LIPOPHILIC PROBES FOR TUMOR CELL SURFACES

用于肿瘤细胞表面的亲脂性探针

• 批准号: 3184252
• 负责人: Fritz Sieber
• 金额: $ 11.03万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184252
• 关键词: autologous transplantation; bone marrow transplantation; cell bank /registry; cell membrane; clone cells; drug resistance; electron microscopy; hematopoietic stem cells; human tissue; membrane activity; membrane lipids; mutant; myelogenous leukemia; neoplasm /cancer chemotherapy; neoplasm /cancer diagnosis; neoplasm /cancer photoradiation therapy; neoplastic cell; tissue /cell culture

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.

一段时间以来，人们已经知道血浆的脂质组成