Nitric Oxide in Health and Disease

Therapeutic Applications in Cancer and Inflammatory Disorders

1st Edition - April 13, 2023
Editors: Lucia Morbidelli, Benjamin Bonavida, Jordi Muntané
Language: English
Paperback ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 3 4 2 - 8
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 3 4 3 - 5

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Approx.326 pages

Cover image
Title page
Table of Contents
Copyright
Contributors
About the Editors
Preface
References
Highlights of the II international conference “therapeutic applications of nitric oxide in cancer and inflammatory-related diseases”
Conference Program
Part I: Development of NO donors and derivatives, and new delivery formations
Chapter 1: Nitric oxide and derivatives: Molecular insights and translational opportunities
Abstract
Conflict of interest
Introduction
Bioavailability/biotransformation of NO
Role of NO in regulating inflammation and other functions during normal physiological activities
Role of NO during inflammatory diseases, tumor microenvironment, and cancers progression
Current clinical trials of NO
Ying and Yang of nitric oxide studies: Immunosuppressive tumor microenvironment induced by the nitric oxide production
Conclusion
References
Chapter 2: Biomedical applications of polymeric nitric oxide (NO) donors
Abstract
Acknowledgment
Conflict of interest
Introduction
Nitric oxide detection
NO production in human body
NO-releasing small molecules
Polymeric NO donors
Biomedical applications
Conclusion and future perspectives
References
Part II: Nitric oxide pathway and cancer progression and therapy
Chapter 3: Therapeutic potential for coxib-nitric oxide releasing hybrids in cancer treatment
Abstract
Conflict of interest
Introduction
COX-2 and cancer
Hybrid drugs: NO-releasing COX inhibitors
NO-coxibs based on diarylpyrrole scaffold
Conclusions
References
Chapter 4: Targeting dimethylarginine dimethylaminohydrolase 1 to suppress vasculogenic mimicry in breast cancer: Current evidence and future directions
Abstract
Conflict of interest
Introduction
Vasculogenic mimicry: Molecular mechanisms and pathophysiological significance
Dimethylarginine dimethylaminohydrolase 1: Biology and role in vasculogenic mimicry
Effects of pharmacological DDAH1 inhibition on vasculogenic mimicry in TNBC
General considerations
References
Chapter 5: Cancer stem cells and nitric oxide
Abstract
Acknowledgments
Conflict of interest
Introduction
Cancer stem cells
Nitric oxide
Nitric oxide as a modulator of the tumor microenvironment
Expression of nitric oxide synthases in tumors
Studies concerning CSCs and NO
NO as a novel therapeutic target in cancer
Conclusion
References
Chapter 6: Inducible nitric oxide synthase 2 (NOS2) and antitumor γδ-T cells
Abstract
Acknowledgments
Conflict of interest
Introduction
Cancer immunotherapies
Gamma delta T (γδ-T) cells
INOS/NOS2 expression
NOS2 and γδ-T cells
γδ-T cells in cancer immunotherapy
Perspectives
References
Chapter 7: The regulation of the programmed death ligand 1 (PD-L1) by nitric oxide in breast cancer: Immunotherapeutic implication
Abstract
Acknowledgments
Conflict of interest
Introduction
Evasion of cancer cells from CD8 T-cell–mediated immunotherapy: Role of PD-L1/PD-1 interactions
Programmed death ligand 1
Reversal of resistance to CMI by checkpoint inhibitors
Regulation of PD-L1 expression on cancer cells
Regulation of PD-L1 expression by nitric oxide (NO)
Inhibitors of NO and inhibition of PD-L1: Restoration of cancer cell response to CD8 T-cell–mediated immunotherapy
Remarks and perspectives
References
Chapter 8: Pepper fruit, as a nutraceutical food, shows antiproliferative activity against tumor cells and it is potentiatied by nitric oxide (NO)
Abstract
Conflict of interest
Acknowledgments
Introduction
Pepper fruit as a potential source of antitumoral compounds
Ripening and NO boost the nutritional properties of pepper fruits
Pepper fruits show antiproliferative activity on tumor cells
Conclusions
References
Part III: Nitric oxide donors and cardiovascular and metabolic diseases
Chapter 9: Nitric oxide (NO) donors in kidney damage and diseases
Abstract
Conflict of interest
Acknowledgments
Introduction
Physiological role of nitric oxide in the kidneys
Applicability and limitations of NO donors
Conclusions
References
Chapter 10: Nitric oxide resistance in type 2 diabetes: Potential implications of HNO donors
Abstract
Acknowledgments
Conflict of interest
Introduction
Evidence of NO• resistance in T2DM
Nitroxyl (HNO)
HNO donation, Angeli’s salt, and NO• resistance in T2DM
Conclusion and perspectives
References
Chapter 11: Inhaled nitric oxide (iNO) administration in intubated and nonintubated patients: Delivery systems, interfaces, dose administration, and monitoring techniques
Abstract
Conflict of interest
Inhaled nitric oxide in intubated patients
Inhaled nitric oxide in nonintubated patients
Inhaled nitric oxide administration in clinical practice
References
Chapter 12: Inhaled nitric oxide (iNO): Clinical applications in critical care medicine, delivery devices, and measuring techniques
Abstract
Conflict of interest
Introduction
NO sources
References
Chapter 13: Mechanistic insights on the role of nitric oxide in ischemia-reperfusion injury
Abstract
Conflict of interest
Introduction
Nitric oxide derivatives
Nitric oxide pathophysiology in ischemic reperfusion injury
Signaling pathways mediated by nitric oxide involved in ischemia-reperfusion injury
Conclusion
References
Part IV: Nitric oxide derivatives in ocular diseases
Chapter 14: Effect of nitric oxide inhibitors in retinitis pigmentosa
Abstract
Acknowledgments
Conflict of interest
Nitric oxide (NO) in the retina
Retinitis pigmentosa
Nitric oxide inhibitors
Nitric oxide inhibitors in retinitis pigmentosa
Conclusion
References
Chapter 15: Advances in the discovery of novel agents for the treatment of glaucoma: The role of nitric oxide donors
Abstract
Conflict of interest
Introduction
Carbonic anhydrase inhibitors as antiglaucoma agents
Carbonic anhydrase inhibitor: NO donor hybrids
Prostaglandin receptor agonists as antiglaucoma agents
PG agonists: NO donor hybrids
Nitric oxide donors per se
Conclusions
References
Conclusions and future perspectives
References
Index

Lucia Morbidelli

Dr. Morbidelli’s experience is within the molecular and biochemical pharmacology of angiogenesis and microcirculation and its biological application in diseases and cancer. Through of a plethora of in vitro and in vivo models, she has contributed to the characterization of the pro- and antiangiogenic activities of designed synthetic molecules and natural products and their potential applications in angiogenesis-dependent diseases of the cardiovascular system, ocular disorders, neurovascular diseases and cancer. She co-organized with Professor Bonavida the Fourth International Workshop on “Nitric Oxide in Cancer” held in Sevilla in March 13-14, 2015. The meeting addressed different topics such as NO, mutagenesis, carcinogenesis, tumor promotion and tumor growth; NO regulation of cell death pathways; NO and proliferation and epithelial-mesenchymal transition; Regulation of immune response by NO; Antitumoral activity of NO-based releasing strategies: pre-clinical studies; Antitumoral activity of NO-based releasing strategies: clinical trials.

Affiliations and expertise

Professor, Department of Life Sciences, University of Siena, Siena, Italy

Benjamin Bonavida

Dr. Bonavida has vast expertise and various reported publications in the field of tumor cell sensitization to chemotherapy (a total of greater than 500 publications) and in particular the novel role of Nitric Oxide (NO) donors in chemo-sensitization and reversal of drug resistance. In addition, he was the first scientist to co-organize an international meeting on the topic (First International Workshop on NO and Cancer, 2005).

Affiliations and expertise

Professor, Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, USA

Jordi Muntané

Dr. Muntané’s scientific career has been all devoted to the study of the relevance of oxidative and nitrosative stress in cell proliferation and death in different experimental models and clinical settings such as acute hepatocellular injury and hepatocarcinoma. The relevance of the temporal, dose and compartmentalization of nitric oxide (NO) release has been related to cytotoxicity, as well as the cytoprotective properties of classical antioxidants, prostanoids and alpha-tocopherol in different experimental models of liver injury. The anti-tumoral properties of NO has also been demonstrated using NO-donors and nitric oxide synthase type III (NOS3) overexpression in in vivo and in vitro models. The involvement of NO in the antitumoral properties of the molecular recommended therapies for patients with advanced hepatocarcinoma, such as the tyrosine kinase inhibitor Sorafenib, has also been studied comprehensively by Dr. Muntané’s lab.

Affiliations and expertise

Dept Medical Physiology and Biophysics, Institute of Biomedicine of Seville (IBiS), Spain