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）：扩展体育活动行为改变研究以包括与健康和福祉有关的结果，评估体育活动增加是否足以改善健康。此外，很少有研究检查参加身体活动行为改变干预措施后癌症幸存者的细胞因子变化，其机械重点是细胞因子，这可能会影响肌肉强度，疲劳和对干预措施的睡眠反应。因此，提出了一项具有以下研究目的的随机对照试验：研究目标1：将与对照组进行比较，以检查参加身体活动行为改变干预之前和之后的体育活动，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，干预组将表明肌肉强度的增加以及疲劳和睡眠功能障碍的降低。根据试点数据，我们进一步假设，根据评估的维度，疲劳和睡眠功能障碍的变化将有所不同（例如，干预的改进可能是“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睡眠延迟的最大程度的最大程度）。研究目的2：研究可能是身体活动行为改变干预对肌肉力量，疲劳和睡眠的影响的机制，我们将在炎症的细胞因子标记物变化方面将干预组与对照组进行比较，并评估这种变化是否与肌肉强度的变化并介导肌肉强度，疲劳，疲劳，和睡眠不足。我们将测量的细胞因子是根据对运动训练，疲劳和睡眠功能障碍的肌肉力量反应的关联而选择的，以及我们在试验测试期间检测这些细胞因子的能力。肿瘤坏死因子（TNF）-1，白介素（IL）-6，IL-8和IL-10将在血清中测量。根据初步数据和文献综述，我们假设干预将增加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，但我们推测它将由于IL-10和促炎性细胞因子（例如TNF）之间的反馈回路而降低。我们还假设这些细胞因子的变化至少部分地介导了干预对测得的健康结果的影响。七十四名女性，乳腺癌幸存者将被随机分配。措施包括体育锻炼（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）以及血清细胞因子水平（Luminex（R）多重技术）。将评估潜在的协变量。将对Freedman-Schatzkin差异差异测试进行混合模型方差分析和调解分析。该R21提案将提出为生物行为干预益处的基础的机械理论，并为设计这些理论机制所需的足够动力的R01试验提供了所需的效果信息。 公共卫生相关性：确认参加身体活动行为改变干预后，乳腺癌幸存者经历的健康益处很重要。这些好处可能包括提高力量，减少疲倦和更好的睡眠。同样，很少有科学家研究乳腺癌幸存者中的炎症如何影响体育活动对这些益处的影响。这样的信息有可能更好地理解体育活动为何有益，并增强了帮助改善身体功能并减轻乳腺癌幸存者中的麻烦症状（例如疲劳，睡眠不良）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.

• DOI: 10.1002/pon.3594
• 发表时间: 2015-03
• 期刊: PSYCHO-ONCOLOGY
• 影响因子: 3.6
• 作者: Rogers, Laura Q.;Fogleman, Amanda;Trammell, Rita;Hopkins-Price, Patricia;Spenner, Allison;Vicari, Sandra;Rao, Krishna;Courneya, Kerry S.;Hoelzer, Karen;Robbs, Randall;Verhulst, Steven
• 通讯作者: Verhulst, Steven