ADRENERGIC REGULATION OF HUMAN PROSTATE GROWTH

人类前列腺生长的肾上腺素调节

• 批准号: 6177824
• 负责人: VICTOR K LIN
• 金额: $ 22.76万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6177824
• 关键词: alpha adrenergic agent; alpha adrenergic receptor; benign prostate hyperplasia; cell growth regulation; clinical research; cytoskeletal proteins; human subject; immunocytochemistry; pathologic process; prostate; protein isoforms; protein structure function; smooth muscle; tissue /cell culture

DESCRIPTION (Adapted from the Applicant's Abstract): Benign prostate hyperplasia (BPH) is primarily a disease of stromal proliferation. Smooth muscle (SM) is a major component of prostatic stroma. Therefore, it is likely that the progression of BPH requires smooth muscle proliferation. In many smooth muscle tissues, the state of contractile protein gene regulation is modulated during proliferation, with a loss of normal contractile proteins during active growth and a re-acquisition of contractile proteins once growth has been arrested. Little is known regarding the phenotypic modulation of stromal SM cells during the initiation and progression of BPH. In addition, the impact of therapy, specifically a blockade, on the SM phenotype is unknown. In preliminary studies, they have demonstrated that men with established BPH have evidence of a smooth muscle de-differentiation process, compatible with past but not ongoing SM proliferation. In addition, they have demonstrated that a blockade significantly affects the SM phenotype. They propose to characterize the expression of SM phenotypic markers, including myosin heavy chain and caldesmon, to determine whether the smooth muscle phenotype is altered during the natural history and progression of BPH. In addition, they will expand or preliminary studies to determine to what extent the SM phenotype is regulated by alpha adrenergic signal transduction pathways. They will utilize two unique tissue banks for these studies. First, a large number of normal and hyperplastic prostates from men of a variety of age groups banked as part of the UT Southwestern NIH O'Brien Center Repository and from the NIH Medical Therapy of Prostate Symptoms (MTOPS) clinical trial which will permit longitudinal observation of single patients in correlation with clinical outcome. Quantitative RT_PCR, immunohistochemical and morphometric analysis will be utilized to address the following specific aims: (1) to establish and validate methods of archived tissue analysis suitable for a multi-center trial; (2) to define changes in the SM phenotype which occur during the natural history of BPH; (3) to determine whether the SM phenotypes is modulated by alpha adrenergic signals; (4) using a prostate SM culture system, elucidate the regulatory role of alpha1A adrenergic stimulation in prostatic SM growth and differentiation.

描述（改编自申请人的摘要）：良性前列腺 增生（BPH）主要是一种基质增殖疾病。 光滑的 肌肉（SM）是前列腺基质的主要组成部分。 因此，它是 BPH 的进展可能需要平滑肌增殖。 在 许多平滑肌组织，收缩蛋白基因调控的状态 在增殖过程中受到调节，失去正常的收缩能力 活跃生长期间的蛋白质和收缩蛋白的重新获得 一旦增长受到抑制。 关于表型知之甚少 BPH 发生和进展过程中基质 SM 细胞的调节。 此外，治疗（特别是阻断）对 SM 的影响 表型未知。 在初步研究中，他们已经证明 患有前列腺增生症的男性有平滑肌去分化的证据 过程，与过去但不正在进行的 SM 扩散兼容。 在 此外，他们还证明封锁会严重影响 SM表型。 他们提出表征 SM 表型的表达 标记物，包括肌球蛋白重链和钙结合蛋白，以确定是否 平滑肌表型在自然历史过程中发生改变，并且 BPH 的进展。 此外，他们还将扩大或初步研究 确定 SM 表型受 α 肾上腺素能调节的程度 信号转导途径。 他们将利用两个独特的组织库 这些研究。 一、大量正常和增生的前列腺 来自 UT 西南大学不同年龄段的男性 NIH 奥布莱恩中心存储库和 NIH 前列腺医学治疗 允许纵向观察的症状 (MTOPS) 临床试验 单个患者的数量与临床结果的相关性。 定量 RT_PCR、免疫组织化学和形态计量学分析将用于 解决以下具体目标：（1）建立和验证方法 适用于多中心试验的存档组织分析； (2) 定义 BPH 自然史期间发生的 SM 表型变化； (3)确定SM表型是否受α肾上腺素能调节 信号； (4) 利用前列腺SM培养系统，阐明其调控机制 α1A 肾上腺素刺激在前列腺 SM 生长中的作用 差异化。