de Groot John F, Yung Wai Kwan Alfred
Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Cancer J. 2008 Sep-Oct;14(5):279-85. doi: 10.1097/PPO.0b013e3181867bd6.
Rapidly dividing glioma cells maintain adequate oxygen and nutrient delivery through co-opting existing host blood vessels or promoting the formation of new vessels, a process called angiogenesis. Vascular endothelial growth factor is a mediator of hypoxia-induced endothelial cell proliferation and migration and is highly expressed in gliomas, where it acts as a potent regulator of angiogenesis. The use of vascular endothelial growth factor receptor antagonists and vascular endothelial growth factor scavenging antibodies has generated excitement in neuro-oncology because of the rapid but reversible decrease in vascular permeability. This decrease in vascular permeability is marked by a decrease in cerebral edema and a decrease in contrast enhancement visualized on magnetic resonance imaging. These effects on the tumor vasculature are mistakenly referred to as tumor responses because the historical method of measuring tumor response and progression was based on tumor size assessed by contrast permeability through a leaky blood brain barrier. Despite the difficulties in accurately measuring the effect of antivascular endothelial growth factor therapy on tumor viability, several studies confirm that the antivascular endothelial growth factor human monoclonal antibody bevacizumab combined with irinotecan can significantly improve 6-month progression free survival of patients with malignant gliomas compared with historical controls. The impact of cytotoxic chemotherapy on the efficacy of bevacizumab and the effect of this therapy on overall survival are important questions that remain to be answered.
快速分裂的胶质瘤细胞通过利用现有的宿主血管或促进新血管形成来维持充足的氧气和营养供应，这一过程称为血管生成。血管内皮生长因子是缺氧诱导的内皮细胞增殖和迁移的介质，在胶质瘤中高度表达，在其中它作为血管生成的有效调节因子发挥作用。血管内皮生长因子受体拮抗剂和血管内皮生长因子清除抗体的使用在神经肿瘤学领域引起了关注，因为血管通透性会迅速但可逆地降低。这种血管通透性的降低表现为脑水肿减轻以及磁共振成像上可见的对比增强减弱。这些对肿瘤血管系统的影响被错误地称为肿瘤反应，因为以往测量肿瘤反应和进展的方法是基于通过渗漏的血脑屏障的对比通透性评估的肿瘤大小。尽管准确测量抗血管内皮生长因子疗法对肿瘤生存能力的影响存在困难，但多项研究证实，与历史对照相比，抗血管内皮生长因子人源单克隆抗体贝伐单抗联合伊立替康可显著提高恶性胶质瘤患者的6个月无进展生存率。细胞毒性化疗对贝伐单抗疗效的影响以及这种疗法对总生存期的影响是有待解答的重要问题。
