Characterizing the tumor response to treatment with combretastatin A4 phosphate.
OBJECTIVE
To examine the pathophysiologic impact of treatment with combretastatin A4 phosphate (CA4P) in regions of tumors that ultimately either necrose or survive treatment with this agent.


METHODS
Proliferation, perfusion, vessel density, and expression of vascular endothelial growth factor (VEGF) were analyzed in the KHT tumor model after treatment with CA4P. Analyses were conducted in the whole tumor and the tumor periphery.


RESULTS
Perfusion in the tumor periphery decreased 4 h after treatment, but returned to baseline 20 h later. Whole-tumor perfusion also decreased 4 h after treatment, but did not return to baseline. Vessel density decreased in the tumor as a whole, but not in the tumor periphery. No significant effect on the expression of VEGF was observed, but a decrease in proliferation in the whole tumor and the periphery was noted.


CONCLUSIONS
The present study shows that those areas of a tumor that survive treatment with CA4P are affected by CA4P exposure, though only transiently. The decrease in perfusion could negatively affect therapies utilizing the combination of CA4P and conventional anticancer agents by decreasing drug delivery and tissue oxygenation. These findings suggest that the timing of CA4P treatments when used in conjunction with conventional anticancer therapies should be considered carefully.
Salmon
Beth A
BA
Department of Pharmacology and Therapeutics, Shands Cancer Center, University of Florida, Gainesville, FL 32610, USA.
Siemann
Dietmar W
DW
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012513:Sarcoma, Experimental / Q000098:blood supply / Q000737:chemistry / Q000188:drug therapy*; D013267:Stilbenes / Q000627:therapeutic use*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D042442:Vascular Endothelial Growth Factors; C058728:fosbretabulin