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Abstract

In this work we studied the functional differences between the microcirculation of murine tumours that only express single isoforms of vascular endothelial growth factor-A (VEGF), VEGF120 and VEGF188, and the effect of VEGF receptor tyrosine kinase (VEGF-R TK) inhibition on their functional response to the vascular disrupting agent, combretastatin A-4 phosphate (CA-4-P). We used measurement of fluorescently- labelled red blood cell (RBC) velocities in tumour microvessels to study this functional response. RBC velocity for control VEGF120-expressing tumours was over 50% slower than for control VEGF188- expressing tumours, which may be due to the immature and haemorrhagic vasculature of the VEGF120 tumour. After chronic treatment with a VEGF-R tyrosine kinase inhibitor, SU5416, RBC velocities in VEGF120 tumours were significantly increased compared to control VEGF120 tumours, and similar to velocities in both VEGF188 treatment groups. Control and SU5416 treated VEGF188 tumours were not different from each other. Treatment of VEGF120 tumours with SU5416 reduced their vascular response to CA-4-P to a similar level to the VEGF188 tumours. Differential expression of VEGF isoforms not only affected vascular function in untreated tumours but also impacted on response to a vascular disrupting drug, CA-4-P, alone and in combination with an anti-angiogenic approach involving VEGF-R TK inhibition. Analysis of RBC velocities is a useful tool in measuring functional responses to vascular targeted treatments.

Publication Type:	Conference or Workshop Item (Paper)
Additional Information:	NOTICE: this is the author’s version of a work that was accepted for publication in Medical Engineering & Physics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Akerman, S., Reyes-Aldasoro, C. C., Fisher, M., Pettyjohn, K. L., Björndahl, M. A., Evans, H. & Tozer, G. M. (2011). Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to vascular targeting agents. Medical Engineering & Physics, 33(7), pp. 805-809, http://dx.doi.org/10.1016/j.medengphy.2010.09.006
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) T Technology > TA Engineering (General). Civil engineering (General)
Departments:	School of Science & Technology > Engineering School of Science & Technology > Computer Science > giCentre
Related URLs:	Author

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