150 research outputs found
El consumo de cannabis y derivados en la provincia de Barcelona : analítica de las muestras aprehendidas
No full textTesi de Llicenciatura per a la obtenció del Grau de Farmàcia. Facultat de Farmàcia. Universitat de Barcelona. Director: Carmen de la Torre Boronat, Rafael Codony Salcedo. 1983
STAT3 as a potential immunotherapy biomarker in oncogene-addicted non-small cell lung cancer
No full textImmune checkpoint blockade has modified the treatment landscape for many types of tumors, including lung cancer. Still our knowledge on the biology of the interaction between tumor cells and the microenvironment is limited, preventing the optimal use of these new compounds and the maximum benefit that the patients can derive from them. We have actively worked on the role of STAT3, a transcriptional factor that causes innate resistance to targeted therapies in oncogene-addicted tumors. In this short review we take the opportunity to express our opinion and review existing knowledge on the immune role of STAT3 and the possible implications that this may have for the discovery of new biomarkers to predict response to immunotherapy, as well as new partners to combine with and increase the efficacy of immune checkpoint inhibitors
Incorporación de aceites poliinsaturados, alfatocoferol y minerales en pienso: Efectos sobre la composición y oxidación lipídica de plasma, hígado y carne de conejo
No full text[spa] En la presente Tesis Doctoral se estudió el efecto de la incorporación de aceites poliinsaturados, α-tocoferol y minerales en piensos sobre la composición en ácidos grasos, el contenido en α-tocoferol, la oxidación (índice del ATB) y la susceptibilidad a la oxidación (método inducido del naranja de xylenol) de plasma, hígado y carne de conejo. También se estudiarion los efectos de la cocción y la conservación a refrigeración de la carne cocida sobre estos parámetros. En un primer estudio se ensayaron diferentes dosis y tipos (girasol y linaza) de grasas en pienso, y la suplementación de la dieta con AT (100 mg/kg). Dosis y tipo de aceite, así como la suplementación con AT modificaron la composición en AG de plasma, hígado y carne, tanto por incorporación de AG de la dieta, como por modificación de la biosíntesis de ciertos AG. También alteraron la oxidación (índice del ATB) y la susceptibilidad a la oxidación (índice del naranja de xilenol o FOX) de plasma, hígado y carne de conejo. Cocción y refrigeración produjeron incrementos en la oxidación de la carne, que fueron menores tras suplementar las dietas con AT, siendo esto menos efectivo cuando los piensos contenían un 3% de linaza. El contenido en α-tocoferol del plasma fue indictivo del contenido en α-tocoferol de hígado y carne, y de su estado oxidativo. La cocción y la refrigeración de la carne cocida implicaron una pérdida de α-tocoferol y un incremento en la oxidación de la carne. La evaluación de la susceptibilidad a la oxidación mediante el método inducido del naranja de xilenol fue un buen predictor de la oxidación alcanzada tras la cocción. Entre los tratamientos estudiados, el que ofreció una composición en AG nutricionalmente más favorable y una mejor estabilidad oxidativa fue el que contenía 1,5% de linaza y 100 mg/kg de AT. En el segundo estudio se ensayaron diferentes niveles de oxidación en el aceite añadido a los piensos (sin oxidar, alto contenido en compuestos de oxidación primaria, y alto contenido en compuestos de oxidación secundaria), y la suplementación con AT y con Zn. La incorporación de aceites oxidados a los piensos no modificó de forma sustancial la composición en AG de plasma, hígado y carne de conejo, ni su oxidación. Sin embargo, cuando el aceite presentaba un alto contenido en compuestos de oxidación primaria, se redujo el contenido en αT en ellos, y aumentó la oxidabilidad en carne de conejo. Ésta fue reducida por la suplementación con AT, pero de forma menos efectiva cuando el aceite del pienso presentaba un alto contenido en compuestos de oxidación primaria. El contenido en Zn, Fe o Se en la carne no se modificó por los factores estudiados, pero la suplementación con Zn redujo en contenido en Cu en la carne, aunque esto no afectó a su oxidación. Tal como sucedió en el primer estudio, la cocción y la refrigeración aumentaron la oxidación en la carne, pero los valores de ATB alcanzados fueron menores que en el primer estudio. La evaluación de la susceptibilidad a la oxidación en carne cruda mediante el método inducido del naranja de xilenol fue indicativa de la oxidación alcanzada en la carne tras la cocción.[eng] The effects of the addition of different doses and sources (sunflower and linseed oil) of polyunsaturated oils to rabbit feeds, as well as the dietary supplementation with α-tocopheryl acetate (TA) on the fatty acid composition, the α-tocopherol content, the oxidation (TBA value) and the susceptibility to oxidation (FOX value) of rabbit plasma, liver and meat were assessed. The fatty acid composition of rabbit plasma, liver and meat was modified by the dose and source of oil added to feeds, and the dietary supplementation with TA, both by direct incorporation of fatty acids from diets and by the modification of some biosynthetic pathways. Also, liver and meat oxidation and susceptibility to oxidation were altered. Cooking and refrigeration of cooked meat decreased its α-tocoferol content and increased its TBA value. This increase was lower in meats from TA supplemented diets. From the studied diets, the 1.5% linseed oil (plus 1.5% animal fat) and 100 mg/kg of TA was the diet that produced meat with a more nutritionally favorable fatty acid composition and a better oxidative stability. In a second study, the effects of the addition of oils with a different oxidation level (not oxidized, high content of primary oxidation compounds or high content of secondary oxidation compounds) to rabbit feeds on the fatty acid composition, α-tocopherol content, oxidation (TBA value) and susceptibility to oxidation (FOX value) were assessed. Also, the effects of the dietary supplementation with TA and zinc were assessed. The incorporation of oxidized oils to feeds did not substantially alter the fatty acid composition of rabbit plasma, liver and meat, but when oil presented a high content of primary oxidation compounds it led to a reduced α-tocopherol content in rabbit plasma, liver and meat, as well as to an increase in meat susceptibility to oxidation. This was reduced by the dietary supplementation with TA, but it was less effective than when the oil added to feeds was not oxidized or contained a high content of secondary oxidation compounds
Evaluation of total hydroxytyrosol and tyrosol in extra virgin olive oils
No full textOlive oil phenolic compounds have been correlated to several health benefits. Nevertheless, the use of such information for commercial purposes was forbidden until 2006, when a European Regulation on health claims in food products was enacted (Reg. 1924/2006). In the case of olive oil, Regulation 432/2012 states that the health effect can be claimed only if the oil contains more than 5 mg of hydroxytyrosol and its derivatives (e.g., oleuropein complex and tyrosol) in 20 g of oil. The present work deals with the optimization of a method for performing hydrolysis after the extraction of polyphenols from olive oil was optimized, followed by derivatization and gas chromatographic analysis. The derivatization step was carefully optimized comparing different reagents and testing their efficiency, both on a standard solution and in a real sample conveniently spiked. Some commercial samples were analyzed and the results compared with the total amount of polyphenols calculated according the recommended method reported by the International Olive Council. A good correlation was obtained between the two methods (higher than 0.900)
Biogas upgrading: Optimal activated carbon properties for siloxane removal
No full textA total of 12 commercial activated carbons (ACs) have been tested for the removal of octamethylcyclotetrasiloxane (D4) in dynamic adsorption experiments using different carrier gases and D4 concentrations. Characterization of the ACs included several physical and chemical techniques. The D4 adsorption capacities were strongly related with the textural development of the ACs. Results showed that the optimum adsorbent for D4 is a wood-based chemically activated carbon, which rendered an adsorption capacity of 1732 ± 93 mg g-1 using 1000 ppm (v/v) of D4 with dry N2 as the carrier gas. When the concentration of D4 was lowered to typical values found in biogas, the adsorption capacity was halved. The presence of major biogas compounds (i.e., CH4 and CO2) and humidity further reduced the D4 adsorption capacity. The polymerization of D4 over the surface of all ACs was found to be relevant after prolonged contact times. The extent of this phenomenon, which may negatively affect the thermal regeneration of the AC, correlated reasonably well with the presence of phenolic and carboxylic groups on the carbon surfacesThis work was funded by the Ministerio de Innovacion y Ciencia (MICINN) (SIRENA CTQ2011-24114 and NOVE-DAR CSD2007-00055). Alba Cabrera-Codony thanks Generalitat de Catalunya DEC for her predoctoral grant (2013F1_B100054). Rafael Gonzalez-Olmos also thanks MICINN for his Juan de la Cierva fellowship (JCI-2010-07104
Regeneration of siloxane-exhausted activated carbon by advanced oxidation processes
No full textIn the context of the biogas upgrading, siloxane exhausted activated carbons need to be regenerated in order to avoid them becoming a residue. In this work, two commercial activate carbons which were proved to be efficient in the removal of octamethylcyclotetrasiloxane (D4) from biogas, have been regenerated through advanced oxidation processes using both O3 and H2O2.After the treatment with O3, the activated carbon recovered up to 40% of the original adsorption capacity while by the oxidation with H2O2 the regeneration efficiency achieved was up to 45%. In order to enhance the H2O2 oxidation, activated carbon was amended with iron. In this case, the regeneration efficiency increased up to 92%This work was funded by Ministerio de Innovacion y Ciencia (MICINN) (SIRENA CTQ2011-24114). A. Cabrera-Codony thanks Generalitat de Catalunya DEC for her predoctoral grant (2013FI_B1 00054). R. Gonzalez-Olmos also wants to thank MICINN for his Juan de la Cierva fellowship (JCI-2010-07104). LEQUIA has been recognized as consolidated research group by the Catalan Government with code 2014-SGR-1168. Authors thank Gemma Rustullet for technical suppor
Abstract 3077: Tumor cells with acquired resistance to EGFR inhibitors and overexpression or activation of AXL, MET and FGFR1 are insensitive to single-agent treatment targeting AXL, MET or FGFR
No full textAbstract
Background: Aberrant activity of the MET, FGFR1 and AXL receptors has been associated with the development of resistance to first, second and third generation EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutated non-small cell lung cancer (NSCLC) patients.
Methods: We obtained 6 resistant lines by treating EGFR-mutated (exon 19), TKI sensitive PC9 cells with increasing concentrations of gefitinib or erlotinib. The p.T790M resistance mutation emerged in two cell lines (GR1, GR4), which remained sensitive to osimertinib, a third generation EGFR TKI. Six new cell lines to resistant to “second line” osimertinib were generated from GR1 and GR4 by exposure to increasing concentrations of the inhibitor. Finally, six more cell lines resistant to “first line” osimertinib were derived from the PC9 parental cells. All resistant cell lines were genotyped for selected genes (including EGFR) and characterized for AXL, MET and FGFR1 expression and activation by Q-RT-PCR, immunohistochemistry and Western blotting. The effects of AXL (BGB324), MET (crizotinib, capmatinib) and FGFR1 (nindetanib) inhibitors on the parental and the 18 resistant cell lines were analyzed by MTT and, in some cases, by colony formation. AXL was stably silenced in some of the resistant cell lines.
Results: All cell lines resistant to “first line” gefitinib, erlotinib and osimertinib maintained the exon 19 EGFR sensitizing mutation. In contrast, three of the resistant cell lines to “second line” osimertinib lost the exon 19 and the p.T790M mutations. In two more, the p.T790M dropped to low allelic fractions (1% and 0.03%). Regardless of the EGFR status, AXL overexpression was the most common event related to EGFR TKI resistance in our panel of 18 cell lines, with FGFR1 and MET overexpression or activation as less frequent events. In proliferation assays, the IC50 of the EGFR TKI resistant cell lines for BGB324 (AXL inhibitor) was indistinguishable from the IC50 of the parental, EGFR TKI sensitive cell line. Similar results were obtained in the case of capmatinib, crizotinib (MET inhibitors) and nintedanib (FGFR inhibitor). Stable silencing of AXL on some of the AXL-overexpressing resistant cell lines had no effects in terms of doubling times, morphology of cells or sensitivity to EGFR TKIs. In combination experiments, the effect of BGB and MET inhibitors was found to be additive.
Conclusions: In tumor cell line models of acquired resistance to EGFR TKIs, overexpression or activation of AXL, MET and FGFR1 was not associated to sensitivity to single-agent treatment with AXL, MET or FGFR inhibitors. Multitargeted approaches might be more effective in this setting.
Citation Format: Jordi Bertran-Alamillo, Miguel Angel Molina-VIla, Cristina Teixidó, Jordi Codony-Servat, Ana Giménez-Capitán, Carles Codony-Servat, Silvia García-Román, Erika Aldeguer, Sonia Rodríguez, Rafael Rosell. Tumor cells with acquired resistance to EGFR inhibitors and overexpression or activation of AXL, MET and FGFR1 are insensitive to single-agent treatment targeting AXL, MET or FGFR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3077. doi:10.1158/1538-7445.AM2017-3077</jats:p
Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC
No full textThe efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) is limited by adaptive activation of cell survival signals. We hypothesized that both signal transducer and activator of transcription 3 (STAT3) and Src-YES-associated protein 1 (YAP1) signaling are dually activated during EGFR TKI treatment to limit therapeutic response
Desarrollo y aplicación de un sistema de información para la elaboración de tablas de composición de alimentos
No full text[spa] Las tablas de composición de alimentos (TCA) son herramientas imprescindibles para evaluar la alimentación de los individuos o poblaciones con la finalidad de establecer cuales son sus necesidades y, conociendo estas, planificar su alimentación. Normalmente, se elaboran destinadas a un ámbito nacional ya que cada país tiene sus particularidades en cuanto a los alimentos consumidos. Las TCA se pueden elaborar mediante tres métodos diferentes: el directo, el indirecto y el combinado. El primero consiste en la planificación y ejecución de un plan de muestreo y análisis. El segundo, en la recopilación y escrutinio de datos de composición ya existentes. El tercero consiste en aplicar el método directo para los alimentos que tienen un mayor peso en la alimentación de la población y el método indirecto para aquellos que tienen un peso menor. En España existen diferentes TCA publicadas, pero en general presentan los siguientes inconvenientes: 1) Están basadas en datos antiguos. 2) Las fuentes de datos no están bien documentadas. 3) Los componentes no están bien documentados. Estos problemas limitan la fiabilidad de los datos y su comparabilidad. Estos problemas pueden ser debidos al hecho que no se ha profundizado suficientemente en el desarrollo de métodos para compilar TCA. El objetivo principal de la tesis fue desarrollar y aplicar un método de trabajo para compilar datos de composición de alimentos en una base de datos de composición de alimentos (BDCA) y generar a partir de ésta una TCA españoles destinada al análisis nutricional de la alimentación de poblaciones e individuos. Para conseguir este objetivo se marcaron los siguientes objetivos secundarios: 1) Desarrollar un SI para compilar datos de composición; 2) Desarrollar un método de evaluación de los datos; 3) Diseñar una aplicación informática para el tratamiento de la información recopilada; 4) Finalmente, generar una TCA sin valores desconocidos que ofrezca datos de composición para el máximo de componentes y alimentos. El método seguido para compilar la BDCA es el indirecto y su desarrollo implicó el diseño y elaboración de todo un Sistema de Información (SI). Éste constaba de dos subsistemas: uno de Archivo en el cual los datos estaban en soporte papel, y otro Informático en el cual los datos se encontraban en una base de datos. Se aplicaron algunas de las recomendaciones y códigos propuestos por INFOODS y EUROFOODS. Los datos recopilados procedentes de diferentes fuentes eran introducidos en unos formularios donde se convertían a unidades y formas de expresión estándar y eran evaluados siguiendo un sistema de puntuaciones diseñado específicamente. Posteriormente los datos se introducían dentro del sistema informático donde eran seleccionados y/o agregados para pasar a formar parte de la base de datos destinada a los usuarios. Los valores desconocidos eran estimados siguiendo un protocolo pre-establecido. A partir de datos extraídos de esta base de datos se elaboró una TCA impresa sin valores desconocidos. Además, pudieron extraerse algunas observaciones importantes respecto a las recomendaciones INFOODS y EUROFOODS. El SI elaborado permite una actualización continua de la base de datos y la documentación completa de todos los valores.[eng] Food composition tables (FCT) are basic tools in the nutritional assessment of individuals or populations in order to establish which are their necessities in terms of nutrient intake and, once established these, FCT are used for planning food and nutrient intakes. Three different methods for elaborating a FCT have been distinguished: direct, indirect and the combination method. Spanish FCT presents three main disadvantages: 1) They contain rather old food composition data; 2) Data sources are not documented properly; 3) Components are not documented adequately. These inconveniences limit reliability and comparability of results obtained using Spanish FCT. So, the main objective of this thesis were to develop and deploy a system to compile food composition data in a food composition data base, and generate a FCT appropriate for its use in the nutritional assessment of populations and individuals. To accomplish this objective, four specific objectives were established: 1) To develop an information system for compiling food composition data; 2) To develop a method for assessing the quality of data; 3) To design a software for the treatment of the compiled information; 4) To generate a FCT without unknown values. The food composition data base was compiled using the indirect method. The information system elaborated consist of an archival system and computer programme. Some of the recommendations and codes proposed by INFOODS and EUROFOODS were applied. Data gathered from different sources were introduced in forms where they were converted to standard units and modes of expression and evaluated following the scoring system designed. Then, data were introduced in the computer programme where they were selected or aggregated. Unknown values were estimated following pre-established procedures, and the user database were finally generated. Some important observations were extracted from the application of INFOODS and EUROFOODS recommendations. The information system created allows a continuos actualization of the data base and the complete documentation of values
Siloxane removal in the energy recovery of biogas: sequential adsorption/oxidation processes
No full textThe thesis deals with removal of organosilicon compounds in the energy recovery of biogas. Alternative adsorbents for the siloxane removal were studied, and the physical and chemical mechanisms involved in the siloxane adsorption were discovered, which improved the yield of the adsorption and regeneration technologies using both activated carbons and zeolites. Moreover, several technologies based on advanced oxidation processes have been applied in order to regenerate and reuse the exhausted adsorbents.
The thesis studies the siloxane removal at lab-scale close to real scenario conditions, including the competitive adsorption with compounds usually found in biogas, in the presence of humidity and with the same gas matrix, which allowed to select the most efficient materials for this purpose. Therefore, the knowledge reported in the thesis dissertation is directly transferable to field application to upgrade the siloxane removal systemAquesta tesi estudia l'eliminació de compostos volàtis de silici (siloxans) per la recuperació energètica del biogàs. Es van estudiar diferents adsorbents per l'adsorció de siloxans, determinants les propietats físico-químiques superficials que en condicionen l'eficiència, permetent millorar el rendiment de l'adsorció i permetent la regeneració en carbons actius i zeolites esgotats.
La tesi estudia l'eliminació de siloxans a escala de laboratori en condicions properes a les reals del biogàs, incloent l'adosrció competitiva amb altres compostos orgànics volàtics, en presència d'humitat i amb diferents matrius gasoses, la qual cosa va permetre seleccionar els materials òptims per aquest propòsit.Per tant el coneixement derivat d'aquesta tesi és directament transferible per tal de millorar els sistemes d'eliminació siloxane
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