Therapeutic Applications of Nitric Oxide in Cancer and Inflammatory Disorders. Third International Conference on Therapeutic Application of Nitric Oxide in Cancer and Inflammatory Disorders

Table of Contents

Contributors
About the editors
Preface
UDINE 2023
Objective of this volume
Highlights

I General introduction

1. Nitric oxide pathophysiology and applications in patients undergoing major cardiac surgery
Signori Davide, Mattias Carlstr�m, Lorenzo Berra, and Rezoagli Emanuele

Abbreviations
Introduction
Pathophysiology of CSA-AKI and NO dysregulation
Renal vasoconstriction
Direct free-hemoglobin and catalytic iron injury
Ischemiaereperfusion injury
Conclusions
Conflict of interest statement
Acknowledgments
References

II Nitric oxide and cancer

2. The emerging role of dimethylarginine dimethylaminohydrolase 2 in regulating vasculogenic mimicry in cancer
Arduino A. Mangoni, Lashika Weerakoon, Vinitha N. Ragavan, Natalia Jarzebska, Roman N. Rodionov, and Sara Tommasi

Abbreviations
Introduction
Vasculogenic mimicry: Pathogenesis and clinical significance
Dimethylarginine dimethylaminohydrolase 1: Biology and role in vasculogenic mimicry
Recent developments in understanding the biological role of DDAH2 and its possible effects in vasculogenic mimicry
General considerations
Conflict of interest statement
References

III Nitric oxide reactions in the cells and models to check its biological properties

3. Decoding S-nitrosylation: Theoretical aspects and analytical approaches
Gianmarco Matrullo, Chiara Pecorari, and Giuseppe Filomeni

Abbreviations
Introduction
NO signaling
Nitric oxide in physiology and pathology
S-nitrosylation detection: Approaches and challenges
Conclusion
Conflict of interest
Acknowledgments
References

4. Preclinical models to assess the pharmacological properties of NO derivatives
Lucia Morbidelli and Valerio Ciccone

Abbreviations
From preclinical to clinical trials of drugs
Cell-based in vitro pharmacological screening and safety assessment
Ex vivo experiments
In vivo experiments to assess efficacy and safety of NO derivatives
Conclusions
Acknowledgements
References

IV
Nitric oxide and neurodegeneration

5. Nitric oxide-mediated neuroinflammatory pathways as treatment targets in neurodegeneration
Jennifer Cale, Tracy D. Farr, Sebastien Serres, and Joern R. Steinert

Abbreviations
Introduction
Neurovascular oxidative and nitrergic stress
Redox stress in the vascular, neuronal, and astrocytic compartments
Therapeutic targets of NO signaling
Conclusions
Acknowledgments
References

V Nitric oxide and therapeutics

6. Role of nitric oxide in gemcitabine resistance in pancreatic cancer cells
Mariachiara Gani, Eros Di Giorgio, Raffaella Picco, Luigi E. Xodo, and Valentina Rapozzi

Abbreviations
Introduction
Acknowledgments
References
Further reading

7. Exploring the dual role of nitric oxide in glioblastoma: Therapeutic implications
Inesa Navasardyan and Benjamin Bonavida

Abbreviations
Introduction
Treatment of GBM
NO production and its biological process
Role of the INOS/NO pathway in GBM
NO-targeted therapies in GBM
Discussion
Perspectives and future directions
Acknowledgments
References

8. Nitric oxide donating systems and their potential in shaping tumor immunoregulation
Greta Varchi

Introduction
The tumor microenvironment
The enigmatic dual nature of nitric oxide in cancer
Nitric oxide donors
Nitric oxide donors and the immune system
Conclusions and future directions
References

9. Control of nitric oxide synthase 2: Role of NRF2-regulated distal enhancer
Eros Di Giorgio, Valentina Rapozzi, and Luigi E. Xodo

Abbreviations
Introduction
NOS2 structure and function
NOS2 and cancer
Transcription factors activating NOS2 expression
NRF2 controls the expression of NOS2
RF2 binds to a distal enhancer of NOS2
PDAC-spheroids formation depends on NOS2: Therapeutic implications
Concluding remarks
Conflict of interest
References
Further Reading

10. Nitric oxide in tumor biology: From stemness to metabolic reprogramming
Antonio Rodr�guez-Ariza

Abbreviations
Introduction
Role of NO in the acquisition of stem characteristics and therapy resistance in breast cancer
Role of NO in the biology of intestinal cancer cells
Metabolic shift underlies tumor progression and immune evasion in S-nitrosoglutathione reductase-deficient cancer
Conclusions
Acknowledgments
References

11. Impact of nitric oxide on hemeprotein maturation and its relevance to cancer and pulmonary diseases
Chaitali Ghosh, Mamta Sumi, and Arnab Ghosh

Abbreviations
Introduction
Impact of NO on hemeprotein maturation
NO in cancer
Significance of the NO-sGC-cGMP pathway in globin maturation and relevance to cancer progression
NO in asthma and pulmonary diseases
Conclusion and future directions
Acknowledgments
References

VI Educational session

12. Using artificial intelligence to discover new cancer therapies
Apostolos Zaravinos

Index 000

Authors

Valentina Rapozzi Associate Professor in Biochemistry, University of Udine, Italy. Valentina Rapozzi is an Associate Professor in Biochemistry at the Department of Medicine in the University of Udine, President of the Italian Society of Photobiology, Founder and Member of the International Society for Nitric Oxide and Cancer, and Member of the board of the PhD in Biomedical Science and Biotechnology at the University of Udine.
Valentina Rapozzi has a strong background in cell biology, molecular biology, and in vivo animal tumor.
Her research interests can be divided into three fields: (1) Application of new photosensitizers in tumor cells culture and in vivo system and study of molecular pathways involved in host's response to the photodynamic therapy; (2) Molecular strategies (antigene and antisense) to study neoplastic proliferation; (3) Influence of psychological stress on metastasis progression in animal model.
Her current research interest is the study of molecular mechanisms in the tumor response, particularly in the field of redox signaling and photooxidative stress. She is focusing on some aspects of cell response to photodynamic therapy and its relevance in molecular oncology and cancer.
She has contributed to the understanding of the molecular mechanisms involving reactive oxygen and nitric species (ROS/RNS) in coordinating cellular responses to photooxidative stress in different cell/animal models.
She is the coauthor of about 80 international publications, 10 book chapters, and a participant in 138 congresses, Guest Editor for Forum on Immunopathological Diseases and Therapeutics in 2011 with the Volume Molecular Pathways in the Response of Tumors to Photodynamic Therapy, and Editor together with Prof. Giulio Jori from the University of Padova, Italy, for the Volume Resistance to Photodynamic Therapy in Cancer 2015, Vol 5. Resistance to Targeted Anti-Cancer Therapeutics, Series Editor Benjamin Bonavida, Springer. Guest Editor together Prof. Benjamin Bonavida for "Circadian Rhythms and Oncogenesis� for Critical Reviews in Oncogenesis, 2021. Luigi Xodo Full Professor in Biochemistry, University of Udine, Italy.

Luigi Xodo is a Full Professor of Biochemistry at the Department of Medicine of the University of Udine, Italy. His work focuses on unraveling the oncogenes involved in carcinogenesis and on the development of new cancer therapies. In particular, Dr. Xodo's work led to the discovery that the KRAS oncogene, a key player in cellular transformation toward malignancy, is intricately regulated by guanine-rich sequences that adopt unique G-quadruplex structures. This discovery paved the way for targeted interventions against KRAS-related cancers. Dr. Xodo developed effective anticancer drugs that could inhibit the KRAS oncogene. One notable approach has been the use of cationic porphyrins that specifically target G-quadruplexes in KRAS mRNA and trigger transcript degradation upon photoactivation. In addition, Dr. Xodo's studies contribute to the discovery of a metabolic reprogramming phenomenon in KRAS-related cancers by elucidating how arginine metabolism shifts to promote the production of polyamines, phosphocreatine, and nitric oxide. He is the author of 120 publications in high-quality peer-reviewed journals. His academic contributions are evidenced by 120 publications in peer-reviewed journals with high-impact factor, underlining his profound impact on the field of biochemistry and oncology.

Benjamin Bonavida Distinguished Research Professor, Department of Microbiology, Immunology and Molecular Genetics, David Ge? en School of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, California, USA. Dr. Benjamin Bonavida is currently a Distinguished Research Professor at the University of California, Los Angeles (UCLA). He is affiliated with the Department of Microbiology, Immunology and Molecular Genetics, UCLA David Geffen School of Medicine, and the Jonsson Comprehensive Cancer Center at UCLA. His research career, thus far, has focused on investigations in the fields of basic immunochemistry and cancer immunobiology. His research investigations have ranged from the biochemical, molecular, and genetic mechanisms of cell-mediated killing and tumor cell resistance to chemo-immuno cytotoxic drugs. The reversal of tumor cell resistance was investigated by the use of various selected sensitizing agents based on molecular mechanisms of resistance. In these investigations, there was the newly characterized dysregulated NF-kB/ Snail/YY1/RKIP/PTEN loop in many cancers that was reported to regulate cell survival, proliferation, invasion, metastasis, and resistance. Emphasis was focused on the roles of the tumor suppressor Raf kinase inhibitor protein (RKIP) and the tumor promoter Yin Yang 1 (YY1) and the role of nitric oxide (NO) as a chemo-immuno-sensitizing factor. Many of the aforementioned studies are centered on the clinical challenging features of cancer patients' failure to respond to both conventional and targeted therapies.
Dr. Bonavida has been active in the organization of regular sequential international miniconferences that are highly focused on the roles of YY1, RKIP, and nitric oxide in cancer and their potential therapeutic applications. Several books edited or coedited have been published. In addition, he is the Series Editor of books (over 20) published by Springer/Nature: Resistance to Anti-Cancer Targeted Therapeutics. In addition, he is presently the Series Editor of Three Series published by Elsevier/Academic Press on "Cancer Sensitizing Agents for Chemotherapy,� "Sensitizing Agents for Cancer Resistance to Cell Mediated Immunotherapy,� and "Breaking Tolerance to Anti-Cancer Antibody Immunotherapy.� He is the Editor-in-Chief of the Journal Critical Reviews in Oncogenesis, Editor-in-Chief of Onco Therapeutics, and Associate Editor of "Critical Reviews in Immunology.� Dr. Bonavida has published over 500 research publications and reviews in various scientific journals of high impact.