Physical activity benefits after breast cancer: exploring cytokine mechanisms

描述（由申请人提供）：扩展体力活动行为改变研究，以包括与健康和福祉相关的结果，评估体力活动的增加是否足以改善健康状况。此外，很少有研究检查癌症幸存者参与身体活动行为改变干预后细胞因子的变化，其机制重点是可能影响肌肉力量，疲劳和睡眠对干预的反应的细胞因子。因此，提出了一项随机对照试验，其研究目的如下：研究目的1：将干预组与对照组进行比较，以检查参与体力活动行为改变干预前后的体力活动、肌肉力量、疲劳和睡眠功能障碍的变化。我们假设，与对照组相比，干预组将表现出肌肉力量的增加和疲劳和睡眠功能障碍的减少。基于试点数据，我们进一步假设疲劳和睡眠功能障碍的变化将根据评估的维度而变化（例如，对于“过去一周的平均疲劳”、自我报告的睡眠效率和加速度计测量的睡眠潜伏期的维度，干预的改善可能是最大的）。研究目的二：为了研究身体活动行为改变干预对肌肉力量、疲劳和睡眠影响的机制，我们将比较干预组与对照组炎症细胞因子标志物的变化，并评估这些变化是否与肌肉力量、疲劳和睡眠功能障碍的变化一致，是否可能介导这些变化。我们将测量的细胞因子是基于它们与运动训练、疲劳和睡眠功能障碍的肌肉力量反应的关联以及我们在试点测试期间检测这些细胞因子的能力来选择的。将测量血清中的肿瘤坏死因子（TNF）-1、白细胞介素（IL）-6、IL-8和IL-10。基于初步数据和文献综述，我们假设干预将增加IL-6，降低IL-8，TNF-1和IL-10。虽然IL-10是一种抗炎细胞因子，但我们推测，由于IL-10和促炎细胞因子（如TNF）之间的反馈回路，IL-10将减少。我们还假设，这些细胞因子的变化将介导，至少部分地，对测量的健康结果的干预效果。将对74例女性乳腺癌幸存者进行随机分组。测量包括身体活动（加速度计和自我报告）、肌肉力量、疲劳、睡眠（加速度计和自我报告）和血清细胞因子水平（Luminex（r）多重技术）。将评估潜在协变量。将使用Freedman-Schatzkin系数差异检验进行混合模型ANOVA和中介分析。该R21提案将提出生物行为干预益处的机制理论，并为设计充分把握度的R 01试验提供所需的效应量信息，以测试这些理论机制。 公共卫生相关性：重要的是要确认乳腺癌幸存者在参与身体活动行为改变干预后所经历的健康益处。这些好处可能包括改善力量，减少疲劳和更好的睡眠。此外，很少有科学家研究乳腺癌幸存者的炎症如何影响体育活动对这些益处的影响。这些信息有可能导致更好地理解为什么身体活动是有益的，并加强帮助改善身体功能和减少令人烦恼的症状的方法（例如，疲劳、睡眠不佳）。

DESCRIPTION (provided by applicant): Extending physical activity behavior change studies to include outcomes related to health and well-being assess whether the physical activity increases are adequate for improved health. Moreover, few studies have examined cytokine changes in cancer survivors after participation in a physical activity behavior change intervention with a mechanistic focus on cytokines which may influence the muscle strength, fatigue, and sleep response to the intervention. Therefore, a randomized controlled trial with the following study aims is proposed: Study aim 1: The intervention group will be compared with the control group to examine the change in physical activity, muscle strength, fatigue, and sleep dysfunction before and after participation in a physical activity behavior change intervention. We hypothesize that as compared with the control group, the intervention group will demonstrate an increase in muscle strength and a decrease in fatigue and sleep dysfunction. Based on pilot data, we further hypothesize that the change in fatigue and sleep dysfunction will vary based on dimension assessed (e.g., improvements with the intervention may be greatest for the dimensions of "average fatigue over the past week", self-reported sleep efficiency, and accelerometer measured sleep latency). Study aim 2: To investigate mechanisms that may underlie the effects of the physical activity behavior change intervention on muscle strength, fatigue, and sleep, we will compare the intervention group with the control group in terms of changes in cytokine markers of inflammation and evaluate whether such changes are consistent with and may mediate changes in muscle strength, fatigue, and sleep dysfunction. The cytokines we will measure were selected based on their associations with muscle strength response to exercise training, fatigue, and sleep dysfunction and our ability to detect these cytokines during pilot testing. Tumor necrosis factor (TNF)-1, interleukin (IL)-6, IL-8, and IL-10 will be measured in serum. Based on preliminary data and literature review, we hypothesize that the intervention will increase IL-6 and reduce IL-8, TNF-1, and IL-10. Although IL-10 is an anti-inflammatory cytokine, we speculate that it will be reduced due to the feedback loop between IL-10 and pro-inflammatory cytokines such as TNF. We also hypothesize that changes in these cytokines will mediate, at least in part, the intervention effects on the measured health outcomes. Seventy-four female, breast cancer survivors will be randomized. Measures include physical activity (accelerometer and self-report), muscle strength, fatigue, sleep (accelerometer and self-report), and serum cytokine levels (Luminex(r) multiplex technology). Potential covariates will be assessed. Mixed model ANOVA and mediation analyses with the Freedman-Schatzkin difference-in-coefficients test will be performed. This R21 proposal will suggest mechanistic theories underlying the benefits of biobehavioral interventions and provide the required effect size information for designing the adequately powered R01 trials required to test these theoretical mechanisms. PUBLIC HEALTH RELEVANCE: It is important to confirm health benefits experienced by breast cancer survivors after participation in a physical activity behavior change intervention. Such benefits may include improved strength, less tiredness, and better sleep. Also, few scientists have studied how inflammation in breast cancer survivors may influence the effect of physical activity on these benefits. Such information has the potential to lead to a better understanding of why physical activity is beneficial and enhance ways to help improve physical functioning and reduce bothersome symptoms (e.g., fatigue, poor sleep) in breast cancer survivors.