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。这个项目试图确定各个方面 内皮细胞对这些因素的反应以及对 利用这些信息作为开发新的癌症治疗方法的基础 影响内皮细胞功能的物质。使用小学的培养物 人脐静脉内皮细胞，本项目的具体目标 包括对扩散具有选择性毒性的药物的定义 正常内皮细胞；细胞表面决定因素的定义 增殖的内皮细胞，因为这些分子可以发展为 输送选择性有毒分子的目标；更详细 细胞增殖标记物的特征，包括细胞 增殖相关抗原，内皮细胞反应检查 可能介导抗肿瘤活性的途径，包括一氧化氮 氧化物产生系统，以及促进凝血剂活性的阐述； 血管内皮细胞在血管内皮细胞调控中的作用 各种生物反应调节剂观察到的毒性包括 细胞因子诱导的细胞连接不稳定；以及 血管内皮细胞对抗增殖剂的敏感性 细胞因子和毒素。最近的研究已经定义了 葫芦素特别是抑制内皮细胞增殖 葫芦素E(神经干细胞106399)通过一种可能干扰肌动蛋白的机制 细胞骨架。然而，令人信服的葫芦素的生物效应 证明体内抗血管生成活性尚未完成。 利用基于聚合酶链式反应的基因差异显示策略 扩增，增殖过程中差异表达的候选基因 血管内皮细胞已经被定义。

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 cell proliferation-related antigens, 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 sensitivity to antiproliferative agents 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. However, convincing biologic effects of cucurbitacin to demonstrate anti-angiogenic activity in vivo has not been accomplished. Using the PCR-based strategies of differentially displayed mRNA amplification, candidate genes differentially expressed in proliferating endothelial cells have been defined.