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hepatocellular carcinoma models

肿瘤

关键词肿瘤 实验动物 肝癌

词汇介绍

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解析

Hepatocellular   /,hepətəu'seljulə/

释    义   adj. 肝细胞的

例    句   Expression of MT1E during the formation of hepatocellular carcinoma and its function in hepatocarcinoma cells. MT1E在肝癌形成过程中的表达及其在肝癌细胞中的作用。

 

Carcinoma   英 /ˌkɑːsɪˈnəʊmə/   美 /ˌkɑːrsɪˈnoʊmə/

释    义   n. [肿瘤] 癌

例    句   You may see undifferentiated carcinoma of the oesophagus' in your medical reports if you have this type of oesophageal cancer. 如果您有这种食道癌,在您的医疗报告中就会看到这种食道中未分化的癌。

 

Models

释    义   n. 航模型式

例    句   How do I handle models that should have one and only one row in their database? 如何处理数据库中只有一行的模型?

概述

肝癌是影响人体生命健康的一类恶性疾病,其发病机制至今尚未阐明。建立肝癌动物模型(HCC models)为阐明肝癌致病机理,观察其发生发展过程及探索其治疗手段等具有极其重要的价值。常见的肝癌动物模型有诱发性肝癌动物模型、移植性肝癌动物模型、基因工程肝癌动物模型等。 模型动物的选择 目前常见的肝癌模型动物实验用动物有小鼠、大鼠、裸鼠、仓鼠、家兔及猪等。小鼠是构建肝癌模型最经济的动物,主要包括化学诱导模型、移植模型、转基因模型和裸鼠肝癌模型。   化学诱导型小鼠肝癌模型具有人类肝癌损伤

Dose-Dependent Sorafenib-Induced Immunosuppression Is Associated with Aberrant NFAT Activation and Expression of PD-1 in T Cells复制标题

剂量依赖性索拉非尼诱导的免疫抑制与T细胞中异常的NFAT激活和PD-1表达相关

发表时间:2019-05-18

影响因子:6.2

作者: Renuka V. Iyer

期刊:Cancers (Basel)

The multikinase inhibitor sorafenib is the only standard first-line therapy for hepatocellular carcinoma (HCC). Here, we report the dose-dependent effects of sorafenib on the immune response, which is related to nuclear factor of activated T cells 1 (NFAT1) activity. In vitro and in vivo experiments were performed with low and high doses of sorafenib using human T cells and spontaneous developed woodchuck HCC models.   In vitro studies demonstrated that following exposure to a high dose of sorafenib the baseline activity of NFAT1 in T cells was significantly increased. In a parallel event, high dose sorafenib resulted in a significant decrease in T cell proliferation and increased the proportion of PD-1 expressing CD8+ T cells with NFAT1 activation.   In the in vivo model, smaller tumors were detected in the low-dose sorafenib treated group compared to the placebo and high-dose treated groups. The low-dose sorafenib group showed a significant tumor growth delay with significantly more CD3+ cells in tumor. This study demonstrates that sorafenib has immunomodulatory effects in a dose- and time-dependent manner. Higher dose of sorafenib treatment was associated with immunosuppressive action. This observed effect of sorafenib should be taken into consideration in the selection of optimum starting dose for future trials.

译文

多激酶抑制剂索拉非尼是治疗肝细胞癌(HCC)的唯一标准一线疗法。在此,我们报道了索拉非尼对免疫反应的剂量依赖性影响,这与活化T细胞1(NFAT1)活性的核因子有关。利用人T细胞和自然发育的土拨鼠肝癌模型,用低剂量和高剂量索拉非尼进行体外和体内实验。体外研究表明,大剂量索拉非尼暴露后,T细胞中NFAT1的基线活性显著增加。在一个平行事件中,高剂量索拉非尼导致T细胞增殖显著下降,并且增加了NFAT1激活的表达CD8+T细胞的PD-1比例。在体内模型中,与安慰剂组和高剂量治疗组相比,低剂量索拉非尼治疗组发现较小的肿瘤。低剂量索拉非尼组肿瘤生长明显延迟,CD3+细胞明显增多。本研究表明索拉非尼具有剂量和时间依赖性的免疫调节作用。较高剂量的索拉非尼治疗与免疫抑制作用有关。在选择今后试验的最佳起始剂量时,应考虑到索拉非尼的这一观察效果。