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Evaluation of the Response of Intracranial Xenografts to VEGF Signaling Inhibition Using Multiparametric MRI.
- Source :
-
Neoplasia (New York, N.Y.) [Neoplasia] 2017 Sep; Vol. 19 (9), pp. 684-694. Date of Electronic Publication: 2017 Aug 04. - Publication Year :
- 2017
-
Abstract
- Vascular 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 <superscript>luc</superscript> 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 <superscript>luc</superscript> tumors, this was associated with lower K <superscript>trans</superscript> (compound biomarker of perfusion and vascular permeability) than in vehicle-treated controls. Cediranib also induced significant reductions in both K <superscript>trans</superscript> 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 <superscript>trans</superscript> , 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.<br /> (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Brain Neoplasms drug therapy
Brain Neoplasms pathology
Cell Line, Tumor
Diffusion Magnetic Resonance Imaging
Disease Models, Animal
Humans
Image Enhancement
Luminescent Measurements methods
Mice
Molecular Imaging
Molecular Targeted Therapy
Neovascularization, Pathologic diagnosis
Neovascularization, Pathologic diagnostic imaging
Neovascularization, Pathologic drug therapy
Treatment Outcome
Xenograft Model Antitumor Assays
Angiogenesis Inhibitors pharmacology
Brain Neoplasms diagnostic imaging
Brain Neoplasms metabolism
Magnetic Resonance Imaging methods
Protein Kinase Inhibitors pharmacology
Signal Transduction drug effects
Vascular Endothelial Growth Factor A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5586
- Volume :
- 19
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Neoplasia (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 28780387
- Full Text :
- https://doi.org/10.1016/j.neo.2017.05.007