PAZOPANIB COMPARED TO AVASTIN, GLEEVEC, SUTENT FOR TUMOR ANGEIOGENESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究将集中于表征帕唑帕尼对肿瘤生物学和生理学的影响。对照肿瘤的研究(仅限车辆)将用于比较。将研究两种剂量的药物，每天30 mg/kg和100 mg/kg。这个目前的项目只涉及侧翼肿瘤。 所有治疗小鼠将被分成一个亚组，其中肿瘤接受组织学和蛋白质组分析，另一个亚组，肿瘤正在接受葛兰素史克的药物浓度分析。后一个子集还将分析肠液压力(IFP)，因为我们希望避免IFP测量与蛋白质组分析的任何潜在干扰。如前所述，我们将(除肿瘤外)取出、称重和快速冷冻最重要的器官进行生物分布研究，如肾脏、肝脏、大脑和心脏。我们将使用光学、超声和动态对比增强(DCE)-MRI方法来评估肿瘤的氧化还原状态和渗透性/灌注的变化。 这项研究的安排如下： 将使用3种不同的肿瘤细胞系：HCT116、A549、H520 每株小鼠分3组：对照组、低剂量组、高剂量组 MCE将进行两次分析：在开始治疗之前，当肿瘤大小达到8 mm时 小鼠将接受14天的治疗，然后进行第二次超声检查

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will focus on characterization of the effects of Pazopanib only on tumor biology and physiology. Studies in control tumors (vehicle only) will be done for comparison. Two doses of drug will be studied, 30 and 100 mg/kg/day. This current project deals with flank tumors only. All treatment mice will be split up into one subgroup where tumors undergo histological and proteomic analysis and another subset where tumors are being analyzed for the drug concentration by GlaxoSmithKline. This latter subset will also be analyzed for intestitial fluid pressure (IFP), since we want to avoid any potential interference of IFP measurement with proteomic analyses. As discussed previously, we will (additional to the tumors) remove, weigh, and snap freeze the most important organs for a biodistribution study, such as kidneys, liver, brain and heart. We will use optical, ultrasound and dynamic contrast-enhanced (DCE)-MRI methods to assess tumors for changes in redox status and permeability/perfusion. The study is organized as follows: + 3 different tumor cell lines will be used: HCT116, A549, H520 + Per cell line 3 groups of mice: control group, low dose group, high dose group + Mce will be analyzed twice: before start of therapy, when tumor reached a size of 8mm + Mice will be treated for 14 days and then the second US will be performed