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Antitumor effect of the vascular-disrupting agent ZD6126 in a murine renal cell carcinoma model
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 3591656
Author(s) Medinger, M.; Esser, N.; Soltau, J.; Lehmann, K. M.; Konerding, M. A.; Wolloscheck, T.; Ryan, A. J.; Drevs, J.
Author(s) at UniBasel Medinger, Michael
Year 2011
Title Antitumor effect of the vascular-disrupting agent ZD6126 in a murine renal cell carcinoma model
Journal International journal of oncology
Volume 38
Number 2
Pages / Article-Number 455-64
Abstract ZD6126 is a vascular-disrupting agent that affects the endothelial tubulin cytoskeleton causing selective occlusion of tumor vasculature and extensive tumor cell necrosis. The present study evaluated the antitumor and antivascular activities of ZD6126 in the clinically relevant murine renal cell carcinoma (RENCA) model and also evaluated biological response to therapy using color Doppler imaging as biomarker. Mice were implanted with RENCA tumor cells (day 0) and established tumors were treated with ZD6126 (100 mg/kg i.p.) or vehicle with repeated intermittent doses on day 10, 14 and 18. ZD6126 treatment led to a significant reduction in tumor size and was associated with extensive tumor necrosis and a reduction in tumor blood flow versus controls. MVD increased with intermittent treatment (day 10, 14 and 18). In an additional study, animals were treated at day 19 and quantitative three-dimensional microvascular corrosion casting was performed to enable detailed assessment of the tumor vascular architecture. Corrosion casting showed that tumor vessel architecture is affected by treatment, whereas pre-existing vessels in control tissues are practically not affected. Inter-vessel and inter-branch distances as well as vessel diameters are influenced by treatment. In conclusion, ZD6126 showed potent antitumor efficacy in the RENCA model and our data suggest that decrease in tumor blood flow may be a useful surrogate marker of treatment effect.
Publisher Spandidos Publications
ISSN/ISBN 1791-2423
edoc-URL http://edoc.unibas.ch/43920/
Full Text on edoc No
Digital Object Identifier DOI 10.3892/ijo.2010.867
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/21152862
ISI-Number WOS:000286702600018
Document type (ISI) Journal Article
 
   

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