Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma
Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma
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DOI：
10.1034/j.1600-0609.2001.00348.x
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发表时间：
2001-02-01
影响因子：
3.1
通讯作者：
Possinger, K
中科院分区：
文献类型：
--
作者：
Sezer, O;Jakob, C;Possinger, K
血管生成是肿瘤生长和发展的关键过程，越来越多的证据表明新生血管在血液恶性肿瘤中很重要。由于在多发性骨髓瘤中血管生成潜力增加，我们同时通过ELISA测定了67例多发性骨髓瘤或意义不明的单克隆γ病（MGUS）患者和20例对照患者的循环血清中细胞因子bFGF、VEGF、HGF和IL-6的水平。健康志愿者bFGF的中位数为4.7 pg/ml， MGUS为6.2 pg/ml，骨髓瘤I期为6.3 pg/ml，骨髓瘤II期为13.4 pg/ml，骨髓瘤III期为21.7 pg/ml。骨髓瘤患者血清bFGF水平明显高于对照组（p < 0.001）。预处理后bFGF水平在Salmon和Durie I- iii期有显著差异（p = 0.02），在II-III期与I期骨髓瘤相比显著升高（p = 0.02）。在根据CLMTF标准对化疗有反应的患者中，血清bFGF、VEGF和HGF水平显著下降（bFGF预处理值中位数为23.9 pg/ml，治疗后为6.5 pg/ml; p < 0.001, VEGF 223 pg/ml vs 105 pg/ml, p = 0.02; HGF 1429 pg/ml vs 1077 pg/ml, p = 0.02）。在11例未达到缓解的患者中，bFGF、VEGF和HGF水平没有显著下降。这些数据表明，II期和III期骨髓瘤与血清bFGF浓度升高相关，并且首次报道了有效化疗伴随着血管生成因子bFGF、VEGF和HGF的显著降低，而在无反应的患者中未发现这些因子的降低。
Angiogenesis is a crucial process in growth and progression of cancer and there is growing evidence that neovascularisation is important in hematological malignancies. Since an increased angiogenic potential has been identified in multiple myeloma, we simultaneously measured circulating serum levels of the cytokines bFGF, VEGF, HGF and IL-6 by ELISA in 67 patients with multiple myeloma or monoclonal gammopathies of undetermined significance (MGUS) and in 20 controls. Median values of bFGF were 4.7 pg/ml in healthy volunteers, 6.2 in MGUS, 6.3 in myeloma stage I, 13.4 in stage II and 21.7 in stage III. Myeloma patients had significantly higher bFGF serum levels than controls (p < 0.001). Pretreatment bFGF levels differed significantly in the Salmon and Durie stages I-III (p = 0.02) and were significantly elevated in stage II-III compared to stage I myeloma (p = 0.02). In patients responding to chemotherapy according to the CLMTF criteria, a significant decrease in serum bFGF, VEGF and HGF levels occurred (median pretreatment values for bFGF 23.9 pg/ml, post-treatment 6.5 pg/ml; p < 0.001, for VEGF 223 pg/ml versus 105 pg/ml; p = 0.02 and for HGF 1429 pg/ml versus 1077 pg/ml, p = 0.02, respectively). In 11 patients who did not achieve a remission, there was no significant decrease in bFGF, VEGF and HGF levels. These data show that myeloma in stages II and III is associated with an increase in serum bFGF concentrations and give the first report that effective chemotherapy is accompanied by a significant decrease in the angiogenic factors bFGF, VEGF and HGF, while no decrease of these factors could be found in nonresponders.