Biomarkers of Obesity, Prostate Tissue Inflammation, and BPH Progression

肥胖、前列腺组织炎症和 BPH 进展的生物标志物

• 批准号: 7866087
• 负责人: Jay H. Fowke
• 金额: $ 40.15万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7866087
• 关键词: Acute; Address; Animal Model; Arachidonic Acids; Arts; Basic Science; Benign Prostatic Hypertrophy; Biological Markers; Biopsy; Blood; Body fat; C-reactive protein; Cell Count; Chronic; Clinical; Clinical Sciences; Clinical Treatment; Communities; Core Biopsy; Data; Development; Diabetes Mellitus; Diagnostic; Dinoprostone; Disease; Epidemiologic Studies; Epidemiology; F2-Isoprostanes; Free Radicals; Frequencies; Goals; Histologic; Hyperplasia; Immune; Infiltration; Inflammation; Inflammatory; Intervention; Lead; Leukocytes; Link; Lipid Peroxidation; Location; Logistics; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Mediating; Metabolic; Metabolism; Methods; Modeling; Monitor; Mus; NF-kappa B; National Institute of Diabetes and Digestive and Kidney Diseases; Obese Mice; Obesity; Outcome; Oxidative Stress; Participant; Pathway interactions; Patient Self-Report; Phenotype; Prospective Studies; Prostaglandin-Endoperoxide Synthase; Prostate; Prostatic Intraepithelial Neoplasias; Prostatic hypertrophy; Protein C; Reporting; Research; Research Methodology; Research Priority; Risk Factors; Role; Severities; Signal Transduction; Strategic Planning; Symptoms; Time; Tissues; Urine; Waist-Hip Ratio; adiponectin; base; cytokine; electric impedance; high risk men; indexing; insight; lower urinary tract symptoms; men; modifiable risk; mouse development; mouse model; multidisciplinary; novel; prospective; prostate enlargement; public health relevance; repository; waist circumference

DESCRIPTION (provided by applicant): Obesity increases cytokine levels and generates a state of chronic oxidative stress that may facilitate prostate tissue inflammation. Several prior prospective studies report obesity is associated with clinical symptoms of benign prostatic hyperplasia (BPH). However, the relationship between obesity and prostate tissue inflammation remains unclear, and the relevance of obesity-induced inflammation and oxidative stress is undetermined. Our goal is first to determine if obesity (BMI, waist circumference, waist-hip ratio, % body fat from bioelectric impedance analysis) is associated with inflammatory leukocyte cell count and inflammation severity in prostate biopsy cores from 500 men without prostate cancer or prostatic intraepithelial neoplasia. We will also investigate the association between prostate inflammation and four promising and validated biomarkers of inflammation and oxidative stress (urine prostaglandin E2 (PGE-M) and F2-isoprostane (F2iP-M) metabolites), and blood adiponectin and C-reactive protein (CRP) levels, that may mediate the effects of obesity on BPH progression. We will also characterize the mechanisms by which obesity and NF-kB activity induce the development of prostate hyperplasia in two mouse models of obesity (ob/ob and agouti). To describe the clinical impact of obesity on BPH progression, we will then prospectively follow study participants for changes in lower urinary tract symptoms and initiation of BPH treatment. Using multivariable linear, logistic, and COX regression, we will describe the associations between obesity, adiponectin, PGE-M, CRP, and F2iP-M levels with indices of prostate tissue inflammation and changes in symptom severity and BPH progression. Our approach is novel, multi-disciplinary, and translational; and will more rapidly lead to new insights into the etiologic and clinical roles of obesity in prostate tissue inflammation and BPH progression. Results may argue for one of several plausible interventions targeting obesity, inflammation, or oxidative stress to delay BPH progression.

描述（由申请人提供）：肥胖会增加细胞因子水平并产生慢性氧化应激状态，以促进前列腺组织炎症。一些先前的前瞻性研究报告肥胖与良性前列腺增生（BPH）的临床症状有关。但是，肥胖与前列腺组织炎症之间的关系尚不清楚，肥胖引起的炎症和氧化应激的相关性尚不确定。我们的目标首先是确定肥胖（BMI，腰围，腰围比，生物电障碍分析的体内脂肪％）是否与来自500名无前列性癌症或前列腺内部内部静脉内的炎症性白细胞细胞计数和前列腺活检核心的炎症白细胞计数和炎症严重程度有关。我们还将研究前列腺炎症与炎症和氧化应激的四种有希望的和验证的生物标志物（尿液前列腺素E2（PGE-M）和F2-异丙烷（F2IP-M）代谢物），以及血液脂肪核定素和C-反应性蛋白质（CRP）水平，这可能会培养bphs of OseSity的效果。我们还将表征肥胖和NF-KB活性在两种肥胖小鼠模型（ob/ob和agouti）中诱导前列腺增生的发展的机制。为了描述肥胖对BPH进展的临床影响，然后我们将前瞻性地跟随研究参与者，以改变较低的尿路症状和BPH治疗的开始。使用多变量的线性，逻辑和COX回归，我们将描述肥胖，脂联素，PGE-M，CRP和F2IP-M水平之间的关联，以及前列腺组织炎症指标以及症状严重程度和BPH进展的变化之间的关联。我们的方法是新颖，多学科和翻译。并将更快地导致对肥胖症在前列腺组织炎症和BPH进展中的病因和临床作用的新见解。结果可能会争论针对肥胖，炎症或氧化应激以延迟BPH进展的几种合理干预措施之一。