Effects of Tyrosine Kinase Inhibitors and CXCR4 Antagonist on Tumor Growth and Angiogenesis in Rat Glioma Model: MRI and Protein Analysis Study |
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Authors: | Meser M. Ali Sanath Kumar Adarsh Shankar Nadimpalli R.S. Varma A.S.M. Iskander Branislava Janic Wilson B. Chwang Rajan Jain Abbas Babajeni-Feremi Thaiz F. Borin Hassan Bagher-Ebadian Stephen L. Brown James R. Ewing Ali S. Arbab |
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Affiliation: | 2. Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI;3. Division of Clinical Neurosciences, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN;4. Department of Neurology, Henry Ford Hospital, Detroit, MI;5. Department of Radiology, Wayne State University School of Medicine, Detroit, MI |
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Abstract: | The aim of the study was to determine the antiangiogenic efficacy of vatalanib, sunitinib, and AMD3100 in an animal model of human glioblastoma (GBM) by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and tumor protein expression analysis. Orthotopic GBM-bearing animals were randomly assigned either to control group or vatalanib, sunitinib, and AMD3100 treatment groups. Following 2 weeks of drug treatment, tumor growth and vascular parameters were measured using DCE-MRI. Expression of different angiogenic factors in tumor extracts was measured using a membrane-based human antibody array kit. Tumor angiogenesis and invasion were determined by immunohistochemistry. DCE-MRI showed a significant increase in tumor size after vatalanib treatment. AMD3100-treated group showed a significant decrease in a number of vascular parameters determined by DCE-MRI. AMD3100 significantly decreased the expression of different angiogenic factors compared to sunitinib or vatalanib; however, there were no significant changes in vascular density among the groups. Sunitinib-treated animals showed significantly higher migration of the invasive cells, whereas in both vatalanib- and AMD3100-treated animals the invasive cell migration distance was significantly lower compared to that of control. Vatalanib and sunitinib resulted in suboptimal therapeutic effect, but AMD3100 treatment resulted in a significant reduction in tumor growth, permeability, interstitial space volume, and invasion of tumor cells in an animal model of GBM. |
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