LIPOPHILIC PROBES FOR TUMOR CELL SURFACES

一段时间以来，人们已经知道， 许多肿瘤细胞的膜与其细胞膜的组成不同， 正常的同行。 然而，很少有人尝试利用这一点， 用于诊断和治疗目的。 是主要 该建议的目的是确定亲脂性，阴离子染料， 例如，可以使用微传感器540（MC 540）来识别和选择性地识别微传感器540。 摧毁白血病细胞 MC 540染色血液的流式细胞术分析 来自接受化疗的白血病患者或骨髓的样本 移植将进行测试染料的潜力， 诊断剂。 两种人急性髓性白血病动物模型， 耐药突变细胞系和正常和 白血病人类造血干细胞将被用来评估染料的 ppotential作为清除残留肿瘤细胞的手段， 自体缓解骨髓移植。 试图阐明的一些方面， 作为染料介导的光敏作用的基础的分子机制将 是基于光显微镜、电子显微镜、生物化学 和光敏细胞的生物学分析。 MC 540的类似物将 用于定义染色反应的结构要求 和光敏化过程。 拟议的工作可能导致 白血病复发的早期检测，从而实现有用的个体化 的治疗。 MC 540介导的光敏化可能会得到应用 在体外清除自体缓解的残余肿瘤细胞中 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.