Anti-vascular approaches to solid tumour therapy: evaluation of combretastatin A4 phosphate.

摘要: Combretastatin A4 phosphate has recently been identified by us as an agent which can selectively damage tumour neovasculature. In the current study we establish that combretastatin induces extensive blood flow shutdown in compared to normal tissues. Histological assessment of vascular shows over 90% vessels are rendered non-functional 6 hrs post-treatment with 100 mg/kg i.p. Measurement using a diffusible tracer 86RbCl indicates overall reduction perfusion only 50-60%. This discrepancy probably reflects increased tissue vasculature supplying rim, is caused ischaemia-induced release vasoactive mediators. The induced administration results cell loss 24 following treatment, however this not translated into any significant effect on growth. continued growth attributed actively proliferating population cells at periphery tumour, dependent for their survival. We have attempted target residual combining cytotoxic approaches. Cis platinum and radiation used. show significantly enhance response both cis radiation. summary, studies confirm novel targets damages and, moreover, indicate its potential therapeutic usefulness adjuvant conventional