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.

项目摘要/摘要 全身性炎症与结肠癌的癌症复发和死亡率更高有关 患者。全身性炎症促进了现有微焦点酶的生长和发展和 开发新的遥远转移。减少系统性炎症可能会降低发展的风险 结肠癌患者的复发和转移性疾病。流行病学数据表明物理 结肠癌诊断后的活性将复发和死亡率的风险降低了50％。体育锻炼 具有有效的抗炎特性。但是，体育锻炼可以正常化的程度 主机微环境通过中断炎症与生长和进展之间的串扰 现有的微焦点和新的遥远转移的发展尚不清楚。我们假设 该体育活动介导炎症与癌症复发与死亡率之间的关系。目的 1将确定体育活动是否介导血浆炎症标记与癌症之间的关系 结肠癌患者的复发和死亡率。为了完成此目标，我们将利用来自 最近在2,526例结肠癌患者中完成了NCI赞助的试验。 AIM 2将决定初步 两种不同剂量运动的效应大小估计值，以减少结肠的血浆炎症标记 癌症患者。为了完成此目标，我们将利用来自最近完成的NCI赞助的II期的数据 试验将39例结肠癌患者随机分为低剂量（150分钟/周）或高剂量（300分钟/周）中等 强度有氧运动或六个月的通常护理控制组。目标1和2的结果将指导 AIM 3的设计和实施将决定锻炼的功效减少血浆 结肠癌患者的炎症标记。为了完成这一目标，我们将进行充分的 结肠癌患者中的前瞻性随机试验。该研究和培训计划将：1） 提供所需的先进跨学科培训，以加速流行病学的翻译 发现有效的个人和人口水平干预措施； 2）将申请人放置为 能源平衡和癌症成果研究领域的国际领导者，以及； 3）验证a 翻译平台可以在其上检查其他生物学途径，以通过未来的研究来资助 项目赠款计划（R01）。了解身体活动可能会改变炎症为有利 影响结肠癌患者的疾病结局，对结肠癌生物学和 通过优化治疗策略并确定其他 治疗靶标。这项研究与NCI关键优先区域一致，以通过 哪些运动可能会影响癌症的结果，以优化运动处方的目的 最大化患者的预后。