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罕见遗传性胆汁淤积性疾病与肝癌发生的分子关联。

Rare Inherited Cholestatic Disorders and Molecular Links to Hepatocarcinogenesis.

机构信息

National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London WC1N 1EH, UK.

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.

出版信息

Cells. 2022 Aug 18;11(16):2570. doi: 10.3390/cells11162570.

DOI:10.3390/cells11162570
PMID:36010647
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9406938/
Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer affecting adults and the second most common primary liver cancer affecting children. Recent years have seen a significant increase in our understanding of the molecular changes associated with HCC. However, HCC is a complex disease, and its molecular pathogenesis, which likely varies by aetiology, remains to be fully elucidated. Interestingly, some inherited cholestatic disorders that manifest in childhood are associated with early HCC development. This review will thus explore how three genes that are associated with liver disease in childhood ( and ) might play a role in the initiation and progression of HCC. Specifically, chronic bile-induced damage (caused by changes), disruption of intercellular junction formation (caused by changes) and loss of normal apical-basal cell polarity (caused by changes) will be discussed as possible mechanisms for HCC development.

摘要

肝细胞癌(HCC)是影响成人的最常见原发性肝癌,也是影响儿童的第二大常见原发性肝癌。近年来,我们对与 HCC 相关的分子变化有了更深入的了解。然而,HCC 是一种复杂的疾病,其分子发病机制(可能因病因而异)仍有待充分阐明。有趣的是,一些在儿童时期表现出的遗传性胆汁淤积性疾病与 HCC 的早期发生有关。因此,本综述将探讨与儿童期肝病相关的三个基因( 和 )如何在 HCC 的发生和发展中发挥作用。具体而言,将讨论慢性胆汁诱导的损伤(由 变化引起)、细胞间连接形成的破坏(由 变化引起)和正常顶底细胞极性的丧失(由 变化引起)作为 HCC 发展的可能机制。

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本文引用的文献

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Risk of primary liver cancer in acute hepatic porphyria patients: A matched cohort study of 1244 individuals.急性肝性血卟啉症患者原发性肝癌的风险:1244 例个体的匹配队列研究。
J Intern Med. 2022 Jun;291(6):824-836. doi: 10.1111/joim.13463. Epub 2022 Mar 2.
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Liver Disease and Risk of Hepatocellular Carcinoma in Children With Mutations in TALDO1.TALDO1 基因突变儿童的肝脏疾病与肝细胞癌风险。
Hepatol Commun. 2022 Mar;6(3):473-479. doi: 10.1002/hep4.1824. Epub 2021 Oct 22.
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The Genetic Changes of Hepatoblastoma.肝母细胞瘤的基因变化
Front Oncol. 2021 Jul 21;11:690641. doi: 10.3389/fonc.2021.690641. eCollection 2021.
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Effects of odevixibat on pruritus and bile acids in children with cholestatic liver disease: Phase 2 study.奥地维西巴特对胆汁淤积性肝病患儿瘙痒和胆汁酸的影响:2期研究。
Clin Res Hepatol Gastroenterol. 2021 Sep;45(5):101751. doi: 10.1016/j.clinre.2021.101751. Epub 2021 Jun 26.
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Tight junction protein ZO-2 modulates the nuclear accumulation of transcription factor TEAD.紧密连接蛋白 ZO-2 调节转录因子 TEAD 的核积累。
Mol Biol Cell. 2021 Jul 15;32(15):1347-1358. doi: 10.1091/mbc.E20-07-0470. Epub 2021 May 19.
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VPS33B suppresses lung adenocarcinoma metastasis and chemoresistance to cisplatin.VPS33B抑制肺腺癌转移和顺铂化疗耐药。
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VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer.VPS33B 通过与 NESG1 相互作用抑制卵巢癌细胞生长和顺铂化疗耐药性。
Cancer Sci. 2021 May;112(5):1785-1797. doi: 10.1111/cas.14864. Epub 2021 Mar 31.
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Nat Rev Dis Primers. 2021 Jan 21;7(1):6. doi: 10.1038/s41572-020-00240-3.
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Am J Med Genet A. 2021 Mar;185(3):719-731. doi: 10.1002/ajmg.a.62028. Epub 2020 Dec 24.
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