Inflammation, Physical Activity, and Colon Cancer Recurrence and Survival

项目总结/摘要 全身炎症与结肠癌中较高的癌症复发风险和死亡率相关 患者全身性炎症促进现有微转移瘤的生长和进展， 发生新的远处转移。减少全身性炎症可能会降低发生 结肠癌患者的复发和转移性疾病。流行病学数据表明， 结肠癌诊断后的活动可将复发和死亡的风险降低50%。身体活动 具有有效的抗炎特性。然而，身体活动可以正常化的程度 通过阻断炎症与生长和进展之间的相互作用， 现有的微转移和新的远处转移的发展是未知的。我们假设 身体活动介导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和癌症之间的关系 结肠癌患者的复发率和死亡率。为了实现这一目标，我们将利用来自 最近完成的一项在2,526名结肠癌患者中进行的NCI赞助的试验。目标2将确定初步 两种不同运动剂量降低结肠炎性标志物的效应量估计 癌症患者。为了完成这一目标，我们将利用最近完成的NCI赞助的第二阶段的数据 试验将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）中- 高强度有氧运动组或常规护理对照组进行为期6个月的研究。目标1和2的结果将指导 目标3的设计和实施，这将确定运动降低血浆 结肠癌患者的炎症标志物。为了达到这个目的，我们会进行一个充分的- 在结肠癌患者中进行的前瞻性随机试验。本研究和培训计划将：1） 提供必要的先进的跨学科培训，以加快流行病学的翻译 有效的个人和群体水平干预措施的发现; 2）将申请人定位为 能量平衡和癌症结果研究领域的国际领导者; 3）验证 翻译平台，在此平台上研究通过未来研究资助的其他生物途径 项目赠款方案（R 01）。了解身体活动如何改变炎症， 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额外的治疗方案， 治疗目标这项研究与NCI的一个关键优先领域保持一致，通过以下方式阐明分子基础： 运动可能会影响癌症的结果，朝着优化运动处方的目标， 最大限度地提高患者疗效。

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.