149 results on '"Brizuela L"'
Search Results
2. Impact du blocage du métabolisme de la sphingosine 1-phosphate sur les manifestations spondyloarthritiques dans le modèle d’enthésopathie des souris TgA86±
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Briolay, A., primary, Brizuela, L., additional, Magne, D., additional, and Bougault, C., additional
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- 2023
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3. Brazil nut treatment attenuates vascular calcification in mouse vascular smooth muscle cells
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da Cruz, B.O., primary, Cardozo, L.F., additional, Mebarek, S., additional, Brizuela, L., additional, and Stockler-Pinto, M.B., additional
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- 2023
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4. O.58 - Implication de la voie métabolique sphingosine kinase / sphingosine 1-phosphate dans la spondyloarthrite
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Bougault, C., El Jamal, A., Briolay, A., Mebarek, S., Boutet, M.A, Le Goff, B., Blanchard, F., Magne, D., and Brizuela, L.
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- 2016
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5. POS0404 VOLUNTARY WHEEL RUNNING MODEL IN MICE TO MECHANICALLY STIMULATE THE ENTHESIS OF THE ACHILLES TENDON
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Briolay, A., primary, Delplace, S., additional, Duboeuf, F., additional, Peyruchaud, O., additional, Magne, D., additional, Brizuela, L., additional, and Bougault, C., additional
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- 2021
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6. SCFβ-TRCP and phosphorylation dependent ubiquitination of IκBα catalyzed by Ubc3 and Ubc4
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Strack, P, Caligiuri, M, Pelletier, M, Boisclair, M, Theodoras, A, Beer-Romero, P, Glass, S, Parsons, T, Copeland, R A, Auger, K R, Benfield, P, Brizuela, L, and Rolfe, M
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- 2000
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7. Involvement of phospholipase D in mineralization process in cultured osteoblasts
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Abdallah, D., Skafi, N., Hamade, E., Reibel, S., Vitale, N., El Jamal, A., Bougault, C., Laroche, B., Vico, L., Badran, B., Hussein, N., Magne, D., Buchet, R., Brizuela, L, Mebarek, S., ICBMS, UMR5246, Métabolisme, Enzymes et Mécanismes Moléculaires (MEM²), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
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[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2019
8. Multi-scale mechanical characterization of prostate cancer cell lines: Relevant biological markers to evaluate the cell metastatic potential
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Zouaoui, J., primary, Trunfio-Sfarghiu, A.M., additional, Brizuela, L., additional, Piednoir, A., additional, Maniti, O., additional, Munteanu, B., additional, Mebarek, S., additional, Girard-Egrot, A., additional, Landoulsi, A., additional, and Granjon, T., additional
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- 2017
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9. Osteoblast-derived sphingosine 1-phosphate to induce proliferation and confer resistance to therapeutics to bone metastasis-derived prostate cancer cells
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Brizuela, L., Martin, C., Jeannot, P., Ader, I., Gstalder, C., Andrieu, Guillaume, Bocquet, Michael, Lafosse, J.M., Gomez-Brouchet, A.M., Malavaud, B., Sabaddini, R., Cuvillier, O., Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service d'orthopédie et traumatologie, CHU Toulouse [Toulouse], Service d'anatomopathologie, Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]
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Sphingosine kinase ,Osteoblasts ,Radiotherapy ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,organic chemicals ,Differentiation ,Sphingomab ,lipids (amino acids, peptides, and proteins) ,Docetaxel ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] - Abstract
International audience; Sphingosine 1-phosphate (S1P) plays important roles in cell proliferation, differentiation or survival mainly through its surface G-protein-coupled receptors S1P1-5. Bone represents the major site of metastasis for prostate cancer (CaP) cells, which rely on bone-derived factors to support their proliferation and resistance to therapeutics. In the present work we have found that conditioned medium (CM) from the MC3T3 osteoblastic cell line or primary murine and human osteoblast-like cells, as well as co-culture with MC3T3 stimulate proliferation of CaP lines in S1P-dependent manner. In addition, osteoblastic-derived S1P induces resistance of CaP cells to therapeutics including chemotherapy and radiotherapy. When S1P release from osteoblastic cells is decreased (inhibition of SphK1, knock-down of SphK1 or the S1P transporter, Spns2 by siRNA) or secreted S1P neutralized with anti-S1P antibody, the proliferative and survival effects of osteoblasts on CaP cells are abolished. Because of the paracrine nature of the signaling, we studied the role of the S1P receptors expressed on CaP cells in the communication with S1P secreted by osteoblasts. Strategies aimed at down-regulating S1P1, S1P2 or S1P3 (siRNA, antagonists), established the exclusive role of the S1P/S1P1 signaling between osteoblasts and CaP cells. Bone metastases from CaP are associated with osteoblastic differentiation resulting in abnormal bone formation. We show that the autocrine S1P/S1P3 signaling is central during differentiation to mature osteoblasts by regulating Runx2 level, a key transcription factor involved in osteoblastic maturation. Importantly, differentiated osteoblasts exhibited enhanced secretion of S1P and further stimulated CaP cell proliferation in a S1P-dependent manner. By establishing the dual role of osteoblast-borne S1P on both osteoblastic differentiation and CaP cell proliferation and survival, we uncover the importance of S1P in the bone metastatic microenvironment, which may open a novel area of study for the treatment of CaP bone metastasis by targeting S1P.
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- 2014
10. Polyphenols in prostate cancer
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Brizuela, L., Cuvillier, O., Métabolisme, Enzymes et Mécanismes Moléculaires (MEM²), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Depierre, Frédérique
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[CHIM.ORGA]Chemical Sciences/Organic chemistry ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,[CHIM.ORGA] Chemical Sciences/Organic chemistry ,[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2014
11. Implication de la voie métabolique sphingosine kinase / sphingosine 1-phosphate dans la spondyloarthrite
- Author
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Bougault, C., primary, El Jamal, A., additional, Briolay, A., additional, Mebarek, S., additional, Boutet, M.A, additional, Le Goff, B., additional, Blanchard, F., additional, Magne, D., additional, and Brizuela, L., additional
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- 2016
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12. Characterization of cell cultures in contact with different orthopedic implants biomaterials
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Ouenzerfi, G, primary, Hannoun, A, additional, Hassler, M, additional, Brizuela, L, additional, Youjil, S, additional, Bougault, C, additional, and Trunfio-Sfarghiu, A-M, additional
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- 2016
- Full Text
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13. Essential role for SphK1/S1P signaling to regulate hypoxia-inducible factor 2α expression and activity in cancer
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Bouquerel, P, primary, Gstalder, C, additional, Müller, D, additional, Laurent, J, additional, Brizuela, L, additional, Sabbadini, R A, additional, Malavaud, B, additional, Pyronnet, S, additional, Martineau, Y, additional, Ader, I, additional, and Cuvillier, O, additional
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- 2016
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14. Caracterización del secado de pimiento para pimentón en un tendalero solar activo tipo túnel
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Iriarte, Adolfo Antonio, Bistoni, S., Luque, V., García, V., Rodriguez, C., and Brizuela, L.
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Pre-drying treatments ,Active solar dryer ,Ingeniería ,Rack dryer ,Pepper for paprika ,INGENIERÍAS Y TECNOLOGÍAS ,Pimiento para pimentón ,purl.org/becyt/ford/2.7 [https] ,Ingeniería del Petróleo, Energía y Combustibles ,purl.org/becyt/ford/2 [https] ,Secadero tendalero ,Tratamientos presecado ,Ingeniería del Medio Ambiente ,Ciencias Agrarias ,Secadero solar activo - Abstract
Las aromáticas son los productos que principalmente se producen en el Dpto. Belén, Provincia de Catamarca, destacándose especialmente el pimiento para pimentón, anís, ajo y comino. También hay producciones de frutas que son destinadas al deshidratado. Estos cultivos son realizados por pequeños productores. La renta derivada de estos productos deshidratados no es la óptima debido a que la conservación es inadecuada. En el presente trabajo se propone un secadero solar mixto construido sobre un tendalero cubierto con un plástico y con convección forzada. Está formado por dos partes: un colector solar y a continuación la cámara de secado. La circulación del aire se realiza mediante dos ventiladores. Se muestra la caracterización del secado del pimiento para pimentón durante los meses de invierno, para muestras sin y con tratamiento (blanqueado y metabisulfito de sodio); se analizan las variaciones de temperaturas y humedades, la velocidad de secado en función del contenido de humedad y del tiempo. Si bien el secado fue adecuado y el producto de buena calidad, la baja radiación y temperatura ambiente, aumentaron el tiempo de secado. Los tratamientos mejoraron el color del producto seco y disminuyeron el tiempo de secado en un 25 % y 12,5 % respectivamente., Spice and condiment are mainly produced by small farmers in Belén, Province of Catamarca, including particularly the pepper for paprika, anise, garlic and cumin. There are also productions of fruits to be dehydrated. The income from these dehydrated products is not optimal because the preservation is inadequate. In this paper a mixed force convection solar tunnel drier is proposed. It consists of a transparent plastic covered flat plate collector and a drying chamber connected in series. The air circulates by means of two fans. The characterization of drying pepper for paprika is shown in samples with and without treatment, during winter. The variations of temperatures and humidity’s and the drying rate as a function of moisture content and time are analyzed. Even though the final product was of good quality, low radiation and ambient temperature increased drying time. Blanching and sulphiting treatment improved the dry pepper´s color and reduced drying time in a 25% and 12.5 % respectively., Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES)
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- 2012
15. Análisis de un secadero solar tendalero con torre central en convección natural
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Iriarte, Adolfo Antonio, Bistoni Silvia, Watkins, Marcelo, Luque, Víctor, Sanchez, H., and Brizuela, L.
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EFICIENCIA DE SECADO ,SECADO SOLAR ,purl.org/becyt/ford/2 [https] ,HUMEDAD ,CONVECCIÓN NATURAL ,Otras Ingeniería del Medio Ambiente ,Ingeniería del Medio Ambiente ,INGENIERÍAS Y TECNOLOGÍAS ,purl.org/becyt/ford/2.7 [https] - Abstract
El trabajo muestra los resultados de los ensayos realizados en un secadero solar tendalero mixto con chimenea solar, en convección natural, y la simulación del funcionamiento de la chimenea solar. El sistema está constituido por un colector solar, una cámara de secado y chimenea solar con ganancia directa. Los ensayos se realizaron sin producto y con pimiento para pimentón. Para la simulación numérica se utilizó el software SIMUSOL. Los resultados muestran que esta configuración de secadero incrementa el flujo de aire de 0,5 a 0,7 kg s-1, respecto al modelo anterior. Se analiza el proceso de secado de pimiento para pimentón, verificándose que para el producto cortado la duración del proceso fue de 58 horas. El ajuste del modelo se realizó con respecto a las temperaturas de salida de la chimenea, obteniéndose un error del 2 %. This paper shows the results of the tests in a solar dryer type “tendalero” with solar chimney in natural convection, and the simulation of the solar chimney. The system consists of a solar collector, a drying chamber and a direct solar gain chimney. The system was tested without product and during the drying of pepper for paprika. The software SIMUSOL was used for the numerical simulation. The results shows that this configuration increases the air flow from 0,5 kg s-1 to 0,7 kg s-1 respect to the previous system. The drying process is analyzed and it is observed that the cut pepper dried in 58 hours. The simulation was fitted with the outlet chimney temperature with an error of 2 %. Fil: Iriarte, Adolfo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Investigaciones en Energía no Convencional; Argentina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; Argentina Fil: Bistoni Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Investigaciones en Energía no Convencional; Argentina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; Argentina Fil: Watkins, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Investigaciones en Energía no Convencional; Argentina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; Argentina Fil: Luque, Víctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Investigaciones en Energía no Convencional; Argentina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; Argentina Fil: Sanchez, H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Investigaciones en Energía no Convencional; Argentina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina Fil: Brizuela, L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Investigaciones en Energía no Convencional; Argentina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina
- Published
- 2011
16. Consumo de tabaco y alcohol en pacientes con cáncer esofágico en el Hospital Vargas de Caracas durante el período 2004 - 2009
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Veitía, Guillermo, Otero, J, Ruiz, N, Graterol, A, and Brizuela, L
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Introducción: El Cáncer de Esófago ocupa el noveno lugar entre las neoplasias malignas a nivel mundial y está asociado al hábito tabáquico y alcohólico. En el Hospital Vargas de Caracas ocupa el lugar número 11 entre las primeras 15 (2.5%) causas de egresos por cáncer al año. Objetivo: Determinar el consumo de tabaco y alcohol en pacientes ingresados por Cáncer de esófago en el Hospital Vargas de Caracas durante el período 2004 - 2009. Métodos: Se realizó estudio retrospectivo y descriptivo, luego de la revisión de historias de 24 pacientes ingresados por cáncer de esófago con diagnóstico de cáncer de esófago. Se utilizaron medidas de tendencia central para interpretación de resultados. Resultados: 21(87.5%) de los pacientes fueron masculinos y 3(12.5%), femeninos. La edad promedio fue de 61 años. El 83.3%(20) refirieron hábito tabáquico de más de 24 paquetes/año y hábito alcohólico mayor a 120 gr/día. Histológicamente 87.5% (21) correspondió a Carcinoma Epidermoide localizados en 1/3 medio de esófago en 58.3% (14). Adenocarcinoma fue diagnosticado en 3 pacientes (12.5%) Conclusión y Recomendación: El hallazgo histopatológico más frecuente fue el carcinoma epidermoide en el 87.5% de las historias revisadas. El 83% de los pacientes tenían una asociación importante al hábito tabáquico y alcohólico, por lo que recomendamos implementación de Programa conjunto de promoción y prevención en salud entre la Sociedad Venezolana de Gastroenterología y la Sociedad Anticancerosa de Venezuela, de lucha contra los factores de riesgo de esta enfermedad. Background: Esophageal cancer ranks ninth among malignancies worldwide and is associated with smoking and alcoholism. In Hospital Vargas de Caracas is ranked number 11 among the top 15 (2.5%) causes of cancer discharges per year. Objective: To determine the consumption of tobacco and alcohol in patients admitted due to esophageal cancer in Hospital Vargas de Caracas during 2004-2009. Methods: A retrospective descriptive study was performed after reviewing the charts of 24 patients admitted with esophageal cancer. We used central tendency measures for interpretation of results. Results: 21 (87.5%) patients were male and three (12.5%) female. The average age was 61 years-old. 83.3% (20) reported smoking over 24 pack/years and become an alcoholic greater than 120 g/day. Histologically, 87.5% (21) corresponded to epidermoid carcinoma located in 1/3 of the esophagus in 58.3% (14). Adenocarcinoma was diagnosed in 3 patients (12.5%). Conclusion and Recommendation: The most common histopathological fi nding was squamous cell carcinoma in 87.5% of the charts reviewed. 83% of patients had a signifi cant association with smoking and alcoholism, that’s why, we recommend the implementation of a joint program in health promotion and disease prevention among the Venezuelan Society of Gastroenterology and Cancer Society of Venezuela, to fight against the risk factors of this disease.
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- 2010
17. AB0149 Role of Sphingosine 1-Phosphate Metabolic Pathway in Spondyloarthritis Physiopathology
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Bougault, C., primary and Brizuela, L., additional
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- 2015
- Full Text
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18. Consumo de tabaco y alcohol en pacientes con cáncer esofágico y su relación con el tipo histológico: Hospital Vargas de Caracas período 2004 - 2009
- Author
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Veitía, G, Otero, J, Ruiz, N, Graterol, A, and Brizuela, L
- Abstract
Introducción: El Cáncer de Esófago ocupa el noveno lugar entre las neoplasias malignas a nivel mundial y está asociado al hábito tabáquico y alcohólico.En el Hospital Vargas de Caracas ocupa el lugar número 11 entre las primeras 15 (2.5%) causas de egresos por cáncer al año. Objetivo: Determinar el consumo de tabaco y alcohol en pacientes ingresados por Cáncer de esófago en el "Hospital Vargas de Caracas" durante el período 2004 - 2009. Métodos: Se realizó estudio retrospectivo y descriptivo, luego de la revisión de historias de 24 pacientes ingresados con diagnóstico de cáncerde esófago. Se utilizaron medidas de tendencia central para interpretación de resultados. Resultados: 21 (87.5%) de los pacientes fueron masculinos y 3 (12.5%) femeninos. La edad promedio fue de 61 años. El 83.3% (20) refirieron hábito tabáquico de más de 24 paquetes/año y hábito alcohólico mayor a 120 gr/día. Histológicamente 87.5% (21) correspondió a Carcinoma Epidermoide localizado en 1/3 medio de esófago en 58.3% (14). Adenocarcinoma fue diagnosticado en 3 pacientes (12.5%). Conclusión y Recomendación: El hallazgo histopatológico más frecuente fue el carcinoma epidermoide en el 87.5% de las historias revisadas. El 83% de los pacientes tenía una asociación importante al hábito tabáquico y alcohólico, por lo que recomendamos implementación de Programa conjunto de promocióny prevención en salud entre la Sociedad Venezolana de Gastroenterologíay la Sociedad Anticancerosa de Venezuela, de lucha contra los factores de riesgo de esta enfermedad Introduction: Esophageal Cancer ranks ninth among malignant neoplasias worldwide and is associated to smoking and alcohol consumption. In „HospitalVargas de Caracas‰ its ranked number 11 among the top 15 (2.5%) cases of cancer annually discharged. Objective: Determine the tobacco and alcohol consumption in patients admitted for esophageal cancer in "Hospital Vargas de Caracas" during the period 2004 to 2009. Methods: We performeda retrospective, descriptive study, after reviewing the charts of 24 patients admitted for esophageal cancer diagnosis. We used central tendency measures for interpretation of results. Results: 21 (87.5%) patients were male and 3 (12.5%) female. The average age was 61 years. 83.3% (20) reported smoking over 24 packs-years and alcohol consumption greater than 120 g / day. Histologically, 87.5% (21) corresponded to squamous cell carcinoma located in 1 / 3 of the esophagus in 58.3% (14). 3 patients (12.5%) were diagnosed with Adenocarcinoma. Conclusion and Recommendation: Squamous cell carcinoma in 87.5% was the most common histopathological finding among the reviewed charts. 83% of patients had a significant association to smoking and alcohol, thus, we recommend the implementation of a joint prevention and health promotionprogram about the management of risk factors of this disease between the Venezuelan Society of Gastroenterology and VenezuelaÊs Anti-Cancer Society, the control of risk factors of this disease
- Published
- 2010
19. Lesiones gástricas premalignas en familiares en primer grado de pacientes con cáncer gástrico evaluados en la consulta de gastroenterología de dos hospitales universitarios de Caracas
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Veitía, G, Ruiz, N, Graterol, A, Brizuela, L, Otero, J, Angarita, L, Rodríguez, M, Sandoval, C, Khassale, M, Gledhill, T, Pernalete, B, Rodríguez, L, La Cruz, M, and Villarreal, Lara
- Abstract
Introducción: Las alteraciones morfológicas de la mucosa gástrica que predisponen al desarrollo de cáncer gástrico son atrofia, metaplasia y displasia. Diversos factores etiológicos han sido estudiados, destacándose el parentescoen primer grado con una probabilidad de presentar cáncer gástrico 2veces más que la población general. Objetivo: Diagnosticar lesiones gástricas premalignas en familiares de pacientes con cáncer gástrico, evaluados en las consultas de Gastroenterología del Hospital Vargas de Caracas y Hospital Militar „Dr. Carlos Arvelo‰. Pacientes y Métodos: Se realizó un estudio descriptivo, prospectivo, longitudinal, desde Octubre 2008 a Mayo 2009. Se incluyeron 75 individuos con edades comprendidas entre 18 y 80 años, familiares en primer grado de pacientes con cáncer gástrico, a los cuales se les practicó endoscopia digestiva superior con toma de biopsia. Resultados: En 51 pacientes femeninos (68%) y 24 (32%) masculinos, se encontraron los siguientes hallazgos endoscópicos: endoscopia normal 52%, gastropatía crónica 33%, úlcera gástrica 5,33%, pólipos gástricos 3,33% y úlcera duodenal 1,33%. El estudio histológico determinó que la atrofia estuvo presente en 25 pacientes (33,3%), metaplasia intestinal en 17 pacientes (22,67%), displasia en 4 pacientes (5,33%), la mitad de ellas de alto grado y 1 (1,33%) indefinido para displasia. Conclusión y recomendación: En el grupo estudiado se encontró un 42,6% de lesiones gástricas premalignas, de las cuales el 5,33% correspondió a displasia, ninguno de estos con lesiones endoscópicas de malignidad; lo que nos hace recomendar de rutina en todos los servicios de gastroenterología del país un programa de pesquisa en familiares en primer grado de pacientes de cáncer gástrico Introduction: Morphological alterations of the gastric mucosa that predispose to the development of gastric cancer are atrophy, metaplasia and dysplasia. Various etiologic factors have been studied, especially in first degree relatives,with a probability of gastric cancer double than that of the general population. Objective: To diagnose premalignant gastric lesions in relatives of patients with gastric cancer evaluated in the Gastroenterology consultation of „Hospital Vargas de Caracas‰ and „Hospital Militar Dr. Carlos Arvelo‰. Patients and Methods: A descriptive, prospective, longitudinal study was made, from October 2008 to May 2009. We included 75 individuals aged 18 to 80 years in first degree relatives of patients with gastric cancer, who underwent upper gastrointestinal endoscopy with biopsy guided. Results: We found 51 (68%) female and 24 (32%) male, with these endoscopic findings: normal in 52% of the patients, with chronic gastropathy 37, 33%, gastric ulcer in 5,3%, gastric polyps in 3,33% and duodenal ulcer in 1,33%. The histological study found that atrophy was present in 25 (33.3%) patients, intestinal metaplasia in 17 (22, 67%) and dysplasia in 4(5, 33%) and 1(1,33%) indefinite to dysplasia. Conclusion and recommendation: In this group of patients it was found a 42.6% of premalignant gastric lesions, of which 5.33% corresponded to dysplasia. Neither one had endoscopic malignant lesions. We recommend as a routine in all Gastroenterology Divisions in the country a program of screening in first degree families of patients of gastric cancer
- Published
- 2010
20. Secadero tendalero con chimenea solar
- Author
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Iriarte, Adolfo Antonio, Bistoni, S., Luque, V., Lara, M., and Brizuela, L.
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Otras Ingenierías y Tecnologías ,purl.org/becyt/ford/2 [https] ,secadero ,Simulación secadero ,secadero solar pasivo ,INGENIERÍAS Y TECNOLOGÍAS ,Ciencias Agrarias ,Simulación ,chimenea solar ,purl.org/becyt/ford/2.11 [https] - Abstract
El secado solar de frutas y hortalizas está siendo utilizado en distintos lugares del mundo y particularmente en Argentina. Si bien existen numerosos diseños de distinta complejidad, se presentan algunos problemas que requieren atención y estudio, especialmente en lo que se refiere a la tecnología de secaderos en convección natural. En el presente trabajo se detallan los aspectos constructivos de un tendalero adaptado para funcionar como secadero solar pasivo con una chimenea solar incorporada. El sistema básicamente consiste de un colector solar, cámara de secado y chimenea. Para el modelo de simulación se utilizó el SIMUSOL. Se analiza el sistema térmicamente y los resultados del ajuste de la simulación. Se muestran los resultados de los ensayos realizados: secado de pimiento para pimentón y membrillos. La simulación permitió determinar el flujo másico de aire dentro del secadero y resultó ser una herramienta útil a la hora del diseño. Los productos obtenidos son de buena calidad y el tiempo de secado se considera razonable para este tipo de secadero., Solar drying of fruits and vegetables is being used worldwide and particularly in Argentina. Although there are numerous designs of different complexity, they present some problems that require attention and study, especially when natural convection driers are used. This paper describes building aspects of a “tendalero” adapted for working as a passive solar drier with an incorporated solar chimney. The system essentially consists of a solar collector, a drying unit and a chimney. The simulation model used was SIMUSOL. A thermal analysis of the system is done and the results of adjustment simulation are considered. The results of the assays carried out, pepper for paprika and quince, are also shown. The simulation allowed to determine the mass flow rate of air inside the drier, and proved to be an important tool for design. The quality of dried products is good and the drying time is considered reasonable for this type of driers., Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES)
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- 2010
21. Prevalencia de enfermedad por reflujo gastroesofágico en la población adulta Venezolana
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Veitia, G, Ruiz, N, Armas, V, Graterol, A, Del Valle, D, Mago, E, Brizuela, L, Marelli, A, Angarita, L, Romero, G, Aponte, R, Dolfo, W, Casado, V, Álvarez, M, Escobar, E, and Rojas, G
- Abstract
La enfermedad por reflujo gastroesofágico (ERGE) es una enfermedad crónica recurrente, que constituye uno de los trastornos gastrointestinales que afecta con mayor frecuencia a población mundial. Objetivo: Determinar la prevalencia de enfermedad por reflujo gastroesofágico en la población adulta venezolana. Pacientes y Métodos: Se realiza un estudio descriptivo, de corte transversal, multicéntrico durante los meses de abril y mayo de 2008. Se entrevistaron a individuos en edades comprendidas entre 15 - 65 años de diferentes estados del país (Aragua, Anzoátegui, Barinas, Carabobo, Delta Amacuro, Distrito Capital, Mérida, Miranda, Sucre, Zulia) escogidos a través del azar simple, realizándose un muestreo por conglomerados, de donde, en cada estado se seleccionó un Municipio y de éste, lugares como iglesias, centro comerciales, cines y paradas de autobuses. Se tomó en consideración la población de cada municipio según el Censo Nacional 2001. Resultados: Un total de 1318 individuos fueron encuestados en los estados incluidos, 814 mujeres (61,76%) y 504 Hombres (38,24%). En cuanto a la distribución por categoría de edad, el grupo de 25-35 años constituyó el de mayor predominio. Se obtuvo una Prevalencia Nacional de 11,54%, donde los síntomas cardinales pirosis y regurgitación ácida representaron 16,62% y 12,75% respectivamente. Conclusión: La prevalencia nacional de enfermedad por reflujo gastroesofágico en la población venezolana es del 11,54%. The gastroesophageal reflux disease (GERD) is a chronic recurrent illness that represents one of the most common gastrointestinal disorders that affects worldwide population. Aim: To determine the prevalence of gastroesophageal reflux disease in the Venezuelan adult population. Patients and Methods: A Descriptive, cross section, multicentric study was made. A survey was done to people in ages between 15 - 65 years of different states of the country (Aragua, Anzoátegui, Barinas, Carabobo, Delta Amacuro, Distrito Capital, Mérida, Miranda, Sucre, Zulia) chosen randomly. Cluster sampling was performed, where in each State was selected a municipality and, of which one places like churches, malls, cinemas and bus stops. To calculate de amount of people The National Census 2001 was taken in account in each municipality. Results: A total of 1318 individuals were surveyed in the mentioned States including, 814 women (61.76%) and 504 men (38.24%). The predominant distribution by age was the group of 25-35 years old. A National Prevalence of 11.54% was obtained, where the cardinal symptoms were heartburn and acid regurgitation represented 16.62% and 12.75% respectively. Conclusion: The national prevalence of gastroesophageal reflux disease in the Venezuelan adult population is 11.54%.
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- 2009
22. Consumo de alcohol en los pacientes que acudieron por consulta externa del Hospital Vargas de Caracas durante el período Marzo - Mayo 2008
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Marelli, A, Brizuela, L, Del Valle, D, Mago, E, Armas, V, Ruiz, N, Graterol, A, Rodríguez, M, Angarita, L, Sandoval, C, Vásquez, F, and Veitía, G
- Abstract
El consumo de alcohol en nuestro país constituye un problema de salud pública relacionado con el desarrollo de eventos que afectan la esfera biopsicosocial del individuo. Objetivo: Caracterizar los patrones de consumo de alcohol en personas de 14 años y más que consultaron a los servicios de gastroenterología, Medicina Interna, Endocrinología y Cirugía del Hospital Vargas de Caracas. Pacientes y Métodos: El levantamiento de los datos se realizó durante el trimestre marzo-mayo 2008, en horario matutino y vespertino, de lunes a viernes. Se entrevistó una muestra intencional, heterogénea de 450 pacientes. Se aplicó una encuesta de preguntas abiertas en la cual se incluyeron los datos de identificación (nombre, apellido, sexo, edad, teléfono), consumo de alcohol (edad de inicio, número de tragos, frecuencia) y las preguntas del Test de Cage. Para medir el consumo de alcohol se utilizó una clasificación que permitió conocer el riesgo de Alcoholismo. Resultados: Se realizaron un total de 450 encuestas, en 149 pacientes masculinos y 301 femeninos. Del total de la muestra se identificaron 186 pacientes que consumen alcohol y 264 que no consumen, con un 41,55% y 58,45% respectivamente. El riesgo alto de consumo de alcohol estuvo presente en 16 pacientes y el consumo perjudicial en 50 pacientes, con un 8,60% y 26,88% respectivamente. Cabe destacar, que el riesgo alto de consumo fue mas elevado en el sexo femenino 10,34%, mientras que el consumo perjudicial en el sexo masculino con 43,87%. Conclusiones: El consumo de alcohol en los pacientes que acudieron a las Consultas Externas del Hospital Vargas de Caracas es alto, en un 41,55 % de los encuestados, con un riesgo de consumo de alcohol de 35,48 %. Alcohol intake in our country is a public health problem related with the development of many events that affect the bio - psychosocial area of the patients. Objective: Characterize the patterns of alcohol intake in people from 14 years old on; that attended the gastroenterology, Internal Medicine, Endocrinology and Surgery Divisions at the Hospital Vargas in Caracas. Patients and Methods: the data was collected during March-May 2008, in the morning and afternoon, from Monday through Friday. Interviews were done in an intentional, heterogeneous sample of 450 patients. An opened questions survey was applied, in which the identification data (name, last name, sex, age, telephone), alcohol intake were included (age of beginning, number of drinks, frequency), as well as the Cage Test questions. In order to measure alcohol intake, we used a classification that allowed knowing the risk of Alcoholism. Results: A total of 450 surveys were made, in 149 male patients and 301 females. Of the total of the sample, 186 patients consume alcohol and 264 do not, 41.55% and 58.45% respectively. 16 patients, presented with high risk of alcohol intake and 50 patients with severe intake, 8.60% and 26.88% respectively. It is important to stress out that females presented a high risk of intake (10.34%), whereas the detrimental intake in males was 43.87%. Conclusions: Alcohol intake in patients who attended "Hospital Vargas de Caracas" outpatient clinic is high, with a 41.55% of the patients, and an alcohol intake risk of 35.48 %.
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- 2009
23. Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets
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Green, R. D., Ren, B., Nguyen, L., Bhattacharjee, A., Koch, C. M., Dunham, I., Nix, D. A., Trinklein, N. D., Farnham, P. J., Bieda, M., Anton, E., Hawkins, D., Gordon, D. B., Zhang, X., Song, J. S., Ching, K., Johnson, D. S., Brizuela, L., Curry, B., Flicek, P., Jiang, N., Gingeras, T. R., Kapranov, P., Ghosh, J., Xu, X., Holster, H., Brown, M., Ye, Z., Li, W., Carroll, J. S., McCuine, S. A., and Scacheri, P. C.
- Abstract
The most widely used method for detecting genome-wide protein–DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first objective analysis of tiling array platforms, amplification procedures, and signal detection algorithms in a simulated ChIP-chip experiment. Mixtures of human genomic DNA and “spike-ins” comprised of nearly 100 human sequences at various concentrations were hybridized to four tiling array platforms by eight independent groups. Blind to the number of spike-ins, their locations, and the range of concentrations, each group made predictions of the spike-in locations. We found that microarray platform choice is not the primary determinant of overall performance. In fact, variation in performance between labs, protocols, and algorithms within the same array platform was greater than the variation in performance between array platforms. However, each array platform had unique performance characteristics that varied with tiling resolution and the number of replicates, which have implications for cost versus detection power. Long oligonucleotide arrays were slightly more sensitive at detecting very low enrichment. On all platforms, simple sequence repeats and genome redundancy tended to result in false positives. LM-PCR and WGA, the most popular sample amplification techniques, reproduced relative enrichment levels with high fidelity. Performance among signal detection algorithms was heavily dependent on array platform. The spike-in DNA samples and the data presented here provide a stable benchmark against which future ChIP platforms, protocol improvements, and analysis methods can be evaluated.
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- 2008
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24. Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection
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Albert, F. W., Hodges, E., Jensen, J. D., Besnier, F., Xuan, Z., Rooks, M., Bhattacharjee, A., Brizuela, L., Good, J. M., Green, R. E., Burbano, H. A., Plyusnina, I. Z., Trut, L., Andersson, Leif, Schoeneberg, T., Carlborg, Örjan, Hannon, G. J., Pääbo, Svante, Albert, F. W., Hodges, E., Jensen, J. D., Besnier, F., Xuan, Z., Rooks, M., Bhattacharjee, A., Brizuela, L., Good, J. M., Green, R. E., Burbano, H. A., Plyusnina, I. Z., Trut, L., Andersson, Leif, Schoeneberg, T., Carlborg, Örjan, Hannon, G. J., and Pääbo, Svante
- Abstract
The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.
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- 2011
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25. Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection
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Albert, F W, primary, Hodges, E, additional, Jensen, J D, additional, Besnier, F, additional, Xuan, Z, additional, Rooks, M, additional, Bhattacharjee, A, additional, Brizuela, L, additional, Good, J M, additional, Green, R E, additional, Burbano, H A, additional, Plyusnina, I Z, additional, Trut, L, additional, Andersson, L, additional, Schöneberg, T, additional, Carlborg, Ö, additional, Hannon, G J, additional, and Pääbo, S, additional
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- 2011
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26. Brizuela
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Brizuela, L, primary
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- 2009
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27. Screens Using RNAi and cDNA Expression as Surrogates for Genetics in Mammalian Tissue Culture Cells
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PEARLBERG, J., primary, DEGOT, S., additional, ENDEGE, W., additional, PARK, J., additional, DAVIES, J., additional, GELFAND, E., additional, SAWYER, J., additional, CONERY, A., additional, DOENCH, J., additional, LI, W., additional, GONZALEZ, L., additional, BOYCE, F.M., additional, BRIZUELA, L., additional, LABAER, J., additional, GRUENEBERG, D., additional, and HARLOW, E., additional
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- 2005
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28. P19INK4D/CDK6 COMPLEX
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Brotherton, D.H., primary, Dhanaraj, V., additional, Wick, S., additional, Brizuela, L., additional, Domaille, P.J., additional, Volyanik, E., additional, Xu, X., additional, Parisini, E., additional, Smith, B.O., additional, Archer, S.J., additional, Serrano, M., additional, Brenner, S.L., additional, Blundell, T.L., additional, and Laue, E.D., additional
- Published
- 1999
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29. Yeast FKBP-13 is a membrane-associated FK506-binding protein encoded by the nonessential gene FKB2.
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Nielsen, J B, primary, Foor, F, additional, Siekierka, J J, additional, Hsu, M J, additional, Ramadan, N, additional, Morin, N, additional, Shafiee, A, additional, Dahl, A M, additional, Brizuela, L, additional, and Chrebet, G, additional
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- 1992
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30. Antifungal properties of the immunosuppressant FK-506: identification of an FK-506-responsive yeast gene distinct from FKB1.
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Brizuela, L, primary, Chrebet, G, additional, Bostian, K A, additional, and Parent, S A, additional
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- 1991
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31. A role for the p34cdc2 kinase and phosphatases in the regulation of phosphorylation and disassembly of lamin B2 during the cell cycle.
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Lüscher, B., primary, Brizuela, L., additional, Beach, D., additional, and Eisenman, R. N., additional
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- 1991
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32. FKB1 encodes a nonessential FK 506-binding protein in Saccharomyces cerevisiae and contains regions suggesting homology to the cyclophilins.
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Wiederrecht, G., primary, Brizuela, L., additional, Elliston, K., additional, Sigal, N. H., additional, and Siekierka, J. J., additional
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- 1991
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33. SCFβ-TRCP and phosphorylation dependent ubiquitination of IκBα catalyzed by Ubc3 and Ubc4.
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Strack, P, Caligiuri, M, Pelletier, M, Boisclair, M, Theodoras, A, Beer-Romero, P, Glass, S, Parsons, T, Copeland, R A, Auger, K R, Benfield, P, Brizuela, L, and Rolfe, M
- Subjects
PHOSPHORYLATION ,UBIQUITIN ,LIGASES - Abstract
NFκB is an important transcriptional regulator of multiple pro-inflammatory genes. In non-stimulated cells NFκB is anchored in the cytoplasm via the inhibitory protein IκBα. Following exposure to diverse pro-inflammatory signals (e.g. TNFα, IL1, LPS) various signal transduction cascades are initiated converging on the IκB kinase (IKK). IKK phosphorylates IκBα on serines 32 and 36 signaling the inhibitory protein for ubiquitin-mediated degradation. The SCF
β-TRCP complex is the ubiquitin ligase responsible for mediating phosphorylation dependent ubiquitination of IκBα. Here we reconstitute phosphorylation dependent ubiquitination of IκBα using recombinant components. Our results suggest that the cullin specificity of the SCF complex may reflect its ability to associate with Rbx1. We demonstrate specific ubiquitination of IκBα by Ubc3 and Ubc4 in a phosphorylation and SCFβ-TRCP dependent manner and that both are capable of associating with the SCFβ-TRCP complex isolated from human cells. Finally, we show that Ubc4 is in excess to Ubc3 in THP.1 cells and 19 times more efficient in catalyzing the reaction, suggesting that Ubc4 is the preferentially used Ubc in this reaction in vivo. Our results also suggest that ubiquitin is transferred directly from the Ubc to phospho-IκBα in a SCFβ-TRCP dependent reaction. Oncogene (2000) 19, 3529–3536 [ABSTRACT FROM AUTHOR]- Published
- 2000
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34. Phosphorylation of large tumour antigen by cdc2 stimulates SV40 DNA replication.
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McVey, D. and Brizuela, L.
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- *
DNA - Abstract
Presents research demonstrating that simian virus 40 large tumor antigen is regulated by phosphorylation and provides a model for cdc2 function in the control of DNA replication. Thr (threonine residue) 124 phosphorylation; Origin binding; DNA synthesis.
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- 1989
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35. FLEXGene repository: from sequenced genomes to gene repositories for high-throughput functional biology and proteomics
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Brizuela, L., Braun, P., and LaBaer, J.
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- 2001
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36. p13suc1 acts in the fission yeast cell division cycle as a component of the p34cdc2 protein kinase.
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Brizuela, L., Draetta, G., and Beach, D.
- Abstract
cdc2+ encodes a protein kinase that is required during both G1 and G2 phases of the cell division cycle in fission yeast. suc1+ is an essential gene that was originally identified as a plasmid‐borne sequence that could rescue certain temperature‐sensitive cdc2 mutants. To investigate the role of the suc1+ gene product in the cell cycle p13suc1 has been expressed in Escherichia coli and purified. An immunoaffinity purified anti‐p13suc1 polyclonal serum has been prepared and used to identify p13suc1 in fission yeast. The abundance of this protein did not alter either during the cell cycle or during entry into stationary phase. p13suc1 was found in yeast lysates in a complex with the cdc2+ gene product. Approximately 5% of cellular p34cdc2 was associated with p13suc1, and this fraction of p34cdc2 was active as a protein kinase. The stability of the complex was disrupted in yeast strains carrying temperature‐sensitive alleles of cdc2 that are suppressible by overexpression of suc1+. The level of association between p13suc1 and p34cdc2 was not affected by cell cycle arrest in adverse nutritional conditions. p13suc1 is not a substrate of the p34cdc2 protein kinase. We propose instead that it acts as a regulatory component of p34cdc2 that facilitates interaction with other proteins.
- Published
- 1987
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37. Cyclin is a component of the sea urchin egg M‐phase specific histone H1 kinase.
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Meijer, L., Arion, D., Golsteyn, R., Pines, J., Brizuela, L., Hunt, T., and Beach, D.
- Abstract
A so‐called ‘growth‐associated’ or ‘M‐phase specific’ histone H1 kinase (H1K) has been described in a wide variety of eukaryotic cell types; p34cdc2 has previously been shown to be a catalytic subunit of this protein kinase. In fertilized sea urchin eggs the activity of H1K oscillates during the cell division cycle and there is a striking temporal correlation between H1K activation and the accumulation of a phosphorylated form of cyclin. H1K activity declines in parallel with proteolytic cyclin destruction of the end of the first cell cycle. By virtue of the high affinity of the fission yeast p13suc1 for the p34cdc2 protein, H1K strongly binds to p13‐Sepharose beads. Cyclin, p34cdc2 and H1K co‐purify on this affinity reagent as well as through several conventional chromatographic procedures. Anticyclin antibodies immunoprecipitate the M‐phase specific H1K in crude extracts or in purified fractions. Sea urchin eggs appear to contain much less cyclin than p34cdc2, suggesting that p34cdc2 may interact with other proteins. These results demonstrate that cyclin and p34cdc2 are major components of the M‐phase specific H1K.
- Published
- 1989
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38. Activation of human CDC2 protein as a histone H1 kinase is associated with complex formation with the p62 subunit.
- Author
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Brizuela, L, Draetta, G, and Beach, D
- Abstract
p34 kinase, the product of the CDC2 gene, is a cell-cycle regulated protein kinase that is most active during mitosis. In HeLa cells, p34 kinase has previously been shown to exist in both a low- and a high-molecular-mass form, the latter of which is only found in cells in the G2/M phase of the cell cycle and contains a 62-kDa subunit. Here we show that although each form of the kinase phosphorylates casein in vitro, only the high-molecular-mass form uses histone H1 as substrate. The high-molecular-mass form of p34 kinase from nocodazole-treated HeLa cells was purified 6700-fold. The apparent molecular mass of the mitotic CDC2-encoded protein kinase complex was 220 kDa. The purified enzyme phosphorylated not only its endogenous 62-kDa subunit but also phosphorylated histone H1 with a Km of 3 microM and used ATP 40 times more efficiently than GTP (Km 54 microM and 2 mM, respectively). The enzyme activity was unaffected by cAMP, calcium/calmodulin, or by the heat-stable inhibitor of cAMP-dependent protein kinase. These characteristics are typical of growth-associated histone H1 kinase from different organisms. These results suggest that CDC2 protein may be activated as an M-phase-specific protein kinase in part by its association with the p62 subunit.
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- 1989
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39. Identification of selective inhibitors of cyclin dependent kinase 4
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Carini, D. J., III, R. F. Kaltenbach, Liu, J., Benfield, P. A., Boylan, J., Boisclair, M., Brizuela, L., Burton, C. R., Cox, S., and Grafstrom, R.
- Published
- 2001
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40. Erratum: Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d) (Nature (1998) 395 (244-250))
- Author
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Brotherton, D. H., Dhanaraj, V., Wick, S., Brizuela, L., Domaille, P. J., Volyanik, E., Xu, X., Parisini, E., Smith, B. O., Archer, S. J., Serrano, M., Brenner, S. L., Blundell, T. L., and Ernest Laue
41. Identification of p34 and p13, human homologs of the cell cycle regulators of fission yeast encoded by cdc2+ and suc1+
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Draetta, G., primary, Brizuela, L., additional, Potashkin, J., additional, and Beach, D., additional
- Published
- 1987
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42. Regulation of the Vertebrate Cell Cycle by the cdc2 Protein Kinase
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Draetta, G., primary, Brizuela, L., additional, Moran, B., additional, and Beach, D., additional
- Published
- 1988
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43. Voluntary exercise in mice triggers an anti-osteogenic and pro-tenogenic response in the ankle joint without affecting long bones.
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Briolay A, Duboeuf F, Delplace S, Brizuela L, Peyruchaud O, Magne D, and Bougault C
- Abstract
Biomechanical stimulation is proposed to occupy a central place in joint homeostasis, but the precise contribution of exercise remains elusive. We aimed to characterize in vivo the impact of mechanical stimulation on the cell-controlled regulation of ossification within the ankles of healthy mice undergoing mild physical activity. DBA/1 male mice were subjected to voluntary running exercise for two weeks, and compared to mice housed in standard conditions ( n = 20 per group). Free access to activity wheels resulted in a running exercise of 5.5 ± 0.8 km/day at 14.5 ± 0.5 m/min. Serum levels of alkaline phosphatase, IL-6, IL-8/Kc, IL-17a, and TNF-α were measured. No change in systemic inflammation was detected. The bone architecture of the femur and the calcaneus was unchanged, as revealed by μCT and histology of the enthesis of the Achilles tendon. mRNAs were extracted from femurs, tibias, and ankle joints before RT-qPCR analysis. The expression of the mechanosensitive genes Sclerostin ( Sost ) and Periostin ( Postn ) was not impacted by the exercise in long bones. Oppositely, Sost and Postn levels were modulated by exercise in joints, and osteogenic markers ( Col10a1 , Runx2 , Osx , and Dmp1 ) were downregulated in the exercise group. In addition, the tenogenic markers Scx , Mkx , and Tnmd were upregulated by exercise. Thus, voluntary exercise affected the phenotype of joint cells without impacting long bones. As gene expression of Bmp2 , Bmp4 , and Id1 was also reduced in these cells, an off-regulation of BMP signaling could be partly responsible for their mechanosensitive response. Running exercise seemed to preserve the tendon from its progressive ossification, as seen in numerous enthesopathies. This study paves the way to future experiments for investigating the effects of mechanical stimulation in various mouse models., Competing Interests: All the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
- Published
- 2024
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44. Positive impact of pyrocarbon and mechanical loading on cartilage-like tissue synthesis in a scaffold-free process.
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De Gaudemaris I, Hannoun A, Gauthier R, Attik N, Brizuela L, Mebarek S, Hassler M, Bougault C, and Trunfio-Sfarghiu AM
- Abstract
Aiming to build a tissue analogue engineered cartilage from differentiated chondrocytes, we investigated the potential of a pyrocarbon (PyC)-based and scaffold-free process, under mechanical stimulation. PyC biomaterial has shown promise in arthroplasty and implant strategies, and mechanical stimulation is recognized as an improvement in regeneration strategies. The objective was to maintain the cell phenotype to produce constructs with cartilage-like matrix composition and mechanical properties. Primary murine chondrocytes were deposited in drop form between two biomaterial surfaces expanded to 500 μm and a uniaxial cyclic compression was applied thanks to a handmade tribo-bioreactor (0.5 Hz, 100 μm of amplitude, 17 days). Histology and immunohistochemistry analysis showed that PyC biomaterial promoted expression of cartilage-like matrix components (glycosaminoglycans, type II collagen, aggrecan). Importantly, constructs obtained in dynamic conditions were denser and showed a cohesive and compact shape. The most promising condition was the combined use of PyC and dynamic stimulation, resulting in constructs of low elasticity and high viscosity, thus with an increased damping factor. We verified that no calcium deposits were detectable and that type X collagen was not expressed, suggesting that the cells had not undergone hypertrophic maturation. While most studies focus on the comparison of different biomaterials or on the effect of different mechanical stimuli separately, we demonstrated the value of combining the two approaches to get as close as possible to the biological and mechanical qualities of natural hyaline articular cartilage., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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45. Brazil nut-enriched diet modulates bone mineral density and body composition in an experimental model of chronic kidney disease.
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Da Cruz BO, Almeida PP, Silva-Costa N, Brito ML, Degani VAN, da Silva EM, Magliano DC, Mebarek S, Brizuela L, Cardozo LFMF, and Stockler-Pinto MB
- Subjects
- Animals, Male, Rats, Absorptiometry, Photon, Calcium blood, Nuts, Bone Density, Rats, Wistar, Body Composition, Renal Insufficiency, Chronic diet therapy, Renal Insufficiency, Chronic physiopathology, Disease Models, Animal, Diet methods, Bertholletia, Femur physiopathology
- Abstract
Objective: This study investigates the effects of a Brazil nut-enriched diet on body composition and bone parameters in CKD animal model., Methods: Male Wistar rats were assigned to the following groups: Sham (n=8), Nx (n=6), nephrectomized rats, and NxBN (n=6), nephrectomized rats and an enricheddiet with 5% Brazil nut. Body composition parameters were obtained by dual-energy X- ray absorptiometry (DXA). Bioclin kits determined plasmatic calcium. The femurs werecollected to determine absolute mass and length, bone mineral density, and biomechanical tests., Results: The NxBN group exhibited a higher total body bone mineral density (BMD) value than the Nx group (0.177±0.004g/cm
2 vs 0,169±0.003g/cm2 ; p=0.0397). No significant differences were observed regarding absolute mass, length, BMD, and biomechanical parameters in the femurs of the groups. Moreover, no significant differences were found in plasmatic calcium levels among the groups., Conclusions: Brazil-nut enriched diet modulated BMD in CKD experimental model, and further studies are demanded to understand the pathways involved in this finding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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46. Small Bowel Obstruction Following Dislodgement of an Intragastric Balloon: A Case Report.
- Author
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Brizuela L, Samarah H, and Cardona N
- Abstract
Obesity remains a significant health burden worldwide, requiring diverse and effective treatment strategies. The intragastric balloon (IGB), developed in the 1980s, offers a non-surgical option for weight management. Despite a decrease in usage, the IGB procedure continues to be an option for patients both domestically and abroad. In this article, we present the case involving a 30-year-old female who presented with severe abdominal complications 18 months after IGB placement in the Dominican Republic, well beyond the recommended six-month period for removal. This case highlights the critical risks associated with delayed IGB removal, including balloon rupture, migration, and symptoms indicative of gastric outlet obstruction. The literature supports increased complication rates with prolonged balloon retention, including risks such as gastric perforation, ulceration, and small bowel obstruction, emphasizing the importance of adhering to removal schedules. Furthermore, the case stresses the need for psychosocial evaluations before weight loss procedures and the necessity of alternative methods like laparoscopic removal when endoscopic extraction is unsuccessful. As obesity management evolves with new treatments like glucagon-like peptide-1 (GLP-1) analogs, ongoing research to understand their interaction with IGBs is crucial. This case underlines the importance of rigorous follow-up care, educating patients about procedural timelines, and conducting comprehensive evaluations to ensure the safety and effectiveness of IGB therapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Brizuela et al.)
- Published
- 2024
- Full Text
- View/download PDF
47. Do Media Extracellular Vesicles and Extracellular Vesicles Bound to the Extracellular Matrix Represent Distinct Types of Vesicles?
- Author
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Mebarek S, Buchet R, Pikula S, Strzelecka-Kiliszek A, Brizuela L, Corti G, Collacchi F, Anghieri G, Magrini A, Ciancaglini P, Millan JL, Davies O, and Bottini M
- Subjects
- Humans, Extracellular Matrix, Chondrocytes, Hypertrophy, Extracellular Vesicles, Calcinosis
- Abstract
Mineralization-competent cells, including hypertrophic chondrocytes, mature osteoblasts, and osteogenic-differentiated smooth muscle cells secrete media extracellular vesicles (media vesicles) and extracellular vesicles bound to the extracellular matrix (matrix vesicles). Media vesicles are purified directly from the extracellular medium. On the other hand, matrix vesicles are purified after discarding the extracellular medium and subjecting the cells embedded in the extracellular matrix or bone or cartilage tissues to an enzymatic treatment. Several pieces of experimental evidence indicated that matrix vesicles and media vesicles isolated from the same types of mineralizing cells have distinct lipid and protein composition as well as functions. These findings support the view that matrix vesicles and media vesicles released by mineralizing cells have different functions in mineralized tissues due to their location, which is anchored to the extracellular matrix versus free-floating.
- Published
- 2023
- Full Text
- View/download PDF
48. Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.
- Author
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Mebarek S, Skafi N, and Brizuela L
- Abstract
Prostate cancer (PC) is the second most common cancer in men worldwide. More than 65% of men diagnosed with PC are above 65. Patients with localized PC show high long-term survival, however with the disease progression into a metastatic form, it becomes incurable, even after strong radio- and/or chemotherapy. Sphingosine 1-phosphate (S1P) is a bioactive lipid that participates in all the steps of oncogenesis including tumor cell proliferation, survival, migration, invasion, and metastatic spread. The S1P-producing enzymes sphingosine kinases 1 and 2 (SK1 and SK2), and the S1P degrading enzyme S1P lyase (SPL), have been shown to be highly implicated in the onset, development, and therapy resistance of PC during the last 20 years. In this review, the most important studies demonstrating the role of S1P and S1P metabolic partners in PC are discussed. The different in vitro, ex vivo, and in vivo models of PC that were used to demonstrate the implication of S1P metabolism are especially highlighted. Furthermore, the most efficient molecules targeting S1P metabolism that are under preclinical and clinical development for curing PC are summarized. Finally, the possibility of targeting S1P metabolism alone or combined with other therapies in the foreseeable future as an alternative option for PC patients is discussed. Research Strategy: PubMed from INSB was used for article research. First, key words "prostate & sphingosine" were used and 144 articles were found. We also realized other combinations of key words as "prostate cancer bone metastasis" and "prostate cancer treatment". We used the most recent reviews to illustrate prostate cancer topic and sphingolipid metabolism overview topic.
- Published
- 2023
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49. Nano/micro implant debris affect osteogenesis by chondrocytes: Comparison between ceramic and UHMWPE from hip walking simulator.
- Author
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Ben Braham M, Trunfio-Sfarghiu AM, Brizuela L, Mebarek S, Essefi I, Geringer J, Berthier Y, and Hamza S
- Subjects
- Ceramics, Chondrocytes, Humans, Materials Testing, Osteogenesis, Polyethylenes, Prosthesis Failure, Walking, Hip Prosthesis adverse effects
- Abstract
A new generation of ceramic on ceramic (BIOLOX ®delta) bearings has emerged more than 10 years ago proving a high resistance to wear and good clinical results. However, biological reactions to wear debris, particularly the nanoparticles, need to be evaluated. The first originality of this study is to start from real wear particles obtained by the hip walking simulator (CERsim). These particles were compared with particles obtained by usual methods to assess the biocompatibility of materials: press machine (CERpress). Two ranges of ceramic particles were thus observed: ceramic particles with micron (intergranular fractures) and nano sizes (intragranular fractures), and characterized compared to ultra-high molecular weight polyethylene (UHMWPE). The second originality of this work is to assess the cellular reaction using the primary joint chondrocyte cultures simulating the osteogenesis process and not the cell lines, which are used to simulate the biological reaction of osteolysis. The first results showed a significant difference in cell viability between the cells in contact with particles from the walking simulator and those obtained with the press machine. On the other hand, it was found that the way of extraction of the particles from the lubricant could significantly affect the biological reaction. More interestingly, nano-sized ceramic particles showed a significant impact on the secretion of functional inflammatory mediators, agreeing with recent results in vivo. These novel methods of characterizing the osteogenic impact of UHMWPE and ceramic wear debris can complement the conventional expertise method focusing previously on the osteolysis aspect., (© 2021 Wiley Periodicals LLC.)
- Published
- 2022
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50. Phospholipase D inhibitors screening: Probing and evaluation of ancient and novel molecules.
- Author
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Arhab Y, Bessaa K, Abla H, Aydin M, Rahier R, Comte A, Brizuela L, Mebarek S, Perret F, Cherrier MV, Abousalham A, and Noiriel A
- Subjects
- Alcohols pharmacology, High-Throughput Screening Assays, Humans, Hydrolysis, Phospholipase D metabolism, Salts pharmacology, Scattering, Small Angle, Vanadates pharmacology, Vigna enzymology, X-Ray Diffraction, Drug Evaluation, Preclinical, Enzyme Inhibitors analysis, Enzyme Inhibitors pharmacology, Phospholipase D antagonists & inhibitors
- Abstract
Phospholipase D (PLD) is a ubiquitous enzyme that cleaves the distal phosphoester bond of phospholipids generating phosphatidic acid (PA). In plants, PA is involved in numerous cell responses triggered by stress. Similarly, in mammals, PA is also a second messenger involved in tumorigenesis. PLD is nowadays considered as a therapeutic target and blocking its activity with specific inhibitors constitutes a promising strategy to treat cancers. Starting from already described PLD inhibitors, this study aims to investigate the effect of their structural modifications on the enzyme's activity, as well as identifying new potent inhibitors of eukaryotic PLDs. Being able to purify the plant PLD from Vigna unguiculata (VuPLD), we obtained a SAXS model of its structure. We then used a fluorescence-based test suitable for high-throughput screening to review the effect of eukaryotic PLD inhibitors described in the literature. In this regard, we found that only few molecules were in fact able to inhibit VuPLD and we confirmed that vanadate is the most potent of all with an IC
50 around 58 μM. Moreover, the small-scale screening of a chemical library of 3120 compounds allowed us to optimize the different screening's steps and paved the way towards the discovery of new potent inhibitors., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
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