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Salicylketoximes That Target Glucose Transporter 1 Restrict Energy Supply to Lung Cancer Cells 下载免费PDF全文
Dr. Carlotta Granchi Dr. Yanrong Qian Dr. Hyang Yeon Lee Ilaria Paterni Carolina Pasero Jessica Iegre Kathryn E. Carlson Prof. Dr. Tiziano Tuccinardi Prof. Dr. Xiaozhuo Chen Prof. Dr. John A. Katzenellenbogen Prof. Dr. Paul J. Hergenrother Prof. Dr. Filippo Minutolo 《ChemMedChem》2015,10(11):1892-1900
The glucose transporter GLUT1 is frequently overexpressed in most tumor tissues because rapidly proliferating cancer cells rely primarily on glycolysis, a low‐efficiency metabolic pathway that necessitates a very high rate of glucose consumption. Because blocking GLUT1 is a promising anticancer strategy, we developed a novel class of GLUT1 inhibitors based on the 4‐aryl‐substituted salicylketoxime scaffold. Some of these compounds are efficient inhibitors of glucose uptake in lung cancer cells and have a notable antiproliferative effect. In contrast to their 5‐aryl‐substituted regioisomers, the newly synthesized compounds reported herein do not display significant binding to the estrogen receptors. The inhibition of glucose uptake in cancer cells by these compounds was further observed by fluorescence microscopy imaging using a fluorescent analogue of glucose. Therefore, blocking the ability of tumor cells to take up glucose by means of these small molecules, or by further optimized derivatives, may be a successful approach in the development of novel anticancer drugs. 相似文献
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Asylbek Kulmyrzaev Carlotta Cancelliere David Julian McClements 《Journal of the science of food and agriculture》2000,80(9):1314-1318
A solution of heat‐denatured whey proteins was prepared by heating 100 g kg−1 whey protein isolate (WPI) at pH 7.0 to 75 °C for 15 min in the absence of salt. Heat treatment caused the globular protein molecules to unfold, but electrostatic repulsion opposed strong protein–protein aggregation and so prevented gel formation. When the heat‐denatured whey protein solution was cooled to room temperature and mixed with 15 mM CaCl2, it formed a gel. We investigated the influence of the presence of sucrose in the protein solutions prior to CaCl2 addition on the gelation rate. At relatively low concentrations (0–100 g kg−1), sucrose decreased the gelation rate, presumably because sucrose increased the aqueous phase viscosity. At higher concentrations (100–300 g kg−1), sucrose decreased the gelation rate, probably because sugar competes for the water of hydration and therefore increases the attraction between proteins. These data have important implications for the application of cold‐setting WPI ingredients in sweetened food products such as desserts. © 2000 Society of Chemical Industry 相似文献
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Michele Massa Mirko Rivara Gaetano Donofrio Luigi Cristofolini Erica Peracchia Carlotta Compari Franco Bacciottini Davide Orsi Valentina Franceschi Emilia Fisicaro 《International journal of molecular sciences》2022,23(6)
The pandemic emergency determined by the spreading worldwide of the SARS-CoV-2 virus has focused the scientific and economic efforts of the pharmaceutical industry and governments on the possibility to fight the virus by genetic immunization. The genetic material must be delivered inside the cells by means of vectors. Due to the risk of adverse or immunogenic reaction or replication connected with the more efficient viral vectors, non-viral vectors are in many cases considered as a preferred strategy for gene delivery into eukaryotic cells. This paper is devoted to the evaluation of the gene delivery ability of new synthesized gemini bis-pyridinium surfactants with six methylene spacers, both hydrogenated and fluorinated, in comparison with compounds with spacers of different lengths, previously studied. Results from MTT proliferation assay, electrophoresis mobility shift assay (EMSA), transient transfection assay tests and atomic force microscopy (AFM) imaging confirm that pyridinium gemini surfactants could be a valuable tool for gene delivery purposes, but their performance is highly dependent on the spacer length and strictly related to their structure in solution. All the fluorinated compounds are unable to transfect RD-4 cells, if used alone, but they are all able to deliver a plasmid carrying an enhanced green fluorescent protein (EGFP) expression cassette, when co-formulated with 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE) in a 1:2 ratio. The fluorinated compounds with spacers formed by six (FGP6) and eight carbon atoms (FGP8) give rise to a very interesting gene delivery activity, greater to that of the commercial reagent, when formulated with DOPE. The hydrogenated compound GP16_6 is unable to sufficiently compact the DNA, as shown by AFM images. 相似文献
87.
Guoxian YuAuthor VitaeGuoji ZhangAuthor Vitae Zhiwen YuAuthor Vitae Carlotta DomeniconiAuthor VitaeJane YouAuthor Vitae Guoqiang HanAuthor Vitae 《Applied Soft Computing》2012,12(5):1511-1522
Graph-based semi-supervised classification depends on a well-structured graph. However, it is difficult to construct a graph that faithfully reflects the underlying structure of data distribution, especially for data with a high dimensional representation. In this paper, we focus on graph construction and propose a novel method called semi-supervised ensemble classification in subspaces, SSEC in short. Unlike traditional methods that execute graph-based semi-supervised classification in the original space, SSEC performs semi-supervised linear classification in subspaces. More specifically, SSEC first divides the original feature space into several disjoint feature subspaces. Then, it constructs a neighborhood graph in each subspace, and trains a semi-supervised linear classifier on this graph, which will serve as the base classifier in an ensemble. Finally, SSEC combines the obtained base classifiers into an ensemble classifier using the majority-voting rule. Experimental results on facial images classification show that SSEC not only has higher classification accuracy than the competitive methods, but also can be effective in a wide range of values of input parameters. 相似文献
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Guoxian Yu Guoji Zhang Carlotta Domeniconi Zhiwen Yu Jane You 《Pattern recognition》2012,45(3):1119-1135
Graph structure is vital to graph based semi-supervised learning. However, the problem of constructing a graph that reflects the underlying data distribution has been seldom investigated in semi-supervised learning, especially for high dimensional data. In this paper, we focus on graph construction for semi-supervised learning and propose a novel method called Semi-Supervised Classification based on Random Subspace Dimensionality Reduction, SSC-RSDR in short. Different from traditional methods that perform graph-based dimensionality reduction and classification in the original space, SSC-RSDR performs these tasks in subspaces. More specifically, SSC-RSDR generates several random subspaces of the original space and applies graph-based semi-supervised dimensionality reduction in these random subspaces. It then constructs graphs in these processed random subspaces and trains semi-supervised classifiers on the graphs. Finally, it combines the resulting base classifiers into an ensemble classifier. Experimental results on face recognition tasks demonstrate that SSC-RSDR not only has superior recognition performance with respect to competitive methods, but also is robust against a wide range of values of input parameters. 相似文献
89.
Rida T. Farouki Carlotta Giannelli Carla Manni Alessandra Sestini 《Computer Aided Geometric Design》2008,25(4-5):274-297
The problem of specifying the two free parameters that arise in spatial Pythagorean-hodograph (PH) quintic interpolants to given first-order Hermite data is addressed. Conditions on the data that identify when the “ordinary” cubic interpolant becomes a PH curve are formulated, since it is desired that the selection procedure should reproduce such curves whenever possible. Moreover, it is shown that the arc length of the interpolants depends on only one of the parameters, and that four (general) helical PH quintic interpolants always exist, corresponding to extrema of the arc length. Motivated by the desire to improve the fairness of interpolants to general data at reasonable computational cost, three selection criteria are proposed. The first criterion is based on minimizing a bivariate function that measures how “close” the PH quintic interpolants are to a PH cubic. For the second criterion, one of the parameters is fixed by first selecting interpolants of extremal arc length, and the other parameter is then determined by minimizing the distance measure of the first method, considered as a univariate function. The third method employs a heuristic but efficient procedure to select one parameter, suggested by the circumstances in which the “ordinary” cubic interpolant is a PH curve, and the other parameter is then determined as in the second method. After presenting the theory underlying these three methods, a comparison of empirical results from their implementation is described, and recommendations for their use in practical design applications are made. 相似文献
90.
Carlotta M. Grossi Peter Brimblecombe Rosa M. Esbert Francisco Javier Alonso 《Color research and application》2007,32(4):320-331
This article investigates the impact of sulfur dioxide attack, deposition of dark particles in urban environments and laser cleaning with Nd:YAG 1064 nm on color change in a range of ornamental limestones. We have used the CIELAB and CIELCH systems to compare the relative importance of the variation of each coordinate for the color change. Sulfur dioxide and dark particle deposition seems to increase the chroma, most particularly in the yellow component. Particle deposition also leads to an obvious darkening of stone surfaces. Laser irradiation at 1064 nm affects the red component of limestone, particularly if they already possess a reddish color. In general, the more intense the original color of the stone the greater are the chromatic changes, but the direction change of the color‐parameter affected by a particular process remains the same. It has always been apparent in an atmosphere heavily polluted with soot that the main changes to light‐colored stones are the exponential decrease in the parameter L* (darkening–blackening). This has important aesthetic and social implications. However, in the near future it may be that in cleaner atmospheres, perhaps more dominated by organic pollutants, a yellowing process may be of greater concern. © 2007 Wiley Periodicals, Inc. Col Res Appl, 32, 320–331, 2007 相似文献