ENDOTHELIAL CELL TARGETED CANCER TREATMENT

内皮细胞被诱导增殖的影响下， 从肿瘤细胞中释放的因子。 该项目旨在确定 内皮细胞对这些因子的反应方面 并将这些信息作为开发新癌症的基础 影响内皮细胞功能的治疗。 使用的文化 原代人脐静脉内皮细胞，其特定目标是 项目包括对具有选择性毒性的制剂的定义， 增殖正常内皮细胞;细胞表面的定义 决定因素的增殖内皮细胞，因为这些分子可以 被开发为用于递送选择性毒性分子的靶标; 更详细的细胞增殖标志物表征，包括 TEC 4和TEC 11抗体识别的抗原; 可能介导抗肿瘤的内皮细胞反应途径 活动，包括一氧化氮生成系统，并阐述 促凝活性的影响;审查 内皮细胞在阐述毒性观察到的各种 生物反应调节剂，包括奎宁诱导的去稳定化 细胞连接和内皮细胞阻力的改变， 对细胞因子和毒素的反应。 最近的研究表明， 葫芦素抑制内皮细胞增殖的能力 特别是葫芦素E（NSC 106399），其机制可能破坏 肌动蛋白细胞骨架

Endothelial cells are induced to proliferate under the influence of factors released from tumor cells. This project seeks to identify aspects of the response to these factors on the part of endothelial cells and to use this information as a basis for developing novel cancer treatments which influence endothelial cell function. Using cultures of primary human umbilical vein endothelial cells, specific goals for this project include the definition of agents with selective toxicity for proliferating normal endothelial cells; a definition of cell surface determinants on proliferating endothelial cells, as these molecules could be developed as targets for the delivery of selectively toxic molecules; more detailed characterization of cell proliferation markers, including antigens recognized by the TEC4 and TEC11 antibodies; examination of endothelial cell response pathways which might mediate anti-tumor activity, including the nitric oxide generating system, and elaboration of pro-coagulant activities; examination of the role played by endothelial cells in the elaboration of toxicities observed by various biological response modifiers including cytokine-induced destabilization of cellular junctions and alteration of endothelial cell resistance in response to cytokines and toxins. Recent studies have defined the potent capacity of cucurbitacins to inhibit endothelial cell proliferation especially cucurbitacin E (NSC 106399) by a mechanism that may disrupt the actin cytoskeleton.