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Teodosio C.,University of Salamanca | Garcia-Montero A.C.,University of Salamanca | Jara-Acevedo M.,University of Salamanca | Pedreira C.E.,Federal University of Rio de Janeiro | And 7 more authors.
Journal of Allergy and Clinical Immunology | Year: 2013

Background: Despite the fact that a great majority (>90%) of patients with systemic mastocytosis (SM) carry a common genetic lesion, the D816V KIT mutation, little is known regarding the molecular and biological pathways underlying the clinical heterogeneity of the disease. Objective: We sought to analyze the gene expression profile (GEP) of bone marrow mast cells (BMMCs) in patients with SM and its association with distinct clinical variants of the disease. Methods: GEP analyses were performed by using DNA-oligonucleotide microarrays in highly purified BMMCs from patients with SM carrying the D816V KIT mutation (n = 26) classified according to the diagnostic subtype of SM versus normal/reactive BMMCs (n = 7). Validation of GEP results was performed with flow cytometry in the same set of samples and in an independent cohort of 176 subjects. Results: Overall, 758 transcripts were significantly deregulated in patients with SM, with a common GEP (n = 398 genes) for all subvariants of SM analyzed. These were characterized by upregulation of genes involved in the innate and inflammatory immune response, including interferon-induced genes and genes involved in cellular responses to viral antigens, together with complement inhibitory molecules and genes involved in lipid metabolism and protein processing. Interestingly, aggressive SM additionally showed deregulation of apoptosis and cell cycle-related genes, whereas patients with indolent SM displayed increased expression of adhesion-related molecules. Conclusion: BMMCs from patients with different clinical subtypes of SM display distinct GEPs, which might reflect new targetable pathways involved in the pathogenesis of the disease. © 2013 American Academy of Allergy, Asthma & Immunology.

Redondo A.M.,Hospital Universitario Of Salamanca And Ibsal | Munez O.B.,Hospital Universitario Of Salamanca And Ibsal | Sebastian E.,Hospital Universitario Of Salamanca And Ibsal | Alcoceba M.,Hospital Universitario Of Salamanca And Ibsal | And 3 more authors.
Annals of Hematology | Year: 2015

This study analyzes patients with head and neck diffuse large B cell lymphoma (HN-DLBCL), focusing on the differences in the biological characteristics and prognosis of lymphomas of nodal and extranodal origin. We have included 72 patients with stage I–II HN-DLBCL who had updated survival information and diagnostic paraffin-embedded tissue blocks available for review. Non-germinal center phenotype (73.7 vs. 32.4 %, P = 0.001) and high level of Bcl-2 expression (78.9 vs. 52.9 %, P = 0.025) were more frequent in nodal than extranodal lymphomas. Univariate analyses indicated that bulky disease, Ann Arbor stage II, high level of Ki-67 expression, and primary nodal disease had adverse effects on complete remission (CR), but these effects were confirmed in a multivariate analysis for primary nodal disease and bulky disease. Patients with primary extranodal lymphoma also had better overall survival (OS) (87.7 vs. 72.5 %, P = 0.04) and event-free survival (EFS) (84 vs. 58.5 %, P = 0.046) than patients with nodal disease, although in the multivariate analysis, only Ann Arbor stage II continued to predict worse OS and EFS, whereas bulky disease was an independent prognostic factor only for EFS. We found significant differences in the biological characteristics and prognosis between primary nodal and extranodal HN-DLBCL. © 2014, Springer-Verlag Berlin Heidelberg.

Muniz C.,University of Salamanca | Muniz C.,Institute Salud Carlos III | Teodosio C.,University of Salamanca | Teodosio C.,Rotterdam University | And 14 more authors.
Stem Cell Research and Therapy | Year: 2015

Introduction: Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and multilineage differentiation. Their multipotential capacity and immunomodulatory properties have led to an increasing interest in their biological properties and therapeutic applications. Currently, the definition of MSCs relies on a combination of phenotypic, morphological and functional characteristics which are typically evaluated upon in vitro expansion, a process that may ultimately lead to modulation of the immunophenotypic, functional and/or genetic features of these cells. Therefore, at present there is great interest in providing markers and phenotypes for direct in vivo and ex vivo identification and isolation of MSCs. Methods: Multiparameter flow cytometry immunophenotypic studies were performed on 65 bone marrow (BM) samples for characterization of CD13high CD105+ CD45- cells. Isolation and expansion of these cells was performed in a subset of samples in parallel to the expansion of MSCs from mononuclear cells following currently established procedures. The protein expression profile of these cells was further assessed on (paired) primary and in vitro expanded BM MSCs, and their adipogenic, chondrogenic and osteogenic differentiation potential was also determined. Results: Our results show that the CD13high CD105+ CD45- immunophenotype defines a minor subset of cells that are systematically present ex vivo in normal/reactive BM (n = 65) and that display immunophenotypic features, plastic adherence ability, and osteogenic, adipogenic and chondrogenic differentiation capacities fully compatible with those of MSCs. In addition, we also show that in vitro expansion of these cells modulates their immunophenotypic characteristics, including changes in the expression of markers currently used for the definition of MSCs, such as CD105, CD146 and HLA-DR. Conclusions: BM MSCs can be identified ex vivo in normal/reactive BM, based on a robust CD13high CD105+ and CD45- immunophenotypic profile. Furthermore, in vitro expansion of these cells is associated with significant changes in the immunophenotypic profile of MSCs. © 2015 Muñiz et al.

Redondo A.M.,Hospital Universitario Of Salamanca And Ibsal | Pomares H.,Institute Catala dOncologia Duran i Reynals | Vidal M.J.,Hospital Donostia | Pascual M.J.,Hospital Carlos Haya | And 17 more authors.
British Journal of Haematology | Year: 2014

Summary: The use of highly effective rituximab-containing therapy for treating diffuse large B-cell lymphoma (DLBCL) makes it more difficult to salvage relapsed or refractory patients. Autologous stem-cell transplantation (ASCT) is the reference treatment for these patients, but the impact of previous exposure to rituximab on the subsequent results of ASCT remains unknown. We analysed 248 patients with relapsed or refractory DLBCL or grade 3B follicular lymphoma pre-treated with rituximab as part of first-line therapy (R+ group) who received ASCT, in comparison with a control group of 127 patients without previous exposure to rituximab (R- group). The complete remission (CR) rates were similar in both groups. Multivariate analysis identified age-adjusted International Prognostic Index at diagnosis, extranodal involvement and disease status at transplant, and the number of previous chemotherapy lines as independent factors with a negative influence on CR rate. Compared with R- patients, those in the R+ group had a significantly better progression-free survival (63% vs. 48% at 5 years) and overall survival (72% vs. 61% at 5 years). This observation was independent of other prognostic factors that affected these outcomes. In conclusion, ASCT is no less effective in patients with relapsed or refractory aggressive B-cell lymphoma pre-treated with first-line rituximab-containing therapy than in rituximab-naive patients. © 2013 John Wiley & Sons Ltd.

Lozano F.S.,Hospital Universitario Of Salamanca And Ibsal | March J.R.,Hospital Universitario Of Getafe | Gonzalez-Porras J.R.,Hospital Universitario Of Salamanca And Ibsal | Areitio-Aurtena A.,Hospital Universitario Of Salamanca And Ibsal
Vasa - Journal of Vascular Diseases | Year: 2013

Background: Th e Walking Impairment Questionnaire (WIQ) is a short, easy to complete, disease-specifi c questionnaire to assess intermittent claudication. A Spanish version of the WIQ for Hispanic Americans has recently been validated in Texas, but it needs to be validated for European Spanish people. Patients and methods: Aft er translation and cultural adaptation of the WIQ, 920 patients with intermittent claudication (ankle brachial index < 0.9) completed two questionnaires (Spanish version of the WIQ and European Quality of Life 5 Dimension [EQ-5D]). Th e validity of the WIQ was determined by correlating WIQ and EQ-5D. Test-retest reliability and internal consistency were determined using the intra-class correlation coeffi cient (ICC) and Cronbach's alpha, respectively. Results: Th e three domains of the WIQ were moderately correlated with the EQ-5D health outcome (r = 0.54 to 0.60; p < 0.001). Test-retest reliabilities ranged from ICC = 0.89 to 0.91 and internal consistency (Cronbach's alpha = 0.92) was high. Conclusions: Th e Spanish version of the WIQ for European Spanish patients was valid and reproducible, suggesting that it could be used in Spanish patients with intermittent claudication. © 2013 Hans Huber Publishers, Hogrefe AG, Bern.

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