Regorafenib Effects on Human Colon Carcinoma Xenografts Monitored by Dynamic Contrast-Enhanced Computed Tomography with Immunohistochemical Validation: e76009

Objective 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. Materials and Methods Colon carcinoma xenogr...

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Veröffentlicht in:PloS one 2013-09, Vol.8 (9)
Hauptverfasser: Cyran, Clemens C, Kazmierczak, Philipp M, Hirner, Heidrun, Moser, Matthias, Ingrisch, Michael, Havla, Lukas, Michels, Alexandra, Eschbach, Ralf, Schwarz, Bettina, Reiser, Maximilian F
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Sprache:eng
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Zusammenfassung:Objective 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. Materials and Methods 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). Results Regorafenib suppressed tumor vascularity (15.7 plus or minus 5.3 to 5.5 plus or minus 3.5%; p
ISSN:1932-6203
DOI:10.1371/journal.pone.0076009