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

描述（由申请人提供）：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中的主要癌症，每年导致超过33000名男性死亡。美国南部的死亡率特别高，那里的肥胖症是一种流行病。肥胖和超重与侵袭性疾病的风险有关，能量平衡可能在前列腺癌进展中起主要作用。临床前研究表明，热量限制和增加体力活动导致的负能量平衡可能会抑制几种驱动肿瘤生长的激素和炎症因子，例如，瘦素、血管内皮生长因子（VEGF）、磷脂酰肌醇3激酶（PI 3 K）和雷帕霉素的哺乳动物靶蛋白（mTOR），并且可能最终影响肿瘤增殖速率和凋亡。然而，在人类身上的实验是有限的。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，旨在对40名新诊断为前列腺癌的超重或肥胖男性进行试点/可行性研究，他们计划进行前列腺切除术。这项研究将利用我们在术前阶段的经验，探索通过健康的能量限制饮食和增加体力活动（PA）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局的影响。接受治疗的患者将被区组随机分配至2个研究组中的1个：1）健康饮食+运动干预，以促进体重减轻至2磅/周;或2）等待名单对照，一旦研究期结束，将接受干预。本研究将探索并对比10周研究期间在干预组与等待名单对照组中观察到的体重指数（BMI）变化，并监测身体成分、能量摄入和PA的变化;将研究这些变化与以下终点的关系：a）与癌症进展、激素状态、炎症和其他能量相关因素相关的选定循环生物标志物和基因表达的变化; b）肿瘤增殖和凋亡的速率; c）胰岛素受体、VEGF、AKT和NF κ B的肿瘤免疫组织化学标志物;和d）功能和健康相关结果，即，副作用和医疗结果、生活质量（QoL）和功能状态。这些数据是基础性的，并可能最终导致该患者人群的新的补充疗法。

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.