INHIBITION OF PROTON TRANSPORT IN QUIMIOPREVENTION AND TREATMENT OF ESOPHAGUS ADENOCARCINOMA (Q3170893): Difference between revisions
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(Removed claim: summary (P836): The alteration of the intra/extracellular pH gradient resulting from increased expression of membrane H+ conveyors is a characteristic of neoplastic cells that has a huge impact on the energy metabolism of the cell and has been implicated in both the neoplastic transformation and the progression and metastasis of tumors. OBJECTIVE: analyse the role that different H+ conveyors play in the neoplastic progression of the Barret esophagus to esopha...) |
(Created claim: summary (P836): The alteration of the intra/extracellular pH gradient resulting from increased expression of membrane H+ conveyors is a characteristic of neoplastic cells that has a huge impact on the energy metabolism of the cell and has been implicated in both the neoplastic transformation and the progression and metastasis of tumors. OBJECTIVE: analyse the role that different H+ conveyors play in the neoplastic progression of the Barret esophagus to esophagu...) |
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The alteration of the intra/extracellular pH gradient resulting from increased expression of membrane H+ conveyors is a characteristic of neoplastic cells that has a huge impact on the energy metabolism of the cell and has been implicated in both the neoplastic transformation and the progression and metastasis of tumors. OBJECTIVE: analyse the role that different H+ conveyors play in the neoplastic progression of the Barret esophagus to esophagus adenocarcinoma (ACE). Secondly, to evaluate whether the pharmacological inhibition of those transporters involved is capable of inducing selective acidosis in neoplastic cells that ultimately determines their cell death and thus inhibits tumor progression and metastatic process. METHODOLOGY: Expression analysis by immunohistochemistry of different H+ conveyors (NHE1, H+VATPase, carbonic anhydrase IX and XII and monocarboxylate transporter (MC1 and MC4) in human samples of Barrett, high-grade dysplasia and ACE. IN VITRO STUDIES: it will be assessed whether the inhibition of these transporters using drugs for clinical use is capable of reversing the intra/extracellular pH gradient in two experimental conditions (with/without glucose overload) and its impact on phenomena of autophagia, apoptosis, proliferation, migration/invasion, formation of colonies in soft agar, in different ACE cell lines with different degrees of malignancy. The mechanisms involved will be studied. IN VIVO STUDIES: the ability of different treatments to inhibit tumor growth and metastases in an orthotopic model of ACE in immunodepressed mouse will be evaluated. (English) | |||||||||||||||
| Property / summary: The alteration of the intra/extracellular pH gradient resulting from increased expression of membrane H+ conveyors is a characteristic of neoplastic cells that has a huge impact on the energy metabolism of the cell and has been implicated in both the neoplastic transformation and the progression and metastasis of tumors. OBJECTIVE: analyse the role that different H+ conveyors play in the neoplastic progression of the Barret esophagus to esophagus adenocarcinoma (ACE). Secondly, to evaluate whether the pharmacological inhibition of those transporters involved is capable of inducing selective acidosis in neoplastic cells that ultimately determines their cell death and thus inhibits tumor progression and metastatic process. METHODOLOGY: Expression analysis by immunohistochemistry of different H+ conveyors (NHE1, H+VATPase, carbonic anhydrase IX and XII and monocarboxylate transporter (MC1 and MC4) in human samples of Barrett, high-grade dysplasia and ACE. IN VITRO STUDIES: it will be assessed whether the inhibition of these transporters using drugs for clinical use is capable of reversing the intra/extracellular pH gradient in two experimental conditions (with/without glucose overload) and its impact on phenomena of autophagia, apoptosis, proliferation, migration/invasion, formation of colonies in soft agar, in different ACE cell lines with different degrees of malignancy. The mechanisms involved will be studied. IN VIVO STUDIES: the ability of different treatments to inhibit tumor growth and metastases in an orthotopic model of ACE in immunodepressed mouse will be evaluated. (English) / rank | |||||||||||||||
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| Property / summary: The alteration of the intra/extracellular pH gradient resulting from increased expression of membrane H+ conveyors is a characteristic of neoplastic cells that has a huge impact on the energy metabolism of the cell and has been implicated in both the neoplastic transformation and the progression and metastasis of tumors. OBJECTIVE: analyse the role that different H+ conveyors play in the neoplastic progression of the Barret esophagus to esophagus adenocarcinoma (ACE). Secondly, to evaluate whether the pharmacological inhibition of those transporters involved is capable of inducing selective acidosis in neoplastic cells that ultimately determines their cell death and thus inhibits tumor progression and metastatic process. METHODOLOGY: Expression analysis by immunohistochemistry of different H+ conveyors (NHE1, H+VATPase, carbonic anhydrase IX and XII and monocarboxylate transporter (MC1 and MC4) in human samples of Barrett, high-grade dysplasia and ACE. IN VITRO STUDIES: it will be assessed whether the inhibition of these transporters using drugs for clinical use is capable of reversing the intra/extracellular pH gradient in two experimental conditions (with/without glucose overload) and its impact on phenomena of autophagia, apoptosis, proliferation, migration/invasion, formation of colonies in soft agar, in different ACE cell lines with different degrees of malignancy. The mechanisms involved will be studied. IN VIVO STUDIES: the ability of different treatments to inhibit tumor growth and metastases in an orthotopic model of ACE in immunodepressed mouse will be evaluated. (English) / qualifier | |||||||||||||||
point in time: 12 October 2021
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Revision as of 18:09, 12 October 2021
Project Q3170893 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | INHIBITION OF PROTON TRANSPORT IN QUIMIOPREVENTION AND TREATMENT OF ESOPHAGUS ADENOCARCINOMA |
Project Q3170893 in Spain |
Statements
29,750.0 Euro
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59,500.0 Euro
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50.0 percent
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1 January 2015
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31 March 2018
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INSTITUTO ARAGONES DE CIENCIAS DE LA SALUD
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41°39'7.67"N, 0°52'51.38"W
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50297
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La alteración del gradiente de pH intra/extracelular consecuencia del aumento de expresión de transportadores de H+ de membrana es una característica de las células neoplásicas que tiene un enorme impacto en el metabolismo energético de la célula y se ha visto implicado tanto en la transformación neoplásica como en la progresión y metástasis de los tumores. OBJETIVO: analizar el papel que los diferentes transportadores de H+ juegan en la progresión neoplásica del esófago de Barret a adenocarcinoma de esófago (ACE). En segundo término, evaluar si la inhibición farmacológica de aquellos transportadores implicados es capaz de inducir una acidosis selectiva en las células neoplásicas que en última instancia determine su muerte celular y por tanto inhiba la progresión tumoral y el proceso metastático. METODOLOGIA: Análisis de expresión mediante inmunohistoquímica de diferentes transportadores de H+ (NHE1, H+VATPasa, anhidrasas carbónicas IX y XII y transportador monocarboxilato (MC1 y MC4) en muestras humanas de Barrett, displasia de alto grado y ACE. ESTUDIOS IN VITRO: se evaluará si la inhibición de estos transportadores utilizando fármacos de uso clínico es capaz de revertir el gradiente de pH intra/extracelular en dos condiciones experimentales (con/sin sobrecarga de glucosa) y su impacto en fenómenos de autofagia, apoptosis, proliferación, migración/invasión, formación de colonias en agar blando, en distintas líneas celulares de ACE con diferente grado de malignidad. Se estudiarán los mecanismos implicados. ESTUDIOS IN VIVO: se evaluará la capacidad de los diferentes tratamientos para inhibir el crecimiento tumoral y metástasis en un modelo ortotópico de ACE en ratón inmunodeprimido. (Spanish)
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The alteration of the intra/extracellular pH gradient resulting from increased expression of membrane H+ conveyors is a characteristic of neoplastic cells that has a huge impact on the energy metabolism of the cell and has been implicated in both the neoplastic transformation and the progression and metastasis of tumors. OBJECTIVE: analyse the role that different H+ conveyors play in the neoplastic progression of the Barret esophagus to esophagus adenocarcinoma (ACE). Secondly, to evaluate whether the pharmacological inhibition of those transporters involved is capable of inducing selective acidosis in neoplastic cells that ultimately determines their cell death and thus inhibits tumor progression and metastatic process. METHODOLOGY: Expression analysis by immunohistochemistry of different H+ conveyors (NHE1, H+VATPase, carbonic anhydrase IX and XII and monocarboxylate transporter (MC1 and MC4) in human samples of Barrett, high-grade dysplasia and ACE. IN VITRO STUDIES: it will be assessed whether the inhibition of these transporters using drugs for clinical use is capable of reversing the intra/extracellular pH gradient in two experimental conditions (with/without glucose overload) and its impact on phenomena of autophagia, apoptosis, proliferation, migration/invasion, formation of colonies in soft agar, in different ACE cell lines with different degrees of malignancy. The mechanisms involved will be studied. IN VIVO STUDIES: the ability of different treatments to inhibit tumor growth and metastases in an orthotopic model of ACE in immunodepressed mouse will be evaluated. (English)
12 October 2021
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Zaragoza
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Identifiers
PI14_01931
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