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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Neuronal Death in Amyotrophic Lateral Sclerosis (ALS): What Can We Learn from Genetics?
CNS & Neurological Disorders - Drug Targets The mTOR Pathway: A New Target in Cancer Therapy
Current Cancer Drug Targets BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK
Anti-Cancer Agents in Medicinal Chemistry Towards Drug Discovery for Brain Tumours: Interaction of Kinins and Tumours at the Blood Brain Barrier Interface
Recent Patents on CNS Drug Discovery (Discontinued) Hyaluronan/Hyaladherins - a Promising Axis for Targeted Drug Delivery in Cancer
Current Drug Delivery PET-MRI Based Molecular Imaging as a Response Marker in Cervical Cancer: A Systematic Review
Current Molecular Imaging (Discontinued) Small Molecule Inhibitors of NF-κB and JAK/STAT Signal Transduction Pathways as Promising Anti-Inflammatory Therapeutics
Mini-Reviews in Medicinal Chemistry Oncolytic Viruses for Induction of Anti-Tumor Immunity
Current Pharmaceutical Biotechnology Wrap-and-Strip Technology of Protein–Polyelectrolyte Complex for Biomedical Application
Current Medicinal Chemistry Development of Hedgehog Pathway Inhibitors (HPI) in Treatment of Cancer
Current Chemical Biology An Overview of Labeled Porphyrin Molecules in Medical Imaging
Recent Patents and Topics on Imaging (Discontinued) Injectable Thermosensitive Chitosan/Glycerophosphate-Based Hydrogels for Tissue Engineering and Drug Delivery Applications: A Review
Recent Patents on Drug Delivery & Formulation Patents in Cancer Stem Cells
Recent Patents on Biomarkers When Ubiquitin Meets NF-κB: A Trove for Anti-cancer Drug Development
Current Pharmaceutical Design Tyrosine Kinases as Targets for Anti-Inflammatory Therapy
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry CD4+ T Cell Responses in the Immune Control Against Latent Infection by Epstein-Barr Virus
Current Molecular Medicine Management of Glioblastoma Multiforme by Phytochemicals: Applications of Nanoparticle-Based Targeted Drug Delivery System
Current Drug Targets mTOR: A Novel Therapeutic Target for Diseases of Multiple Systems
Current Drug Targets Liposome Technology for Drug Delivery Against Mycobacterial Infections
Current Pharmaceutical Design Alternatively Spliced Genes as Biomarkers for Schizophrenia, Bipolar Disorder and Psychosis: A Blood-Based Spliceome-Profiling Exploratory Study (Supplementry Table)
Current Pharmacogenomics and Personalized Medicine