483 research outputs found
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
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
SRC and PIM1 as potential co-targets to overcome resistance in MET deregulated non-small cell lung cancer
No full textBackground: The role of MET alterations in non-small cell lung cancer (NSCLC) is increasing and several targeted agents are under evaluation. MET exon 14 skipping mutations and MET amplifications are associated with potential sensitivity to MET inhibition, though resistance mechanisms are emerging. In MET addicted cells, MET inhibition leads to activation of proviral integration site for Moloney murine leukemia virus-1 (PIM1). PIM1 and proto-oncogene tyrosine-protein kinase Src (SRC) can regulate the expression of receptor tyrosine kinases (RTKs), potentially inducing resistance to MET inhibition through cross-activation. Methods: We evaluated the activity of class I-II MET inhibitors, the SRC inhibitor dasatinib, and pan-PIM inhibitors in four MET addicted cell lines. We assessed the effect of the dual MET/PIM and MET/ SRC inhibition on cell viability and at the protein level. We evaluated RNA expression profiles of the cell lines. Advanced NSCLCs were also screened for MET alterations. Results: All cell lines were sensitive to class I-II MET inhibitors. All cell lines were resistant to single PIM and SRC inhibition. Dual MET/PIM inhibition was synergistic or additive in MET amplified cell lines and dual MET/SRC inhibition was highly synergistic in all MET addicted cell lines. The addition of an SRC inhibitor partially prevents the RTKs cross-activation. MET alterations were found in 9 out of 97 evaluable samples (9.3%); median overall survival in MET altered patients was 5 months (95% CI, 3 m-NA). Conclusions: We identified a potential role of PIM inhibition in MET amplified tumors and of SRC inhibition in MET addicted tumors. Potential applications of this new treatment strategy warrant further evaluation
A monoclonal antibody that specifically recognizes m6A nucleoside
No full textA hybridoma against the nucleoside m6A has been obtained from mouse spleen. This hybridoma was named H65 and it secretes monoclonal antibodies anti-m6A. The competition assays showed that the monoclonal antibody was highly specific for m6A nucleoside.This work was supported by PGC grant no PB92-0004. C. Codony was recipient of a fellowship from PGC.Peer Reviewe
Biochar-based polymeric film as sustainable and efficient sorptive phase for preconcentration of steroid hormones in environmental waters and wastewaters
No full textThe Imp licit So lu t ion of the Con servat ive Hyperbo lic System sand the Determ inat ion of the Shock and Rarefact ionW ave
No full textAbs tra c t The imp licit so lu t ion s of the in it ial2boundary value con servat ive hyperbo lic
p rob lem are suggested and so lved by the algeb raic iterat ive m ethod num erically. Th is can be
u sed in the so lu t ion of the smoo th part fo r the hyperbo lic system to som e ex ten t. By the geo2
m et ric m ethod, the po sit ion of the shock and rarefact ion w ave fo r the scalar con servat ive hy2
perbo lic equat ion is determ inated.国家自然科学基金资助项目(19771069
Rapid Impact Assessment Matrix (RIAM) - An Analytical Tool in the Prioritization of Water Resources Management Problems in Ghana
No full textThe rapid impact assessment (RIAM), which was developed in Denmark, is a new tool for the execution of environmental impact assessments. RIAM is quite flexible, transparent and leaves a permanent record, which can be independently checked, validated or updated. RIAM has successfully been used to prioritize water resources management problems in Ghana in the order of which problems call for the most urgent attention. The priority list was easily validated and accepted to be the true reflection of the situation at a national workshop in which experts and representatives from water agencies, donor agencies, university faculties and departments, research institutes, private institutions and organizations including Non Governmental Organizations (NGOs) participated. The study has shown that RIAM, which can also be used in a developing country like Ghana, is a very useful tool in such prioritization process as has been applied in this exercise
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)
U n ifo rm Second2O rder A ccu rate D ifference Schem es fo r NonSelf2adjo in t Singu lar Pertu rbat ion P rob lem in Con servat ion Form
No full text摘要 考虑带小参数的守恒型非自共轭奇异摄动问题, 建立并证明一个二阶一致收格式.
Abs tra c t Non self2adjo in t singu lar pertu rbat ion p rob lem in con servat ion fo rm is
discu ssed. A un ifo rm ly second2o rder accu rate difference schem e is p resen ted and p roven
Update on HER-2 as a target for cancer therapy: alternative strategies for targeting the epidermal growth factor system in cancer
No full textThe epidermal growth factor (EGF) family of ligands and receptors interact to influence cell division, differentiation and motility. Much evidence supports their importance in causing and sustaining cell transformation in model systems and in human cancer. The exact mechanism by which this is achieved varies in different tumour types and from case to case. The EGF system is a target for new types of targeted chemotherapy. The choice of strategy will depend on the mechanism involved, however, and several approaches are under development or evaluation in clinical trials. Each will have a different spectrum of side effects and the potential for development of drug resistance
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