Abstract
Tumor necrosis factor alpha (TNF-α) is a multi-functional cytokine that regulates a variety of signaling pathways implicated in inflammation, immunity, cell death (apoptosis), cell survival (anti-apoptosis), and even tumorigenesis. TNF-α is predominantly produced by macrophages (or Kupffer cells within the liver), but generated by lymphoid cells, astrocytes, endothelial cells, and smooth muscle cells to some degree. In the liver, TNF-α not only serves as a key mediator of hepatocyte apoptosis resulting in the liver damage, but also plays an important role in cellular proliferation leading to liver regeneration or even hepatocarcinogenesis. TNF-α may indirectly contribute to carcinogenesis via various inflammatory conditions such as alcoholic and non-alcoholic fatty liver diseases and chronic viral hepatitis. On the one hand, in inflammation, TNF-α induces apoptosis repeatedly and subsequently enhances the chance of formation of anomalous cells during the process of regeneration and dysplasia. On the other hand, TNF-α exerts as an anti-angiogenic factor depending on its concentration. It shows an anti-tumorous effect by increasing vascular permeability in the tumors. When it is perfused in combination with chemotherapeutic drugs using isolated hepatic infusion, TNF-α may increase the responsiveness of hepatocellular carcinoma (HCC) or metastatic cancers to anti-cancer agents as isolated limb perfusion methods in an unresectable soft tissue sarcoma or melanoma. This article reviews the TNF-α signaling pathway in hepatocarcinogenesis and the new challenge of TNF-α as a new therapeutic strategy in HCC.
Keywords: Tumor necrosis factor alpha, hepatocarcinogenesis, hepatocellular carcinoma, single nucleotide polymorphism, anti-cancer therapy.
Current Pharmaceutical Design
Title:Clinical Aspects of Tumor Necrosis Factor-α Signaling in Hepatocellular Carcinoma
Volume: 20 Issue: 17
Author(s): Myoung-Kuk Jang, Hyoung Su Kim and Young-Hwa Chung
Affiliation:
Keywords: Tumor necrosis factor alpha, hepatocarcinogenesis, hepatocellular carcinoma, single nucleotide polymorphism, anti-cancer therapy.
Abstract: Tumor necrosis factor alpha (TNF-α) is a multi-functional cytokine that regulates a variety of signaling pathways implicated in inflammation, immunity, cell death (apoptosis), cell survival (anti-apoptosis), and even tumorigenesis. TNF-α is predominantly produced by macrophages (or Kupffer cells within the liver), but generated by lymphoid cells, astrocytes, endothelial cells, and smooth muscle cells to some degree. In the liver, TNF-α not only serves as a key mediator of hepatocyte apoptosis resulting in the liver damage, but also plays an important role in cellular proliferation leading to liver regeneration or even hepatocarcinogenesis. TNF-α may indirectly contribute to carcinogenesis via various inflammatory conditions such as alcoholic and non-alcoholic fatty liver diseases and chronic viral hepatitis. On the one hand, in inflammation, TNF-α induces apoptosis repeatedly and subsequently enhances the chance of formation of anomalous cells during the process of regeneration and dysplasia. On the other hand, TNF-α exerts as an anti-angiogenic factor depending on its concentration. It shows an anti-tumorous effect by increasing vascular permeability in the tumors. When it is perfused in combination with chemotherapeutic drugs using isolated hepatic infusion, TNF-α may increase the responsiveness of hepatocellular carcinoma (HCC) or metastatic cancers to anti-cancer agents as isolated limb perfusion methods in an unresectable soft tissue sarcoma or melanoma. This article reviews the TNF-α signaling pathway in hepatocarcinogenesis and the new challenge of TNF-α as a new therapeutic strategy in HCC.
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Cite this article as:
Jang Myoung-Kuk, Kim Su Hyoung and Chung Young-Hwa, Clinical Aspects of Tumor Necrosis Factor-α Signaling in Hepatocellular Carcinoma, Current Pharmaceutical Design 2014; 20 (17) . https://dx.doi.org/10.2174/13816128113199990587
DOI https://dx.doi.org/10.2174/13816128113199990587 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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