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肝癌的临床前模型。

PRECLINICAL MODELS OF LIVER CÂNCER.

机构信息

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, São Paulo, SP, Brasil.

Laboratório de Transplante e Cirurgia do Fígado (LIM-37), São Paulo, SP, Brasil.

出版信息

Arq Gastroenterol. 2023 Jul-Sep;60(3):383-392. doi: 10.1590/S0004-2803.230302023-58.

DOI:10.1590/S0004-2803.230302023-58
PMID:37792769
Abstract

•In this review, we described different murine models of carcinogenesis: classic models, new transgenic and combined models, that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic physiopathological, and environmental abnormalities. •Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches. •Cholangiocarcinoma has been highlighted, with an increase in prevalence. This review has an important role in understanding the pathophysiology and the development of new drugs. Background - This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective - A review through MEDLINE and EMBASE was performed to assess articles until August 2022.Methods - Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results - In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion - Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

摘要

在这篇综述中,我们描述了不同的肝癌发生的小鼠模型:经典模型、新的转基因和联合模型,这些模型再现了 HCC 和 CCA 发生的关键点,有助于更好地理解其遗传、生理病理和环境异常。

每个模型都有其优点、缺点、相似之处和与相应人类疾病的差异,应根据研究的特异性选择。最终,这些模型也可用于测试新的抗癌治疗方法。

胆管癌的发病率有所增加,这一点得到了强调。本综述在理解其生理病理和开发新药方面具有重要作用。

背景

本文综述了肝癌(HCC)和胆管癌(CCA)小鼠模型中的肝发生癌。

目的

通过 MEDLINE 和 EMBASE 进行综述,评估截至 2022 年 8 月的文章。

方法

对整个电子数据库进行搜索,使用的关键词是 HCC、CCA、致癌作用、动物模型和肝脏。根据与主题缺乏密切关系,排除了文章。HCC 的致癌模型包括衰老转基因动物中的 HCC、饮食诱导的 HCC、化学致癌剂诱导的 HCC、异种移植、癌基因和 B 和 C 病毒接种的转基因动物中的 HCC。CCA 的模型包括使用二甲基亚硝胺(DMN)、二乙基亚硝胺(DEN)、硫代乙酰胺(TAA)和四氯化碳(CCl4)。CCA 的小鼠模型也可由 CCA 细胞、遗传操作、Smad4、PTEN 和 p53 缺失、异种移植和 DEN-左肝中胆管结扎诱导。

结果

在这篇综述中,我们描述了不同的肝癌发生的小鼠模型,这些模型再现了 HCC 和 CCA 发生的关键点,有助于更好地理解其遗传、生理病理和环境异常。

结论

每个模型都有其优点、缺点、相似之处和与相应人类疾病的差异,应根据研究的特异性选择。最终,这些模型也可用于测试新的抗癌治疗方法。

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Genomic Profiling of Combined Hepatocellular Cholangiocarcinoma Reveals Genomics Similar to Either Hepatocellular Carcinoma or Cholangiocarcinoma.联合肝细胞胆管细胞癌的基因组分析显示其基因组与肝细胞癌或胆管癌相似。
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