CHRONOBIOLOGY OF INTERFERON THERAPY

时间生物学是对生物节律的研究。 有许多 时间生物学效应可能具有重要的临床意义， 抗肿瘤疗法 例如，时间生物学对 某些类型的肿瘤细胞的复制，某些药物的表达 毒性和细胞毒性效应细胞的数量。 干扰素治疗目前正在临床试验中进行评估， 它们作为抗肿瘤剂的潜力。 该提案侧重于可能的 时间生物学效应可能影响各种药物的效力， 干扰素疗法 我们建议评估时间生物学效应 干扰素对肿瘤生长的影响（1）作为单一药剂疗法给药; (2)作为多种干扰素疗法（IFN-γ加IFN-α或IFN-γ）， β）;（3）作为具有高热的多药剂疗法;以及，作为多药剂疗法， 药物治疗与苯妥英。 这些研究将在以下两个地点进行： 体外，使用B-16黑色素瘤细胞进行克隆研究，体内，使用 B-1/6黑素瘤/C57/B1/6肿瘤系统。 同时治疗和各种 将比较连续治疗，以确定最有效的 治疗方案。 我们还建议评估时间生物学 对IFN介导的集落刺激骨髓抑制的影响 因素管理。 这些研究将在体外使用 骨髓集落生长测定和使用总白色血细胞的体内测定 也是骨髓抑制的指标

Chronobiology is the study of biological rhythms. There are a number of chronobiological effects which may have important clinical implications for antitumor therapies. For example, chronobiological effects on the replication of some types of tumor cells, the expression of certain drug toxicities, and the number of cytotoxic effector cells have been described. Interferon therapies are currently being evaluated in clinical trials for their potential as antitumor agents. This proposal focuses on possible chronobiological effects which may effect the potencies of various interferon therapies. We propose to evaluate the chronobiological effects on tumor growth of interferons administered (1) as single agent therapy; (2) as multiple interferon therapies (IFN-gamma plus IFN-alpha or IFN- beta); (3) as multiple agent therapies with hyperthermia; and, as multiple agent therapies with phenytoin. These studies will be performed both in vitro, using B-16 melanoma cells in cloning studies, and in vivo, using the B-16 melanoma/C57/B1/6 tumor system. Simultaneous treatments and various sequential treatments will be compared to identify the most potent treatment protocol. We also propose to evaluate the chronobiological effects on IFN-mediated bone marrow suppression of colony stimulating factor administration. These studies will be performed both in vitro using bone marrow colony growth assays and in vivo using total white blood cell counts as an indicator of bone marrow suppression.