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为什么集成HBV DNA可能会导致肝癌:.下面的文章提供了一些解释.
The direct and indirect roles of HBV in liver cancer: prospective markers for HCC screening and potential therapeutic targets
Marc Ringelhan1,2,3,*, Tracy O'Connor1, Ulrike Protzer1 andMathias Heikenwalder1,*
Article first published online: 11 DEC 2014
DOI: 10.1002/path.4434
Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Issue
The Journal of Pathology
The Journal of Pathology
Special Issue: Viruses and Disease
Volume 235, Issue 2, pages 355–367, January 2015
Article has an altmetric score of 2
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Author Information
1
Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany
2
Second Medical Department, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
3
German Centre for Infection research (DZIF), Munich Partner Site, Germany
*Correspondence to: Marc Ringelhan or Mathias Heikenwalder, Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Schneckenburgerstrasse 8, D-81675 München, Germany. E-mail: [email protected] or [email protected]
No conflicts of interest were declared.
Keywords:
HBV;chronic hepatitis B;HBs antigen;HBx;X-protein;liver cancer;HCC;direct role of viral proteins;hepatocarcinogenesis
Abstract
Chronic hepatitis B virus (HBV) infection remains the number one risk factor for hepatocellular carcinoma (HCC), accounting for more than 600 000 deaths/year. Despite highly effective antiviral treatment options, chronic hepatitis B (CHB), subsequent end-stage liver disease and HCC development remain a major challenge worldwide. In CHB, liver damage is mainly caused by the influx of immune cells and destruction of infected hepatocytes, causing necro-inflammation. Treatment with nucleoside/nucleotide analogues can effectively suppress HBV replication in patients with CHB and thus decrease the risk for HCC development. Nevertheless, the risk of HCC in treated patients showing sufficient suppression of HBV DNA replication is significantly higher than in patients with inactive CHB, regardless of the presence of baseline liver cirrhosis, suggesting direct, long-lasting, predisposing effects of HBV. Direct oncogenic effects of HBV include integration in the host genome, leading to deletions, cis/trans-activation, translocations, the production of fusion transcripts and generalized genomic instability, as well as pleiotropic effects of viral transcripts (HBsAg and HBx). Analysis of these viral factors in active surveillance may allow early identification of high-risk patients, and their integration into a molecular classification of HCC subtypes might help in the development of novel therapeutic approaches. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
乙肝病毒的肝癌的直接和间接作用:肝癌筛选和潜在的治疗靶标准标记
马克Ringelhan1,2,3,*,麦蒂O'Connor1,乌尔里克Protzer1 andMathias Heikenwalder1,*
文章首次在线发表时间:2014年12月11日
:10.1002 / path.4434
英国和爱尔兰的版权©2014病理学协会。由John Wiley&Sons出版有限公司
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该病理学杂志
该病理学杂志
特刊:病毒和疾病
卷235,第2期,页355-367,2015年1月
制品具有为2的altmetric得分
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作者信息
1
病毒学,慕尼黑工业大学/亥姆霍兹慕尼黑中心,德国慕尼黑研究所
2
其次医学部,KLINIKUM Rechts伊萨尔河畔,慕尼黑工业大学,德国慕尼黑
3
德国感染研究中心(DZIF),慕尼黑合作网站德国
*通讯作者:马克·Ringelhan或马蒂亚斯Heikenwalder病毒学研究所,慕尼黑工业大学/亥姆霍兹慕尼黑中心,Schneckenburgerstrasse 8,D-81675慕尼黑,德国。电子邮件:[email protected]或h[email protected]
没有利益冲突进行声明。
乙肝病毒;慢性乙型肝炎; HBs抗原; HBx蛋白; X蛋白;肝癌;肝癌;病毒蛋白的直接作用;肝癌
抽象
慢性乙型肝炎病毒(HBV)感染仍是肝细胞癌(HCC)的头号危险因素,占比超过600万例死亡/年。尽管非常有效的抗病毒治疗方案,慢性乙型肝炎(CHB),随后的终末期肝病和肝癌发展仍然是全球的一大挑战。在慢性乙型肝炎,肝损害主要是由免疫细胞的流入和感染的肝细胞的破坏,引起坏死炎症。核苷/核苷酸类似物治疗能有效地抑制CHB患者HBV的复制,从而减少肝癌发展的风险。尽管如此,肝癌中示出HBV DNA复制的足够的抑制治疗的患者的风险的患者比无活性CHB显著更高,不管基线肝硬化的存在,这表明直接,持久的,乙型肝炎病毒的诱发作用。乙肝病毒的直接致癌效应包括在宿主基因组中的整合,导致缺失,顺式/反式激活,易位,生产融合转录物和广义的基因不稳定性,以及病毒转录(HBsAg和HBx蛋白)的多效作用。在主动监测这些病毒的因素分析可允许的高危患者早期识别,并将其纳入肝癌亚型的分子分型可能会在新的治疗方法的发展有所帮助。英国和爱尔兰的版权©2014病理学协会。由John Wiley&Sons出版有限公司 |
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