PAZOPANIB COMPARED TO AVASTIN, GLEEVEC, SUTENT FOR TUMOR ANGEIOGENESIS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 本研究将集中于表征帕唑帕尼仅对肿瘤生物学和生理学的影响。将进行对照肿瘤（仅溶剂）研究以进行比较。将研究两种剂量的药物，30和100 mg/kg/天。目前的项目只涉及侧腹肿瘤。 将所有治疗小鼠分成一个亚组，其中肿瘤进行组织学和蛋白质组学分析，另一个亚组由GlaxoSmithKline分析肿瘤的药物浓度。还将分析后一个子集的肠液压（IFP），因为我们希望避免IFP测量对蛋白质组学分析的任何潜在干扰。如前所述，我们将（除肿瘤外）取出、称重并快速冷冻生物分布研究中最重要的器官，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。 研究报告的组织如下： + 将使用3种不同的肿瘤细胞系：HCT 116、A549、H520 + 每细胞系3组小鼠：对照组、低剂量组、高剂量组 + MCE将进行两次分析：治疗开始前，肿瘤大小达到8 mm时 + 小鼠将接受14天治疗，然后进行第二次US

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