PAZOPANIB COMPARED TO AVASTIN, GLEEVEC, SUTENT FOR TUMOR ANGEIOGENESIS

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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