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The first study on therapeutic efficacies of a vascular disrupting agent CA4P among primary hepatocellular carcinomas with a full spectrum of differentiation and vascularity: Correlation of MRI-microangiography-histopathology in rats 期刊论文

编号：

724c65be-fdb7-4161-a19f-660410f46b10
作者：

Liu, Yewei#^[1,2,3,4,5]De Keyzer, Frederik^[1];Wang, Yixin^[1];Wang, Fengna^[1];Feng, Yuanbo^[1];Chen, Feng^[1];Yu, Jie^[1];Liu, Jianjun^[3];Song, Shaoli^[3];Swinnen, Johan^[1];Bormans, Guy^[1];Oyen, Raymond^[1];Huang, Gang(黄钢)*^[2,3,4,5]Ni, Yicheng*^[1]
语种：

英文
期刊：

INTERNATIONAL JOURNAL OF CANCER ISSN：0020-7136 2018 年 143 卷 7 期 (1817 - 1828) ; OCT 1
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关键词：

vascular-disrupting agent combretastatin A4 phosphate hepatocellular carcinoma magnetic resonance imaging rats
摘要：

To better inform the next clinical trials of vascular disrupting agent combretastatin-A4-phosphate (CA4P) in patients with hepatic malignancies, this preclinical study aimed at evaluating CA4P therapeutic efficacy in rats with primary hepatocellular carcinomas (HCCs) of a full spectrum of differentiation and vascularity by magnetic resonance imaging (MRI), microangiography and histopathology. Ninety-six HCCs were raised in 25 rats by diethylnitrosamine gavage. Tumor growth was monitored by T2-/T1-weighted-MRI (T2WI, T1WI) using a 3.0 T scanner. Early vascular response and later intratumoral necrosis were detected by dynamic-contrast-enhanced (DCE) MRI and diffusion-weighted-imaging (DWI) before, 1 and 12 hr after CA4P iv-administration. In vivo MRI-findings were validated by postmortem-techniques. Multi-parametric MRI revealed rapid CA4P-induced tumor vascular shutdown within 1 hr, followed by variable intratumoral necrosis at 12 hr. Tumor volumes decreased by 10% at 1 hr (p < 0.05), but resumed at 12 hr. Correlations of semi-quantitative DCE parameter initial-area-under-the-gadolinium-curve (IAUGC30) with histopathology proved partial vascular closure and compensational reopening (p < 0.05). The higher grades of vascularity prevented those residual tumor tissues from CA4P-caused ischemic necrosis. By histopathology using a 4-scale cellular-differentiation criteria and a 4-grade tumor-vascularity classification, percentage of CA4P-induced necrosis negatively correlated with HCC differentiation (r = -0.404, p < 0.001) and tumor vascularity (r = -0.370, p < 0.001). Ordinal-logistic-regression helped to predict early tumor responses to CA4P in terms of tumoral differentiation and vascularity. Our study demonstrated that CA4P could induce vascular shutdown in primary HCCs within 1 hr, resulting in various degrees of tumor necrosis at 12 hr. MRI as a real-time imaging biomarker may help to define tumor vascularity and differentiation and further to predict CA4P therapeutic outcomes.
推荐引用方式
GB/T 7714：

Liu Yewei,De Keyzer Frederik,Wang Yixin, et al. The first study on therapeutic efficacies of a vascular disrupting agent CA4P among primary hepatocellular carcinomas with a full spectrum of differentiation and vascularity: Correlation of MRI-microangiography-histopathology in rats [J].INTERNATIONAL JOURNAL OF CANCER,2018,143(7):1817-1828.
APA：

Liu Yewei,De Keyzer Frederik,Wang Yixin,Wang Fengna,&Ni Yicheng.(2018).The first study on therapeutic efficacies of a vascular disrupting agent CA4P among primary hepatocellular carcinomas with a full spectrum of differentiation and vascularity: Correlation of MRI-microangiography-histopathology in rats .INTERNATIONAL JOURNAL OF CANCER,143(7):1817-1828.
MLA：

Liu Yewei, et al. "The first study on therapeutic efficacies of a vascular disrupting agent CA4P among primary hepatocellular carcinomas with a full spectrum of differentiation and vascularity: Correlation of MRI-microangiography-histopathology in rats" .INTERNATIONAL JOURNAL OF CANCER 143,7(2018):1817-1828.
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