MICROVESSEL PERMEABILITY AND TUMOR METASTASIS

描述：(改编自调查人员的摘要)这是第一次 提交由新设立的学术研究促进奖(地区)拨款 旨在研究微血管通透性在肿瘤中的作用的研究人员 用大鼠在体肠系膜血管模型进行细胞外渗。整体而言 该提案的目的是量化微血管之间的关系 微血管通透性与肿瘤生长转移的关系 血管内皮生长因子诱导的高通透性与增强性有关的假说 肿瘤细胞黏附和渗出。四个假设将被检验。1.那个 血管内皮生长因子诱导的高通透性增强肿瘤细胞的黏附和外渗， 2.这种外渗需要乳腺癌中特定的信号分子 细胞，3.诱导内皮细胞内cAMP增加的药物 降低血管内皮生长因子引起的高通透性；4.这些药物抑制 肿瘤细胞黏附和渗出。使用的体内模型包括 大鼠肠系膜微血管灌流，其中通透性 通过注射荧光染色的分子和 由荧光视频显微镜监控。肿瘤粘连和渗出 同样，通过跟踪荧光标记的肿瘤细胞来评估细胞。 根据提出的4个假设，该提案有4个具体目标。在AIM 1、观察血管内皮生长因子对微血管通透性的影响。在……里面 特异靶向2：血管内皮生长因子对肿瘤细胞黏附和渗出的影响 将会被确定。特效靶3，8种溴代环磷腺苷及其制剂的作用 福司可林或罗利普兰等增加血管内皮生长因子cAMP诱导 我们将检查高渗透性。在具体目标4中，这些措施的效果 治疗肿瘤细胞渗出的药物将会被研究。预计这将是 该项目将为肿瘤的定量评估提供一个有用的工具 微血管传输和帮助定义新的靶点类别 化疗药物设计。

DESCRIPTION: (Adapted from the investigator's abstract) This is a first submission of an Academic Research Enhancement Award (AREA) grant from a new investigator aimed at examining the role of microvessel permeability in tumor cell extravasation using an in vivo rat mesentery vessels model. The overall objective of the proposal is to quantify the relationship between microvessel permeability and tumor growth and metastasis in intact microvessels and to test the hypothesis that VEGF induced hyperpermeability is associated with enhanced tumor cell adhesion and extravasation. Four hypotheses will be tested. 1. That VEGF induced hyperpermeability enhances tumor cell adhesion and extravasation, 2. That extravasation requires specific signaling molecules in breast cancer cells, 3. That agents that induce an increase in cAMP in endothelial cells decrease hyperpermeability caused by VEGF and 4. that these agents inhibit tumor cell adhesion and extravasation. The in vivo model used consists of perfused mesenteric microvessels from rat in which permeability is quantitatively determined by injection of fluorescently dyed molecules and monitored by fluorescent video microscopy. Adhesion and extravasation of tumor cells is similarly evaluated by following fluorescently labeled tumor cells. The proposal has 4 specific aims according to the 4 hypotheses proposed. In aim 1, the effect of VEGF on microvessel permeability will be evaluated. In specific aim 2, the effect of VEGF on tumor cell adhesion and extravasation will be determined. In specific aim 3, the effect of 8 bromo-cAMP and agents that increase cAMP such as forskolin or rolipram on VEGF induces hyperpermeability will be examined. In specific aim 4 the effect of these agents on tumor cell extravasation will be studied. It is anticipated that this project will provide a useful tool in the quantitative assessment of tumor microvessel transport and help define a new class of target for chemotherapeutic drug design.