Dalal Surita, Burchill Susan A
Candlelighter's Children's Cancer Research Group, Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, St. James's University Hospital, Beckett Street, Leeds, West Yorkshire LS9 7TF, UK.
Eur J Cancer. 2009 Mar;45(4):713-22. doi: 10.1016/j.ejca.2008.11.045. Epub 2009 Jan 10.
The effects of the tubulin-binding vascular-disrupting agents (VDAs), combretastatin A4 phosphate (CA4P), OXi4503/CA1P and OXi8007, in subcutaneous mouse models of the Ewing's sarcoma family of tumours (ESFTs) have been investigated alone and in combination with doxorubicin. Delay in subcutaneous tumour growth was observed following treatment of mice with multiple doses of OXi4503/CA1P but not with CA4P or OXi8007. A single dose of OXi4503/CA1P caused complete shutdown of vasculature by 24h and extensive haemorrhagic necrosis by 48h. However, a viable rim of proliferating cells remained, which repopulated the tumour within 10 days following the withdrawal of treatment. Combined treatment with doxorubicin 1h prior to administration of OXi4503/CA1P enhanced the effects of OXi4503/CA1P causing a synergistic delay in tumour growth (p<0.001). This study demonstrates that OXi4503/CA1P is a potent VDA in ESFT and in combination with conventional cytotoxic agents represents a promising treatment strategy for this tumour group.
已对微管蛋白结合型血管破坏剂（VDA）——磷酸考布他汀A4（CA4P）、OXi4503/CA1P和OXi8007在尤因肉瘤家族性肿瘤（ESFT）皮下小鼠模型中的作用进行了单独研究，并研究了其与多柔比星联合使用的效果。用多剂量的OXi4503/CA1P治疗小鼠后观察到皮下肿瘤生长延迟，但用CA4P或OXi8007治疗则未观察到这种延迟。单剂量的OXi4503/CA1P在24小时时导致血管完全关闭，在48小时时导致广泛的出血性坏死。然而，仍有一圈存活的增殖细胞，在停止治疗后10天内肿瘤重新生长。在给予OXi4503/CA1P前1小时与多柔比星联合治疗增强了OXi4503/CA1P的效果，导致肿瘤生长出现协同延迟（p<0.001）。本研究表明，OXi4503/CA1P在ESFT中是一种有效的VDA，与传统细胞毒性药物联合使用代表了针对该肿瘤组的一种有前景的治疗策略。
