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血小板衍生生长因子-AB 在多发性骨髓瘤中与其他血管生成细胞因子相关的肿瘤生长和血管生成中的作用。

Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma.

机构信息

Department of Hematology, University Hospital of Heraklion, Crete, Greece.

出版信息

Hematol Oncol. 2012 Sep;30(3):131-6. doi: 10.1002/hon.1014. Epub 2011 Sep 14.

Abstract

Angiogenesis is a complex process essential for the growth, invasion, and metastasis of various malignant tumours, including multiple myeloma (MM). Various angiogenic cytokines have been implicated in the angiogenic process. Among them, platelet-derived growth factor-AB (PDGF-AB) has been reported to be a potent stimulator of angiogenesis in many solid tumours and haematological malignancies, including MM. The aim of the study was to investigate the relationship between PDGF-AB, microvascular density (MVD), and various angiogenic cytokines, such as basic fibroblast growth factor (b-FGF), angiogenin (ANG), and interleukin-6 (IL-6), in MM patients. Forty-seven MM patients before treatment, 22 of whom were in plateau phase, were studied. We determined the serum levels of the aforementioned cytokines and MVD in bone marrow biopsies before and after treatment. Mean serum values of PDGF-AB, b-FGF, ANG, and MVD were significantly higher in patients compared with controls and with increasing disease stage. Significant positive correlations were observed between serum PDGF-AB, ANG, and IL-6 levels and MVD. Furthermore, we found significant positive correlations between PDGF-AB and b-FGF, IL-6, ANG, and β2 microglobulin. We also found that patients with high MVD had statistically significantly higher serum levels of PDGF-AB when a median MVD value of 7.7 was used as the cutoff point. Furthermore, a significant difference was found in serum levels of PDGF-AB between pre- and post-treatment patients. Finally, survival time was significantly higher in the low MVD group versus the high MVD group (76 vs 51 months). Our results showed that there is a strong positive correlation between PDGF-AB and the studied angiogenic cytokines and MVD. It seems that PDGF-AB plays a role in the complex network of cytokines inducing bone marrow neovascularization in patients with MM.

摘要

血管生成是各种恶性肿瘤(包括多发性骨髓瘤)生长、侵袭和转移所必需的复杂过程。各种血管生成细胞因子都与血管生成过程有关。其中,血小板衍生生长因子-AB(PDGF-AB)已被报道在许多实体瘤和血液恶性肿瘤中,包括多发性骨髓瘤,是一种强有力的血管生成刺激因子。本研究旨在探讨 PDGF-AB 与微血管密度(MVD)以及各种血管生成细胞因子,如碱性成纤维细胞生长因子(b-FGF)、血管生成素(ANG)和白细胞介素-6(IL-6)之间的关系在 MM 患者中。研究了 47 例治疗前的 MM 患者,其中 22 例处于平台期。我们测定了治疗前后骨髓活检中上述细胞因子和 MVD 的血清水平。与对照组和疾病进展期相比,患者的血清 PDGF-AB、b-FGF、ANG 和 MVD 的平均血清值显著升高。血清 PDGF-AB、ANG 和 IL-6 水平与 MVD 之间存在显著正相关。此外,我们发现 PDGF-AB 与 b-FGF、IL-6、ANG 和β2 微球蛋白之间存在显著正相关。我们还发现,当以中位数 MVD 值 7.7 作为截断值时,MVD 较高的患者血清 PDGF-AB 水平显著较高。此外,治疗前后患者的血清 PDGF-AB 水平存在统计学差异。最后,低 MVD 组的生存时间明显高于高 MVD 组(76 个月与 51 个月)。我们的结果表明,PDGF-AB 与研究的血管生成细胞因子和 MVD 之间存在很强的正相关。PDGF-AB 似乎在多发性骨髓瘤患者骨髓新血管生成的细胞因子复杂网络中发挥作用。

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