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颅咽管瘤中血管生成因子的表达:与肿瘤复发的关系。

Expression of angiogenic factors in craniopharyngiomas: implications for tumor recurrence.

机构信息

Marmara University, Institute of Neurological Sciences, Molecular Neurosurgery Laboratory, Istanbul, Turkey.

出版信息

Neurosurgery. 2010 Apr;66(4):744-50; discussion 750. doi: 10.1227/01.NEU.0000367553.65099.14.

Abstract

BACKGROUND

The primary treatment for craniopharyngiomas is total excision, but recurrence is common. However, current knowledge on the mechanisms of recurrence is limited.

OBJECTIVE

We hypothesized that recurrence is linked to the angiogenesis of the tumor. Recurrent and nonrecurrent tumor samples were compared with regard to expression of angiogenesis-related factors and angiogenic capacity in a corneal angiogenesis model.

METHODS

Specimens of 4 recurrent and 6 nonrecurrent tumors were selected from 57 patients with adamantinomatous craniopharyngiomas. Sections were immunohistochemically stained with antibodies for vascular endothelial growth factor (VEGF), fibronectin, fibroblast growth factor (FGF)-2, platelet-derived growth factor (PDGF)-A, PDGF-B, platelet-derived growth factor receptor (PDGFR)-alpha, and PDGFR-beta. Expression levels were graded using a 4-point scoring system and were compared. For corneal angiogenesis assay, tissue samples were inoculated in a micropocket created on the rat eye, and microvessels were counted on days 3, 5, 7, and 9 to evaluate angiogenic potential.

RESULTS

Expression of PDGFR-alpha and FGF-2 were significantly higher for recurrent tumors (P = .02 and P = .01). However, recurrent and nonrecurrent tumors did not differ in the expressions of other ligands and receptors (PDGF-A, PDGF-B, and PDGFR-beta). Recurrent tumors displayed a higher angiogenic potential starting from the fifth day of corneal angiogenesis assay.

CONCLUSION

These findings suggest a relationship between recurrence of craniopharyngiomas and angiogenesis. New treatment modalities with selective PDGFR-alpha blockers may represent a novel and effective therapeutic option for the treatment of craniopharyngiomas.

摘要

背景

颅咽管瘤的主要治疗方法是完全切除,但复发很常见。然而,目前对复发机制的了解有限。

目的

我们假设复发与肿瘤的血管生成有关。在角膜血管生成模型中,比较了复发性和非复发性肿瘤样本的血管生成相关因子表达和血管生成能力。

方法

从 57 例颅咽管瘤患者中选择 4 例复发性和 6 例非复发性肿瘤标本。用血管内皮生长因子(VEGF)、纤维连接蛋白、成纤维细胞生长因子(FGF)-2、血小板衍生生长因子(PDGF)-A、PDGF-B、血小板衍生生长因子受体(PDGFR)-alpha 和 PDGFR-beta 抗体进行免疫组织化学染色。使用 4 分制评分系统对表达水平进行分级并进行比较。对于角膜血管生成实验,将组织样本接种在大鼠眼睛上创建的微囊中,并在第 3、5、7 和 9 天计数微血管以评估血管生成潜能。

结果

复发性肿瘤中 PDGFR-alpha 和 FGF-2 的表达明显更高(P =.02 和 P =.01)。然而,其他配体和受体(PDGF-A、PDGF-B 和 PDGFR-beta)在复发性和非复发性肿瘤中的表达没有差异。从角膜血管生成实验的第五天开始,复发性肿瘤表现出更高的血管生成潜能。

结论

这些发现表明颅咽管瘤的复发与血管生成有关。具有选择性 PDGFR-alpha 阻滞剂的新治疗方法可能代表治疗颅咽管瘤的一种新的有效治疗选择。

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