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脑膜瘤中血管内皮生长因子信使核糖核酸表达与瘤周血管源性脑水肿的相关性

Correlation of vascular endothelial growth factor messenger RNA expression with peritumoral vasogenic cerebral edema in meningiomas.

作者信息

Kalkanis S N, Carroll R S, Zhang J, Zamani A A, Black P M

机构信息

Neurosurgical Service, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

出版信息

J Neurosurg. 1996 Dec;85(6):1095-101. doi: 10.3171/jns.1996.85.6.1095.

Abstract

Intracranial meningiomas are often complicated by peritumoral vasogenic cerebral edema, which appears to result from increased microvascular permeability and extravasation of proteinaceous and plasma fluid into the adjacent peritumoral space. The source of such edema has long been mysterious. The contents of this paper support the concept that vascular endothelial growth factor (VEGF) production plays a significant role in edema formation. Vascular endothelial growth factor messenger RNA expression has been found in a wide range of intracranial neoplasms, including malignant gliomas, metastatic melanomas, meningiomas, and other benign tumors. Several studies have confirmed the importance of VEGF in tumorigenesis, neovascularization, and edema production. This study tests the hypothesis that the presence of peritumoral edema in meningiomas is positively correlated with increased expression of VEGF mRNA. To investigate this hypothesis, 31 meningioma specimens were subjected to Northern blot analysis, hybridization with a complementary DNA VEGF probe, and laser densitometry to determine the relative levels of VEGF mRNA expression. Magnetic resonance imaging was then used in a double-blind fashion to correlate the neuropathological tissue samples with the presence of preoperative peritumoral edema. Of 31 patients studied, 14 exhibited no edema and 17 exhibited some level of peritumoral fluid accumulation. There was a marked increase in VEGF expression in patients with edema (p = 0.0004, Wilcoxon-Mann-Whitney rank-sum test). Meningiomas with peritumoral edema exhibited 3.4 times the level of VEGF mRNA as those without edema. These data demonstrate a strong link between VEGF mRNA expression and peritumoral edema and indicate that VEGF expression is an important factor in the etiology of edema around meningiomas.

摘要

颅内脑膜瘤常伴有瘤周血管源性脑水肿,这似乎是由于微血管通透性增加以及蛋白质和血浆液体外渗至邻近的瘤周间隙所致。这种水肿的来源长期以来一直是个谜。本文的内容支持血管内皮生长因子(VEGF)的产生在水肿形成中起重要作用这一观点。在包括恶性胶质瘤、转移性黑色素瘤、脑膜瘤和其他良性肿瘤在内的多种颅内肿瘤中都发现了血管内皮生长因子信使核糖核酸(mRNA)的表达。多项研究证实了VEGF在肿瘤发生、新生血管形成和水肿产生中的重要性。本研究检验了脑膜瘤瘤周水肿的存在与VEGF mRNA表达增加呈正相关这一假设。为了研究这一假设,对31份脑膜瘤标本进行了Northern印迹分析、用互补DNA VEGF探针杂交以及激光密度测定法,以确定VEGF mRNA表达的相对水平。然后以双盲方式使用磁共振成像将神经病理学组织样本与术前瘤周水肿的存在情况进行关联。在研究的31例患者中,14例未出现水肿,17例出现了一定程度的瘤周液体蓄积。水肿患者的VEGF表达显著增加(p = 0.0004,Wilcoxon-Mann-Whitney秩和检验)。有瘤周水肿的脑膜瘤的VEGF mRNA水平是无水肿脑膜瘤的3.4倍。这些数据表明VEGF mRNA表达与瘤周水肿之间存在紧密联系,并表明VEGF表达是脑膜瘤周围水肿病因中的一个重要因素

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