The VEGF receptor tyrosine kinase inhibitor, ZD6474, inhibits angiogenesis and affects microvascular architecture within an orthotopically implanted renal cell carcinoma.

摘要: The proangiogenic vascular endothelial growth factor-A (VEGF) is essential for the development of new tumor vessels. ZD6474 a novel inhibitor VEGF receptor-2 (VEGFR-2) tyrosine kinase activity, which also has additional activity against epidermal factor (EGF) receptor kinase. antitumor different schedules in clinically relevant, metastasizing, murine renal cell carcinoma (RENCA) model was evaluated this study. RENCA cells were inoculated into left kidney 24 mice (day 0). Daily (50 mg/kg p.o.) treatment initiated 1 day or 10 days after inoculation and continued until 21. Following treatment, weight volume assessed blood vessel density determined by CD31 staining. Visible metastases lungs, spleen, lymph nodes quantified using dissection microscope. In an study, animals treated according to same regimen quantitative three-dimensional microvascular corrosion casting performed enable detailed assessment architecture. Therapy on resulted 79% 59% reduction primary volume, 60% number lung metastases, 58% tumors compared with control group, respectively. Corrosion proved 5.4- 3.2-fold lower untreated tumors, observations that paralleled significant architectural alterations. model, highly active angiogenesis, metastasis.