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经动脉化疗栓塞联合索拉非尼局部给药治疗肝细胞癌:VX-2兔肝肿瘤模型的可行性、疗效及安全性

Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model.

作者信息

Seidensticker Max, Streit Sebastian, Nass Norbert, Wybranski Christian, Jürgens Julian, Brauner Jan, Schulz Nadine, Kalinski Thomas, Seidensticker Ricarda, Garlipp Benjamin, Steffen Ingo, Ricke Jens, Dudeck Oliver

机构信息

Klinik für Radiologie und Nuklearmedizin, Universitätsklinik Magdeburg, Magdeburg, Germany.

出版信息

Diagn Interv Radiol. 2016 Jul-Aug;22(4):378-84. doi: 10.5152/dir.2016.15462.

Abstract

PURPOSE

We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model.

METHODS

VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy.

RESULTS

The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE.

CONCLUSION

SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity.

摘要

目的

我们旨在评估在VX-2荷瘤兔模型中,在传统经动脉化疗栓塞术(TACE)中局部应用索拉非尼的可行性、有效性和安全性。

方法

在10只新西兰白兔的左肝叶诱导VX-2肿瘤。两周后,通过对比增强计算机断层扫描(CT)确认肿瘤生长情况。5只兔子接受使用索拉非尼与碘化油乳剂的经动脉化疗栓塞术治疗(称为SORATACE;n = 5)。接受口服索拉非尼两周的兔子(n = 2)和未治疗的兔子(n = 3)作为对照。两周后,进行对比增强CT检查,随后进行动物尸检。

结果

与其他组相比,SORATACE组基线和随访之间肿瘤直径的变化有显著差异;仅在SORATACE组观察到肿瘤缩小(P = 0.016)。在两个对照组中,除一个肿瘤外,所有肿瘤在随访CT中均可见保留的高血供。SORATACE组所有肿瘤在随访CT中均出现血供消失。重要的是,接受SORATACE治疗的兔子在荷瘤肝叶的非靶向区域出现了实质性的肝实质损伤。

结论

SORATACE在治疗实验性VX-2肝肿瘤方面显示出高效,但也与严重的肝实质毒性相关。

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