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载顺铂超吸水性聚合物微球用于 VX2 肝癌化疗栓塞的体内评价。

In vivo evaluation of cisplatin-loaded superabsorbent polymer microspheres for use in chemoembolization of VX2 liver tumors.

机构信息

Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

J Vasc Interv Radiol. 2012 Mar;23(3):397-404.e1. doi: 10.1016/j.jvir.2011.10.024. Epub 2011 Dec 29.

Abstract

PURPOSE

To investigate the pharmacokinetics and efficacy of chemoembolization with a cisplatin-loaded superabsorbent polymer (SAP) suspension in a rabbit model with transplanted liver VX2 tumors.

MATERIALS AND METHODS

VX2 tumors were implanted into the left lobe of the liver in eight rabbits. Embolization of the proper hepatic artery was performed with cisplatin-loaded or unloaded SAP. In the cisplatin-loaded SAP group (n = 4), 5 mg of SAP (106-150 μm) loading 2.35 mg of cisplatin and 0.5 mL of ionic contrast material (ioxaglic acid 320 mgI/mL) was injected into the proper hepatic artery. In the control group (hepatic arterial infusion [HAI] + SAP; n = 4), 5 mg of SAP loading 0.5 mL of ioxaglic acid alone was injected after a bolus infusion of an equivalent amount of cisplatin. Sequential change of the plasma platinum concentration within the first 24 hours was measured. Blood sampling and histopathologic examination were performed at 1-week follow-up. Magnetic resonance (MR) images were used to calculate the growth rate of the VX2 tumor.

RESULTS

All animals underwent successful embolization. Both total and free plasma platinum mean concentrations within the first 24 hours remained lower in the cisplatin-loaded SAP group, although without statistical significance (P > .05). The mean tumor growth rate was significantly lower in the cisplatin-loaded SAP group than the control group (20% vs 116%; P = .049). Histopathologic examination revealed coagulative necrosis to nontumorous liver parenchyma in two rabbits in the cisplatin-loaded SAP group, although no deaths occurred.

CONCLUSIONS

These results suggested that chemoembolization with cisplatin-loaded SAP was a safe and tolerable treatment and was more effective in suppressing the tumor growth.

摘要

目的

研究顺铂载超吸收聚合物(SAP)混悬剂在兔VX2 移植性肝癌模型中的药代动力学和疗效。

材料与方法

将 VX2 肿瘤植入 8 只兔的左叶肝脏。经肝固有动脉栓塞顺铂载 SAP 或未载 SAP。在顺铂载 SAP 组(n=4)中,将 5mg(106-150μm)载有 2.35mg 顺铂和 0.5mL 离子型对比剂(ioxaglic acid 320mgI/mL)的 SAP 注入肝固有动脉。在对照组(肝动脉灌注[HAI]+SAP;n=4)中,在推注等量顺铂后,注入 5mg 载有 0.5mL ioxaglic acid 的 SAP。在第 1 周随访时测量前 24 小时内的血浆铂浓度变化。采血并进行组织病理学检查。磁共振(MR)图像用于计算 VX2 肿瘤的生长率。

结果

所有动物均成功栓塞。顺铂载 SAP 组在第 1 天的前 24 小时内的总血浆铂浓度和游离血浆铂浓度均较低,但无统计学意义(P>.05)。顺铂载 SAP 组的肿瘤生长速度明显低于对照组(20%对 116%;P=0.049)。顺铂载 SAP 组的 2 只兔的非肿瘤肝实质组织出现凝固性坏死,但未发生死亡。

结论

这些结果表明,顺铂载 SAP 化疗栓塞是一种安全、耐受的治疗方法,可更有效地抑制肿瘤生长。

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