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Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P 期刊论文

编号：

d712f3c8-f451-463d-9624-7d050e35c55b
作者：

Liu, Yewei#^[1,2,3,4,5]Yin, Ting^[1];De Keyzer, Frederik^[1];Feng, Yuanbo^[1];Chen, Feng^[1];Liu, Jianjun^[2];Song, Shaoli^[2];Yu, Jie^[1];Vandecaveye, Vincent^[1];Swinnen, Johan^[1];Bormans, Guy^[1];Himmelreich, Uwe^[1];Oyen, Raymond^[1];Zhang, Jian^[6];Huang, Gang(黄钢)*^[2,3,4,5]Ni, Yicheng*^[1,6]
语种：

英文
期刊：

ONCOTARGET ISSN：1949-2553 2017 年 8 卷 33 期 (55204 - 55215) ; AUG
收录：
关键词：

vascular-disrupting agents combretastatin A4 phosphate therapeutic response microcancer hepatocellular carcinoma
摘要：

We sought to investigate anticancer efficacy of a vascular disrupting agent (VDA) combretastatin A-4 phosphate (CA4P) in relation to tumor size among hepatocellular carcinomas (HCCs) in rats using magnetic resonance imaging (MRI) and postmortem techniques. Nineteen rats with 43 chemically-induced HCCs of 2.8-20.9 mm in size on liver cirrhosis received CA4P intravenously at 10 mg/kg. Tumor-diameter was measured by T2-weighted imaging (T2WI) to define microcancers (< 5 mm) versus larger HCCs. Vascular responses and tissue necrosis were detected by diffusionweighted imaging (DWI), contrast-enhanced T1-weighted imaging (CE-T1WI) and dynamic contrast enhanced (DCE-) MRI, which were validated by microangiography and histopathology. MRI revealed nearly complete necrosis in 5 out of 7 microHCCs, but diverse therapeutic necrosis in larger HCCs with a positive correlation with tumor size. Necrosis in micro-HCCs was 36.9% more than that in larger HCCs. While increased diffusion coefficient (ADCdiff) suggested tumor necrosis, perfusion coefficient (ADCperf) indicated sharply decreased blood perfusion in cirrhotic liver together with a reduction in micro-HCCs. DCE revealed lowered tumor blood flow from intravascular into extravascular extracellular space (EES). Microangiography and histopathology revealed hypo-and hypervascularity in 4 and 3 micro-HCCs, massive, partial and minor degrees of tumoral necrosis in 5, 1 and 1 micro-HCCs respectively, and patchy necrotic foci in cirrhotic liver. CD34-PAS staining implicated that poorly vascularized micro-HCCs growing on liver cirrhosis tended to respond better to CA4P treatment. In this study, more complete CA4P-response occurred unexpectedly in micro-HCCs in rats, along with CA4P-induced necrotic foci in cirrhotic liver. These may help to plan clinical applications of VDAs in patients with HCCs and liver cirrhosis.
推荐引用方式
GB/T 7714：

Liu Yewei,Yin Ting,De Keyzer Frederik, et al. Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P [J].ONCOTARGET,2017,8(33):55204-55215.
APA：

Liu Yewei,Yin Ting,De Keyzer Frederik,Feng Yuanbo,&Ni Yicheng.(2017).Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P .ONCOTARGET,8(33):55204-55215.
MLA：

Liu Yewei, et al. "Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P" .ONCOTARGET 8,33(2017):55204-55215.
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