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Abstract

In this work we studied the functional differences between the microcirculation of murine tumours that express only single isoforms of vascular endothelial growth factor-A (VEGF), namely 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), using measurement of red blood cell (RBC) velocity by a 'keyhole' tracking algorithm. RBC velocities in VEGF188 tumours were unaffected by chronic treatment with a VEGF-R tyrosine kinase inhibitor, SU5416, whereas RBC velocities in VEGF120 tumours were significantly increased compared to control VEGF120 tumours. This effect was accompanied by a reduced tumour vascularisation. Pre-treatment of VEGF120 tumours with SU5416 made them much more resistant to CA-4-P treatment, with a RBC velocity response that was very similar to that of the more mature vasculature of the VEGF188 tumours. This study shows that vascular normalisation following anti-angiogenic treatment with a VEGF-R tyrosine kinase inhibitor reduced the response of a previously sensitive tumour line to CA-4-P.

Publication Type:	Article
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 Medical Engineering & Physics, Volume 33, Issue 7, September 2011, Pages 805–809
Publisher Keywords:	Animals, Antineoplastic Agents, Blood Vessels, Erythrocytes, Fluorescent Dyes, Gene Expression Regulation, Neoplastic, Hemodynamics, Male, Mice, Neoplasms, Protein Isoforms, Protein Kinase Inhibitors, Receptor Protein-Tyrosine Kinases, Stilbenes, Vascular Endothelial Growth Factor A
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
SWORD Depositor:	Symplectic Administrator

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