CHRONOBIOLOGY OF INTERFERON THERAPY

时间生物学是研究生物节律的学科。有很多种 可能具有重要临床意义的时间生物学效应 抗肿瘤疗法。例如，时间生物学对人类的影响 复制某些类型的肿瘤细胞，表达某些药物 毒性，以及细胞毒效应细胞的数量已经被描述。 干扰素疗法目前正在进行临床试验，以 它们作为抗肿瘤药物的潜力。这项建议侧重于可能 时间生物学效应可能影响不同物种的能力 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)单药治疗； (2)作为多种干扰素疗法(干扰素-γ+干扰素-α或干扰素-α) β)；(3)作为热疗的多药疗法；以及，作为多种 使用苯妥英钠的药物疗法。这些研究将在两个国家进行 体外，在克隆研究中使用B-16黑色素瘤细胞，在体内，使用 B-16黑色素瘤/C57/B1/6肿瘤系统。同时治疗和各种不同的 将对顺序治疗进行比较，以确定最有效的 治疗方案。我们还建议评估时间生物学 干扰素介导的集落刺激对骨髓抑制的影响 因子管理。这些研究将在体外使用 骨髓集落生长试验和体内使用总白细胞 算作骨髓抑制的一个指标。

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.