Assessing tumor vascularization as a potential biomarker of imatinib resistance in gastrointestinal stromal tumors by dynamic contrast-enhanced magnetic resonance imagingReportar como inadecuado




Assessing tumor vascularization as a potential biomarker of imatinib resistance in gastrointestinal stromal tumors by dynamic contrast-enhanced magnetic resonance imaging - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Gastric Cancer

, Volume 20, Issue 4, pp 629–639

First Online: 19 December 2016Received: 20 July 2016Accepted: 20 November 2016DOI: 10.1007-s10120-016-0672-7

Cite this article as: Consolino, L., Longo, D.L., Sciortino, M. et al. Gastric Cancer 2017 20: 629. doi:10.1007-s10120-016-0672-7

Abstract

BackgroundMost metastatic gastrointestinal stromal tumors GISTs develop resistance to the first-line imatinib treatment. Recently, increased vessel density and angiogenic markers were reported in GISTs with a poor prognosis, suggesting that angiogenesis is implicated in GIST tumor progression and resistance. The purpose of this study was to investigate the relationship between tumor vasculature and imatinib resistance in different GIST mouse models using a noninvasive magnetic resonance imaging MRI functional approach.

MethodsImmunodeficient mice n = 8 for each cell line were grafted with imatinib-sensitive GIST882 and GIST-T1 and imatinib-resistant GIST430 human cell lines. Dynamic contrast-enhanced MRI DCE-MRI was performed on GIST xenografts to quantify tumor vessel permeability K and vascular volume fraction vp. Microvessel density MVD, permeability mean dextran density, MDD, and angiogenic markers were evaluated by immunofluorescence and western blot assays.

ResultsDynamic contrast-enhanced magnetic resonance imaging showed significantly increased vessel density P < 0.0001 and permeability P = 0.0002 in imatinib-resistant tumors compared to imatinib-sensitive ones. Strong positive correlations were observed between MRI estimates, K and vp, and their related ex vivo values, MVD r = 0.78 for K and r = 0.82 for vp and MDD r = 0.77 for K and r = 0.94 for vp. In addition, higher expression of vascular endothelial growth factor receptors VEGFR2 and VEFGR3 was seen in GIST430.

ConclusionsDynamic contrast-enhanced magnetic resonance imaging highlighted marked differences in tumor vasculature and microenvironment properties between imatinib-resistant and imatinib-sensitive GISTs, as also confirmed by ex vivo assays. These results provide new insights into the role that DCE-MRI could play in GIST characterization and response to GIST treatment. Validation studies are needed to confirm these findings.

KeywordsGastrointestinal stromal tumor Angiogenesis DCE-MRI Imatinib Gadolinium contrast agent Electronic supplementary materialThe online version of this article doi:10.1007-s10120-016-0672-7 contains supplementary material, which is available to authorized users.

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Autor: Lorena Consolino - Dario Livio Longo - Marianna Sciortino - Walter Dastrù - Sara Cabodi - Giovanni Battista Giovenzana -

Fuente: https://link.springer.com/







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