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

描述（由申请人提供）：探索前列腺癌患者负能量平衡的影响前列腺癌是美国男性的主要癌症，每年导致超过3.3万男性死亡。美国南部的死亡率特别高，肥胖在那里很普遍。肥胖和超重与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起主要作用。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抑制几种驱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）和哺乳动物雷帕霉素靶点（mTOR），最终可能影响肿瘤增殖率和细胞凋亡。然而，在人类身上的实验有限。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名超重或肥胖的新诊断为前列腺癌并计划进行前列腺切除术的男性进行试点/可行性研究。本研究将利用我们在手术前的经验，探索通过健康的能量限制饮食和增加身体活动（PA）来减轻体重对循环激素、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组到1 / 2研究组：1)健康饮食+运动干预，以促进体重减轻2磅/周；或者2)在研究期结束后接受干预的候补对照者。本研究将探索和对比干预组与等候名单对照组在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、能量摄入和PA的变化；这些变化将与以下终点相关：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)肿瘤增殖和凋亡率；c)胰岛素受体、VEGF、AKT、NFkB的肿瘤免疫组化标志物；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。这些数据是基础的，可能最终导致新的补充疗法在这一患者群体。

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.