47 results on '"Antolín, C."'
Search Results
2. Prognostic Potential of Candidate miRNAs in Lung Cancer: Insights from Tissue and Liquid Biopsies
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Garcia, A., Vera, O., Sanchez-Cabrero, D., Gutierrez, L., Higueras, O., Esteban, I., Rodriguez-Antolín, C., Losantos, I., De Castro, J., and De Caceres, I. Ibanez
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- 2023
- Full Text
- View/download PDF
3. Glioma Patient Management: Utilizing MGMT Methylation in Extracellular Vesicle-Based Liquid Biopsy
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De Caceres, I. Ibanez, Rosas-Alonso, R., Pernia, O., Burdiel, M., Rodriguez-Antolin, C., Moreno, R., Esteban-Rodriguez, I., Martinez, V., and de Castro, J.
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- 2023
- Full Text
- View/download PDF
4. EP16.02-014 A Comparative Analysis of Gene Alteration Detected With NGS in Tumor Tissue and Peripheral Blood in Lung Cancer
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Ozaez, I., primary, Hernández, I., additional, Cruz-Castellanos, P., additional, Gutiérrez-Sainz, L., additional, Rosas-Alonso, R., additional, Castillo, R., additional, Higuera, O., additional, Losantos, I., additional, Rodríguez-Antolín, C., additional, Ibanez de Caceres, I., additional, Rodríguez, I. Esteban, additional, and de Castro Carpeño, J., additional
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- 2022
- Full Text
- View/download PDF
5. EP16.01-007 Molecular Characterization by Next-Generation Sequencing (NGS) of Patients with Non-Small Cell Lung Cancer (NSCLC) Treated with Immunotherapy
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Castellanos, P. Cruz, primary, Alonso, R. Rosas, additional, Ozaez, I., additional, Hernández, I., additional, Losantos, I., additional, Gutiérrez Sainz, L., additional, Gómez, O. Higuera, additional, Antolín, C. Rodríguez, additional, Rodríguez, I. Esteban, additional, Ibáñez de Cáceres, I., additional, and De Castro Carpeño, J., additional
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- 2022
- Full Text
- View/download PDF
6. EP08.02-088 Mutational Status of KRAS, STK11 and CDKN2A Genes as Predictors of Response to Antiangiogenic Agents in Non-small Cell Lung Cancer Patients
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Cruz Castellanos, P., primary, Rosas Alonso, R., additional, Ozaez, I., additional, Hernández, I., additional, Losantos, I., additional, Gutiérrez Sainz, L., additional, Higuera Gómez, O., additional, Rodríguez Antolín, C., additional, Esteban Rodríguez, I., additional, Ibáñez de Cáceres, I., additional, and De Castro Carpeño, J., additional
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- 2022
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- View/download PDF
7. EP.12C.04 Location of Metastases and Prognosis of Patients with Metastatic KRAS-Mutant Non-Small Cell Lung Cancer
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Gutiérrez Sainz, L., Ozáez, I., Higuera Gómez, O., Villamayor, J., Esteban Rodríguez, I., Regojo Zapata, R.M., Peláez García, A., Heredia Soto, V., Mendiola, M., Rosas Alonso, R., Rodríguez Antolín, C., Ibáñez de Cáceres, I., and de Castro Carpeño, J.
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- 2024
- Full Text
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8. Identidad de género y cuidados intensivos: influencia de la masculinidad y la feminidad en la percepción de los cuidados enfermeros
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Via Clavero, G., Sanjuán Naváis, M., Martínez Mesas, M., Pena Alfaro, M., Utrilla Antolín, C., and Zarragoikoetxea Jáuregui, I.
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- 2010
- Full Text
- View/download PDF
9. CERUTTI GULDBERG, HORACIO. Filosofar desde nuestra América. Ensayo problematizador de su modus operandi.
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Antolín C. Sánchez Cuervo
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Philosophy. Psychology. Religion ,Philosophy (General) ,B1-5802 - Published
- 2016
10. Sobre Aurelia Valero Pie: José Gaos en México. Una biografía intelectual
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Antolín C. Sánchez Cuervo
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History ,intellectuals ,philosophy ,media_common.quotation_subject ,Art ,Valero ,F1201-3799 ,20th Century ,E-F ,exile ,History America ,Latin America. Spanish America ,Mexico ,Humanities ,media_common - Published
- 2018
11. Performance of some diversity and biotic indices in rivers affected by coal mining in northwestern Spain
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García-Criado, F., Tomé, A., Vega, F. J., and Antolín, C.
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- 1999
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- View/download PDF
12. The Politics of Traumatic Literature: Narrating Human Psyche and Memory
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Önder Çakırtaş, Editor, Şahin Kızıltaş, Editor, Antolin C. Trinidad, Editor, Önder Çakırtaş, Editor, Şahin Kızıltaş, Editor, and Antolin C. Trinidad, Editor
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- Psychology and literature, Psychic trauma in literature
- Abstract
This book is a collection of essays offering an inside view into the inner analysis of traumatic literary studies wherein language is used as a medium of expression so as to interpret man, psyche and memory. By making literature the partner of a dialogue with psychology, in order to better comprehend the psyche, it serves to alter the way of understanding the literary phenomenon.Featuring relevant coverage on topics such as literary production, psychology in literature, identity, and traumatic studies, this book provides in-depth analysis that is suitable for academicians, students, professionals, and researchers interested in discovering more about the relationship between psychology and literature and their effects on thinking.
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- 2018
13. 26P Analysis of prognostic and predictive factors of response in squamous cell carcinoma using NGS techniques
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Castellanos, P. Cruz, Sainz, L. Gutierrez, Gomez, O. Higuera, Antolin, C., Alonso, R. Rosas, Ibañez, I., Castelo, B., Rubio, X. Mielgo, and De Castro Carpeno, J.
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- 2021
- Full Text
- View/download PDF
14. CERUTTI GULDBERG, HORACIO. Filosofar desde nuestra América. Ensayo problematizador de su modus operandi.
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Sánchez Cuervo, Antolín C. and Sánchez Cuervo, Antolín C.
- Published
- 2016
15. 1419P - Next-generation sequencing panel verification to detect low frequency single nucleotide and copy number variants from mixing cell line studies
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Rosas-Alonso, R., Rodriguez-Antolin, C., Esteban Rodriguez, I., Cruz Castellanos, P., de Castro Carpeño, J., and Ibanez de Caceres, I.
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- 2019
- Full Text
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16. Xavier Mina. Fronteras de libertad Manuel Ortuño Martínez
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Cuervo, Antolín C. Sánchez
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- 2005
17. Viabilidad y determinación del periodo de transformación a la agricultura ecológica. Aplicación en dos comarcas del País Valenciano: Canal de Navarrés y Ribera Alta
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Roselló, Josep, Añó, C., Antolín, C., Mateu, E., and Pomares, Fernando
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La Ribera Alta ,P31 Soil surveys and mapping ,P36 Soil erosion, conservation and reclamation ,La Canal de Navarrés ,B10 Geography ,Estructura económica ,P30 Soil science and management ,Estructura social ,Agricultura ecológica - Abstract
En agricultura ecológica se plantea la necesidad de conocer el tiempo aconsejable para realizar la reconversión desde la agricultura convencional y su viabilidad biofísica y socioeconómica. En municipios de La Canal de Navarrés y La Ribera Alta se estudia la estructura económica y social comarcal, y se valora, mediante la selección de parámetros físicos y químicos del suelo y del entorno, el potencial del medio natural, expresando sus resultados cartográficamente a escala 1:50.000. A través de encuestas realizadas en las áreas cultivadas de la zona de estudio se establece la calidad de las prácticas agrícolas. En las encuestas se analiza la intensidad de uso de los insumos, su peligrosidad potencial y las prácticas de conservación, elaborándose un índice que indica el periodo de adecuación física a la agricultura ecológica de una zona concreta. Este índice, combinado con los factores económicos, sociales y biofísicos discriminan el territorio en diferentes unidades, válidas para la planificación comarcal de usos del suelo.
- Published
- 1998
18. Plant availability of heavy metals in a soil amended with a high dose of sewage sludge under drought conditions
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Universidad de Navarra, Pascual, Inmaculada, Antolín, C., García Izquierdo, Carlos, Polo, Alfredo, Sánchez-Díaz, Manuel, Universidad de Navarra, Pascual, Inmaculada, Antolín, C., García Izquierdo, Carlos, Polo, Alfredo, and Sánchez-Díaz, Manuel
- Abstract
The objective of this research was to study the effect of water deficit on soil heavy metal availability and metal uptake by ryegrass (Lolium multiflorum Lam.) plants grown in a soil amended with a high dose of rural sewage sludge. Three fertility treatments were applied: sewage sludge (SS), mineral fertilizer (M), and control (C); unamended). The levels of irrigation were: well-watered (W) and water deficit (D). Microbial respiration decreased the total organic C (TOC) in sludge-treated soils, but this did not enhance soil DTPA-extractable heavy metal concentrations. Indeed, Zn, Cu, Mn and Ni availability decreased during the experiment. C- and M-treated soils showed either no changes or increases of some trace element concentrations during the incubation. In the plant experiment, ryegrass dry matter (DM) yield, relative water content (RWC) and leaf water potential (PSgrw) decreased in drought conditions. Sludge addition increased metal concentrations in plants. However, in some instances, SS-treated plants showed either similar or lower transfer coefficient (Tc) values than did plants in the C and M treatments. Water deficit decreased the concentration and the Tc of some metals in roots of M and SS plants. Results indicate that sludge-borne heavy metals were maintained in chemical forms of low availability. The lower metal uptake by SS and M plants under dry conditions cannot be attributed to a lower availability of these elements in soil.
- Published
- 2004
19. EXILIO ESPAÑOL Y MEMORIA DE OCCIDENTE.
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Sánchez Cuervo, Antolín C.
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EXILE (Punishment) ,SPANISH history, 1939-1975 ,SPANISH exiles' writings ,NATIONALISM & collective memory ,HISTORIOGRAPHY - Abstract
Copyright of Acta Sociologica (0186-6028) is the property of Instituto de Investigaciones Filosoficas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2004
20. Anales de Edafología y Agrobiología Tomo 38 Número 5-6
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Hoyos de Castro, Ángel, Palomar, M. L., Hernando Costa, J., Fernández Bermejo, C., Poyato Ferrera, J., González García, F., García Ramos, G., Pérez Rodríguez, José Luis, Dorronsoro, C., Aguilar, J., Antolín, C., Corral Mora, L., Bellinfante, N., Medina Carnicer, M., Paneque Guerrero, Guillermo, Olmedo Pujol, J. de, Fernández Caldas, E., Pérez Méndez, J. A., Gutiérrez Jerez, F., Borges Pérez, A., Barragán Landa, Elisa, Íñiguez, J., Romero Díaz, Roque, Velasco, F., Lozano, J. M., Arrúe Ugarte, José Luis, Martín Aranda, José, Moreno, F., García de Leaniz, J., Mangas Martín, V. J., Sánchez de la Puente, L., González Ponce, R., Fábregas, R., Viéitez Cortizo, Ernesto, Arines, J., Puerto Martín, A., Escudero Berian, Alfonso, Gómez Gutiérrez, J. M., Valdés Amado, A., García Criado, Balbino, Trujillo Jacinto del Castillo, I., Álvarez-Tinaut, M. C., Leal, A., Agüi, I., Recalde, Luis, Gómez, M., Hernansáez Rabay, A., Parra Gilabert, María, Ortuño, A., Sánchez, Benito, Dios, Gerardo, Ordás Pérez, Amando, Mazuelos Vela, Carmen, Prieto, J., Liñán, J., and Esteban Velasco, Eduardo
- Abstract
Suelos. Estudio genético del suelo tipo del Alto de los Leones (Madrid) por A. Hoyos de Castro, Mª L. Palomar G. Villamil y J. Hernando Costa.-- Desarrollo del suelo sobre material silícico en función del tiempo, clima y vegetación, por A. Hoyos de Castro, Mª L. Palomar, Gª. Villamil y C. Fernández Bermejo.-- Estqdio de materiales caoliníticos de Sierra Morena occidental. I. Propiedades y proceso de génesis de caolines de Cerro Colora (Riotinto, Huelva), por J. Poyata Ferrera, F. González García, G. García Ramos y J. L. Pérez Rodríguez.-- Estudio de materiales caoliníticos de Sierra Morena occidental. II. Propiedades y proceso de génesis de caolines de Traslasierra (Huelva), por J. Poyato Ferrera. F. González García, J. L. Pérez Rodríguez y G. García Ramos.-- Estudio edáfico del sector Jabalcuz-Los Villares. IV. Mineralogía de la fracción arcilla, por C. Dorronsoro. J. Aguilar y C. Antolín.-- Estudio del Cambisol «Los Labrados» sobre granito de El Pedroso (Sevilla). I. Datos del medio, morfología y propiedades generales, por L. Corral Mora, N. Bellinjante Crocci, M. Medina Carnicer y G. Paneque Guerrero.-- Meteorización de sedimentos carbonatados blandos bajo clima mediterráneo, por Juan L. de Olmedo Pujol.-- Contenido en fósforo total y su relación con otros parámetros en una cronosecuencia de Andepts de las Islas Canarias, por E. Fernández Caldas, J. A. Pérez Méndez, F. Gutiérrez Jerez y A. Borges Pérez .-- Influencia del pH en la génesis de gibsita-clorit.a-vermiculita y caolinita en suelos de Navarra, por Elisa Barragán Landa y Jaime Iñíguez Herrero.-- Evaluación para riegos de los suelos de la Estación Experimental La Mayora, por Juan de Olmedo Pujol y Roque Romero Díaz.-- Cambios sinecológicos de la microflora telúrica asociados a las repoblaciones forestales con especies exóticas, por F. Velasco de Pedro y J. M. Lozano Calle.-- Propiedades físicas y químicas en relación con la porosidad de los suelos: Influencia del ciclo natural de humectación-desecación. II. Porosidad total y diferencial, por J. L. Arrúe Ugarte y J. Martín Aranda.-- Propiedades físicas y químicas en relación con la porosidad de los suelos : Influencia del ciclo natural de humectación-desecación. III. Porosidad y fracción arcilla, por J: L. Arrúe Ugarte, F. Moreno, J. L. Pérez Rodríguez y J. Martín Aranda.-- Influjo del ion Mg++ en la evolución del ortofosfato dicálcico dihidrato en contacto con suspensiones de minerales de la arcilla, por J. García de Leániz, F. González García y J. A. Pinilla Barrau.—Fertilidad de Suelos. Ahijamiento y producción del trigo de primavera. II. Respuesta al calcio y manganeso e interacciones de los nutrientes, por V. J. Mangas Martín y L. Sanchez de la Puente.-- Respuesta de la asociación trigo-avena loca a la fertilización potásica, por R. González Ponce.-- Respuesta de la asociación trigo-avena loca a la fertilización nitrogenada, por R. González Ponce.-- Efectos del tamaño de grano de fertilizantes PK en la producción de praderas, por R. Fábregas, E. Vieitez y J. Ariñes.--Aplicación de los espectros de diversidad al estudio de la heterogeneidad en comunidades de pastizal, por A. Puerto Martín, A. Escudero Berián y J. M. Gómez Gtrrez.-- Correlaciones entre bioelementos en especies pratenses bajo los efectos de la madurez. II. Gramíneas, por A. Valdés Amado, B. García Criado y J. M. Gómez Gutiérrez.-- Estudio comparativo de métodos para la determinación de fósforo orgánico total en andosoles, por F. Gutiérrez Jeres, E. Fernández Caldas, J. A. Pérez Méndez e l. Trujillo Jacinto del Castillo.—Nutrición y Fisiología Vegetal.-- Efectos fisiológicos de la interacción boro-manganeso en plantas de tomate. II. Absorción y distribución de macroelementos, por M. C. Alvarez-Tinaut, A. Leal, l. Agüi y L. Recalde.-- Efectos fisiológicos de la interacción boro-manganeso en plantas de tomate. III. Absorción y distribución de los microelementos Mn, Cu y Zn, por M. C. Alvarez.-Tinaut, A. Leal, M. Gómez y. L. Recalde.-- Relaciones fisiológicas de bioelementos durante el crecimiento y desarrollo de la hoja y el brote de limoneros cultivados en suelos salinos, por A. H ernansáez, M.a Parra y A. Ortuño.-- Los macronutrientes catiónicos en el maíz (Zea mays L.). I. Variaciones de la composición con el desarrollo, por Benito Sánchez y Gerardo Dios.-- Los macronutrientes catiónicos en el maíz (Zea mays L.). II. Evolución de la acumulación de K. Ca y Mg, y de sus relaciones durante el cultivo, por Benito Sánchez y Gerardo Dios.-- Empleo de unidades térmicas y capa negra en la clasificación de híbridos de maíz para Galicia, por A. Ordás.-- Evolución de los equilibrios fisiológicos y sus relaciones con el metabolismo de macro y micronutrientes en cultivos de olivar, por C Mazuelos Vela, J. Prieto Alcántara J. Liñán Benjunzea y E. Esteban Velasco.-- Influencia de compuestos fenólicos sobre la destrucción auxínica, por M. C. Mato.-- Notas. Peer reviewed 2019-08.- CopyBook.- Libnova.- Biblioteca ICA
- Published
- 1979
21. Anales de Edafología y Agrobiología Tomo 38 Número 3-4
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Guerra, A., Moreno Álvarez, J. L., Vyzcaino Muñoz, J., García Vicente, J., García-González, M. T., Aleixandre, T., Pinilla, A., Aguilar, J., Dorronsoro, C., Antolín, C., García, A., Rodríguez Pascual, C., Fernández Caldas, E., Rodríguez-Hernández, C. M., Chaves Sánchez, M., Murillo Carpio, J. M., Mazuelos Vela, Carmen, Poyato Ferrera, J., Pérez Rodríguez, José Luis, García Ramos, G., González García, F., Martín Aranda, José, Arrúe Ugarte, José Luis, Tschapek, M., Torres Sánchez, R. M., Wasowski, C., Felipo, M. T., Verdonck, O., Cappeart, I., Boodt, M. de, Reverte, P., Reverte, Luis, Costa, F., Lax, A., Gómez Amorós, Francisco, Gil, F., Caballero, A., Guadilla, D., Serrano, M., Piñol, Mª T., Hernando Fernández, Valentín, Orihuel Gasque, B., Mangas Martín, V. J., Sánchez de la Puente, L., Buschiazzo, D. E., and Peinemann, N.
- Abstract
Suelos. Procesos geoedáficos de la génesis, evolución y desarrollo de la tierra parda meridional. IV perfiles desarrollados sobre roca filoniana: características morfológicas y físico-químicas, por A. Guerra Delgado y J. L. Moreno Alvarez.-- Suelos volcánicos españoles. V. Campo de Calatrava (Ciudad Real). Características morfológicas y químicas, por C. Vizcayno Muñoz, J. García Vicente y M. T. García González.-- Suelos volcánicos españoles. VI. Campo de Calatrava (Ciudad Real). Mineralogía de la fracción arcilla, por C. Vizcayno Muñoz, M. T. García González y J. García Vicente.-- Suelos volcánicos españoles. VII. Olot (Gerona). Mineralogía de las fracciones arena y limo, por C. Vizcayno Mu1ioz, T. Aleixandre y A. Pinilla.-- Estudio edáfico del sector Jabalcuz-Los Villares. l. Características generales, por J. Aguilar, C. Dorronsoro. C. Antolín y A. García.-- Vertisoles formados sobre materiales volcánicos (Islas Canarias). Typic chromusterts. II. Mineralogía de las arcillas. Interpretación y clasificación, por C. RodríguezPascual. E. Fernández-Caldas y C. M. Rodríguez-Hernández.-- Relaciones entre los elementos mayoritarios, minoritarios y traza en dos suelos de las Islas Canarias, por C. Vizcayno Muñoz, M. T. García González y J. García Vicente.-- Características del suelo y vegetación de un área salina limítrofe de la Marisma del Guadalquivir (Isla Menor), por M. Chaves Sánchez y J. M. Murillo Carpio.-- Suelo y vegetación de dos zonas salinas de la Marisma de Lebrija (Sevilla). II. Características de la vegetación por J. M. Murillo Carpio, M. Chaves Sánchez y C. Mazuelos Vela.-- Estudio de materiales coaliníticos de Sierra Morena occidental. III. Mineralogía y génesis de los materiales caoliníticos de los yacimientos paleozoicos de S. Telmo y Sta. Bárbara (Huelva) y el Álamo (Sevilla), por J. Poyato Perrera, J. L. Pérez Rodríguez, G. García Ramos y F. González García.-- Propiedades físicas y químicas en relación con la porosidad de los suelos : influencia del ciclo natural de humectación-desecación. l. Perfiles representativos, condiciones ambientales y muestreos considerado., en el estudio, por J. Martín Aranda y J. L. Arrue Ugarte.-- The PZC of Al,O, + SiO, mixtures, hy M. Tschapek, R. M. Torres Sánchez and C. Wasowski.—Fertilidad de los suelos. El uso de tensiómetros para medir la humedad de substratos orgamcos, por M. T. Felipó Oriol, O. Vendonck, l. Cappaert, J. Cardus y M. de Boodt.-- Estudio de las propiedades físicas de los substratos hortícolas, por M. T. Felipó Oriol, O. Verdonck, l. Cappaert y M. de Boodt.-- Estudio del umbral de coagulación de ácidos húmicos con Ca, Mn y Zn, por P. Reverte, T. Hernández, L. Reverte y F. Costa.-- Interacción de ácidos húmicos con Ca. Mn y Zn. Estudio de infrarrojo, por T. Hernández. P. Reverte, L. Reverte y F. Costa.-- Contribución al conocimiento del equilibrio de cationes en suelos calizos, por Antonio Lax v Francisco Gómez Amorós.-- Acción diferencial del nitrato y del amonio en la producción de Lolium perenne cultivado en prado artificial de siega continua, por F. Gil, A. Caballero y D. Guadilla.—Nutrición y Fisiología Vegetal. Crecimiento y metabolismo nitrogenado en plantas de Nicotiana rustica L. irradiadas con UV cercano. III. Nicotina, por M. Serrano y Mª T. Piñol.-- Los efectos del régimen hídrico y de distintos niveles de fertilidad sobre el rendimiento, calidad y tamaño del tomate de invierno. IV Efectos del régimen hídrico y del PK sobre el crecimiento y rendimiento del tomate, por V. Hernando y B. Orihuel Gasque.-- Ahijamiento y producción del trigo de primavera. l. Respuesta al nitrógeno, por V. J. Mangas Martín y L. Sánchez de la Puente.-- Absorción de nutrientes por trigo y malezas en el Sur de la provincia de Buenos Aires (Argentina), por D. E. Buschiazzo y N. Peinemann.-- Notas.—Bibliografía Peer reviewed 2019-08.- CopyBook.- Libnova.- Biblioteca ICA
- Published
- 1979
22. Anales de Edafología y Agrobiología Tomo 38 Número 11-12
- Author
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Sánchez Díaz, J., Guerra, A., Fernández Caldas, E., Dorronsoro, C., Antolín, C., Rodríguez-Rodríguez, Álvaro, Tejedor Salguero, M. L., Vizcaíno Muñoz, C., Aleixandre, T., Pinilla, A., Alías Pérez, Luis J., Ortiz, R., Albaladejo, J., Calvo de Anta, R. Mª, Paz, A., Díaz Fierros, F., Almendros, G., Polo, A., Dorado, E., González García, S., Bruckert, S., Rosa, D. de la, Carlisle, V. W., Barahona Fernández, E., Linares González, J., Martín Patino, M. T., Casas Sáinz de Aja, J., Medina, J. A., Ruiz Amil, A., Vitón Barbolla, C., Aragón de la Cruz, F., Viéitez Cortizo, Ernesto, Fábregas, R., Arines, J., Ramos del Arco, M. L., Cuadrado Sánchez, S., Recalde, Luis, Hernando Fernández, Valentín, Orihuel Gasque, B., Lachica, M., Kosche, R., González, C., Blesa, A. Carlos, Jiménez, M. Soledad, Caballero, A., Jiménez Parrondo, M. S., García García, J. E., Egea Ibáñez, L., Martínez-Carrasco, Rafael, Sánchez de la Puente, L., Díaz Pineda, F., González Bernáldez, F., Nicolás, J. P. de, Morey, M., Sánchez Díaz, J., Guerra, A., Fernández Caldas, E., Dorronsoro, C., Antolín, C., Rodríguez-Rodríguez, Álvaro, Tejedor Salguero, M. L., Vizcaíno Muñoz, C., Aleixandre, T., Pinilla, A., Alías Pérez, Luis J., Ortiz, R., Albaladejo, J., Calvo de Anta, R. Mª, Paz, A., Díaz Fierros, F., Almendros, G., Polo, A., Dorado, E., González García, S., Bruckert, S., Rosa, D. de la, Carlisle, V. W., Barahona Fernández, E., Linares González, J., Martín Patino, M. T., Casas Sáinz de Aja, J., Medina, J. A., Ruiz Amil, A., Vitón Barbolla, C., Aragón de la Cruz, F., Viéitez Cortizo, Ernesto, Fábregas, R., Arines, J., Ramos del Arco, M. L., Cuadrado Sánchez, S., Recalde, Luis, Hernando Fernández, Valentín, Orihuel Gasque, B., Lachica, M., Kosche, R., González, C., Blesa, A. Carlos, Jiménez, M. Soledad, Caballero, A., Jiménez Parrondo, M. S., García García, J. E., Egea Ibáñez, L., Martínez-Carrasco, Rafael, Sánchez de la Puente, L., Díaz Pineda, F., González Bernáldez, F., Nicolás, J. P. de, and Morey, M.
- Abstract
Suelos. El orden Alfisol en la isla Gran Canaria, por J. Sánchez Días, A . Guerra Delgado y E. Fernández Caldas.-- Estudio edáfico del sector J abalcuz-Los Villares. li. Estudio mineralógico de la fracción arena gruesa (2-0,2 mm.) por C. Dorronsoro, J. Aguilar y C. Antolín.-- Estudio edáfico del sector Jabalcuz-Los Villares. III. Estudio micromorfologico, por J . Aguilar, C. Dorronsoro y C. Antolin.-- Suelos fersialíticos sobre lapillis basálticos. II. Características micromorfológicas. Interpretación y clasificación, por A. Rodríguez Rodríguez, M. L. Tejedor Salguero y E. Fernández Caldas.-- Suelos volcánicos españoles. VIII. Campo de Calatrava (Ciudad Real). Mineralogía de las fracciones arena y limo, por C. Vizcayno M., T. Alei.randre y A. Pinilla. Estudio de la fracción arcilla de un Paleargid xerálfico del campo de Cartagena, por L. J. Alías, R. Ortiz y J. Albaladejo.-- Nuevos datos sobre la influencia de la vegetación en la formación del suelo en Galicia.III. Aportes por hojarasca, pérdidas por drenaje y escorrentía. Balance del agua y los elementos a través del suelo, por R. Mª Calvo de Anta, A. Paz González y F. Díaz-Fierros Viqueira.-- Caracterización de las sustancias húmicas en la fracción humina de los suelos, por G. Almendros, A. Polo y E. Dorado. Estudio de un suelo pseudogley de la provincia de Burgos. Distribución de ácidos húmicos en las diferentes fracciones físicas, por S . González G. y S . Bruckert. An approach to the clas-sification of agricultura! and nonagricultural soil evaluation systems, por D. de la Rosa and V . W. Carlise.-- Sobre la coexistencia de los procesos edáficos y geomorfológicos , por E. Barahona Fernández y J. Linares González.-- Estudio de la textura superficial de granos de cuarzo procedentes de granito por medio del micrnscopio electrónico de barrido, por M. T. Martín Patino, J. Casas Sáinz de Aja y J. A. Medina.-- Sorción interlaminar de aminas alifáticas en minerales interestratificados mica-montmorillonita por A. Ruiz Am
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- 1979
23. Geoscientific maps for planning in semi-arid regions: Valencia and Gran Canaria, Spain
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Cendrero, A., Sánchez, J., Antolin, C., Arnal, S., Diaz de Terán, J.R., Francés, E., Martínez, V., Moiun˜o, M., Nieto, M., Nogales, I., Pérez, E., Rios, C., Robles, F., Romero, A., and Suaárez, C.
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- 1990
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24. Molecular diagnosis of cystic fibrosis by RNA obtained from nasal epithelial cells.
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Prior-de Castro C, Martínez Gallego MÁ, Gómez-González C, de Sancho Martín R, Rodríguez-Antolín C, Rodríguez-Jiménez C, Del Pozo Mate Á, Zamarrón de Lucas E, Ruiz de Valbuena Maiz M, de Manuel Gómez C, Alcolea Batres S, Prados Sánchez MC, and J Torres R
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- Humans, Male, Female, Epithelial Cells metabolism, Exons genetics, RNA, Messenger genetics, RNA Splicing, Mutation, Cystic Fibrosis genetics, Cystic Fibrosis diagnosis, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Nasal Mucosa metabolism
- Abstract
Background: The diagnosis of cystic fibrosis (CF) is established when characteristic clinical signs are coupled with biallelic CFTR pathogenic variants. No previously reported non-canonical splice site variants have to be considered as variants of uncertain significance unless their effect on splicing has been validated., Methods: Two variants identified by next-generation sequencing were evaluated. We assayed their effects on splicing employing RNA analysis and real-time expression quantification from RNA obtained from the nasal epithelial cells of a patient with clinically suspected CF and of two patients with milder phenotypes (CFTR-related disorders)., Results: The variant c.164+2dup causes skipping of exon 2 (p.(Ser18_Glu54del)) and exon 2 plus 3 (p.(Ser18Argfs*16)) in CFTR mRNA. Exon 2 expression in the patient heterozygous for c.164+2dup was decreased to 7 % of the exon 2 expression in the controls. The synonymous variant c.1584G>A causes a partial skipping of exon 11. The exon 11 expression in the two patients heterozygous for this variant was 22 % and 42 % of that of the controls, respectively., Conclusion: We conclude that variant c.164+2dup affects mRNA processing and can be considered a CF-causing variant. The results of the functional assay also showed that the p.(Glu528=) variant, usually categorized as a neutral variant based on epidemiological data, partially affects mRNA processing in our patients. This finding would allow us to reclassify the variant as a CFTR-related variant with incomplete penetrance. RNA obtained from nasal epithelial cells is an easy and accurate tool for CFTR functional studies in patients with unclassified splice variants., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)
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- 2024
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25. Evaluation of the clinical use of MGMT methylation in extracellular vesicle-based liquid biopsy as a tool for glioblastoma patient management.
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Rosas-Alonso R, Colmenarejo-Fernández J, Pernía O, Burdiel M, Rodríguez-Antolín C, Losantos-García I, Rubio T, Moreno-Velasco R, Esteban-Rodríguez I, Martínez-Marín V, Yubero P, Costa-Fraga N, Díaz-Lagares A, López-López R, Díaz-Martin E, García JF, Sánchez CV, Gandía-González ML, Moreno-Bueno G, de Castro J, and de Cáceres II
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- Humans, Liquid Biopsy methods, Male, Female, Middle Aged, Aged, Adult, Prognosis, Glioblastoma genetics, Glioblastoma pathology, Glioblastoma diagnosis, Extracellular Vesicles metabolism, Extracellular Vesicles genetics, DNA Modification Methylases genetics, DNA Modification Methylases metabolism, DNA Repair Enzymes genetics, DNA Repair Enzymes metabolism, DNA Methylation, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms diagnosis
- Abstract
Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings., (© 2024. The Author(s).)
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- 2024
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26. Whole-Exome Sequencing of 21 Families: Candidate Genes for Early-Onset High Myopia.
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Sánchez-Cazorla E, González-Atienza C, López-Vázquez A, Arruti N, Nieves-Moreno M, Noval S, Mena R, Rodríguez-Jiménez C, Rodríguez-Solana P, González-Iglesias E, Guerrero-Carretero M, D'Anna Mardero O, Coca-Robinot J, Acal JC, Blasco J, Castañeda C, Fraile Maya J, Del Pozo Á, Gómez-Pozo MV, Montaño VEF, Dios-Blázquez L, Rodríguez-Antolín C, Gómez-Cano MLÁ, Delgado-Mora L, and Vallespín E
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- Child, Humans, Exome Sequencing, Myopia genetics
- Abstract
High myopia is the most severe and pathological form of myopia. It occurs when the spherical refractive error exceeds -6.00 spherical diopters (SDs) or the axial length (AL) of the eye is greater than 26 mm. This article focuses on early-onset high myopia, an increasingly common condition that affects children under 10 years of age and can lead to other serious ocular pathologies. Through the genetic analysis of 21 families with early-onset high myopia, this study seeks to contribute to a better understanding of the role of genetics in this disease and to propose candidate genes. Whole-exome sequencing studies with a panel of genes known to be involved in the pathology were performed in families with inconclusive results: 3% of the variants found were classified as pathogenic, 6% were likely pathogenic and the remaining 91% were variants of uncertain significance. Most of the families in this study were found to have alterations in several of the proposed genes. This suggests a polygenic inheritance of the pathology due to the cumulative effect of the alterations. Further studies are needed to validate and confirm the role of these alterations in the development of early-onset high myopia and its polygenic inheritance.
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- 2023
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27. MiR-151a: a robust endogenous control for normalizing small extracellular vesicle cargo in human cancer.
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Burdiel M, Jiménez J, Rodríguez-Antolín C, García-Guede Á, Pernía O, Sastre-Perona A, Rosas-Alonso R, Colmenarejo J, Rodríguez-Jiménez C, Diestro MD, Martínez-Marín V, Higueras O, Cruz P, Losantos-García I, Peinado H, Vera O, de Castro J, and Ibáñez de Cáceres I
- Abstract
Small extracellular vesicles (sEVs) in the blood of cancer patients contain higher amounts of tumor markers than those identified as free-circulating. miRNAs have significant biomedical relevance due to their high stability and feasible detection. However, there is no reliable endogenous control available to measure sEVs-miRNA content, impairing the acquisition of standardized consistent measurements in cancer liquid biopsy. In this study, we identified three miRNAs from a panel of nine potential normalizers that emerged from a comprehensive analysis comparing the sEV-miRNA profile of six lung and ovarian human cancer cell lines in the absence of or under different conditions. Their relevance as normalizers was tested in 26 additional human cancer cell lines from nine different tumor types undergoing chemotherapy or radiotherapy treatment. The validation cohorts were comprised of 242 prospective plasma and ascitic fluid samples from three different human tumor types. Variability and normalization properties were tested in comparison to miR-16, the most used control to normalize free-circulating miRNAs in plasma. Our results indicate that miR-151a is consistently represented in small extracellular vesicles with minimal variability compared to miR-16, providing a novel normalizer to measure small extracellular vesicle miRNA content that will benefit liquid biopsy in cancer patients., (© 2023. Yumed Inc. and BioMed Central Ltd., part of Springer Nature.)
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- 2023
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28. Advancing pharmacogenetic testing in a tertiary hospital: a retrospective analysis after 10 years of activity.
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Stewart S, Dodero-Anillo JM, Guijarro-Eguinoa J, Arias P, Gómez López De Las Huertas A, Seco-Meseguer E, García-García I, Ramírez García E, Rodríguez-Antolín C, Carcas AJ, Rodriguez-Novoa S, Rosas-Alonso R, and Borobia AM
- Abstract
The field of pharmacogenetics (PGx) holds great promise in advancing personalized medicine by adapting treatments based on individual genetic profiles. Despite its benefits, there are still economic, ethical and institutional barriers that hinder its implementation in our healthcare environment. A retrospective analysis approach of anonymized data sourced from electronic health records was performed, encompassing a diverse patient population and evaluating key parameters such as prescribing patterns and test results, to assess the impact of pharmacogenetic testing. A head-to-head comparison with previously published activity results within the same pharmacogenetic laboratory was also conducted to contrast the progress made after 10 years. The analysis revealed significant utilization of pharmacogenetic testing in daily clinical practice, with 1,145 pharmacogenetic tests performed over a 1-year period and showing a 35% growth rate increase over time. Of the 17 different medical departments that sought PGx tests, the Oncology department accounted for the highest number, representing 58.47% of all genotyped patients. A total of 1,000 PGx tests were requested for individuals susceptible to receive a dose modification based on genotype, and 76 individuals received a genotype-guided dose adjustment. This study presents a comprehensive descriptive analysis of real-world data obtained from a public tertiary hospital laboratory specialized in pharmacogenetic testing, and presents data that strongly endorse the integration of pharmacogenetic testing into everyday clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Stewart, Dodero-Anillo, Guijarro-Eguinoa, Arias, Gómez López De Las Huertas, Seco-Meseguer, García-García, Ramírez García, Rodríguez-Antolín, Carcas, Rodriguez-Novoa, Rosas-Alonso and Borobia.)
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- 2023
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29. NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells.
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Ibáñez-Navarro M, Fernández A, Escudero A, Esteso G, Campos-Silva C, Navarro-Aguadero MÁ, Leivas A, Caracuel BR, Rodríguez-Antolín C, Ortiz A, Navarro-Zapata A, Mestre-Durán C, Izquierdo M, Balaguer-Pérez M, Ferreras C, Martínez-López J, Valés-Gómez M, Pérez-Martínez A, and Fernández L
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- Humans, Child, Mice, Animals, NK Cell Lectin-Like Receptor Subfamily K metabolism, Cell Line, Tumor, Memory T Cells, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma therapy, Receptors, Chimeric Antigen
- Abstract
Introduction: Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation., Methods: In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA
- ) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells' cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality., Results: In vitro , we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo , NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo , they exhibited functional properties of leukemia initiating cells., Discussion: The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL., Competing Interests: MB-P was previously employed by the company Medpace Germany, GmbH, though not at the time of the study, and is currently employed by the company Medpace Spain. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor FM declared a shared committee the National Network of Advanced therapies TerAv with the author AP-M at the time of review., (Copyright © 2023 Ibáñez-Navarro, Fernández, Escudero, Esteso, Campos-Silva, Navarro-Aguadero, Leivas, Caracuel, Rodríguez-Antolín, Ortiz, Navarro-Zapata, Mestre-Durán, Izquierdo, Balaguer-Pérez, Ferreras, Martínez-López, Valés-Gómez, Pérez-Martínez and Fernández.)- Published
- 2023
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30. miR-124 as a Liquid Biopsy Prognostic Biomarker in Small Extracellular Vesicles from NSCLC Patients.
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Sanchez-Cabrero D, Garcia-Guede Á, Burdiel M, Pernía O, Colmenarejo-Fernandez J, Gutierrez L, Higuera O, Rodriguez IE, Rosas-Alonso R, Rodriguez-Antolín C, Losantos-García I, Vera O, De Castro-Carpeño J, and Ibanez de Caceres I
- Subjects
- Humans, Prognosis, Prospective Studies, Biomarkers, Tumor metabolism, Neoplasm Recurrence, Local metabolism, Liquid Biopsy, Proteoglycans metabolism, alpha Karyopherins metabolism, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms diagnosis, Lung Neoplasms genetics, Lung Neoplasms pathology, MicroRNAs metabolism, Exosomes metabolism
- Abstract
Despite advances in non-small cell lung cancer (NSCLC) research, this is still the most common cancer type that has been diagnosed up to date. microRNAs have emerged as useful clinical biomarkers in both tissue and liquid biopsy. However, there are no reliable predictive biomarkers for clinical use. We evaluated the preclinical use of seven candidate miRNAs previously identified by our group. We collected a total of 120 prospective samples from 88 NSCLC patients. miRNA levels were analyzed via qRT-PCR from tissue and blood samples. miR-124 gene target prediction was performed using RNA sequencing data from our group and interrogating data from 2952 NSCLC patients from two public databases. We found higher levels of all seven miRNAs in tissue compared to plasma samples, except for miR-124. Our findings indicate that levels of miR-124, both free-circulating and within exosomes, are increased throughout the progression of the disease, suggesting its potential as a marker of disease progression in both advanced and early stages. Our bioinformatics approach identified KPNA4 and SPOCK1 as potential miR-124 targets in NSCLC. miR-124 levels can be used to identify early-stage NSCLC patients at higher risk of relapse.
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- 2023
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31. Hereditary spastic paraplegia associated with a novel homozygous intronic noncanonical splice site variant in the AP4B1 gene.
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Gómez-González C, Pizarro-Sánchez C, Rodríguez-Antolín C, Pascual-Pascual I, Garcia-Romero M, Rodriguez-Jiménez C, de Sancho-Martín R, Del Pozo-Mate Á, Solís-López M, Prior-de Castro C, and Torres RJ
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- Adaptor Protein Complex 4, Adaptor Protein Complex beta Subunits, Homozygote, Humans, Introns, Mutation, Pedigree, RNA, RNA, Messenger genetics, Spastic Paraplegia, Hereditary genetics
- Abstract
Pathogenic variants in the AP4B1 gene lead to a rare form of hereditary spastic paraplegia (HSP) known as SPG47. We report on a patient with a clinical suspicion of complicated HSP of the lower limbs with intellectual disability, as well as a novel homozygous noncanonical splice site variant in the AP4B1 gene, in which the effect on splicing was validated by RNA analysis. We sequenced 152 genes associated with HSP using Next-Generation Sequencing (NGS). We isolated total RNA from peripheral blood and generated cDNA using reverse transcription-polymerase chain reaction (RT-PCR). A region of AP4B1 mRNA was amplified by PCR and the fragments obtained were purified from the agarose gel and sequenced. We found a homozygous variant of uncertain significance in the AP4B1 gene NM_006594.4: c.1511-6C>G in the proband. Two different AP4B1 mRNA fragments were obtained in the patient and his carrier parents. The shorter fragment was the predominant fragment in the patient and revealed a deletion with skipping of the AP4B1 exon 10. The patient's longer fragment corresponded to an insertion of the last five nucleotides of AP4B1 intron 9. We confirmed that this variant affects the normal splicing of RNA, sustaining the molecular diagnosis of SPG47 in the patient., (© 2021 John Wiley & Sons Ltd/University College London.)
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- 2022
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32. Analytical validation of a laboratory-development multigene pharmacogenetic assay.
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Rosas-Alonso R, Queiruga J, Arias P, Del Monte Á, Yuste F, Rodríguez-Antolín C, Losantos-Garcia I, Borobia AM, and Rodríguez-Nóvoa S
- Subjects
- Humans, Laboratories, Pharmacogenomic Testing, Reproducibility of Results, Laboratories, Clinical, Pharmacogenetics
- Abstract
Objective: The implementation of pharmacogenetics (PGx) in clinical practice is an essential tool for personalized medicine. However, clinical laboratories must validate their procedures before being used to perform PGx studies in patients, in order to confirm that they are adequate for the intended purposes., Methods: We designed a validation process for our in-house pharmacogenetic PCR-based method assay., Results: The concordance to reference, repeatability and reproducibility was 100%. Sensitivity and specificity were 100% for the detection of variant diplotypes in CYP2C9, CYP3A5, TPMT, DPYD and UGT1A1 genes. The sensitivity was lower in the detection of CYP2C19 variants due to a limitation in the design that prevents the detection of CYP2C19 *2/*10 diplotype., Conclusions: The success of implementing clinical pharmacogenetic testing into routine clinical practice is dependent on the precision of genotyping. Limitations must be bearing in mind to guarantee the quality of PGx assays in clinical laboratory practice. We provided objective evidence that the necessary requirements in our laboratory-development assay were fulfilled., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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33. Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.
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Soto JA, Rodríguez-Antolín C, Vera O, Pernía O, Esteban-Rodríguez I, Dolores Diestro M, Benitez J, Sánchez-Cabo F, Alvarez R, De Castro J, and Ibanez de Cáceres I
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Cell Line, Tumor drug effects, Cisplatin therapeutic use, Drug Resistance, Neoplasm drug effects, Female, Gene Expression Regulation, Neoplastic drug effects, Genetic Variation, Humans, Middle Aged, Spain, Adaptor Proteins, Signal Transducing genetics, Carcinoma, Ovarian Epithelial drug therapy, DNA Methylation drug effects, Epigenesis, Genetic drug effects, Ovarian Neoplasms drug therapy, PAX9 Transcription Factor genetics, Platinum Compounds therapeutic use
- Abstract
Background: In an effort to contribute to overcoming the platinum resistance exhibited by most solid tumors, we performed an array of epigenetic approaches, integrating next-generation methodologies and public clinical data to identify new potential epi-biomarkers in ovarian cancer, which is considered the most devastating of gynecological malignancies., Methods: We cross-analyzed data from methylome assessments and restoration of gene expression through microarray expression in a panel of four paired cisplatin-sensitive/cisplatin-resistant ovarian cancer cell lines, along with publicly available clinical data from selected individuals representing the state of chemoresistance. We validated the methylation state and expression levels of candidate genes in each cellular phenotype through Sanger sequencing and reverse transcription polymerase chain reaction, respectively. We tested the biological role of selected targets using an ectopic expression plasmid assay in the sensitive/resistant tumor cell lines, assessing the cell viability in the transfected groups. Epigenetic features were also assessed in 189 primary samples obtained from ovarian tumors and controls., Results: We identified PAX9 and FKBP1B as potential candidate genes, which exhibited epigenetic patterns of expression regulation in the experimental approach. Re-establishment of FKBP1B expression in the resistant OVCAR3 phenotype in which this gene is hypermethylated and inhibited allowed it to achieve a degree of platinum sensitivity similar to the sensitive phenotype. The evaluation of these genes at a translational level revealed that PAX9 hypermethylation leads to a poorer prognosis in terms of overall survival. We also set a precedent for establishing a common epigenetic signature in which the validation of a single candidate, MEST, proved the accuracy of our computational pipelines., Conclusions: Epigenetic regulation of PAX9 and FKBP1B genes shows that methylation in non-promoter areas has the potential to control gene expression and thus biological consequences, such as the loss of platinum sensitivity. At the translational level, PAX9 behaves as a predictor of chemotherapy response to platinum in patients with ovarian cancer. This study revealed the importance of the transcript-specific study of each gene under potential epigenetic regulation, which would favor the identification of new markers capable of predicting each patient's progression and therapeutic response., (© 2021. The Author(s).)
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- 2021
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34. Novel SLC12A2-ROS1 Fusion in Non-Small Cell Lung Cancer with a Significant Response to Crizotinib: The Importance of Choosing the Appropriate Next-Generation Sequencing Assay.
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Rodríguez-Antolín C, Rosas-Alonso R, Cruz P, Higuera O, Sánchez-Cabrero D, Esteban-Rodríguez I, Peláez-García A, Fernández Montaño VE, Rodríguez-Jiménez C, Ibáñez de Cáceres I, and de Castro J
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- Crizotinib pharmacology, Crizotinib therapeutic use, High-Throughput Nucleotide Sequencing, Humans, In Situ Hybridization, Fluorescence, Oncogene Proteins, Fusion genetics, Protein-Tyrosine Kinases genetics, Proto-Oncogene Proteins genetics, Solute Carrier Family 12, Member 2, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics
- Abstract
Identifying the druggable target is crucial for patients with nonsquamous advanced non-small cell lung cancer (NSCLC). This article adds to the spectrum of ROS1 fusion cases described in NSCLC. We describe a novel SLC12A2-ROS1 rearrangement that has not been previously reported in other cancers: a fusion that has clinical and radiological sensitivity to crizotinib. Fluorescence in situ hybridization detected the SLC12A2-ROS1 fusion and it was confirmed through hybrid capture-based next-generation sequencing (NGS); however, the fusion could not be detected by amplicon-based assay. The success of implementing NGS into routine clinical practice depends on the accuracy of testing. The test's methodological features should then be considered because they significantly affect the results. Given this patient's response to crizotinib, identifying patients with undescribed ROS1 fusions has important therapeutic implications. KEY POINTS: This is the first known description of an SLC12A2-ROS1 fusion. Considering the patient's clinical features and tumor response observed after crizotinib therapy, the authors confirm that this new rearrangement has relevant clinical impact for patients with non-small cell lung cancer. The success of implementing next-generation sequencing (NGS) into routine clinical practice depends on the accuracy of the testing. Different assays and NGS platforms can achieve differing results. Each assay's limitations need to be considered to ensure the quality of precision medicine in clinical practice., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)
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- 2021
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35. Symptomatic heterozygous X-Linked myotubular myopathy female patient with a large deletion at Xq28 and decrease expression of normal allele.
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Gómez-González C, Rosas-Alonso R, Rodríguez-Antolín C, García-Guede A, Ibáñez de Caceres I, Sanguino J, Pascual SI, Esteban I, Pozo AD, Mori MÁ, Torres RJ, and Prior C
- Subjects
- Adaptor Proteins, Signal Transducing metabolism, Adolescent, Chromosomes, Human, X genetics, Female, Heterozygote, Humans, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Myopathies, Structural, Congenital metabolism, Myopathies, Structural, Congenital pathology, Nuclear Proteins metabolism, Protein Tyrosine Phosphatases, Non-Receptor metabolism, Tumor Suppressor Proteins metabolism, Adaptor Proteins, Signal Transducing genetics, Chromosome Deletion, Myopathies, Structural, Congenital genetics, Nuclear Proteins genetics, Protein Tyrosine Phosphatases, Non-Receptor genetics, Tumor Suppressor Proteins genetics
- Abstract
X-linked myotubular myopathy (XLMTM; OMIM 310400) is a centronuclear congenital muscular disorder of X-linked recessive inheritance. Although female carriers are typically asymptomatic, affected heterozygous females have been described. Here, we describe the case of a sporadic female patient with suspicion of centronuclear myopathy and a heterozygous large deletion at Xq28 encompassing the MAMLD1, MTM1, MTMR1, CD99L2, and HMGB3 genes. The deletion was first detected using a custom next generation sequencing (NGS)-based multigene panel and finally characterized by comparative genomic hybridization array and multiplex ligation probe assay techniques. In this patient we have confirmed, by MTM1 mRNA quantification, a MTM1 gene expression less than the expected 50 percent in patient muscle. The significant 20% reduction in MTM1 mRNA expression in muscle, precludes low level of the normal myotubularin protein as the cause of the phenotype in this heterozygous female. We have also found that BIN1 expression in patient muscle biopsy was significantly increased, and postulate that BIN1 expression will be increased in XLMTM patient muscle as an attempt to maintain muscle function., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
- Published
- 2021
- Full Text
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36. Clinical validation of a novel quantitative assay for the detection of MGMT methylation in glioblastoma patients.
- Author
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Rosas-Alonso R, Colmenarejo-Fernandez J, Pernia O, Rodriguez-Antolín C, Esteban I, Ghanem I, Sanchez-Cabrero D, Losantos-Garcia I, Palacios-Zambrano S, Moreno-Bueno G, de Castro J, Martinez-Marin V, and Ibanez-de-Caceres I
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Alkylating therapeutic use, Brain Neoplasms mortality, Cohort Studies, CpG Islands, DNA Methylation, DNA Modification Methylases genetics, DNA Repair Enzymes genetics, Epigenomics, Female, Glioblastoma drug therapy, Glioblastoma surgery, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Polymerase Chain Reaction methods, Polymerase Chain Reaction trends, Prognosis, Progression-Free Survival, Promoter Regions, Genetic genetics, Prospective Studies, ROC Curve, Sensitivity and Specificity, Temozolomide therapeutic use, Tumor Suppressor Proteins genetics, Biomarkers, Tumor genetics, Brain Neoplasms pathology, Glioblastoma diagnosis, Glioblastoma genetics
- Abstract
Background: The promoter hypermethylation of the methylguanine-DNA methyltransferase gene is a frequently used biomarker in daily clinical practice as it is associated with a favorable prognosis in glioblastoma patients treated with temozolamide. Due to the absence of adequately standardized techniques, international harmonization of the MGMT methylation biomarker is still an unmet clinical need for the diagnosis and treatment of glioblastoma patients., Results: In this study we carried out a clinical validation of a quantitative assay for MGMT methylation detection by comparing a novel quantitative MSP using double-probe (dp_qMSP) with the conventional MSP in 100 FFPE glioblastoma samples. We performed both technologies and established the best cutoff for the identification of positive-methylated samples using the quantitative data obtained from dp_qMSP. Kaplan-Meier curves and ROC time dependent curves were employed for the comparison of both methodologies., Conclusions: We obtained similar results using both assays in the same cohort of patients, in terms of progression free survival and overall survival according to Kaplan-Meier curves. In addition, the results of ROC(t) curves showed that dp_qMSP increases the area under curve time-dependent in comparison with MSP for predicting progression free survival and overall survival over time. We concluded that dp_qMSP is an alternative methodology compatible with the results obtained with the conventional MSP. Our assay will improve the therapeutic management of glioblastoma patients, being a more sensitive and competitive alternative methodology that ensures the standardization of the MGMT-biomarker making it reliable and suitable for clinical use.
- Published
- 2021
- Full Text
- View/download PDF
37. Evaluation of two automated low-cost RNA extraction protocols for SARS-CoV-2 detection.
- Author
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Lázaro-Perona F, Rodriguez-Antolín C, Alguacil-Guillén M, Gutiérrez-Arroyo A, Mingorance J, and García-Rodriguez J
- Subjects
- Automation, Laboratory economics, Automation, Laboratory standards, COVID-19 Nucleic Acid Testing economics, COVID-19 Nucleic Acid Testing standards, Costs and Cost Analysis, Humans, RNA, Viral chemistry, RNA, Viral genetics, Reagent Kits, Diagnostic economics, Reagent Kits, Diagnostic standards, Sensitivity and Specificity, Automation, Laboratory methods, COVID-19 Nucleic Acid Testing methods, RNA, Viral standards
- Abstract
Background: Two automatable in-house protocols for high-troughput RNA extraction from nasopharyngeal swabs for SARS-CoV-2 detection have been evaluated., Methods: One hundred forty one SARS-CoV-2 positive samples were collected during a period of 10-days. In-house protocols were based on extraction with magnetic beads and designed to be used with either the Opentrons OT-2 (OT-2in-house) liquid handling robot or the MagMAXTM Express-96 system (MMin-house). Both protocols were tested in parallel with a commercial kit that uses the MagMAXTM system (MMkit). Nucleic acid extraction efficiencies were calculated from a SARS-CoV-2 DNA positive control., Results: No significant differences were found between both in-house protocols and the commercial kit in their performance to detect positive samples. The MMkit was the most efficient although the MMin-house presented, in average, lower Cts than the other two. In-house protocols allowed to save between 350€ and 400€ for every 96 extracted samples compared to the commercial kit., Conclusion: The protocols described harness the use of easily available reagents and an open-source liquid handling system and are suitable for SARS-CoV-2 detection in high throughput facilities., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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38. Optimizing the Procedure to Manufacture Clinical-Grade NK Cells for Adoptive Immunotherapy.
- Author
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Fernández A, Navarro-Zapata A, Escudero A, Matamala N, Ruz-Caracuel B, Mirones I, Pernas A, Cobo M, Casado G, Lanzarot D, Rodríguez-Antolín C, Vela M, Ferreras C, Mestre C, Viejo A, Leivas A, Martínez J, Fernández L, and Pérez-Martínez A
- Abstract
Natural killer (NK) cells represent promising tools for cancer immunotherapy. We report the optimization of an NK cell activation-expansion process and its validation on clinical-scale., Methods: RPMI-1640, stem cell growth medium (SCGM), NK MACS and TexMACS were used as culture mediums. Activated and expanded NK cells (NKAE) were obtained by coculturing total peripheral blood mononuclear cells (PBMC) or CD45RA
+ cells with irradiated K562mbIL15-41BBL or K562mbIL21-41BBL. Fold increase, NK cell purity, activation status, cytotoxicity and transcriptome profile were analyzed. Clinical-grade NKAE cells were manufactured in CliniMACS Prodigy., Results: NK MACS and TexMACs achieved the highest NK cell purity and lowest T cell contamination. Obtaining NKAE cells from CD45RA+ cells was feasible although PBMC yielded higher total cell numbers and NK cell purity than CD45RA+ cells. The highest fold expansion and NK purity were achieved by using PBMC and K562mbIL21-41BBL cells. However, no differences in activation and cytotoxicity were found when using either NK cell source or activating cell line. Transcriptome profile showed to be different between basal NK cells and NKAE cells expanded with K562mbIL21-41BBL or K562mbIL15-41BBL. Clinical-grade manufactured NKAE cells complied with the specifications from the Spanish Regulatory Agency., Conclusions: GMP-grade NK cells for clinical use can be obtained by using different starting cells and aAPC.- Published
- 2021
- Full Text
- View/download PDF
39. Tumor stem cells fuse with monocytes to form highly invasive tumor-hybrid cells.
- Author
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Aguirre LA, Montalbán-Hernández K, Avendaño-Ortiz J, Marín E, Lozano R, Toledano V, Sánchez-Maroto L, Terrón V, Valentín J, Pulido E, Casalvilla JC, Rubio C, Diekhorst L, Laso-García F, Del Fresno C, Collazo-Lorduy A, Jiménez-Munarriz B, Gómez-Campelo P, Llanos-González E, Fernández-Velasco M, Rodríguez-Antolín C, Pérez de Diego R, Cantero-Cid R, Hernádez-Jimenez E, Álvarez E, Rosas R, Dies López-Ayllón B, de Castro J, Wculek SK, Cubillos-Zapata C, Ibáñez de Cáceres I, Díaz-Agero P, Gutiérrez Fernández M, Paz de Miguel M, Sancho D, Schulte L, Perona R, Belda-Iniesta C, Boscá L, and López-Collazo E
- Subjects
- Animals, Cell Fusion, Humans, Hybrid Cells, Mice, Lung Neoplasms, Monocytes, Neoplastic Stem Cells
- Abstract
The 'cancer cell fusion' theory is controversial due to the lack of methods available to identify hybrid cells and to follow the phenomenon in patients. However, it seems to be one of the best explanations for both the origin and metastasis of primary tumors. Herein, we co-cultured lung cancer stem cells with human monocytes and analyzed the dynamics and properties of tumor-hybrid cells (THC), as well as the molecular mechanisms beneath this fusion process by several techniques: electron-microscopy, karyotyping, CRISPR-Cas9, RNA-seq, immunostaining, signaling blockage, among others. Moreover, mice models were assessed for in vivo characterization of hybrids colonization and invasiveness. Then, the presence of THCs in bloodstream and samples from primary and metastatic lesions were detected by FACS and immunofluorescence protocols, and their correlations with TNM stages established. Our data indicate that the generation of THCs depends on the expression of CD36 on tumor stem cells and the oxidative state and polarization of monocytes, the latter being strongly influenced by microenvironmental fluctuations. Highly oxidized M2-like monocytes show the strongest affinity to fuse with tumor stem cells. THCs are able to proliferate, colonize and invade organs. THC-specific cell surface signature CD36
+ CD14+ PANK+ allows identifying them in matched primary tumor tissues and metastases as well as in bloodstream from patients with lung cancer, thus functioning as a biomarker. THCs levels in circulation correlate with TNM classification. Our results suggest that THCs are involved in both origin and spread of metastatic cells. Furthermore, they might set the bases for future therapies to avoid or eradicate lung cancer metastasis., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)- Published
- 2020
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40. A Novel Role for the Tumor Suppressor Gene ITF2 in Tumorigenesis and Chemotherapy Response.
- Author
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Pernía O, Sastre-Perona A, Rodriguez-Antolín C, García-Guede A, Palomares-Bralo M, Rosas R, Sanchez-Cabrero D, Cruz P, Rodriguez C, Diestro M, Martín-Arenas R, Pulido V, Santisteban P, Castro J, Vera O, and Ibáñez de Cáceres I
- Abstract
Despite often leading to platinum resistance, platinum-based chemotherapy continues to be the standard treatment for many epithelial tumors. In this study we analyzed and validated the cytogenetic alterations that arise after treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines by 1-million microarray-based comparative genomic hybridization (array-CGH) and qRT-PCR methodologies. RNA-sequencing, functional transfection assays, and gene-pathway activity analysis were used to identify genes with a potential role in the development of this malignancy. The results were further explored in 55 lung and ovarian primary tumors and control samples, and in two extensive in silico databases. Long-term cell exposure to platinum induces the frequent deletion of ITF2 gene. Its expression re-sensitized tumor cells to platinum and recovered the levels of Wnt/β-catenin transcriptional activity. ITF2 expression was also frequently downregulated in epithelial tumors, predicting a worse overall survival. We also identified an inverse correlation between ITF2 and HOXD9 expression, revealing that Non-small cell lung cancer (NSCLC) patients with lower expression of HOXD9 had a better overall survival rate. We defined the implication of ITF2 as a molecular mechanism behind the development of cisplatin resistance probably through the activation of the Wnt-signaling pathway. This data highlights the possible role of ITF2 and HOXD9 as novel therapeutic targets for platinum resistant tumors.
- Published
- 2020
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41. Metagenomic Detection of Two Vientoviruses in a Human Sputum Sample.
- Author
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Lázaro-Perona F, Dahdouh E, Román-Soto S, Jiménez-Rodríguez S, Rodríguez-Antolín C, de la Calle F, Agrifoglio A, Membrillo FJ, García-Rodríguez J, and Mingorance J
- Subjects
- Humans, Phylogeny, Viral Proteins genetics, DNA Viruses classification, DNA Viruses genetics, Genome, Viral, Metagenomics methods, Respiratory Tract Infections virology, Sputum virology
- Abstract
We used metagenomics to analyze one sputum sample from a patient with symptoms of a respiratory infection that yielded negative results for all pathogens tested. We detected two viral genomes that could be assembled and showed sequence similarity to redondoviruses, a recently described group within the CRESS-DNA viruses. One hundred sputum samples were screened for the presence of these viruses using specific primers. One sample was positive for the same two viruses, and another was positive for one of them. These findings raise questions about a possible role of redondoviruses in respiratory infections in humans.
- Published
- 2020
- Full Text
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42. [Protein expression of PD-L1 and clinico-pathological data in a cohort of 53 patients with resectable non small cell lung cancer (NSCLC). Concordance between clones (22C3 and 28-8) and observers. Correlation and prognostic value of clinico-pathological data].
- Author
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Esteban-Rodríguez I, Ruiz Bravo-Burguillos E, Rosas R, Losantos I, Rodríguez-Antolín C, and de Castro J
- Subjects
- Adenocarcinoma chemistry, Adenocarcinoma classification, Adenocarcinoma pathology, Adenocarcinoma therapy, Aged, Carcinoma, Non-Small-Cell Lung classification, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung therapy, Carcinoma, Squamous Cell chemistry, Carcinoma, Squamous Cell classification, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell therapy, Female, Humans, Immunity, Cellular, Immunotherapy, Lung Neoplasms classification, Lung Neoplasms pathology, Lung Neoplasms therapy, Male, Neoplasm Grading, Pathologists, Patient Selection, Prognosis, Retrospective Studies, B7-H1 Antigen analysis, Biomarkers, Tumor analysis, Carcinoma, Non-Small-Cell Lung chemistry, Lung Neoplasms chemistry
- Abstract
Introduction: 85% of lung cancers are non-small cell carcinomas (NSCLC), the majority of which are diagnosed in an advanced stage. Immunotherapy has changed the treatment pattern for these tumors and created the need to find a marker for patient selection. Although not ideal, PD-L1 is the biomarker currently used in clinical practice., Material and Methods: Retrospective review by two pathologists of 53 cases of NSCLC from 2005 to 2007 in Hospital Universitario La Paz, using the WHO 2015 classification studying PD-L1 with clones 22C3 and 28-8. The consistency between observers and clones was assessed and all data studied were correlated with survival rates., Results: We found a prevalence of PD-L1 expression in tumor cells (TC) similar to that previously reported in the literature and a very good consistency between clones in the evaluation of TC and immune cells (ICC 0.99-0.93, p<.001). Interobserver concordance was very good in the evaluation of TC (ICC 0.902, 95% CI: 0.836-0.942, p<.001 for clone 22C3 and ICC 0.927, 95% CI: 0.877-0.957, p<.001 for clone 28-8) and poor for immune cells (ICC of 0.413, 95% CI: 0.163-0.613, p=.001 with clone 22C3 and ICC of 0.313, 95% CI: 0.053-0.534, p=.010 with clone 28-8). Subtype and histological grade were the only variables related to prognosis., Conclusions: The clones of PD-L1 22C3 and 28-8 are equivalent and there is good interobserver consistency in the evaluation of TC but not in immune cells., (Copyright © 2019 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)
- Published
- 2020
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43. miR-7 methylation as a biomarker to predict poor survival in early-stage non-small cell lung cancer patients.
- Author
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Rodríguez-Antolín C, Felguera-Selas L, Pernía O, Vera O, Esteban I, Losantos García I, de Castro J, Rosas-Alonso R, and Ibanez de Caceres I
- Abstract
Non-small-cell lung cancer (NSCLC) is the most common malignancy worldwide. Platinum-based chemotherapy is the standard of care for these patients. Recent research showed that miR-7 methylation status is a biomarker of cisplatin resistance in lung and ovarian cancer cells, which is one of the major limitations associated with their clinical management. The aim of the present study is to provide clinical insights associated with this novel potential biomarker in NSCLC patients by comparing the miR-7 methylation status with the cisplatin treatment response. Our results analyzed in 81 samples show that miR-7 methylation is a common event in tumor tissue and it is more frequent as the stage of the disease advances, remaining in 75% of metastatic patients. Tumor miR-7 unmethylation trend to a better PFS in early stages, and when our data was validated in an extended " in silico" cohort of 969 patients we obtained a significant increment in PFS and OS in those patients harboring miR-7 unmethylated (p = 0.010 and p = 0.007 respectively). When we select those early-stages patients harbouring miR-7 methylation, we observed that adenocarcinoma patients present a dramatic decrease in PFS compared with squamous cell carcinoma patients (median 18.9 versus 59.7 months, p = 0.002). In conclusion, our results show that presence of miR-7 methylation in early-stage NSCLC is suggestive of aggressive behavior, especially for adenocarcinoma patients. One major challenge in early diagnosis in NSCLC is identify the subgroup of patients that could benefit for adjuvant therapy, our data establish the basis for epigenetic classification on early-stage NSCLC that could influence treatment decisions in the future., Competing Interests: Competing interestsThe authors declare that they have no competing interests.
- Published
- 2019
- Full Text
- View/download PDF
44. Functional analysis of new variants at the low-density lipoprotein receptor associated with familial hypercholesterolemia.
- Author
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Rodríguez-Jiménez C, Pernía O, Mostaza J, Rodríguez-Antolín C, de Dios García-Díaz J, Alonso-Cerezo C, García-Polo I, Blanco A, Lahoz C, Arrieta F, Beltrán L, Díaz de Bustamante A, Garzón-Lorenzo L, Álvarez-Sala LA, Asenjo Á, Ibáñez de Cáceres I, and Rodríguez-Nóvoa S
- Subjects
- Adolescent, Adult, Aged, Animals, CHO Cells, Child, Cricetulus, Early Diagnosis, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Hyperlipoproteinemia Type II genetics, Hyperlipoproteinemia Type II metabolism, Male, Middle Aged, Sequence Analysis, DNA methods, Young Adult, High-Throughput Nucleotide Sequencing methods, Hyperlipoproteinemia Type II diagnosis, Mutation, Receptors, LDL genetics, Receptors, LDL metabolism
- Abstract
Familial hypercholesterolemia is an autosomal dominant disease of lipid metabolism caused by defects in the genes LDLR, APOB, and PCSK9. The prevalence of heterozygous familial hypercholesterolemia (HeFH) is estimated between 1/200 and 1/250. Early detection of patients with FH allows initiation of treatment, thus reducing the risk of coronary heart disease. In this study, we performed in vitro characterization of new LDLR variants found in our patients. Genetic analysis was performed by Next Generation Sequencing using a customized panel of 198 genes in DNA samples of 516 subjects with a clinical diagnosis of probable or definitive FH. All new LDLR variants found in our patients were functionally validated in CHO-ldlA7 cells. The LDLR activity was measured by flow cytometry and LDLR expression was detected by immunofluorescence. Seven new variants at LDLR were tested: c.518 G>C;p.(Cys173Ser), c.[684 G>T;694 G>T];p.[Glu228Asp;Ala232Ser], c.926C>A;p.(Pro309His), c.1261A>G;p.(Ser421Gly), c.1594T>A;p.(Tyr532Asn), and c.2138delC;p.(Thr713Lysfs*17). We classified all variants as pathogenic except p.(Ser421Gly) and p.(Ala232Ser). The functional in vitro characterization of rare variants at the LDLR is a useful tool to classify the new variants. This approach allows us to confirm the genetic diagnosis of FH, avoiding the classification as "uncertain significant variants", and therefore, carry out cascade family screening., (© 2019 Wiley Periodicals, Inc.)
- Published
- 2019
- Full Text
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45. Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer.
- Author
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Moncho-Amor V, Pintado-Berninches L, Ibañez de Cáceres I, Martín-Villar E, Quintanilla M, Chakravarty P, Cortes-Sempere M, Fernández-Varas B, Rodriguez-Antolín C, de Castro J, Sastre L, and Perona R
- Subjects
- Actin Cytoskeleton metabolism, Adenocarcinoma of Lung enzymology, Adenocarcinoma of Lung pathology, Adherens Junctions metabolism, Animals, Carcinogenesis genetics, Carcinogenesis pathology, Carcinoma, Non-Small-Cell Lung pathology, Cell Adhesion genetics, Cell Line, Tumor, Cell Movement genetics, Cell Shape genetics, Disease Progression, Dual Specificity Phosphatase 6 metabolism, Focal Adhesions metabolism, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meier Estimate, Lung Neoplasms pathology, MAP Kinase Signaling System, Mice, Nude, Transforming Growth Factor beta metabolism, Carcinoma, Non-Small-Cell Lung enzymology, Carcinoma, Non-Small-Cell Lung genetics, Dual Specificity Phosphatase 6 genetics, Genes, Tumor Suppressor, Lung Neoplasms enzymology, Lung Neoplasms genetics
- Abstract
DUSP6/MKP3 is a dual-specific phosphatase that regulates extracellular regulated kinase ERK1/2 and ERK5 activity, with an increasingly recognized role as tumor suppressor. In silico studies from Gene expression Omnibus (GEO) and Cancer Genome atlas (TCGA) databases reveal poor prognosis in those Non-small cell lung cancer (NSCLC) patients with low expression levels of DUSP6 . In agreement with these data, here we show that DUSP6 plays a major role in the regulation of cell migration, motility and tumor growth. We have found upregulation in the expression of several genes involved in epithelial to mesenchymal transition (EMT) in NSCLC- DUSP6 depleted cells. Data obtained in RNA-seq studies carried out in DUSP6 depleted cells identified EGFR, TGF-β and WNT signaling pathways and several genes such as VAV3, RUNXR2, LEF1, FGFR2 whose expression is upregulated in these cells and therefore affecting cellular functions such as integrin mediated cell adhesion, focal adhesion and motility. Furthermore, EGF signaling pathway is activated via ERK5 and not ERK1/2 and TGF-β via SMAD2/3 in DUSP6 depleted cells. In summary DUSP6 is a tumor suppressor in NSCLC and re-establishment of its expression may be a potential strategy to revert poor outcome in NSCLC patients.
- Published
- 2019
- Full Text
- View/download PDF
46. [Aggregation of cases of legionella pneumonia in workers related to the ceramic industry in Castellon, Spain, 2006].
- Author
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Bellido-Blasco JB, Pelaz-Antolín C, Delas-González MA, Sarrión-Martínez J, Moreno-Muñoz MR, and Herrero-Carot C
- Subjects
- Adult, Catchment Area, Health, Female, Humans, Male, Middle Aged, Spain epidemiology, Ceramics, Industry, Legionnaires' Disease epidemiology, Legionnaires' Disease etiology, Lung microbiology, Occupational Diseases epidemiology
- Abstract
Background: Cases of legionellosis sometimes arise in the form of aggregations which are difficult to interpret. This study provides an analysis of these groupings having arisen one summer in Castellon., Methods: Microbiological, clinical and epidemiological field methods were employed., Results: Within a few days, there were five (5) cases of legionella pneumonia in workers related to various ceramic industries within an area where a large number of these plants are located. Two constituted a minor outbreak. By means of molecular biology techniques performed on the strains, the common origins of three of the cases were ruled out., Conclusions: It is debated whether this episode of an outbreak having arisen within the context of a broader-ranging cluster of cases of a multi-focal origin was a chance event or whether it was the manifestation of a risk related to this industrial activity which might repeat itself.
- Published
- 2008
- Full Text
- View/download PDF
47. [Prevalence of Legionella in cooling towers in the Community of Madrid].
- Author
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Ordóñez-Iriarte JM, Ferrer-Simó JB, Pelaz-Antolín C, and García-Comas L
- Subjects
- Humans, Legionnaires' Disease epidemiology, Risk Factors, Spain epidemiology, Legionella pneumophila isolation & purification, Legionnaires' Disease etiology, Legionnaires' Disease prevention & control, Water Microbiology, Water Supply
- Published
- 2006
- Full Text
- View/download PDF
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