Abstract
Cancer cachexia is a complex catabolic state in patients with a malignancy, associated with increased morbidity and mortality. This syndrome is characterized by a redistribution of the body’s protein content and a subsequent muscle wasting. The aetiology of this syndrome seems multifactorial, but remains unclear. It is suggested that this catabolic state occurs in response to the alterations in immune interactions between tumor and host. The amino acid arginine and its derivate nitric oxide (NO) play various roles in anti-tumor immune response and the body’s homeostasis. Glutamine is the precursor for arginine de novo synthesis and the most abundant amino acid in the body, mainly stored in skeletal muscle. Tumors develop a protection mechanism against the specific anti-tumor attack of the immune system by recruiting myeloid derived suppressor cells (MDSC). The MDSC deplete arginine levels and disturb NO production. We here hypothesize that the perturbation of the arginine/NO metabolism plays a significant role in the aetiology of cancer cachexia. Arginine/ NO metabolism is disturbed in patients with cancer. The body will try to correct this perturbation by mobilizing arginine and glutamine from muscles. The decreased arginine levels and the disturbed NO production activate several cascades, which in turn inhibit protein synthesis and promote proteolysis, leading to cachexia. Cachexia remains one of the most frequent and damaging opportunistic syndromes in cancer patients. In this review we will elaborate on a new hypothesised concept and the underlying mechanisms of this syndrome. New studies are essential to ground this hypothesis and to develop interventions to break through the pathological mechanisms underlying cachexia.
Keywords: Arginase, arginine, cancer cachexia, glutamine, immune system, iNOS, MDSC, nitric oxide, protein synthesis, proteolysis
Current Medicinal Chemistry
Title:The Role of a Disturbed Arginine/NO Metabolism in the Onset of Cancer Cachexia: A Working Hypothesis
Volume: 19 Issue: 31
Author(s): N. Buijs, J. Luttikhold, A.P.J. Houdijk and P.A.M. van Leeuwen
Affiliation:
Keywords: Arginase, arginine, cancer cachexia, glutamine, immune system, iNOS, MDSC, nitric oxide, protein synthesis, proteolysis
Abstract: Cancer cachexia is a complex catabolic state in patients with a malignancy, associated with increased morbidity and mortality. This syndrome is characterized by a redistribution of the body’s protein content and a subsequent muscle wasting. The aetiology of this syndrome seems multifactorial, but remains unclear. It is suggested that this catabolic state occurs in response to the alterations in immune interactions between tumor and host. The amino acid arginine and its derivate nitric oxide (NO) play various roles in anti-tumor immune response and the body’s homeostasis. Glutamine is the precursor for arginine de novo synthesis and the most abundant amino acid in the body, mainly stored in skeletal muscle. Tumors develop a protection mechanism against the specific anti-tumor attack of the immune system by recruiting myeloid derived suppressor cells (MDSC). The MDSC deplete arginine levels and disturb NO production. We here hypothesize that the perturbation of the arginine/NO metabolism plays a significant role in the aetiology of cancer cachexia. Arginine/ NO metabolism is disturbed in patients with cancer. The body will try to correct this perturbation by mobilizing arginine and glutamine from muscles. The decreased arginine levels and the disturbed NO production activate several cascades, which in turn inhibit protein synthesis and promote proteolysis, leading to cachexia. Cachexia remains one of the most frequent and damaging opportunistic syndromes in cancer patients. In this review we will elaborate on a new hypothesised concept and the underlying mechanisms of this syndrome. New studies are essential to ground this hypothesis and to develop interventions to break through the pathological mechanisms underlying cachexia.
Export Options
About this article
Cite this article as:
Buijs N., Luttikhold J., Houdijk A.P.J. and van Leeuwen P.A.M., The Role of a Disturbed Arginine/NO Metabolism in the Onset of Cancer Cachexia: A Working Hypothesis, Current Medicinal Chemistry 2012; 19 (31) . https://dx.doi.org/10.2174/092986712803833290
DOI https://dx.doi.org/10.2174/092986712803833290 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
HCV and Autoimmunity in Rheumatic Diseases
Current Rheumatology Reviews PDGF-D Signaling: A Novel Target in Cancer Therapy
Current Drug Targets CD47 Functionalization of Nanoparticles as a Poly(ethylene glycol) Alternative: A Novel Approach to Improve Drug Delivery
Current Drug Targets Targeted Therapy Options for Treatment of Bone Metastases; Beyond Bisphosphonates
Current Pharmaceutical Design Vascular Endothelial Growth Factor Receptor as Target for Advanced Non-Small Cell Lung Cancer Therapy
Current Drug Targets TNFR1 Regulates Ovarian Cancer Cell Tumorigenicity Through PIK3CB-p110Beta
Current Molecular Medicine Immunomodulatory Activity of MicroRNAs: Potential Implications for Multiple Myeloma Treatment
Current Cancer Drug Targets The Metabolite Trimethylamine-N-Oxide is an Emergent Biomarker of Human Health
Current Medicinal Chemistry Pharmacology and Therapeutic Applications of Enediyne Antitumor Antibiotics
Current Molecular Pharmacology The Antiangiogenic and Antitumoral Activity of Titanocene Y* In Vivo
Letters in Drug Design & Discovery Clinical Importance of Assessment of Type 2 Diabetes Mellitus with Visceral Obesity. A Japanese Perspective
Current Diabetes Reviews Artificial Intelligence Techniques for Colorectal Cancer Drug Metabolism: Ontologies and Complex Networks
Current Drug Metabolism Pharmacological Therapy of Pericardial Diseases
Current Pharmaceutical Design Molecular Classification and Drug Response Prediction in Cancer
Current Drug Targets Oral Factor Xa (FXa) Inhibitors for Treatment of Heparin-induced Thrombocytopenia (HIT)
Current Drug Therapy Third Generation Radiopharmaceuticals for Imaging and Targeted Therapy
Current Pharmaceutical Analysis Role of Metabolic Enzymes P450 (CYP) on Activating Procarcinogen and their Polymorphisms on the Risk of Cancers
Current Drug Metabolism MicroRNA Pathways: An Emerging Role in Identification of Therapeutic Strategies
Current Gene Therapy Non Peptidic Urotensin II Antagonists: Perspectives for a New Class of Drugs
Cardiovascular & Hematological Agents in Medicinal Chemistry Current and Future Medical Therapy, and the Molecular Features of Adrenocortical Cancer
Recent Patents on Anti-Cancer Drug Discovery