Focan C
C.H. Saint Joseph Espérance, Liège, Belgium.
In Vivo. 1995 Nov-Dec;9(6):573-81.
Circadian rhythmicity in cell division has been proved in the actively proliferating healthy tissues of rodents (cornea, G.I.-tract, bone marrow, gonads, epidermis) as well as in most spontaneous or transplanted tumors growing in solid or ascites fluid phases. This circadian division accounts in part for the circadian varying sensitivity of healthy target tissues to oncolytic agents (chronotoxicity/chronotolerance). Similarly, antitumor activity as gauged from analysis of impact on cell kinetics and/or tumor shrinkage or cure was also shown to depend upon the dose and doing time of anticancer drug administration. Variations in the timing of internal cell kinetics after initial drug administration were also shown to depend on the type of drug (alkylating agent, antimitotic, or antimetabolite agent). Interestingly, internal desynchronization may occur in both healthy and tumor tissues, it may allow the selection of given circadian stages for the administration of a second drug at the point of highest tumor sensitivity and healthy tissue resistance (time of least sensitivity). These observations have been utilized to test strategies in sequential drug scheduling aimed at improving the overall therapeutic index. Observations indicate that in some instances these approaches could be translated to human beings.
细胞分裂的昼夜节律已在啮齿动物的活跃增殖健康组织（角膜、胃肠道、骨髓、性腺、表皮）以及大多数处于实体或腹水期生长的自发或移植肿瘤中得到证实。这种昼夜节律性细胞分裂部分解释了健康靶组织对溶瘤药物的昼夜敏感性变化（时辰毒性/时辰耐受性）。同样，从对细胞动力学的影响和/或肿瘤缩小或治愈情况分析得出的抗肿瘤活性也显示取决于抗癌药物给药的剂量和时间。初次给药后内部细胞动力学时间的变化也显示取决于药物类型（烷化剂、抗有丝分裂剂或抗代谢剂）。有趣的是，健康组织和肿瘤组织都可能发生内部不同步，这可能允许在肿瘤敏感性最高和健康组织抵抗力最强（敏感性最低的时间）的时刻选择特定的昼夜节律阶段来施用第二种药物。这些观察结果已被用于测试旨在提高总体治疗指数的序贯药物给药策略。观察表明，在某些情况下，这些方法可以应用于人类。
