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Search Results: 1 - 10 of 8039 matches for " Felipe Prósper "
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Long Non-Coding RNAs in Haematological Malignancies
Andoni Garitano-Trojaola,Xabier Agirre,Felipe Prósper,Puri Fortes
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms140815386
Abstract: Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides in length. LncRNAs are as diverse as mRNAs and they normally share the same biosynthetic machinery based on RNA polymerase II, splicing and polyadenylation. However, lncRNAs have low coding potential. Compared to mRNAs, lncRNAs are preferentially nuclear, more tissue specific and expressed at lower levels. Most of the lncRNAs described to date modulate the expression of specific genes by guiding chromatin remodelling factors; inducing chromosomal loopings; affecting transcription, splicing, translation or mRNA stability; or serving as scaffolds for the organization of cellular structures. They can function in cis, cotranscriptionally, or in trans, acting as decoys, scaffolds or guides. These functions seem essential to allow cell differentiation and growth. In fact, many lncRNAs have been shown to exert oncogenic or tumor suppressor properties in several cancers including haematological malignancies. In this review, we summarize what is known about lncRNAs, the mechanisms for their regulation in cancer and their role in leukemogenesis, lymphomagenesis and hematopoiesis. Furthermore, we discuss the potential of lncRNAs in diagnosis, prognosis and therapy in cancer, with special attention to haematological malignancies.
Amniotic Membrane as a Scaffold for Melanocyte Transplantation in Patients with Stable Vitiligo
Pedro Redondo,Ana Giménez de Azcarate,Laura Marqués,María García-Guzman,Enrique Andreu,Felipe Prósper
Dermatology Research and Practice , 2011, DOI: 10.1155/2011/532139
Abstract: Vitiligo is an acquired skin disease that significantly impacts the quality of life of patients. Medical treatment of vitiligo includes the use of melanocyte transplant, but the results are variable. We have treated 4 patients with either focal or generalized stable vitiligo using a graft of autologous melanocytes' culture on a denuded amniotic membrane (AM). A culture biopsy was obtained in every patient and grown in melanocytes' media for 10–14 days after which cells were transferred to a denuded AM and transplanted into the achromic lesions. Patients were followed for up to 6 months using clinical assessment of achromic lesions. Treated areas ranged between 4?cm2 and 210.6?cm2. Response to treatment was excellent in all patients with 90–95% repigmentation success rate. Our results demonstrate that transplantation of autologous melanocytes cultured on AM is a new, simple, and effective treatment for stable vitiligo. 1. Introduction Vitiligo is an acquired skin disease that affects 0.1–3% of the world’s population, characterized by loss of melanocytes from the epidermis, and leads to the development of achromic lesions. The basic pathogenesis of vitiligo remains unknown, although several studies suggest genetic predisposition, relationship to other autoimmune disorders, biochemical and neurohormonal imbalance, and environmental toxin/stressors [1–3]. The cosmetic disfigurement caused by vitiligo has profound psychological effects in approximately two-thirds of the patients, with depression, low self-esteem, social rejection, and even job discrimination [4]. In patients affected by focal vitiligo, the causative factors usually disappear, leaving well-defined achromic lesions. In stable generalized vitiligo, the size and number of lesions are stationary for several years and the Koebner phenomenon is absent. Current conventional medical treatment of vitiligo consists of UV therapy (narrowband UV-B or psoralen plus UV-A), local steroids, tacrolimus, pimecrolimus, and calcipotriol. In patients with stable vitiligo, lack of reliably effective medical therapies has led to the development of surgical treatment options using transplantation of autologous melanocytes. This technique includes split-thickness grafts, punch grafts, and suction blister grafts, which do not require cell expansion [5, 6]. Complications of these surgical methods can lead to the appearance of a cobblestone surface, peripheral hypopigmentation, spotty pigmentation, or lack of pigmentation of the treated areas, as well as to scarring and pigmentary alterations of the donor sites [7].
MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations
Edurne San José-Enériz, José Román-Gómez, Antonio Jiménez-Velasco, Leire Garate, Vanesa Martin, Lucia Cordeu, Amaia Vilas-Zornoza, Paula Rodríguez-Otero, María José Calasanz, Felipe Prósper, Xabier Agirre
Molecular Cancer , 2009, DOI: 10.1186/1476-4598-8-69
Abstract: The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML) [1]. Treatment with IM induces a complete hematological and cytogenetic response in more than 90 and 80% of newly diagnosed patients with chronic phase CML respectively, [2] which has established IM as the standard therapy for CML. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients [1]. Different mechanisms of resistance have been described, including the presence of point mutations in the tyrosine kinase domain of BCR-ABL1, amplification and overexpression of BCR-ABL1, overexpression of efflux transporters (such as ABCB1, also known as MDR1 or p-glycoprotein, and ABCG2) and underexpression of uptake transporters (such as SLC22A1, also known as hOCT1) [1]. However, it is currently impossible to predict whether a patient will develop resistance to IM. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML.MicroRNAs (miRNAs) are non-coding, single-stranded RNAs of 21-25 nucleotides that have recently been implicated in the regulation of a number of biological processes such as development, differentiation, apoptosis, proliferation and hematopoiesis. They regulate gene expression by promoting degradation of the mRNA or repressing its translation [3]. In addition, miRNAs have been implicated in the development of human cancers, either as tumor suppressors or as oncogenes. Aberrant miRNA expression has recently been described for a variety of solid tumors (lung, breast or colorectal cancer among others) and hematological malignancies (chronic lymphocytic leukemia, B-cell lymphomas, acute promyelocytic leukemias, acute lymphocytic leukemia and CML). In CML, abnormal ex
Células madre adultas
Prósper,F.; Verfaillie,C.M.;
Anales del Sistema Sanitario de Navarra , 2003, DOI: 10.4321/S1137-66272003000500002
Abstract: one of the fields of medicine that has created the greatest expectations in recent years is cellular therapy with stem cells. the isolation of human embryo cells, the apparent and unexpected potential of adult stem cells, and the development of gene therapy lead us to imagine a hopeful future for a significant number of diseases that are at present incurable. in the following pages we offer a sketch of the panorama of research with stem cells, describing the main achievements in this field as well as some of the questions awaiting answers. in spite of the great expectations, it is essential that we maintain a critical and realistic spirit when it comes to analysing the scientific advances in this area.
Células madre adultas Adult stem cells
F. Prósper,C.M. Verfaillie
Anales del Sistema Sanitario de Navarra , 2003,
Abstract: Uno de los campos de la medicina que más expectativas han levantado en los últimos a os es la terapia celular con células madre. El aislamiento de células embrionarias humanas, la aparente e inesperada potencialidad de las células madre adultas y el desarrollo de la terapia génica nos lleva a imaginar un futuro esperanzador para un importante número de enfermedades actualmente incurables. A lo largo de las siguientes páginas vamos a tratar de dibujar el panorama de la investigación con células madre, describiendo los principales logros en este campo así como algunas de las preguntas pendientes de responder. A pesar de las grandes expectativas, es fundamental que mantengamos un espíritu crítico y realista a la hora de analizar los avances científicos en esta área. One of the fields of medicine that has created the greatest expectations in recent years is cellular therapy with stem cells. The isolation of human embryo cells, the apparent and unexpected potential of adult stem cells, and the development of gene therapy lead us to imagine a hopeful future for a significant number of diseases that are at present incurable. In the following pages we offer a sketch of the panorama of research with stem cells, describing the main achievements in this field as well as some of the questions awaiting answers. In spite of the great expectations, it is essential that we maintain a critical and realistic spirit when it comes to analysing the scientific advances in this area.
DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia
Sara Alvarez,Javier Suela,Ana Valencia,Agustín Fernández,Mark Wunderlich,Xabier Agirre,Felipe Prósper,José Ignacio Martín-Subero,Alba Maiques,Francesco Acquadro,Sandra Rodriguez Perales,María José Calasanz,Jose Roman-Gómez,Reiner Siebert,James C. Mulloy,José Cervera,Miguel Angel Sanz,Manel Esteller,Juan C. Cigudosa
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012197
Abstract: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required.
Mutation Patterns of 16 Genes in Primary and Secondary Acute Myeloid Leukemia (AML) with Normal Cytogenetics
Marta Fernandez-Mercado, Bon Ham Yip, Andrea Pellagatti, Carwyn Davies, María José Larrayoz, Toshinori Kondo, Cristina Pérez, Sally Killick, Emma-Jane McDonald, María Dolores Odero, Xabier Agirre, Felipe Prósper, María José Calasanz, James S. Wainscoat, Jacqueline Boultwood
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042334
Abstract: Acute myeloid leukemia patients with normal cytogenetics (CN-AML) account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL) in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8%) and FLT3 (50.0%), and in secondary cases ASXL1 (48.5%) and TET2 (30.3%). We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML.
Therapeutic Effects of hMAPC and hMSC Transplantation after Stroke in Mice
Silvia Mora-Lee, Ma Salomé Sirerol-Piquer, María Gutiérrez-Pérez, Ulises Gomez-Pinedo, Valerie D. Roobrouck, Tania López, Mayte Casado-Nieto, Gloria Abizanda, Maria Teresa Rabena, Catherine Verfaille, Felipe Prósper, Jose Manuel García-Verdugo
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043683
Abstract: Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs) and human mesenchymal stem cells (hMSCs) on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2?/? γC?/? mice subjected to FeCl3 thrombosis mediated stroke were intracranially injected with 2×105 hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ) and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of stroke.
Frequent and Simultaneous Epigenetic Inactivation of TP53 Pathway Genes in Acute Lymphoblastic Leukemia
Amaia Vilas–Zornoza,Xabier Agirre,Vanesa Martín-Palanco,José Ignacio Martín-Subero,Edurne San José-Eneriz,Leire Garate,Sara álvarez,Estíbaliz Miranda,Paula Rodríguez-Otero,José Rifón,Antonio Torres,María José Calasanz,Juan Cruz Cigudosa,José Román-Gómez,Felipe Prósper
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017012
Abstract: Aberrant DNA methylation is one of the most frequent alterations in patients with Acute Lymphoblastic Leukemia (ALL). Using methylation bead arrays we analyzed the methylation status of 807 genes implicated in cancer in a group of ALL samples at diagnosis (n = 48). We found that 154 genes were methylated in more than 10% of ALL samples. Interestingly, the expression of 13 genes implicated in the TP53 pathway was downregulated by hypermethylation. Direct or indirect activation of TP53 pathway with 5-aza-2′-deoxycitidine, Curcumin or Nutlin-3 induced an increase in apoptosis of ALL cells. The results obtained with the initial group of 48 patients was validated retrospectively in a second cohort of 200 newly diagnosed ALL patients. Methylation of at least 1 of the 13 genes implicated in the TP53 pathway was observed in 78% of the patients, which significantly correlated with a higher relapse (p = 0.001) and mortality (p<0.001) rate being an independent prognostic factor for disease-free survival (DFS) (p = 0.006) and overall survival (OS) (p = 0.005) in the multivariate analysis. All these findings indicate that TP53 pathway is altered by epigenetic mechanisms in the majority of ALL patients and correlates with prognosis. Treatments with compounds that may reverse the epigenetic abnormalities or activate directly the p53 pathway represent a new therapeutic alternative for patients with ALL.
TET2 Mutations Are Associated with Specific 5-Methylcytosine and 5-Hydroxymethylcytosine Profiles in Patients with Chronic Myelomonocytic Leukemia
Cristina Pérez, Nicolas Martínez-Calle, José Ignacio Martín-Subero, Victor Segura, Eric Delabesse, Marta Fernandez-Mercado, Leire Garate, Sara Alvarez, José Rifon, Sara Varea, Jacqueline Boultwood, James S. Wainscoat, Juan Cruz Cigudosa, María José Calasanz, Nicholas C. P. Cross, Felipe Prósper, Xabier Agirre
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031605
Abstract: Chronic myelomonocytic leukemia (CMML) has recently been associated with a high incidence of diverse mutations in genes such as TET2 or EZH2 that are implicated in epigenetic mechanisms. We have performed genome-wide DNA methylation arrays and mutational analysis of TET2, IDH1, IDH2, EZH2 and JAK2 in a group of 24 patients with CMML. 249 genes were differentially methylated between CMML patients and controls. Using Ingenuity pathway analysis, we identified enrichment in a gene network centered around PLC, JNK and ERK suggesting that these pathways, whose deregulation has beenrecently described in CMML, are affected by epigenetic mechanisms. Mutations of TET2, JAK2 and EZH2 were found in 15 patients (65%), 4 patients (17%) and 1 patient (4%) respectively while no mutations in the IDH1 and IDH2 genes were identified. Interestingly, patients with wild type TET2 clustered separately from patients with TET2 mutations, showed a higher degree of hypermethylation and were associated with higher risk karyotypes. Our results demonstrate the presence of aberrant DNA methylation in CMML and identifies TET2 mutant CMML as a biologically distinct disease subtype with a different epigenetic profile.
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