22 results on '"Castellà, Maria"'
Search Results
2. What will (and should) be improved in CAR immunotherapy?
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González-Navarro, Europa Azucena, primary, Español, Marta, additional, Egri, Natalia, additional, Castellà, Maria, additional, Calderón, Hugo, additional, España, Carolina, additional, Guijarro, Carla, additional, Heredia, Libertad, additional, Pascal, Mariona, additional, and Juan Otero, Manel, additional
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- 2022
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3. The academic point‐of‐care anti‐CD19 chimeric antigen receptor T‐cell product varnimcabtagene autoleucel (ARI‐0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B‐cell non‐Hodgkin lymphoma
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Martínez‐Cibrián, Núria, Ortiz‐Maldonado, Valentín, Español‐Rego, Marta, Blázquez, Andrea, Cid, Joan, Lozano, Miquel, Magnano, Laura, Giné, Eva, Correa, Juan G., Mozas, Pablo, Rodríguez‐Lobato, Luis Gerardo, Rivero, Andrea, Montoro‐Lorite, Mercedes, Ayora, Pilar, Navarro, Sergio, Alserawan, Leticia, González‐Navarro, E. Azucena, Castellà, Maria, Sánchez‐Castañón, María, and Cabezón, Raquel
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CHIMERIC antigen receptors ,NON-Hodgkin's lymphoma ,CYTOKINE release syndrome ,T cells ,HOCKEY - Abstract
Summary: Varnimcabtagene autoleucel (var‐cel) is an academic anti‐CD19 chimeric antigen receptor (CAR) product used for the treatment of non‐Hodgkin lymphoma (NHL) in the CART19‐BE‐01 trial. Here we report updated outcomes of patients with NHL treated with var‐cel. B‐cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL). Forty‐five patients with NHL were treated. Cytokine release syndrome (any grade) occurred in 84% of patients (4% grade ≥3) and neurotoxicity in 7% (2% grade ≥3). The objective response rate was 73% at Day +100, and the 3‐year duration of response was 56%. The 3‐year progression‐free and overall survival were 40% and 52% respectively. High lactate dehydrogenase was the only covariate with an impact on progression‐free survival. The 3‐year incidence of B‐cell recovery was lower in patients with NHL compared to ALL (25% vs. 60%). In conclusion, in patients with NHL, the toxicity of var‐cel was manageable, while B‐cell recovery was significantly prolonged compared to ALL. This trial was registered as NCT03144583. [ABSTRACT FROM AUTHOR]
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- 2024
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4. The academic point‐of‐care anti‐CD19 chimeric antigen receptor T‐cell product varnimcabtagene autoleucel (ARI‐0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B‐cell non‐Hodgkin lymphoma
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Martínez‐Cibrián, Núria, primary, Ortiz‐Maldonado, Valentín, additional, Español‐Rego, Marta, additional, Blázquez, Andrea, additional, Cid, Joan, additional, Lozano, Miquel, additional, Magnano, Laura, additional, Giné, Eva, additional, Correa, Juan G., additional, Mozas, Pablo, additional, Rodríguez‐Lobato, Luis Gerardo, additional, Rivero, Andrea, additional, Montoro‐Lorite, Mercedes, additional, Ayora, Pilar, additional, Navarro, Sergio, additional, Alserawan, Leticia, additional, González‐Navarro, E. Azucena, additional, Castellà, Maria, additional, Sánchez‐Castañón, María, additional, Cabezón, Raquel, additional, Benítez‐Ribas, Daniel, additional, Setoaín, Xavier, additional, Rodríguez, Sonia, additional, Brillembourg, Helena, additional, Varea, Sara, additional, Olesti, Eulalia, additional, Guillén, Elena, additional, Sáez‐Peñataro, Joaquín, additional, de Larrea, Carlos Fernández, additional, López‐Guillermo, Armando, additional, Pascal, Mariona, additional, Urbano‐Ispizua, Álvaro, additional, Juan, Manel, additional, and Delgado, Julio, additional
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- 2023
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5. Data from Overcoming CAR-Mediated CD19 Downmodulation and Leukemia Relapse with T Lymphocytes Secreting Anti-CD19 T-cell Engagers
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Blanco, Belén, primary, Ramírez-Fernández, Ángel, primary, Bueno, Clara, primary, Argemí-Muntadas, Lidia, primary, Fuentes, Patricia, primary, Aguilar-Sopeña, Óscar, primary, Gutierrez-Agüera, Francisco, primary, Zanetti, Samanta Romina, primary, Tapia-Galisteo, Antonio, primary, Díez-Alonso, Laura, primary, Segura-Tudela, Alejandro, primary, Castellà, Maria, primary, Marzal, Berta, primary, Betriu, Sergi, primary, Harwood, Seandean L., primary, Compte, Marta, primary, Lykkemark, Simon, primary, Erce-Llamazares, Ainhoa, primary, Rubio-Pérez, Laura, primary, Jiménez-Reinoso, Anaïs, primary, Domínguez-Alonso, Carmen, primary, Neves, Maria, primary, Morales, Pablo, primary, Paz-Artal, Estela, primary, Guedan, Sonia, primary, Sanz, Laura, primary, Toribio, María L., primary, Roda-Navarro, Pedro, primary, Juan, Manel, primary, Menéndez, Pablo, primary, and Álvarez-Vallina, Luis, primary
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- 2023
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6. Supplementary Data from Overcoming CAR-Mediated CD19 Downmodulation and Leukemia Relapse with T Lymphocytes Secreting Anti-CD19 T-cell Engagers
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Blanco, Belén, primary, Ramírez-Fernández, Ángel, primary, Bueno, Clara, primary, Argemí-Muntadas, Lidia, primary, Fuentes, Patricia, primary, Aguilar-Sopeña, Óscar, primary, Gutierrez-Agüera, Francisco, primary, Zanetti, Samanta Romina, primary, Tapia-Galisteo, Antonio, primary, Díez-Alonso, Laura, primary, Segura-Tudela, Alejandro, primary, Castellà, Maria, primary, Marzal, Berta, primary, Betriu, Sergi, primary, Harwood, Seandean L., primary, Compte, Marta, primary, Lykkemark, Simon, primary, Erce-Llamazares, Ainhoa, primary, Rubio-Pérez, Laura, primary, Jiménez-Reinoso, Anaïs, primary, Domínguez-Alonso, Carmen, primary, Neves, Maria, primary, Morales, Pablo, primary, Paz-Artal, Estela, primary, Guedan, Sonia, primary, Sanz, Laura, primary, Toribio, María L., primary, Roda-Navarro, Pedro, primary, Juan, Manel, primary, Menéndez, Pablo, primary, and Álvarez-Vallina, Luis, primary
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- 2023
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7. Overcoming CAR-Mediated CD19 Downmodulation and Leukemia Relapse with T Lymphocytes Secreting Anti-CD19 T-cell Engagers
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Blanco, Belén, primary, Ramírez-Fernández, Ángel, additional, Bueno, Clara, additional, Argemí-Muntadas, Lidia, additional, Fuentes, Patricia, additional, Aguilar-Sopeña, Óscar, additional, Gutierrez-Agüera, Francisco, additional, Zanetti, Samanta Romina, additional, Tapia-Galisteo, Antonio, additional, Díez-Alonso, Laura, additional, Segura-Tudela, Alejandro, additional, Castellà, Maria, additional, Marzal, Berta, additional, Betriu, Sergi, additional, Harwood, Seandean L., additional, Compte, Marta, additional, Lykkemark, Simon, additional, Erce-Llamazares, Ainhoa, additional, Rubio-Pérez, Laura, additional, Jiménez-Reinoso, Anaïs, additional, Domínguez-Alonso, Carmen, additional, Neves, Maria, additional, Morales, Pablo, additional, Paz-Artal, Estela, additional, Guedan, Sonia, additional, Sanz, Laura, additional, Toribio, María L., additional, Roda-Navarro, Pedro, additional, Juan, Manel, additional, Menéndez, Pablo, additional, and Álvarez-Vallina, Luis, additional
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- 2022
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8. Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations
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Castella, Maria, Pujol, Roser, Callén, Elsa, Trujillo, Juan P., Casado, José A., Gille, Hans, Lach, Francis P., Auerbach, Arleen D., Schindler, Detlev, Benítez, Javier, Porto, Beatriz, Ferro, Teresa, Muñoz, Arturo, Sevilla, Julián, Madero, Luis, Cela, Elena, Beléndez, Cristina, de Heredia, Cristina Díaz, Olivé, Teresa, de Toledo, José Sánchez, Badell, Isabel, Torrent, Montserrat, Estella, Jesús, Dasí, Ángeles, Rodríguez-Villa, Antonia, Gómez, Pedro, Barbot, José, Tapia, María, Molinés, Antonio, Figuera, Ángela, Bueren, Juan A., and Surrallés, Jordi
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- 2011
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9. In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1
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Río, Paula, Meza, Néstor W., González-Murillo, África, Navarro, Susana, Álvarez, Lara, Surrallés, Jordi, Castella, Maria, Guenechea, Guillermo, Segovia, José C., Hanenberg, Helmut, and Bueren, Juan A.
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- 2008
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10. CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies
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Ortíz-Maldonado, Valentín, primary, Rives, Susana, additional, Castellà, Maria, additional, Alonso-Saladrigues, Anna, additional, Benítez-Ribas, Daniel, additional, Caballero-Baños, Miguel, additional, Baumann, Tycho, additional, Cid, Joan, additional, Garcia-Rey, Enric, additional, Llanos, Cristina, additional, Torrebadell, Montserrat, additional, Villamor, Neus, additional, Giné, Eva, additional, Díaz-Beyá, Marina, additional, Guardia, Laia, additional, Montoro, Mercedes, additional, Català, Albert, additional, Faura, Anna, additional, González, E. Azucena, additional, Español-Rego, Marta, additional, Klein-González, Nela, additional, Alsina, Laia, additional, Castro, Pedro, additional, Jordan, Iolanda, additional, Fernández, Sara, additional, Ramos, Federico, additional, Suñé, Guillermo, additional, Perpiñá, Unai, additional, Canals, Josep M., additional, Lozano, Miquel, additional, Trias, Esteve, additional, Scalise, Andrea, additional, Varea, Sara, additional, Sáez-Peñataro, Joaquín, additional, Torres, Ferran, additional, Calvo, Gonzalo, additional, Esteve, Jordi, additional, Urbano-Ispizua, Álvaro, additional, Juan, Manel, additional, and Delgado, Julio, additional
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- 2021
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11. 41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo
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Libero Baroni, Matteo, Sánchez Martínez, Diego, Gutiérrez-Agüera, Francisco, Roca Ho, Heleia, Castellà, Maria, Zanetti, S. R., Velasco-Hernández, Talia, Díaz de la Guardia, Rafael, Castaño Cardoso, Julio, Anguita, Eduardo, Vives, S., Nomdedeu, Josep, Lapillone, H., Bras, A. E., van der Velden, V. H. J., Junca, Jordi, Marin, P., Bataller, Alex, Esteve Reyner, Jordi, Vick, B., Jeremias, I., Lopez, A., Sorigue, Marc, Bueno, Clara, Menéndez, Pablo, Universitat Autònoma de Barcelona, and Immunology
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Cancer Research ,Myeloid ,medicine.medical_treatment ,Immunology ,T lymphocytes ,Immunotherapy, adoptive ,cell engineering ,adoptive ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,hemic and lymphatic diseases ,immunotherapy, adoptive ,Immunology and Allergy ,Medicine ,Progenitor cell ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Immune Cell Therapies and Immune Cell Engineering ,business.industry ,Cell engineering ,Myeloid leukemia ,Immunotherapy ,Chimeric antigen receptor ,Cell Engineering ,Adoptive ,T Lymphocytes ,3. Good health ,Haematopoiesis ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Interleukin-3 receptor ,immunotherapy ,business - Abstract
Altres ajuts: We thank CERCA/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for their institutional support. PM acknowledges financial support from theSpanish Cancer Research Association (AECC-Semilla19), the Fundación Uno entre Cienmil, the Obra Social La Caixa (LCF/PR/HR19/52160011), the Leo Messi Foundation, the Banco Santander Foundation and the "Heroes hasta la médula" initiative. BACKGROUND: Acute myeloid leukemia (AML) is a hematopoietic malignancy which is biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies for patients with refractory or relapse (R/R) AML are challenging because of the absence of a universal pan-AML target antigen and the shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs), which may lead to life-threating on-target/off-tumor cytotoxicity. CD33-redirected and CD123-redirected CARTs for AML are in advanced preclinical and clinical development, and they exhibit robust antileukemic activity. However, preclinical and clinical controversy exists on whether such CARTs are myeloablative. METHODS: We set out to comparatively characterize in vitro and in vivo the efficacy and safety of 41BB-based and CD28-based CARCD123. We analyzed 97 diagnostic and relapse AML primary samples to investigate whether CD123 is a suitable immunotherapeutic target, and we used several xenograft models and in vitro assays to assess the myeloablative potential of our second-generation CD123 CARTs. RESULTS: Here, we show that CD123 represents a bona fide target for AML and show that both 41BB-based and CD28-based CD123 CARTs are very efficient in eliminating both AML cell lines and primary cells in vitro and in vivo. However, both 41BB-based and CD28-based CD123 CARTs ablate normal human hematopoiesis and prevent the establishment of de novo hematopoietic reconstitution by targeting both immature and myeloid HSPCs. CONCLUSIONS: This study calls for caution when clinically implementing CD123 CARTs, encouraging its preferential use as a bridge to allo-HSCT in patients with R/R AML.
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- 2020
12. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells
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Raya, Ángel, Rodríguez-Pizà, Ignasi, Guenechea, Guillermo, Vassena, Rita, Navarro, Susana, Barrero, María José, Consiglio, Antonella, Castellà, Maria, Río, Paula, Sleep, Eduard, González, Federico, Tiscornia, Gustavo, Garreta, Elena, Aasen, Trond, Veiga, Anna, Verma, Inder M., Surrallés, Jordi, Bueren, Juan, and Belmonte, Juan Carlos Izpisúa
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- 2009
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13. Chimeric Antigen Receptor T Cells Targeting CD19 and Ibrutinib for Chronic Lymphocytic Leukemia
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Delgado, Julio, primary, Caballero-Baños, Miguel, additional, Ortiz-Maldonado, Valentín, additional, Castellà, Maria, additional, Magnano, Laura, additional, Juan, Manel, additional, and Urbano-Ispizua, Álvaro, additional
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- 2019
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14. Future of Chimeric Antigen Receptors (Cars): Could it Drive Solutions Beyond Cancer? Examples in Autoimmune Diseases
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Español-Rego Marta, Marzal Berta, Castellà Maria, Boronat Anna, and Llobell Arturo
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0301 basic medicine ,medicine.medical_treatment ,Cancer ,Immunotherapy ,Biology ,medicine.disease_cause ,medicine.disease ,Chimeric antigen receptor ,Immunopharmacology ,Autoimmunity ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neuroimmunology ,Immune system ,Antigen ,Immunology ,medicine ,030215 immunology - Published
- 2017
15. CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+Relapsed/Refractory Malignancies
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Ortíz-Maldonado, Valentín, Rives, Susana, Castellà, Maria, Alonso-Saladrigues, Anna, Benítez-Ribas, Daniel, Caballero-Baños, Miguel, Baumann, Tycho, Cid, Joan, Garcia-Rey, Enric, Llanos, Cristina, Torrebadell, Montserrat, Villamor, Neus, Giné, Eva, Díaz-Beyá, Marina, Guardia, Laia, Montoro, Mercedes, Català, Albert, Faura, Anna, González, E. Azucena, Español-Rego, Marta, Klein-González, Nela, Alsina, Laia, Castro, Pedro, Jordan, Iolanda, Fernández, Sara, Ramos, Federico, Suñé, Guillermo, Perpiñá, Unai, Canals, Josep M., Lozano, Miquel, Trias, Esteve, Scalise, Andrea, Varea, Sara, Sáez-Peñataro, Joaquín, Torres, Ferran, Calvo, Gonzalo, Esteve, Jordi, Urbano-Ispizua, Álvaro, Juan, Manel, and Delgado, Julio
- Abstract
We evaluated the administration of ARI-0001 cells (chimeric antigen receptor T cells targeting CD19) in adult and pediatric patients with relapsed/refractory CD19+malignancies. Patients received cyclophosphamide and fludarabine followed by ARI-0001 cells at a dose of 0.4–5 × 106ARI-0001 cells/kg, initially as a single dose and later split into 3 fractions (10%, 30%, and 60%) with full administration depending on the absence of cytokine release syndrome (CRS). 58 patients were included, of which 47 received therapy: 38 with acute lymphoblastic leukemia (ALL), 8 with non-Hodgkin’s lymphoma, and 1 with chronic lymphocytic leukemia. In patients with ALL, grade ≥3 CRS was observed in 13.2% (26.7% before versus 4.3% after the amendment), grade ≥3 neurotoxicity was observed in 2.6%, and the procedure-related mortality was 7.9% at day +100, with no procedure-related deaths after the amendment. The measurable residual disease-negative complete response rate was 71.1% at day +100. Progression-free survival was 47% (95% IC 27%–67%) at 1 year: 51.3% before versus 39.5% after the amendment. Overall survival was 68.6% (95% IC 49.2%–88%) at 1 year. In conclusion, the administration of ARI-0001 cells provided safety and efficacy results that are comparable with other academic or commercially available products. This trial was registered as ClinicalTrials.gov: NCT03144583.
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- 2021
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16. Monsieur André Aubusson, Secretary of great merit of the Committee of Public Safety, or the control of correspondence in the first year of the Republic (part 2)
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Castellà, Maria Betlem and Universitat Pompeu Fabra [Barcelona] (UPF)
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Comité des pétitions et de correspondance ,[SHS.SOCIO]Humanities and Social Sciences/Sociology ,commis ,secrétaires ,General Secretariat of the executive Directory ,Committee on Petitions and Correspondence ,Comité de salut public ,[SHS.SCIPO]Humanities and Social Sciences/Political science ,Committee of Public Safety ,Secretary-clerks ,Commission des dépêches ,[SHS.DROIT]Humanities and Social Sciences/Law ,André Aubusson ,[SHS.HIST]Humanities and Social Sciences/History ,Commission of Dispatches ,Secrétariat général du Directoire exécutif - Abstract
Varia; International audience; In following the professional progress of a former military man, André Aubusson, who began to take charge of the correspondence received by the legislature in the first days of the revolutionary process, who was appointed the principal secretary of the Committee of Public Safety in September 1793, and who went on to become section head of the General Secretariat of the executive Directory on 13 Brumaire of Year IV, the purpose of the present article—which is in fact the second part of an earlier study published under the title “Monsieur André Aubusson, the man who knew everything, or the control of the correspondence under the parliamentary assemblies”, is to explain who managed the correspondence, and how, during the first year of the Republic; the impact that the setting up of the Committee of Public Safety had on the filters put in place to manage that correspondence; the professional career of Mr. Aubusson in the National Convention and the Executive Directory, and the continuity that can be identified within the body of administrative staff in the offices and committees responsible for managing correspondence under the different parliamentary assemblies. The deputies were replaced from time to time, but the secretary-clerks who worked there, as some of them had since the first days of the Constituent Assembly, were not, and thus constituted a corps of experienced personnel who continued to perform their functions throughout the first three Assemblies, and in some cases, in the years that followed.; En suivant l’ascension professionnelle d’un ancien militaire, M. André Aubusson, qui commença à gérer la correspondance reçue par le corps législatif dès les premiers jours du processus révolutionnaire, fût nommé secrétaire principal du Comité de salut public au mois de septembre 1793 et finit par devenir le chef de la division du Secrétariat général du Directoire exécutif le 13 brumaire de l’an IV, nous voulons expliquer dans cet article, qui est en fait la deuxième partie d’un autre travail publié sous le titre : « Monsieur André Aubusson, l’homme qui sait tout, ou gérer la correspondance sous les assemblées parlementaires », qui gérait la correspondance, et comment, sous la première année de la République, l’impact que l’établissement du Comité de salut public eut sur les filtres établis sur la correspondance, le parcours professionnel de M. Aubusson sous la Convention nationale et le Directoire ainsi que la continuité qu’on peut apprécier d’un même personnel administratif dans le cadre des bureaux et des comités qui s’occupent de gérer la correspondance sous les différentes assemblées parlementaires. Les députés sont renouvelés de temps en temps, mais les secrétaires-commis qui y travaillent, certains d’entre eux depuis les premiers jours de l’Assemblée nationale constituante, ne le sont pas, configurant ainsi un corps d’employés expérimentés qui conservent leurs fonctions au long des trois premières assemblées, et parfois, dans les années qui suivent.
- Published
- 2015
17. New Antibcma-CAR for Multiple Myeloma
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Perez Amill, Lorena, Suñe Rodriguez, Guillermo, Najjar, Amer, Castella Castella, Maria, Urbano-Ispizua, Alvaro, and Martin-Antonio, Beatriz
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- 2017
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18. Análisis de la variabilidad genética de la anemia de Fanconi en España
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Castellà Castellà, Maria, Surrallés i Calonge, Jordi, and Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia
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Ciències Experimentals ,Enfermedades raras ,Mutaciones ,Anemia de Fanconi - Abstract
La anemia de Fanconi (FA) se caracteriza por malformaciones, fallo medular progresivo y predisposición al cáncer. El transplante de médula es actualmente la única opción terapéutica aunque incrementa el riesgo oncológico y son pocos los pacientes con donante compatible lo que ha promovido la investigación en terapia génica y medicina regenerativa basada en reprogramación celular de fibroblastos de pacientes FA a celulas madre pluripotentes (iPS). Son 12 los genes Fanconi hasta ahora descritos, 3 de ellos implicados en predisposición al cancer en portadores (FANCD1/BRCA2, PALB2 y BRIP1). La FA se caracteriza por fragilidad cromosómica lo que se utiliza como herramienta diagnóstica. El objetivo de esta tesis es el análisis de la variabilidad en cuanto al fenotipo celular y clínico de los pacientes de AF en España y la determinación de la contribución de la variabilidad genética dentro de los propios genes FA. Los resultados de los primeros 200 test de fragilidad cromosómica realizados en el grupo ha permitido cuantificar la variabilidad interindividual, establecer niveles umbral y determinar que el 15% de los pacientes FA presentan mosaicismo somático. Se ha determinado que la fragilidad espontánea de los pacientes se debe también a horquillas de replicación bloqueadas, ya que correlaciona con la fragilidad inducida por DEB. En cuanto a la caracterización genética de la población española de pacientes, se ha completado los estudios de subtipaje en 102 familias. Este estudio ha revelado que el 75% de los pacientes españoles pertenecen al grupo de complementación FA-A. Una vez completado el subtipaje, se ha determinado el espectro mutacional de la población. Se ha completado el estudio en 66 pacientes FA-A y se han determinado las mutaciones más frecuentes, creando, a partir de estos resultados, un protocolo para la optimización del análisis mutacional en los pacientes españoles. También se han caracterizado molecular y funcionalmente, algunas de las mutaciones encontradas, como la determinación del haplotipo asociado a la mutación más frecuente, la determinación de los puntos de rotura de una gran deleción para determinar el mecanismo molecular que la originó y también el estudio funcional de las mutaciones no truncadoras encontradas. Se ha determinado que el subtipo genético condiciona la sensibilidad celular de los pacientes a agentes inductores de ICLs, mientras que el tipo de mutación (truncadora/no truncadora) no tendría relevancia. Del mismo modo, el tipo de mutación parece no condicionar el fenotipo clínico de los pacientes. Se ha determinado que la incapacidad de las células de reparar los enlaces intercruzantes en el ADN es directamente responsable de las malformaciones congénitas que presentan los pacientes, mientras que la evolución hematológica estaría condicionada por otros factores. Finalmente, se ha llevado a cabo un estudio de proteómica diferencial para determinar proteínas y procesos celulares que se encuentran desregulados en las células FA, y así determinar que otros factores podrían ser responsables del fenotipo de los pacientes. En este estudio se han encontrado varias proteínas implicadas en la respuesta a IFN-gamma, metabolismo oxidativo, homeostasis mitocondrial, transporte intracelular y procesamiento del ARN., Fanconi anemia (FA) is characterized by congenital malformations, bone marrow failure and predisposition to cancer. Bone marrow transplant is the only possible treatment to overcome haematological disease, even if it increases the risk of cancer and not all patients have a compatible donor. These facts promoted the development of clinical protocols for gene therapy and regenerative medicine based on reprogramming fibroblast cells from FA patients to hematopoietic stem cells. There are 12 known genes causing FA, 3 of them involved also in predisposition to breast/ovarian cancer (FANCD1/BRCA2, PALB2 and BRIP1). FA is characterized by chromosome instability. Therefore, this endpoint is used in diagnosis. The aim of this thesis is to analyze the variability associated to cellular and clinical phenotype of FA patients and its relationship to genetic variability found in FA genes. We have performed 200 chromosome fragility tests. This analysis allowed the determination of interindividual variability, creation of diagnostic thresholds and the identification of FA mosaic patients (15%). We have seen that spontaneous chromosome fragility correlates to DEB-induced chromosome fragility, indicating that spontaneous DNA damage is also due to stalled replication forks. We have genetically characterized the Spanish FA population, including subtype determination and mutational analysis. Subtyping analysis of 102 Spanish FA families showed that FA-A group is the most frequent, accounting for 75% of patients. Once complementation group is defined, we conducted mutational analysis. We completed the study on 66 FA-A patients, to uncover the Spanish mutational spectrum for this gene. Several frequent mutations were found. Based on these results, we created a work-flow that allows optimization of mutation analysis on Spanish patients. We also characterized some of the mutations found at the molecular and functional level: we determined the haplotype associated to the most frequent mutation on this gene, we found the breakpoints for a large deletion so that the molecular mechanism responsible for the origination of this deletion was revelled and, finally, we performed functional analysis of non-truncating mutations. We showed that genetic subtype conditions cellular sensitivity to ICLs, while mutation type (truncating/non-truncating) does not seem to play an important role. In a similar way, mutation type does not influence severity of clinical phenotype. We have seen that FA cell inability to resolve stalled replication forks is directly responsible for congenital malformations seen in FA patients, while hematologic evolution seems to be conditioned by other factors. Finally, we also conducted a study of differential proteomics to look for differentially expressed proteins and subsequent altered cellular processes. These processes could be responsible for part of the FA patients' phenotype. In this study we found several proteins involved in response to gamma-IFN, oxidative metabolism, mitochondrial homeostasis, intracellular transport and RNA processing.
- Published
- 2009
19. Análisis de la variabilidad genética de la anemia de Fanconi en España
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Surrallés i Calonge, Jordi, Castellà Castellà, Maria, Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia, Surrallés i Calonge, Jordi, Castellà Castellà, Maria, and Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia
- Abstract
Descripció del recurs: el 10 d'agost de 2010, La anemia de Fanconi (FA) se caracteriza por malformaciones, fallo medular progresivo y predisposición al cáncer. El transplante de médula es actualmente la única opción terapéutica aunque incrementa el riesgo oncológico y son pocos los pacientes con donante compatible lo que ha promovido la investigación en terapia génica y medicina regenerativa basada en reprogramación celular de fibroblastos de pacientes FA a celulas madre pluripotentes (iPS). Son 12 los genes Fanconi hasta ahora descritos, 3 de ellos implicados en predisposición al cancer en portadores (FANCD1/BRCA2, PALB2 y BRIP1). La FA se caracteriza por fragilidad cromosómica lo que se utiliza como herramienta diagnóstica. El objetivo de esta tesis es el análisis de la variabilidad en cuanto al fenotipo celular y clínico de los pacientes de AF en España y la determinación de la contribución de la variabilidad genética dentro de los propios genes FA. Los resultados de los primeros 200 test de fragilidad cromosómica realizados en el grupo ha permitido cuantificar la variabilidad interindividual, establecer niveles umbral y determinar que el 15% de los pacientes FA presentan mosaicismo somático. Se ha determinado que la fragilidad espontánea de los pacientes se debe también a horquillas de replicación bloqueadas, ya que correlaciona con la fragilidad inducida por DEB. En cuanto a la caracterización genética de la población española de pacientes, se ha completado los estudios de subtipaje en 102 familias. Este estudio ha revelado que el 75% de los pacientes españoles pertenecen al grupo de complementación FA-A. Una vez completado el subtipaje, se ha determinado el espectro mutacional de la población. Se ha completado el estudio en 66 pacientes FA-A y se han determinado las mutaciones más frecuentes, creando, a partir de estos resultados, un protocolo para la optimización del análisis mutacional en los pacientes españoles. También se han caracterizado molecular y funcionalmente, algunas de las mutaciones encontra
- Published
- 2010
20. Histone H2AX and Fanconi anemia FANCD2 function in the same pathway to maintain chromosome stability
- Author
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Bogliolo, Massimo, primary, Lyakhovich, Alex, additional, Callén, Elsa, additional, Castellà, Maria, additional, Cappelli, Enrico, additional, Ramírez, María J, additional, Creus, Amadeu, additional, Marcos, Ricard, additional, Kalb, Reinhard, additional, Neveling, Kornelia, additional, Schindler, Detlev, additional, and Surrallés, Jordi, additional
- Published
- 2007
- Full Text
- View/download PDF
21. Methylen Blue Photoinactivated Plasma vs Fresh Frozen Plasma in Thrombotic Thrombocytopenic Purpura Treatment: A Multicentric Prospective Cohort Study.
- Author
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Alvarez-Larrán, Alberto, Del Río-Garma, Julio, de la Rubia, Javier, Zamora, Concepción, Galmés, Antonio, Ramírez, Consuelo, Rodríguez-Vicente, Pilar, Martínez, Clara, Alegre, Adrian, Viejo, Aurora, Arbona, Cristina, Serrano, Alfons, Castellá, María Dolors, Corral, Mercedes, Peña, Francisco, and Pereira, Arturo
- Published
- 2007
- Full Text
- View/download PDF
22. CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19 + Relapsed/Refractory Malignancies.
- Author
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Ortíz-Maldonado V, Rives S, Castellà M, Alonso-Saladrigues A, Benítez-Ribas D, Caballero-Baños M, Baumann T, Cid J, Garcia-Rey E, Llanos C, Torrebadell M, Villamor N, Giné E, Díaz-Beyá M, Guardia L, Montoro M, Català A, Faura A, González EA, Español-Rego M, Klein-González N, Alsina L, Castro P, Jordan I, Fernández S, Ramos F, Suñé G, Perpiñá U, Canals JM, Lozano M, Trias E, Scalise A, Varea S, Sáez-Peñataro J, Torres F, Calvo G, Esteve J, Urbano-Ispizua Á, Juan M, and Delgado J
- Subjects
- Cell- and Tissue-Based Therapy, Drug Resistance, Neoplasm, Female, Humans, Male, Neoplasm Grading, Neoplasm Staging, Neoplasms pathology, Recurrence, T-Lymphocytes metabolism, Antigens, CD19 immunology, Immunotherapy, Adoptive, Neoplasms immunology, Neoplasms therapy, Receptors, Chimeric Antigen immunology, T-Lymphocytes immunology
- Abstract
We evaluated the administration of ARI-0001 cells (chimeric antigen receptor T cells targeting CD19) in adult and pediatric patients with relapsed/refractory CD19
+ malignancies. Patients received cyclophosphamide and fludarabine followed by ARI-0001 cells at a dose of 0.4-5 × 106 ARI-0001 cells/kg, initially as a single dose and later split into 3 fractions (10%, 30%, and 60%) with full administration depending on the absence of cytokine release syndrome (CRS). 58 patients were included, of which 47 received therapy: 38 with acute lymphoblastic leukemia (ALL), 8 with non-Hodgkin's lymphoma, and 1 with chronic lymphocytic leukemia. In patients with ALL, grade ≥3 CRS was observed in 13.2% (26.7% before versus 4.3% after the amendment), grade ≥3 neurotoxicity was observed in 2.6%, and the procedure-related mortality was 7.9% at day +100, with no procedure-related deaths after the amendment. The measurable residual disease-negative complete response rate was 71.1% at day +100. Progression-free survival was 47% (95% IC 27%-67%) at 1 year: 51.3% before versus 39.5% after the amendment. Overall survival was 68.6% (95% IC 49.2%-88%) at 1 year. In conclusion, the administration of ARI-0001 cells provided safety and efficacy results that are comparable with other academic or commercially available products. This trial was registered as ClinicalTrials.gov: NCT03144583., (Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
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