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Myriam Gonzlez María Ovejero-Snchez Alba Vicente-Blzquez Raquel lvarez Ana B. Herrero Manuel Medarde Rogelio Gonzlez-Sarmiento Rafael Pelez 《International journal of molecular sciences》2021,22(4)
Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers. 相似文献
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Cecilia Arriagada Viviana A. Cavieres Charlotte Luchsinger Alexis E. Gonzlez Vanessa C. Muoz Jorge Cancino Patricia V. Burgos Gonzalo A. Mardones 《International journal of molecular sciences》2020,21(22)
Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation. 相似文献
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Gonzalo Martínez‐Barrera Enrique Vigueras‐Santiago Susana Hernndez‐Lpez Gonzalo Martínez‐Barrera Witold Brostow Carmina Menchaca‐Campos 《Polymer Engineering and Science》2005,45(10):1426-1431
Fiber reinforced concrete (FRC) contains fibers physically mixed with gravel, sand, cement, and water. So far, adequate mechanical performance of FRC has been obtained at high cost and using complex technologies; important here is the geometry and surface characteristics of the polymers. We have modified polymeric‐fiber surfaces by using gamma radiation. Irradiated polypropylene (PP) fibers were submitted to 0, 5, 10, 50, and 100 kGy of gamma irradiation dosages. First, tensile strength of PP fibers was evaluated, and then fibers blended at 0, 1.0, 1.5, and 2.0% in volume with Portland cement, gravel, sand, and water. The highest values of compressive strength were obtained with irradiated‐fibers at 10 kGy and 1.5% in volume of fiber. The result is 101 MPa, as compared to 35 MPa for simple concrete without fibers. POLYM. ENG. SCI., 45:1426–1431, 2005. © 2005 Society of Plastics Engineers 相似文献
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Ricardo Beristain‐Cardoso Anne‐Claire Texier Reyes Sierra‐Álvarez Jim A Field Elías Razo‐Flores Jorge Gómez 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2008,83(9):1197-1203
BACKGROUND: Simultaneous removal of sulfur, nitrogen and carbon compounds from wastewaters is a commercially important biological process. The objective was to evaluate the influence of the CH3COO?/NO3? molar ratio on the sulfide oxidation process using an inverse fluidized bed reactor (IFBR). RESULTS: Three molar ratios of CH3COO?/NO3? (0.85, 0.72 and 0.62) with a constant S2?/NO3? molar ratio of 0.13 were evaluated. At a CH3COO?/NO3? molar ratio of 0.85, the nitrate, acetate and sulfide removal efficiencies were approximately 100%. The N2 yield (g N2 g?1 NO3?‐N consumed) was 0.81. Acetate was mineralized, resulting in a yield of 0.65 g inorganic‐C g?1 CH3COO?‐C consumed. Sulfide was partially oxidized to S0, and 71% of the S2? consumed was recovered as elemental sulfur by a settler installed in the IFBR. At a CH3COO?/NO3? molar ratio of 0.72, the efficiencies of nitrate, acetate and sulfide consumption were of 100%, with N2 and inorganic‐C yields of 0.84 and 0.69, respectively. The sulfide was recovered as sulfate instead of S0, with a yield of 0.92 g SO42?‐S g?1 S2? consumed. CONCLUSIONS: The CH3COO?/NO3? molar ratio was shown to be an important parameter that can be used to control the fate of sulfide oxidation to either S0 or sulfate. In this study, the potential of denitrification for the simultaneous removal of organic matter, sulfide and nitrate from wastewaters was demonstrated, obtaining CO2, S0 and N2 as the major end products. Copyright © 2008 Society of Chemical Industry 相似文献
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Joaquín Cortés Eliana Valencia Gonzalo Aguila Esteban Orellana Paulo Araya 《Catalysis Letters》2008,126(1-2):63-71
An experimental study is made of the time decay of activity of the CO–NO reaction on a Pd/Al2O3 looking at the effect on reaction order and apparent activation energy. The optimum kinetics parameters fitting the steady state data at moderate pressures are determined. The time decay curves are analyzed through various catalyst deactivation models. 相似文献