Exploring the Impact of Negative Energy Balance in Men with Prostate Cancer

描述(申请人提供)：探索负能量平衡对前列腺癌男性的影响前列腺癌是美国男性的头号癌症，每年导致超过33,000名男性死亡。在肥胖盛行的美国南部，死亡率尤其高。肥胖和超重与患侵袭性疾病的风险相关，能量平衡可能在前列腺癌的进展中发挥重要作用。临床前研究表明，热量限制和体力活动增加导致体重减轻的负能量平衡可能会抑制几种推动肿瘤生长的激素和炎症因子，如瘦素、血管内皮生长因子(VEGF)、磷脂酰肌醇3激酶(PI3K)和哺乳动物靶标雷帕霉素(MTOR)，并可能最终影响肿瘤的增殖率和细胞凋亡。然而，在人体上进行的实验一直受到限制。我们的多学科研究团队由营养、运动和基础科学家、生物统计学家和临床医生组成，试图在40名新诊断为前列腺癌的超重或肥胖男性中进行一项试点/可行性研究，这些男性计划接受前列腺切除术。这项研究将利用我们的经验来探讨通过健康的能量限制饮食和增加的体力活动(PA)来减肥对循环激素、细胞因子和生长因子的潜在影响，以及对肿瘤生物学和其他临床结果的影响。同意的患者将被随机分为两组中的一组：1)健康的饮食运动干预，以促进每周最多2磅的体重减轻；或2)等待名单的对照组，他们将在研究期结束后接受干预。这项研究将探索和对比在干预和等待名单对照组的10周研究期间观察到的体重指数(BMI)的变化，并监测身体成分、能量摄入量和PA的变化；这些变化将被研究与下列终点有关：a)与癌症进展、激素状态、炎症和其他能量相关因素相关的循环生物标记物和基因表达的变化；b)肿瘤增殖和凋亡率；c)胰岛素受体、血管内皮生长因子、AKT和NFkB的肿瘤免疫组织化学标志物；和d)与功能和健康相关的结果，即副作用和医疗结果、生活质量和功能状态。这些数据是基础性的，并可能最终在这一患者群体中导致新的补充疗法。 公共卫生相关性：前列腺癌是美国男性的头号癌症，也是癌症相关死亡的第二大原因。本项目将探索在超重和肥胖的前列腺癌患者中进行减肥干预作为术前补充治疗的可行性，并将探讨干预对血清生物标记物、肿瘤特征和临床结果的影响。

DESCRIPTION (provided by applicant): Exploring the Impact of Negative Energy Balance in Men with Prostate Cancer Prostate cancer is the leading cancer among US males, and kills more than 33 thousand men annually. Mortality rates are especially high in the southern US, where obesity is pandemic. Obesity and overweight are associated with the risk of aggressive disease, and energy balance may play a major role in prostate cancer progression. Preclinical studies suggest that negative energy balance from both caloric restriction and increased physical activity that results in weight loss may suppress several hormonal and inflammatory factors that drive tumor growth, e.g., leptin, vascular endothelial growth factor (VEGF), phosphatidylinositol 3 kinase (PI3K), and the mammalian target of rapamycin (mTOR), and may ultimately affect tumor proliferation rate and apoptosis. Experiments in humans however have been limited. Our multidisciplinary research team comprised of nutrition, exercise and basic scientists, biostatisticians, and clinicians seeks to conduct a pilot/feasibility study among 40 overweight or obese men newly diagnosed with prostate cancer who are scheduled for prostatectomy. This study will capitalize on our experience of using the presurgical period to explore the potential impact of weight loss via a healthy energy-restricted diet and increased physical activity (PA) on circulating hormones, cytokines, and growth factors, as well as effects on tumor biology and other clinical outcomes. Consenting patients will be block randomized to 1-of-2 study arms: 1) a healthful diet + exercise intervention to promote a weight loss of up to 2 pounds/week; or 2) a wait-list control who will receive the intervention once the study period is complete. This study will explore and contrast changes in body mass index (BMI) observed over the 10-week study period in the intervention vs. wait-list control arms, and also monitor changes in body composition, energy intake and PA; these changes will be studied in relation to the following endpoints: a) changes in select circulating biomarkers and gene expression related to cancer progression, hormonal status, inflammation and other energy-related factors; b) rates of tumor proliferation and apoptosis; c) tumor immunohistochemical markers of insulin receptor, VEGF, AKT, and NFkB; and d) functional and health-related outcomes, i.e., side-effects and medical outcomes , quality of life (QoL), and functional status. Such data are foundational and may ultimately lead to novel complementary therapies in this patient population. PUBLIC HEALTH RELEVANCE: Prostate cancer is the leading cancer among US males and is the 2nd leading cause of cancer-related death. This project will explore the feasibility of a weigh loss intervention among overweight and obese prostate cancer patients as a complementary treatment during the presurgical period, and will explore the intervention effect on serum biomarkers, tumor characteristics and clinical outcomes.