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dc.contributor.authorBoult, JKRen_US
dc.contributor.authorBox, Gen_US
dc.contributor.authorVinci, Men_US
dc.contributor.authorPerryman, Len_US
dc.contributor.authorEccles, SAen_US
dc.contributor.authorJones, Cen_US
dc.contributor.authorRobinson, SPen_US
dc.identifier.citationNeoplasia (New York, N.Y.), 2017, 19 (9), pp. 684 - 694en_US
dc.description.abstractVascular endothelial growth factor A (VEGF-A) is considered one of the most important factors in tumor angiogenesis, and consequently, a number of therapeutics have been developed to inhibit VEGF signaling. Therapeutic strategies to target brain malignancies, both primary brain tumors, particularly in pediatric patients, and metastases, are lacking, but targeting angiogenesis may be a promising approach. Multiparametric MRI was used to investigate the response of orthotopic SF188<sup>luc</sup> pediatric glioblastoma xenografts to small molecule pan-VEGFR inhibitor cediranib and the effects of both cediranib and cross-reactive human/mouse anti-VEGF-A antibody B20-4.1.1 in intracranial MDA-MB-231 LM2-4 breast cancer xenografts over 48 hours. All therapeutic regimens resulted in significant tumor growth delay. In cediranib-treated SF188<sup>luc</sup> tumors, this was associated with lower K<sup>trans</sup> (compound biomarker of perfusion and vascular permeability) than in vehicle-treated controls. Cediranib also induced significant reductions in both K<sup>trans</sup> and apparent diffusion coefficient (ADC) in MDA-MB-231 LM2-4 tumors associated with decreased histologically assessed perfusion. B20-4.1.1 treatment resulted in decreased K<sup>trans</sup>, but in the absence of a change in perfusion; a non-significant reduction in vascular permeability, assessed by Evans blue extravasation, was observed in treated tumors. The imaging responses of intracranial MDA-MB-231 LM2-4 tumors to VEGF/VEGFR pathway inhibitors with differing mechanisms of action are subtly different. We show that VEGF pathway blockade resulted in tumor growth retardation and inhibition of tumor vasculature in preclinical models of pediatric glioblastoma and breast cancer brain metastases, suggesting that multiparametric MRI can provide a powerful adjunct to accelerate the development of antiangiogenic therapies for use in these patient populations.en_US
dc.format.extent684 - 694en_US
dc.subjectCell Line, Tumoren_US
dc.subjectBrain Neoplasmsen_US
dc.subjectDisease Models, Animalen_US
dc.subjectNeovascularization, Pathologicen_US
dc.subjectAngiogenesis Inhibitorsen_US
dc.subjectVascular Endothelial Growth Factor Aen_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectMagnetic Resonance Imagingen_US
dc.subjectDiffusion Magnetic Resonance Imagingen_US
dc.subjectImage Enhancementen_US
dc.subjectTreatment Outcomeen_US
dc.subjectLuminescent Measurementsen_US
dc.subjectXenograft Model Antitumor Assaysen_US
dc.subjectSignal Transductionen_US
dc.subjectMolecular Imagingen_US
dc.subjectMolecular Targeted Therapyen_US
dc.titleEvaluation of the Response of Intracranial Xenografts to VEGF Signaling Inhibition Using Multiparametric MRI.en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNeoplasia (New York, N.Y.)en_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.embargo.termsNo embargoen_US
icr.researchteamGlioma Teamen_US
icr.researchteamPre-Clinical MRIen_US
dc.contributor.icrauthorBoult, Jessicaen_US
dc.contributor.icrauthorJones, Chrisen_US
dc.contributor.icrauthorRobinson, Simonen_US

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