Uckun F M, Ramakrishnan S, Haag D, Houston L L
Leuk Res. 1985;9(1):83-95. doi: 10.1016/0145-2126(85)90023-2.
Studies were performed to evaluate the anti-tumor activity of mafosfamid, a new synthetic derivative of cyclophosphamide. We tested its ability to eliminate lymphoblastic leukemia cells from autologous bone marrow grafts following a 30 min preincubation in a highly sensitive clonogenic assay. Treatment with 50-100 micrograms mafosfamid/ml eliminated more than 4 logs of contaminating clonogenic tumor cells from a 200-fold excess of normal bone marrow. Flow cytometric studies showed differences in cell cycle kinetics between mafosfamid-resistant and mafosfamid-susceptible tumor cell clones. Compared to drug susceptible clonogenic tumor cells, clones that resisted treatment with 100 micrograms mafosfamid/ml exhibited a smaller percentage of cells in S-phase, indicating that mafosfamid is mostly cytotoxic to rapidly cycling tumor cells. The combination of mafosfamid and a target cell selective immunotoxin containing pokeweed anti-viral protein was superior to mafosfamid alone or immunotoxin alone for purging mafosfamid-resistant leukemic cells from human marrow.
开展了多项研究以评估马磷酰胺（一种新的环磷酰胺合成衍生物）的抗肿瘤活性。在一项高灵敏度克隆形成试验中，我们测试了其在30分钟预孵育后从自体骨髓移植物中清除淋巴细胞白血病细胞的能力。用50 - 100微克马磷酰胺/毫升处理可从200倍过量的正常骨髓中清除超过4个对数的污染性克隆形成肿瘤细胞。流式细胞术研究显示，马磷酰胺耐药和敏感的肿瘤细胞克隆在细胞周期动力学方面存在差异。与药物敏感的克隆形成肿瘤细胞相比，对100微克马磷酰胺/毫升处理有抗性的克隆在S期的细胞百分比更小，这表明马磷酰胺对快速增殖的肿瘤细胞大多具有细胞毒性。马磷酰胺与一种含有商陆抗病毒蛋白的靶细胞选择性免疫毒素联合使用，在从人骨髓中清除对马磷酰胺耐药的白血病细胞方面优于单独使用马磷酰胺或免疫毒素。
