who would benefit from these strategies. For those men who already have androgen-independent clones, prevention strategies will be ineffective, and novel therapies directed at killing or controlling androgen-independent clones will need to be developed. Protein changes discovered by this proposal will likely be good targets for these cytotoxic or suppressive therapies.

描述（由申请人提供）：前列腺癌是第二大 美国男性癌症死亡的原因，绝大多数 这些死亡是雄激素非依赖性疾病的结果。当前 没有有效的手段来防止雄激素非依赖性的发展， 前列腺癌或治疗患者，一旦他们已经发展这种致命的 疾病 本研究的目的是：1）鉴定差异表达蛋白， 雄激素非依赖性前列腺癌，2）验证临床 这些蛋白质的差异表达的意义，通过检查大的 一系列人体手术标本CWR 22异种移植和人类外科手术 本研究将使用样本。激光捕获显微切割将是 用于获取特定癌细胞的纯群体。蛋白 表达模式将通过2D-PAGE进行比较， 差异表达的蛋白质将通过质谱法测定 测序蛋白质表达改变的频率及其与 细胞增殖和进展为雄激素的临床证据 独立性将通过完整的免疫组织化学研究进行评估。 CWR 22异种移植物系列以及从晚期乳腺癌中获得的系列活检 前列腺癌患者在去势之前和之后的间隔。 这项提案的长期目标是找到新的可以使用的生物标志物 在此之前识别患有雄激素非依赖性前列腺癌克隆的男性 临床雄激素非依赖性发作。这将有助于发展 预防进展为雄激素非依赖性疾病的治疗， 使临床医生能够识别那些将从中受益的男性， 战略布局对于那些已经有雄激素非依赖性克隆的男性来说， 预防策略将是无效的，新的治疗方法针对 需要开发杀死或控制雄激素非依赖性克隆的技术。 这项提案发现的蛋白质变化可能是很好的目标， 这些细胞毒性或抑制性疗法。