Physical activity benefits after breast cancer: exploring cytokine mechanisms

乳腺癌后体力活动的益处：探索细胞因子机制

• 批准号: 8034379
• 负责人: LAURA Q ROGERS
• 金额: $ 15.35万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2012-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034379
• 关键词: Adverse effects; Aftercare; Anti-Inflammatory Agents; Anti-inflammatory; Behavior; Biological Markers; Breast Cancer Treatment; Cancer Survivor; Chronic Disease; Control Groups; Data; Dimensions; Disease; Effectiveness; Exercise; Fatigue; Feedback; Female Breast Carcinoma; Functional disorder; Health; Health Benefit; Immune; Inflammation; Inflammatory; Interleukin-10; Interleukin-6; Interleukin-8; Intervention; Lead; Measures; Mediating; Mediation; Modeling; Nature; Outcome; Outcome Study; Patient Self-Report; Patients; Pattern; Personal Satisfaction; Physical Function; Physical activity; Physiological; Population; Quality of life; Randomized; Randomized Controlled Trials; Reporting; Research Design; Review Literature; Role; Scientist; Serum; Sleep; Symptoms; Technology; Testing; Training; Tumor Necrosis Factor-alpha; Validation; base; behavior change; biobehavior; breast cancer diagnosis; cytokine; design; experience; group intervention; improved; inflammatory marker; insight; intervention effect; malignant breast neoplasm; mortality; muscle strength; psychologic; public health relevance; response; strength training; theories

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.

描述（由申请人提供）：扩展身体活动行为改变研究，纳入与健康和福祉相关的结果，评估身体活动的增加是否足以改善健康。此外，很少有研究检查癌症幸存者参与体力活动行为改变干预后细胞因子的变化，重点关注可能影响肌肉力量、疲劳和睡眠对干预反应的细胞因子。因此，提出一项具有以下研究目的的随机对照试验： 研究目的一：将干预组与对照组进行比较，考察参与干预前后体力活动、肌力、疲劳、睡眠障碍等方面的变化。体力活动行为改变干预。我们假设与对照组相比，干预组将表现出肌肉力量的增加以及疲劳和睡眠功能障碍的减少。根据试点数据，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有所不同（例如，干预的改善可能对于“过去一周的平均疲劳”、自我报告的睡眠效率等维度而言最大） ，以及加速度计测量的睡眠潜伏期）。研究目标2：为了探讨体力活动行为改变干预对肌肉力量、疲劳和睡眠的影响可能的机制，我们将比较干预组与对照组炎症细胞因子标志物的变化，并评估是否这些变化与肌肉力量、疲劳和睡眠功能障碍一致，并可能介导这些变化。我们将测量的细胞因子是根据它们与运动训练、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。根据初步数据和文献综述，我们假设干预措施将增加 IL-6 并减少 IL-8、TNF-1 和 IL-10。尽管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（例如TNF）之间的反馈回路，它会被减少。我们还假设这些细胞因子的变化将至少部分地介导对测量的健康结果的干预效果。七十四名女性乳腺癌幸存者将被随机分组​​。测量包括体力活动（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）。将评估潜在的协变量。将使用 Freedman-Schatzkin 系数差异检验进行混合模型方差分析和中介分析。该 R21 提案将提出生物行为干预益处背后的机制理论，并提供所需的效应大小信息，以设计测试这些理论机制所需的充分动力的 R01 试验。 公共卫生相关性：确认乳腺癌幸存者在参与体育活动行为改变干预后所经历的健康益处非常重要。这些好处可能包括增强体力、减少疲劳和改善睡眠。此外，很少有科学家研究乳腺癌幸存者的炎症如何影响体力活动对这些益处的影响。这些信息有可能使人们更好地理解为什么身体活动是有益的，并增强帮助乳腺癌幸存者改善身体机能和减少令人烦恼的症状（例如疲劳、睡眠质量差）的方法。

项目成果

Inflammation and psychosocial factors mediate exercise effects on sleep quality in breast cancer survivors: pilot randomized controlled trial.

炎症和心理社会因素介导运动对乳腺癌幸存者睡眠质量的影响：试点随机对照试验。

• 发表时间: 2015-03
• 影响因子: 3.6
• 作者: Rogers, Laura Q;Fogleman, Amanda;Trammell, Rita;Hopkins;Spenner, Allison;Vicari, Sandra;Rao, Krishna;Courneya, Kerry S;Hoelzer, Karen;Robbs, Randall;Verhulst, Steven
• 通讯作者: Verhulst, Steven

Biobehavioral factors mediate exercise effects on fatigue in breast cancer survivors.

生物行为因素介导运动对乳腺癌幸存者疲劳的影响。

• 发表时间: 2014-06
• 影响因子: 4.1
• 作者: Rogers, Laura Q;Vicari, Sandra;Trammell, Rita;Hopkins;Fogleman, Amanda;Spenner, Allison;Rao, Krishna;Courneya, Kerry S;Hoelzer, Karen S;Robbs, Randall;Verhulst, Steven
• 通讯作者: Verhulst, Steven