The Morphological Evaluation of Walker 256 Tumors after Antiangiogenetic Therapy in Rats

Alexandra IRIMIE, Attila Tamas SZORA, Mihai SOCAIU, Alexandru Flaviu TÄ‚BÄ‚RAN, Raluca VIDRIGHINESCU, Cornel CÄ‚TOI



Sunitinib Malate is a multi-targeted receptor tyrosine kinase inhibitor, including the vascular endothelial growth factor receptors, and is used for treatment of pancreatic neuroendocrine, renal cell carcinoma and gastrointestinal stromal tumors. The formation of new blood vessels (angiogenesis) may consequently lead to the development of metastases and so the aim of this study was to evaluate the microvessel density (MVD) after sunitinib malate treatment. In this study 11 albino Wistar rats were inoculated subcutaneously with Walker 256 tumor (breast carcinoma cells) and after 5 weeks, 5 rats were administered sunitinib malate at a dosage of 40 mg/kg every 3 days for 2 weeks. After another 4 weeks the tumors were removed and morphologically evaluated (weighted, measured). The MVD determined and quantified by calculating the average between 3 random fields. In the tumoral stroma we calculated also the vascular area. The immunohistochemical analysis of the neovascularization was performed using an anti-rat antibody against CD34. The difference between tumor weights were statistical significant (p<0.05) (3.746 ± 1.633; 1.019 ± 0.812) but the tumor sizes and most importantly MVD between the control group and the experimental group were not statistical significant (p>0.05) (32.55 ± 18.83; 18.6 ± 4.734).   As a conclusion, the rats treated with Sunitinib malate did not show a lower microvessel density comparative to the untreated ones. The number of rats used in this research was too small and further studies are needed.


Keywords: Angiogenesis, MVD, Sunitinib Malate, Walker 256

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