Zoledronic-acid-induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients
Zoledronic-acid-induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients
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DOI：
10.1159/000087286
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Cognetti, F
中科院分区：
文献类型：
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作者：
Ferretti, G;Fabi, A;Cognetti, F
背景评价首次单次静脉输注唑来膦酸（ZA）后循环血管生成因子、金属蛋白酶和急性时相细胞因子的变化。实验设计：对18例乳腺癌骨转移患者的循环血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）、金属蛋白酶1（MMP-1）、金属蛋白酶2（MMP-2）、白细胞介素1 β、6和8（IL-1 β，IL-6，IL-8），干扰素γ，肿瘤坏死因子α（TNF-α）和转化生长因子P，就在ZA输注之前和输注后2和7天。结果如下：在ZA后48小时，MMP-2基础值显示出统计学显著降低（p = 0.01），在第7天高于第2天的值（p = 0.03）。ZA输注后48小时，VEGF基础值显示统计学显著性降低（p = 0.03），7天时增加至高于基础水平（p = 0.07）。输注后2天，bFGF基础水平几乎显著降低（p = 0.06），第7天高于基础值（p = 0.09）。将第2天的值与基础值进行比较，线性回归模型显示IL-8与bFGF（p = 0.02）、IL-8与TNF-α（p < 0.0001）、bFGF与TNF-α（p = 0.01）、MMP-1与TNF-α（p = 0.02）之间存在显著正相关。结论：ZA可通过瞬时降低VEGF、bFGF和MMP-2的循环水平发挥抗血管生成活性和抑制肿瘤细胞的骨侵袭。版权所有（C）2005 S. Karger AG，巴塞尔。
Background. To evaluate the modifications of circulating angiogenic factors, metalloproteinases and acute-phase cytokines after the first single zoledronic acid (ZA) intravenous infusion. Experimental Design: Eighteen consecutive breast cancer patients with bone metastases were evaluated for circulating levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinase 1 (MMP-1), metalloproteinase 2 (MMP-2), interleukins 1 beta, 6 and 8 (IL-1 beta, IL-6, IL-8), interferon gamma, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor P, just before and 2 and 7 days after ZA infusion. Results: The MMP-2 basal value showed a statistically significant decrease 48 h after ZA (p = 0.01), being at 7 days higher than the day 2 value (p = 0.03). The VEGF basal value showed a statistically significant decrease 48 h after ZA infusion (p = 0.03), increasing above the basal level at 7 days (p = 0.07). The bFGF basal level almost significantly decreased 2 days after infusion (p = 0.06), being at 7 days higher than the basal value (p = 0.09). Comparing the day 2 values with basal ones, the linear regression model showed a significant positive correlation between IL-8 and bFGF (p = 0.02), IL-8 and TNF-alpha (p < 0.0001), bFGF and TNF-alpha (p = 0.01), MMP-1 and TNF-alpha (p = 0.02). Conclusions: ZA could exert an antiangiogenic activity and inhibition of tumor cell bone invasiveness by a transient reduction of VEGF, bFGF and MMP-2 circulating levels after infusion. Copyright (C) 2005 S. Karger AG, Basel.