LIPOPHILIC PROBES FOR TUMOR CELL SURFACES

已经知道一段时间了，血浆中的脂质成分 许多肿瘤细胞的膜不同于它们的组成 正常的对应物。然而，很少有人尝试利用这一点。 不同的诊断和治疗目的。它是主要的 这项建议的目的是确定亲脂性、阴离子染料， 可使用花菁540(MC 540)来识别和选择性地 摧毁白血病细胞。MC-540染色血液的流式细胞术分析 白血病患者化疗或骨髓标本 将进行移植以测试染料作为一种 诊断试剂。人类急性髓系白血病的两种动物模型， 耐药突变细胞系及其体外克隆培养的研究 白血病的人造血干细胞将被用来评估染料的 作为一种清除残留肿瘤细胞的方法 自体缓解骨髓移植。试图澄清某些方面的问题 染料介导的光敏作用背后的分子机制将 基于光学显微镜、电子显微镜、生化 以及光敏细胞的生物学分析。MC 540的类似产品将 用于确定染色反应的结构要求 以及光敏化过程。拟议的工作可能会导致 更早发现白血病复发，从而实现有用的个体化 关于治疗的问题。MC 540介导的光敏作用可能会有应用 自体缓解后残留肿瘤细胞的体外清除 骨髓移植。

It has been known for some time that the lipid composition of the plasma membranes of many neoplastic cells differs from the composition of their normal counterparts. However, few attempts have been made to exploit this difference for diagnostic and therapeutic purposes. It is the main objective of this proposal to determine if the lipophilic, anionic dye, merocyanine 540 (MC 540), can be employed to both identify and selectively destroy leukemic cells. Flow cytometric analyses of MC 540 stained blood samples from leukemia patients undergoing chemotherapy or bone marrow transplantation will be performed to test the dye's potential as a diagnostic agent. Two animal models of human acute myelogenous leukemia, drug-resistant mutant cell lines and in vitro clonal cultures of normal and leukemic human hematopoietic stem cells will be used to assess the dye's ppotential as a means for the purging of residual tumor cells from autologous remission marrow grafts. Attempts to elucidate some aspects of the molecular mechanisms that underlie dye-mediated photosensitization will be based on a combined light microscopic, electron microscopic, biochemical and biological analysis of photosensitized cells. Analogs of MC 540 will be employed to define the structural requirements of the staining reaction and the photosensitization process. The proposed work could lead to an earlier detection of leukemic relapse and thus to useful individualizations of treatment. MC 540-mediated photosensitization may find an application in the in vitro purging of residual tumor cells from autologous remission bone marrow grafts.