45 results on '"González-Sánchez, Laura"'
Search Results
2. Properdin deficiency associated with systemic meningococcal disease due to a novel p.Cys337Arg pathogenic variant
- Author
-
González-Sánchez, Laura, Agudo, Ana Mei, Van Den Rym, Anne, Begiristain, María Isabel, Saizar, Alazne, Pérez de Diego, Rebeca, Nozal, Pilar, López-Lera, Alberto, López-Trascasa, Margarita, and Corvillo, Fernando
- Published
- 2024
- Full Text
- View/download PDF
3. 144 FH desialylation as an acquired cause of Complement dysregulation in atypical Haemolytic Uraemic Syndrome
- Author
-
Corvillo, Fernando, primary, González-Sánchez, Laura, additional, García-Sánchez, Rosario, additional, Gómez Delgado, Irene, additional, Márquez-Tirado, Bárbara, additional, Goicoechea de Jorge, Elena, additional, and Sánchez-Corral, Pilar, additional
- Published
- 2023
- Full Text
- View/download PDF
4. Downregulation of specific FBXW7 isoforms with differential effects in T-cell lymphoblastic lymphoma
- Author
-
Vázquez-Domínguez, Irene, González-Sánchez, Laura, López-Nieva, Pilar, Fernández-Navarro, Pablo, Villa-Morales, María, Cobos-Fernández, María Á., Sastre, Isabel, F. Fraga, Mario, F. Fernández, Agustín, Malumbres, Marcos, Salazar-Roa, María, Graña-Castro, Osvaldo, Santos, Javier, Llamas, Pilar, López-Lorenzo, José L., and Fernández-Piqueras, José
- Published
- 2019
- Full Text
- View/download PDF
5. Data from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion
- Author
-
Santos, Javier, primary, González-Sánchez, Laura, primary, Matabuena-deYzaguirre, María, primary, Villa-Morales, María, primary, Cozar, Patricia, primary, López-Nieva, Pilar, primary, Fernández-Navarro, Pablo, primary, Fresno, Manuel, primary, Díaz-Muñoz, Manuel D., primary, Guenet, Jean-Louis, primary, Montagutelli, Xavier, primary, and Fernández-Piqueras, José, primary
- Published
- 2023
- Full Text
- View/download PDF
6. Supplementary Figure 3 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion
- Author
-
Santos, Javier, primary, González-Sánchez, Laura, primary, Matabuena-deYzaguirre, María, primary, Villa-Morales, María, primary, Cozar, Patricia, primary, López-Nieva, Pilar, primary, Fernández-Navarro, Pablo, primary, Fresno, Manuel, primary, Díaz-Muñoz, Manuel D., primary, Guenet, Jean-Louis, primary, Montagutelli, Xavier, primary, and Fernández-Piqueras, José, primary
- Published
- 2023
- Full Text
- View/download PDF
7. Supplementary Figure 1 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion
- Author
-
Santos, Javier, primary, González-Sánchez, Laura, primary, Matabuena-deYzaguirre, María, primary, Villa-Morales, María, primary, Cozar, Patricia, primary, López-Nieva, Pilar, primary, Fernández-Navarro, Pablo, primary, Fresno, Manuel, primary, Díaz-Muñoz, Manuel D., primary, Guenet, Jean-Louis, primary, Montagutelli, Xavier, primary, and Fernández-Piqueras, José, primary
- Published
- 2023
- Full Text
- View/download PDF
8. Supplementary Figure 2 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion
- Author
-
Santos, Javier, primary, González-Sánchez, Laura, primary, Matabuena-deYzaguirre, María, primary, Villa-Morales, María, primary, Cozar, Patricia, primary, López-Nieva, Pilar, primary, Fernández-Navarro, Pablo, primary, Fresno, Manuel, primary, Díaz-Muñoz, Manuel D., primary, Guenet, Jean-Louis, primary, Montagutelli, Xavier, primary, and Fernández-Piqueras, José, primary
- Published
- 2023
- Full Text
- View/download PDF
9. Supplementary Table 1 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion
- Author
-
Santos, Javier, primary, González-Sánchez, Laura, primary, Matabuena-deYzaguirre, María, primary, Villa-Morales, María, primary, Cozar, Patricia, primary, López-Nieva, Pilar, primary, Fernández-Navarro, Pablo, primary, Fresno, Manuel, primary, Díaz-Muñoz, Manuel D., primary, Guenet, Jean-Louis, primary, Montagutelli, Xavier, primary, and Fernández-Piqueras, José, primary
- Published
- 2023
- Full Text
- View/download PDF
10. Supplementary Figure Legends 1-3 from A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion
- Author
-
Santos, Javier, primary, González-Sánchez, Laura, primary, Matabuena-deYzaguirre, María, primary, Villa-Morales, María, primary, Cozar, Patricia, primary, López-Nieva, Pilar, primary, Fernández-Navarro, Pablo, primary, Fresno, Manuel, primary, Díaz-Muñoz, Manuel D., primary, Guenet, Jean-Louis, primary, Montagutelli, Xavier, primary, and Fernández-Piqueras, José, primary
- Published
- 2023
- Full Text
- View/download PDF
11. Detection of novel fusion-transcripts by RNA-Seq in T-cell lymphoblastic lymphoma
- Author
-
López-Nieva, Pilar, Fernández-Navarro, Pablo, Graña-Castro, Osvaldo, Andrés-León, Eduardo, Santos, Javier, Villa-Morales, María, Cobos-Fernández, María Ángeles, González-Sánchez, Laura, Malumbres, Marcos, Salazar-Roa, María, and Fernández-Piqueras, José
- Published
- 2019
- Full Text
- View/download PDF
12. Complement factor D (adipsin) levels are elevated in acquired partial lipodystrophy (Barraquer-Simons syndrome)
- Author
-
Instituto de Salud Carlos III, European Commission, Comunidad de Madrid, Asociación Española de Familiares y Afectados de Lipodistrofias, Xunta de Galicia, National Institute of Diabetes and Digestive and Kidney Diseases (US), Corvillo, Fernando [0000-0001-6418-5647], González-Sánchez, Laura [0000-0002-4749-2423], López-Lera, Alberto [0000-0002-9596-6910], Arjona, Emilia [0000-0002-0753-3657], Ceccarini, Giovanni [0000-0003-0701-642X], Santini, Ferruccio [0000-0002-1706-0822], Araújo-Vilar, David [0000-0003-2852-7851], Brown, Rebecca J. [0000-0002-2589-7382], Villarroya, Francesc [0000-0003-1266-9142], Rodríguez de Córdoba, Santiago [0000-0001-6401-1874], Caballero, Teresa [0000-0003-3005-9858], Nozal, Pilar [0000-0002-8981-4312], López-Trascasa, Margarita [0000-0001-8594-282X], Corvillo, Fernando, González-Sánchez, Laura, López-Lera, Alberto, Arjona, Emilia, Ceccarini, Giovanni, Santini, Ferruccio, Araújo-Vilar, David, Brown, Rebecca J., Villarroya, Joan, Villarroya, Francesc, Rodríguez de Córdoba, Santiago, Caballero-Velázquez, Teresa, Nozal, Pilar, López-Trascasa, Margarita, Instituto de Salud Carlos III, European Commission, Comunidad de Madrid, Asociación Española de Familiares y Afectados de Lipodistrofias, Xunta de Galicia, National Institute of Diabetes and Digestive and Kidney Diseases (US), Corvillo, Fernando [0000-0001-6418-5647], González-Sánchez, Laura [0000-0002-4749-2423], López-Lera, Alberto [0000-0002-9596-6910], Arjona, Emilia [0000-0002-0753-3657], Ceccarini, Giovanni [0000-0003-0701-642X], Santini, Ferruccio [0000-0002-1706-0822], Araújo-Vilar, David [0000-0003-2852-7851], Brown, Rebecca J. [0000-0002-2589-7382], Villarroya, Francesc [0000-0003-1266-9142], Rodríguez de Córdoba, Santiago [0000-0001-6401-1874], Caballero, Teresa [0000-0003-3005-9858], Nozal, Pilar [0000-0002-8981-4312], López-Trascasa, Margarita [0000-0001-8594-282X], Corvillo, Fernando, González-Sánchez, Laura, López-Lera, Alberto, Arjona, Emilia, Ceccarini, Giovanni, Santini, Ferruccio, Araújo-Vilar, David, Brown, Rebecca J., Villarroya, Joan, Villarroya, Francesc, Rodríguez de Córdoba, Santiago, Caballero-Velázquez, Teresa, Nozal, Pilar, and López-Trascasa, Margarita
- Abstract
Complement overactivation has been reported in most patients with Barraquer–Simons syndrome (BSS), a rare form of acquired partial lipodystrophy. Complement Factor D (FD) is a serine protease with a crucial role in the activation of the alternative pathway of the complement system, which is mainly synthesized by adipose tissue. However, its role in the pathogenesis of BSS has not been addressed. In this study, plasma FD concentration was measured in 13 patients with BSS, 20 patients with acquired generalized lipodystrophy, 22 patients with C3 glomerulopathy (C3G), and 50 healthy controls. Gene expression and immunohistochemistry studies were assayed using atrophied adipose tissue from a patient with BSS. We found significantly elevated FD levels in BSS cases compared with the remaining cohorts (p < 0.001). There were no significant differences in FD levels between sexes but FD was strongly and directly associated with age in BSS (r = 0.7593, p = 0.0036). A positive correlation between FD and C3 was seen in patients with C3G, characterized by decreased FD levels due to chronic C3 consumption, but no correlation was detected for BSS. Following mRNA quantification in the patient’s adipose tissue, we observed decreased CFD and C3 but elevated C5 transcript levels. In contrast, the increased FD staining detected in the atrophied areas reflects the effects of persistent tissue damage on the adipose tissue, thus providing information on the ongoing pathogenic process. Our results suggest that FD could be a reliable diagnostic biomarker involved in the pathophysiology of BSS by promoting unrestrained local complement system activation in the adipose tissue environment.
- Published
- 2021
13. Treatment of Peritoneal Surface Malignancies by Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Spain: Results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP).
- Author
-
Manzanedo, Israel, Pereira, Fernando, Cascales-Campos, Pedro, Muñoz-Casares, Cristobal, Asensio, Enrique, Torres-Melero, Juan, Prada-Villaverde, Arancha, Caravaca-García, Ibán, Gutiérrez-Calvo, Alberto, Vaqué, Javier, Ortega, Gloria, Titos-García, Alberto, González-Sánchez, Laura, Pérez-Viejo, Estíbalitz, Serrano, Ángel, and Martínez-Torres, Beatriz
- Subjects
HYPERTHERMIC intraperitoneal chemotherapy ,ONCOLOGIC surgery ,CYTOREDUCTIVE surgery ,PERITONEAL cancer ,CANCER patients ,STOMACH cancer - Abstract
Introduction: Treatment of Peritoneal Surface Malignancies (PSM) with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved results never seen before in these patients, which classically have a poor prognosis. The possibility of conducting clinical trials in these diseases is complicated, since some of them are rare, so the analysis of large databases provides very valuable scientific information. The aim of this study is to analyze the global results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP), whose objective is to register all patients scheduled for HIPEC nationwide. Methods: This is a retrospective analysis of the data recorded in the REGECOP from 36 Spanish hospitals from 2001 to 2021. There were 4159 surgical interventions in 3980 patients. Results: 66% are women and 34% are men with a median age of 59 years (range 17–86). 41.5% of the patients were treated for Peritoneal Metastases (PM) of colorectal cancer (CRC); 32.4% were women with ovarian cancer (OC) with PM; 12.8% were treated for pseudomyxoma peritonei (PMP); 6.2% had PM from gastric cancer (GC); 4.9% had PM of non-conventional origin; and, finally, 2.1% of cases were patients diagnosed with peritoneal mesothelioma. The median Peritoneal Cancer Index (PCI) was 9 (0–39), and complete cytoreduction was achieved in 81.7% of the procedures. Severe morbidity (Dindo–Clavien grade III–IV) was observed in 17.7% of surgeries, with 2.1% mortality. Median hospital stay was 11 days (0–259). Median overall survival (OS) was 41 months for CRC patients, 55 months for women with OC, was not reached in PMP patients, was 14 months for GC patients, and 66 months in mesothelioma patients. Conclusions: large databases provide extremely useful data. CRS with HIPEC in referral centers is a safe treatment with encouraging oncologic results in PSM. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
14. Toxicidad aguda de una formulacion comercial de glifosato sobre Poecilla reticulata (pisces: poecilidae) en condiciones de laboratorio
- Author
-
Herrera Jacquelin, Francois, Beltran González, Karenn Eliana, Garzón González, Jennifer Andrea, González Sánchez, Laura, Herrera Rivera, Laura Milena, and Torres Cequerra, Andrés Felipe
- Published
- 2016
15. Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome)
- Author
-
Corvillo, Fernando, primary, González-Sánchez, Laura, additional, López-Lera, Alberto, additional, Arjona, Emilia, additional, Ceccarini, Giovanni, additional, Santini, Ferruccio, additional, Araújo-Vilar, David, additional, Brown, Rebecca J, additional, Villarroya, Joan, additional, Villarroya, Francesc, additional, Rodríguez de Córdoba, Santiago, additional, Caballero, Teresa, additional, Nozal, Pilar, additional, and López-Trascasa, Margarita, additional
- Published
- 2021
- Full Text
- View/download PDF
16. Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome)
- Author
-
Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Corvillo, Fernando, González Sánchez, Laura, López Lera, Alberto, Arjona, Emilia, Ceccarini, Giovanni, Santini, Ferruccio, Araújo Vilar, David, Brown, Rebecca, Villarroya, Joan, Villarroya, Francesc, Rodriguez de Cordoba, Santiago, Caballero, Teresa, Nozal, Pilar, López Trascasa, Margarita, Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Corvillo, Fernando, González Sánchez, Laura, López Lera, Alberto, Arjona, Emilia, Ceccarini, Giovanni, Santini, Ferruccio, Araújo Vilar, David, Brown, Rebecca, Villarroya, Joan, Villarroya, Francesc, Rodriguez de Cordoba, Santiago, Caballero, Teresa, Nozal, Pilar, and López Trascasa, Margarita
- Abstract
Complement overactivation has been reported in most patients with Barraquer–Simons syndrome (BSS), a rare form of acquired partial lipodystrophy. Complement Factor D (FD) is a serine protease with a crucial role in the activation of the alternative pathway of the complement system, which is mainly synthesized by adipose tissue. However, its role in the pathogenesis of BSS has not been addressed. In this study, plasma FD concentration was measured in 13 patients with BSS, 20 patients with acquired generalized lipodystrophy, 22 patients with C3 glomerulopathy (C3G), and 50 healthy controls. Gene expression and immunohistochemistry studies were assayed using atrophied adipose tissue from a patient with BSS. We found significantly elevated FD levels in BSS cases compared with the remaining cohorts (p < 0.001). There were no significant differences in FD levels between sexes but FD was strongly and directly associated with age in BSS (r = 0.7593, p = 0.0036). A positive correlation between FD and C3 was seen in patients with C3G, characterized by decreased FD levels due to chronic C3 consumption, but no correlation was detected for BSS. Following mRNA quantification in the patient’s adipose tissue, we observed decreased CFD and C3 but elevated C5 transcript levels. In contrast, the increased FD staining detected in the atrophied areas reflects the effects of persistent tissue damage on the adipose tissue, thus providing information on the ongoing pathogenic process. Our results suggest that FD could be a reliable diagnostic biomarker involved in the pathophysiology of BSS by promoting unrestrained local complement system activation in the adipose tissue environment
- Published
- 2021
17. Genetically modified mouse models in cancer studies
- Author
-
Santos, Javier, Fernández-Navarro, Pablo, Villa-Morales, María, González-Sánchez, Laura, and Fernández-Piqueras, José
- Published
- 2008
- Full Text
- View/download PDF
18. Abdominal compartment syndrome due to severe acute pancreatitis after anterior separation of components
- Author
-
López Fernández, José, primary, García Plaza, Gabriel, additional, Soto Darias, Iván C., additional, Alcalá Serrano, Francisco Javier, additional, González Sánchez, Laura, additional, and Hernández Hernández, Juan Ramón, additional
- Published
- 2021
- Full Text
- View/download PDF
19. More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment
- Author
-
López-Nieva, Pilar, primary, González-Sánchez, Laura, additional, Cobos-Fernández, María Ángeles, additional, Córdoba, Raúl, additional, Santos, Javier, additional, and Fernández-Piqueras, José, additional
- Published
- 2020
- Full Text
- View/download PDF
20. EPHA7, a new target gene for 6q deletion in T-cell lymphoblastic lymphomas
- Author
-
López-Nieva, Pilar, Vaquero, Concepción, Fernández-Navarro, Pablo, González-Sánchez, Laura, Villa-Morales, María, Santos, Javier, Esteller, Manel, and Fernández-Piqueras, José
- Published
- 2012
- Full Text
- View/download PDF
21. Síndrome compartimental abdominal por pancreatitis aguda grave tras separación anterior de componentes.
- Author
-
Fernández, José López, García Plaza, Gabriel, Soto Darias, Iván C., Alcalá Serrano, Francisco Javier, González Sánchez, Laura, and Hernández Hernández, Juan Ramón
- Subjects
INTRA-abdominal hypertension ,OBESITY in women ,ABDOMINAL wall ,ABDOMINAL surgery ,POSTOPERATIVE period ,VENTRAL hernia - Abstract
Copyright of Revista Hispanoamericana de Hernia is the property of Aran Ediciones S.L. 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
- 2023
- Full Text
- View/download PDF
22. Fundación Heidelberg en Añorga, San Sebastián
- Author
-
González Sánchez, Laura María and Rodríguez Ramírez, Fernando
- Subjects
Arquitectura - Abstract
El paisaje queda definido por sus fragmentos: el agua, la roca, la densidad de vegetación, el vacío industrial, lo rural y lo urbano. Fragmentos que conforman el paisaje de Añorga y que ahora aparecen disgregados a causa de la actividad extractiva de la fábrica. Ante esta situación se impone un sistema lineal que jerarquiza el espacio y sus componentes. Un sistema que elige entrar en el paisaje mismo. En lugar de describirlo se une a él. De este modo nos sumergimos en su entorno, a través de la cualidades de volumen, materia y luz. De esta manera se propone la construcción de la Fundación Heidelberg como una obra que se introduce en el espacio para cambiarlo, dando así un nuevo concepto de nuestra interacción con él mismo. No trata de describir el paisaje, si no unirse a él. Es la construcción de un eje cuya función es ser centro de la nueva experiencia de la realidad espacial. Donde el usuario deja de controlar y abarcar el espacio para experimentarlo como tránsito. La fundación se presenta como oportunidad para extender las actividades que definen su entorno: cultura, investigación, tecnología e industria, dotando a Añorga de un nuevo espacio público que además, transforma el territorio, funcionando como una instalación viva, una infraestructura pública que aprovecha la morfología de la cantera para integrar estrategias de recogida, canalización y reutilización del agua. Un ejemplo de cooperación entre arquitectura y naturaleza desde la escala perceptiva y más poética de la propuesta hasta la transformación de la ruina en un sistema sostenible que trabaja entre naturaleza y arquitectura a través del agua.
- Published
- 2019
23. Exploiting the passenger ACO1-deficiency arising from 9p21 deletions to kill T-cell lymphoblastic neoplasia cells
- Author
-
Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Universidad Autónoma de Madrid, Asociación Española Contra el Cáncer, Fundación Ramón Areces, Banco Santander, González-Sánchez, Laura, Coboa-Fernández, María A., López-Nieva, Pilar, Villa-Morales, María, Stamatakis, Konstantinos, Cuezva, José M., Marin Rubio, José L., Vázquez-Dominguez, Irene, González-Vasconcelos, Iria, Salido, Eduardo, Llamas, Pilar, López-Lorenzo, José L., Santos, Javier, Fernández-Piqueras, José, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Universidad Autónoma de Madrid, Asociación Española Contra el Cáncer, Fundación Ramón Areces, Banco Santander, González-Sánchez, Laura, Coboa-Fernández, María A., López-Nieva, Pilar, Villa-Morales, María, Stamatakis, Konstantinos, Cuezva, José M., Marin Rubio, José L., Vázquez-Dominguez, Irene, González-Vasconcelos, Iria, Salido, Eduardo, Llamas, Pilar, López-Lorenzo, José L., Santos, Javier, and Fernández-Piqueras, José
- Abstract
Precursor T-cell lymphoblastic neoplasms are aggressive malignancies in need for more effective and specific therapeutic treatments. A significant fraction of these neoplasms harbor deletions on the locus 9p21, targeting the tumor suppressor CDKN2A but also deleting the aconitase 1 gene (ACO1), a neighboring housekeeping gene involved in cytoplasm and mitochondrial metabolism. Here we show that reducing the aconitase activity with fluorocitrate decreases the viability of T-cell lymphoblastic neoplasia cells in correlation to the differential aconitase expression. The consequences of the treatment were evidenced in vitro using T-cell lymphoblastic neoplasia cell lines exhibiting 9p21 deletions and variable levels of ACO1 expression or activity. Similar results were observed in melanoma cell lines, suggesting a true potential for fluorocitrate in different cancer types. Notably, ectopic expression of ACO1 alleviated the susceptibility of cell lines to fluorocitrate and, conversely, knockdown experiments increased susceptibility of resistant cell lines. These findings were confirmed in vivo on athymic nude-mice by using tumor xenografts derived from two T-cell lines with different levels of ACO1. Taken together, our results indicate that the non-targeted ACO1 deficiency induced by common deletions exerts a collateral cellular lethality that can be used as a novel therapeutic strategy in the treatment of several types of cancer.
- Published
- 2019
24. Detection of novel fusion-transcripts by RNA-Seq in T-cell lymphoblastic lymphoma
- Author
-
Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Asociación Española Contra el Cáncer, Fundación Ramón Areces, Banco Santander, López-Nieva, Pilar, Fernández-Navarro, Pablo, Graña-Castro, Osvaldo, Andrés-León, Eduardo, Santos, Javier, Villa-Morales, María, Cobos-Fernández, M. A., González-Sánchez, Laura, Malumbres, Marcos, Salazar-Roa, María, Fernández-Piqueras, José, Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Asociación Española Contra el Cáncer, Fundación Ramón Areces, Banco Santander, López-Nieva, Pilar, Fernández-Navarro, Pablo, Graña-Castro, Osvaldo, Andrés-León, Eduardo, Santos, Javier, Villa-Morales, María, Cobos-Fernández, M. A., González-Sánchez, Laura, Malumbres, Marcos, Salazar-Roa, María, and Fernández-Piqueras, José
- Abstract
Fusions transcripts have been proven to be strong drivers for neoplasia-associated mutations, although their incidence in T-cell lymphoblastic lymphoma needs to be determined yet. Using RNA-Seq we have selected 55 fusion transcripts identified by at least two of three detection methods in the same tumour. We confirmed the existence of 24 predicted novel fusions that had not been described in cancer or normal tissues yet, indicating the accuracy of the prediction. Of note, one of them involves the proto oncogene TAL1. Other confirmed fusions could explain the overexpression of driver genes such as COMMD3-BMI1, LMO1 or JAK3. Five fusions found exclusively in tumour samples could be considered pathogenic (NFYG-TAL1, RIC3-TCRBC2, SLC35A3-HIAT1, PICALM MLLT10 and MLLT10-PICALM). However, other fusions detected simultaneously in normal and tumour samples (JAK3-INSL3, KANSL1-ARL17A/B and TFG-ADGRG7) could be germ-line fusions genes involved in tumour-maintaining tasks. Notably, some fusions were confirmed in more tumour samples than predicted, indicating that the detection methods underestimated the real number of existing fusions. Our results highlight the potential of RNA-Seq to identify new cryptic fusions, which could be drivers or tumour-maintaining passenger genes. Such novel findings shed light on the searching for new T-LBL biomarkers in these haematological disorders.
- Published
- 2019
25. Viabilidad del materialismo termodinámico en la obra de Philippe Rahm
- Author
-
González Sánchez, Laura María and Giménez Molina, Mª del Carmen
- Subjects
Medio Ambiente ,Arquitectura - Abstract
La arquitectura del clima se abre paso, cada vez con más fuerza, en la nueva sociedad actual, preocupada por el creciente problema del calentamiento global. Este trabajo pretende realizar un análisis o reflexión de las implicaciones del desarrollo de esta nueva arquitectura en el proceso de diseño. Sentará las bases de la filosofía de hoy en día a través del estudio evolutivo de la historia de la arquitectura, llegando hasta la línea de actuación actual en el desarrollo de la práctica de la profesión, la sostenibilidad. La presentación del modelo termodinámico, tiene como objetivo estudiar la importancia y posibilidades del empleo de los componentes atmosféricos, en la definición del espacio arquitectónico. En esta línea, se presenta como mayor exponente el arquitecto suizo Philippe Rahm. Se abordará la evolución de su trabajo a lo largo de distintas fases, para concluir la viabilidad del desarrollo material de estas obras. La propuesta del arquitecto, cuestiona el proceso compositivo tradicional y propone una nueva metodología que define un nuevo lenguaje formal de la arquitectura.
- Published
- 2018
26. More Insights on the Use of γ‐Secretase Inhibitors in Cancer Treatment.
- Author
-
López‐Nieva, Pilar, González‐Sánchez, Laura, Cobos‐Fernández, María Ángeles, Córdoba, Raúl, Santos, Javier, and Fernández‐Piqueras, José
- Subjects
THERAPEUTIC use of antineoplastic agents ,CARCINOGENS ,CELLULAR signal transduction ,DRUG efficacy ,DRUG toxicity ,LIGANDS (Biochemistry) ,LYMPHOBLASTIC leukemia ,MOLECULAR structure ,MONOCLONAL antibodies ,GENETIC mutation ,PROTEOLYTIC enzymes ,T cells ,TUMORS ,TREATMENT effectiveness ,T-cell lymphoma ,CHEMICAL inhibitors - Abstract
The NOTCH1 gene encodes a transmembrane receptor protein with activating mutations observed in many T‐cell acute lymphoblastic leukemias (T‐ALLs) and lymphomas, as well as in other tumor types, which has led to interest in inhibiting NOTCH1 signaling as a therapeutic target in cancer. Several classes of Notch inhibitors have been developed, including monoclonal antibodies against NOTCH receptors or ligands, decoys, blocking peptides, and γ‐secretase inhibitors (GSIs). GSIs block a critical proteolytic step in NOTCH activation and are the most widely studied. Current treatments with GSIs have not successfully passed clinical trials because of side effects that limit the maximum tolerable dose. Multiple γ‐secretase–cleavage substrates may be involved in carcinogenesis, indicating that there may be other targets for GSIs. Resistance mechanisms may include PTEN inactivation, mutations involving FBXW7, or constitutive MYC expression conferring independence from NOTCH1 inactivation. Recent studies have suggested that selective targeting γ‐secretase may offer an improved efficacy and toxicity profile over the effects caused by broad‐spectrum GSIs. Understanding the mechanism of GSI‐induced cell death and the ability to accurately identify patients based on the activity of the pathway will improve the response to GSI and support further investigation of such compounds for the rational design of anti‐NOTCH1 therapies for the treatment of T‐ALL. Implications for Practice: γ‐secretase has been proposed as a therapeutic target in numerous human conditions, including cancer. A better understanding of the structure and function of the γ‐secretase inhibitor (GSI) would help to develop safe and effective γ‐secretase–based therapies. The ability to accurately identify patients based on the activity of the pathway could improve the response to GSI therapy for the treatment of cancer. Toward these ends, this study focused on γ‐secretase inhibitors as a potential therapeutic target for the design of anti‐NOTCH1 therapies for the treatment of T‐cell acute lymphoblastic leukemias and lymphomas. Understanding the mechanism of γ‐secretase inhibitor (GSI)–induced cell death and the ability to accurately identify patients based on the activity of the pathway could improve the response to GSI therapy for the treatment of cancer. This article focuses on γ‐secretase inhibitors as a potential therapeutic target to treat T‐cell acute lymphoblastic leukemias and lymphomas. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
27. RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas
- Author
-
Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Fundación Ramón Areces, Banco Santander, López-Nieva, Pilar, Fernández-Navarro, Pablo, Vaquero-Lorenzo, Concepción, Villa-Morales, María, Graña-Castro, Osvaldo, Cobos-Fernández, M. A., López-Lorenzo, José L., Llamas, Pilar, González-Sánchez, Laura, Sastre, Isabel, Pollán, Marina, Malumbres, Marcos, Santos, Javier, Fernández-Piqueras, José, Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Fundación Ramón Areces, Banco Santander, López-Nieva, Pilar, Fernández-Navarro, Pablo, Vaquero-Lorenzo, Concepción, Villa-Morales, María, Graña-Castro, Osvaldo, Cobos-Fernández, M. A., López-Lorenzo, José L., Llamas, Pilar, González-Sánchez, Laura, Sastre, Isabel, Pollán, Marina, Malumbres, Marcos, Santos, Javier, and Fernández-Piqueras, José
- Abstract
Background Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As in other cancers, the loss of cell cycle control plays a prominent role in the pathogenesis in these malignancies that is primarily attributed to loss of CDKN2A (encoding protein p16INK4A). However, the impact of the deregulation of other genes such as CDKN1C, E2F1, and TP53 remains to be clarified. Interestingly, experiments in mouse models have proven that conditional T-cell specific deletion of Cdkn1c gene may induce a differentiation block at the DN3 to DN4 transition, and that the loss of this gene in the absence of Tp53 led to aggressive thymic lymphomas. Results In this manuscript, we demonstrated that the simultaneous deregulation of CDKN1C, E2F1, and TP53 genes by epigenetic mechanisms and/or the deregulation of specific microRNAs, together with additional impairing of TP53 function by the expression of dominant-negative isoforms are common features in primary human T-LBLs. Conclusions Previous experimental work in mice revealed that T-cell specific deletion of Cdkn1c accelerates lymphomagenesis in the absence of Tp53. If, as expected, the consequences of the deregulation of the CDKN1C-E2F1-TP53 axis were the same as those experimentally demonstrated in mouse models, the disruption of this axis might be useful to predict tumor aggressiveness, and to provide the basis towards the development of potential therapeutic strategiesin human T-LBL.
- Published
- 2018
28. Viabilidad del materialismo termodinámico en la obra de Philippe Rahm
- Author
-
Giménez Molina, Mª del Carmen, González Sánchez, Laura María, Giménez Molina, Mª del Carmen, and González Sánchez, Laura María
- Abstract
La arquitectura del clima se abre paso, cada vez con más fuerza, en la nueva sociedad actual, preocupada por el creciente problema del calentamiento global. Este trabajo pretende realizar un análisis o reflexión de las implicaciones del desarrollo de esta nueva arquitectura en el proceso de diseño. Sentará las bases de la filosofía de hoy en día a través del estudio evolutivo de la historia de la arquitectura, llegando hasta la línea de actuación actual en el desarrollo de la práctica de la profesión, la sostenibilidad. La presentación del modelo termodinámico, tiene como objetivo estudiar la importancia y posibilidades del empleo de los componentes atmosféricos, en la definición del espacio arquitectónico. En esta línea, se presenta como mayor exponente el arquitecto suizo Philippe Rahm. Se abordará la evolución de su trabajo a lo largo de distintas fases, para concluir la viabilidad del desarrollo material de estas obras. La propuesta del arquitecto, cuestiona el proceso compositivo tradicional y propone una nueva metodología que define un nuevo lenguaje formal de la arquitectura.
- Published
- 2018
29. Propuesta para la prevención y mitigación de la contaminación por la actividad minera de oro sobre el canal del Dique
- Author
-
González Sánchez, Laura, Barragán G., Rafael G., and Carranza, Rosny
- Subjects
Canal del Dique ,Contaminación ,Ingeniería ambiental - Abstract
Una problemática ambiental que no ha tenido mucha trascendencia en el panorama colombiano es la posible afectación de la minería del oro en las costas y mares del Caribe colombiano. Los daños generados a los ecosistemas marinos y costeros podrían afectar económica, social y ambientalmente al país al reducir o modificar patrones de pesca, disminuir la demanda turística, cambiar los hábitos de alimentación de la población, modificar las condiciones físico-químicas de las aguas y alterar la biodiversidad marina. En este trabajo se analizó el problema de la contaminación marina por minería de oro ilegal en el departamento de Bolívar, el cual no solo es considerado un problema ambiental, sino que además tiene implicaciones de carácter social, económico pues contribuye a un riesgo para la salud humana y la seguridad alimentaria de los pobladores locales. El análisis del problema así como la propuesta para su solución, involucró diversas áreas de la ingeniería, dentro de las cuales se destacan la ingeniería de procesos al contemplarse el panorama global de la actividad minera como una actividad no solo productiva, sino que involucra aspectos sociales, ambientales y económicos que se desarrollan e interactúan entre sí. Para la propuesta de solución del problema se destacó la aplicación de tecnologías existentes, así como nuevamente la ingeniería de procesos al detectar el comportamiento de las causas del problema y generar a partir de su relación y profundidad, la medida pertinente para solucionar el problema de la contaminación marina por la actividad minera de oro. Como resultados se obtuvieron un documento diagnóstico de la problemática y un plan de trabajo para prevenir y mitigar esta contaminación. Ingeniero Ambiental Pregrado
- Published
- 2015
30. Transcriptomic analysis reveals sex-specific differences in the expression of Dcl1 and Fis1 genes in the radio-adaptive response of thymocytes to TRP53-mediated apoptosis
- Author
-
Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, López-Nieva, Pilar, Malavé, Manuel, González-Sánchez, Laura, Fernández-Piqueras, José, Fernández-Navarro, Pablo, Santos, Javier, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, López-Nieva, Pilar, Malavé, Manuel, González-Sánchez, Laura, Fernández-Piqueras, José, Fernández-Navarro, Pablo, and Santos, Javier
- Abstract
Radio-Adaptive Response (RAR) is a biological defense mechanism whereby exposure to low dose ionizing radiation (IR) mitigates the detrimental effects of high dose irradiation. RAR has been widely observed in vivo using as endpoint less induction of apoptosis. However, sex differences associated with RAR and variations between males and females on global gene expression influenced by RAR have not been still investigated. In addition, the response to radiation-induced apoptosis is associated with phosphorylation of TRP53 at both the serine 15 (ser-18 in the mouse) and serine 392 (ser-389 in mice) residues, but the role of these two phosphorylated forms in male and female RAR remains to be elucidated
- Published
- 2016
31. Contribution of JAK2 mutations to T-cell lymphoblastic lymphoma development
- Author
-
Asociación Española Contra el Cáncer, Comunidad de Madrid, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Roncero, Alejandro M., López-Nieva, Pilar, Cobos-Fernández, M. A., Villa-Morales, María, González-Sánchez, Laura, Arriba, M. C., Piris, M.A., Fernández-Navarro, Pablo, Fernández, A.F., Fraga, Mario F., Santos, Javier, Fernández-Piqueras, José, Asociación Española Contra el Cáncer, Comunidad de Madrid, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Roncero, Alejandro M., López-Nieva, Pilar, Cobos-Fernández, M. A., Villa-Morales, María, González-Sánchez, Laura, Arriba, M. C., Piris, M.A., Fernández-Navarro, Pablo, Fernández, A.F., Fraga, Mario F., Santos, Javier, and Fernández-Piqueras, José
- Abstract
The JAK-STAT pathway has a substantial role in lymphoid precursor cell proliferation, survival and differentiation. Nonetheless, the contribution of JAK2 to T-cell lymphoblastic lymphoma (T-LBL) development remains poorly understood. We have identified one activating TEL-JAK2 translocation and four missense mutations accumulated in 2 out of 16 T-LBL samples. Two of them are novel JAK2 mutations and the other two are reported for the first time in T-LBL. Notably, R683G and I682T might have arisen owing to RNA editing. Mutated samples showed different mutated transcripts suggesting sub-clonal heterogeneity. Functional approaches revealed that two JAK2 mutations (H574R and R683G) constitutively activate JAK-STAT signaling in ¿2A cells and can drive the proliferation of BaF3-EpoR cytokine-dependent cell line. In addition, aberrant hypermethylation of SOCS3 might contribute to enhance the activation of JAK-STAT signaling. Of utmost interest is that primary T-LBL samples harboring JAK2 mutations exhibited increased expression of LMO2, suggesting a mechanistic link between JAK2 mutations and the expression of LMO2, which was confirmed for the four missense mutations in transfected ¿2A cells. We therefore propose that active JAK2 contribute to T-LBL development by two different mechanisms, and that the use of pan-JAK inhibitors in combination with epigenetic drugs should be considered in future treatments.
- Published
- 2016
32. Analisis y valoración del sistema de regadio tradicional de la huerta de Murcia como patrimonio cultural
- Author
-
González Sánchez, Laura
- Subjects
Traditional irrigation ,Huerta ,PINTURA ,Máster Universitario en Conservación y Restauración de Bienes Culturales-Màster Universitari en Conservació i Restauració de Béns Culturals ,Regadío tradicional ,Cultural heritage ,CONSERVACION Y RESTAURACION DE BIENES CULTURALES (UPV) ,Landscape ,Patrimonio cultural - Abstract
[EN] The Traditional Irrigation Network in the “Huerta” of Murcia is in danger of disappearing. It is a material good with an extension of more than 500 km in which the “Tribunal de los Hombres Buenos” is sustained. This network has been declared an intangible World Heritage from 2009. However only a few elements o its constituents are protected by different Administrative Bodies that, although they coincide in these objects, they do no agree in order to put into practice a global model for the protection for all the irrigation network, The Administratrion Body is not the only resposible entity of this situation. Farmers are forced to choose between the implementation of modern irrigation systems or the hope of a change in the use of the land wich might provide them a profit that farming is currently not. Citizens, on the other hand, aspire to a model o development in the opposite direction. This model abandons these infrastructures and converts then in underground sewers dissociated from the landscape of which they were recently part of, but without stopping celebrating, though is just one day a year, “El Bando de la Huerta” festivity., [ES] La Tradicional Red de Regadíos de la Huerta de Murcia se encuentra en peligro de desaparición. Es un bien material con mas de 500km de extensión, en el que se apoya el Tribunal de los Hombres Buenos, que desde 2009 es Patrimonio Intangible de la Humanidad. Sin embargo, solo unos pocos elementos que la componen están protegidos por distintos órganos administrativos, por lo que es necesario poner en práctica un modelo de protección global para el conjunto de ellos. No solo la Administración es responsable de esta situación. Los agricultores se ven obligados a elegir entre la sistematización de los modernos sistemas de riego o la esperanza de cambio en el uso del suelo, que les proporcione la rentabilidad que no les da la tierra. Los ciudadanos, por otro lado, aspiran a un modelo de desarrollo en la dirección opuesta, que abandona estas infraestructuras y las convierte en alcantarillas, bajo tierra, disociadas del paisaje del que han formado parte hasta hace poco, pero sin dejar de celebrar aunque sea un solo día al año “El Bando de la Huerta”.
- Published
- 2014
33. Toxicidad aguda de una formulación comercial de glifosato sobre Poecilla reticulata (pisces:poecilidae) en condiciones de laboratorio
- Author
-
Herrera Jacquelin, Francois, primary, Beltran González, Karenn Eliana, additional, Garzón González, Jennifer Andrea, additional, González Sánchez, Laura, additional, Herrera Rivera, Laura Milena, additional, and Torres Cequerra, Andrés Felipe, additional
- Published
- 2016
- Full Text
- View/download PDF
34. Transcriptomic analysis reveals sex-specific differences in the expression of Dcl1 and Fis1 genes in the radio-adaptive response of thymocytes to TRP53-mediated apoptosis
- Author
-
López-Nieva, Pilar, primary, Malavé, Manuel, additional, González-Sánchez, Laura, additional, Fernández-Piqueras, José, additional, Fernández-Navarro, Pablo, additional, and Santos, Javier, additional
- Published
- 2016
- Full Text
- View/download PDF
35. Deregulated FADD expression and phosphorylation in T-cell lymphoblastic lymphoma
- Author
-
Marín-Rubio, José L., primary, de Arriba, María C., additional, Cobos-Fernández, María A., additional, González-Sánchez, Laura, additional, Ors, Inmaculada, additional, Sastre, Isabel, additional, Fernández-Piqueras, José, additional, and Villa-Morales, María, additional
- Published
- 2016
- Full Text
- View/download PDF
36. Analisis y valoración del sistema de regadio tradicional de la huerta de Murcia como patrimonio cultural
- Author
-
Carabal Montagud, María Angeles, Santamarina Campos, Virginia, Universitat Politècnica de València. Servicio de Alumnado - Servei d'Alumnat, González Sánchez, Laura, Carabal Montagud, María Angeles, Santamarina Campos, Virginia, Universitat Politècnica de València. Servicio de Alumnado - Servei d'Alumnat, and González Sánchez, Laura
- Abstract
[EN] The Traditional Irrigation Network in the “Huerta” of Murcia is in danger of disappearing. It is a material good with an extension of more than 500 km in which the “Tribunal de los Hombres Buenos” is sustained. This network has been declared an intangible World Heritage from 2009. However only a few elements o its constituents are protected by different Administrative Bodies that, although they coincide in these objects, they do no agree in order to put into practice a global model for the protection for all the irrigation network, The Administratrion Body is not the only resposible entity of this situation. Farmers are forced to choose between the implementation of modern irrigation systems or the hope of a change in the use of the land wich might provide them a profit that farming is currently not. Citizens, on the other hand, aspire to a model o development in the opposite direction. This model abandons these infrastructures and converts then in underground sewers dissociated from the landscape of which they were recently part of, but without stopping celebrating, though is just one day a year, “El Bando de la Huerta” festivity., [ES] La Tradicional Red de Regadíos de la Huerta de Murcia se encuentra en peligro de desaparición. Es un bien material con mas de 500km de extensión, en el que se apoya el Tribunal de los Hombres Buenos, que desde 2009 es Patrimonio Intangible de la Humanidad. Sin embargo, solo unos pocos elementos que la componen están protegidos por distintos órganos administrativos, por lo que es necesario poner en práctica un modelo de protección global para el conjunto de ellos. No solo la Administración es responsable de esta situación. Los agricultores se ven obligados a elegir entre la sistematización de los modernos sistemas de riego o la esperanza de cambio en el uso del suelo, que les proporcione la rentabilidad que no les da la tierra. Los ciudadanos, por otro lado, aspiran a un modelo de desarrollo en la dirección opuesta, que abandona estas infraestructuras y las convierte en alcantarillas, bajo tierra, disociadas del paisaje del que han formado parte hasta hace poco, pero sin dejar de celebrar aunque sea un solo día al año “El Bando de la Huerta”.
- Published
- 2014
37. Pobreza, resistencia a los medicamentos, diagnóstico, VIH-SIDA y su impacto en la evolución de la tuberculosis en Mexico
- Author
-
Mariscal Méndez, Araceli, Ramírez Palacios, Claudia de Jesús, González Sánchez, Laura, and Zenteno Cuevas, Roberto
- Subjects
Ciencias biomédicas ,Medical Sciences ,Medicina ,Innovations in health ,Research ,Investigaciones ,Biomedical Sciences ,Life Sciences ,Ciencias de la salud ,Health Sciences ,Medicine ,Ciencias de la vida ,Ciencias médicas ,Innovaciones en salud - Abstract
ResumenCon 10 millones de nuevos casos y tres millones de muertes al año, la tuberculosis (TB) es una de las enfermedades infectocontagiosas más importantes del mundo, antesedida solamente por la malaria y el VIH-SIDA, por lo que se mantiene como una de las enfermedades transmisibles de gran preocupación y ocupación para los sistemas de salud.[Mariscal A, RamÍrez CJ, González L, Zenteno R. Pobreza, resistencia a los medicamentos, diagnóstico, VIH-SIDA y su impacto en la evolución de la tuberculosis en México. MedUNAB 2005; 8(1):37-42].Palabras clave: Tuberculosis. pobreza, VIH, diagnóstico, resistencia a los medicamentos.
- Published
- 2005
38. Toxicidad aguda de una formulación comercial de glifosato sobre Poecilla reticulata (pisces: poecilidae) en condiciones de laboratorio.
- Author
-
Jacquelin, Francois Herrera, Beltran González, Karenn Eliana, Garzón González, Jennifer Andrea, González Sánchez, Laura, Milena Herrera Rivera, Laura, and Torres Cequerra, Andrés Felipe
- Abstract
Copyright of Revista Elementos (2027-923X) is the property of Revista Elementos 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
- 2016
- Full Text
- View/download PDF
39. EPHA7 , a new target gene for 6q deletion in T-cell lymphoblastic lymphomas
- Author
-
López-Nieva, Pilar, primary, Vaquero, Concepción, additional, Fernández-Navarro, Pablo, additional, González-Sánchez, Laura, additional, Villa-Morales, María, additional, Santos, Javier, additional, Esteller, Manel, additional, and Fernández-Piqueras, José, additional
- Published
- 2011
- Full Text
- View/download PDF
40. A Role for Stroma-Derived Annexin A1 as Mediator in the Control of Genetic Susceptibility to T-Cell Lymphoblastic Malignancies through Prostaglandin E2 Secretion
- Author
-
Santos, Javier, primary, González-Sánchez, Laura, additional, Matabuena-deYzaguirre, María, additional, Villa-Morales, María, additional, Cozar, Patricia, additional, López-Nieva, Pilar, additional, Fernández-Navarro, Pablo, additional, Fresno, Manuel, additional, Díaz-Muñoz, Manuel D., additional, Guenet, Jean-Louis, additional, Montagutelli, Xavier, additional, and Fernández-Piqueras, José, additional
- Published
- 2009
- Full Text
- View/download PDF
41. Crepitación abdominal
- Author
-
Bajo Santos, José Ángel, primary, Bernad Vallés, Mercedes, additional, and González Sánchez, Laura, additional
- Published
- 2006
- Full Text
- View/download PDF
42. Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome)
- Author
-
Margarita López-Trascasa, Giovanni Ceccarini, Teresa Caballero, Santiago Rodríguez de Córdoba, David Araújo-Vilar, Ferruccio Santini, Fernando Corvillo, Rebecca J. Brown, Laura González-Sánchez, Alberto López-Lera, Pilar Nozal, Joan Villarroya, Emilia Arjona, Francesc Villarroya, Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Instituto de Salud Carlos III, European Commission, Comunidad de Madrid, Asociación Española de Familiares y Afectados de Lipodistrofias, Xunta de Galicia, National Institute of Diabetes and Digestive and Kidney Diseases (US), Corvillo, Fernando, González-Sánchez, Laura, López-Lera, Alberto, Arjona, Emilia, Ceccarini, Giovanni, Santini, Ferruccio, Araújo-Vilar, David, Brown, Rebecca J., Villarroya, Francesc, Rodríguez de Córdoba, Santiago, Caballero, Teresa, Nozal, Pilar, López-Trascasa, Margarita, UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ), Corvillo, Fernando [0000-0001-6418-5647], González-Sánchez, Laura [0000-0002-4749-2423], López-Lera, Alberto [0000-0002-9596-6910], Arjona, Emilia [0000-0002-0753-3657], Ceccarini, Giovanni [0000-0003-0701-642X], Santini, Ferruccio [0000-0002-1706-0822], Araújo-Vilar, David [0000-0003-2852-7851], Brown, Rebecca J. [0000-0002-2589-7382], Villarroya, Francesc [0000-0003-1266-9142], Rodríguez de Córdoba, Santiago [0000-0001-6401-1874], Caballero, Teresa [0000-0003-3005-9858], Nozal, Pilar [0000-0002-8981-4312], and López-Trascasa, Margarita [0000-0001-8594-282X]
- Subjects
0301 basic medicine ,Male ,Lipodystrophy ,Adipose tissue ,Barraquer–Simons syndrome ,Acquired Partial Lipodystrophy ,Pathogenesis ,Cohort Studies ,0302 clinical medicine ,Complement Factor D ,Medicine ,Biology (General) ,Child ,Spectroscopy ,Acquired partial lipodystrophy ,General Medicine ,Ophthalmopathies ,Middle Aged ,Computer Science Applications ,Chemistry ,030220 oncology & carcinogenesis ,Adispin ,Female ,Oftalmopaties ,Adult ,medicine.medical_specialty ,Complement system ,Adolescent ,QH301-705.5 ,Medicina ,Complement factor D ,Acquired generalized lipodystrophy ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Young Adult ,Internal medicine ,Adipsin ,Aged ,Biomarkers ,Case-Control Studies ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,QD1-999 ,business.industry ,Organic Chemistry ,Adipose tissues ,medicine.disease ,Teixit adipós ,030104 developmental biology ,Endocrinology ,Alternative complement pathway ,sense organs ,business - Abstract
14 p.-7 fig.-2 tab., Complement overactivation has been reported in most patients with Barraquer–Simons syndrome (BSS), a rare form of acquired partial lipodystrophy. Complement Factor D (FD) is a serine protease with a crucial role in the activation of the alternative pathway of the complement system, which is mainly synthesized by adipose tissue. However, its role in the pathogenesis of BSS has not been addressed. In this study, plasma FD concentration was measured in 13 patients with BSS, 20 patients with acquired generalized lipodystrophy, 22 patients with C3 glomerulopathy (C3G), and 50 healthy controls. Gene expression and immunohistochemistry studies were assayed using atrophied adipose tissue from a patient with BSS. We found significantly elevated FD levels in BSS cases compared with the remaining cohorts (p < 0.001). There were no significant differences in FD levels between sexes but FD was strongly and directly associated with age in BSS (r = 0.7593, p = 0.0036). A positive correlation between FD and C3 was seen in patients with C3G, characterized by decreased FD levels due to chronic C3 consumption, but no correlation was detected for BSS. Following mRNA quantification in the patient’s adipose tissue, we observed decreased CFD and C3 but elevated C5 transcript levels. In contrast, the increased FD staining detected in the atrophied areas reflects the effects of persistent tissue damage on the adipose tissue, thus providing information on the ongoing pathogenic process. Our results suggest that FD could be a reliable diagnostic biomarker involved in the pathophysiology of BSS by promoting unrestrained local complement system activation in the adipose tissue environment., This study was funded by the Spanish Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund from the European Union (grant PI15-00255), by the Spanish Autonomous Region of Madrid (Complement II-CM network; S2017/BMD-3673), by the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP), by an intramural grant from the Xunta de Galicia (grant number ED431B 2020/37), and by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases.
- Published
- 2021
43. Estudio de la regulación del gen FBXW7 y el papel de sus isoformas en linfoma linfoblástico de células T
- Author
-
Vázquez Domínguez, Irene, Fernández Piqueras, José (dir.), González Sánchez, Laura (dir.), UAM. Departamento de Biología, Centro de Biología Molecular Severo Ochoa (CBM), Fernández Piqueras, José, and González Sánchez, Laura
- Subjects
Linfomas no Hodgkin - Tesis doctorales ,Biología y Biomedicina / Biología - Abstract
Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología. Fecha de lectura: 26-09-2018, Esta tesis tiene embargado el acceso al texto completo hasta el 26-03-2020, El gen FBXW7 es una E3 ubiquin-ligasa implicada en la degradación de una gran variedad de proteínas oncogénicas relacionadas con distintos tipos de cáncer. Este gen codifica tres isoformas diferentes (α, β y γ) que, a pesar de compartir los mismos dominios funcionales, se localizan en distintos compartimentos subcelulares. A pesar de la importancia de este gen como supresor tumoral en los linfomas linfoblásticos de células T precursoras (T-LBL), su tasa de mutación está en torno al 14%, pero se desconoce el posible efecto de su desregulación en linfomas primarios humanos. En este trabajo se evidencia que la gran mayoría de los T-LBL analizados muestra un descenso significativo de la expresión de FBXW7, que afecta principalmente a las isoformas α y β, aunque ninguno de los tumores analizados presentaba mutaciones inactivantes. Nuestros análisis revelan que la alteración de factores implicados directamente en su regulación junto a mecanismos epigenéticos y la desregulación de miRNAs convergen para actuar en combinaciones diferentes capaces de modular la expresión de FBXW7. Por otro lado, los ensayos in vitro demuestran que la sobreexpresión simultánea de dos de sus proteínas diana (CCNE1 y c-MYC) en la línea celular SUP-T1, usada como modelo, condiciona un aumento de la proliferación celular. Asimismo, el estudio de líneas celulares que expresan de manera estable las diferentes isoformas demuestra que cada una de ellas tiene preferencia por diferentes sustratos. De esta manera, las isoformas α y γ son responsables de la regulación de la proteína CCNE1 mientras que la isoforma β está implicada en la regulación de c-MYC. Además, nuestros resultados sugieren la existencia de mecanismos de regulación entre las propias isoformas, algo que no se había descrito con anterioridad. Por tanto, sería razonable pensar que cualquier estrategia enfocada a contrarrestar la reducción de las isoformas α y β de FBXW7 sería un tratamiento de interés para en este tipo de enfermedades hematológicas.
- Published
- 2018
44. Properdin deficiency associated with systemic meningococcal disease due to a novel p.Cys337Arg pathogenic variant.
- Author
-
González-Sánchez L, Agudo AM, Van Den Rym A, Begiristain MI, Saizar A, Pérez de Diego R, Nozal P, López-Lera A, López-Trascasa M, and Corvillo F
- Published
- 2023
- Full Text
- View/download PDF
45. Purification and biochemical characterisation of endoplasmic reticulum alpha1,2-mannosidase from Sporothrix schenckiil.
- Author
-
Mora-Montes HM, Robledo-Ortiz CI, González-Sánchez LC, López-Esparza A, López-Romero E, and Flores-Carreón A
- Subjects
- Mannosidases chemistry, Sporothrix classification, Sporothrix cytology, Endoplasmic Reticulum enzymology, Mannosidases isolation & purification, Sporothrix enzymology
- Abstract
Alpha 1,2-mannosidases from glycosyl hydrolase family 47 participate in N-glycan biosynthesis. In filamentous fungi and mammalian cells, alpha1,2-mannosidases are present in the endoplasmic reticulum (ER) and Golgi complex and are required to generate complex N-glycans. However, lower eukaryotes such Saccharomyces cerevisiae contain only one alpha1,2-mannosidase in the lumen of the ER and synthesise high-mannose N-glycans. Little is known about the N-glycan structure and the enzyme machinery involved in the synthesis of these oligosaccharides in the dimorphic fungus Sporothrix schenckii. Here, a membrane-bound alpha-mannosidase from S. schenckii was solubilised using a high-temperature procedure and purified by conventional methods of protein isolation. Analytical zymograms revealed a polypeptide of 75 kDa to be responsible for enzyme activity and this purified protein was recognised by anti-alpha1,2-mannosidase antibodies. The enzyme hydrolysed Man(9)GlcNAc(2) into Man(8)GlcNAc(2) isomer B and was inhibited preferentially by 1-deoxymannojirimycin. This alpha1,2-mannosidase was localised in the ER, with the catalytic domain within the lumen of this compartment. These properties are consistent with an ER-localised alpha1,2-mannosidase of glycosyl hydrolase family 47. Our results also suggested that in contrast to other filamentous fungi, S. schenckii lacks Golgi alpha1,2-mannosidases and therefore, the processing of N-glycans by alpha1,2-mannosidases is similar to that present in lower eukaryotes.
- Published
- 2010
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.