Santini Daniele, Vincenzi Bruno, Avvisati Giuseppe, Dicuonzo Giordano, Battistoni Fabrizio, Gavasci Michele, Salerno Alfredo, Denaro Vincenzo, Tonini Giuseppe
Università Campus Bio-Medico, 00155 Rome, Italy.
Clin Cancer Res. 2002 May;8(5):1080-4.
Recently, new experimental data suggested that, besides inhibiting osteoclasts, bisphosphonate may also have an antitumor effect. Antiangionetetic activity is one of the possible mechanisms of anticancer activity attributed to bisphosphonates. The purpose of this study was to evaluate the modifications in angiogenic cytokines levels after pamidronate infusion.
Twenty-five consecutive cancer patients with bone metastases treated monthly with disodium pamidronate infusion were evaluated prospectively for circulating levels of vascular endothelial growth factor (VEGF), gamma-IFN, interleukin (IL)-6, and IL-8 at different time points: just before and after 1, 2, and 7 days after pamidronate infusion.
Basal VEGF levels decreased significantly 1, 2, and 7 days after pamidronate infusion. gamma-IFN and IL-6 levels increased 1 day after the infusion but rapidly decreased after 2 days. Moreover, our data showed a statistically significant negative correlation between VEGF and gamma-IFN levels (P < 0.0001) and a positive correlation between VEGF and IL-8 (P = 0.04).
This study confirms that pamidronate could have antiangiogenic properties through a significant and lasting decrease of VEGF serum levels.
最近,新的实验数据表明,双膦酸盐除了抑制破骨细胞外,可能还具有抗肿瘤作用。抗血管生成活性是双膦酸盐抗癌活性的可能机制之一。本研究的目的是评估帕米膦酸钠输注后血管生成细胞因子水平的变化。
对25例连续接受每月一次帕米膦酸二钠输注治疗的骨转移癌患者进行前瞻性评估,在不同时间点检测其循环血管内皮生长因子(VEGF)、γ干扰素、白细胞介素(IL)-6和IL-8水平:帕米膦酸钠输注前、输注后1天、2天和7天。
帕米膦酸钠输注后1天、2天和7天,基础VEGF水平显著降低。γ干扰素和IL-6水平在输注后1天升高,但2天后迅速下降。此外,我们的数据显示VEGF与γ干扰素水平之间存在统计学显著负相关(P < 0.0001),VEGF与IL-8之间存在正相关(P = 0.04)。
本研究证实,帕米膦酸钠可通过显著且持久地降低VEGF血清水平而具有抗血管生成特性。