Leontovich Alexey A, Dronca Roxana S, Suman Vera J, Ashdown Martin L, Nevala Wendy K, Thompson Michael A, Robinson Andrew, Kottschade Lisa A, Kaur Judith S, McWilliams Robert R, Ivanov Leonid V, Croghan Gary A, Markovic Svetomir N
Department of Health Science research, Mayo Clinic, Rochester, MN 55901, USA.
Front Biosci (Elite Ed). 2012 Jan 1;4(3):958-75. doi: 10.2741/E433.
Evidence suggests that immunological response in chronic inflammation is dynamic, oscillating between active immunity and tolerance. We hypothesized that a similar dynamic exists in melanoma and administration of therapy during a unique phase of such oscillation could impact clinical outcome. Patients with metastatic melanoma eligible to undergo temozolomide underwent serial measurements of C-reactive protein (CRP) and immune biomarkers every 2-3 days for 2 weeks before starting therapy. Treatment was initiated prior to the estimated next CRP peak, or on day 14 post-registration if a peak was not identified. Time profiles of measured biomarkers were analyzed by fitting serially measured data points to 9 mathematical functions and were correlated to time of therapy and outcome. Data suggested that metastatic melanoma patients exhibit a dynamic immune response. The fluctuation of several biomarkers fitted cosine functions with periods which were multiples of 3-4 days. Chemotherapy delivery during a unique phase of this cycle seemed to correlate with improved response. Individualized conventional chemotherapy delivery by synchronizing treatment with pre-existing patient-specific biorhythms may improve clinical outcomes in metastatic melanoma.
有证据表明，慢性炎症中的免疫反应是动态的，在主动免疫和耐受之间振荡。我们假设黑色素瘤中存在类似的动态变化，在此类振荡的独特阶段进行治疗可能会影响临床结果。符合接受替莫唑胺治疗条件的转移性黑色素瘤患者在开始治疗前2周内每2 - 3天对C反应蛋白（CRP）和免疫生物标志物进行系列测量。在估计的下一个CRP峰值之前开始治疗，如果未识别出峰值，则在登记后第14天开始治疗。通过将系列测量的数据点拟合到9个数学函数来分析测量的生物标志物的时间曲线，并将其与治疗时间和结果相关联。数据表明转移性黑色素瘤患者表现出动态免疫反应。几种生物标志物的波动拟合了周期为3 - 4天倍数的余弦函数。在这个周期的独特阶段进行化疗似乎与更好的反应相关。通过将治疗与患者预先存在的特定生物节律同步来进行个体化的传统化疗给药可能会改善转移性黑色素瘤的临床结果。
