Hokanson J A, Brown B W, Thompson J R, Jansson B, Drewinko B
Cell Tissue Kinet. 1986 Jan;19(1):1-10. doi: 10.1111/j.1365-2184.1986.tb00710.x.
We present a computer-based mathematical model that can simulate characteristic features of the clinical time course of human myeloma. It asserts that therapy resistance in myeloma cells is an inherited trait associated with the longer inter-mitotic times of some cells and that the strength of this trait affects tumour growth characteristics. These kinetic differences within the malignant cell clone may also influence therapeutic efficacy. In the model, the same total therapy, administered in different time-dose fractions, could be 'curative' or 'minimally effective' depending on kinetic properties. For example, as others have shown, in myeloma pulsed intermittent therapy is often more effective than low dose continuous therapy. According to our model this finding is compatible with a high coefficient of inheritability of resistance from one cell generation to the next. The model also suggests that if there are subclones of varying resistance, a therapy must have some effect on each of them if it is to be employed in a curative fashion. While many aspects of the model are not yet clinically testable, exploration of its concepts might increase knowledge about fundamental neoplastic mechanisms.
我们提出了一种基于计算机的数学模型，该模型可以模拟人类骨髓瘤临床病程的特征。它认为骨髓瘤细胞中的治疗抗性是一种遗传特征，与某些细胞较长的分裂间期相关，并且这种特征的强度会影响肿瘤生长特性。恶性细胞克隆内的这些动力学差异也可能影响治疗效果。在该模型中，相同的总治疗量，以不同的时间剂量分割方式给药，根据动力学特性可能是“治愈性的”或“疗效甚微的”。例如，正如其他人所表明的，在骨髓瘤中脉冲间歇疗法通常比低剂量持续疗法更有效。根据我们的模型，这一发现与抗性从一个细胞世代到下一个细胞世代的高遗传系数相一致。该模型还表明，如果存在抗性不同的亚克隆，一种疗法若要以治愈的方式应用，就必须对每个亚克隆都有一定作用。虽然该模型的许多方面尚未能在临床上进行测试，但对其概念的探索可能会增加对肿瘤基本机制的认识。
