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Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to vascular targeting agents

journal contribution
posted on 2023-06-07, 20:25 authored by Simon Akerman, Constantino Carlos Reyes-Aldasoro, Matthew Fisher, Katie L Pettyjohn, Meit A Björndahl, Helen Evans, Gillian M Tozer
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.

History

Publication status

  • Published

Journal

Medical Engineering & Physics

ISSN

1350-4533

Publisher

Elsevier

Issue

7

Volume

33

Page range

805-809

Department affiliated with

  • Engineering and Design Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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