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肝癌兔射频消融及手术切除后残余癌中的血管生成以及HIF-1α、VEGF和MMP-9在残余癌发生发展中的作用

Angiogenesis in residual cancer and roles of HIF-1α, VEGF, and MMP-9 in the development of residual cancer after radiofrequency ablation and surgical resection in rabbits with liver cancer.

作者信息

Li H, Zhao B, Liu Y, Deng W, Zhang Y

机构信息

Department of Ultrasound, The First Hospital Affiliated to Inner Mongolia Medical University, Hohhot, People's Republic of China.

出版信息

Folia Morphol (Warsz). 2020;79(1):71-78. doi: 10.5603/FM.a2019.0059. Epub 2019 May 20.

Abstract

BACKGROUND

The aim of the study was to investigate the changes of blood flow signal in residual cancer after ultrasound-guided radiofrequency ablation (RFA) treatment of rabbit liver cancer over time, and to analyse the correlation between changes in blood flow signal and changes in hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) in residual cancer tissue after RFA.

MATERIALS AND METHODS

One hundred and ten rabbits were randomly selected, VX2 tumour cells were implanted subcutaneously, tumour cells were implanted in liver. Ninety rabbits were divided into three groups: Group 1 - untreated controls, Group 2 - RFA group, Group 3 - surgical resection group. Tumour size, blood flow signal, microvessel density (MVD) in liver cancer were assessed.

RESULTS

Correlation of HIF-1a, VEGF, MMP-9 mRNA and protein expressions with blood flow signal in residual cancer were observed. Liver tumour was 2.3 ± 0.32 cm, significant differences in the grade of blood flow signal were noted among different time points (days 0, 3, 7, and 14; p < 0.05). Significant differences were also observed between the surgical resection and RFA groups at the same time points (p < 0.05). The MVD in the RFA group was lower than that in the control group, but higher than that in the surgical resection group. The immunohistochemical scores for VEGF and MMP-9 in the RFA group were lower than those in the control group, but higher than those in the surgical resection group. The grade of ultrasound blood flow signal was positively correlated with the expression of two angiogenesis-related factors, VEGF and MMP-9, and the MVD in the control, RFA, and surgical resection groups.

CONCLUSIONS

There is a higher risk of tumour recurrence with RFA than with surgical resection.

摘要

背景

本研究的目的是探讨兔肝癌超声引导下射频消融(RFA)治疗后残余癌组织血流信号随时间的变化,并分析RFA后残余癌组织中血流信号变化与缺氧诱导因子1-α(HIF-1α)、血管内皮生长因子(VEGF)和基质金属蛋白酶-9(MMP-9)变化之间的相关性。

材料与方法

随机选取110只兔,皮下植入VX2肿瘤细胞,然后将肿瘤细胞植入肝脏。90只兔分为三组:第1组 - 未治疗对照组,第2组 - RFA组,第3组 - 手术切除组。评估肝癌的肿瘤大小、血流信号、微血管密度(MVD)。

结果

观察到残余癌中HIF-1α、VEGF、MMP-9 mRNA和蛋白表达与血流信号的相关性。肝肿瘤大小为2.3±0.32 cm,不同时间点(第0、3、7和14天)的血流信号分级存在显著差异(p<0.05)。在相同时间点,手术切除组和RFA组之间也观察到显著差异(p<0.05)。RFA组的MVD低于对照组,但高于手术切除组。RFA组中VEGF和MMP-9的免疫组化评分低于对照组,但高于手术切除组。超声血流信号分级与对照组、RFA组和手术切除组中两种血管生成相关因子VEGF和MMP-9的表达以及MVD呈正相关。

结论

与手术切除相比,RFA后肿瘤复发风险更高。

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