Effects of PTK787/ZK 222584, a Specific Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, on Primary Tumor, Metastasis, Vessel Density, and Blood Flow in a Murine Renal Cell Carcinoma Model

摘要: Antiangiogenic therapy is a promising new strategy to inhibit tumor growth and formation of metastases. Vascular endothelial factor (VEGF) its receptors, VEGF-receptor 1 (VEGF-R1; FLT-1) VEGF-R2 (KDR), have been shown play major role in angiogenesis. PTK787/ZK 222584, specific inhibitor both tyrosine kinases, was investigated for antitumoral antiangiogenic activity murine renal cell carcinoma model. After intrarenal application the cells, mice develop primary metastases lung abdominal lymph nodes. Daily oral with 222584 at dose 50 mg/kg resulted significant decrease 61 67% tumors after 14 21 days, respectively. The occurrence significantly inhibited time points (98% reduction 78% reduction, respectively). no node developed 222584-treated group, whereas days treatment, were reduced by 87%. Vessel density tissues, detected immunohistochemistry an anti-CD31 antibody, decreased 222584. Using color Doppler imaging ultrasound, changes blood flow feeding artery found under treatment Blood correlated vessel but not volume. compound well tolerated all vivo experiments had effects on body weight or general well-being animals. This contrast animals treated agent TNP-470. s.c. 30 TNP-470 every other day be discontinued 13 because animal loss (>20%) ataxia. These results demonstrate that potent growth, formation, vascularization carcinoma. Furthermore, we able ultrasound can used measure correlates density. Thus, this may valuable noninvasive method monitoring agents such as vasculature.