ArticlePloS one2013
Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed.
- Trial
- Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal cancer patients treated with regorafenib.European journal of nuclear medicine and molecular imaging · 2017Trial
- Enhancing Colorectal Cancer Treatment Through VEGF/VEGFR Inhibitors and Immunotherapy.Current treatment options in oncology · 2025Review
- Article
- Article
- Efficacy of regorafenib in acute pulmonary carcinomatous lymphangitis as a manifestation of rectal cancer: A case report.Oncology letters · 2019Article
- Anti-tumoral activity of single and combined regorafenib treatments in preclinical models of liver and gastrointestinal cancers.Experimental & molecular medicine · 2019Review
- Translational research and application of basic biology to clinical trial development in GI cancers.Annals of translational medicine · 2018Review
- Article
- Article
- Management of regorafenib-related toxicities: a review.Therapeutic advances in gastroenterology · 2015Review
- Targeting Angiogenesis in Cancer Therapy: Moving Beyond Vascular Endothelial Growth Factor.The oncologist · 2015Review
- Article
- Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer.PloS one · 2015Article
- Article
- miR-21 improves the neurological outcome after traumatic brain injury in rats.Scientific reports · 2014Article
- Dual-energy computed tomography for the assessment of early treatment effects of regorafenib in a preclinical tumor model: comparison with dynamic contrast-enhanced CT and conventional contrast-enhanced single-energy CT.European radiology · 2014Article
- Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo 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
methodsColon 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).
resultsRegorafenib 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).
conclusionsRegorafenib 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.
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