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Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro.
肿瘤来源的外来体在小鼠肝癌模型和体外人类中引起肿瘤抑制。

摘要

UNLABELLED:Hepatocellular carcinoma (HCC) remains a global challenge due to high morbidity and mortality rates and poor response to treatment. Immunotherapy, based on introduction of dendritic cells (DCs) activated by tumor cell lysates as antigens ex vivo, shows limited response rates in HCC patients. Here, we demonstrate that tumor cell-derived exosomes (TEXs), displaying an array of HCC antigens, can elicit a stronger immune response than cell lysates in vitro and in vivo. Significant tumor growth inhibition was achieved in ectopic and orthotopic HCC mice treated with TEX-pulsed DCs. Importantly, the tumor immune microenvironment was significantly improved in orthotopic HCC mice treated by TEX-pulsed DCs, demonstrated by increased numbers of T lymphocytes, elevated levels of interferon-γ, and decreased levels of interleukin-10 and tumor growth factor-β in tumor sites. As expected, T cells played an essential role in the TEX-pulsed DC-mediated immune response. Notably, exosomes from HCC cells not only promoted HCC-specific cytolysis but also provided cross-protective effects against pancreatic cancer cells. Moreover, HCC-specific cytolysis, elicited by DCs pulsed with human HepG2 cell-derived exosomes, was observed across different human HCC cells irrespective of human leukocyte antigen types.
CONCLUSION:HCC TEXs can potently carry HCC antigens, trigger a strong DC-mediated immune response, and improve the HCC tumor microenvironment. (Hepatology 2016;64:456-472).

译文

UNLABELLED: 由于高发病率和死亡率以及治疗反应不佳,肝细胞癌 (HCC) 仍然是一个全球性挑战。免疫治疗,基于肿瘤细胞裂解物激活的树突状细胞 (DCs) 作为体外抗原的引入,在肝癌患者中显示出有限的应答率。在这里,我们证明了显示一系列肝癌抗原的肿瘤细胞来源的外来体 (TEXs) 在体外和体内可以引起比细胞裂解物更强的免疫反应。在用 TEX 脉冲 DCs 处理的异位和原位肝癌小鼠中实现了显著的肿瘤生长抑制。重要的是,通过 TEX 脉冲 DCs 处理的原位肝癌小鼠的肿瘤免疫微环境得到显著改善,证明是 T 淋巴细胞数量增加,干扰素-γ 水平升高, 以及肿瘤部位 interleukin-10 和肿瘤生长因子-β 水平的降低。不出所料,T 细胞在 TEX 脉冲 DC 介导的免疫反应中发挥了重要作用。值得注意的是,来自肝癌细胞的 exosomes 不仅促进了肝癌特异性细胞溶解,而且提供了对胰腺癌细胞的交叉保护作用。此外,在不同的人肝癌细胞中观察到肝癌特异性细胞溶解,由与人肝癌细胞来源的 exosomes 脉冲的 DCs 引发,而与人类白细胞抗原类型无关。
结论: 肝癌 TEXs 能有效携带肝癌抗原,引发强烈的 DC 介导的免疫反应,改善肝癌肿瘤微环境。(肝病学 2016; 64: 456-472)。

hepatocellular carcinoma models

肿瘤 肝癌 实验动物
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

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?

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