Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research
Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Harguindey, Salvador [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2013 |
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| Schlagwörter: |
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| Anmerkung: |
© Harguindey et al.; licensee BioMed Central Ltd. 2013 |
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| Übergeordnetes Werk: |
Enthalten in: Journal of translational medicine - London : BioMed Central, 2003, 11(2013), 1 vom: 06. Nov. |
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| Übergeordnetes Werk: |
volume:11 ; year:2013 ; number:1 ; day:06 ; month:11 |
| Links: |
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| DOI / URN: |
10.1186/1479-5876-11-282 |
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| Katalog-ID: |
SPR028949382 |
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| 245 | 1 | 0 | |a Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research |
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| 520 | |a Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑$ pH_{i} $/↓$ pH_{e} $, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both $ pH_{i} $ and $ pH_{e} $ in tumors is the $ Na^{+} $/$ H^{+} $ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. | ||
| 650 | 4 | |a pH and cancer |7 (dpeaa)DE-He213 | |
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| 650 | 4 | |a Proton transporters |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Proton transport inhibitors |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Cariporide in cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a NHE1 and cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Cancer treatment |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Multiple drug resistance |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a New therapeutic paradigm in cancer |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Arranz, Jose Luis |4 aut | |
| 700 | 1 | |a Polo Orozco, Julian David |4 aut | |
| 700 | 1 | |a Rauch, Cyril |4 aut | |
| 700 | 1 | |a Fais, Stefano |4 aut | |
| 700 | 1 | |a Cardone, Rosa Angela |4 aut | |
| 700 | 1 | |a Reshkin, Stephan J |4 aut | |
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10.1186/1479-5876-11-282 doi (DE-627)SPR028949382 (SPR)1479-5876-11-282-e DE-627 ger DE-627 rakwb eng Harguindey, Salvador verfasserin aut Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Harguindey et al.; licensee BioMed Central Ltd. 2013 Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑$ pH_{i} $/↓$ pH_{e} $, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both $ pH_{i} $ and $ pH_{e} $ in tumors is the $ Na^{+} $/$ H^{+} $ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. pH and cancer (dpeaa)DE-He213 Cancer etiopathogenesis (dpeaa)DE-He213 Proton transporters (dpeaa)DE-He213 Proton transport inhibitors (dpeaa)DE-He213 Cariporide in cancer (dpeaa)DE-He213 NHE1 and cancer (dpeaa)DE-He213 Cancer treatment (dpeaa)DE-He213 Multiple drug resistance (dpeaa)DE-He213 New therapeutic paradigm in cancer (dpeaa)DE-He213 Arranz, Jose Luis aut Polo Orozco, Julian David aut Rauch, Cyril aut Fais, Stefano aut Cardone, Rosa Angela aut Reshkin, Stephan J aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 11(2013), 1 vom: 06. Nov. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:11 year:2013 number:1 day:06 month:11 https://dx.doi.org/10.1186/1479-5876-11-282 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2013 1 06 11 |
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10.1186/1479-5876-11-282 doi (DE-627)SPR028949382 (SPR)1479-5876-11-282-e DE-627 ger DE-627 rakwb eng Harguindey, Salvador verfasserin aut Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Harguindey et al.; licensee BioMed Central Ltd. 2013 Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑$ pH_{i} $/↓$ pH_{e} $, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both $ pH_{i} $ and $ pH_{e} $ in tumors is the $ Na^{+} $/$ H^{+} $ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. pH and cancer (dpeaa)DE-He213 Cancer etiopathogenesis (dpeaa)DE-He213 Proton transporters (dpeaa)DE-He213 Proton transport inhibitors (dpeaa)DE-He213 Cariporide in cancer (dpeaa)DE-He213 NHE1 and cancer (dpeaa)DE-He213 Cancer treatment (dpeaa)DE-He213 Multiple drug resistance (dpeaa)DE-He213 New therapeutic paradigm in cancer (dpeaa)DE-He213 Arranz, Jose Luis aut Polo Orozco, Julian David aut Rauch, Cyril aut Fais, Stefano aut Cardone, Rosa Angela aut Reshkin, Stephan J aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 11(2013), 1 vom: 06. Nov. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:11 year:2013 number:1 day:06 month:11 https://dx.doi.org/10.1186/1479-5876-11-282 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2013 1 06 11 |
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10.1186/1479-5876-11-282 doi (DE-627)SPR028949382 (SPR)1479-5876-11-282-e DE-627 ger DE-627 rakwb eng Harguindey, Salvador verfasserin aut Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Harguindey et al.; licensee BioMed Central Ltd. 2013 Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑$ pH_{i} $/↓$ pH_{e} $, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both $ pH_{i} $ and $ pH_{e} $ in tumors is the $ Na^{+} $/$ H^{+} $ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. pH and cancer (dpeaa)DE-He213 Cancer etiopathogenesis (dpeaa)DE-He213 Proton transporters (dpeaa)DE-He213 Proton transport inhibitors (dpeaa)DE-He213 Cariporide in cancer (dpeaa)DE-He213 NHE1 and cancer (dpeaa)DE-He213 Cancer treatment (dpeaa)DE-He213 Multiple drug resistance (dpeaa)DE-He213 New therapeutic paradigm in cancer (dpeaa)DE-He213 Arranz, Jose Luis aut Polo Orozco, Julian David aut Rauch, Cyril aut Fais, Stefano aut Cardone, Rosa Angela aut Reshkin, Stephan J aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 11(2013), 1 vom: 06. Nov. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:11 year:2013 number:1 day:06 month:11 https://dx.doi.org/10.1186/1479-5876-11-282 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2013 1 06 11 |
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10.1186/1479-5876-11-282 doi (DE-627)SPR028949382 (SPR)1479-5876-11-282-e DE-627 ger DE-627 rakwb eng Harguindey, Salvador verfasserin aut Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Harguindey et al.; licensee BioMed Central Ltd. 2013 Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑$ pH_{i} $/↓$ pH_{e} $, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both $ pH_{i} $ and $ pH_{e} $ in tumors is the $ Na^{+} $/$ H^{+} $ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. pH and cancer (dpeaa)DE-He213 Cancer etiopathogenesis (dpeaa)DE-He213 Proton transporters (dpeaa)DE-He213 Proton transport inhibitors (dpeaa)DE-He213 Cariporide in cancer (dpeaa)DE-He213 NHE1 and cancer (dpeaa)DE-He213 Cancer treatment (dpeaa)DE-He213 Multiple drug resistance (dpeaa)DE-He213 New therapeutic paradigm in cancer (dpeaa)DE-He213 Arranz, Jose Luis aut Polo Orozco, Julian David aut Rauch, Cyril aut Fais, Stefano aut Cardone, Rosa Angela aut Reshkin, Stephan J aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 11(2013), 1 vom: 06. Nov. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:11 year:2013 number:1 day:06 month:11 https://dx.doi.org/10.1186/1479-5876-11-282 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2013 1 06 11 |
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10.1186/1479-5876-11-282 doi (DE-627)SPR028949382 (SPR)1479-5876-11-282-e DE-627 ger DE-627 rakwb eng Harguindey, Salvador verfasserin aut Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Harguindey et al.; licensee BioMed Central Ltd. 2013 Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑$ pH_{i} $/↓$ pH_{e} $, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both $ pH_{i} $ and $ pH_{e} $ in tumors is the $ Na^{+} $/$ H^{+} $ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. pH and cancer (dpeaa)DE-He213 Cancer etiopathogenesis (dpeaa)DE-He213 Proton transporters (dpeaa)DE-He213 Proton transport inhibitors (dpeaa)DE-He213 Cariporide in cancer (dpeaa)DE-He213 NHE1 and cancer (dpeaa)DE-He213 Cancer treatment (dpeaa)DE-He213 Multiple drug resistance (dpeaa)DE-He213 New therapeutic paradigm in cancer (dpeaa)DE-He213 Arranz, Jose Luis aut Polo Orozco, Julian David aut Rauch, Cyril aut Fais, Stefano aut Cardone, Rosa Angela aut Reshkin, Stephan J aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 11(2013), 1 vom: 06. Nov. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:11 year:2013 number:1 day:06 month:11 https://dx.doi.org/10.1186/1479-5876-11-282 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2013 1 06 11 |
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Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research |
| abstract |
Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑$ pH_{i} $/↓$ pH_{e} $, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both $ pH_{i} $ and $ pH_{e} $ in tumors is the $ Na^{+} $/$ H^{+} $ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. © Harguindey et al.; licensee BioMed Central Ltd. 2013 |
| abstractGer |
Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑$ pH_{i} $/↓$ pH_{e} $, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both $ pH_{i} $ and $ pH_{e} $ in tumors is the $ Na^{+} $/$ H^{+} $ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. © Harguindey et al.; licensee BioMed Central Ltd. 2013 |
| abstract_unstemmed |
Abstract In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [$ H^{+} $]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑$ pH_{i} $/↓$ pH_{e} $, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both $ pH_{i} $ and $ pH_{e} $ in tumors is the $ Na^{+} $/$ H^{+} $ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. © Harguindey et al.; licensee BioMed Central Ltd. 2013 |
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Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research |
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https://dx.doi.org/10.1186/1479-5876-11-282 |
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Arranz, Jose Luis Polo Orozco, Julian David Rauch, Cyril Fais, Stefano Cardone, Rosa Angela Reshkin, Stephan J |
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