Hospital Universitario Of Vigo
Hospital Universitario Of Vigo
Garcia-Sobrino T.,Hospital Clinico |
Garcia-Sobrino T.,Institute Investigaciones Sanitarias IDIS |
Blanco-Arias P.,Institute Investigaciones Sanitarias IDIS |
Blanco-Arias P.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer |
And 11 more authors.
Neuromuscular Disorders | Year: 2017
There are few reports on axonal CMT due to dominant GDAP1 mutations. We describe two unrelated Spanish families with a dominant axonal CMT. A novel in frame GAA deletion in exon 5 of the GDAP1 gene (c.677_679del; p.R226del) was identified in both families. Disease onset varied from early childhood to adulthood. Affected family members complained of distal lower limb weakness, cramps and foot deformities with variable CMTNS score in both families. Several individuals were asymptomatic or had paraesthesia only, however neurological examination and nerve conduction studies demonstrated neuropathic signs. Transfection of HeLa cells with the p.R226del mutation led to an increased mitochondrial aggregation. We report an AD-CMT2K with large phenotypic variability due to a novel dominant GDAP1 variant. This is the second founder GDAP1 pathogenic variant reported in Spain. © 2017 Elsevier B.V.
Jimenez-Ubieto A.,Hospital Universitario 12 Of Octubre |
Grande C.,Hospital Universitario 12 Of Octubre |
Caballero D.,Hospital Universitario Of Salamanca Ibsal |
Yanez L.,Hospital Universitario Marques Of Valdecilla |
And 23 more authors.
Biology of Blood and Marrow Transplantation | Year: 2017
High-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) has contributed to modify the natural history of follicular lymphoma (FL); however, an overall survival (OS) benefit has been demonstrated at relapse only after a rituximab-free chemotherapy regimen. A total of 655 patients with FL were reported to the Spanish GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) registry and underwent first ASCT between 1989 and 2007. A total of 203 patients underwent ASCT in first complete response (CR1), 174 in second complete response (CR2), 28 in third complete response (CR3), 140 in first partial response (PR1), 81 in subsequent PR, and 29 with resistant/refractory disease; 184 patients received rituximab before ASCT. With a median follow-up of 12 years from ASCT, median progression-free survival (PFS) and overall survival (OS) were 9.7 and 21.3 years, respectively. Actuarial 12-year PFS and OS were 63% (95% confidence interval [CI], 58%-68%) and 73% (95% CI, 68%-78%), respectively, for patients in CR (with a plateau in the curve beyond 15.9 years), 25% (95% CI, 19%-28%) and 49% (95% CI 42%-56%), respectively, for patients in PR, and 23% (95% CI, 8%-48%) and 28% (95% CI, 9%-45%), respectively, for patients with resistant/refractory disease (P < .001). In patients who received rituximab before ASCT, the estimated 9-year PFS and OS from ASCT were 59.5% (95% CI, 51%-67%) and 75% (95% CI, 68%-83%), respectively. Interestingly, for patients who underwent transplantation in CR ≥2 or PR ≥2 who had received rituximab before ASCT (n = 90), 9-year PFS and OS were 61% (95% CI, 51%-73%) and 75% (95% CI, 65%-80%), respectively, with no relapses occurring beyond 5.1 years after ASCT. The cumulative incidence of second malignancies in the global series was 6.7% at 5 years and 12.8% at 10 years. This analysis strongly suggests that ASCT is a potentially curative option for eligible patients with FL. In the setting of relapse, it is of especial interest in pretransplantation rituximab-sensitive patients with FL. © 2017 The American Society for Blood and Marrow Transplantation.
Aldea M.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer |
Aldea M.,Autonomous University of Madrid |
Clofent J.,Hospital Universitario Of Vigo |
Nunez de Arenas C.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer |
And 6 more authors.
Cancer Letters | Year: 2011
A reverse phase protein microarray approach has been applied to quantify proteins of energy metabolism in normal and tumor biopsies of colorectal cancer (CRC) patients. The metabolic proteome of CRC specimens revealed a profound shift towards and enhanced glycolytic phenotype and concurrent mitochondrial alteration. The metabolic signature discriminated CRC patients with highly significant differences in overall and disease-free prognosis. The quantification of the bioenergetic signature of the tumor offers a relevant biomarker of CRC that could contribute in the handling of these patients. © 2011 Elsevier Ireland Ltd.
PubMed | Hospital Vall dHebro, Hospital Universitario Gregorio Maranon, Hospital Universitario Of Canarias, Hospital Universitario Virgen Of La Victoria and 5 more.
Type: Journal Article | Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico | Year: 2016
Soft-tissue sarcomas are uncommon and heterogeneous tumors of mesenchymal origin. A soft-tissue mass that is increasing in size, greater than 5cm, or located under deep fascia are criteria for suspicion of sarcoma. Diagnosis, treatment, and management should preferably be performed by a multidisciplinary team in reference centers. MRI and lung CT scan are mandatory for local and distant assessment. A biopsy indicating histological type and grade is needed previous to the treatment. Wide surgical resection with tumor-free tissue margin is the primary treatment for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not likely of being improved with reexcision. Neoadjuvant and adjuvant chemotherapy improve survival in selected cases, usually in high-grade sarcomas of the extremities. In the case of metastatic disease, patients with exclusive lung metastasis could be considered for surgery. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. New drugs have shown activity in second-line therapy and in specific histological subtypes.
Sanchez-Arago M.,Autonomous University of Madrid |
Formentini L.,Autonomous University of Madrid |
Martinez-Reyes I.,Autonomous University of Madrid |
Garcia-Bermudez J.,Autonomous University of Madrid |
And 11 more authors.
Oncogenesis | Year: 2013
Recent findings in colon cancer cells indicate that inhibition of the mitochondrial H+-adenosine triphosphate (ATP) synthase by the ATPase inhibitory factor 1 (IF1) promotes aerobic glycolysis and a reactive oxygen species (ROS)-mediated signal that enhances proliferation and cell survival. Herein, we have studied the expression, biological relevance, mechanism of regulation and potential clinical impact of IF1 in some prevalent human carcinomas. We show that IF1 is highly overexpressed in most (>90%) of the colon (n=64), lung (n=30), breast (n=129) and ovarian (n=10) carcinomas studied as assessed by different approaches in independent cohorts of cancer patients. The expression of IF1 in the corresponding normal tissues is negligible. By contrast, the endometrium, stomach and kidney show high expression of IF1 in the normal tissue revealing subtle differences by carcinogenesis. The overexpression of IF1 also promotes the activation of aerobic glycolysis and a concurrent ROS signal in mitochondria of the lung, breast and ovarian cancer cells mimicking the activity of oligomycin. IF1-mediated ROS signaling activates cell-type specific adaptive responses aimed at preventing death in these cell lines. Remarkably, regulation of IF1 expression in the colon, lung, breast and ovarian carcinomas is exerted at post-transcriptional levels. We demonstrate that IF1 is a short-lived protein (t1/2 ~ 100 min) strongly implicating translation and/or protein stabilization as main drivers of metabolic reprogramming and cell survival in these human cancers. Analysis of tumor expression of IF1 in cohorts of breast and colon cancer patients revealed its relevance as a predictive marker for clinical outcome, emphasizing the high potential of IF1 as therapeutic target. © 2013 Macmillan Publishers Limited.
PubMed | Autonomous University of Madrid, Hospital Universitario Of Vigo and Research Center Biomedica En Red Of Enfermedades Raras Ciberer
Type: | Journal: Journal of translational medicine | Year: 2015
Muscle diseases have been associated with changes in the expression of proteins involved in energy metabolism. To this aim we have developed a number of monoclonal antibodies against proteins of energy metabolism.Herein, we have used Reverse Phase Protein Microarrays (RPMA), a high throughput technique, to investigate quantitative changes in protein expression with the aim of identifying potential biomarkers in rare neuromuscular diseases. A cohort of 73 muscle biopsies that included samples from patients diagnosed of Duchenne (DMD), Becker (BMD), symptomatic forms of DMD and BMD in female carriers (Xp21 Carriers), Limb Girdle Muscular Dystrophy Type 2C (LGMD2C), neuronal ceroid lipofuscinosis (NCL), glycogenosis type V (Mc Ardle disease), isolated mitochondrial complex I deficiency, intensive care unit myopathy and control donors were investigated. The nineteen proteins of energy metabolism studied included members of the mitochondrial oxidation of pyruvate, the tricarboxylic acid cycle, -oxidation of fatty acids, electron transport and oxidative phosphorylation, glycogen metabolism, glycolysis and oxidative stress using highly specific antibodies.The results indicate that the phenotype of energy metabolism offers potential biomarkers that could be implemented to refine the understanding of the biological principles of rare diseases and, eventually, the management of these patients.We suggest that some biomarkers of energy metabolism could be translated into the clinics to contribute to the improvement of the clinical handling of patients affected by rare diseases.
Damman P.,University of Amsterdam |
Iniguez A.,Hospital Universitario Of Vigo |
Klomp M.,University of Amsterdam |
Beijk M.,University of Amsterdam |
And 9 more authors.
Circulation Journal | Year: 2011
Background: We evaluated the Genous™ Bio-engineered R stent™ in elderly patients undergoing non-urgent percutaneous coronary intervention. The elderly have an increased risk of (temporary) discontinuation of clopidogrel, which is associated with a higher risk of developing stent thrombosis (ST). Methods and Results: In the e-HEALING registry, 2,651 patients were <65, 1,403 were 65-74 and 869 were =75 years old. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction and target vessel revascularization. Secondary outcomes included target lesion revascularization (TLR) and ST. Cumulative event rates were estimated with the Kaplan-Meier method and compared with a log-rank test. TVF occurred significantly more often in elderly patients compared with younger patients (7.0% in patients aged <65, 8.8% in patients aged 65-74 and 11.7% in patients aged =75 years, P<0.001). There was a trend to higher TLR with increasing age (log-rank P=0.06) and no difference in ST. Conclusions: The 1-year results of the Genous stent in a population of elderly patients show a significantly higher TVF rate compared with younger patients, mainly driven by a higher mortality. Although there was a trend to higher TLR rates with increasing age, there was no difference in ST. This attests to the safety of this therapy for the elderly, in whom there could be concerns with administering long-term dual antiplatelet therapy.
PubMed | Hospital Universitario Virgen del Rocio, Hospital Universitario La Paz, Hospital Universitario Of San Juan, Hospital Clinico Universitario Of Santiago Of Compostela and 11 more.
Type: Journal Article | Journal: Revista espanola de cardiologia (English ed.) | Year: 2016
Few data exist on the outcomes of valvular cardiomyopathy patients referred for defibrillator implantation for primary prevention. The aim of the present study was to describe the outcomes of this cardiomyopathy subgroup.This multicenter retrospective study included consecutive patients referred for defibrillator implantation to 15 Spanish centers in 2010 and 2011, and to 3 centers after 1 January 2008.Of 1174 patients, 73 (6.2%) had valvular cardiomyopathy. These patients had worse functional class, wider QRS, and a history of atrial fibrillation vs patients with ischemic (n=659; 56.1%) or dilated (n=442; 37.6%) cardiomyopathy. During a follow-up of 38.1 21.3 months, 197 patients (16.7%) died, without significant differences among the groups (19.2% in the valvular cardiomyopathy group, 15.8% in the ischemic cardiomyopathy group, and 17.9% in the dilated cardiomyopathy group; P=.2); 136 died of cardiovascular causes (11.6%), without significant differences among the groups (12.3%, 10.5%, and 13.1%, respectively; P=.1). Although there were no differences in the proportion of appropriate defibrillator interventions (13.7%, 17.9%, and 18.8%; P=.4), there was a difference in inappropriate interventions (8.2%, 7.1%, and 12.0%, respectively; P=.03).All-cause and cardiovascular mortality in patients with valvular cardiomyopathy were similar to those in other patients referred for defibrillator implantation. They also had similar rates of appropriate interventions. These data suggest that defibrillator implantation in this patient group confers a similar benefit to that obtained by patients with ischemic or dilated cardiomyopathy.