Batchelor Tracy T, Sorensen A Gregory, di Tomaso Emmanuelle, Zhang Wei-Ting, Duda Dan G, Cohen Kenneth S, Kozak Kevin R, Cahill Daniel P, Chen Poe-Jou, Zhu Mingwang, Ancukiewicz Marek, Mrugala Maciej M, Plotkin Scott, Drappatz Jan, Louis David N, Ivy Percy, Scadden David T, Benner Thomas, Loeffler Jay S, Wen Patrick Y, Jain Rakesh K
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Cancer Cell. 2007 Jan;11(1):83-95. doi: 10.1016/j.ccr.2006.11.021.
Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171-an oral tyrosine kinase inhibitor of VEGF receptors-has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1alpha, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor.
利用磁共振成像（MRI）技术，我们在此表明，通过每日给予AZD2171（一种口服的血管内皮生长因子（VEGF）受体酪氨酸激酶抑制剂）使复发性胶质母细胞瘤患者的肿瘤血管正常化起效迅速、作用持久但可逆，并且具有减轻水肿的显著临床益处。正常化的逆转在28天时开始，不过有些特征可持续长达四个月。当肿瘤逃避治疗时，碱性成纤维细胞生长因子（bFGF）、基质细胞衍生因子1α（SDF1α）和存活循环内皮细胞（CEC）增加，而当药物中断后肿瘤进展时，循环祖细胞（CPC）增加。我们的研究深入了解了这类药物在复发性胶质母细胞瘤患者中的不同作用机制，并表明联合治疗的时机对于优化针对该肿瘤的活性可能至关重要。
