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  1. Article: The Prime and Integral Cause of Cancer in the Post-Warburg Era.

    Harguindey, Salvador / Reshkin, Stephan J / Alfarouk, Khalid O

    Cancers

    2023  Volume 15, Issue 2

    Abstract: Back to beginnings. ...

    Abstract Back to beginnings.
    Language English
    Publishing date 2023-01-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15020540
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  2. Article ; Online: Hydrogen Ion Dynamics as the Fundamental Link between Neurodegenerative Diseases and Cancer: Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis on Multiple Sclerosis.

    Harguindey, Salvador / Alfarouk, Khalid / Polo Orozco, Julián / Reshkin, Stephan J / Devesa, Jesús

    International journal of molecular sciences

    2022  Volume 23, Issue 5

    Abstract: The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally assessed for the first time in order to integrate neurodegeneration within the energetics ... ...

    Abstract The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally assessed for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study (molecular, biochemical, metabolic, and clinical), the intimate nature of both processes appears to consist of opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranging original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows us to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) is an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Furthermore, within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth. Finally, and for the first time, a new and integrated model of treatment for MS can now be advanced.
    MeSH term(s) Humans ; Mitochondria/metabolism ; Multiple Sclerosis/pathology ; Neoplasms ; Neurodegenerative Diseases/metabolism ; Protons
    Chemical Substances Protons
    Language English
    Publishing date 2022-02-23
    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/ijms23052454
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  3. Article ; Online: "The new pH-centric anticancer paradigm in Oncology and Medicine"; SCB, 2017.

    Harguindey, Salvador / Reshkin, Stephan J

    Seminars in cancer biology

    2017  Volume 43, Page(s) 1–4

    Language English
    Publishing date 2017-02-27
    Publishing country England
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 1033980-2
    ISSN 1096-3650 ; 1044-579X
    ISSN (online) 1096-3650
    ISSN 1044-579X
    DOI 10.1016/j.semcancer.2017.02.008
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2922: Show issues Location:
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  4. Article: Curing cancer? Further along the new pH-centric road and paradigm.

    Harguindey, S / Koltai, T / Reshkin, S J

    Oncoscience

    2018  Volume 5, Issue 5-6, Page(s) 132–133

    Language English
    Publishing date 2018-06-24
    Publishing country United States
    Document type Editorial
    ISSN 2331-4737
    ISSN 2331-4737
    DOI 10.18632/oncoscience.422
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  5. Article ; Online: Hydrogen Ion Dynamics of Cancer and a New Molecular, Biochemical and Metabolic Approach to the Etiopathogenesis and Treatment of Brain Malignancies.

    Harguindey, Salvador / Polo Orozco, Julian / Alfarouk, Khalid O / Devesa, Jesús

    International journal of molecular sciences

    2019  Volume 20, Issue 17

    Abstract: The treatment of cancer has been slowly but steadily progressing during the last fifty years. Some tumors with a high mortality in the past are curable nowadays. However, there is one striking exception: glioblastoma multiforme. No real breakthrough has ... ...

    Abstract The treatment of cancer has been slowly but steadily progressing during the last fifty years. Some tumors with a high mortality in the past are curable nowadays. However, there is one striking exception: glioblastoma multiforme. No real breakthrough has been hitherto achieved with this tumor with ominous prognosis and very short survival. Glioblastomas, being highly glycolytic malignancies are strongly pH-dependent and driven by the sodium hydrogen exchanger 1 (NHE1) and other proton (H
    MeSH term(s) Animals ; Brain Neoplasms/metabolism ; Glioblastoma/metabolism ; Glycolysis ; Humans ; Hydrogen-Ion Concentration ; Protons ; Sodium-Hydrogen Exchanger 1/metabolism
    Chemical Substances Protons ; Sodium-Hydrogen Exchanger 1
    Language English
    Publishing date 2019-09-01
    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/ijms20174278
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  6. Article ; Online: Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H

    Harguindey, Salvador / Alfarouk, Khalid / Polo Orozco, Julián / Fais, Stefano / Devesa, Jesús

    International journal of molecular sciences

    2020  Volume 21, Issue 20

    Abstract: A brand new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this unitarian perspective, ...

    Abstract A brand new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this unitarian perspective, based upon the hydrogen ion (H
    MeSH term(s) Animals ; Antineoplastic Agents ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/etiology ; Breast Neoplasms/metabolism ; Cation Transport Proteins/antagonists & inhibitors ; Cation Transport Proteins/metabolism ; Cell Respiration/drug effects ; Clinical Studies as Topic ; Combined Modality Therapy ; Disease Management ; Drug Resistance, Neoplasm ; Female ; Humans ; Hydrogen/metabolism ; Hydrogen-Ion Concentration ; Intracellular Space ; Molecular Targeted Therapy ; Proton Pump Inhibitors/pharmacology ; Proton Pump Inhibitors/therapeutic use ; Proton Pumps/metabolism ; Protons ; Sodium-Hydrogen Exchangers/metabolism ; Translational Research, Biomedical ; Treatment Outcome ; Tumor Microenvironment
    Chemical Substances Antineoplastic Agents ; Biomarkers, Tumor ; Cation Transport Proteins ; Proton Pump Inhibitors ; Proton Pumps ; Protons ; Sodium-Hydrogen Exchangers ; Hydrogen (7YNJ3PO35Z)
    Keywords covid19
    Language English
    Publishing date 2020-10-10
    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/ijms21207475
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  7. Article: Integrating fields of cancer research through pivotal mechanisms and synthetic final pathways: a unifying and creative overview.

    Harguindey, S

    Medical hypotheses

    2002  Volume 58, Issue 6, Page(s) 444–452

    Abstract: From cancer etiopathogenesis to selective apoptosis, from multiple drug resistance to oncogen activation and from the phenomena of spontaneous regression of cancer to certain aspects of cancer chemotherapy, all these subfields of biology and oncology ... ...

    Abstract From cancer etiopathogenesis to selective apoptosis, from multiple drug resistance to oncogen activation and from the phenomena of spontaneous regression of cancer to certain aspects of cancer chemotherapy, all these subfields of biology and oncology research share some deep-seated, both basic and clinical, essential features and characteristics. Certain apoptosis-inducing agents of unrelated families, ranging from ether lipids to Na(+)/H(+)-antiporter inhibitors to Delta(9)-tetrahydrocannabinol all have been reported to induce selective cancer-cell death. Behind a wide array of intermediary factors and mechanisms involved in their activity, they seem to share common pivotal and/or final pathways in inducing cell death mediated by a 'pathological' accumulation of intracellular hydrogen ions as a mechanism underlying core changes in intracellular signaling pathways. An H(+)-concentration initial perspective indicates that from pathogenesis to apoptosis and multiple drug resistance, as well as oncogen activity, tumor progression and even the phenomenon of spontaneous regression, all can be interpreted from their deep (H(+))-related basic and clinical essential characteristics. This speculative review discusses the potential integration of these previously disparate subfields of cancer research, through a model which also seems to lead toward improving understanding of the fundamental nature of malignant processes. It is concluded that this synthetic and universal approach allows advancement toward a combining of different areas of oncology into deeper and more comprehensive forms of rational understanding, with the hope of paving the way towards more selective, effective and all-encompassing forms of treatment.
    MeSH term(s) Apoptosis ; Humans ; Neoplasms/pathology ; Research
    Language English
    Publishing date 2002-08-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 193145-3
    ISSN 1532-2777 ; 0306-9877
    ISSN (online) 1532-2777
    ISSN 0306-9877
    DOI 10.1054/mehy.2001.1415
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1132: Show issues Location:
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  8. Article ; Online: A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics.

    Harguindey, Salvador / Alfarouk, Khalid / Orozco, Julián Polo / Hardonniere, Kevin / Stanciu, Daniel / Fais, Stefano / Devesa, Jesús

    International journal of molecular sciences

    2020  Volume 21, Issue 3

    Abstract: Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient at all. Indeed, the accumulated experience clearly indicates that new ... ...

    Abstract Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient at all. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contribution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, pathogenesis, and treatment of this multifactorial disease. For the first time, the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective-based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most of the fields and subfields of breast cancer etiopathogenesis and treatment. This single and integrated approach allows advancing towards a unidirectional, concerted and synergistic program of treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor and every individual patient in every phase of the disease.
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Drug Resistance, Neoplasm ; Female ; Humans ; Proton Pump Inhibitors/therapeutic use ; Proton Pumps/metabolism ; Protons ; Tumor Microenvironment
    Chemical Substances Antineoplastic Agents ; Proton Pump Inhibitors ; Proton Pumps ; Protons
    Language English
    Publishing date 2020-02-07
    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/ijms21031110
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  9. Article ; Online: Investigating Protein-Nanocrystal Interactions for Photodriven Activity.

    Harris, Alexander W / Harguindey, Albert / Patalano, Ryan E / Roy, Shambojit / Yehezkeli, Omer / Goodwin, Andrew P / Cha, Jennifer N

    ACS applied bio materials

    2020  Volume 3, Issue 2, Page(s) 1026–1035

    Abstract: We illustrate how intermolecular interactions facilitate ATP-free electron transfer between either native or engineered MoFe protein (MoFeP) from nitrogenase and a CdS nanorod (NR) by following the reduction of ... ...

    Abstract We illustrate how intermolecular interactions facilitate ATP-free electron transfer between either native or engineered MoFe protein (MoFeP) from nitrogenase and a CdS nanorod (NR) by following the reduction of H
    Language English
    Publishing date 2020-01-16
    Publishing country United States
    Document type Journal Article
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.9b01025
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  10. Article ; Online: Enzymes Photo-Cross-Linked to Live Cell Receptors Retain Activity and EGFR Inhibition after Both Internalization and Recycling.

    Roy, Shambojit / Brasino, Michael / Beirne, Jonathan M / Harguindey, Albert / Chapnick, Douglas A / Liu, Xuedong / Cha, Jennifer N / Goodwin, Andrew P

    Bioconjugate chemistry

    2019  Volume 31, Issue 1, Page(s) 104–112

    Abstract: In this work, we show that a prodrug enzyme covalently photoconjugated to live cell receptors survives endosomal proteolysis and retains its catalytic activity over multiple days. Here, a fusion protein was designed with both an antiepidermal growth ... ...

    Abstract In this work, we show that a prodrug enzyme covalently photoconjugated to live cell receptors survives endosomal proteolysis and retains its catalytic activity over multiple days. Here, a fusion protein was designed with both an antiepidermal growth factor receptor (EGFR) affibody and the prodrug enzyme cytosine deaminase, which can convert prodrug 5-fluorocytosine to the anticancer drug 5-fluorouracil. A benzophenone group was added at a site-specific mutation within the affibody, and the fusion protein was selectively photoconjugated to EGFR receptors expressed on membranes of MDA-MB-468 breast cancer cells. The fusion protein was next labeled with two dyes for tracking uptake: AlexaFluor 488 and pH-sensitive pHAb. Flow cytometry showed that fusion proteins photo-cross-linked to EGFR first underwent receptor-mediated endocytosis within 12 h, followed by recycling back to the cell membrane within 24 h. These findings were also confirmed by confocal microscopy. The unique cross-linking of the affibody-enzyme fusion proteins was utilized for two anticancer treatments. First, the covalent linking of the protein to the EGFR led to inhibition of ERK signaling over a two-day period, whereas conventional antibody therapy only led to 6 h of inhibition. Second, when the affibody-CodA fusion proteins were photo-cross-linked to EGFR overexpressed on MDA-MB-468 breast cancer cells, prodrug conversion was found even 48 h postincubation without any apparent decrease in cell killing, while without photo-cross-linking no cell killing was observed 8 h postincubation. These studies show that affinity-mediated covalent conjugation of the affibody-enzymes to cell receptors allows for prolonged expression on membranes and retained enzymatic activity without genetic engineering.
    MeSH term(s) Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Cell Line, Tumor ; Cytosine Deaminase/pharmacokinetics ; Cytosine Deaminase/pharmacology ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/metabolism ; Female ; Flucytosine/pharmacokinetics ; Flucytosine/pharmacology ; Fluorouracil/pharmacokinetics ; Fluorouracil/pharmacology ; Humans ; Prodrugs/pharmacokinetics ; Prodrugs/pharmacology ; Protein Kinase Inhibitors/pharmacokinetics ; Protein Kinase Inhibitors/pharmacology ; Recombinant Fusion Proteins/pharmacokinetics ; Recombinant Fusion Proteins/pharmacology
    Chemical Substances Antineoplastic Agents ; Prodrugs ; Protein Kinase Inhibitors ; Recombinant Fusion Proteins ; Flucytosine (D83282DT06) ; ErbB Receptors (EC 2.7.10.1) ; Cytosine Deaminase (EC 3.5.4.1) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2019-12-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1024041-x
    ISSN 1520-4812 ; 1043-1802
    ISSN (online) 1520-4812
    ISSN 1043-1802
    DOI 10.1021/acs.bioconjchem.9b00781
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