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Your search keyword '"García Frade, Javier"' showing total 33 results
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33 results on '"García Frade, Javier"'

1. Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma

Author

Casanova Espinosa, María, Zamudio, José Luís Guzman, Ríos Herranz, Eduardo, Rios Tamayo, Rafael, Martín Sánchez, Jesús, Palomera Bernal, Luís, González Rodríguez, Ana Pilar, González García, María Esther, Mayol, Antonia Sampol, Bargay Lleonart, Joan, Suárez, Alexia, Hernández García, Miguel Teodoro, Gaisán, Carmen Montes, Hernández Ruiz, Belén, Casado Montero, Felipe, Miguel Llorente, Dunia de, Ramos, Fernando Solano, Ibañez Garcia, Ángela, Manteca, Mariví Mateos, Mariano Hernández Martín, José, Escalante Barrigón, Fernando, García Frade, Javier, de Coca, Alfonso García, Franco, Carlos Aguilar, Labrador Gómez, Jorge, Cabezudo Pérez, Elena, Bladé Creixentí, Joan, Balari, Ana M<ce:sup loc='post">a</ce:sup> Sureda, González Montes, Yolanda, Teigell, Lourdes Escoda, García Guiñón, Antonio, Abella Monreal, Eugenia, Alfonso Soler Campos, Juan, Martí Tutusaus, Josep M<ce:sup loc='post">a</ce:sup>, Rocafiguera, Albert Oriol, Gorrochategui, Miquel Granell, Mesa, Mercedes Gironella, Silva, Carmen Cabrera, González Pérez, Marta Sonia, Loureiro, Ana Dios, Méndez Sánchez, José Angel, Irazu, María Josefa Nájera, Párraga, Francisco Javier Peñalver, Lahuerta Palacios, Juan José, Barahona, Pilar Bravo, Rodríguez, Cristina Encinas, Hernández Rivas, José Ángel, Oteyza, Jaime Pérez de, Iglesias del Barrio, Rebeca, López de la Guia, Ana, Amor, Adrián Alegre, Prieto Pareja, Elena, Castelló, Isabel Krsnik, Blanchard Rodríguez, M<ce:sup loc='post">a</ce:sup> Jesús, Martínez Martínez, Rafael, Riaza Grau, Rosalía, Mesa, Eugenio Giménez, Ruiz Sainz, Elena, Arriba, Felipe de, Moraleda Jiménez, Jose María, Romera, Marta, Cardoso, Felipe Prósper, Arguiñano Pérez, José M<ce:sup loc='post">a</ce:sup>, Pomposo, María Puente, Pérez Persona, Ernesto, Teruel Casasús, Ana Isabel, García, Paz Ribas, Jarque Ramos, Isidro, Villarrubia Lor, María Blanca, Fernández García, Pedro Luis, Martínez Chamorro, Carmen, Guerrero, Camila, Puig, Noemi, Cedena, María-Teresa, Calasanz, María-José, Gutierrez, Norma C., Fernandez, Manuela, Oriol, Albert, Ríos-Tamayo, Rafael, Hernandez, Miguel-Teodoro, Martínez-Martínez, Rafael, Bargay, Joan, de Arriba, Felipe, Palomera, Luis, Gonzalez-Rodriguez, Ana Pilar, Gonzalez Perez, Marta-Sonia, Orfao, Alberto, Mateos, María-Victoria, Martinez-Lopez, Joaquin, Rosiñol, Laura, Bladé, Joan, Lahuerta, Juan-Jose, San-Miguel, Jesus F., and Paiva, Bruno

Published
2024
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3. Use of eltrombopag for secondary immune thrombocytopenia in clinical practice

Author

González‐López, Tomás J., Alvarez‐Román, María T., Pascual, Cristina, Sánchez‐González, Blanca, Fernández‐Fuentes, Fernando, Pérez‐Rus, Gloria, Hernández‐Rivas, José A., Bernat, Silvia, Bastida, José M., Martínez‐Badas, María P., Martínez‐Robles, Violeta, Soto, Inmaculada, Olivera, Pavel, Bolaños, Estefanía, Alonso, Rafael, Entrena, Laura, Gómez‐Nuñez, Marta, Alonso, Arancha, Yera Cobo, María, Caparrós, Isabel, Tenorio, María, Arrieta‐Cerdán, Esther, Lopez‐Ansoar, Elsa, García‐Frade, Javier, and González‐Porras, José R.

Published
2017
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4. Comparison of Neointimal Hyperplasia With Drug-Eluting Stents Versus Bare Metal Stents in Patients Undergoing Intracoronary Bone-Marrow Mononuclear Cell Transplantation Following Acute Myocardial Infarction

Author

Villa, Adolfo, Arnold, Roman, Sánchez, Pedro L., Gimeno, Federico, Ramos, Benigno, Cantero, Teresa, Fernández, Maria Eugenia, Sanz, Ricardo, Gutiérrez, Oliver, Mota, Pedro, García-Frade, Javier, San Román, José Alberto, and Fernández-Avilés, Francisco

Published
2009
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5. Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction—Angiographic and intravascular ultrasound—Results from the TErapia Celular Aplicada al Miocardio Pilot study

Author

Arnold, Roman, Villa, Adolfo, Gutiérrez, Hipólito, Sánchez, Pedro L., Gimeno, Federico, Fernández, Maria E., Gutiérrez, Oliver, Mota, Pedro, Sánchez, Ana, García-Frade, Javier, Fernández-Avilés, Francisco, and San Román, Jose A.

Published
2010

6. Unraveling the Influence of Common von Willebrand factor variants on von Willebrand Disease Phenotype: An Exploratory Study on the Molecular and Clinical Profile of von Willebrand Disease in Spain Cohort

Author

Borràs, Nina, additional, Garcia-Martínez, Iris, additional, Batlle, Javier, additional, Pérez-Rodríguez, Almudena, additional, Parra, Rafael, additional, Altisent, Carme, additional, López-Fernández, María Fernanda, additional, Costa Pinto, Joana, additional, Batlle-López, Fernando, additional, Cid, Ana Rosa, additional, Bonanad, Santiago, additional, Cabrera, Noelia, additional, Moret, Andrés, additional, Mingot-Castellano, María Eva, additional, Navarro, Nira, additional, Pérez-Montes, Rocío, additional, Marcellini, Shally, additional, Moreto, Ana, additional, Herrero, Sonia, additional, Soto, Inmaculada, additional, Fernández-Mosteirín, Núria, additional, Jiménez-Yuste, Víctor, additional, Alonso, Nieves, additional, de Andrés-Jacob, Aurora, additional, Fontanes, Emilia, additional, Campos, Rosa, additional, Paloma, María José, additional, Bermejo, Nuria, additional, Berrueco, Rubén, additional, Mateo, José, additional, Arribalzaga, Karmele, additional, Marco, Pascual, additional, Palomo, Ángeles, additional, Castro Quismondo, Nerea, additional, Iñigo, Belén, additional, del Mar Nieto, María, additional, Vidal, Rosa, additional, Martínez, María Paz, additional, Aguinaco, Reyes, additional, Tenorio, Maria, additional, Ferreiro, María, additional, García-Frade, Javier, additional, Rodríguez-Huerta, Ana María, additional, Cuesta, Jorge, additional, Rodríguez-González, Ramón, additional, García-Candel, Faustino, additional, Dobón, Manuela, additional, Aguilar, Carlos, additional, Corrales, Irene, additional, and Vidal, Francisco, additional

Published
2020
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7. Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Author

Borràs, Nina, Orriols, Gerard, Batlle, Javier, Pérez-Rodríguez, Almudena, Fidalgo, Teresa, Martinho, Patricia, López-Fernández, María Fernanda, Rodríguez-Trillo, Ángela, Lourés, Esther, Parra, Rafael, Altisent, Carme, Cid, Ana Rosa, Bonanad, Santiago, Cabrera, Noelia, Moret, Andrés, Mingot-Castellano, María Eva, Navarro, Nira, Pérez-Montes, Rocío, Marcellin, Sally, Moreto, Ana, Herrero, Sonia, Soto, Inmaculada, Fernández-Mosteirín, Núria, Jiménez-Yuste, Víctor, Alonso, Nieves, de Andrés-Jacob, Aurora, Fontanes, Emilia, Campos, Rosa, Paloma, María José, Bermejo, Nuria, Berrueco, Ruben, Mateo, José, Arribalzaga, Karmele, Marco, Pascual, Palomo, Ángeles, Quismondo, Nerea Castro, Iñigo, Belén, Nieto, María del Mar, Vidal, Rosa, Martínez, María Paz, Aguinaco, Reyes, Tenorio, Jesús María, Ferreiro, María, García-Frade, Javier, Rodríguez-Huerta, Ana María, Cuesta, Jorge, Rodríguez-González, Ramón, García-Candel, Faustino, Dobón, Manuela, Aguilar, Carlos, Vidal, Francisco, Corrales, Irene, and Universitat Autònoma de Barcelona

Subjects
Blood Platelets, Male, Genotype, RNA Splicing, Mutation, Missense, Biology, medicine.disease_cause, Article, DNA sequencing, Processamento de RNA, Exon, Gene Frequency, Von Willebrand factor, von Willebrand Factor, Leukocytes, medicine, Humans, Missense mutation, Gene Silencing, RNA, Messenger, Mutação, Alleles, Genetics, Hemostasis, Mutation, Base Sequence, Intron, Computational Biology, High-Throughput Nucleotide Sequencing, Exons, Hematology, Introns, Exon skipping, von Willebrand Diseases, RNA splicing, biology.protein, Female, RNA Splice Sites
Abstract

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074.

Published
2019

10. Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial

Author

González-Barca, E., Canales, M., Salar Silvestre, Antonio, Ferreiro-Martínez, J. J., Ferrer-Bordes, S., García-Marco, J. A., Sánchez-Blanco, J. J., García-Frade, Javier, Peñalver, Francisco-Javier, Bello-López, J. L., Sancho, José María, Caballero, Dolores, and GELTAMO Group

Subjects
Male, Oncology, Limfomes, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Risk Factors, Prednisone, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Injections, Spinal, Aged, 80 and over, Cytarabine, Diffuse large B-cell lymphoma, Hematology, General Medicine, Middle Aged, Survival Rate, Vincristine, 030220 oncology & carcinogenesis, Vomiting, Original Article, Female, Lymphoma, Large B-Cell, Diffuse, medicine.symptom, Rituximab, Post-Exposure Prophylaxis, medicine.drug, Adult, Antimetabolites, Antineoplastic, medicine.medical_specialty, Liposomal cytarabine, Adolescent, Cyclophosphamide, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Adverse effect, Survival rate, Aged, Sistema nerviós central, Prophylaxis, business.industry, medicine.disease, Surgery, Central nervous system, Doxorubicin, business, Follow-Up Studies, 030215 immunology
Abstract

The dissemination in the central nervous system (CNS) is an uncommon but fatal complication occurring in patients with diffuse large B-cell lymphoma (DLBCL). Standard prophylaxis has been demonstrated to reduce CNS relapse and improve survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated drug levels in the cerebrospinal fluid for an extended period of time. Data on the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients with DLBCL are still insufficient. The objective of the present study was to evaluate the effectiveness and safety of the prophylaxis with IT liposomal cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were included in a trial of first line systemic therapy with 6 cycles of dose-dense R-CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to have risk factors for CNS involvement, defined as follows: >30 % bone marrow infiltration, testes infiltration, retroperitoneal mass ≥10 cm, Waldeyer ring, or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R-CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were headache (one patient) and nausea/vomiting (one patient). With a median follow-up of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS prophylaxis, causing few associated risks and little discomfort to patients with DLBCL. The study was conducted with the help of a grant from BRedes Temáticas de Investigación Cooperativa en Cáncer (RTICC).

Published
2016

11. Role of multimeric analysis of von Willebrand factor (VWF) in von Willebrand disease (VWD) diagnosis: Lessons from the PCM-EVW-ES Spanish project

Author

Pérez-Rodríguez, Almudena, Batlle, Javier, Corrales Insa, Irene, Borràs, Nina, Rodríguez-Trillo, Ángela, Lourés, Esther, Cid, Ana Rosa, Bonanad, Santiago, Cabrera, Noelia, Moret, Andrés, Parra, Rafael, Mingot-Castellano, María Eva, Navarro, Nira, Altisent, Carmen, Pérez-Montes, Rocío, Marcellini, Shally, Moreto, Ana, Herrero, Sonia, Soto, Inmaculada, Fernández Mosteirín, Nuria, Jiménez-Yuste, Víctor, Alonso, Nieves, de Andrés Jacob, Aurora, Fontanes, Emilia, Campos, Rosa, Paloma, María José, Bermejo, Nuria, Berrueco, Rubén, Mateo, José, Arribalzaga, Karmele, Marco, Pascual, Palomo Bravo, Ángeles, Castro Quismondo, Nerea, Iñigo, Belén, Nieto Hernández, Maria del Mar, Vidal, Rosa, Martínez, María Paz, Aguinaco, Reyes, Tenorio, Maria, Ferreiro, María, García-Frade, Javier, Rodríguez-Huerta, Ana María, Cuesta, Jorge, Rodríguez-González, Ramón, García-Candel, Faustino, Dobón, Manuela, Aguilar, Carlos, Batlle, Fernando, Vidal, Francisco, López-Fernández, María Fernanda, and Universitat Autònoma de Barcelona

Subjects
Male, Heredity, Gene Identification and Analysis, lcsh:Medicine, 030204 cardiovascular system & hematology, Biochemistry, Geographical locations, 0302 clinical medicine, hemic and lymphatic diseases, Genotype, Medicine and Health Sciences, Medicine, lcsh:Science, Child, Aged, 80 and over, Multidisciplinary, biology, High-Throughput Nucleotide Sequencing, Middle Aged, Europe, Phenotypes, von Willebrand Diseases, Phenotype, Child, Preschool, Female, Research Article, circulatory and respiratory physiology, Adult, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, 03 medical and health sciences, Young Adult, Von Willebrand factor, Diagnostic Medicine, von Willebrand Factor, Von Willebrand disease, Genetics, Humans, Mutation detection, European Union, Mutation Detection, Aged, business.industry, lcsh:R, Structural integrity, Biology and Life Sciences, Proteins, Human Genetics, medicine.disease, Spain, Immunology, biology.protein, lcsh:Q, People and places, business, Collagens, 030215 immunology
Abstract

The multimeric analysis (MA) of plasma von Willebrand factor (VWF) evaluates structural integrity and helps in the diagnosis of von Willebrand disease (VWD). This assay is a matter of controversy, being considered by some investigators cumbersome and only slightly informative. The centralised study 'Molecular and Clinical Profile of von Willebrand Disease in Spain (PCM-EVW-ES)' has been carried out by including the phenotypic assessment and the genetic analysis by next generation sequencing (NGS) of the VWF gene (VWF). The aim of the present study was to evaluate the role of MA to the diagnosis of these patients and their potential discrepancies. Two hundred and seventy out of 480 patients centrally diagnosed with VWD had normal multimers, 168 had abnormal multimers and 42 a total absence of multimers. VWF MA was of great significance in the diagnosis of 83 patients (17.3%), it was also of help in the diagnosis achieved in 365 additional patients (76%) and was not informative in 32 cases (6.7%). With regard to discrepancies, 110 out of 480 (23%) patients centrally diagnosed with VWD presented some kind of discordance between VWF:RCo/VWF:Ag and/or VWF:CB/VWF:Ag ratios, multimeric study and/or genetic results. The VWF MA was key in the presence of novel mutations as well as in cases with phenotypic discrepancies. A comparison between the contribution of MA and VWF:CB showed a clearly higher contribution of the former in the diagnostic process. These data seem to reinforce the relevance of the VWF MA in VWD diagnosis, despite all its limitations.

Published
2018

12. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients

Author

Borràs, Nina, Batlle, Javier, Pérez-Rodríguez, Almudena, López-Fernández, María Fernanda, Rodríguez-Trillo, Ángela, Lourés, Esther, Cid, Ana Rosa, Bonanad, Santiago, Cabrera, Noelia, Moret, Andrés, Parra, Rafael, Mingot-Castellano, María Eva, Balda, Ignacia, Altisent, Carmen, Pérez-Montes, Rocío, Fisac, Rosa María, Iruín, Gemma, Herrero, Sonia, Soto, Inmaculada, de Rueda, Beatriz, Jiménez-Yuste, Víctor, Alonso, Nieves, Vilariño, Dolores, Arija, Olga, Campos, Rosa, Paloma, María José, Bermejo, Nuria, Berrueco, Rubén, Mateo, José, Arribalzaga, Karmele, Marco, Pascual, Palomo Bravo, Ángeles, Sarmiento, Lizheidy, Iñigo, Belén, Nieto Hernández, Maria del Mar, Vidal, Rosa, Martínez, María Paz, Aguinaco, Reyes, César, Jesús María, Ferreiro, María, García-Frade, Javier, Rodríguez-Huerta, Ana María, Cuesta, Jorge, Rodríguez-González, Ramón, García-Candel, Faustino, Cornudella, Rosa, Aguilar, Carlos, Vidal, Francisco, Corrales Insa, Irene, and Universitat Autònoma de Barcelona

Subjects
Genetic counseling, In silico, 030204 cardiovascular system & hematology, Bioinformatics, Genetic analysis, Article, 03 medical and health sciences, 0302 clinical medicine, Von Willebrand factor, von Willebrand Factor, Von Willebrand disease, Humans, Medicine, Prospective cohort study, Genetic Association Studies, Hemostasis, biology, business.industry, High-Throughput Nucleotide Sequencing, Hematology, medicine.disease, von Willebrand Diseases, Spain, Mutation, biology.protein, Microsatellite, business, Asymptomatic carrier, 030215 immunology
Abstract

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population.

Published
2017

13. Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Author

Borràs, Nina, primary, Orriols, Gerard, additional, Batlle, Javier, additional, Pérez-Rodríguez, Almudena, additional, Fidalgo, Teresa, additional, Martinho, Patricia, additional, López-Fernández, María Fernanda, additional, Rodríguez-Trillo, Ángela, additional, Lourés, Esther, additional, Parra, Rafael, additional, Altisent, Carme, additional, Cid, Ana Rosa, additional, Bonanad, Santiago, additional, Cabrera, Noelia, additional, Moret, Andrés, additional, Mingot-Castellano, María Eva, additional, Navarro, Nira, additional, Pérez-Montes, Rocío, additional, Marcellin, Sally, additional, Moreto, Ana, additional, Herrero, Sonia, additional, Soto, Inmaculada, additional, Fernández-Mosteirín, Núria, additional, Jiménez-Yuste, Víctor, additional, Alonso, Nieves, additional, de Andrés-Jacob, Aurora, additional, Fontanes, Emilia, additional, Campos, Rosa, additional, Paloma, María José, additional, Bermejo, Nuria, additional, Berrueco, Ruben, additional, Mateo, José, additional, Arribalzaga, Karmele, additional, Marco, Pascual, additional, Palomo, Ángeles, additional, Quismondo, Nerea Castro, additional, Iñigo, Belén, additional, Nieto, María del Mar, additional, Vidal, Rosa, additional, Martínez, María Paz, additional, Aguinaco, Reyes, additional, Tenorio, Jesús María, additional, Ferreiro, María, additional, García-Frade, Javier, additional, Rodríguez-Huerta, Ana María, additional, Cuesta, Jorge, additional, Rodríguez-González, Ramón, additional, García-Candel, Faustino, additional, Dobón, Manuela, additional, Aguilar, Carlos, additional, Vidal, Francisco, additional, and Corrales, Irene, additional

Published
2018
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14. Multimorbidity in type 1 Gaucher disease patients under miglustat therapy

Author

Engay, Blanca Medrano, primary, Roy, Ana, additional, Atutxa, Koldo, additional, Diaz-Morant, Vicente, additional, García-Frade, Javier, additional, Hernández-Martín, Roberto, additional, Luño, Elisa, additional, Noya, Soledad, additional, de la Serna, Javier, additional, Villalón, Lucía, additional, and Giraldo, Pilar, additional

Published
2018
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15. Diagnosis and management of von willebrand disease in Spain

Author

Batlle, Javier, primary, Pérez-Rodríguez, Almudena, additional, Corrales, Irene, additional, Borràs, Nina, additional, Rodríguez-Trillo, Ángela, additional, Lourés, Esther, additional, Cid, Ana Rosa, additional, Bonanad, Santiago, additional, Cabrera, Noelia, additional, Moret, Andrés, additional, Parra, Rafael, additional, Mingot-Castellano, María Eva, additional, Navarro, Nira, additional, Altisent, Carmen, additional, Pérez-Montes, Rocío, additional, Marcellini, Shally, additional, Moretó, Ana, additional, Herrero, Sonia, additional, Soto, Inmaculada, additional, Fernández-Mosteirín, Nuria, additional, Jiménez-Yuste, Víctor, additional, Alonso, Nieves, additional, de Andrés Jacob, Aurora, additional, Fontanes, Emilia, additional, Campos, Rosa, additional, Paloma, María José, additional, Bermejo, Nuria, additional, Berrueco, Rubén, additional, Mateo, José, additional, Arribalzaga, Karmele, additional, Marco, Pascual, additional, Palomo, Ángeles, additional, Quismondo, Nerea Castro, additional, Iñigo, Belén, additional, del Mar Nieto, María, additional, Vidal, Rosa, additional, Martínez, María Paz, additional, Aguinaco, Reyes, additional, Tenorio, María, additional, Ferreiro, María, additional, García-Frade, Javier, additional, Rodríguez-Huerta, Ana María, additional, Cuesta, Jorge, additional, Rodríguez-González, Ramón, additional, García-Candel, Faustino, additional, Dobón, Manuela, additional, Aguilar, Carlos, additional, López, Fernando Batlle, additional, Vidal, Francisco, additional, and López-Fernández, María Fernanda, additional

Published
2018
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16. Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma

Author

Guerrero, Camila, Puig, Noemi, Cedena, María-Teresa, Calasanz, María-José, Gutierrez, Norma C., Fernandez, Manuela, Oriol, Albert, Ríos-Tamayo, Rafael, Hernandez, Miguel-Teodoro, Martínez-Martínez, Rafael, Bargay, Joan, de Arriba, Felipe, Palomera, Luis, Gonzalez-Rodriguez, Ana Pilar, Gonzalez Perez, Marta-Sonia, Orfao, Alberto, Mateos, María-Victoria, Martinez-Lopez, Joaquin, Rosiñol, Laura, Bladé, Joan, Lahuerta, Juan-Jose, San-Miguel, Jesus F., Paiva, Bruno, Casanova Espinosa, María, Zamudio, José Luís Guzman, Ríos Herranz, Eduardo, Rios Tamayo, Rafael, Martín Sánchez, Jesús, Palomera Bernal, Luís, González Rodríguez, Ana Pilar, González García, María Esther, Mayol, Antonia Sampol, Bargay Lleonart, Joan, Suárez, Alexia, Hernández García, Miguel Teodoro, Gaisán, Carmen Montes, Hernández Ruiz, Belén, Casado Montero, Felipe, Miguel Llorente, Dunia de, Ramos, Fernando Solano, Ibañez Garcia, Ángela, Manteca, Mariví Mateos, Mariano Hernández Martín, José, Escalante Barrigón, Fernando, García Frade, Javier, de Coca, Alfonso García, Franco, Carlos Aguilar, Labrador Gómez, Jorge, Cabezudo Pérez, Elena, Bladé Creixentí, Joan, Balari, Ana MaSureda, González Montes, Yolanda, Teigell, Lourdes Escoda, García Guiñón, Antonio, Abella Monreal, Eugenia, Alfonso Soler Campos, Juan, Martí Tutusaus, Josep Ma, Rocafiguera, Albert Oriol, Gorrochategui, Miquel Granell, Mesa, Mercedes Gironella, Silva, Carmen Cabrera, González Pérez, Marta Sonia, Loureiro, Ana Dios, Méndez Sánchez, José Angel, Irazu, María Josefa Nájera, Párraga, Francisco Javier Peñalver, Lahuerta Palacios, Juan José, Barahona, Pilar Bravo, Rodríguez, Cristina Encinas, Hernández Rivas, José Ángel, Oteyza, Jaime Pérez de, Iglesias del Barrio, Rebeca, López de la Guia, Ana, Amor, Adrián Alegre, Prieto Pareja, Elena, Castelló, Isabel Krsnik, Blanchard Rodríguez, MaJesús, Martínez Martínez, Rafael, Riaza Grau, Rosalía, Mesa, Eugenio Giménez, Ruiz Sainz, Elena, Arriba, Felipe de, Moraleda Jiménez, Jose María, Romera, Marta, Cardoso, Felipe Prósper, Arguiñano Pérez, José Ma, Pomposo, María Puente, Pérez Persona, Ernesto, Teruel Casasús, Ana Isabel, García, Paz Ribas, Jarque Ramos, Isidro, Villarrubia Lor, María Blanca, Fernández García, Pedro Luis, Fernández García, Pedro Luis, and Martínez Chamorro, Carmen

Abstract

•ISS 3, high CTC levels, and a longer time to first MRD negativity are significant predictors of MRD resurgence and/or progressive disease.

Published
2024
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17. Molecular and clinical profile of von Willebrand disease in Spain (PCM–EVW–ES): Proposal for a new diagnostic paradigm

Author

Batlle, Javier, primary, Pérez-Rodríguez, Almudena, primary, Corrales, Irene, primary, López-Fernández, María Fernanda, primary, Rodríguez-Trillo, Ángela, primary, Lourés, Esther, primary, Cid, Ana Rosa, primary, Bonanad, Santiago, primary, Cabrera, Noelia, primary, Moret, Andrés, primary, Parra, Rafael, primary, Mingot-Castellano, María Eva, primary, Balda, Ignacia, primary, Altisent, Carmen, primary, Pérez-Montes, Rocío, primary, Fisac, Rosa María, primary, Iruín, Gemma, primary, Herrero, Sonia, primary, Soto, Inmaculada, primary, Rueda, Beatriz de, primary, Jiménez-Yuste, Víctor, primary, Alonso, Nieves, primary, Vilariño, Dolores, primary, Arija, Olga, primary, Campos, Rosa, primary, Paloma, María José, primary, Bermejo, Nuria, primary, Toll, Teresa, primary, Mateo, José, primary, Arribalzaga, Karmele, primary, Marco, Pascual, primary, Palomo, Ángeles, primary, Sarmiento, Lizheidy, primary, Iñigo, Belén, primary, Nieto, María del Mar, primary, Vidal, Rosa, primary, Martínez, María Paz, primary, Aguinaco, Reyes, primary, Ferreiro, María, primary, García-Frade, Javier, primary, Rodríguez-Huerta, Ana María, primary, Cuesta, Jorge, primary, Rodríguez-González, Ramón, primary, García-Candel, Faustino, primary, Cornudella, Rosa, primary, Aguilar, Carlos, primary, Borràs, Nina, primary, Vidal, Francisco, primary, and César, Jesús María, additional

Published
2016
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18. Efficacy and Safety of Eltrombopag in Persistent and Newly Diagnosed ITP

Author

González-López, Tomás José, primary, Sánchez-González, Blanca, additional, Pascual, Cristina, additional, Alvarez-Roman, María Teresa, additional, Pérez-Rus, Gloria, additional, Fernández-Fuentes, Fernando, additional, Bernat, Silvia, additional, Hernández-Rivas, José Angel, additional, Cortés, Montserrat, additional, Andrade, Marcio, additional, Olivera, Pavel, additional, Jarque, Isidro, additional, Pérez-Crespo, Susana, additional, Gómez-Nuñez, Marta, additional, Fernández-Rodríguez, Angeles, additional, Martínez-Robles, Violeta, additional, Fernández-Miñano, Carmen, additional, Fuertes-Palacio, Miguel Angel, additional, Bárez, Abelardo, additional, Fisac, Rosa, additional, Aguilar, Carlos, additional, Peñarrubia, María Jesús, additional, de Cabo, Erik, additional, Mingot, Eva, additional, Ranedo-Zaldo, Raquel, additional, Arrieta-Cerdán, Esther, additional, Sanz, Miguel A., additional, García-Frade, Javier, additional, and González-Porras, José Ramón, additional

Published
2015
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19. Usefulness of Eltrombopag in Secondary ITP Patients in Clinical Practice

Author

González-López, Tomás José, primary, Alvarez-Roman, María Teresa, additional, Pascual, Cristina, additional, Sánchez-González, Blanca, additional, Fernández-Fuentes, Fernando, additional, Pérez-Rus, Gloria, additional, Hernández-Rivas, José Angel, additional, Bernat, Silvia, additional, Cortés, Montserrat, additional, Bastida, José María, additional, Martínez-Robles, Violeta, additional, Fernández-Rodríguez, Angeles, additional, Olivera, Pavel, additional, Bolaños, Estefanía, additional, Alonso, Rafael, additional, Entrena, Laura, additional, Gómez-Nuñez, Marta, additional, Bermejo, Nuria, additional, Martínez-Badas, María Paz, additional, Peñarrubia, María Jesús, additional, Alonso, Arancha, additional, Soto, Inmaculada, additional, Yera Cobo, María, additional, Casaus, Alberto, additional, Caparrós, Isabel, additional, Perera, María, additional, Jiménez Bárcenas, Reyes, additional, Heras, Cecilia, additional, Calbacho, María, additional, Tenorio, Maria, additional, Luaña, Armando, additional, Lopez-Ansoar, Elsa, additional, Hermida, Gerardo, additional, García-Frade, Javier, additional, González-Porras, José Ramón, additional, and Sanz, Miguel A., additional

Published
2015
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20. Prospective National-Base Multicenter Study to Standardize the Follow-up of Type 1Gaucher Disease Patients Treated with Eliglustat Under Standard of Care Practice. Trazelga Project

Author

Andrade-Campos, Marcio M, Cebolla, Jorge J, Lopez de Frutos, Laura, Irun, Pilar, Noya, Soledad, Nieto, Santiago, Villalon, Lucia, Arribas, Ana I, Barez, Abelardo, Garcia-Frade, Javier, Hermosin, Maria Lourdes, Hernández-Rivas, Jesús-María, Ibarretxe, Daiana, Lozano, Maria L, Molero, Teresa, Perez-Saenz, Maria Angeles, Villarrubia, Jesus, and Giraldo, Pilar

Published
2018
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21. Use of Eltrombopag after Romiplostim in Primary ITP Patients

Author

González-López, Tomás José, primary, Pascual, Cristina, additional, Álvarez-Román, María Teresa, additional, Fernández-Fuentes, Fernando, additional, Sánchez-González, Blanca, additional, Caparrós, Isabel, additional, Jarque, Isidro, additional, Mingot, María Eva, additional, Hernández-Rivas, José Angel, additional, Martín-Salces, Mónica, additional, Solán, Laura, additional, Beneit, Paola, additional, Jiménez, Reyes, additional, Bernat, Silvia, additional, Andrade, Marcio M., additional, Cortés, Montserrat, additional, Cortti, María José, additional, Pérez-Crespo, Susana, additional, Gómez-Núñez, Marta, additional, Olivera, Pavel E., additional, Pérez-Rus, Gloria, additional, Martínez-Robles, Violeta, additional, Alonso, Rafael, additional, Fernández-Rodríguez, Angeles, additional, Arratibel, María Carmen, additional, Perera, María, additional, Fernández-Miñano, Carmen, additional, Fuertes-Palacio, Miguel Angel, additional, Vázquez-Paganini, Juan Andrés, additional, Juárez-Salcedo, Luis Miguel, additional, Valcarce, Inés, additional, Díaz-Gálvez, Francisco Javier, additional, Sainz, Adriana, additional, Fisac, Rosa, additional, Aguilar, Carlos, additional, Martínez-Badas, María Paz, additional, Peñarrubia, María Jesús, additional, García-Frade, Javier, additional, Calbacho, Maria, additional, de Cos, Carmen, additional, González-Silva, Manuel, additional, Coria, Erika, additional, Alonso, Arancha, additional, Casaus, Alberto, additional, Luaña, Armando, additional, Galán, Pilar, additional, Fernández-Canal, Cristina, additional, and González-Porras, José Ramón, additional

Published
2014
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22. Design and Validate of Next-Generation Sequencing Panel for Inherited Platelet Disorders

Author

Bastida, Jose Maria, primary, del Rey, Mónica, additional, Benito, Rocío, additional, Sanchez-Guiu, Isabel, additional, Riesco, Susana, additional, Peñarrubia, Maria Jesús, additional, Fisac, Rosa, additional, García Frade, Javier, additional, Aguilar, Carlos, additional, Cebeiro, Maria Jose, additional, Martinez-Badás, Paz, additional, Pardal, Emilia, additional, Aguilera, Carmen, additional, Fontecha, Elena, additional, Perez, Beatriz, additional, Llinares, Esther, additional, Fuster, Jose Luis, additional, Rivera, Jose, additional, Lozano, Maria Luisa, additional, Vicente, Vicente, additional, Del Canizo, Consuelo, additional, Hernandez, Jesus Maria, additional, and Gonzalez, José Ramón, additional

Published
2014
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23. Efficacy and Safety Of Temsirolimus In Patients With Relapsed Or Refractory Mantle Cell Lymphoma: Results From The Spanish Experience

Author

Fuente, Adolfo de la, primary, González, Gloria, additional, García-Carbonero, Iciar, additional, García-Frade, Javier, additional, Munárriz, Javier, additional, Aguiar, David, additional, Cuevas, Beatriz, additional, Cuevas, María Victoria, additional, Aporta, Rafael, additional, Bárez, Abelardo, additional, Callejas, Marta, additional, Murias, Adolfo, additional, Altés, Albert, additional, Salar, Antonio, additional, Sanchez-Gonzalez, Blanca, additional, Grande, Carlos, additional, Garcia-Marco, Jose A., additional, López, Ángeles, additional, Morán, Marina, additional, Viqueira, Andrea, additional, and Briones, Javier, additional

Published
2013
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24. A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma

Author

Rosiñol, Laura, Pérez-Simón, José Antonio, Sureda, Anna, de la Rubia, Javier, de Arriba, Felipe, Lahuerta, Juan José, González, José David, Díaz-Mediavilla, Joaquín, Hernández, Belén, García-Frade, Javier, Carrera, Dolores, León, Angel, Hernández, Miguel, Abellán, Pascual Fernández, Bergua, Juan Miguel, San Miguel, Jesús, and Bladé, Joan

Published
2008
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25. Long-Term Follow-Up of a Phase II Trial of Six Cycles of Dose-Dense R-CHOP-14 for First-Line Treatment of Diffuse Large B-Cell Lymphoma in Young and Elderly Patients.

Author

González-Barca, Eva, Canales, Miguel a., Salar, antonio, Ferrer, Secundino, Domingo-Domenech, Eva, Vidal, María-Jesús, Grande, Carlos, Bargay, Joan, Gardella, Santiago, Oriol, albert, Briones, Javier, García-Frade, Javier, Bello, Jose L., Sánchez-Blanco, Jose J., Peñalver, Francisco Javier, Tomás, Jose Francisco, asensio, antonio, López, andrés, and Caballero, Dolores

Subjects
DIFFUSE large B-cell lymphomas, RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE, PREDNISONE, THERAPEUTICS
Abstract

Background/Aims: Rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 14 days seems to achieve better outcomes than R-CHOP every 21 days in diffuse large B-cell lymphoma (DLBCL) patients. Currently, the standard regimen is R-CHOP every 21 days. Methods: This is a phase II clinical trial of treatment with 6 cycles of R-CHOP-14 with pegfilgrastim support in 2 populations of previously untreated DLBCL patients aged ≥ 65 years (n = 73) or <65 years (n = 51) with low-risk International Prognostic Index scores (0-2). Results: With a median follow-up of 63.7 months, the 5-year event-free survival rate was 53.8% in patients aged ≥ 65 years and 71.0% in patients aged <65 years. The 5-year overall survival rate was 71.4 and 89.8%, respectively. The complete remission rate was 69.9% for older and 80.4% for younger patients. The median relative dose intensity of cytotoxic drugs was 143.2% in the elderly and 149.1% in the young patients. Febrile neutropenia was the most common grade 3-4 adverse event, being higher in elderly patients (21.3 vs. 9.3%). Eight deaths (7 in elderly patients) were considered treatment related. Conclusion: In conclusion, the R-CHOP-14 regimen is feasible and very active, though it is more toxic in elderly patients mainly due to an increased incidence of infections. New strategies, such as new monoclonal antibodies or new targeted therapies, are needed to improve the outcomes of DLBCL patients. [ABSTRACT FROM AUTHOR]

Published
2016
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26. Influence of Pre- and Post-Transplantation Responses on Outcome of Patients With Multiple Myeloma: Sequential Improvement of Response and Achievement of Complete Response Are Associated With Longer Survival

Author

Lahuerta, Juan José, primary, Mateos, Maria Victoria, additional, Martínez-López, Joaquin, additional, Rosiñol, Laura, additional, Sureda, Anna, additional, de la Rubia, Javier, additional, García-Laraña, José, additional, Martínez-Martínez, Rafael, additional, Hernández-García, Miguel T., additional, Carrera, Dolores, additional, Besalduch, Joan, additional, de Arriba, Felipe, additional, Ribera, José María, additional, Escoda, Lourdes, additional, Hernández-Ruiz, Belén, additional, García-Frade, Javier, additional, Rivas-González, Concepción, additional, Alegre, Adrían, additional, Bladé, Joan, additional, and San Miguel, Jesús F., additional

Published
2008
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27. Effect of Pre and Post-Transplantation Responses on Outcome of Multiple Myeloma Patients: CR and near-CR Should Not Be Considered as Equivalent Prognostic Markers. Results of a PETHEMA/Gem Prospective Study

Author

Lahuerta, Juan José, primary, Mateos, Maria Victoria, primary, Martínez-López, Joaquin, primary, Rosinol, Laura, primary, Sureda, Anna, primary, de la Rubia, Javier, primary, García-Laraña, José, primary, Martínez-Martínez, Rafael, primary, Hernández-García, Miguel-Teodoro, primary, Carrera, Dolores, primary, Besalduch, Juan, primary, de Arriba, Felipe, primary, Ribera, Jose-Maria, primary, Escoda, Lourdes, primary, Hernández-Ruiz, María-Belen, primary, García-Frade, Javier, primary, Rivas-González, Concepción, primary, Alegre, Adrian, primary, Blade, Joan, primary, and Miguel, J.F. San, primary

Published
2008
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28. Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction

Author

Fernández-Avilés, Francisco, primary, San Román, José Alberto, additional, García-Frade, Javier, additional, Fernández, María Eugenia, additional, Peñarrubia, María Jesús, additional, de la Fuente, Luis, additional, Gómez-Bueno, Manuel, additional, Cantalapiedra, Alberto, additional, Fernández, Jesús, additional, Gutierrez, Oliver, additional, Sánchez, Pedro L., additional, Hernández, Carolina, additional, Sanz, Ricardo, additional, García-Sancho, Javier, additional, and Sánchez, Ana, additional

Published
2004
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29. The Unfolded Protein Response and the Phosphorylations of Activating Transcription Factor 2 in the trans-Activation of il23a Promoter Produced by β-Glucans.

Author

Rodríguez, Mario, Domingo, Esther, Alonso, Sara, García Frade, Javier, Eiros, José, Sánchez Crespo, Mariano, and Fernández, Nieves

Subjects
*GLUCANS, *TRANSCRIPTION factors, *PROTEINS, *POLYSACCHARIDES, *BIOLOGICAL control of fungi
Abstract

Current views on the control of IL-23 production focus on the regulation of il23a, the gene encoding IL-23 p19, by NF-κB in combination with other transcription factors. C/EBP homologous protein (CHOP), X2-Box-binding protein 1 (XBP1), activator protein 1 (AP1), SMAD, CCAAT/enhancer-binding protein (C/EBPβ), and cAMP-response element-binding protein (CREB) have been involved in response to LPS, but no data are available regarding the mechanism triggered by the fungal mimic and β-glucan-containing stimulus zymosan, which produces IL-23 and to a low extent the related cytokine IL-12 p70. Zymosan induced the mobilization of CHOP from the nuclear fractions to phagocytic vesicles. Hypha-forming Candida also induced the nuclear disappearance of CHOP. Assay of transcription factor binding to the il23a promoter showed an increase of Thr(P)-71-Thr(P)-69-activating transcription factor 2 (ATF2) binding in response to zymosan. PKC and PKA/mitogen- and stress-activated kinase inhibitors down-regulated Thr(P)-71-ATF2 binding to the il23a promoter and il23a mRNA expression. Consistent with the current concept of complementary phosphorylations on N-terminal Thr-71 and Thr-69 of ATF2 by ERK and p38 MAPK, MEK, and p38 MAPK inhibitors blunted Thr(P)-69-ATF2 binding. Knockdown of atf2 mRNA with siRNA correlated with inhibition of il23a mRNA, but it did not affect the expression of il12/23b and il10 mRNA. These data indicate the following: (i) zymosan decreases nuclear proapoptotic CHOP, most likely by promoting its accumulation in phagocytic vesicles; (ii) zymosan-induced il23a mRNA expression is best explained through coordinated κB-and ATF2-dependent transcription; and (iii) il23a expression relies on complementary phosphorylation of ATF2 on Thr-69 and Thr-71 dependent on PKC and MAPK activities. [ABSTRACT FROM AUTHOR]

Published
2014
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30. Bone remodelation markers are useful in the management of monoclonal gammopathies.

Author

Hernández, José M, Suquía, Begoña, Queizan, José A, Fisac, Rosa M, Sanchez, José J, Fernández-Calvo, Francisco J, García-Sanz, Ramón, Olivier, Carmen, Bárez, Abelardo, Calmuntia, María J, García-Frade, Javier, Portero, Juan A, López, Rosa, Aguilera, Carmen, Navajo, Jose A, and San-Miguel, Jesús F

Subjects
*BONE diseases, *MULTIPLE myeloma, *MONOCLONAL gammopathies, *OSTEOPOROSIS, *BONE remodeling, *MEDICAL radiology
Abstract

The evaluation of bone disease in multiple myeloma (MM) by conventional radiology has low reproducibility. In the last decade, several serum and urine biochemical parameters, for evaluation of bone turnover, have become available. The present study was designed to explore the value of six bone remodelation markers. It was studied in a series of 176 newly diagnosed patients with monoclonal gammopathies (107 MM and 69 monoclonal gammopathies of unknown significance (MGUS)). As control groups we used 25 patients with benign osteoporosis (BO) and 32 healthy individuals (HI). The bone markers analyzed included: bone resorption markers (BRM) (total pyridinoline, total deoxypyridinoline, free deoxypyridinoline and C-terminal telopeptide of collagen I) and bone formation markers (BFM) (bone alkaline phosphatase (bAP) and osteocalcin (OC)). Serum or urinary levels of BRM were significantly higher in MM patients than in MGUS patients, BO patients or HI (P<0.001, respectively). BRM were higher in MM patients with lytic lesions. However, only C-terminal telopeptide discriminated MM patients without bone lesions from MGUS patients. BFM did not show significant differences in the aforementioned comparisons, although a trend toward higher values of OC and lower values of bAP in patients with early bone affectation was observed. Ratios BRM/BFM that contained bAP exhibited differences that were most significant between the MM group and other entities, as well as between the different MM subgroups. In fact, the ratios BRM/bAP provided discrimination between the MM subgroup without lyses and MGUS group (P<0.01). BRM and BFM, especially the ratios, are useful in the evaluation of bone lesions in patients with monoclonal gammopathies.The Hematology Journal (2004) 5, 480-488. doi:10.1038/sj.thj.6200564 [ABSTRACT FROM AUTHOR]

Published
2004
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31. Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA.

Author

Borràs N, Orriols G, Batlle J, Pérez-Rodríguez A, Fidalgo T, Martinho P, López-Fernández MF, Rodríguez-Trillo Á, Lourés E, Parra R, Altisent C, Cid AR, Bonanad S, Cabrera N, Moret A, Mingot-Castellano ME, Navarro N, Pérez-Montes R, Marcellin S, Moreto A, Herrero S, Soto I, Fernández-Mosteirín N, Jiménez-Yuste V, Alonso N, de Andrés-Jacob A, Fontanes E, Campos R, Paloma MJ, Bermejo N, Berrueco R, Mateo J, Arribalzaga K, Marco P, Palomo Á, Quismondo NC, Iñigo B, Nieto MDM, Vidal R, Martínez MP, Aguinaco R, Tenorio JM, Ferreiro M, García-Frade J, Rodríguez-Huerta AM, Cuesta J, Rodríguez-González R, García-Candel F, Dobón M, Aguilar C, Vidal F, and Corrales I

Subjects
Alleles, Base Sequence, Blood Platelets metabolism, Computational Biology, Exons, Female, Gene Frequency, Genotype, High-Throughput Nucleotide Sequencing, Humans, Leukocytes metabolism, Male, RNA Splice Sites, RNA, Messenger genetics, von Willebrand Diseases genetics, Gene Silencing, Introns, Mutation, Missense, RNA Splicing, von Willebrand Factor genetics
Abstract

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7&#95;3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074 ., (Copyright© 2019 Ferrata Storti Foundation.)

Published
2019
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32. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.

Author

Borràs N, Batlle J, Pérez-Rodríguez A, López-Fernández MF, Rodríguez-Trillo Á, Lourés E, Cid AR, Bonanad S, Cabrera N, Moret A, Parra R, Mingot-Castellano ME, Balda I, Altisent C, Pérez-Montes R, Fisac RM, Iruín G, Herrero S, Soto I, de Rueda B, Jiménez-Yuste V, Alonso N, Vilariño D, Arija O, Campos R, Paloma MJ, Bermejo N, Berrueco R, Mateo J, Arribalzaga K, Marco P, Palomo Á, Sarmiento L, Iñigo B, Nieto MDM, Vidal R, Martínez MP, Aguinaco R, César JM, Ferreiro M, García-Frade J, Rodríguez-Huerta AM, Cuesta J, Rodríguez-González R, García-Candel F, Cornudella R, Aguilar C, Vidal F, and Corrales I

Subjects
Genetic Association Studies, High-Throughput Nucleotide Sequencing, Humans, Mutation, Spain epidemiology, von Willebrand Diseases diagnosis, von Willebrand Factor genetics, von Willebrand Diseases genetics
Abstract

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF , including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF , 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population., (Copyright© 2017 Ferrata Storti Foundation.)

Published
2017
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33. Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study.

Author

Lahuerta JJ, Mateos MV, Martínez-López J, Grande C, de la Rubia J, Rosiñol L, Sureda A, García-Laraña J, Díaz-Mediavilla J, Hernández-García MT, Carrera D, Besalduch J, de Arriba F, Oriol A, Escoda L, García-Frade J, Rivas-González C, Alegre A, Bladé J, and San Miguel JF

Subjects
Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Male, Multiple Myeloma mortality, Retrospective Studies, Transplantation, Autologous, Busulfan administration & dosage, Busulfan adverse effects, Melphalan administration & dosage, Melphalan adverse effects, Multiple Myeloma therapy, Myeloablative Agonists administration & dosage, Myeloablative Agonists adverse effects, Stem Cell Transplantation, Transplantation Conditioning
Abstract

Background: The aim of this study was to compare the long-term safety and efficacy of oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) and melphalan 200 mg/m(2) as conditioning regimens for autologous stem cell transplantation in newly diagnosed patients with multiple myeloma in the GEM2000 study., Design and Methods: The first 225 patients received oral busulfan 12 mg/kg plus melphalan 140 mg/m(2); because of a high frequency of veno-occlusive disease, the protocol was amended and a further 542 patients received melphalan 200 mg/m(2)., Results: Engraftment and hospitalization times were similar in both groups. Oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) resulted in higher transplant-related mortality (8.4% versus 3.5%; P=0.002) due to the increased frequency of veno-occlusive disease in this group. Response rates were similar in both arms. With respective median follow-ups of 72 and 47 months, the median progression-free survival was significantly longer with busulfan plus melphalan (41 versus 31 months; P=0.009), although survival was similar to that in the melphalan 200 mg/m(2) group. However, access to novel agents as salvage therapy after relapse/progression was significantly lower for patients receiving busulfan plus melphalan (43%) than for those receiving melphalan 200 mg/m(2) (58%; P=0.01)., Conclusions: Conditioning with oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) was associated with longer progression-free survival but equivalent survival to that achieved with melphalan 200 mg/m(2) but this should be counterbalanced against the higher frequency of veno-occlusive disease-related deaths. This latter fact together with the limited access to novel salvage therapies in patients conditioned with oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) may explain the absence of a survival difference. Oral busulfan was used in the present study; use of the intravenous formulation may reduce toxicity and result in greater efficacy, and warrants further investigation in myeloma patients. (Clinicaltrials.gov identifier: NCT00560053).

Published
2010
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