Inflammation, Physical Activity, and Colon Cancer Recurrence and Survival

炎症、体力活动与结肠癌复发和生存

• 批准号: 9366924
• 负责人: Justin C Brown
• 金额: $ 12.04万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9366924
• 关键词: Aerobic Exercise; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Area; Award; Behavior Therapy; Behavioral Sciences; Biological Assay; Biometry; Blood specimen; Cancer Biology; Cancer and Leukemia Group B; Catalogs; Clinical; Colon Carcinoma; Control Groups; Data; Data Set; Development; Diagnosis; Dietary Practices; Disease; Disease Outcome; Distant Metastasis; Dose; Epidemiology; Exercise; Foundations; Funding; Goals; Growth; Growth Factor; Health Services Research; High-Risk Cancer; Human; Individual; Inflammation; Interleukin-6; International; Interruption; Intervention; Malignant Neoplasms; Mediating; Mediator of activation protein; Metabolic; Molecular; National Cancer Institute; Neoplasm Metastasis; Obesity; Operative Surgical Procedures; Outcome; Outcomes Research; Pathologic; Pathway interactions; Patient-Focused Outcomes; Patients; Performance Status; Physical activity; Physical assessment; Plasma; Population; Positioning Attribute; Postoperative Period; Program Research Project Grants; Property; Randomized Controlled Trials; Recurrence; Research; Research Training; Residual state; Risk; Risk Factors; Series; Testing; Training; Transducers; Translations; United States; United States National Institutes of Health; cancer recurrence; cancer risk; cancer survival; cancer therapy; career; clinical care; colon cancer patients; design; energy balance; epidemiologic data; exercise prescription; experience; follow-up; immune function; inflammatory marker; insight; mortality; phase II trial; pilot trial; pre-clinical; prospective; randomized trial; response; therapeutic target; treatment as usual; treatment effect; treatment strategy; trial design

PROJECT SUMMARY/ABSTRACT Systemic inflammation is associated with a higher risk of cancer recurrence and mortality among colon cancer patients. Systemic inflammation promotes the growth and progression of existing micro-metastases and the development of new distant metastases. Reducing systemic inflammation may decrease the risk of developing recurrent and metastatic disease among colon cancer patients. Epidemiologic data suggests that physical activity after diagnosis of colon cancer reduces the risk of recurrence and mortality by 50%. Physical activity possesses potent anti-inflammatory properties. However, the extent to which physical activity can normalize the host microenvironment by interrupting the crosstalk between inflammation and the growth and progression of existing micro-metastases and the development of new distant metastases is not known. We hypothesize that physical activity mediates the relationship between inflammation and cancer recurrence and mortality. Aim 1 will determine if physical activity mediates the relationship between plasma inflammatory markers and cancer recurrence and mortality among colon cancer patients. To complete this aim, we will utilize data from a recently-completed NCI-sponsored trial among 2,526 colon cancer patients. Aim 2 will determine preliminary effect size estimates for two distinct doses of exercise to reduce plasma inflammatory markers among colon cancer patients. To complete this aim, we will utilize data from a recently-completed NCI-sponsored phase II trial that randomized 39 colon cancer patients to low-dose (150 min/wk) or high-dose (300 min/wk) moderate- intensity aerobic exercise or a usual care control group for six-months. The results from Aims 1 and 2 will guide the design and implementation of Aim 3, which will determine the efficacy of exercise to reduce plasma inflammatory markers among colon cancer patients. To complete this aim, we will conduct an adequately- powered prospective randomized trial among colon cancer patients. This research and training plan will: 1) provide the advanced transdisciplinary training necessary to accelerate the translation of epidemiologic discoveries into efficacious individual and population level interventions; 2) position the applicant to emerge as an international leader in the field of energy balance and cancer outcomes research, and; 3) validate a translational platform on which to examine other biologic pathways to be funded through future research project grant programs (R01s). Understanding how physical activity may alter inflammation to favorably influence disease outcomes among colon cancer patients offers unique insight into colon cancer biology and provides new paradigms in cancer therapy by optimizing treatment strategies and identifying additional therapeutic targets. This research aligns with an NCI key priority area to elucidate the molecular basis through which exercise may influence cancer outcomes, towards the goal of optimizing exercise prescription to maximize patient outcomes.

项目概要/摘要 全身炎症与结肠癌中癌症复发和死亡率较高的风险相关 患者。全身炎症促进现有微转移的生长和进展， 新的远处转移的发展。减少全身炎症可能会降低患上这种疾病的风险 结肠癌患者的复发和转移性疾病。流行病学数据表明，身体 结肠癌诊断后的活动可将复发和死亡的风险降低 50%。体力活动 具有有效的抗炎特性。然而，身体活动可以恢复正常的程度 通过中断炎症与生长和进展之间的串扰来调节宿主微环境 现有的微转移和新的远处转移的发展尚不清楚。我们假设 体力活动调节炎症与癌症复发和死亡率之间的关系。目的 1 将确定体力活动是否介导血浆炎症标志物与癌症之间的关系 结肠癌患者的复发和死亡率。为了实现这一目标，我们将利用来自 最近完成了 NCI 资助的一项针对 2,526 名结肠癌患者的试验。目标2将确定初步 两种不同剂量的运动减少结肠血浆炎症标志物的效应大小估计 癌症患者。为了实现这一目标，我们将利用最近完成的 NCI 赞助的第二阶段的数据 将 39 名结肠癌患者随机分为低剂量（150 分钟/周）或高剂量（300 分钟/周）的试验 强度有氧运动或常规护理对照组为期六个月。目标 1 和 2 的结果将指导 目标 3 的设计和实施，将决定运动降低血浆的功效 结肠癌患者的炎症标志物。为了实现这一目标，我们将进行充分的—— 为结肠癌患者进行前瞻性随机试验。该研究和培训计划将：1) 提供加速流行病学转化所需的高级跨学科培训 发现有效的个人和群体干预措施； 2) 使申请人成为 能量平衡和癌症结果研究领域的国际领导者； 3）验证 转化平台，用于检查通过未来研究资助的其他生物途径 项目资助计划（R01s）。了解身体活动如何有利地改变炎症 影响结肠癌患者的疾病结果提供了对结肠癌生物学的独特见解 通过优化治疗策略和确定其他方法，为癌症治疗提供了新的范例 治疗目标。这项研究与 NCI 的关键优先领域相一致，通过以下方式阐明分子基础： 哪些运动可能会影响癌症结果，以达到优化运动处方的目标 最大限度地提高患者治疗效果。