Effects of Exercise on Visceral Adiposity & Hyperinsulinemia in Colon Cancer Survivor

运动对内脏肥胖的影响

• 批准号: 8835980
• 负责人: Justin C Brown
• 金额: $ 4.31万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-06 至 2017-03-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8835980
• 关键词: Address; Adipose tissue; Adjuvant Chemotherapy; Aerobic Exercise; Attenuated; Award; Behavior Therapy; Biological; Biological Markers; Blood specimen; Cancer Biology; Cancer Prognosis; Cancer Survivor; Cancer Survivorship; Charge; Clinical Research; Clinical Trials; Colon Carcinoma; Control Groups; Coupled; Development; Diagnosis; Disease; Disease-Free Survival; Doctor of Philosophy; Dose; Epidemiology Nursing; Excision; Exercise; Fasting; Funding; Glean; Growth; Health; Hyperinsulinism; Insulin; Intervention; Knowledge; Life Style; Longevity; Malignant Neoplasms; Measurement; Measures; Mentors; Metastatic/Recurrent; Methodology; Methods; Molecular; Nature; Obesity; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Pennsylvania; Persons; Phase; Physical activity; Play; Positioning Attribute; Prognostic Marker; Progressive Disease; Randomized; Recurrence; Recurrent disease; Regional Disease; Research; Research Personnel; Research Project Grants; Risk; Role; Scanning; Science; Site; Students; Survival Rate; Translating; Translational Research; United States; United States National Institutes of Health; Universities; Visceral; Waiting Lists; X-Ray Computed Tomography; base; cancer cell; cancer epidemiology; cancer recurrence; catalyst; clinical epidemiology; cohort; epidemiologic data; experience; improved; innovation; lifestyle intervention; lymph nodes; mortality; non-diabetic; novel; nutrition; public health relevance; response

DESCRIPTION (provided by applicant): The high rate of recurrent disease is a critical barrier to promote the health and longevity of colon cancer (CC) survivors. An approach to reduce this barrier is to develop interventions to minimize recurrence that CC survivors can accomplish autonomously, such as lifestyle and behavioral modification. Observational epidemiologic data suggest physical activity after diagnosis of CC reduces the risk of cancer recurrence by 40%, CC-specific mortality by 45-71%, and all-cause mortality by 57-63%. However, the underlying biological pathway of this association remains uncharacterized. Excess visceral adipose tissue (VAT) and hyperinsulinemia play a pivotal role in the development of recurrent and metastatic disease among CC survivors. VAT is an independent predictor of disease-free survival, CC-specific mortality, and all-cause mortality among CC survivors. VAT is metabolically active and lends rise to the development of hyperinsulinemia. Insulin stimulates the growth and proliferation of CC cells, acting as a catalyst to promote the initiation and progression of recurrent and metastatic disease. Reducing VAT and insulin may favorably alter the risk of developing recurrent and metastatic disease, and improve the quality and longevity of CC survivorship. Aerobic exercise reduces VAT and insulin in dose-response fashion among non-diabetic persons with obesity. However, the dose-response effects of exercise on VAT and insulin have not been characterized specifically among CC survivors. To address this knowledge gap, we will leverage the commencement of a phase II, randomized, six-month, dose-response exercise trial (The COURAGE Trial; R21 CA182767) that will compare 150 min�wk-1 or 300 min�wk-1 of moderate-intensity aerobic exercise to a wait-list control group among 39 CC survivors. We will harness this trial by adding an innovative and recently-validated dual energy x-ray absorptiometry-based methodology to quantify VAT, and use existing blood samples to quantify fasting insulin. The primary aims of this trial are to quantify and describe the dose response effects of moderate-intensity aerobic exercise on VAT and fasting insulin. We will explore the correlation between improvements in VAT and improvements in fasting insulin. Equipping the COURAGE trial with these measurements provides a unique opportunity to glean complementary knowledge about the dose-response effects of exercise on biomarkers, such as VAT and insulin, which are implicated in CC outcomes. This research experience is coupled with a set of didactic courses with cross-cutting themes that include cancer epidemiology, nursing science, and cancer biology. The aims of this research are consistent with NCI provocative question PQA-2, which seeks to elucidate how varying doses of exercise influence cancer prognosis and prognostic biomarkers.

描述（由申请人提供）：高复发率是促进结肠癌（CC）幸存者健康和长寿的关键障碍。减少这一障碍的方法是制定干预措施，以尽量减少 CC 幸存者可以自主完成的复发，例如生活方式和行为改变。观察流行病学数据表明，诊断 CC 后进行体力活动可降低癌症复发风险 40%，CC 特异性死亡率降低 45-71%，全因死亡率降低 57-63%。然而，这种关联的潜在生物学途径仍然未知。过多的内脏脂肪组织 (VAT) 和高胰岛素血症在 CC 幸存者复发和转移性疾病的发展中发挥着关键作用。 VAT 是 CC 幸存者中无病生存率、CC 特异性死亡率和全因死亡率的独立预测因子。 VAT 具有代谢活性，会导致高胰岛素血症的发生。胰岛素刺激 CC 细胞的生长和增殖，充当促进复发和转移性疾病的发生和进展的催化剂。减少增值税和胰岛素可能会有利地改变发生复发和转移性疾病的风险，并提高 CC 生存的质量和寿命。有氧运动以剂量反应方式降低非糖尿病肥胖者的增值税和胰岛素。然而，运动对增值税和胰岛素的剂量反应效应尚未在 CC 幸存者中得到具体表征。为了解决这一知识差距，我们将利用 II 期、随机、为期 6 个月的剂量反应运动试验（The COURAGE 试验；R21 CA182767）的启动，该试验将在 39 名 CC 幸存者中将每周 150 分钟或每周 300 分钟的中等强度有氧运动与等待名单上的对照组进行比较。我们将通过添加一种基于双能 X 射线吸收测定法的创新方法来量化增值税，并使用现有的血液样本来量化空腹胰岛素，从而利用这项试验。该试验的主要目的是量化和描述中等强度有氧运动对增值税和空腹胰岛素的剂量反应影响。我们将探讨增值税改善与空腹胰岛素改善之间的相关性。为 COURAGE 试验配备这些测量数据提供了一个独特的机会，可以收集有关运动对生物标志物（例如增值税和胰岛素）的剂量反应影响的补充知识，这些生物标志物与 CC 结果有关。这种研究经验与一系列跨领域主题的教学课程相结合，包括癌症流行病学、护理科学和癌症生物学。这项研究的目的与 NCI 的挑衅性问题 PQA-2 一致，该问题旨在阐明不同剂量的运动如何影响癌症预后和预后生物标志物。