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上调促血管生成因子和在恶性胸腔积液中建立耐受。

Up-regulation of pro-angiogenic factors and establishment of tolerance in malignant pleural effusions.

机构信息

Mayo Graduate School, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, United States.

出版信息

Lung Cancer. 2013 Oct;82(1):63-8. doi: 10.1016/j.lungcan.2013.07.007. Epub 2013 Aug 12.

DOI:10.1016/j.lungcan.2013.07.007
PMID:23948549
Abstract

INTRODUCTION

Malignant pleural effusions (MPEs) are a significant source of cancer morbidity and mortality. Currently there is no cure for MPEs and treatments only palliate the symptoms. The purpose of this study was to determine if there are differences in markers of angiogenesis and immune phenotypes between adenocarcinoma-induced MPEs and benign pleural effusions (BPEs).

METHODS

Pleural effusions were collected from patients with MPEs and BPEs. Cells were isolated from effusions and characterized using fluorescent cell sorting (FACS). Pleural effusions were evaluated by ELISA for VEGF-A. An angiogenesis protein array was completed to compare protein expression in malignant and non-malignant effusions.

RESULTS

FACS analysis demonstrated lower accumulation of cytotoxic T-cells and significantly higher accumulation of monocytes, dendritic cells, mesothelial and tumor cells in MPEs compared to benign pleural effusions. MPEs were found to have 77-fold higher VEGF-A levels compared to BPEs. The angiogenesis protein array demonstrated elevated levels of pro-angiogenic factors VEGF-A, CXCL4 and MMP-8, and low levels of pro-inflammatory cytokines IL-8, MCP-1, and TGF-β1 in MPEs.

CONCLUSIONS

MPE is biased toward a Th2 dominant state. There is an increase in expression of VEGF-A and other pro-angiogenic factors in MPE. These data suggest there is a role for anti-angiogenesis therapy in patients with MPEs.

摘要

简介

恶性胸腔积液(MPE)是癌症发病率和死亡率的重要来源。目前,MPE 尚无治愈方法,治疗只能缓解症状。本研究旨在确定腺癌引起的 MPE 和良性胸腔积液(BPE)之间的血管生成和免疫表型标志物是否存在差异。

方法

从患有 MPE 和 BPE 的患者中收集胸腔积液。使用荧光细胞分选(FACS)从胸腔积液中分离细胞并进行特征描述。通过 ELISA 评估胸腔积液中 VEGF-A 的水平。完成了血管生成蛋白阵列以比较恶性和非恶性胸腔积液中的蛋白表达。

结果

FACS 分析表明,与良性胸腔积液相比,MPE 中细胞毒性 T 细胞的积累量较低,单核细胞、树突状细胞、间皮细胞和肿瘤细胞的积累量显著增加。MPE 中的 VEGF-A 水平比 BPE 高 77 倍。血管生成蛋白阵列显示 MPE 中促血管生成因子 VEGF-A、CXCL4 和 MMP-8 的水平升高,而促炎细胞因子 IL-8、MCP-1 和 TGF-β1 的水平较低。

结论

MPE 偏向于 Th2 优势状态。MPE 中 VEGF-A 和其他促血管生成因子的表达增加。这些数据表明,抗血管生成治疗在 MPE 患者中具有一定作用。

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