ENDOTHELIAL CELL TARGETED CANCER TREATMENT

内皮细胞靶向癌症治疗

• 批准号: 3838151
• 负责人: E SAUSVILLE
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838151
• 关键词: biological response modifiers; biomarker; cell communication molecule; cell cycle; cytokine; gene expression; hemostatics; human tissue; intercellular connection; neoplasm /cancer therapy; neoplastic cell; nitric oxide; surface antigens; toxin; vascular endothelium; von Willebrand factor

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.

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 该项目包括一个细胞表面决定因素的定义， 增殖的内皮细胞，因为这些分子可以被开发出来 作为选择性毒性分子传递的靶点; 在人类肿瘤的组织切片中， 内皮细胞活化标记物，例如最近描述的EDG 1 基因，（在刺激分化的内皮细胞后出现 肿瘤坏死因子、白细胞介素-1或肿瘤坏死因子 促进佛波醇酯）和内皮细胞增殖标记物， 包括由EN 2/3和70-1抗体识别的抗原; 检查可能介导的内皮细胞反应途径 抗肿瘤活性，包括一氧化氮生成系统， 促凝血活性的阐述，包括血管性血友病 因子;内皮细胞在血管生成中作用的检查 通过各种生物反应观察到的毒性的详细说明 修饰剂，包括奎宁诱导的细胞不稳定 连接和内皮细胞阻力的改变 细胞因子和毒素。