De Miguel D.,University of Zaragoza |
De Miguel D.,Institute Investigacion Sanitaria Of Aragon Iss |
De Miguel D.,University College London |
Gallego-Lleyda A.,University of Zaragoza |
And 21 more authors.
Cancer Letters | Year: 2016
During the last years, a great effort has been invested into developing new TRAIL formulations with increased bioactivity, trying to overcome the resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumours. In our group, we have generated artificial lipid nanoparticles decorated with sTRAIL (LUV-TRAIL), emulating the physiological TRAIL-containing exosomes by which T-cells release TRAIL upon activation. We already demonstrated that LUV-TRAIL has greater cytotoxicity against both chemoresistant haematologic tumour cells and epithelial carcinoma cells compared to a form of sTRAIL similar to that used in clinical trials. In this study we have tested LUV-TRAIL in several human colon cancer cell lines with different sensitivity to sTRAIL. LUV-TRAIL significantly improved sTRAIL cytotoxicity in all colon cancer cell lines tested. Trying to ascertain the molecular mechanism by which LUV-TRAIL exhibited improved cytotoxicity, we demonstrated that TRAIL-coated lipid nanoparticles were able to activate DR5 more efficiently than sTRAIL, and this relied on LUV-TRAIL ability to promote DR5 clustering on the cell surface. Moreover, we show that TRAIL molecules are arranged in higher order oligomers only in LUV-TRAIL, which may explain their enhanced DR5 clustering ability. Finally, LUV-TRAIL showed significantly better antitumour activity than sTRAIL in an in vivo model using HCT-116 xenograft tumours in nude mice, validating its potential clinical application. © 2016 Elsevier Ireland Ltd
De Miguel D.,University of Zaragoza |
Gallego-Lleyda A.,University of Zaragoza |
Ayuso J.M.,University of Zaragoza |
Ayuso J.M.,Institute Investigacion En Ingenieria Of Aragon |
And 17 more authors.
Nanotechnology | Year: 2016
Purpose. Non-small cell lung cancer (NSCLC) is one the types of cancer with higher prevalence and mortality. Apo2-Ligand/TRAIL is a TNF family member able to induce apoptosis in tumor cells but not in normal cells. It has been tested in clinical trials against different types of human cancer including NSCLC. However, results of clinical trials have shown a limited efficacy of TRAIL-based therapies. Recently we have demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) greatly improved TRAIL cytotoxic ability being capable of killing chemoresistant hematological cancer cells. In the present work we have extended the study to NSCLC. Methods/patients. LUV-TRAIL-induced cytotoxicity was assessed on different NSCLC cell lines with different sensitivity to soluble TRAIL and on primary human tumor cells from three patients suffering from NSCLC cancer. We also tested LUV-TRAIL-cytotoxic ability in combination with several anti-tumor agents. Results. LUV-TRAIL exhibited a greater cytotoxic effect compared to soluble TRAIL both in A549 cells and primary human NSCLC cells. LUV-TRAIL-induced cell death was dependent on caspase-8 and caspase-3 activation. Moreover, combination of LUV-TRAIL with other anti-tumor agents such as flavopiridol, and SNS-032 clearly enhanced LUV-TRAIL-induced cytotoxicity against NSCLC cancer cells. Conclusion. The novel formulation of TRAIL based on displaying it on the surface of lipid nanoparticles greatly increases its anti-tumor activity and has clinical potential in cancer treatment. © 2016 IOP Publishing Ltd.
de Miguel D.,University of Zaragoza |
de Miguel D.,Institute Investigacion Sanitaria Of Aragon Iss |
Gallego-Lleyda A.,University of Zaragoza |
Ayuso J.M.,Institute Investigacion Sanitaria Of Aragon Iss |
And 16 more authors.
Recent Patents on Anti-Cancer Drug Discovery | Year: 2016
Background: Apo2-ligand/TRAIL, a member of the TNF cytokine superfamily capable of inducing apoptosis on tumor cells while sparing normal cells, is a promising anti-tumor agent. However, about 50% of human cancer are TRAIL resistant. Consequently, future TRAIL-based therapies will require the use of novel highly bioactive forms of TRAIL and/or the addition of sensitizing agents to TRAIL-induced apoptosis. Recently, we demonstrated that artificial lipid nanoparticles coated with bioactive TRAIL (LUV-TRAIL) greatly improved TRAIL activity and were able to induce apoptosis in chemoresistant hematological tumor cells. Objective: In this study, we have tested LUV-TRAIL-pro-apoptotic potential in human breast cancer. Method: Comparative analysis of cytotoxicity induced by sTRAIL and LUV-TRAIL was performed using several human breast tumor cell lines with different sensitivity to TRAIL. In vivo anti-tumor activity of LUV-TRAIL was also studied using a xeno-graft tumor model. Results: LUV-TRAIL improved not only sTRAIL in vitro cytotoxicity in all breast tumor cell lines tested but also showed more anti-tumor activity than sTRAIL in an in vivo xeno-graft tumor model. On the other hand, the concomitant treatment of LUV-TRAIL with the sensitizing agent flavopiridol (FVP) induced a higher level of cell death in TRAIL-resistant cell lines. TRAIL-sensitization induced by FVP was mediated by DR5 up-regulation, and interestingly TRAIL-apoptotic signaling was completely shifted towards DR5 upon FVP treatment. LUV-TRAIL could especially take advantage of this DR5 up-regulation, while sTRAIL was not able. Conclusion: To date, no special attention had been paid to this aspect of FVP-induced TRAIL-sensitization, may be because sTRAIL used were not able to take advantage of this DR5 up-regulation. Hence, LUV-TRAIL could be a better choice than sTRAIL to be used in combination with anti-tumor drugs inducing DR5 over-expression, since LUV-TRAIL is especially effective activating this death-receptor. © 2016 Bentham Science Publishers.
Enhancement of motor relearning and functional recovery in stroke patients: Non-invasive strategies for modulating the central nervous system [Potenciación del reaprendizaje motor y la recuperación funcional en pacientes con ictus: Estrategias no invasivas de modulación del sistema nervioso central]
Bravo-Esteban E.,San Jorge University |
Bravo-Esteban E.,Hospital Nacional Of Paraplejicos |
Lopez-Larraz E.,University of Zaragoza |
Lopez-Larraz E.,Institute Investigacion En Ingenieria Of Aragon
Revista de Neurologia | Year: 2016
Introduction. Most of the stroke survivors do not recover the basal state of the affected upper limb, suffering from a severe disability which remains during the chronic phase of the illness. This has an extremely negative impact in the quality of life of these patients. Hence, neurorehabilitation strategies aim at the minimization of the sensorimotor dysfunctions associated to stroke, by promoting neuroplasticity in the central nervous system. Development. Brain reorganization can facilitate motor and functional recovery in stroke subjects. Nonetheless,after the insult, maladaptive neuroplastic changes can also happen, which may lead to the appearance of certain sensorimotor disorders such as spasticity. Noninvasive brain stimulation strategies, like transcranial direct current stimulation or transcranial magnetic stimulation, are widely used techniques that, when applied over the primary motor cortex, can modify neural networks excitability, as well as cognitive functions, both in healthy subjects and individuals with neurological disorders. Similarly, brain-machine-interface systems also have the potential to induce a brain reorganization by the contingent and simultaneous association between the brain activation and the peripheral stimulation. Conclusion. This review describes the positive effects of the previously mentioned neurorehabilitation strategies for the enhancement of cortical reorganization after stroke, and how they can be used to alleviate the symptoms of the spasticity syndrome. © 2016 Revista de Neurología.
Rios R.,Institute Investigacion En Ingenieria Of Aragon |
Puertolas J.A.,Institute Investigacion En Ingenieria Of Aragon |
Puertolas J.A.,University of Zaragoza |
Martinez-Nogues V.,Institute Investigacion En Ingenieria Of Aragon |
And 5 more authors.
Journal of Applied Polymer Science | Year: 2013
The aim of this study was to explore the impact of the sequential irradiation and annealing process on the microstructure, thermooxidation behavior and mechanical properties of GUR 1050 ultrahigh molecular weight polyethylene (UHMWPE) with respect to the postirradiation annealed material. For this purpose, the effects of a variety of irradiation and annealing conditions on microstructure and mechanical properties were investigated. Differential scanning calorimetry was performed to characterize melting temperature, crystalline content and crystal thickness, whereas transmission electron microscopy provided additional insights into crystal morphology. Thermogravimetric experiments in air served to assess thermooxidation resistance and changes associated to radiation-induced crosslinking. Fatigue properties were studied from three different approaches, namely short-term cyclic stress-strain tests, long-term fatigue experiments and crack propagation behavior. Likewise, three experimental techniques (uniaxial tensile test, impact experiments, and load to fracture of compact tension specimens) allowed evaluation of the fracture resistance. The present findings confirm sequentially crosslinked UHMWPE exhibited improved thermooxidation resistance and thermal stability compared to post-irradiation annealed UHMWPE. Also, the mechanical behavior, including the fatigue and fracture resistance, of these materials was generally comparable regardless of the annealing strategy. Therefore, the sequential irradiation and annealing process might provide higher oxidation resistance, but not a significant improvement in mechanical properties compared to the single radiation dose and subsequent annealing procedure. Copyright © 2013 Wiley Periodicals, Inc.
Lopez-Larraz E.,University of Zaragoza |
Lopez-Larraz E.,Institute Investigacion En Ingenieria Of Aragon |
Montesano L.,University of Zaragoza |
Montesano L.,Institute Investigacion En Ingenieria Of Aragon |
And 4 more authors.
Journal of NeuroEngineering and Rehabilitation | Year: 2014
Background: Brain-machine interfaces (BMI) have recently been integrated within motor rehabilitation therapies by actively involving the central nervous system (CNS) within the exercises. For instance, the online decoding of intention of motion of a limb from pre-movement EEG correlates is being used to convert passive rehabilitation strategies into active ones mediated by robotics. As early stages of upper limb motor rehabilitation usually focus on analytic single-joint mobilizations, this paper investigates the feasibility of building BMI decoders for these specific types of movements. Methods: Two different experiments were performed within this study. For the first one, six healthy subjects performed seven self-initiated upper-limb analytic movements, involving from proximal to distal articulations. For the second experiment, three spinal cord injury patients performed two of the previously studied movements with their healthy elbow and paralyzed wrist. In both cases EEG neural correlates such as the event-related desynchronization (ERD) and movement related cortical potentials (MRCP) were analyzed, as well as the accuracies of continuous decoders built using the pre-movement features of these correlates (i.e., the intention of motion was decoded before movement onset). Results: The studied movements could be decoded in both healthy subjects and patients. For healthy subjects there were significant differences in the EEG correlates and decoding accuracies, dependent on the moving joint. Percentages of correctly anticipated trials ranged from 75% to 40% (with chance level being around 20%), with better performances for proximal than for distal movements. For the movements studied for the SCI patients the accuracies were similar to the ones of the healthy subjects. Conclusions: This paper shows how it is possible to build continuous decoders to detect movement intention from EEG correlates for seven different upper-limb analytic movements. Furthermore we report differences in accuracies among movements, which might have an impact on the design of the rehabilitation technologies that will integrate this new type of information. The applicability of the decoders was shown in a clinical population, with similar performances between healthy subjects and patients. © 2014 López-Larraz et al.; licensee BioMed Central Ltd.
Montijano E.,Centro Universitario Of La Defensa |
Aragues R.,CNRS Pascal Institute |
Sagues C.,Institute Investigacion En Ingenieria Of Aragon
IEEE Transactions on Robotics | Year: 2013
We address the data association problem of features that are observed by a robotic network. Every robot in the network has limited communication capabilities and can only exchange localmatches with its neighbors.We propose a distributed algorithm that takes these local matches and, by their propagation in the network, computes global correspondences. When the algorithm finishes, each robot knows the correspondences between its features and the features of all the other robots, even if they cannot directly communicate. The presence of spurious local correspondences may produce inconsistent global correspondences,which are association paths between features observed by the same robot. The contributions of this study are the propagation of the local matches and the detection and resolution of these inconsistencies. We formally prove that after executing the algorithm, all the robots finish with a data association that is free of inconsistencies.We provide a fully decentralized solution to the problem that is valid for any fixed communication topology and with bounded communications between the robots. Simulations and experimental results with real images show the performance of the method considering different features, matching functions, and robotic applications. © 2013 IEEE.
Pedro S.G.-D.,Biosensors |
Puyol M.,Biosensors |
Izquierdo D.,Institute Investigacion En Ingenieria Of Aragon |
Salinas I.,Institute Investigacion En Ingenieria Of Aragon |
And 2 more authors.
Nanoscale | Year: 2012
In this paper, a computer controlled microreactor to synthesize water soluble CdS and CdS/ZnS nanocrystals with in situ monitoring of the reaction progress is developed. It is based on ceramic tapes and the Low-Temperature Co-fired Ceramics technology (LTCC). As well the microsystem set-up, the microreactor fluidic design has also been thoroughly optimized. The final device is based on a hydrodynamic focusing of the reagents followed by a three-dimensional micromixer. This generates monodispersed and stable CdS and core-shell CdS/ZnS nanocrystals of 4.5 and 4.2 nm, respectively, with reproducible optical properties in terms of fluorescence emission wavelengths, bandwidth, and quantum yields, which is a key requirement for their future analytical applications. The synthetic process is also controlled in real time with the integration of an optical detection system for absorbance and fluorescence measurements based on commercial miniaturized optical components. This makes possible the efficient managing of the hydrodynamic variables to obtain the desired colloidal suspension. As a result, a simple, economic, robust and portable microsystem for the well controlled synthesis of CdS and CdS/ZnS nanocrystals is presented. Moreover, the reaction takes place in aqueous medium, thus allowing the direct modular integration of this microreactor in specific analytical microsystems, which require the use of such quantum dots as labels. © 2012 The Royal Society of Chemistry.
Gil A.,University of Lleida |
Medrano M.,University of Lleida |
Martorell I.,University of Lleida |
Lazaro A.,Institute Investigacion En Ingenieria Of Aragon |
And 3 more authors.
Renewable and Sustainable Energy Reviews | Year: 2010
Concentrated solar thermal power generation is becoming a very attractive renewable energy production system among all the different renewable options, as it has have a better potential for dispatchability. This dispatchability is inevitably linked with an efficient and cost-effective thermal storage system. Thus, of all components, thermal storage is a key one. However, it is also one of the less developed. Only a few plants in the world have tested high temperature thermal energy storage systems. In this paper, the different storage concepts are reviewed and classified. All materials considered in literature or plants are listed. And finally, modellization of such systems is reviewed. © 2009 Elsevier Ltd. All rights reserved.
De Matias J.,University of Extremadura |
Guerrero J.J.,Institute Investigacion En Ingenieria Of Aragon |
Moreno J.,University of Extremadura |
De Sanjose J.J.,University of Extremadura
International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences - ISPRS Archives | Year: 2010
Rock glacier is a rare case of study for 3D modelling. We use a stereo feature-based method and multi-view stereo reconstruction algorithms to get different types of cartography. The proposed method has been tested in a real rock glacier example (Veleta in Sierra Nevada, Spain) for producing maps with good results. This rock glacier is of high scientific interest because it is the southernmost active rock glacier in Europe and it has been analyzed every year since 2001. The research on the Veleta rock glacier is devoted to the study of its displacement and cartography through geodetic and photogrammetric techniques.