McCulloch E A
The Ontario Cancer Institute, Toronto, M5G 2M9 Canada.
Clin Cancer Res. 1997 Dec;3(12 Pt 2):2676-81.
Dr. Emil J Freireich is a pioneer in the rational treatment of cancer in general and leukemia in particular. This essay in his honor suggests that the cell kill concept of chemotherapy of acute myeloblastic leukemia be extended to include two additional ideas. The first concept is that leukemic blasts, like normal hemopoietic cells, are organized in hierarchies, headed by stem cells. In both normal and leukemic hemopoiesis, killing stem cells will destroy the system; furthermore, both normal and leukemic cells respond to regulators. It follows that acute myelogenous leukemia should be considered as a dependent neoplasm. The second concept is that cell/drug interaction should be considered as two phases. The first, or proximal phase, consists of the events that lead up to injury; the second, or distal phase, comprises the responses of the cell that contribute to either progression to apoptosis or recovery. Distal responses are described briefly. Regulated drug sensitivity is presented as an example of how distal responses might be used to improve treatment.
埃米尔·J·弗雷雷奇博士是癌症（尤其是白血病）合理治疗领域的先驱。这篇纪念他的文章提出，急性髓细胞白血病化疗的细胞杀伤概念应扩展至纳入另外两个观点。第一个观点是，白血病原始细胞如同正常造血细胞一样，以干细胞为首形成层级结构。在正常和白血病造血过程中，杀死干细胞都会破坏整个系统；此外，正常细胞和白血病细胞都对调节因子有反应。因此，急性髓系白血病应被视为一种依赖肿瘤。第二个观点是，细胞/药物相互作用应被视为两个阶段。第一个阶段，即近端阶段，由导致损伤的事件组成；第二个阶段，即远端阶段，包括细胞导致凋亡进展或恢复的反应。对远端反应进行了简要描述。以调节药物敏感性为例，说明远端反应如何可用于改善治疗。
