Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: An intricate pathway

Romilda Cardin, Marika Piciocchi, Marina Bortolami, Andromachi Kotsafti, Luisa Barzon, Enrico Lavezzo, Alessandro Sinigaglia, Kryssia Isabel Rodriguez-Castro, Massimo Rugge, Fabio Farinati

Research output: Contribution to journalArticlepeer-review

Abstract

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 dys-plastic 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.

Original languageEnglish
Pages (from-to)3078-3086
Number of pages9
JournalWorld Journal of Gastroenterology
Volume20
Issue number12
DOIs
Publication statusPublished - 2014

Keywords

  • Antioxidant mechanisms
  • Cyto-kines
  • Hepatocellular carcinoma
  • MicroR-NA and circulating free DNA
  • Mitochondria
  • Reactive oxygen species
  • Telomere dysfunction
  • Viral hepatitis

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

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