von Ardenne M, von Ardenne A
Arzneimittelforschung. 1975 Jun;25(6):863-70.
After discussion of the causes of natural selectivity of cancerostatics it is pointed out that, thanks to recent advances in cell kinetics (cycle-adequate selection of cancerostatics) combined with microtopography of substrate supply in the intercapillary region of cancer tissue, chemotherapeutic treatment of cancer is developing into a theoretically founded and modifiable therapy. Within the nexus of closely related problems it is especially the studies on pharmacokinetics of cancerostatics that still are in arreals. The discussed course of such an investigation basis oe the carticularly of cancer tissue, i.e., the often inadequate vascularization parameters that deteriorate even further with growing tumor size. -- The given valance equation for a change in the concentration of a cancerostatic in tumor tissue has been evaluated using, for an example, a substance from the alkylating group whose mass number approximately coindices with that of cyclophosphamide in its active form. As far as the better vascularized cancer tissue farther from the capillaries are concerned (e.g. early stages of tumors and metastases) the effective dose only drops from 1 to about 0.7. In poorly vacularized cancer tissue, on the other hand, the respective effective dose is reduced from 1 to approx. 0.25. Unfortunately, however, this drop in effective dose takes place exactly in a location where the most resistant fractions of tumor cells are to be found. A feasible way out this crucial dilemma inherent in the chemotherapy of cancer is to combine a substance of low mass numer that causes a pronounced long-term stimulation of body own defence (e.g. our BA 1, and N-(2-cyanoethylene)-urea) with a cancerostatic like CMT-selectine that -- in optimally hyperacidified cancer tissues -- reaches its active form only at a reduced pH so that (contrary to normal cancerostatics) stimulation of the body-own defence caused by the first mentioned substance is not impaired.
在讨论了抗癌药物自然选择性的原因后指出，由于细胞动力学的最新进展（抗癌药物的周期适应性选择）以及癌组织毛细血管间区域底物供应的微观地形学，癌症的化疗正在发展成为一种有理论依据且可调整的治疗方法。在密切相关问题的关联中，尤其抗癌药物的药代动力学研究仍有欠缺。所讨论的这种研究过程基于癌组织的特殊性，即其血管化参数常常不足，且随着肿瘤大小的增加会进一步恶化。——已使用例如来自烷基化基团的一种物质对肿瘤组织中抗癌药物浓度变化的给定价态方程进行了评估，该物质的质量数与其活性形式下环磷酰胺的质量数大致相符。就离毛细血管较远、血管化较好的癌组织而言（例如肿瘤和转移灶的早期阶段），有效剂量仅从1降至约0.7。另一方面，在血管化不良的癌组织中，相应的有效剂量从1降至约0.25。然而，不幸的是，有效剂量的这种下降恰恰发生在肿瘤细胞最具抗性的部分所在的位置。解决癌症化疗中这种关键困境的一个可行方法是将一种低质量数的物质与一种抗癌药物如CMT - 选择素联合使用，前者会引起机体自身防御的明显长期刺激（例如我们的BA 1和N -（2 - 氰基乙烯） - 脲），而CMT - 选择素在最佳过度酸化的癌组织中仅在较低pH值下达到其活性形式，这样（与正常抗癌药物相反）第一种物质引起的机体自身防御刺激不会受到损害。
