Leukocytic Phenotypes Associated with BPH Progression

与 BPH 进展相关的白细胞表型

• 批准号: 9789816
• 负责人: Simon W Hayward
• 金额: $ 30.59万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789816
• 关键词: Autoimmune Process; Basic Science; Benign; Benign Prostatic Hypertrophy; Bioinformatics; Cells; Characteristics; Charge; Clinical; Collaborations; Communities; Comorbidity; Country; Critiques; Data; Demographic Aging; Disease; Education; Environment; Goals; Health Care Costs; Immune; Incidence; Inflammatory; Intervention; Leukocytes; Link; Malignant - descriptor; Medical; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Operative Surgical Procedures; Pathway interactions; Patients; Phenotype; Physicians; Population; Prostate; Prostatic; Research; Research Project Grants; Resistance; Resources; Scientist; Signal Pathway; Signal Transduction; Symptoms; TNF gene; United States; Urologic Diseases; Urology; Work; extracellular; innovation; lower urinary tract symptoms; macrophage; member; men; new technology; new therapeutic target; next generation; older patient; patient population; programs; response; single-cell RNA sequencing; therapy development; urologic

OVERALL: SUMMARY The goals of this Center for Benign Urological Diseases are: 1) to create and maintain an environment that supports important and innovative research in the field of benign urology by focusing on a Scientific Research Project examining “Leukocyte phenotypes associated with BPH progression,” 2) to educate and inform young scientists and physicians about BPH, and 3) to develop new interactive projects and collaborations involving other groups in the benign urology research community. The program brings together expertise in basic science, bioinformatics, and clinical urology to apply new technologies in the field of benign urologic research. The research team includes members from the benign and malignant urology fields as well as from non- urologic cancers. Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are highly prevalent and will become increasingly more frequent with an aging demographic. Approximately one- third of BPH patients are resistant to current medical therapy, and a further third of initial responders (around 10% of the total patient population) subsequently develop therapy resistance after an initial positive response. So, for around 40% of the patient population there is no effective medical therapy, leaving surgery as the sole treatment option. Approximately 120,000 surgeries are performed annually in the United States to treat men who are resistant to the available medical interventions. Many of these are elderly patients often with significant co-morbidities who are often not ideal surgical candidates. BPH is closely associated with pro- inflammatory co-morbidities. However, the characteristics and pathways linking immune/inflammatory changes to BPH progression are unclear. We show in preliminary data that TNFα antagonists can reduce the incidence of BPH in patients with autoimmune inflammatory conditions suggesting that a more complete understanding of the leukocyte signaling network in the prostate could elucidate new therapeutic targets. This proposal will utilize single-cell (sc)RNA-seq to fully characterize the leukocyte population in patients with small prostates and low IPSS scores vs. those with large prostates, high symptom scores, and progression to surgery specifically for a BPH indication. This will provide a comprehensive picture of the cells that are present and will allow for the application of bioinformatics approaches to define the extracellular signaling pathways that are activated in these inflammatory cells as disease progresses. The Administrative Core coordinates all Center activities, maintains financial and administrative oversight, manages the Educational Enrichment Program charged with the education of the next generation of scientists, and informs scientists and clinicians of our work. The Administrative Core also coordinates with the NIDDK and the other IR-BU Centers and integrates our approaches with the wider benign urologic research community.

总体：摘要 这个良性泌尿外科疾病中心的目标是：1）创建和维护一个环境 通过关注科学研究，支持良性泌尿外科领域的重要和创新研究 项目考试“与BPH进展相关的白细胞表型”，2）教育和通知年轻人 关于BPH的科学家和医生，以及3）开发涉及的新互动项目和合作 良性泌尿外科研究界的其他小组。该计划汇集了基本方面的专业知识 科学，生物信息学和临床泌尿科在良性泌尿科研究领域应用新技术。 研究小组包括良性和恶性泌尿科领域的成员以及非 - 泌尿科癌症。良性前列腺增生（BPH）和相关的下尿路症状（LUTS）为 随着衰老的人口统计，高度普遍，并且越来越频繁地变得越来越频繁。大约一个 三分之一的BPH患者对当前的药物治疗有抵抗力，另外三分之一 最初的阳性反应后，患者总人群的10％随后产生耐药性。 因此，对于大约40％的患者人群，没有有效的医疗疗法，而手术则是唯一的 治疗选项。每年在美国进行大约120,000次手术以治疗男性 对可用的医疗干预措施有抵抗力的人。其中许多是老年患者经常 显着的合并症通常不是理想的外科手术候选人。 BPH与支持密切相关 炎症合并症。但是，连接免疫/炎症变化的特征和途径 BPH的进展尚不清楚。我们在初步数据中表明，TNFα拮抗剂可以减少事件 自身免疫性炎症疾病患者的BPH，表明更完整的了解 前列腺中的白细胞信号网络可以阐明新的治疗靶标。该提议将 利用单细胞（SC）RNA-Seq充分表征小前列腺患者的白细胞种群 低IPS的得分与具有较大前列腺，高符号和进展为手术的较高的iPS得分 用于BPH指示。这将为存在的细胞提供全面的图片，并将允许 生物信息学方法的应用来定义被激活的细胞外信号通路 这些随着疾病进展的这些炎症细胞。行政核心协调所有中心活动， 维护财务和行政监督，管理负责的教育丰富计划 下一代科学家的教育，并向科学家和临床医生通报我们的工作。 行政核心还与NIDDK和其他IR-BU中心协调并整合了我们 与更广泛的良性泌尿外科研究社区接触。