Early effects of combretastatin-A4 disodium phosphate on tumor perfusion and interstitial fluid pressure.
Combretastatin-A4 disodium phosphate (CA4DP) is a vascular-disruptive agent that causes an abrupt decrease in tumor blood flow. The direct actions of CA4DP include increases in vascular permeability and destabilization of the endothelial cytoskeleton, which are thought to contribute to occlusion of the tumor vasculature. It has been proposed that increased permeability causes a transient increase in interstitial fluid pressure (IFP), which in turn could collapse intratumoral blood vessels. We examined the immediate effects of CA4DP on tumor IFP in C3H mammary carcinoma. Mice were treated with 100 mg/kg CA4DP by intraperitoneal injection. Tumor perfusion was recorded by laser Doppler flowmetry at separate time points, and IFP was recorded continuously by the wick-in-needle method. In this study, we found that CA4DP treatment resulted in a rapid reduction in tumor perfusion, followed by a decrease in IFP; no increases in IFP were observed. This suggests that CA4DP-induced reductions in tumor perfusion are not dependent on increases in IFP.
Ley
Carsten D
CD
Laboratory of Experimental Oncology, Institute of Molecular Pathology, University of Copenhagen, Copenhagen, Denmark. science@ley.dk
Horsman
Michael R
MR
Kristjansen
Paul E G
PE
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004354:Drug Screening Assays, Antitumor; D045604:Extracellular Fluid / Q000187:drug effects*; D005260:Female; D005528:Foot; D007274:Injections, Intraperitoneal; D017078:Laser-Doppler Flowmetry; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D008365:Manometry / Q000295:instrumentation / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011312:Pressure; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D016042:Transplantation, Heterotopic; D047368:Tumor Burden
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C058728:fosbretabulin