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经导管动脉化疗栓塞联合索拉非尼对兔VX2肝癌模型肿瘤血管生成的抑制作用

Efficacy of transcatheter arterial chemoembolization combined with sorafenib in inhibiting tumor angiogenesis in a rabbit VX2 liver cancer model.

作者信息

Li WeiZhi, Kong ShuZhen, Su JingWen, Huang Jin, Xue Hui

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.

Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, China.

出版信息

J Interv Med. 2020 Jan 21;3(1):27-33. doi: 10.1016/j.jimed.2020.01.003. eCollection 2020 Feb.

Abstract

BACKGROUND

The aim of this study was to investigate the effects of transcatheter arterial chemoembolization (TACE) combined with sorafenib on tumor angiogenesis.

MATERIALS AND METHODS

Thirty New Zealand rabbit VX2 liver cancer model animals were divided into five groups, which received either normal saline (A), TACE (B), sorafenib (C), sorafenib followed by TACE (D), or TACE followed by sorafenib (E). Serum vascular endothelial growth factor (VEGF) levels were measured before and after TACE via ELISA. Immunohistochemistry for CD34 was performed to evaluate microvessel density (MVD), and ultrasonography was used to access tumor volume.

RESULTS

VEGF levels declined in group C but increased significantly on the 3rd post-operative day in groups B, D, and E. Levels decreased after the 7th post-operative day. Peak levels were significantly lower in group D than in groups B and E. On the 14th post-operative day, VEGF levels were the lowest in group C, followed by those in groups D and B. MVD was the lowest in group C followed by that in group D and E, and was the highest in group B. Group D had the smallest tumor volume. HE staining of tumor tissues from group C showed apoptosis in a scattered patchy pattern, whereas in groups B, D, and E, large areas of tumor cell necrosis were visible.

CONCLUSION

TACE can up-regulate serum VEGF levels, which in turn accelerates the formation of new blood vessels. Thus, TACE combined with sorafenib inhibits VEGF and angiogenesis, and pre-operative administration of sorafenib has a more superior anti-angiogenic effect than post-operative administration.

摘要

背景

本研究旨在探讨经动脉化疗栓塞术(TACE)联合索拉非尼对肿瘤血管生成的影响。

材料与方法

将30只新西兰兔VX2肝癌模型动物分为五组,分别接受生理盐水(A组)、TACE(B组)、索拉非尼(C组)、索拉非尼后行TACE(D组)或TACE后行索拉非尼(E组)治疗。通过酶联免疫吸附测定法(ELISA)在TACE前后检测血清血管内皮生长因子(VEGF)水平。进行CD34免疫组织化学检测以评估微血管密度(MVD),并使用超声检查测量肿瘤体积。

结果

C组VEGF水平下降,而B组、D组和E组在术后第3天显著升高。术后第7天水平下降。D组的峰值水平显著低于B组和E组。术后第14天,C组VEGF水平最低,其次是D组和B组。C组MVD最低,其次是D组和E组,B组最高。D组肿瘤体积最小。C组肿瘤组织的苏木精-伊红(HE)染色显示散在斑片状凋亡,而B组、D组和E组可见大片肿瘤细胞坏死。

结论

TACE可上调血清VEGF水平,进而加速新血管形成。因此,TACE联合索拉非尼可抑制VEGF和血管生成,术前给予索拉非尼的抗血管生成作用优于术后给予。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a07/8562284/6c51de2ae485/gr1.jpg

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