166 research outputs found
MAP17 predicts sensitivity to platinum-based therapy, EGFR inhibitors and the proteasome inhibitor bortezomib in lung adenocarcinoma
Background
The high incidence and mortality of lung tumours is a major health problem. Therefore, the identification both of biomarkers predicting efficacy for therapies in use and of novel efficacious therapeutic agents is crucial to increase patient survival. MAP17 (PDZK1IP1) is a small membrane-bound protein whose upregulation is reported as a common feature in tumours from diverse histological origins. Furthermore, MAP17 is correlated with tumour progression.
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Methods
We assessed the expression of MAP17 in preclinical models, including cell lines and patient-derived xenografts (PDXs), assessing its correlation with sensitivity to different standard-of-care drugs in lung adenocarcinoma, as well as novel drugs. At the clinical level, we subsequently correlated MAP17 expression in human tumours with patient response to these therapies.
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Results
We show that MAP17 expression is induced during lung tumourigenesis, particularly in lung adenocarcinomas, and provide in vitro and in vivo evidence that MAP17 levels predict sensitivity to therapies currently under clinical use in adenocarcinoma tumours, including cisplatin, carboplatin and EGFR inhibitors. In addition, we show that MAP17 expression predicts proteasome inhibitor efficacy in this context and that bortezomib, an FDA-approved drug, may be a novel therapeutic approach for MAP17-overexpressing lung adenocarcinomas.
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Conclusions
Our results indicate a potential prognostic role for MAP17 in lung tumours, with particular relevance in lung adenocarcinomas, and highlight the predictive pot0065ntial of this membrane-associated protein for platinum-based therapy and EGFR inhibitor efficacy. Furthermore, we propose bortezomib treatment as a novel and efficacious therapy for lung adenocarcinomas exhibiting high MAP17 expression
Photodegradation of cytostatic drugs by g-C3N4: Synthesis, properties and performance fitted by selecting the appropriate precursor
Graphitic carbon nitride (g-C3N4) was synthetized by a one-step thermal method from different N-rich precursors,
namely melamine, dicyandiamide, urea, thiourea and cyanamide. The structure, optical and physicochemical
properties of g-C3N4 materials were studied by transmission electron microscopy (TEM), X-ray
photoelectron spectroscopy (XPS) and Raman spectroscopy, among others. Both melamine and dicyandiamide
provided a less porous structure composed by large flake sheets, whereas urea and thiourea favoured g-C3N4
composed by small flat sheets and wrinkles with a larger porosity. The establishment of more condensed g-C3N4
networks with a reduced band gap was also evidenced for melamine and dicyandiamide precursors, while urea
favoured less condensed melem or melon structures. The photoactivity of the different g-C3N4 was assessed for
the removal of an aqueous solution containing 5-fluorouracil (5-FU), cyclophosphamide (CP) or a mixture of both
cytostatic drugs, under near UV-Vis and solar-LED irradiations. The best performing photocatalysts under near
UV-Vis irradiation, were those prepared from melamine (kapp = 14.6 × 10–2 min–1 for 5-FU) and thiourea (kapp =
2.5 × 10–2 min–1 for CP), while urea was the most active under solar-LED irradiation (kapp = 0.183 × 10–2 min–1
for 5-FU). In addition, CP was more resistant to be degraded than 5-FU, and a competitive effect for the generated
hydroxyl radicals was evidenced when both pollutant molecules were in the same solution. The photoactivity of
g-C3N4 materials was justified by the combination of various effects: (i) surface area, (ii) well-connected and
condensed g-C3N4 structures and (iii) high surface C/N ratios with nitrogen vacanciesSpanish Projects from MCIN/AEI/FEDER "Una manera de hacer Europa" RTI2018-099224-B-I00FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades B-RNM-486-UGR20Junta de Andalucia-Consejeria de Universidad, Investigacion e Innovacion -Proyecto P21_00208MICIN/AEIEuropean Social Found (FSE) PRE2019-087946MICIN/AEI RYC-2019-026634-IFSE "El FSE invierte en tu futuro"Universidad de Granada/CBU
Functionalized Graphene Derivatives and TiO2 for High Visible Light Photodegradation of Azo Dyes
Functionalized graphene derivatives including graphene oxide (GO), reduced graphene
oxide (rGO), and heteroatom (nitrogen/sulphur (N/S) or boron (B))-doped graphene were used to
synthesize composites with TiO2 (T). The photocatalytic performance of composites was assessed
for the degradation of Orange G dye (OG) under simulated solar light. All the prepared graphene
derivatives—TiO2 composites showed better photocatalytic performance than bare TiO2. A higher
photocatalytic activity was found for the composites containing GO and N/S co-doped rGO
(kapp = 109.2 × 10−3 and 48.4 × 10−3 min−1
, for GO-T and rGONS-T, respectively). The influence of
both initial solution pH and the reactive species involved in the OG degradation pathway were
studied. The photocatalytic activity of the samples decreased with the increase of the initial pH
(from 3.0 to 10.0) due to the occurrence of electrostatic repulsive forces between the photocatalysts
surface and the molecules of OG, both negatively charged. The use of selective scavengers showed
that although the photogenerated holes dominate the degradation mechanism, radicals and singlet
oxygen also participate in the OG degradation pathway. In addition, reutilization experiments
indicated that the samples were stable under the reaction conditions used.ERDF/Ministry of Science, Innovation and Universities-State Research Agency
RTI2018-099224-B-I0
DTE_SECURITY: herramienta para la distribución segura y limitada de documentos electrónicos
DTE_SECURITY es una herramienta diseñada específicamente para distribuir de forma segura
y limitada libros, apuntes y manuales, generados en cualquier procesador de textos. En realidad,
se trata de un plug-in que se inserta y amplía las funciones de las herramientas de edición
electrónica de ADOBE: ACROBAT y ACROREAD. El objetivo que se persigue es aumentar la
confianza de los autores en la publicación electrónica, mejorando su seguridad y ampliando las
funciones que restringen el acceso a los mismos (consulta limitada, fechas de caducidad, redes
de trabajo, usuarios registrados, ...
Geographic context configuration in fusion algorithms for maritime surveillance
Proceedings of: 17th International Conference on Information Fusion (FUSION 2014): Salamanca, Spain 7-10 July 2014.Real fusion system applications can be required to operate on wide areas for long periods of time. Adaptation is a basic capability under these circumstances. This paper presents a maritime surveillance platform designed to be flexible and robust. It features online configuration capabilities allowing to: (a) change the applied algorithms, (b) modify the operating parameters of the running algorithms, (c) tune the characterization of the available sensors. These configurations can be applied to limited spatial regions and time spans. This allows to use powerful or more specific configurations for localized scenarios (risks, clutter, alarms), or account for exceptional situations that can affect sensors, such as weather anomalies.This work was funded by contract between DEIMOS SPACE, S.L.U. and Universidad Carlos III, by Spanish Ministry of Economy and Competitiveness under grants TEC2012- 37832-C02-01, TEC2011-28626-C02-02, and by Madrid Region Gov., grant CAM CONTEXTS (S2009/TIC-1485).Publicad
Bioinspired Synthesis of Platensimycin from Natural ent-Kaurenoic Acids
Ministerio de
Economía y Competitividad, PID2019-106222RB-C32/SRA
(State Research Agency, 10.13039/501100011033)Universidad de Granada/CBU
Photocatalytic Perfomance of ZnO-Graphene Oxide Composites towards the Degradation of Vanillic Acid under Solar Radiation and Visible-LED
Graphene oxide (GO) is used to enhance the photocatalytic activity of ZnO nanoparticles
for the degradation of vanillic acid (VA) under simulated solar light and visible-LED (λ > 430 nm).
ZnO-GO composites are prepared by a mixing and sonication process with different GO loadings
(i.e., from 1.8 to 6.5 wt.%). The materials are extensively characterized by thermogravimetric analysis
(TGA), physisorption of N2
, X-ray diffraction (XRD), infrared spectroscopy (FTIR), scanning electron
microscopy (SEM), point of zero charge (pHPZC), and UV-Vis diffuse reflectance spectroscopy (DRUV).
The presence of GO increases the photocatalytic activity of all the prepared composites in comparison
with the pristine ZnO. The highest photocatalytic activity is found for the composite containing
5.5 wt.% of GO (i.e., ZnO-GO5.5), reaching a VA degradation of 99% and 35% under solar light
and visible-LED, respectively. Higher TOC removal/VA degradation ratios are obtained from the
experiments carried out under visible-LED, indicating a more effective process for the mineralization
of VA than those observed under simulated solar light. The influence of hole, radical, and non-radical
scavengers is studied in order to assess the occurrence of the reactive oxygen species (ROS) involved
in the photocatalytic mechanism. The study of the photo-stability during three reuse experiments
indicates that the presence of GO in the composites reduces the photocorrosion in comparison with
pristine ZnO.Spanish Project ref. RTI 2018-099224-B100 funded by
ERDF/Ministry of Science, Innovation and UniversitiesState Research Agency and the Nano4Fresh
project (ref. PCI2020-112045), as part of the PRIMA Programme supported by the European Unio
Influencia del “bullying” y el “ciberbullying” en la motivación de los estudiantes de secundaria y su efecto en el rendimiento académico
El acoso escolar es una alarmante realidad en nuestra sociedad. Cuando hablamos de “bullying” nos referimos a situaciones en las que uno o más estudiantes persiguen e intimidan a otro/a por medio de insultos, rumores, humillaciones, aislamiento social, sobrenombres, agresiones físicas, amenazas y coacciones, pudiendo desarrollarse a lo largo de meses e incluso años, evolucionando en “ciberbullying” que hace referencia a una forma de agresión a través de las tecnologías, siendo sus consecuencias devastadoras tanto a nivel social como personal. Por eso la comunidad educativa no puede obviar estas situaciones y tomar conciencia para dar soluciones y procurar prevenirlo.El objetivo principal de este trabajo es diseñar una herramienta para determinar si el acoso escolar, ya sea en posición de víctima o agresor, es el factor determinante de la falta de motivación y el bajo rendimiento académico de los estudiantes en las escuelas de Educación Secundaria en Puerto Rico. A tal fin, se creará un cuestionario para maestros y otro para estudiantes, tanto de la corriente regular como de educación especial, para atender la necesidad y ayudar a entender realmente cuales son los factores asociados al problema objeto de estudio. Eso será precisamente lo que se presente en este artículo, el cuestionario elaborado y ya validado por criterio de jueces expertos y que tras su implementación y la obtención de los resultados servirá para presentar un modelo de intervención para estudiantes y profesorado que pretende potenciar la motivación y el rendimiento escolar de los estudiantes sobre todo cuando son víctimas de acoso escolar en cualquiera de sus modalidades
Identification of reference genes for real-time PCR cytokine gene expression studies in sheep experimentally infected with Fasciola hepatica
The aim of this study was to validate reference genes for gene normalisation using qRT-PCR in hepatic lymph nodes (HLN) and livers from sheep infected with Fasciola hepatica during early and late stages of infection. To this end, a comprehensive statistical approach (RefFinder) encompassing four different methods of analysis (geNorm, BestKeeper, ΔCt method and NormFinder) was used to validate ten candidate reference genes. Stability analysis of gene expression followed by pairwise variation (Vn/Vn + 1) analysis revealed that PGK1, HSP90AA1 and GYPC were the most stable reference genes and suitable for qRT-PCR normalisation in both HLN and liver tissues. These three genes were validated against FoxP3, IL-10, TGF-β, TNF-α and IL-1β genes in the HLN tissue of sheep vaccinated with Cathepsin L1 from F. hepatica and unvaccinated infected and uninfected controls during early stages of infection. In the liver, the three reference genes were validated against TNF-α and IL-1β during chronic stages of infection with F. hepatica and in uninfected controls. Our study is the first to evaluate and validate sheep reference genes in order to provide tools for monitoring cytokines in Fasciola hepatica infected sheep target organs. Our results present an approach to elucidate the role of different cytokines in F. hepatica vaccinated and infected shee
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