Tumour parameters affected by combretastatin A-4 phosphate therapy in a human colorectal xenograft model in nude mice.
Combretastatin A-4 phosphate (CA4-P) is an antivascular agent which inhibits tumour blood flow. The effects of CA4-P were studied at 1 and 24h in colorectal xenografts by the concomitant imaging of multiple physiological parameters (hypoxia, blood vessels and perfusion), selected to demonstrate changes related to vascular shut-down. Untreated tumours were viable, with perfused blood vessels throughout and only small areas of hypoxia. At 1h post-treatment, although blood vessels remained throughout the tumour, perfused vessels were mainly restricted to the rim. However, hypoxia was widespread in both peripheral and central parts of the tumour. Quantitative analysis also revealed a significant decrease in perfusion and a maximum increase in hypoxia at this time-point. Conversely, at 24h after treatment, when most of the tumour was necrotic, pathophysiological conditions in the surviving viable rim were already returning to normal: perfusion was increasing, and hypoxia was greatly reduced and restricted to regions bordering central necrosis. In conclusion, these data provide an insight into the actions by which CA4-P may exert its effects on solid tumours.
El-Emir
Ethaar
E
Cancer Research UK Targeting and Imaging Group, Department of Oncology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK. e.el-emir@ucl.ac.uk
Boxer
Geoffrey M
GM
Petrie
Ingrid A
IA
Boden
Robert W
RW
Dearling
Jason L J
JL
Begent
Richard H J
RH
Pedley
R Barbara
RB
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013267:Stilbenes / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C058728:fosbretabulin