Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.

<h4>Objective</h4>To investigate dynamic contrast-enhanced computed tomography for monitoring the effects of regorafenib on experimental colon carcinomas in rats by quantitative assessments of tumor microcirculation parameters with immunohistochemical validation.<h4>Materials and m...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Clemens C Cyran, Philipp M Kazmierczak, Heidrun Hirner, Matthias Moser, Michael Ingrisch, Lukas Havla, Alexandra Michels, Ralf Eschbach, Bettina Schwarz, Maximilian F Reiser, Christiane J Bruns, Konstantin Nikolaou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6cfe076e2c15477cb2e62b649289aa55
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6cfe076e2c15477cb2e62b649289aa55
record_format	dspace
spelling	oai:doaj.org-article:6cfe076e2c15477cb2e62b649289aa552021-11-18T08:53:16ZRegorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.1932-620310.1371/journal.pone.0076009https://doaj.org/article/6cfe076e2c15477cb2e62b649289aa552013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098755/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>To investigate dynamic contrast-enhanced computed tomography for monitoring the effects of regorafenib on experimental colon carcinomas in rats by quantitative assessments of tumor microcirculation parameters with immunohistochemical validation.<h4>Materials and methods</h4>Colon carcinoma xenografts (HT-29) implanted subcutaneously in female athymic rats (n = 15) were imaged at baseline and after a one-week treatment with regorafenib by dynamic contrast-enhanced computed tomography (128-slice dual-source computed tomography). The therapy group (n = 7) received regorafenib daily (10 mg/kg bodyweight). Quantitative parameters of tumor microcirculation (plasma flow, mL/100 mL/min), endothelial permeability (PS, mL/100 mL/min), and tumor vascularity (plasma volume, %) were calculated using a 2-compartment uptake model. Dynamic contrast-enhanced computed tomography parameters were validated with immunohistochemical assessments of tumor microvascular density (CD-31), tumor cell apoptosis (TUNEL), and proliferation (Ki-67).<h4>Results</h4>Regorafenib suppressed tumor vascularity (15.7±5.3 to 5.5±3.5%; p<0.05) and tumor perfusion (12.8±2.3 to 8.8±2.9 mL/100 mL/min; p = 0.063). Significantly lower microvascular density was observed in the therapy group (CD-31; 48±10 vs. 113±25, p<0.05). In regorafenib-treated tumors, significantly more apoptotic cells (TUNEL; 11844±2927 vs. 5097±3463, p<0.05) were observed. Dynamic contrast-enhanced computed tomography tumor perfusion and tumor vascularity correlated significantly (p<0.05) with microvascular density (CD-31; r = 0.84 and 0.66) and inversely with apoptosis (TUNEL; r = -0.66 and -0.71).<h4>Conclusions</h4>Regorafenib significantly suppressed tumor vascularity (plasma volume) quantified by dynamic contrast-enhanced computed tomography in experimental colon carcinomas in rats with good-to-moderate correlations to an immunohistochemical gold standard. Tumor response biomarkers assessed by dynamic contrast-enhanced computed tomography may be a promising future approach to a more personalized and targeted cancer therapy.Clemens C CyranPhilipp M KazmierczakHeidrun HirnerMatthias MoserMichael IngrischLukas HavlaAlexandra MichelsRalf EschbachBettina SchwarzMaximilian F ReiserChristiane J BrunsKonstantin NikolaouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e76009 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Clemens C Cyran Philipp M Kazmierczak Heidrun Hirner Matthias Moser Michael Ingrisch Lukas Havla Alexandra Michels Ralf Eschbach Bettina Schwarz Maximilian F Reiser Christiane J Bruns Konstantin Nikolaou Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.
description	<h4>Objective</h4>To investigate dynamic contrast-enhanced computed tomography for monitoring the effects of regorafenib on experimental colon carcinomas in rats by quantitative assessments of tumor microcirculation parameters with immunohistochemical validation.<h4>Materials and methods</h4>Colon carcinoma xenografts (HT-29) implanted subcutaneously in female athymic rats (n = 15) were imaged at baseline and after a one-week treatment with regorafenib by dynamic contrast-enhanced computed tomography (128-slice dual-source computed tomography). The therapy group (n = 7) received regorafenib daily (10 mg/kg bodyweight). Quantitative parameters of tumor microcirculation (plasma flow, mL/100 mL/min), endothelial permeability (PS, mL/100 mL/min), and tumor vascularity (plasma volume, %) were calculated using a 2-compartment uptake model. Dynamic contrast-enhanced computed tomography parameters were validated with immunohistochemical assessments of tumor microvascular density (CD-31), tumor cell apoptosis (TUNEL), and proliferation (Ki-67).<h4>Results</h4>Regorafenib suppressed tumor vascularity (15.7±5.3 to 5.5±3.5%; p<0.05) and tumor perfusion (12.8±2.3 to 8.8±2.9 mL/100 mL/min; p = 0.063). Significantly lower microvascular density was observed in the therapy group (CD-31; 48±10 vs. 113±25, p<0.05). In regorafenib-treated tumors, significantly more apoptotic cells (TUNEL; 11844±2927 vs. 5097±3463, p<0.05) were observed. Dynamic contrast-enhanced computed tomography tumor perfusion and tumor vascularity correlated significantly (p<0.05) with microvascular density (CD-31; r = 0.84 and 0.66) and inversely with apoptosis (TUNEL; r = -0.66 and -0.71).<h4>Conclusions</h4>Regorafenib significantly suppressed tumor vascularity (plasma volume) quantified by dynamic contrast-enhanced computed tomography in experimental colon carcinomas in rats with good-to-moderate correlations to an immunohistochemical gold standard. Tumor response biomarkers assessed by dynamic contrast-enhanced computed tomography may be a promising future approach to a more personalized and targeted cancer therapy.
format	article
author	Clemens C Cyran Philipp M Kazmierczak Heidrun Hirner Matthias Moser Michael Ingrisch Lukas Havla Alexandra Michels Ralf Eschbach Bettina Schwarz Maximilian F Reiser Christiane J Bruns Konstantin Nikolaou
author_facet	Clemens C Cyran Philipp M Kazmierczak Heidrun Hirner Matthias Moser Michael Ingrisch Lukas Havla Alexandra Michels Ralf Eschbach Bettina Schwarz Maximilian F Reiser Christiane J Bruns Konstantin Nikolaou
author_sort	Clemens C Cyran
title	Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.
title_short	Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.
title_full	Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.
title_fullStr	Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.
title_full_unstemmed	Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.
title_sort	regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6cfe076e2c15477cb2e62b649289aa55
work_keys_str_mv	AT clemensccyran regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT philippmkazmierczak regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT heidrunhirner regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT matthiasmoser regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT michaelingrisch regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT lukashavla regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT alexandramichels regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT ralfeschbach regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT bettinaschwarz regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT maximilianfreiser regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT christianejbruns regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation AT konstantinnikolaou regorafenibeffectsonhumancoloncarcinomaxenograftsmonitoredbydynamiccontrastenhancedcomputedtomographywithimmunohistochemicalvalidation
_version_	1718421206632235008

Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.

Ejemplares similares