Vila I.K.,University of Houston |
Yao Y.,University of Houston |
Kim G.,Soonchunhyang University |
Xia W.,University of Houston |
And 8 more authors.
Cancer Cell | Year: 2017
UBE2O is localized in the 17q25 locus, which is known to be amplified in human cancers, but its role in tumorigenesis remains undefined. Here we show that Ube2o deletion in MMTV-PyVT or TRAMP mice profoundly impairs tumor initiation, growth, and metastasis, while switching off the metabolic reprogramming of tumor cells. Mechanistically, UBE2O specifically targets AMPKα2 for ubiquitination and degradation, and thereby promotes activation of the mTOR-HIF1α pathway. Notably, inactivation of AMPKα2, but not AMPKα1, abrogates the tumor attenuation caused by UBE2O loss, while treatment with rapamycin or inhibition of HIF1α ablates UBE2O-dependent tumor biology. Finally, pharmacological blockade of UBE2O inhibits tumorigenesis through the restoration of AMPKα2, suggesting the UBE2O-AMPKα2 axis as a potential cancer therapeutic target. Vila et al. show that UBE2O, which is overexpressed in many human cancers, targets AMPKα2 for ubiquitination and degradation, and thereby promotes activation of the mTOR-HIF1α pathway. Genetic deletion or pharmacological blockade of UBE2O inhibits tumorigenesis through the restoration of AMPKα2. © 2017 Elsevier Inc.
Carmona-Bayonas A.,Hospital Universitario Morales Meseguer
British Journal of Cancer | Year: 2017
Background:Our objective was to develop a prognostic stratification tool that enables patients with cancer and pulmonary embolism (PE), whether incidental or symptomatic, to be classified according to the risk of serious complications within 15 days.Methods:The sample comprised cases from a national registry of pulmonary thromboembolism in patients with cancer (1075 patients from 14 Spanish centres). Diagnosis was incidental in 53.5% of the events in this registry. The Exhaustive CHAID analysis was applied with 10-fold cross-validation to predict development of serious complications following PE diagnosis.Results:About 208 patients (19.3%, 95% confidence interval (CI), 17.1–21.8%) developed a serious complication after PE diagnosis. The 15-day mortality rate was 10.1%, (95% CI, 8.4–12.1%). The decision tree detected six explanatory covariates: Hestia-like clinical decision rule (any risk criterion present vs none), Eastern Cooperative Group performance scale (ECOG-PS; <2 vs ⩾2), O2 saturation (<90 vs ⩾90%), presence of PE-specific symptoms, tumour response (progression, unknown, or not evaluated vs others), and primary tumour resection. Three risk classes were created (low, intermediate, and high risk). The risk of serious complications within 15 days increases according to the group: 1.6, 9.4, 30.6%; P<0.0001. Fifteen-day mortality rates also rise progressively in low-, intermediate-, and high-risk patients: 0.3, 6.1, and 17.1%; P<0.0001. The cross-validated risk estimate is 0.191 (s.e.=0.012). The optimism-corrected area under the receiver operating characteristic curve is 0.779 (95% CI, 0.717–0.840).Conclusions:We have developed and internally validated a prognostic index to predict serious complications with the potential to impact decision-making in patients with cancer and PE.British Journal of Cancer advance online publication, 7 March 2017; doi:10.1038/bjc.2017.48 www.bjcancer.com. © 2017 Cancer Research UK
Vilchez J.A.,University of Birmingham |
Vilchez J.A.,Hospital Universitario Virgen Of La Arrixaca |
Gallego P.,University of Birmingham |
Gallego P.,Hospital Universitario Morales Meseguer |
Lip G.Y.H.,University of Birmingham
Therapeutic Advances in Drug Safety | Year: 2014
The recent development of new oral anticoagulants (NOACs) offers the possibility of efficacy, relative safety and convenience compared with warfarin. This could lead to greater patient compliance, with easier management and improved provision of thromboprophylaxis. Safety whilst using NOACs should be focused on bleeding cases, surgery or on the management of patients receiving anticoagulant therapy with concomitant impairment of renal function, especially since many NOACs are dependent on renal excretion. Thus, if the clearance creatinine indicates severe renal impairment, NOACS will be contraindicated or their dose needs to be changed. In patients who need surgery, there are published protocols of management, depending on the severity of the intervention and renal function. In the case of severe hemorrhage, requiring rapid reversal of the anticoagulant effect and in the absence of specific antidotes, alternatives such as one of the nonspecific haemostatic agents must be considered. Clinical evaluation in bleeding situations and a meticulous risk-benefit appraisal for NOACs is needed, and these procoagulant agents and patients must be monitored closely. This article provides an overview of the pharmacology and potential risks, as well as the efficacy and safety of NOACs. © The Author(s), 2013.
Roldan V.,Hospital Universitario Morales Meseguer |
Arroyo A.B.,Hospital Universitario Morales Meseguer |
Salloum-Asfar S.,Hospital Universitario Morales Meseguer |
Manzano-Fernandez S.,University of Murcia |
And 5 more authors.
Thrombosis and Haemostasis | Year: 2014
There are few biomarkers able to forecast new thrombotic events in patients with AF. In this framework, microRNAs have emerged as critical players in cardiovascular biology. In particular, miR-146a-5p is recognised as an important negative regulator of inflammation. This study aims to evaluate the prognostic role and biological effect of functional MIR146A polymorphisms, rs2431697 and rs2910164, in non-valvular atrial fibrillation (AF) patients under oral anticoagulation. We studied 901 patients with permanent/paroxysmal AF stabilized for at least six months. Patients were followed-up for two years and adverse cardiovascular events (ACE) were recorded. In vitro studies were performed in monocytes from healthy homozygous for the two genotypes of rs2431697. Rs2910164 had no association with ACE. However, multivariate analysis (adjusted by CHA2DS2–VASc score) revealed that rs2431697TT was associated with adverse cardiovascular events [HR: 1.64 (1.09–2.47); p=0.017]. The predictive value of usefulness of the CHA2DS2–VASc+IL6+rs2431697 for predicting ACE, was statistically better than that predicted by CHA2DS2–VASc+IL6. Functional studies showed that after 24 hours incubation, monocytes from CC individuals showed a 65 % increase in miR-146a-5p levels, while TT individuals only showed a 28 % increase. Indeed, after 24 hours of LPS activation, TT monocytes showed a higher increase in IL6 mRNA expression than CC (52 % vs 26 %). Our study established MIR146A rs2431697 as a prognostic biomarker for ACE in anticoagulated AF patients. These data suggest that TT individuals, when submitted to an inflammatory stress, may be prone to a highest pro-inflammatory state due, in part, to lower levels of miR-146a-5p. © Schattauer 2014.
Mora R.B.,Hospital Universitario Morales Meseguer
Southern Medical Journal | Year: 2010
Urinothorax or urothorax (UT) is a rare condition which often goes undiagnosed. In published cases of UT, the pleural fluid is usually transudative and is very rarely exudative. We present a case of UT after right nephroureterectomy for urothelial carcinoma, in which the pleural fluid presented characteristics of exudate. The diagnosis of UT was confirmed with the finding of a pleural/serum creatinine ratio above one and after demonstrating the presence of a postsurgical urinoma in the right renal fossa. UT should be included in the differential diagnosis of pleural effusion in patients with a recent urinary tract disorder, even when it is pleural exudate. © 2010 by The Southern Medical Association.
Platelet concentrates from whole-blood donations (buffy-coat) or apheresis: Which one to use? [Concentrados de plaquetas procedentes de sangre total (buffy coat) u obtenidos por aféresis; ¿qué producto emplear?]
Lozano M.L.,Hospital Universitario Morales Meseguer |
Rivera J.,Hospital Universitario Morales Meseguer |
Vicente V.,Hospital Universitario Morales Meseguer
Medicina Clinica | Year: 2012
Platelet concentrates (PCs) prepared either from whole-blood donations by the buffy-coat method (BC), or by plateletpheresis are indicated to prevent or treat acute hemorrhage secondary to thrombocytopenia, and there is an ongoing debate about which platelet product should be used. Usage of each of these two products is highly heterogeneous among countries and individual institutions, ranging from 10 to 90%, with a 50:50 ratio in Europe. In comparison of pooled platelets prepared by the BC method and apheresis PCs, data suggest similar efficacy of the products. Regarding recipients' adverse reactions, there is no advantage for apheresis concentrates. From the donor's point of view, evidence favours using the abundance of platelets available from whole-blood donation. As residual viral transmission risk continues to fall, the advantage of apheresis products related to the decrease to donor exposure lessens. While the cost-effectiveness of apheresis products is comparable to that of other accepted blood safety interventions, in case of emerging pathogens, probably pathogen inactivation of pooled BC PCs would be a more desirable strategy. © 2011 Elsevier España, S.L. All rights reserved.
Alberca-de-las-Parras F.,Hospital Clinico Universitario Virgen Of La Arrixaca |
Marin F.,Hospital Clinico Universitario Virgen Of La Arrixaca |
Roldan-Schilling V.,Hospital Universitario Morales Meseguer |
Carballo-Alvarez F.,Hospital Clinico Universitario Virgen Of La Arrixaca
Revista Espanola de Enfermedades Digestivas | Year: 2015
The use of antithrombotic drugs (anticoagulants and antiplatelets) has increased significantly with our understanding of cardiovascular risk. Encountering patients on these therapies who require an endoscopic procedure is therefore increasingly common. At decision making the endoscopist must rely on other specialists (basically cardiologists and hematologists) as risk not only lies among increased bleeding odds but also in the possibility of thrombosis following dose discontinuation or change. Understanding the pharmacology, indications, and risks of endoscopic procedures is therefore essential if sound decisions are to be made. The efforts of four scientific societies have been brought together to provide clinical answers on the use of antiplatelets and anticoagulants, as well as action algorithms and a practical protocol proposal for endoscopy units. © 2015 Arán Ediciones, S. L.
Alcaraz-Mateos E.,Hospital Universitario Morales Meseguer |
Caballero-Aleman F.,Hospital Universitario Morales Meseguer
Revista Espanola de Patologia | Year: 2015
Pathologists are physicians who specialize in the morphological diagnosis of diseases through the study of cytotissular samples, for which they use, among other things, the optical microscope. This has been associated with musculoskeletal complaints. In order to determine the prevalence of these in pathologists working in Spain, an anonymous online questionnaire was sent to members of the Spanish Society of Pathology. Questions about visual defects and digital pathology were also included. A total of 557 pathologists completed the survey. Results are described and discussed. © 2014 SEAP y SEC.
Font C.,Hospital Universitario Morales Meseguer
Journal of the National Comprehensive Cancer Network : JNCCN | Year: 2014
The purpose of this prospective cohort study was to assess the feasibility of outpatient treatment in patients with cancer and objectively confirmed pulmonary embolism (PE), and to compare the performance of the different prognostic scales available in this setting. Patients were selected for outpatient management according to a set of exclusion criteria. Outcomes at 30 and 90 days of follow-up included thromboembolic recurrences, major bleeding, and all-cause death. The performance of 4 prognostic scales (Pulmonary Embolism Severity Index, Geneva Prognostic Score, POMPE-C, and Registro Informatizado de Enfermedad Tromboembólica [RIETE registry]) was evaluated. Of 138 patients, 62 (45%) were managed as outpatients. Incidental PE constituted 47% of the sample. Most patients treated at home had an incidentally detected PE (89%). The rate of recurrence and major bleeding events was similar in both groups. Mortality rates were higher for patients admitted to the hospital compared with outpatients at 30 days (18% vs 3%; P=.06) and 90 days (34% vs 10%; P=.001) of follow-up. None of the patients selected for home treatment required further admission because of PE complications. None of the prognostic models developed for symptomatic PE was significantly associated with 30-day mortality. Improved survival outcomes were observed in incidentally detected PEs compared with acute symptomatic events (overall mortality rates, 3.2% vs 18.4%; P=.006). A large proportion of patients with cancer and PE may be safely treated as outpatients, especially those with incidental PE. Cancer-specific prognostic scales including incidental PE should be developed for the optimal management of PE in this setting.
Ferrer-Marin F.,Hospital Universitario Morales Meseguer |
Amigo M.L.,Hospital Universitario Morales Meseguer |
Vicente V.,Hospital Universitario Morales Meseguer
Clinical Drug Investigation | Year: 2012
In recent years, there has been an increase in the use of tumour necrosis factor (TNF) inhibitors as treatment for several inflammatory conditions. However, the question of whether TNF inhibitors increase the risk of malignancies (including lymphoma and leukaemia) in these diseases remains controversial. Despite this concern, anti-TNF therapy is being used experimentally in the management of haematological patients with risk of leukaemic transformation such as myeloproliferative neoplasms. We report here the first ever reported case of blastic transformation in a patient with myelofibrosis under etanercept treatment for a severe hidradenitis suppurativa. Although etanercept provided a sustained partial response of the skin disease, the patient developed an acute myeloid leukaemia after 27 months on exclusively etanercept therapy. According to the Dynamic International Prognostic Scoring System-plus score, the patient had a low risk for leukaemic transformation. We discuss here the potential of TNF inhibitors to increase the already elevated risk of leukaemic transformation of these haematological diseases. © 2012 Springer International Publishing AG. All rights reserved.