Crafts D C, Hoshino T, Wilson C B
Bull Cancer. 1977;64(1):115-24.
One must know tumor cell kinetics in order to devise a rational drug regimen for gliomas. With tritiated thymidine, the Labelling Index of astrocytomas is less than 1 per 100; of glioblastomas from 5-10 per 100. The duration of S phase is fairly constant, ranging from 7 to 10 hours. Double radioautography reveals a cell cycle time of 2 to 3 days and a Growth Fraction of 10 to 30 per 100 in glioblastomas. Calculations based on volume of tumor at recurrence after a gross total resection, analysis of primer dependent D.N.A. polymerase (P.D.P.), and analysis of cells by Flow Microfluorometer, all confirm these approximate figures. Thus most of the cells of a glioma are not sensitive to a cell-cycle phase specific drug. Such an agent, if given, should be administered over a 2 to 3 day period, in order to affect as many cells as possible. The most important part of a drug regimen should be an agent which attacks non-proliferating as well as proliferating cells, such as an alkylating agent. The effects of various drugs and schedules can be examined by animal models with the technqiue of colony forming efficiency.
为了设计出合理的神经胶质瘤药物治疗方案,必须了解肿瘤细胞动力学。用氚标记的胸腺嘧啶核苷研究发现,星形细胞瘤的标记指数低于1/100;胶质母细胞瘤的标记指数为5/100至10/100。S期的持续时间相当恒定,为7至10小时。双重放射自显影显示,胶质母细胞瘤的细胞周期时间为2至3天,生长分数为10/100至30/100。根据大体全切术后复发时肿瘤的体积计算、对依赖引物的DNA聚合酶(P.D.P.)的分析以及用流式细胞荧光仪对细胞的分析,均证实了这些近似的数据。因此,神经胶质瘤的大多数细胞对细胞周期特异性药物不敏感。如果使用这种药物,应在2至3天内给药,以便影响尽可能多的细胞。药物治疗方案中最重要的部分应该是一种既能攻击增殖细胞又能攻击非增殖细胞的药物,比如烷化剂。可以通过具有集落形成效率技术的动物模型来研究各种药物及其给药方案的效果。