Prostate Gene Expression Changes Associated with BPH

与 BPH 相关的前列腺基因表达变化

• 批准号: 6666822
• 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/6666822
• 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)。贝勒前列腺中心建议作为MPSA联盟内的一个生物标记单位，该联盟将与其他生物标记单位、病理协调中心和NIDDK项目协调员合作，对BPH的生物标记进行基础和翻译研究。贝勒前列腺中心主任凯文·M·斯劳，医学博士，在MTOPS试验的七年时间里招募和管理了200名患者。共同调查者包括对良性前列腺增生症(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、细胞信号以及复杂生物数据的复杂数据挖掘和统计分析的广泛兴趣和专业知识。凭借他丰富的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联合主任、作为前列腺癌贝勒孢子的血清库主任和资源分配委员会成员以及过去八年作为贝勒的前列腺癌筛查项目主任所获得的资源管理技能，PI拥有领导该中心所需的BPH和生物标记物开发和验证方面的管理、临床和基础研究经验。此外，通过前列腺癌贝勒孢子的BPH分研究获得的大量组织资源，以及在组织采集、编目和储存以及组织微阵列开发和生产方面的专业知识，将成为贝勒中心和其他MPSA联盟成员在对宝贵和有限的MTOPS组织进行测试之前进行生物标记物验证的宝贵资源。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，其中包含一系列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跨越十年随访的10,000多名BPH患者的内科和外科治疗史。贝勒生物标记物中心或其他中心确定的与BPH的存在和严重程度相关的血清标记物或预测药物治疗进展或反应的血清标记物可以在使用这些资源的II期研究中得到验证，只允许使用可耗尽的MTOPS血清和组织库资源进行III期研究的评估的最佳标记物。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，希望回答、识别和验证用于检测BPH和评估疾病进展风险的急需的新生物标记物，并深入了解决定药物治疗反应的分子相关性，主要是针对这种疾病的a受体阻滞剂和5a还原酶抑制剂。