Project: Survivorship Care Physical Activity Initiative to Improve Disparities in HRQoL for Prostate Cancer Survivors (RELate Study)

完整研究项目 1：幸存者护理身体活动倡议，以减少 HRQOL 差异 前列腺癌幸存者（RELate 研究） 摘要 前列腺癌 (PCa) 治疗的后期影响可能会导致独特的身体和心理社会问题， 影响他们的长期健康相关生活质量（HRQOL）。增加体力活动 (PA) 是一种可改变的 可以针对 PCa 生存相关治疗结果和生活方式的风险因素 行为。 PA 增加可能对非洲血统 (AA) PCa 幸存者的预后影响最大，他们 往往具有较低的 HRQOL 和总体生存率，其中缺乏锻炼、不良饮食和 肥胖率最为普遍。众所周知，运动可以改善癌症的预后 对于幸存者来说，人们对 PA 可能改善的生物行为机制和途径知之甚少 HRQOL 并提高总体生存率。晚期糖基化终产物 (AGE) 是反应性代谢物 在正常新陈代谢以及生物大分子的氧化过程中产生。生活方式因素 久坐的生活方式、不良饮食和肥胖等都会增加体内 AGE 水平。调查人员 假设在一项对 PCa 幸存者进行人类 PA/饮食干预的随机试验中 诊断为 I-III 期 PCa (n=120)，较低的 AGE 水平将与改善的 HRQOL 相关，并将导致 AA 和欧洲美洲 (EA) 试验参与者之间免疫反应的差异变化。的 研究人员进一步假设，在小鼠模型干预中，生活方式的机械影响 与肿瘤相关的免疫反应相关的 AGE 和肿瘤生长和/或进展将模仿那些 在人体模型中发现。目标 1 是完成一项为期 1 年、2 组（干预与常规护理）的随机研究 对诊断为 I-III 期 PCa 的男性进行 PA/饮食干预（由 SCSU 的 M. Ahmed 博士和 D. 特纳，MUSC-HCC）。目标 2 是评估生活方式干预对 PA 和饮食的影响，并定义其影响 诊断为 I-III 期 PCa 的男性中 AGE、AGE 前体和 HRQOL 的关系（由 Dr. 艾哈迈德，SCSU）。目标 3 是使用自发 PCa 生活方式小鼠模型来定义 AGE-RAGE 的作用 免疫细胞表型和肿瘤进展的信号传导（由 MUSC-HCC 特纳博士领导）。结果 可以带来药理学和生活方式调整的创新见解，并可以确定保护性的 可能导致 AA 和 EA 男性 PCa 治疗结果差异的因素。这个 该项目与本申请中包含的其他研究项目具有协同相关性

Full Research Project 1: Survivorship Care Physical Activity Initiative to Reduce Disparities in HRQOL for Prostate Cancer Survivors (RELate Study) SUMMARY The late effects of prostate cancer (PCa) treatment can lead to unique physical and psychosocial issues that impact their long-term health-related quality of life (HRQOL). Increased physical activity (PA) is a modifiable risk factor which may be targeted to address PCa survivorship-related treatment outcomes and lifestyle behaviors. Increased PA may have greatest impact on outcomes for African-ancestry (AA) PCa survivors, who tend to have lower HRQOL and overall survival, and in whom factors such as a lack of exercise, poor diet, and rates of obesity are most prevalent. While it is well-known that exercise can improve prognosis among cancer survivors, little is known about the bio-behavioral mechanisms and pathways through which PA may improve HRQOL and increase overall survival. Advanced glycation endproducts (AGEs) are reactive metabolites produced during normal metabolism as well as the oxidation of biological macromolecules. Lifestyle factors such as a sedentary lifestyle, poor diet, and obesity increase AGE levels in the body. The investigators hypothesize that in a randomized trial of a human PA/dietary intervention with PCa survivors previously diagnosed with Stage I-III PCa (n=120), lower AGE levels will correlate with improved HRQOL, and will lead to differential changes in immune response between AA and European American (EA) trial participants. The investigators further hypothesize that in a mouse model intervention, the mechanistic implications of lifestyle- associated AGEs to tumor-associated immune response and tumor growth and/or progression will mimic those found in human models. Aim 1 is to complete a 1-year, 2-arm (intervention vs usual care) randomized PA/dietary intervention in men diagnosed with stage I-III PCa (co-led by Dr. M. Ahmed, SCSU and Dr. D. Turner, MUSC-HCC). Aim 2 is to evaluate the effect of lifestyle intervention on PA and diet, and define their relationship with AGEs, AGEs pre-cursors, and HRQOL in men diagnosed with stage I-III PCa (led by Dr. Ahmed, SCSU). Aim 3 is to use a spontaneous PCa lifestyle mouse model to define the role of AGE-RAGE signaling to immune-cell phenotypes and tumor progression (led by Dr. Turner, MUSC-HCC). The results could lead to innovative insights for pharmacologic and lifestyle adjustment, and could identify protective factors that may underlie observed differences in PCa treatment outcomes between AA and EA men. This project is synergistically related to the other research projects included in this application