IMPACT OF OXIDATIVE STRESS ON INFLAMMATORY CHRONIC DISEASES AND SKIN CANCER. IDENTIFICATION OF NEW MARKERS OF FORECASTING AND THERAPEUTIC TARGETS (Q3145149): Difference between revisions
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Revision as of 10:32, 9 October 2021
Project Q3145149 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | IMPACT OF OXIDATIVE STRESS ON INFLAMMATORY CHRONIC DISEASES AND SKIN CANCER. IDENTIFICATION OF NEW MARKERS OF FORECASTING AND THERAPEUTIC TARGETS |
Project Q3145149 in Spain |
Statements
256,520.0 Euro
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320,650.0 Euro
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80.0 percent
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1 January 2018
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31 December 2020
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UNIVERSIDAD DE MURCIA
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37°59'32.57"N, 1°7'49.94"W
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30030
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LAS ENFERMEDADES INFLAMATORIAS CRONICAS SON DESORDENES MUY COMPLEJOS CUYAS CAUSAS SE DESCONOCEN POR EL MOMENTO. LA PSORIASIS ES UNA DE ESTAS ENFERMEDADES QUE AFECTA DEL 1-3% DE LA POBLACION HUMANA. POR OTRO LADO, EL MELANOMA ES UN CANCER DE PIEL POCO FRECUENTE, PERO DE ELEVADA MORTALIDAD. EL PRESENTE PROYECTO ES CONTINUACION DEL PROYECTO BIO2014-52655-R Y, POR TANTO, PRETENDE CONTINUAR CARACTERIZANDO EL IMPACTO DE LA INFLAMACION Y EL ESTRES OXIDATIVO EN LA PSORIASIS Y EN EL DESARROLLO DEL MELANOMA MEDIANTE UN ENFOQUE MULTIDISCIPLINAR QUE INCLUYE EL PEZ (DANIO RERIO) COMO MODELO ANIMAL IN VIVO EN COMBINACION CON MODELOS IN VITRO DE CELULAS HUMANAS Y MUESTRAS DE SUERO DE PACIENTES. EL PEZ CEBRA ES UN MODELO VERTEBRADO EXCEPCIONAL QUE PERMITE LA VISUALIZACION IN VIVO DE CUALQUIER PROCESO BIOLOGICO, EN ESTE CASO, LA INFLAMACION DE LA PIEL Y EL DESARROLLO DEL MELANOMA, Y SU MANIPULACION FARMACOLOGICA Y GENETICA A UN COSTE MENOR QUE LOS RATONES. LA COMBINACION DE ESTE MODELO, JUNTO CON EL ESCRUTINIO DE DROGAS EN LINEAS CELULARES, ES UNA APROXIMACION MUY PODEROSA QUE PERMITIRA ESTABLECER NUEVAS DIANAS TERAPEUTICAS PARA EL DESARROLLO DE TRATAMIENTOS MAS BARATOS Y CON MENOS EFECTOS SECUNDARIOS PARA LA PSORIASIS Y EL MELANOMA. EL ENFOQUE METABOLOMICO DE MUESTRAS DE SUERO DE PACIENTES CON PSORIASIS Y MELANOMA TAMBIEN ES INNOVADOR Y PUEDE CONDUCIR A LA IDENTIFICACION DE MARCADORES DE PRONOSTICO PARA EVALUAR Y PREDECIR LA PROGRESION DE LA ENFERMEDAD CON UNA EXTRACCION DE SANGRE. LOS OBJETIVOS CONCRETOS SON LOS SIGUIENTES: (1) ANALISIS METABOLOMICO DE MUESTRAS DE SUERO DE PACIENTES DE PSORIASIS Y MELANOMA PARA LA VALIDACION DE MARCADORES DE PRONOSTICO Y DIANAS TERAPEUTICAS; (2) IDENTIFICACION DE INHIBIDORES Y ACTIVADORES FARMACOLOGICOS DE DUOX1 MEDIANTE ESCRUTINIO DE LIBRERIAS DE PEQUEÑOS COMPUESTOS, (3) CARACTERIZACION DEL PAPEL DESEMPEÑADO POR EL ESTRES OXIDATIVO PROMOVIDO POR DUOX1 Y XDH, EL METABOLISMO DEL NAD+, Y LA VITAMINA B6, EN LA PSORIASIS; Y (4) CARACTERIZACION DEL PAPEL DESEMPEÑADO POR EL ESTRES OXIDATIVO PROMOVIDO POR DUOX1 Y XDH EN EL INICIO, PROGRESION Y AGRESIVIDAD DEL MELANOMA. LOS RESULTADOS ESPERABLES BENEFICIARAN A LOS PACIENTES CON AFECCIONES INFLAMATORIAS DE LA PIEL Y CANCER. (Spanish)
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CHRONIC INFLAMMATORY DISEASES ARE VERY COMPLEX DISORDERS WHOSE CAUSES ARE UNKNOWN AT PRESENT. PSORIASIS IS ONE OF THESE DISEASES THAT AFFECT 1-3% OF THE HUMAN POPULATION. ON THE OTHER HAND, MELANOMA IS A RARE SKIN CANCER BUT IT IS VERY AGGRESSIVE AND SHOWS A HIGH MORTALITY RATE. THE PRESENT PROJECT IS THE CONTINUATION OF A PREVIOUS ONE FROM THE SPANISH NATIONAL PLAN OF I+D (BIO2014-52655-R) AND, THEREFORE, ITS AIM IS MODELING THE IMPACT OF INFLAMMATION AND OXIDATIVE STRESS IN PSORIASIS AND MELANOMA USING A MULTIDISCIPLINARY APPROACH THAT INCLUDED THE ZEBRAFISH (DANIO RERIO) IN VIVO ANIMAL MODEL IN COMBINATION WITH IN VITRO HUMAN CELL CULTURES AND PATIENT BLOOD SAMPLES. THE ZEBRAFISH IS AN EXCEPTIONAL VERTEBRATE MODEL THAT ALLOWS THE IN VIVO VISUALIZATION OF ANY BIOLOGICAL PROCESS, IN THIS CASE SKIN INFLAMMATION AND MELANOMA DEVELOPMENT, AND ITS PHARMACOLOGICAL AND GENETIC MANIPULATION AT REDUCED COSTS COMPARED WITH THE MICE. THE COMBINATION OF THIS MODEL, TOGETHER WITH DRUG SCREENING IN HUMAN CELL LINES, IS A VERY POWERFUL APPROACH THAT WILL ALLOW US TO ESTABLISH NEW THERAPEUTIC TARGETS FOR THE DEVELOPMENT OF CHEAPER AND PERSONALIZED TREATMENTS WITH LESS SIDE EFFECTS FOR PSORIASIS AND MELANOMA. THE METABOLOMIC APPROACH OF SERUM SAMPLES IS ALSO INNOVATIVE AND MAY LEAD TO THE IDENTIFICATION OF DIAGNOSIS AND PROGNOSIS MARKERS TO EVALUATE AND PREDICT DISEASE PROGRESSION WITH A SIMPLE BLOOD EXTRACTION. THE SPECIFIC OBJECTIVES OF THIS PROJECT ARE: (1) METABOLOMIC ANALYSIS OF SERUM SAMPLES FROM PSORIASIS AND MELANOMA PATIENTS FOR THE VALIDATIONS OF IDENTIFIED PROGNOSIS MARKERS AND THERAPEUTIC TARGETS; (2) IDENTIFICATION OF PHARMACOLOGICAL INHIBITORS AND ACTIVATORS OF DUOX1 BY CHEMICAL SCREENING OF SMALL COMPOUND LIBRARIES; (3) CHARACTERIZATION OF THE ROLE PLAYED BY OXIDATIVE STRESS PROMOTED BY DUOX1 AND XDH, NAD+ METABOLISM, AND VITAMIN B6 IN PSORIASIS; AND (4) CHARACTERIZATION OF THE ROLE PLAYED BY OXIDATIVE STRESS PROMOTED BY DUOX1 AND XDH IN MELANOMA INITIATION, PROGRESSION AND AGGRESSIVENESS. THEREFORE, THE RESULTS WILL HOPEFULLY BENEFIT PATIENTS WITH SKIN INFLAMMATORY AND CANCER DISORDERS. (English)
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Murcia
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Identifiers
BIO2017-84702-R
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