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端粒酶激活在人类肝癌发生过程中的作用

Telomerase activation in human hepatocarcinogenesis.

作者信息

Hytiroglou Prodromos, Theise Neil D

出版信息

Am J Gastroenterol. 2006 Apr;101(4):839-41. doi: 10.1111/j.1572-0241.2006.00521.x.

DOI:10.1111/j.1572-0241.2006.00521.x
PMID:16635228
Abstract

Active telomerase is present in the majority of malignant human tumors, including most cases of hepatocellular carcinoma (HCC). Telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, has been found to be expressed in HCCs, dysplastic (precancerous) nodules (DNs), and regenerative nodules arising in cirrhosis. In a study reported in this issue of the journal, hTERT mRNA levels were assessed by quantitative real-time RT-PCR in various nodular lesions dissected from liver specimens of patients with chronic hepatitis B. High levels of hTERT mRNA were present in HCCs, high-grade DNs, and occasional low-grade DNs, whereas low levels were found in normal livers, livers with chronic hepatitis B (with or without cirrhosis), large regenerative nodules, and most low-grade DNs. Therefore, quantitative assessment of hTERT mRNA may provide a useful adjunct to histopathologic evaluation of large hepatic nodules. Indeed, emerging data from gene expression analyses of DNs and HCCs suggest that hTERT can be included in sets of select genes that provide "molecular signatures" with utility in the diagnosis and management of nodular hepatic lesions. Most importantly, tackling the mechanisms of telomerase activation may provide new means of therapy for HCC and other cancers.

摘要

活性端粒酶存在于大多数人类恶性肿瘤中,包括大多数肝细胞癌(HCC)病例。端粒酶逆转录酶(hTERT)是端粒酶的催化亚基,已发现在肝癌、发育异常(癌前)结节(DN)以及肝硬化中出现的再生结节中表达。在本期杂志报道的一项研究中,通过定量实时逆转录聚合酶链反应(RT-PCR)评估了从慢性乙型肝炎患者肝脏标本中分离出的各种结节性病变中的hTERT mRNA水平。肝癌、高级别DN以及偶尔的低级别DN中存在高水平的hTERT mRNA,而在正常肝脏、慢性乙型肝炎(伴有或不伴有肝硬化)肝脏、大的再生结节以及大多数低级别DN中发现低水平。因此,hTERT mRNA的定量评估可为大的肝结节的组织病理学评估提供有用的辅助。确实,来自DN和肝癌基因表达分析的新数据表明,hTERT可纳入一组选择基因中,这些基因提供在结节性肝病变的诊断和管理中有用的“分子特征”。最重要的是,解决端粒酶激活机制可能为肝癌和其他癌症提供新的治疗方法。

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Telomerase activation in human hepatocarcinogenesis.端粒酶激活在人类肝癌发生过程中的作用
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