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（由适用提供）：较高的复发疾病率是促进结肠癌（CC）生存的健康和寿命的关键障碍。减少这种障碍的一种方法是制定干预措施，以最大程度地减少CC生存可以自主完成的复发，例如生活方式和行为改变。观察性流行病学数据表明，诊断为CC后的体育活动可将癌症复发的风险降低40％，CC特异性死亡率降低了45-71％，全因死亡率降低了57-63％。但是，该关联的潜在生物学途径仍然没有表征。过量的内脏脂肪组织（VAT）和高胰岛素血症在CC存活中复发和转移性疾病的发展中起关键作用。增值税是无疾病生存，CC特异性死亡率和CC幸存中全因死亡率的独立预测指标。增值税是代谢活跃的，贷款是高胰岛素血症的发展。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主动性和进展的催化剂。减少增值税和胰岛素可能会优先改变发展复发和转移性疾病的风险，并改善CC生存期的质量和寿命。有氧运动可在非糖尿病患者中以剂量反应方式减少增值税和胰岛素。然而，运动对CC存活中的剂量反应对增值税和胰岛素的剂量反应效应尚未得到特征。为了解决这一知识差距，我们将利用II期，随机，六个月的剂量反应运动试验（勇气试验； R21 CA182767）的开始，该试验将比较150分钟。WK-1或300分钟。WK-1或300分钟。WK-1中等强度的有氧运动运动组与39 cc Survivals之间的候补控制组中的中等强度有氧运动组。我们将通过添加创新且最近验证的双能X射线绝对能量方法来量化增值税，并使用现有的血液样本来量化禁食胰岛素来利用这项试验。该试验的主要目的是量化和描述现代强度有氧运动对增值税和禁食胰岛素的剂量反应效应。我们将探讨增值税改进与禁食胰岛素改善之间的相关性。通过这些测量为勇气试验，为勇气试验提供了一个独特的机会，可以全面了解运动对生物标志物（例如增值税和胰岛素）的剂量反应影响，例如CC结果中实现的。这种研究经验与一系列教学课程以及包括癌症流行病学，护士科学和癌症生物学在内的跨切割主题。这项研究的目的与NCI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的预后和预后生物标志物。