TY - JOUR
T1 - Effects of tyrosine kinase inhibitors and CXCR4 antagonist on tumor growth and angiogenesis in rat glioma model
T2 - MRI and protein analysis study
AU - Ali, Meser M.
AU - Kumar, Sanath
AU - Shankar, Adarsh
AU - Varma, Nadimpalli R.S.
AU - Iskander, A. S.M.
AU - Janic, Branislava
AU - Chwang, Wilson B.
AU - Jain, Rajan
AU - Babajeni-Feremi, Abbas
AU - Borin, Thaiz Ferraz
AU - Bagher-Ebadian, Hassan
AU - Brown, Stephen L.
AU - Ewing, James R.
AU - Arbab, Ali Syed
N1 - Funding Information:
Address all correspondence to: Ali S. Arbab, MD, PhD, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, 1 Ford Place, 2F, Box-82, Detroit, MI 48202. E-mail: saali@rad.hfh.edu 1The work is supported by the National Institutes of Health (NIH) grants R01CA122031 (to A.S.A.), 1R01CA160216 (A.S.A.), 1R01CA172048 (A.S.A.), and K25CA129173 (M.M.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 2Equal contribution. Received 21 August 2013; Revised 26 September 2013; Accepted 30 September 2013 Copyright © 2013 Neoplasia Press, Inc. Open access under CC BY-NC-ND license. 1944-7124/13 DOI 10.1593/tlo.13559
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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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U2 - 10.1593/tlo.13559
DO - 10.1593/tlo.13559
M3 - Article
AN - SCOPUS:84891685345
SN - 1936-5233
VL - 6
SP - 660
EP - 669
JO - Translational Oncology
JF - Translational Oncology
IS - 6
ER -
