Spatial Organization of Temperature-Related Circadian and Vasomotor Rhythms

与温度相关的昼夜节律和血管舒缩节律的空间组织

• 批准号: 9152147
• 负责人: Alexander Gorbach
• 金额: $ 6.4万
• 依托单位: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9152147
• 关键词: Acceleration; Ambulatory Monitoring; Biological Markers; Biophysical Process; Body Temperature; Cancer Patient; Chronotherapy; Circadian Rhythms; Coupling; Data Set; Diagnostic Neoplasm Staging; Discriminant Analysis; Experimental Neoplasms; Fourier Transform; Goals; Individual; Intestinal Cancer; Malignant Neoplasms; Measures; Methods; Modeling; Monitor; Patients; Pattern; Periodicity; Peripheral; Phase; Process; Protocols documentation; Rest; Series; Signal Transduction; Site; Skin; Staging; Surface; System; Temperature; Time; Tumor stage; Vasomotor; Wireless Technology; Wrist; circadian pacemaker; endothelial dysfunction; image guided; sensor; tumor; tumor progression; volunteer

Disruption of the temperature circadian rhythm has been associated with cancer progression, while its amplification has been associated with cancer inhibition in experimental tumor models. The current study investigated the relevance of skin surface temperature rhythms as biomarkers of the Circadian Timing System (CTS) in order to optimize chronotherapy timing in individual cancer patients. Baseline skin surface temperature at four sites and wrist accelerations were measured every minute for 4 days in 16 patients with metastatic gastro-intestinal cancer before chronotherapy administration. Temperature and rest-activity were recorded, respectively, with wireless skin surface temperature patches (Respironics, Phillips) and an actigraph (Ambulatory Monitoring). Both variables were further monitored in 10 of these patients during and after a 4-day course of a fixed chronotherapy protocol. Data sets collected at baseline, during and after therapy longitudinal were processed using Fast Fourier Transform and Linear Discriminant Analyses methods. A circadian rhythm was statistically validated with a period of 24 h (p < 0.05) for 49/61 temperature time series (80.3%), and 15/16 rest-activity patterns (93.7%) at baseline. However, individual circadian amplitudes varied from 0.04 C to 2.86 C for skin surface temperature (median, 0.72 C), and from 16.6 to 146.1 acc/min for rest-activity (median, 88.9 acc/min). Thirty-nine pairs of baseline temperature and rest-activity time series (75%) were correlated (r > 0.7; p < 0.05). Individual circadian acrophases at baseline were scattered from 15:18 to 6:05 for skin surface temperature, and from 12:19 to 15:18 for rest-activity, with respective median values of 01:10 (25-75% quartiles, 22:35-3:07) and 14:12 (13:14-14:31). The circadian patterns in skin surface temperature and rest-activity persisted or were amplified during and after fixed chronotherapy delivery for 5/10 patients. By contrast, transient or sustained disruption of these biomarkers was found for the five other patients, as indicated by the lack of any statistically significant dominant period in the circadian range. No consistent correlation (r < 0.7, p >= 0.05) was found between paired rest-activity and temperature time series during fixed chronotherapy delivery. In conclusion, large inter-patient differences in circadian amplitudes and acrophases of skin surface temperature were demonstrated for the first time in cancer patients, despite rather similar rest-activity acrophases. The patient-dependent coupling between both CTS biomarkers, and its possible alteration on a fixed chronotherapy protocol, support the concept of personalized cancer chronotherapy.

温度昼夜节律的破坏与癌症进展有关，而其扩增与实验性肿瘤模型中的癌症抑制有关。当前的研究调查了皮肤表面温度节奏作为昼夜节律定时系统（CTS）的生物标志物的相关性，以优化个别癌症患者的年级疗法时间。在给药之前，每分钟在四个部位的基线皮肤表面温度和腕部加速度进行4天测量4天。分别记录了无线皮肤表面温度斑块（呼吸道，菲利普斯）和动作法（卧床监测），分别记录了温度和静止性。在固定的年度疗法方案进行为期4天的4天过程中，在其中10例患者中进一步监测了这两个变量。使用快速的傅立叶变换和线性判别分析方法处理在基线，在基线期间和治疗后收集的数据集。昼夜节律在49/61温度时间序列（80.3％）和15/16的休息时间模式（93.7％）的周期为24 h（p <0.05）上得到统计验证。然而，单个昼夜节律幅度从0.04 c到2.86 c的皮肤表面温度（中位数为0.72 c），静止活性为16.6至146.1 ACC/min（中位数为88.9 ACC/min）。 39对基线温度和休息时间序列（75％）相关（r> 0.7； p <0.05）。对于皮肤表面温度，基线时的单个昼夜节律从15:18到6:05散布，静止运动为12:19至15:18，相应的中位数为01:10（25-75％四分位数，22：35-3：07）和14:12（13：14-14：14-14：31）。皮肤表面温度和静止活性中的昼夜节律模式在5/10例患者的固定时疗法递送过程中持续或放大。相比之下，对于其他五名患者，发现了这些生物标志物的瞬时或持续破坏，这表明在昼夜节律范围内缺乏任何统计学上显着的显着时期。在固定的年度疗法递送过程中，在配对的静止活性和温度时间序列之间没有发现一致的相关性（r <0.7，p> = 0.05）。总之，尽管相当相似，但在癌症患者中首次证明了昼夜节律幅度和皮肤表面温度峰的巨大差异。两种CTS生物标志物之间的患者依赖性耦合及其对固定年级疗法方案的可能改变，支持个性化癌症年代疗法的概念。