Combretastatin-A4 disrupts neovascular development in non-neoplastic tissue.
Combretastatin-A4 phosphate (cis-CA-4) is a tubulin-binding agent currently undergoing clinical trials as an anti-tumour drug. We have investigated whether CA-4 functions as a tumour-specific anti-vascular agent using the hyperplastic thyroid as a novel in vivo model of neovascularization. CA-4 elicited pathological changes in normal tissue, manifested as the induction of multiple, discrete intravascular thrombi. These vascular-damaging effects indicate that CA-4P does not function as a tumour-specific agent but targets neovasculature irrespective of the primary angiogenic stimulus.
Griggs
J
J
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
Hesketh
R
R
Smith
G A
GA
Brindle
K M
KM
Metcalfe
J C
JC
Thomas
G A
GA
Williams
E D
ED
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D013267:Stilbenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C058728:fosbretabulin