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  • Title: Impact of vessel maturation on antiangiogenic therapy in ovarian cancer.
    Author: Lu C, Thaker PH, Lin YG, Spannuth W, Landen CN, Merritt WM, Jennings NB, Langley RR, Gershenson DM, Yancopoulos GD, Ellis LM, Jaffe RB, Coleman RL, Sood AK.
    Journal: Am J Obstet Gynecol; 2008 Apr; 198(4):477.e1-9; discussion 477.e9-10. PubMed ID: 18395047.
    Abstract:
    OBJECTIVE: The purpose of this study was to examine the functional and therapeutic significance of pericytes in ovarian cancer vasculature. STUDY DESIGN: Tumor vessel morphologic condition and efficacy of endothelial and pericyte targeting were examined with the use of in vivo ovarian cancer models. The expression of platelet-derived growth factor (PDGF) ligands and receptors was examined in endothelial, pericyte-like, and ovarian cancer cells. RESULTS: Relative to normal vessels, tumor vasculature was characterized by loosely attached pericytes in reduced density. PDGF-BB was expressed predominantly by the endothelial and cancer cells, whereas PDGFRbeta was present in pericyte-like cells. PDGF-BB significantly increased the migration of and VEGF production by pericyte-like cells; PDGFRbeta blockade abrogated these effects. Dual VEGF (VEGF-Trap) and PDGF-B (PDGF-Trap) targeted therapy was more effective in inhibiting in vivo tumor growth than either agent alone. CONCLUSION: Aberrations in the tumor microenvironment contribute to endothelial cell survival. Strategies that target both endothelial cells and pericytes should be considered for clinical trials.
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