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 该项目包括对具有选择性毒性的药物的定义 正常内皮细胞的增殖；细胞表面的定义 内皮细胞增殖的决定因素，因为这些分子可能 被开发为输送选择性有毒分子的靶标； 更详细的细胞增殖标记物的特征，包括 由TEC4和TEC11抗体识别的抗原.检验 可能介导抗肿瘤作用的内皮细胞反应通路 活动，包括一氧化氮生成系统，以及详细说明 关于促凝血剂的活性；检查所起的作用 血管内皮细胞在阐述毒性时观察到的各种 包括细胞因子诱导的不稳定在内的生物反应调节剂 细胞连接和内皮细胞阻力的变化 对细胞因子和毒素的反应。最近的研究已经定义了这种强效 葫芦素抑制内皮细胞增殖的能力 尤其是葫芦素E(NSC 106399)通过一种可能破坏 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.