ENDOTHELIAL CELL TARGETED CANCER TREATMENT

血管内皮细胞在血管内皮细胞的影响下增殖 肿瘤细胞释放的因子。这个项目试图确定 血管内皮细胞对这些因素的反应 并利用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。使用的区域性 原代人脐静脉内皮细胞，这方面的具体目标 该项目包括对细胞表面决定因素定义 增殖的内皮细胞，因为这些分子可以被开发出来 作为输送选择性有毒分子的目标；区别 在人类肿瘤的组织切片和组织培养中 内皮细胞激活标志物，例如最近描述的edg1 基因，(在刺激分化的内皮细胞后出现 由肿瘤坏死因子、白介素1或肿瘤等药物 促进佛波酯)和内皮细胞增殖标记物， 包括EN2/3和70-1抗体识别的抗原； 可能介导内皮细胞反应通路的检测 抗肿瘤活性，包括一氧化氮生成系统和 包括冯·威勒布兰德在内的促凝血剂活性的阐述 血管内皮细胞在血管内皮细胞中的作用 阐述各种生物反应观察到的毒性 包括细胞因子在内的修饰剂诱导的细胞失稳 血管内皮细胞阻力的连接和变化 细胞因子和毒素。

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 a definition of cell surface determinants specific for the proliferating endothelial cell, as these molecules could be developed as targets for the delivery of selectively toxic molecules; a distinction and in tissue sections from human tumors and in tissue culture between endothelial cell activation markers, such as the recently described edg1 gene, (which appear after stimulation of differentiated endothelial cells by agents such as tumor necrosis factor, interleukin-1, or tumor promoting phorbol esters) and endothelial cell proliferation markers, including antigens recognized by the EN2/3 and 70-1 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 including von Willebrand's Factor; 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.