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41.
Federica Bovio Samantha Epistolio Alessandra Mozzi Eugenio Monti Paola Fusi Matilde Forcella Milo Frattini 《International journal of molecular sciences》2020,21(22)
The epidermal growth factor receptor (EGFR), through the MAP kinase and PI3K-Akt-mTOR axis, plays a pivotal role in colorectal cancer (CRC) pathogenesis. The membrane-associated NEU3 sialidase interacts with and desialylates EGFR by promoting its dimerization and downstream effectors’ activation. Among the targeted therapies against EGFR, the monoclonal antibody cetuximab is active only in a subgroup of patients not carrying mutations in the MAP kinase pathway. In order to better understand the EGFR-NEU3 interplay and the mechanisms of pharmacological resistance, we investigated the role of NEU3 deregulation in cetuximab-treated CRC cell lines transiently transfected with NEU3 using Western blot analysis. Our results indicate that NEU3 overexpression can enhance EGFR activation only if EGFR is overexpressed, indicating the existence of a threshold for NEU3-mediated EGFR activation. This enhancement mainly leads to the constitutive activation of the MAP kinase pathway. Consequently, we suggest that the evaluation of NEU3 expression cannot entirely substitute the evaluation of EGFR because EGFR-negative cases cannot be stimulated by NEU3. Furthermore, NEU3-mediated hyperactivation of EGFR is counterbalanced by the administration of cetuximab, hypothesizing that a combined treatment of NEU3- and EGFR-targeted therapies may represent a valid option for CRC patients, which must be investigated in the future. 相似文献
42.
Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands
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Dr. Silvia Pace Dr. Giandomenico Brogin Dr. Maria Antonietta Stasi Dr. Teresa Riccioni Franco Borsini Dr. Francesca Capocasa Dr. Francesco Manera Carlo Tallarico Dr. Pietro Grossi Dr. Federica Vacondio Dr. Michele Bassi Dr. Francesca Bartoccini Dr. Simone Lucarini Dr. Giovanni Piersanti Prof. Giorgio Tarzia Walter Cabri Dr. Patrizia Minetti 《ChemMedChem》2015,10(7):1149-1152
Inhibition of adenosine A2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A2AR (Ki=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours). 相似文献
43.
Luca Maria Chiesa Maria Nobile Federica Ceriani Francesco Arioli 《Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment》2018,35(7):1340-1355
Demand for honey is increasing, especially if it is organic and if its nutritional properties are linked to untreated environments in order to guarantee quality for health. Sources of contamination of honey can be divided into environmental and apicultural. Therefore, the distribution of persistent organic pollutants, pesticides and antibiotic residues from geographical areas with different contamination sources (high anthropic impact, intensive farming, husbandry and low anthropic impact) was investigated in order to confirm the potential transfer of xenobiotics into the supply chain and to give beekeepers tools for the selection of areas dedicated to organic production. The presence of polychlorinated biphenyls, polybrominated diphenyl ether and polycyclic aromatic hydrocarbons was confirmed, not only in proximity to highly urbanised centres, where the concentrations were higher, but in all environment contexts, confirming their ubiquity. No antibiotics or neonicotinoids were detected in 95 organic honeys, demonstrating the absence of apicultural treatments and consequently the good quality of honey of different areas. These results are important due to the undefined regulatory European situation on honey antibiotic limits. 相似文献
44.
The Rovereto Emotion and Cooperation Corpus (RECC) is a new resource collected to investigate the relationship between cooperation
and emotions in an interactive setting. Previous attempts at collecting corpora to study emotions have shown that this data
are often quite difficult to classify and analyse, and coding schemes to analyse emotions are often found not to be reliable.
We collected a corpus of task-oriented (MapTask-style) dialogues in Italian, in which the segments of emotional interest are
identified using psycho-physiological indexes (Heart Rate and Galvanic Skin Conductance) which are highly reliable. We then
annotated these segments in accordance with novel multimodal annotation schemes for cooperation (in terms of effort) and facial
expressions (an indicator of emotional state). High agreement was obtained among coders on all the features. The RECC corpus
is to our knowledge the first resource with psycho-physiological data aligned with verbal and nonverbal behaviour data. 相似文献
45.
Gelatin reactivity with isocyanate was studied by using the easy detectable 1-naphthyl-isocyanate (NphI). Four different NphI/gelatin
feed ratios were investigated with NphI molar amount ranging between 1/10 and 1/1 with respect to the possible reactive groups
of gelatin. The reactions were carried out at 45 °C in DMSO as solvent, under nitrogen atmosphere. Modified gelatin samples
were characterized by IR, UV–VIS, fluorescence spectroscopies as well as by proton and DOSY NMR. Spectroscopy results allow
to evidence the presence of both bonded and unbonded naphthyl derivatives in the gelatin samples. Unbonded species were present
particularly at the highest NphI/gelatin feed ratio and their formation was correlated to the increasing competition of the
reaction with water since the amount of available reactive groups on gelatin was comparable or smaller than the amount of
residuum water in dry gelatin. 相似文献
46.
47.
Changes in urokinase-plasminogen activator (u-PA) and u-PA receptor (u-PAR) expression at the protein and mRNA level in resting neutrophils and in neutrophils activated by phorbol myristate acetate (PMA) were examined. Low amounts of u-PA were found intracellularly or membrane-bound in resting neutrophils. However, incubation of resting neutrophils with purified exogenous u-PA (10 IU/ml) revealed extensive binding of u-PA to cell membranes. Excess amino-terminal fragment of the u-PA molecule, a proteolytically inactive fragment of u-PA (amino acids 1-135) blocked binding of exogenous u-PA to the cell membrane. These results, collectively, indicate that the binding of u-PA is specific and that resting neutrophils have unoccupied u-PA receptors on their cell membrane. Addition of PMA led to an increase (P < 0.01) in total cell-associated, membrane-bound u-PA activity and u-PA mRNA expression by bovine neutrophils. In contrast. PMA increased u-PAR mRNA levels but this was accompanied by a decrease (2.5-fold; P < 0.01) in free, unoccupied u-PA binding sites. No significant effects on total cell-associated or membrane-bound u-PA were found when neutrophils were treated with 4-phorbol 12,13 didecanoate, a phorbol ester that does not activate protein kinase C (PKC). Furthermore, addition of 1-(5-isoquinolinesylphonyl)-2-methlylpiperazine dihydrochloride (H-7), a potent PKC inhibitor, blocked the effect of PMA on total cell-associated u-PA activity. Thus, PKC plays a role in the modulation of u-PA and u-PAR by PMA in bovine neutrophils. 相似文献
48.
Characterization of microstructured optical fibers for wideband dispersion compensation 总被引:4,自引:0,他引:4
Poli F Cucinotta A Fuochi M Selleri S Vincetti L 《Journal of the Optical Society of America. A, Optics, image science, and vision》2003,20(10):1958-1962
Microstructured optical fibers (MOFs) with small hole-to-hole spacing and large airholes are designed to compensate the anomalous dispersion and the dispersion slope of single-mode fibers. The geometrical parameters that characterize triangular MOFs are chosen to optimize the fiber length and the compensation over a wide wavelength range. A proper design of the photonic crystal fiber geometry allows us to achieve dispersion values of approximately -1700 ps nm(-1) km(-1) at 1550 nm and to compensate the dispersion of standard fibers within +/- 0.5 ps nm(-1) km(-1) over a 100-nm range. The MOF dispersion properties have been studied by means of a numerical simulator for modal analysis based on the finite-element method. 相似文献
49.
Federica Zaccheria Rinaldo Psaro Nicoletta Ravasio Laura Sordelli Federica Santoro 《Catalysis Letters》2011,141(4):587-591
Abstract
Styrene oxide can be effectively isomerized to phenyl-acetaldehyde (98%) over amorphous silica alumina catalysts under very mild liquid phase conditions. On the other hand, a copper catalyst prepared using a silica zirconia support gave up to 80% yield in the hydrogenation of styrene oxide to 2-phenyl-ethanol. 相似文献50.
María C. Caracoche Jorge A. Martinez Patricia C. Rivas Fernanda Andreola Federica Bondioli Anna Maria Ferrari Tiziano Manfredini 《Journal of the American Ceramic Society》2008,91(7):2357-2359
This paper deals with the phase stability of an aqueous suspension of tetragonal Zr0.9 Pr0.1 O2 (20 wt%/vol%) at room temperature as a function of the aging time. The suspension is investigated in situ using the highly localized Perturbed Angular Correlations technique. The results indicate that an almost fully reversible degradation process toward monoclinic zirconia takes place through a first-order reaction of rate constant k =0.7 day−1 . Two successive diffusion mechanisms are observed that are interpreted as OH− ions' migration in the grain surface and then, as proton defects' diffusion into the bulk. 相似文献