Recent Advances in Implantation-Based Genetic Modeling of Biliary Carcinogenesis in Mice.
Recent Advances in Implantation-Based Genetic Modeling of Biliary Carcinogenesis in Mice.
复制标题
DOI：
10.3390/cancers13102292
复制
发表时间：
2021-05-11
期刊：
影响因子：
5.2
通讯作者：
Hippo Y
中科院分区：
文献类型：
--
作者：
Izumiya M;Kato S;Hippo Y
胆道癌（BTC）通常是传统疗法难以治疗的，并且难以在早期诊断。此外，尽管最近在癌症基因组分析方面取得了进展，但BTC的发病机制尚未完全了解。为了解决这些问题，开发精细的疾病模型对BTC至关重要。虽然数量仍然有限，但由于新兴技术，BTC的遗传模型有各种平台。在这些模型中，基于简化的模型最近因其方便性、灵活性和可扩展性而引起了人们的关注。为了突出这种方法的相关性，我们全面总结了使用不同方法开发的BTC模型的优点和缺点。本文就肝内外胆管细胞癌和胆囊癌的研究现状作一综述。这些信息可能有助于为各种应用选择最佳模型，并基于这些技术开发新的创新模型。胆管系统中的上皮细胞可发展为难治性癌症，其通常与由病毒、寄生虫、结石和化学物质引起的炎症有关。基因组学研究揭示了胆道癌（BTC）中经常发生的遗传变化和失调的信号通路。使用各种基因工程小鼠，至少部分地阐明了因果关系。Cre-LoxP技术的技术进步，连同流体动力学尾注射、CRISPR/Cas9技术、体内电穿孔和类器官培养，使得BTC的建模更加精确。基于类器官的遗传建模，结合小鼠植入，最近引起了人们的注意，作为加速BTC模型开发的一种手段。虽然每种模型可能不能完美地模拟疾病，但它们可以相互补充，或者可以整合两种不同的方法来建立新的模型。此外，这些具有相同基因型的模型之间的结果比较提供了对BTC发病机制中遗传改变和微环境之间相互作用的机制见解。在这里，我们回顾了小鼠BTC遗传模型的现状，以提供有助于明智选择模型的信息，并为理想疾病模型的未来发展提供信息。
Biliary tract cancer (BTC) is often refractory to conventional therapeutics and is difficult to diagnose in the early stages. In addition, the pathogenesis of BTC is not fully understood, despite recent advances in cancer genome analysis. To address these issues, the development of fine disease models is critical for BTC. Although still limited in number, there are various platforms for genetic models of BTC owing to newly emerging technology. Among these, implantation-based models have recently drawn attention for their convenience, flexibility, and scalability. To highlight the relevance of this approach, we comprehensively summarize the advantages and disadvantages of BTC models developed using diverse approaches. Currently available research data on intra- and extrahepatic cholangiocarcinoma and gallbladder carcinoma are presented in this review. This information will likely help in selecting the optimal models for various applications and develop novel innovative models based on these technologies. Epithelial cells in the biliary system can develop refractory types of cancers, which are often associated with inflammation caused by viruses, parasites, stones, and chemicals. Genomic studies have revealed recurrent genetic changes and deregulated signaling pathways in biliary tract cancer (BTC). The causal roles have been at least partly clarified using various genetically engineered mice. Technical advances in Cre-LoxP technology, together with hydrodynamic tail injection, CRISPR/Cas9 technology, in vivo electroporation, and organoid culture have enabled more precise modeling of BTC. Organoid-based genetic modeling, combined with implantation in mice, has recently drawn attention as a means to accelerate the development of BTC models. Although each model may not perfectly mimic the disease, they can complement one another, or two different approaches can be integrated to establish a novel model. In addition, a comparison of the outcomes among these models with the same genotype provides mechanistic insights into the interplay between genetic alterations and the microenvironment in the pathogenesis of BTCs. Here, we review the current status of genetic models of BTCs in mice to provide information that facilitates the wise selection of models and to inform the future development of ideal disease models.
登录
查看更多内容
影响因子：
7
作者：
Cho SW;Kim S;Kim Y;Kweon J;Kim HS;Bae S;Kim JS
通讯作者：
Kim JS
影响因子：
6.4
作者：
Davies LC;Taylor PR
通讯作者：
Taylor PR
影响因子：
3.2
作者：
Deveau, Helene;Barrangou, Rodolphe;Moineau, Sylvain
通讯作者：
Moineau, Sylvain
影响因子：
5.2
作者：
Erlangga, Zulrahman;Wolff, Katharina;Saborowski, Michael
通讯作者：
Saborowski, Michael
DOI：
10.1126/science.1159689
发表时间：
2008-08-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Brouns SJ;Jore MM;Lundgren M;Westra ER;Slijkhuis RJ;Snijders AP;Dickman MJ;Makarova KS;Koonin EV;van der Oost J
通讯作者：
van der Oost J