Rubenstein J L, Kim J, Ozawa T, Zhang M, Westphal M, Deen D F, Shuman M A
Division of Hematology/Oncology, University of California, San Francisco, USA.
Neoplasia. 2000 Jul-Aug;2(4):306-14. doi: 10.1038/sj.neo.7900102.
Vascular endothelial growth factor (VEGF) is an important mediator of the intense angiogenesis which is characteristic of glioblastoma. While genetic manipulation of VEGF/VEGF receptor expression has previously been shown to inhibit glioblastoma growth, to date, no study has examined the efficacy of pharmacologic blockade of VEGF activity as a means to inhibit intracranial growth of human glioblastoma. Using intraperitoneal administration of a neutralizing anti-VEGF antibody, we demonstrate that inhibition of VEGF significantly prolongs survival in athymic rats inoculated in the basal ganglia with G55 human glioblastoma cells. Systemic anti-VEGF inhibition causes decreased tumor vascularity as well as a marked increase in tumor cell apoptosis in intracranial tumors. Although intracranial glioblastoma tumors grow more slowly as a consequence of anti-VEGF treatment, the histologic pattern of growth suggests that these tumors adapt to inhibition of angiogenesis by increased infiltration and cooption of the host vasculature.
血管内皮生长因子（VEGF）是胶质母细胞瘤所特有的强烈血管生成的重要介质。虽然先前已证明对VEGF/VEGF受体表达进行基因操作可抑制胶质母细胞瘤生长，但迄今为止，尚无研究探讨药物阻断VEGF活性作为抑制人胶质母细胞瘤颅内生长手段的疗效。通过腹腔注射中和性抗VEGF抗体，我们证明抑制VEGF可显著延长在基底神经节接种G55人胶质母细胞瘤细胞的无胸腺大鼠的生存期。全身抗VEGF抑制导致颅内肿瘤的肿瘤血管减少以及肿瘤细胞凋亡显著增加。尽管抗VEGF治疗使颅内胶质母细胞瘤肿瘤生长更缓慢，但生长的组织学模式表明这些肿瘤通过增加对宿主脉管系统的浸润和利用来适应血管生成的抑制。
