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Book ; Online ; E-Book: Prostate cancer metabolism

Koltai, Tomas

from biochemistry to therapeutics

2021

Author's details	Tomas Koltai [and more]
Keywords	Prostate / Cancer / Treatment
Language	English
Size	1 Online-Ressource (xxii, 395 Seiten), Illustrationen
Publisher	Academic Press
Publishing place	London
Publishing country	Great Britain
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT021009007
ISBN	978-0-323-90551-0 ; 0-323-90551-X ; 0323905285 ; 9780323905282
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Book ; Online ; E-Book: An innovative approach to understanding and treating cancer

Koltai, Tomas / Reshkin, Stephan J. / Harguindey, Salvador

targeting pH: from etiopathogenesis to new therapeutic avenues

2020

Author's details	Tomas Koltai, Stephan J. Reshkin, Salvador Harguindey
Keywords	Cancer/Pathophysiology
Subject code	616.99407
Language	English
Size	1 Online-Ressource (xvii, 556 Seiten), Illustrationen
Publisher	Elsevier Academic Press
Publishing place	London
Publishing country	Great Britain
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT020384349
ISBN	978-0-12-819060-9 ; 9780128190593 ; 0-12-819060-4 ; 0128190590
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article: Earlier Diagnosis of Pancreatic Cancer: Is It Possible?

Koltai, Tomas

Cancers

2023 Volume 15, Issue 18

Abstract: Pancreatic ductal adenocarcinoma has a very high mortality rate which has been only minimally improved in the last 30 years. This high mortality is closely related to late diagnosis, which is usually made when the tumor is large and has extensively ... ...

Abstract	Pancreatic ductal adenocarcinoma has a very high mortality rate which has been only minimally improved in the last 30 years. This high mortality is closely related to late diagnosis, which is usually made when the tumor is large and has extensively infiltrated neighboring tissues or distant metastases are already present. This is a paradoxical situation for a tumor that requires nearly 15 years to develop since the first founding mutation. Response to chemotherapy under such late circumstances is poor, resistance is frequent, and prolongation of survival is almost negligible. Early surgery has been, and still is, the only approach with a slightly better outcome. Unfortunately, the relapse percentage after surgery is still very high. In fact, early surgery clearly requires early diagnosis. Despite all the advances in diagnostic methods, the available tools for improving these results are scarce. Serum tumor markers permit a late diagnosis, but their contribution to an improved therapeutic result is very limited. On the other hand, effective screening methods for high-risk populations have not been fully developed as yet. This paper discusses the difficulties of early diagnosis, evaluates whether the available diagnostic tools are adequate, and proposes some simple and not-so-simple measures to improve it.
Language	English
Publishing date	2023-09-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15184430
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The complex relationship between multiple drug resistance and the tumor pH gradient: a review.

Koltai, Tomas

Cancer drug resistance (Alhambra, Calif.)

2022 Volume 5, Issue 2, Page(s) 277–303

Abstract: Multiple drug resistance (MDR) is the tumor's way of escaping the cytotoxic effects of various unrelated chemotherapeutic drugs. It can be either innate or acquired. MDR represents the end of the therapeutic pathway, and it practically leaves no ... ...

Abstract	Multiple drug resistance (MDR) is the tumor's way of escaping the cytotoxic effects of various unrelated chemotherapeutic drugs. It can be either innate or acquired. MDR represents the end of the therapeutic pathway, and it practically leaves no treatment alternatives. Reversing MDR is an unfulfilled goal, despite the important recent advances in cancer research. MDR, the main cause of death in cancer patients, is a multi-factorial development, and most of its known causes have been thoroughly discussed in the literature. However, there is one aspect that has not received adequate consideration - intracellular alkalosis - which is part of wider pH deregulation where the pH gradient is inverted, meaning that extracellular pH is decreased and intracellular pH increased. This situation interacts with MDR and with the proteins involved, such as P-gp, breast cancer resistance protein, and multidrug associated resistance protein 1. However, there are also situations in which these proteins play no role at all, and where pH takes the lead. This is the case in ion trapping. Reversing the pH gradient to normal can be an important contribution to managing MDR. The drugs to manipulate pH exist, and most of them are FDA approved and in clinical use for other purposes. Furthermore, they have low or no toxicity and are inexpensive compared with any chemotherapeutic treatment. Repurposing these drugs and combining them in a reasonable fashion is one of the points proposed in this paper, which discusses the relationship between cancer's peculiar pH and MDR.
Language	English
Publishing date	2022-04-03
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2578-532X
ISSN (online)	2578-532X
DOI	10.20517/cdr.2021.134
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Exploring monocarboxylate transporter inhibition for cancer treatment.

Koltai, Tomas / Fliegel, Larry

Exploration of targeted anti-tumor therapy

2024 Volume 5, Issue 1, Page(s) 135–169

Abstract: Cells are separated from the environment by a lipid bilayer membrane that is relatively impermeable to solutes. The transport of ions and small molecules across this membrane is an essential process in cell biology and metabolism. Monocarboxylate ... ...

Abstract	Cells are separated from the environment by a lipid bilayer membrane that is relatively impermeable to solutes. The transport of ions and small molecules across this membrane is an essential process in cell biology and metabolism. Monocarboxylate transporters (MCTs) belong to a vast family of solute carriers (SLCs) that facilitate the transport of certain hydrophylic small compounds through the bilipid cell membrane. The existence of 446 genes that code for SLCs is the best evidence of their importance. In-depth research on MCTs is quite recent and probably promoted by their role in cancer development and progression. Importantly, it has recently been realized that these transporters represent an interesting target for cancer treatment. The search for clinically useful monocarboxylate inhibitors is an even more recent field. There is limited pre-clinical and clinical experience with new inhibitors and their precise mechanism of action is still under investigation. What is common to all of them is the inhibition of lactate transport. This review discusses the structure and function of MCTs, their participation in cancer, and old and newly developed inhibitors. Some suggestions on how to improve their anticancer effects are also discussed.
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2692-3114
ISSN (online)	2692-3114
DOI	10.37349/etat.2024.00210
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Ph paradigm in cancer.

Koltai, Tomas

European journal of clinical nutrition

2020 Volume 74, Issue Suppl 1, Page(s) 14–19

Abstract: Malignant tissues show a peculiar feature regarding pH: while normal tissues have a higher extracellular pH than intracellular pH, in cancer is exactly the opposite. This phenomenon is called the inversion of the pH gradient and is now considered a ... ...

Abstract	Malignant tissues show a peculiar feature regarding pH: while normal tissues have a higher extracellular pH than intracellular pH, in cancer is exactly the opposite. This phenomenon is called the inversion of the pH gradient and is now considered a hallmark of malignancy. For some time, this inverted pH gradient was believed to be a secondary effect of cancer. Now, it is becoming clear that pH inversion is not an innocent consequence, but a key player in the etiopathogenesis of cancer. Therefore, addressing this issue as part of an integral treatment of neoplasia should be a necessary step for improving cancer patients' outcomes. However, the knowledge acquired in this regard through basic research has not reached bedside treatments. The most striking fact is that there are repurposed drugs and nutraceuticals with low or no toxicity that can modify the pH gradient inversion. However, these drugs have not even been tested in cancer treatment.
MeSH term(s)	Humans ; Hydrogen-Ion Concentration ; Neoplasms
Language	English
Publishing date	2020-09-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639358-5
ISSN	1476-5640 ; 0954-3007
ISSN (online)	1476-5640
ISSN	0954-3007
DOI	10.1038/s41430-020-0684-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Targeting the pH Paradigm at the Bedside: A Practical Approach.

Koltai, Tomas

International journal of molecular sciences

2020 Volume 21, Issue 23

Abstract: The inversion of the pH gradient in malignant tumors, known as the pH paradigm, is increasingly becoming accepted by the scientific community as a hallmark of cancer. Accumulated evidence shows that this is not simply a metabolic consequence of a ... ...

Abstract	The inversion of the pH gradient in malignant tumors, known as the pH paradigm, is increasingly becoming accepted by the scientific community as a hallmark of cancer. Accumulated evidence shows that this is not simply a metabolic consequence of a dysregulated behavior, but rather an essential process in the physiopathology of accelerated proliferation and invasion. From the over-simplification of increased lactate production as the cause of the paradigm, as initially proposed, basic science researchers have arrived at highly complex and far-reaching knowledge, that substantially modified that initial belief. These new developments show that the paradigm entails a different regulation of membrane transporters, electrolyte exchangers, cellular and membrane enzymes, water trafficking, specialized membrane structures, transcription factors, and metabolic changes that go far beyond fermentative glycolysis. This complex world of dysregulations is still shuttered behind the walls of experimental laboratories and has not yet reached bedside medicine. However, there are many known pharmaceuticals and nutraceuticals that are capable of targeting the pH paradigm. Most of these products are well known, have low toxicity, and are also inexpensive. They need to be repurposed, and this would entail shorter clinical studies and enormous cost savings if we compare them with the time and expense required for the development of a new molecule. Will targeting the pH paradigm solve the "cancer problem"? Absolutely not. However, reversing the pH inversion would strongly enhance standard treatments, rendering them more efficient, and in some cases permitting lower doses of toxic drugs. This article's goal is to describe how to reverse the pH gradient inversion with existing drugs and nutraceuticals that can easily be used in bedside medicine, without adding toxicity to established treatments. It also aims at increasing awareness among practicing physicians that targeting the pH paradigm would be able to improve the results of standard therapies. Some clinical cases will be presented as well, showing how the pH gradient inversion can be treated at the bedside in a simple manner with repurposed drugs.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers ; Clinical Decision-Making ; Disease Management ; Extracellular Space/metabolism ; Humans ; Hydrogen-Ion Concentration ; Intracellular Space/metabolism ; Molecular Targeted Therapy ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Prognosis ; Sodium-Hydrogen Exchanger 1/antagonists & inhibitors ; Sodium-Hydrogen Exchanger 3/antagonists & inhibitors ; Voltage-Gated Sodium Channel Blockers ; Voltage-Gated Sodium Channels/metabolism
Chemical Substances	Antineoplastic Agents ; Biomarkers ; SLC9A1 protein, human ; SLC9A3 protein, human ; Sodium-Hydrogen Exchanger 1 ; Sodium-Hydrogen Exchanger 3 ; Voltage-Gated Sodium Channel Blockers ; Voltage-Gated Sodium Channels
Language	English
Publishing date	2020-12-03
Publishing country	Switzerland
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21239221
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance.

Koltai, Tomas / Fliegel, Larry

International journal of molecular sciences

2023 Volume 25, Issue 1

Abstract: Trop-2 is a highly conserved one-pass transmembrane mammalian glycoprotein that is normally expressed in tissues such as the lung, intestines, and kidney during embryonic development. It is overexpressed in many epithelial cancers but is absent in non- ... ...

Abstract	Trop-2 is a highly conserved one-pass transmembrane mammalian glycoprotein that is normally expressed in tissues such as the lung, intestines, and kidney during embryonic development. It is overexpressed in many epithelial cancers but is absent in non-epithelial tumors. Trop-2 is an intracellular calcium signal transducer that participates in the promotion of cell proliferation, migration, invasion, metastasis, and probably stemness. It also has some tumor suppressor effects. The pro-tumoral actions have been thoroughly investigated and reported. However, Trop-2's activity in chemoresistance is less well known. We review a possible relationship between Trop-2, chemotherapy, and chemoresistance. We conclude that there is a clear role for Trop-2 in some specific chemoresistance events. On the other hand, there is no clear evidence for its participation in multidrug resistance through direct drug transport. The development of antibody conjugate drugs (ACD) centered on anti-Trop-2 monoclonal antibodies opened the gates for the treatment of some tumors resistant to classic chemotherapies. Advanced urothelial tumors and breast cancer were among the first malignancies for which these ACDs have been employed. However, there is a wide group of other tumors that may benefit from anti-Trop-2 therapy as soon as clinical trials are completed.
MeSH term(s)	Female ; Pregnancy ; Animals ; Drug Resistance, Neoplasm ; Amyloidosis, Familial ; Biological Transport ; Calcium, Dietary ; Cell Proliferation ; Mammals
Chemical Substances	Calcium, Dietary
Language	English
Publishing date	2023-12-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25010087
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Genetic Signature of Human Pancreatic Cancer and Personalized Targeting.

Reshkin, Stephan J / Cardone, Rosa Angela / Koltai, Tomas

Cells

2024 Volume 13, Issue 7

Abstract: Pancreatic cancer is a highly lethal disease with a 5-year survival rate of around 11-12%. Surgery, being the treatment of choice, is only possible in 20% of symptomatic patients. The main reason is that when it becomes symptomatic, IT IS the tumor is ... ...

Abstract	Pancreatic cancer is a highly lethal disease with a 5-year survival rate of around 11-12%. Surgery, being the treatment of choice, is only possible in 20% of symptomatic patients. The main reason is that when it becomes symptomatic, IT IS the tumor is usually locally advanced and/or has metastasized to distant organs; thus, early diagnosis is infrequent. The lack of specific early symptoms is an important cause of late diagnosis. Unfortunately, diagnostic tumor markers become positive at a late stage, and there is a lack of early-stage markers. Surgical and non-surgical cases are treated with neoadjuvant and/or adjuvant chemotherapy, and the results are usually poor. However, personalized targeted therapy directed against tumor drivers may improve this situation. Until recently, many pancreatic tumor driver genes/proteins were considered untargetable. Chemical and physical characteristics of mutated KRAS are a formidable challenge to overcome. This situation is slowly changing. For the first time, there are candidate drugs that can target the main driver gene of pancreatic cancer: KRAS. Indeed, KRAS inhibition has been clinically achieved in lung cancer and, at the pre-clinical level, in pancreatic cancer as well. This will probably change the very poor outlook for this disease. This paper reviews the genetic characteristics of sporadic and hereditary predisposition to pancreatic cancer and the possibilities of a personalized treatment according to the genetic signature.
MeSH term(s)	Humans ; Proto-Oncogene Proteins p21(ras)/genetics ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/diagnosis ; Lung Neoplasms/genetics ; Neoadjuvant Therapy ; Biomarkers, Tumor/genetics
Chemical Substances	Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Biomarkers, Tumor
Language	English
Publishing date	2024-03-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13070602
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Targeting the pH Paradigm at the Bedside

Tomas Koltai

International Journal of Molecular Sciences, Vol 21, Iss 9221, p

A Practical Approach

2020 Volume 9221

Abstract	The inversion of the pH gradient in malignant tumors, known as the pH paradigm, is increasingly becoming accepted by the scientific community as a hallmark of cancer. Accumulated evidence shows that this is not simply a metabolic consequence of a dysregulated behavior, but rather an essential process in the physiopathology of accelerated proliferation and invasion. From the over-simplification of increased lactate production as the cause of the paradigm, as initially proposed, basic science researchers have arrived at highly complex and far-reaching knowledge, that substantially modified that initial belief. These new developments show that the paradigm entails a different regulation of membrane transporters, electrolyte exchangers, cellular and membrane enzymes, water trafficking, specialized membrane structures, transcription factors, and metabolic changes that go far beyond fermentative glycolysis. This complex world of dysregulations is still shuttered behind the walls of experimental laboratories and has not yet reached bedside medicine. However, there are many known pharmaceuticals and nutraceuticals that are capable of targeting the pH paradigm. Most of these products are well known, have low toxicity, and are also inexpensive. They need to be repurposed, and this would entail shorter clinical studies and enormous cost savings if we compare them with the time and expense required for the development of a new molecule. Will targeting the pH paradigm solve the “cancer problem”? Absolutely not. However, reversing the pH inversion would strongly enhance standard treatments, rendering them more efficient, and in some cases permitting lower doses of toxic drugs. This article’s goal is to describe how to reverse the pH gradient inversion with existing drugs and nutraceuticals that can easily be used in bedside medicine, without adding toxicity to established treatments. It also aims at increasing awareness among practicing physicians that targeting the pH paradigm would be able to improve the results of standard ...
Keywords	pH paradigm ; pHtome ; amiloride ; proton pump inhibitors ; acetazolamide ; topiramate ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	501
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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