The Effects of Chemotherapy on Sleep

 描述（由申请人提供）：睡眠中断是乳腺癌患者化疗的最常见和潜在有害的长期副作用之一。大多数接受化疗的患者报告急性睡眠障碍，多达60%的幸存者继续发展慢性睡眠障碍，治疗后可能持续十多年。尽管发病率很高，但乳腺癌患者睡眠中断的病因仍然未知。拟议研究的目标是阐明化疗导致睡眠中断的生理机制。目标1将使用小鼠来确定化疗引起的炎症和睡眠中断之间是否存在因果关系。具体来说，我们将确定与睡眠相关的大脑区域在暴露于化疗后是否增加了促炎细胞因子的表达，以及通过米诺环素（一种已用于癌症患者的抗炎药物）抑制炎症是否可以在化疗期间和化疗后保持睡眠。在目标2中，我们将使用在俄亥俄州州立大学睡眠障碍诊所住院期间收集的自我报告测量和客观活动记录仪、EEG和EMG测量来表征化疗前和生存期内乳腺癌患者的睡眠数量和质量;这些测量将与炎症的血清生物标志物相关。这项研究将提供迄今为止最全面的乳腺癌患者睡眠分析，并与目标1一起确定是否有必要在乳腺癌患者中进行米诺环素干预性睡眠研究。拟议研究的长期目标是通过在化疗治疗期间和整个生存期内使睡眠正常化，改善癌症患者的身心健康及其生活质量。

 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.