Vascular endothelial growth factor expression, vascular volume, and capillary permeability in human brain tumors

Vascular endothelial growth factor expression, vascular volume, and capillary permeability in human brain tumors
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DOI:
10.1097/00006123-199904000-00022
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发表时间:
1999-04-01
期刊:
影响因子:
4.8
通讯作者:
Warnke, PC
Warnke, PC
中科院分区:
医学1区
文献类型:
--
作者:
Machein, MR;Kullmer, J;Warnke, PC

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目的:血管内皮生长因子(VEGF)是一种内皮细胞特异性丝裂原,是一种有效的血管通透性诱导剂。在这项研究中,我们确定了VEGF的表达是否与人类原发性脑肿瘤的毛细血管通透性和血管体积的体内测量相关。方法:对14例患者的肿瘤标本(7例胶质母细胞瘤、1例间变性星形细胞瘤、2例低级别星形细胞瘤、1例毛细胞星形细胞瘤和3例原发性脑淋巴瘤)进行立体定向采集。采用半定量聚合酶链反应定量VEGF信使核糖核酸在肿瘤中的相对表达。通过免疫组化技术在组织切片中检测到VEGF蛋白。采用双室动态计算机断层扫描方法定量测量从活检获得的区域的上述参数。结果:在胶质性肿瘤中,VEGF信使核糖核酸水平与毛细血管通透性(P < 0.05)和血管体积(P < 0.01)有显著相关性。尽管所有原发性脑淋巴瘤均表现出毛细血管通透性和血管体积显著增加,但这些肿瘤中VEGF的表达仅轻微上调。结论:我们的研究结果与VEGF可能与神经胶质肿瘤内皮细胞增殖和血管通透性有关的假设一致。这种关系对临床应用具有重要意义,例如水溶性药物的递送评估、水肿治疗以及基于抑制VEGF功能的抗血管生成治疗。
OBJECTIVE: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and a potent inducer of vascular permeability. In this study, we determined whether expression of VEGF is correlated with in vivo measurements of the capillary permeability and vascular volume of primary human brain tumors.METHODS: Tumor samples (seven glioblastomas, one anaplastic astrocytoma, two low-grade astrocytomas, one pilocytic astrocytoma, and three primary cerebral lymphomas) were stereotactically obtained from 14 patients. A semiquantitative polymerase chain reaction was used to quantify the relative expression of VEGF messenger ribonucleic acid in the tumors. VEGF protein was demonstrated in tissue sections by immunohistochemical techniques. A two-compartment dynamic computed tomographic method was used to quantitatively measure the aforementioned parameters in the regions from which the biopsies were obtained.RESULTS: In glial tumors, there was significant correlation of VEGF messenger ribonucleic acid levels with capillary permeability (P < 0.05) and vascular volume (P < 0.01). Although all primary cerebral lymphomas showed considerable increases in capillary permeability and vascular volume, VEGF expression was only slightly upregulated in these tumors.CONCLUSION: Our findings are consistent with the hypothesis that VEGF may be responsible for endothelial cell proliferation and vascular permeability in glial tumors. This relationship has implications for clinical applications, i.e., assessment of delivery of water-soluble drugs, treatment of edema, and antiangiogenesis therapy based on inhibition of VEGF function.