The Effects of Chemotherapy on Sleep

 描述(申请人提供)：睡眠障碍是乳腺癌患者化疗最常见且可能有害的长期副作用之一。大多数接受化疗的患者报告有急性睡眠障碍，多达60%的幸存者继续发展为慢性睡眠障碍，在治疗后可持续十多年。尽管发病率很高，但乳腺癌患者睡眠障碍的原因仍不清楚。这项研究的目的是阐明化疗导致睡眠障碍的生理机制。目标1将使用小鼠来确定化疗引起的炎症和睡眠障碍之间是否存在因果关系。具体地说，我们将确定与睡眠相关的大脑区域在接受化疗后是否增加了促炎症细胞因子的表达，以及通过米诺环素抑制炎症是否在化疗期间和治疗后保持睡眠。米诺环素是一种已可用于癌症患者的抗炎药物。在目标2中，我们将使用在俄亥俄州立大学睡眠障碍诊所逗留期间收集的自我报告测量和客观活动图、EEG和EMG测量来表征乳腺癌患者在化疗前和生存期的睡眠数量和质量；这些测量将与血清炎症生物标志物相关联。这项研究将提供迄今为止对乳腺癌患者睡眠的最全面的分析，并将与目标1一起确定是否有必要在乳腺癌患者中使用米诺环素进行干预性睡眠研究。这项拟议研究的长期目标是通过在化疗期间和整个生存期内实现睡眠正常化，改善癌症患者的心理和身体健康，以及他们的生活质量。

 DESCRIPTION (provided by applicant): Sleep disruption is one of the most common and potentially detrimental long-term side effects of chemotherapy in breast cancer patients. The majority of patients undergoing chemotherapy report acute sleep disturbances, and as many as 60% of survivors go on to develop chronic sleep disruption, which can persist for more than a decade following treatment. Despite this high incidence, the etiology of sleep disruption among breast cancer patients remains unknown. The goal of the proposed studies is to elucidate the physiological mechanisms through which chemotherapy contributes to the development of sleep disruption. Aim 1 will use mice to establish whether a causal relationship exists between chemotherapy-induced inflammation and sleep disruption. Specifically, we will determine whether regions of the brain associated with sleep have increased expression of proinflammatory cytokines after exposure to chemotherapy, and whether suppressing inflammation via minocycline, an anti-inflammatory drug already available for use in cancer patients, preserves sleep during and after treatment with chemotherapy. In Aim 2, we will characterize sleep quantity and quality in breast cancer patients prior to chemotherapy and during the survivorship period using self-report measures and objective actigraph, EEG and EMG measures collected during stays in the Ohio State University Sleep Disorders Clinic; these measures will be correlated with serum biomarkers of inflammation. This study will provide the most comprehensive analysis of sleep in breast cancer patients to date, and together with Aim 1 will determine whether an interventional sleep study using minocycline is warranted in breast cancer patients. The long-range goal of the proposed research is to improve the mental and physical health of cancer patients, as well as their quality of life, through the normalization of sleep during chemotherapy treatment and throughout the survivorship period.