VEGF Trap induces antiglioma effect at different stages of disease
VEGF Trap induces antiglioma effect at different stages of disease
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DOI：
10.1215/15228517-2008-061
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发表时间：
2008-12-01
期刊：
影响因子：
15.9
通讯作者：
Yung, W. K. Alfred
中科院分区：
文献类型：
--
作者：
Gomez-Manzano, Candelaria;Holash, Jocelyn;Yung, W. K. Alfred
病理性血管生成是癌症的标志，特别是胶质母细胞瘤，最恶性和最常见的原发性脑肿瘤。血管内皮生长因子（VEGF）是调节原发性恶性脑肿瘤高血管表型的关键蛋白。在这项研究中，我们在颅内胶质瘤模型中测试了VEGF Trap，一种VEGF的可溶性诱饵受体。VEGF Trap以短期或长期的时间表给予处于不同疾病阶段的患有人神经胶质瘤的动物。重要的是，VEGF Trap治疗在肿瘤发展的初始和晚期阶段均有效，显著增加了总生存期。此外，这种作用在接受更长时间方案治疗的动物中得到增强。此外，我们观察到出现了一种VEGF Trap耐药表型，其特征是肿瘤生长和侵袭性增加。我们的研究结果表明，VEGF Trap将有效治疗复发性或进行性可切除的胶质母细胞瘤患者和接受过广泛初次手术的患者。最后，我们的研究结果表明，VEGF Trap的临床成功可能取决于联合治疗中的长期治疗，旨在同时抑制血管生成和肿瘤侵袭。Neuro-Oncology 10，940-945，2008（Posted to Neuro-Oncology [serial online]，Doc. D 08 -00085，2008年8月14日。网址http://neuro-oncology.dukejournals.org; DOI：10.1215/15228517-2008-061）
Pathological angiogenesis is a hallmark of cancer, specifically of glioblastomas, the most malignant and common primary brain tumor. Vascular endothelial growth factor ( VEGF) is the key protein in the regulation of the hyper-vascular phenotype of primary malignant brain tumors. In this study, we tested VEGF Trap, a soluble decoy receptor for VEGF, in an intracranial glioma model. VEGF Trap was administered in short or prolonged schedules to animals bearing human gliomas at different stages of disease. Of importance, VEGF Trap treatment was efficacious in both initial and advanced phases of tumor development by significantly increasing overall survival. Furthermore, this effect was enhanced in animals treated with more prolonged regimens. In addition, we observed the emergence of a VEGF Trap-resistant phenotype characterized by tumor growth and increased invasiveness. Our results suggest that VEGF Trap will be effective in treating both patients with recurrent or progressive resectable glioblastoma and patients that have undergone extensive initial surgery. Finally, our results indicate that the clinical success of VEGF Trap may depend on a prolonged treatment in combined therapy aiming to simultaneously inhibit angiogenesis and tumor invasion. Neuro-Oncology 10, 940-945, 2008 (Posted to Neuro-Oncology [serial online], Doc. D08-00085, August 14, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-061)