Proteomic Studiy of Androgen Independent Prostate Cancer

个人描述(申请人提供)：前列腺癌居第二位 导致美国男性癌症死亡的原因，而且绝大多数 这些死亡是雄激素非依赖性疾病的结果。目前在那里 都不是预防雄激素非依赖性发展的有效手段 前列腺癌或一旦患者患上这种致命疾病就进行治疗 疾病。 这项建议的目的是：1)识别相关的差异表达蛋白 雄激素非依赖性前列腺癌和，2)验证临床 通过检测一个大的、不同的 人类外科手术标本系列。CWR22异种移植与人体外科 本研究将使用标本。激光捕获显微解剖将被 用于获得特定癌细胞的纯群体。蛋白 表达模式将通过2D-PAGE和身份进行比较 差异表达的蛋白质将通过质谱学进行测定 测序。蛋白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 独立性将通过免疫组织化学研究来评估 CWR22异种移植系列及系列活组织检查 前列腺癌患者在去势前和去势后的间隔时间。 这项提案的长期目标是找到可以使用的新生物标记物 以确定患有雄激素非依赖性前列腺癌克隆的男性 出现临床雄激素非依赖性。这将促进 防止进展为雄激素非依赖性疾病的治疗方法 使临床医生能够确定哪些男性将从这些措施中受益 战略。对于那些已经拥有雄激素非依赖性克隆的男性来说， 预防战略将无效，新的治疗方法将针对 杀灭或控制雄激素非依赖性克隆将需要开发。 这项提议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。

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.