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pH Deregulation as the Eleventh Hallmark of Cancer
- 1st Edition - June 30, 2023
- Authors: Tomas Koltai, Larry Fliegel, Stephan J. Reshkin, Fatima Baltazar, Rosa Angela Cardone, Khalid Omer Alfarouk, Julieta Afonso
- Language: English
- Paperback ISBN:9 7 8 - 0 - 4 4 3 - 1 5 4 6 1 - 4
- eBook ISBN:9 7 8 - 0 - 4 4 3 - 1 5 4 6 2 - 1
pH Deregulation as the Eleventh Hallmark of Cancer presents key concepts about pH deregulation in a concise and straight-forward manner. The book discusses topics such as pH regula… Read more
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Request a sales quotepH Deregulation as the Eleventh Hallmark of Cancer presents key concepts about pH deregulation in a concise and straight-forward manner. The book discusses topics such as pH regulation and metabolism, sodium hydrogen exchanger, monocarboxylate transporter, V-ATPase proton pump, carbonic anhydrases, and voltage gated sodium channels. In addition, it covers clinical and therapeutic implications and future perspectives. This is a valuable resource for researchers, oncologists, students and members of the biomedical and medical fields who want to learn more about the role of pH deregulation in cancer treatment.
pH deregulation can improve the outcome of classical treatments without adding toxicity to them, and the book shows that treating the pH peculiarities of cancer is simple and can be performed with existing drugs. Based on the classification of tumor malignancy in ten hallmarks, the authors put pH deregulation at the spotlight and separated from metabolic reprogramming due to its impact on all other hallmarks, proposing it as an additional characteristic to evaluate and fight cancer.
- Proposes that pH deregulation should be considered as an independent hallmark of cancer from metabolic reprogramming due to its impact on all other hallmarks (based on seminal work of Hanahan and Weinberg)
- Explains basic issues of cancer pH deregulation and its consequences in a simple and concise manner
- Discusses the subject from the start with very elementary concepts on pH and pH regulation to help readers understand key concepts without proper background
- Presents key concepts through original illustrations and table for easy comprehension
Graduate students and researchers in cancer research, oncologists. Healthcare workers, clinicians
- Cover
- Title page
- Table of Contents
- Copyright
- Dedication
- Acknowledgment
- Introductory words
- Chapter 1: pH Regulation and metabolism: Basic concepts
- Abstract
- pH regulation
- Concentration of protons ([H+]) and pH
- Some basic definitions
- pH homeostasis
- What is the need for these different pH compartments?
- Buffers
- pH and enzymatic activity
- Transport of substances and ions in and out of cells
- The proton extruders
- Metabolism
- Antimetabolite
- Cell respiration and metabolism
- How does CO2 play an important role in acid-base balance?
- In summary [25–28]
- References
- Chapter 2: The pH gradient in cancer: pH deregulation
- Abstract
- Historical background
- Main participants of the pHtome
- When does the pH inversion start?
- How does the pHtome work
- How do cancer cells survive in the acidic microenvironment?
- Extracellular acidity: The origins
- Extracellular acidity: The consequences
- Intracellular alkalinity
- Conclusions
- References
- Chapter 3: The pHtome
- Abstract
- Introduction
- Why are there so many participants in the pHtome?
- Can the pHtome be inhibited?
- References
- Chapter 3.1: Na+/H+ exchangers (NHEs)
- Abstract
- Introduction
- Tissue and subcellular distribution
- NHE's in breast and prostate cancer
- Summary
- References
- Chapter 3.2: Voltage gated sodium channels (VGSCs)
- Abstract
- Structure (Figs. 1 and 2)
- VGSCs in cancer
- NaV1.5 and breast cancer
- Clinical implications
- Discussion
- Other possible combinations
- References
- Chapter 3.3: Carbonic anhydrases (CAs)
- Abstract
- Introduction
- Structure
- Intracellular carbonic anhydrase II (CA II)
- CA II in tumors
- Inhibiting CAs
- Conclusions
- References
- Chapter 3.4: The sodium bicarbonate cotransporter (NBC) family
- Abstract
- General overview
- NBC protein structure, isoforms and tissue distribution
- NBC in normal physiology: Role and regulation
- NBC in disease: Role in the cancer pHtome
- NBC expression in malignancy and clinical significance
- Targeting NBC for cancer treatment
- Conclusions
- References
- Chapter 3.5: Monocarboxylate transporters (MCTs) and lactate
- Abstract
- Lactic acid or lactate?
- Role of lactate in cancer
- MCT structure, function and role in cancer
- MCTs as targets for cancer therapy
- Lactate tracers for patient treatment monitoring
- Conclusions
- References
- Chapter 3.6: The vacuolar type-ATPase proton pump
- Abstract
- Introduction
- Structure
- Function
- V-ATPase proton pump in cancer
- Proton pump inhibitors
- The proton sink
- Conclusions
- References
- Chapter 3.7: Voltage gated proton channel (Hv1)
- Abstract
- Introduction
- Mechanism of action
- Role in cancer
- A hypothesis on how Hv1 works in cancer: The NOX2-Hv1 association
- Inhibitors of Hv1
- Conclusions
- References
- Chapter 4: Coordinated action of the pHtome: Integrating the cancer pH process
- Abstract
- Introduction
- pHtome coordination
- Rules of pH deregulation
- Conclusions
- References
- Chapter 5: How pH deregulation favors the hallmarks of cancer
- Abstract
- A summary of the main concepts of the hallmarks of cancer
- The hallmarks (eight hallmarks and two enabling characteristics) [1–5]
- Sustaining proliferative signaling
- Evading growth suppressors
- Resisting cell death
- Enabling replicative immortality
- Inducing angiogenesis
- Activating invasion and metastasis
- Reprogramming energy metabolism
- Evading immune destruction
- Genome instability
- Inflammation
- Conclusions
- References
- Chapter 6: Deregulated pH: Therapeutic implications and treatment
- Abstract
- Introduction
- pH-centered treatments
- Hydroxycitrate and α-lipoic acid
- Combination of lipoic acid and hydroxycitrate
- Capsaicin
- The pH-centered scheme
- Discussion
- Partial use of the scheme
- Future perspectives
- Conclusions
- References
- Chapter 7: Cancer metabolism and its interplay with pH
- Abstract
- Introduction
- Cancer metabolism
- Beyond Warburg
- Centrality of glucose in cancer metabolism and alternative pathways
- What comes first: The increase in intracellular pH or glycolysis?
- Relationship mitochondria, glycolysis and pH
- Carbon dioxide in pH gradient determination
- Therapeutic targeting of the metabolism-pH relationship
- Targeting tumor metabolism through mitochondria (Mito-booster agents)
- Anti-tumoral actions of ALA
- Conclusions
- References
- Chapter 8: pH and drug resistance
- Abstract
- Introduction
- Increased efflux of drugs
- Drug extrusion proteins
- Relationship between MDR and pH
- Further evidence of the relationship pH-MDR
- Possible role of electric conductivity
- Treatment scheme to target MDR
- Mechanisms to increase drug access
- Conclusions
- References
- Chapter 9: Membrane proton sensing potentiates the pro-tumoral effects of extracellular acidity
- Abstract
- Introduction
- The pH sensing systems
- Effects of AS-GPCRs
- Therapeutic resistance
- Increased anti-apoptotic proteins
- Evidence of ASICs’ pro-tumoral behavior
- Discussion
- The controversies
- Conclusions
- References
- Chapter 10: Final words
- References
- Index
- No. of pages: 200
- Language: English
- Edition: 1
- Published: June 30, 2023
- Imprint: Academic Press
- Paperback ISBN: 9780443154614
- eBook ISBN: 9780443154621
TK
Tomas Koltai
Tomas Koltai is Board Certified Specialist in Medical Oncology (1985), PhD in Chemistry (1997) and Master’s in Sciences in Molecular Oncology, University of Buenos Aires (2011). He has vast experience on cancer treatment at several positions: staff oncologist, Sanatorio Mater Dei, Argentina (1985-1990); Head of Oncology, Central Hospital of the Centro Gallego de Buenos Aires (1990-2000) and Medical Director, at the same institution (2000-2002); Head of the Department of Chemotherapy, National Social Services for Retirees, Argentina (2002-2014); Head of the Department of Oncology, Social Services of the National Food Workers Union, Argentina (2010-2014) and Medical Director at the same institution (2014-2016). He has authored several seminal publications on cancer and created the new “triple-edged cancer treatment”.
Affiliations and expertise
Former Medical Director, Hospital del Centro Gallego de Buenos Aires, ArgentinaLF
Larry Fliegel
Research in Dr. Fliegel’s laboratory investigates membrane proteins’ function, how intracellular pH is regulated and the role of Na+/H+ exchanger in human disease, especially heart disease and breast cancer. The work is funded by CIHR and other sources. Dr. Fliegel has published over 150 publications in numerous journals including J. Biological Chemistry, J. Molecular and Cellular Cardiology, Hypertension, Cancer Research, Basic Research in Cardiology and others. He has authored two books and served on several editorial boards of Journals and grant panels such as CIHR. His awards include a Killam Annual Professor Award (2009-10), a Tier one Basic Science Mentoring Award (2013), McCalla Research Professorship Award (2007) and Alberta Heritage Foundation for Medical Research Scientist Award (2006-2013).
Affiliations and expertise
Professor, Associate Chair, Department of Biochemistry, Faculty of Medicine, University of Alberta, CanadaSR
Stephan J. Reshkin
Stephan Reshkin, PhD, is molecular biologist and Associate Professor at the University of Bari (Italy). Dr. Reshkin has published 108 scientific papers, several book chapters and co-authored An Innovative Approach to Understanding and Treating Cancer: Targeting pH (Elsevier, 2020). His main research interests are cancer cell and pancreatic ductal adenocarcinoma.
Affiliations and expertise
Associate Professor, Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, ItalyFB
Fatima Baltazar
Fátima Baltazar holds a degree in Pharmaceutical Sciences by the University of Coimbra (Portugal, 1991), a PhD by the University of Hull (UK, 1998) and has postdoctoral experience at the University of Minho (Portugal, 1998-2003). She is currently Associate Professor at the Medical School of University of Minho (Portugal). Fatima joined ICVS (Life and Health Sciences Research Institute) team in 2004 and she is currently Principal Investigator and Coordinator of the Surgical Sciences Research Domain (SSRD). She started her research on the Cancer field in 2005 and, in the last years, Fatima’s main research interest has been on cancer metabolism, focusing on the discovery of new prognostic metabolic biomarkers and cancer therapeutic targets, using human samples and suitable in vitro and in vivo cancer models. Fátima has published 104 international peer-reviewed research articles, 8 book chapters and she is also (co-)inventor on two national patent applications.
Affiliations and expertise
Associate Professor, Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalRC
Rosa Angela Cardone
Rosa Angela Cardone is currently Assistant Professor at the Department of Bioscience, Biotechnologies and Biopharmaceutics, Section of Physiology, University of Bari, Italy. She has a long-standing expertise in the pH deregulation and has extensively investigated its role in tumor transformation and malignancy.
Affiliations and expertise
Associate Professor, Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, ItalyKA
Khalid Omer Alfarouk
Khalid O. Alfarouk is currently Assistant Professor at Al-Ghad International Health Sciences Colleges, Al-Madinah Al-Munawarah, Saudi Arabia. His research focus is on cancer metabolism and pH in cancer.
Affiliations and expertise
Assistant Professor, Alfarouk Biomedical Research LLC, Temple Terrace, FL, USA; Hala Alfarouk Cancer Center, Khartoum, SudanJA
Julieta Afonso
Julieta Afonso is currently Assistant Professor at Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho. Her research focus is monocarboxylate transporters.
Affiliations and expertise
Post-doctoral researcher, Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, PortugalRead pH Deregulation as the Eleventh Hallmark of Cancer on ScienceDirect