Elimination of residual tumor cells from autologous bone marrow grafts by dye-mediated photolysis: preclinical data.
Elimination of residual tumor cells from autologous bone marrow grafts by dye-mediated photolysis: preclinical data.
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通过染料介导的光解消除自体骨髓移植物中残留的肿瘤细胞：临床前数据。
DOI：
10.1111/j.1751-1097.1987.tb04738.x
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发表时间：
1987
影响因子：
3.3
通讯作者：
Sieber,F
中科院分区：
文献类型：
--
作者：
Sieber,F
MC540 介导的光解作用有几个特点，使其成为一种具有潜在吸引力的临床净化程序。 (1) 实验性肿瘤的经验表明，MC 540 介导的光解作用可有效对抗多种白血病和实体瘤，包括耐药肿瘤（Sieberet al., 1984b）。耐药肿瘤细胞很可能出现在接受过大量治疗的患者中。 (2) MC540 介导的光解作用不依赖于细胞周期（Manna 和 Sieber，1985）。它会杀死静息细胞和循环细胞。在这方面，MC 540 介导的光解是细胞周期特异性细胞毒性药物的宝贵补充。 (3)正常多能造血干细胞与白血病、神经母细胞瘤细胞的敏感性存在较大差异。 (4) MC 540介导的光解作用机制与凝集素、抗体和大多数细胞毒性药物不同。 MC 540 与质膜的脂质部分结合，膜脂质可能是有毒光产物的主要目标。抗体和凝集素与蛋白质和碳水化合物发生反应，大多数药物都有细胞内靶标（例如核 DNA）。因此，如果 MC 540 介导的光解作用与其他净化程序结合使用，我们预计交叉耐药性很小。 (5) 与骨髓移植物相关并注入患者体内的少量染料大约比 LD10（小鼠）低 100 000 倍，因此不太可能造成任何伤害。该技术首次临床应用的结果支持了这一观点（Sieberet al., 1986c）。更好地了解潜在的分子机制无疑将导致该技术的更有效应用，并可能导致鉴定出更有效的 MC 540 类似物。
MC540‐mediated photolysis has several features that make it potentially attractive as a clinical purging procedure. (1) The experience with experimental tumors suggests that MC 540‐mediated photolysis is effective against a broad range of leukemias and solid tumors, including drug‐resistant tumors (Sieberet al., 1984b). Drug‐resistant tumor cells are likely to occur in heavily pretreated patients. (2) MC540‐mediated photolysis is not cell‐cycle dependent (Manna and Sieber, 1985). It kills both resting and cycling cells. In this regard, MC 540‐mediated photolysis is a valuable complement to cell‐cycle specific cytotoxic drugs. (3) There is a large differential in sensitivity between normal pluripotent hematopoietic stem cells and leukemia and neuroblastoma cells. (4) The mechanism of action of MC 540‐mediated photolysis is different from that of lectins, antibodies and most cytotoxic drugs. MC 540 binds to the lipid portion of the plasma membrane and membrane lipids are probably a primary target of the toxic photoproducts. Antibodies and lectins react with proteins and carbohydrates and most drugs have intracellular targets (e.g. nuclear DNA). We would therefore expect little cross‐resistance if MC 540‐mediated photolysis were used in combination with other purging procedures. (5) The small amounts of dye that remain associated with the marrow graft and are infused into the patient are approximately 100 000‐fold less than the LD10(in mice) and therefore unlikely to cause any harm. The outcome of the first clinical application of the technique supports this view (Sieberet al., 1986c).A better understanding of the underlying molecular mechanisms will undoubtedly lead to more effective applications of the technique and perhaps to the identification of more potent analogs of MC 540.