ENDOTHELIAL CELL TARGETED CANCER TREATMENT

内皮细胞靶向癌症治疗

• 批准号: 3752421
• 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/3752421
• 关键词: antineoplastics; biological response modifiers; biomarker; cell communication molecule; cell cycle; cytokine; gene expression; hemostatics; human tissue; messenger RNA; neoplasm /cancer therapy; neoplastic cell; nitric oxide; polymerase chain reaction; surface antigens; tissue /cell culture; toxin; vascular endothelium

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.

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， 利用这些信息作为开发新的癌症治疗方法的基础 其影响内皮细胞功能。 使用原代培养物 人脐静脉内皮细胞，本项目的具体目标 包括对增殖具有选择性毒性的制剂的定义， 正常内皮细胞;细胞表面决定簇的定义 增殖的内皮细胞，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点;更详细 细胞增殖标志物的表征，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 氧化物生成系统，以及促凝活性的详细说明; 检查内皮细胞在制造 通过各种生物反应调节剂观察到的毒性，包括 苦参碱诱导的细胞连接不稳定; 内皮细胞对抗增殖剂的敏感性 细胞因子和毒素。 最近的研究已经确定了 葫芦素抑制内皮细胞增殖， 葫芦素E（NSC 106399）通过可能破坏肌动蛋白的机制， 细胞骨架 然而，葫芦素的令人信服的生物学作用， 证明体内抗血管生成活性尚未实现。 利用基于PCR的mRNA差异显示策略 扩增，候选基因差异表达在增殖 内皮细胞已经被定义。