Inflammation, Physical Activity, and Colon Cancer Recurrence and Survival

项目摘要/摘要 结肠癌患者全身炎症与癌症复发和死亡率的高风险相关 病人。全身性炎症促进现有微转移瘤的生长和进展 新的远处转移的发展。减少全身炎症可能会降低发病风险 结肠癌患者的复发和转移性疾病。流行病学数据表明，身体上 结肠癌确诊后的活动可将复发和死亡率降低50%。体力活动 具有强大的抗炎特性。然而，体力活动可以正常化的程度 通过阻断炎症与生长发育之间的串扰而影响宿主微环境 现有的微转移和新的远处转移的发展情况尚不清楚。我们假设 体力活动在炎症与癌症复发和死亡率之间的关系中起中介作用。目标 1将确定体育活动是否在血浆炎症标志物和癌症之间的关系中起中介作用 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 最近完成的由NCI赞助的针对2526名结肠癌患者的试验。目标2将初步确定 两种不同剂量运动降低结肠炎性标志物的效果大小估计 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)中剂量组。 强度有氧运动或常规护理对照组，为期6个月。目标1和目标2的结果将指导 目标3的设计和实施，它将决定运动降低血浆的效果 结肠癌患者的炎性标志物。为达致这个目标，我们会进行适当的- 在结肠癌患者中进行的动力性前瞻性随机试验。这项研究和培训计划将：1) 提供必要的高级跨学科培训，以加快流行病学的转化 发现有效的个人和人口层面的干预措施；2)使申请者成为 能量平衡和癌症结果研究领域的国际领先者，以及；3)验证 用于研究未来研究资助的其他生物途径的翻译平台 项目资助计划(R01)。了解体育活动如何将炎症改变为有利的 影响结肠癌患者的疾病结局提供了对结肠癌生物学和 通过优化治疗策略和确定更多 治疗靶点。这项研究与NCI的一个关键优先领域相一致，通过 哪些运动可能会影响癌症的预后，朝着优化运动处方的目标前进 最大限度地提高患者的疗效。

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.