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Barreiro-De Acosta M.,University of Santiago de Compostela | Garcia-Bosch O.,Clinic Hospital | Manosa M.,Germans Trias i Pujol Hospital | Menchen L.,Gregorio Maranon University Hospital | And 2 more authors.
European Journal of Gastroenterology and Hepatology | Year: 2012

Aim: In refractory pouchitis, infliximab (IFX) has been used as rescue therapy; however, there is no clinical evidence for the use of adalimumab (ADA). The aim of this study was to report the efficacy of ADA in patients with refractory pouchitis previously treated with IFX. Methods: A retrospective, open-label, case series was designed. Patients with chronic refractory pouchitis treated with ADA were included. All patients were previously treated with IFX. The short-term and mid-term efficacy of ADA was evaluated. Results: Eight patients with chronic refractory pouchitis treated with ADA were included. After 8 weeks, 13% of the patients achieved remission and 62% showed a clinical response. At week 26, 13% achieved remission and 38% showed a clinical response. At week 52, 50% of the patients avoided a permanent ileostomy but only 25 achieved remission. Conclusion: ADA treatment was found to be an alternative for patients with chronic refractory pouchitis previously treated with IFX. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Perez-Magan E.,Molecular Pathology Research Unit | De Lope A.R.,Virgen de la Salud Hospital | Ribalta T.,Clinic Hospital | Ruano Y.,Molecular Pathology Research Unit | And 7 more authors.
Neuro-Oncology | Year: 2010

The majority of meningiomas are probably benign but a number of tumors display considerable histological and/ or clinical aggressivity, sometimes with unexpectedly high recurrence rates after radical removal. Understanding the potential behavior of these tumors in individual patients is critical for rational therapeutic decision-making. This study aimed to identify gene expression profiles and candidate markers associated with original and recurrent meningiomas. Unsupervised hierarchical clustering of the samples confirmed 2 main groups of meningiomas with distinct clinical behaviors. The gene expression profiling study identified genes and pathways potentially associated with meningioma recurrence, revealing an overall lower level of gene expression. The differential gene expression profiling analyses of original and recurrent meningiomas identified 425 known genes and expressed sequence tags related to meningioma recurrence, with SFRP1 (8p12), TMEM30B (14q23), and CTGF (6q23) showing the most disparate expression. Most of the differentially expressed genes were located at 1p, 6q, and 14q and were underexpressed in recurrences.Loss of such chromosomal regions has previously been associated with a higher risk of meningioma recurrence or malignant progression. Thus, at these locations, we propose the existence of novel candidate genes that could be involved in meningioma recurrence. In addition, the overexpression of genes of histone cluster 1 (6p) in recurrent meningiomas is reported here for the first time. Finally, the altered genes related tomeningioma recurrence are involved in pathways such as Notch, TGFb, andWnt, as described previously, and in other pathways such as cell cycle, oxidative phosphorylation, PPAR, and PDGF, not related before to meningioma recurrence. © The Author(s) 2010. Source

Navarro L.,University of Valencia | Gil-Benso R.,University of Valencia | Megias J.,University of Valencia | Munoz-Hidalgo L.,University of Valencia | And 5 more authors.
Neuroscience | Year: 2015

Glioblastoma (GBM) is the most frequent and malignant primary brain tumor. Conventional therapy of surgical removal, radiation and chemotherapy is largely palliative. Major vault protein (MVP), the main component of the vault organelle has been associated with multidrug resistance by reducing cellular accumulation of chemotherapeutic agents. With regard to cancer, MVP has been shown to be overexpressed in drug resistance development and malignant progression.The aim of the present study was to evaluate the MVP gene dosage levels in 113 archival samples from GBM and its correlation with patients' survival and epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog (PTEN) gene dosages. Fluorescent in situ hybridization revealed polysomy of chromosome 7 in 76.1% of the GBMs and EGFR amplification in a 64.6% of the tumors. Genetic status of EGFR, PTEN and MVP copies was determined by multiplex ligation-dependent probe amplification (MLPA) technique. 31% of the tumors showed the EGFR is variant III mutation (EGFRvIII) mutation and 74.3% of them presented amplification of MVP gene. Amplification of EGFR and MVP was found in a 63.7% and 56.6% of the GBM, respectively. An inverse correlation between MVP and PTEN dosage values was observed. Besides, an inverse relationship between the survival of the patients treated with chemotherapy and the levels of MVP copies was determined. In conclusion, our study reveals an important role of MVP, together with EGFRvIII and PTEN, in the progression of GBM and proposes it as a novel and interesting target for new treatment approaches. © 2015 IBRO. Source

Ascaso J.F.,University of Valencia | Millan J.,University Hospital Gregorio Maranon | Mateo-Gallego R.,Miguel Servet Hospital | Ruiz A.,CS Pinto | And 6 more authors.
European Journal of Internal Medicine | Year: 2011

Background: We aim to study the prevalence of metabolic syndrome (MS), hypertension and diabetes, and their relationship to cardiovascular disease in subjects with hypertriglyceridemia. Methods: This is an observational cross-sectional study, uncontrolled and multicentre study. Selected subjects were patients with hypertriglyceridemia (triglycerides, TG,≥200 mg/dl) visited in the Lipid Units of the Spanish Arteriosclerosis Society who met the inclusion criteria. Prevalence of MS (ATPIII and IDF criteria, MS-ATPIII or MS-IDF), hypertension and diabetes were studied. The presence of cardiovascular disease (CVD) was also determined. Results: The results showed that individuals referred for hypertriglyceridemia had a high prevalence of MS-ATPIII 79.6% and MS-IDF 75.2%. The prevalence of MS was independent of plasma triglyceride levels. The prevalence of hypertension and diabetes were 50.9% and 33.5%, respectively. The prevalence of diabetes was double than in the general population. The prevalence of CVD was 14.6%. 95.9% of CVD events were found in patients with MS-ATPIII and only 4.1% in the group without MS-ATPIII, significant differences. Conclusions: Hypertriglyceridemia is associated to the metabolic syndrome and diabetes, as well as the risk of CVD, independently of the levels of triglycerides. Hypertriglyceridemia may be an important marker in the screening of these severe metabolic and vascular abnormalities. © 2010 European Federation of Internal Medicine. Source

Fernandez-Martos C.,Valencian Institute of Oncology | Garcia-Albeniz X.,Harvard University | Pericay C.,Parc Tauli Hospital | Maurel J.,Clinic Hospital | And 11 more authors.
Annals of Oncology | Year: 2015

Background: The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes. Patients and methods: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A-preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS). Results: A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively. Conclusion: Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

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