Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: An intricate pathway
Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: An intricate pathway
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DOI：
10.3748/wjg.v20.i12.3078
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发表时间：
2014-03-28
影响因子：
4.3
通讯作者：
Farinati, Fabio
中科院分区：
文献类型：
--
作者：
Cardin, Romilda;Piciocchi, Marika;Farinati, Fabio
导致肝细胞癌发生和发展的组织病理学和分子机制仍不明确，然而，越来越多的证据表明，癌变肝细胞中发生的突变、遗传和表观遗传学变化逐渐积累，导致发育不良的病灶、结节，最终导致显性肝细胞癌。与许多其他肿瘤一样，肝癌被认为是一种“炎症性癌症”，发生在炎症的背景下，其特点是炎症相关的机制有利于肿瘤细胞的存活、增殖和侵袭。将炎症和肿瘤联系起来的分子机制已被广泛研究，并已被证实，在这些部位招募的炎症细胞具有持续的炎症活动，释放趋化因子，促进活性氧的产生。后者，反过来，可能在从肝炎开始，然后是慢性炎症，最终导致癌症的连续过程中发挥主要的致病作用。本文从DNA氧化损伤、细胞因子合成、端粒功能障碍和microRNA调控等复杂网络的角度，探讨了慢性肝损伤、自由基产生和肝细胞癌发生发展之间的关系。(C)2014年白石登出版集团有限公司。版权所有。
The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneo-plastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an "inflammatory cancer", arising from a context of inflammation, and characterized by inflammation-related mechanisms that favor tumor cell survival, proliferation, and invasion. Molecular mechanisms that link inflammation and neoplasia have been widely investigated, and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species. The latter, in turn, probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation, and ultimately leading to cancer. The relationship amongst chronic liver injury, free radical production, and development of HCC is explored in the present review, particularly in the light of the complex network that involves oxidative DNA damage, cytokine synthesis, telomere dysfunction, and microRNA regulation. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.