URINE AND BLADDER MARKERS OF INTERSTITIAL CYSTITIS

间质性膀胱炎的尿液和膀胱标志物

• 批准号: 6524589
• 负责人: Deborah Erickson
• 金额: $ 18.28万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6524589
• 关键词: biomarker; biopsy; clinical research; cyclic GMP; disease /disorder etiology; epidermal growth factor; gastrointestinal sign /symptom; glycoproteins; histamine; histology; human subject; hyaluronate; insulinlike growth factor; interleukin 6; interleukin 8; interstitial cystitis; membrane permeability; method development; urinalysis; urinary bladder; urine

Interstitial cystitis (IC) is a multifactorial syndrome, with several proposed etiologies. No clinical or histological factors are pathognomonic, and the diagnosis is essentially one of exclusion. A major problem with current IC research is the lack of objective markers for this symptom complex. The investigators' broad, long-term goals are to identify objective markers of IC, which will be valuable for many purposes. These include: (1) identifying subsets of IC patients with specific etiologies, (2) selecting patients for focused basic research on specific etiologies, (3) selecting patients for treatments directed towards specific etiologies, (4) testing whether the treatments truly are resolving the specific pathophysiologic processes. Since the etiologies of IC are still unknown, the best approach at this time is to seek associations between the proposed marker and other clinical/pathologic features of IC. Several urine components are known to be elevated in IC, and may be useful objective markers. Many of these markers are thought to reflect specific underlying pathophysiologies of IC. The markers include glycosaminoglycans, MUC-1 glycoprotein, hyaluronic acid, methylhistamine, interleukin-6, interleukin-8, cyclic GMP (a reflection of nitric oxide synthase), anti-proliferative factor, epidermal growth factor, heparin-binding epidermal growth factor-like growth factor, insulin-like growth factor and insulin-like growth factor binding protein 3. This study will test for associations between these urine markers and other features of IC, including an objective measurement of bladder permeability (Aims 1 and 2), symptom response to bladder distention (Aim 3) and relevant objective features of bladder biopsies (Aim 4). The ideal outcome will be to identify markers relevant to specific etiologies, which associate strongly with other markers relevant to the same etiologies. The markers with the strongest associations will be useful for future basic and clinical research directed towards specific etiologies of IC. This focused research will lead to improved, specific treatments for IC.

间质性膀胱炎（IC）是一种多因素综合征，有几种病因。 没有临床或组织学因素是特异性的，诊断基本上是排除性的。 目前IC研究的一个主要问题是缺乏这种症状复合体的客观标志物。 研究者广泛的长期目标是确定IC的客观标志物，这对许多目的都有价值。 其中包括：（1）鉴定具有特定病因的IC患者的子集，（2）选择患者用于特定病因的集中基础研究，（3）选择患者用于针对特定病因的治疗，（4）测试治疗是否真正解决特定病理生理过程。 由于IC的病因仍不清楚，目前最好的方法是寻找所提出的标记物与IC的其他临床/病理特征之间的关联。已知几种尿液成分在IC中升高，并且可能是有用的客观标志物。 这些标志物中的许多被认为反映了IC的特定潜在病理生理学。 标记物包括糖胺聚糖、MUC-1糖蛋白、透明质酸、甲基组胺、白细胞介素-6、白细胞介素-8、环GMP（一氧化氮合酶的反映）、抗增殖因子、表皮生长因子、肝素结合表皮生长因子样生长因子、胰岛素样生长因子和胰岛素样生长因子结合蛋白3。 本研究将检测这些尿液标志物与IC的其他特征之间的相关性，包括膀胱渗透性的客观测量（目的1和2）、对膀胱扩张的症状反应（目的3）和膀胱活检的相关客观特征（目的4）。 理想的结果将是确定与特定病因相关的标记物，这些标记物与相同病因相关的其他标记物密切相关。 具有最强相关性的标记物将有助于未来针对IC特定病因的基础和临床研究。 这项集中的研究将导致IC的改进，特异性治疗。