Prostate Gene Expression Changes Associated with BPH

描述（由申请人提供）： 通过此应用程序，贝勒医学院回应RFA：DK-02-017，MTOPS前列腺样本分析联盟（MPSA）。Baylor前列腺中心提议作为MPSA联盟内的生物标志物单位，该联盟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，对BPH生物标志物进行基础和转化研究。PI，Kevin M。色拉/n，医学博士，贝勒前列腺中心主任，招募和管理200名患者的MTOPS试验在其七年的时间。共同研究者在良性前列腺增生（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具有广泛的兴趣和专业知识。凭借其丰富的BPH临床试验经验，以及作为MTOPS试验活检和基础组织研究委员会的共同主任，作为血清库主任和Baylor SPORE前列腺癌资源分配委员会成员，以及作为过去八年Baylor前列腺癌筛查项目主任获得的资源管理技能，PI具有必要的行政管理，在BPH和生物标志物开发和验证方面的临床和基础研究经验，以领导该中心。此外，通过前列腺癌中Baylor SPORE的BPH子研究可获得的大量组织资源，以及组织采集、编目和银行方面的专业知识，以及组织微阵列开发和生产方面的专业知识，将在Baylor中心以及其他MPSA联盟成员对无价和有限的MTOPS组织进行测试之前，作为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药物和手术治疗史，随访时间长达十年。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，由Baylor生物标志物中心或其他中心鉴定，可以在II期研究中使用这些资源进行验证，仅允许最佳进展标志物在III期研究中使用可耗尽的MTOPS血清和组织库资源进行评估。通过这项RFA提案的努力，贝勒MPSA中心，沿着其他中心，生物统计中心和NIDDK，希望回答识别和验证急需的新生物标志物，用于检测BPH和评估疾病进展的风险，以及深入了解决定对药物治疗反应的分子相关性，主要是用于这种疾病的α-阻断剂和5 α-还原酶抑制剂。

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.