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111.
Silvia Carra Germano Gaudenzi Alessandra Dicitore Davide Saronni Maria Celeste Cantone Alice Plebani Anna Ghilardi Maria Orietta Borghi Leo J. Hofland Luca Persani Giovanni Vitale 《International journal of molecular sciences》2021,22(6)
Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)y1 transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant. 相似文献
112.
Matthias Engleder Dr. Tea Pavkov‐Keller Dr. Anita Emmerstorfer Altijana Hromic Sabine Schrempf Dr. Georg Steinkellner Dr. Tamara Wriessnegger Prof. Erich Leitner Dr. Gernot A. Strohmeier Dr. Iwona Kaluzna Dr. Daniel Mink Dr. Martin Schürmann Dr. Silvia Wallner Prof. Peter Macheroux Prof. Karl Gruber Dr. Harald Pichler 《Chembiochem : a European journal of chemical biology》2015,16(12):1730-1734
Hydratases provide access to secondary and tertiary alcohols by regio‐ and/or stereospecifically adding water to carbon‐carbon double bonds. Thereby, hydroxy groups are introduced without the need for costly cofactor recycling, and that makes this approach highly interesting on an industrial scale. Here we present the first crystal structure of a recombinant oleate hydratase originating from Elizabethkingia meningoseptica in the presence of flavin adenine dinucleotide (FAD). A structure‐based mutagenesis study targeting active site residues identified E122 and Y241 as crucial for the activation of a water molecule and for protonation of the double bond, respectively. Moreover, we also observed that two‐electron reduction of FAD results in a sevenfold increase in the substrate hydration rate. We propose the first reaction mechanism for this enzyme class that explains the requirement for the flavin cofactor and the involvement of conserved amino acid residues in this regio‐ and stereoselective hydration. 相似文献
113.
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
114.
Yikai Chen Yang Tan Silvia Tessarini Sanjay Sampath 《Journal of Thermal Spray Technology》2013,22(2-3):110-115
Spray parameters play an important role on the microstructure and properties of plasma-sprayed coatings. Parameters such as spray distance, plasma gas flow and current, raster speed, and spray angle all can be varied. In this paper, an integrated study to investigate the effects and influences of spray angle on properties of yttria-stabilized zirconia coatings was carried out with spray angles of 60°, 75°, and 90° (to the substrate surface). In situ coating property sensor based on beam curvature measurements was used to measure the evolving stress and elastic moduli of the resultant coatings and combined with other characterization tools for thermo-physical property and microstructure analysis, such as laser flash and scanning electron microscopy. The results indicate that the coating with 60° spray angle had the lowest thermal conductivity and more compliant structure. This study seeks to understand the mechanism for this effect and will provide important insight into parametric sensitivities on complex spray parts. 相似文献
115.
Andrea Brenna Silvia Beretta Riccardo Uglietti Luciano Lazzari MariaPia Pedeferri Marco Ormellese 《腐蚀工程科学与技术》2017,52(4):253-260
The criterion used to verify the cathodic protection condition of a structure is based on structure-to-electrolyte potential measurement, which can include an ohmic drop contribution. Among the available techniques, the use of potential probes with internal reference electrode and of corrosion coupons with a so-called soil-access tube represents the most appropriate way to measure the IR-free potential, eliminating the ohmic drop contribution. An alternative is represented by on-off technique if equalising, galvanic or stray currents are not present. Laboratory tests have been carried out in soil-simulating solution on cathodically protected carbon steel in order to evaluate the effectiveness of off-potential for the assessment of cathodic protection. Instant-off potential is not reliable in overprotection condition; moreover, the accuracy of the measurement is strongly influenced by the presence of external current as galvanic or equalising currents. The effect of low-pass filter in the data acquisition system on the potential reading is discussed. 相似文献
116.
Silvia F. Moya Ruth L. Martins Antje Ota Edward L. Kunkes Malte Behrens Martin Schmal 《Applied Catalysis A: General》2012
The Pd on α-Al2O3 catalysts with Pd particles in the low nanometer range have been prepared by a sonochemical reduction and a colloidal method, respectively. The two catalysts differ in their particle size, the widths of their particle size distributions and the amount of carbon incorporation in the Pd lattice.The adsorptive properties of the Pd/Al2O3 samples are different as a result of the different preparation methods. The methane adsorption capacity of that sample with smaller particles is lower than that of the catalyst with larger particles and the energy of activation is nearly doubled. DRIFTS and TPD results of CO adsorption supported by transmission electron microscopy data indicate that the PdSON catalyst with smaller and more homogeneous particles than PdCOL is highly dispersed which influences the coupling-hydrogenolysis process.The catalytic activity evidenced the formation of different adspecies during methane coupling and chemisorption on both catalysts. During the hydrogenation the carbon adspecies formed mainly methane at low adsorption temperatures. The significant amount of adsorbed methane at 773 K is governed by the highly active coordination unsaturated sites at the surface. 相似文献
117.
Mercedes Álvarez Isabel M. Moreno Silvia Pichardo Ana M. Cameán A. Gustavo González 《Food chemistry》2012
Fifty wines from the Denomination of origin (DO) of Condado de Huelva were analysed for mineral content by measuring 12 elements (Al, Ba, Ca, Cu, Fe, K, Mg, Mn, Na, P, Sr and Zn) using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES). Samples were previously digested by heating with H2O2/HNO3 mixture. The results obtained showed that metal data set were non-normally distributed and accordingly, non-parametric statistics were applied. The average levels (medians) of these elements found in the samples are as follows, in mg/L: 2.54 (Al); 0.06 (Ba); 82.58 (Ca); 0.21 (Cu); 3.53 (Fe); 865.34 (K); 68.87 (Mg); 0.71 (Mn); 32.77 (Na); 71.61 (P); 0.48 (Sr); 0.56 (Zn). The interrelation of metal couples was studied through the Spearman non-parametric sample correlation, being Fe/Al, P/Mg, and Zn/Ba the most important correlations established. As a result of this study, we can suggest that the contribution to the safety intake limits (per week) of the studied elements through the wine consumption is not significant. Actually, they range between 0.1% in Fe and 11.9% in Mg, for normal drinkers. 相似文献
118.
Juliana C. Santos Alexandre Funck Isabelle J. L. Silva-Fernandes Silvia H. B. Rabenhorst Carlos A. R. Martinez Marcelo L. Ribeiro 《International journal of molecular sciences》2014,15(10):17333-17343
It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis. 相似文献
119.
120.
In the context of an industrial project, we evaluated the implementation of the software of a casino slot machine. This software has a significant amount of crosscutting concerns that depend on and interact with each other as well as with the modular concerns. We therefore wished to express our design using an appropriate aspect-oriented modeling approach. We therefore evaluated three candidate methodologies: Theme/UML, WEAVR, and RAM to establish their suitability. Remarkably, only the last of the three has shown to allow an adequate expression of the interactions, albeit not fully explicit. The first two fall short because half of the interaction types cannot be expressed at all while the other half need to be expressed using a work-around that hides the intention of the design. Neither does RAM allow a fully explicit expression of interactions, but it would be the most adequate approach for the slot machine case. 相似文献