Prostate Gene Expression Changes Associated with BPH

与 BPH 相关的前列腺基因表达变化

• 批准号: 6577473
• 负责人: Kevin M Slawin
• 金额: $ 45.15万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6577473
• 关键词: RNase protection assay; benign prostate hyperplasia; biomarker; clinical research; enzyme inhibitors; gene expression; genetic markers; genetic transcription; human subject; human tissue; immunocytochemistry; laser capture microdissection; longitudinal human study; mass screening; messenger RNA; microarray technology; neoplasm /cancer genetics; pathologic process; polymerase chain reaction; prognosis; prostate; prostate specific antigen; prostate surgery; proteomics; testosterone 5 alpha reductase; tissue resource /registry; western blottings

DESCRIPTION (provided by applicant): Through this application, Baylor College of Medicine responds to RFA: DK-02-017, MTOPS Prostate Samples Analysis Consortium (MPSA). The Baylor Prostate Center proposes to serve as a Biomarker Unit within the MPSA consortium, which will work cooperatively with the other Biomarker Units, the Pathology Coordinating Center, and the NIDDK Project Coordinator to perform basic and translational research on biomarkers for BPH. The PI, Kevin M. Slaw/n, M.D., Director of the Baylor Prostate Center, recruited and managed 200 patients on the MTOPS trial over its seven-year duration. The co-investigators encompass broad interests and expertise in both clinical and basic research in benign prostatic hyperplasia (BPH), molecular epidemiology, biomarkers research, genetic and tissue microarray technology, cell signaling, and sophisticated data mining and statistical analysis of complex biologic data. Drawing from his extensive BPH clinical trials experience and with the resource management skills gained as co-Director of both the Biopsy and the Basic Tissue Research Committees of the MTOPS trial, as the Serum Bank director and member of the Resource Allocation Committee of the Baylor SPORE in Prostate Cancer, and as director of Baylor's Prostate Cancer Screening Program for the past eight years, the PI has the requisite administrative, clinical and basic research experience in BPH and biomarker development and validation to lead this center. Furthermore, the considerable tissue resources available through BPH-sub-studies of the Baylor SPORE in Prostate Cancer, and the expertise in tissue harvesting, cataloguing and banking, and in tissue microarray development and production will serve as a valuable resource for biomarker validation prior to testing on the invaluable and limited MTOPS tissue for the Baylor Center, as well as, for the other MPSA consortium members. Our large prostate cancer screening serum bank, containing frozen sera obtained through a yearly program, contains serial frozen serum samples and clinical data including IPSS, DRE estimated prostate volume, and medical and surgical treatment history for BPH on over 10,000 patients spanning a decade of follow-up. Serum markers that correlate with the presence and severity of BPH or that predict progression or response to medical therapy, identified either by the Baylor Biomarkers Center, or by other Centers could be validated in a Phase II study with these resources, allowing only the best markers for progression to evaluation in Phase III studies using the exhaustible MTOPS serum and tissue bank resources. Through the efforts of this RFA proposal, the Baylor MPSA Center, along with the other centers, the Biostatistics Center and the NIDDK, hopes to answer identify and validate much needed new biomarkers for the detection of BPH and the assessment of risk for disease progression, as well as to gain insight into the molecular correlates that determine response to medical therapies, primarily a-blockers and 5a-reductase inhibitors for this disease.

描述（由申请人提供）： 通过此应用程序，贝勒医学院响应 RFA：DK-02-017、MTOPS 前列腺样本分析联盟 (MPSA)。贝勒前列腺中心提议作为 MPSA 联盟内的生物标志物单位，该单位将与其他生物标志物单位、病理学协调中心和 NIDDK 项目协调员合作，开展 BPH 生物标志物的基础和转化研究。首席研究员 Kevin M. Slaw/n, M.D.（贝勒前列腺中心主任）在为期七年的 MTOPS 试验中招募并管理了 200 名患者。共同研究人员在良性前列腺增生 (BPH) 的临床和基础研究、分子流行病学、生物标志物研究、遗传和组织微阵列技术、细胞信号传导以及复杂生物数据的复杂数据挖掘和统计分析方面拥有广泛的兴趣和专业知识。凭借其丰富的 BPH 临床试验经验以及过去八年担任 MTOPS 试验活检和基础组织研究委员会联合主任、贝勒 SPORE 前列腺癌血清库主任和资源分配委员会成员以及贝勒前列腺癌筛查项目主任所获得的资源管理技能，PI 在 BPH 和生物标志物开发方面拥有必要的管理、临床和基础研究经验 并验证领导该中心的能力。此外，通过贝勒前列腺癌 SPORE 的 BPH 子研究可获得的大量组织资源，以及组织采集、编目和存储以及组织微阵列开发和生产方面的专业知识，将成为贝勒中心以及其他 MPSA 联盟成员在测试宝贵且有限的 MTOPS 组织之前进行生物标志物验证的宝贵资源。我们的大型前列腺癌筛查血清库包含通过年度计划获得的冷冻血清，包含连续冷冻血清样本和临床数据，包括 IPSS、DRE 估计的前列腺体积以及超过 10,000 名患者的 BPH 医疗和手术治疗史，跨越十年的随访。由贝勒生物标志物中心或其他中心鉴定的与 BPH 的存在和严重程度相关或预测进展或对药物治疗的反应的血清标志物可以在 II 期研究中使用这些资源进行验证，从而仅允许使用可用的 MTOPS 血清和组织库资源在 III 期研究中评估进展的最佳标志物。通过这项 RFA 提案的努力，贝勒 MPSA 中心与其他中心、生物统计中心和 NIDDK 一起，希望能够识别和验证急需的新生物标志物，用于检测 BPH 和评估疾病进展风险，并深入了解决定对该疾病的药物治疗（主要是 α-阻滞剂和 5a-还原酶抑制剂）反应的分子相关性。