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91.
92.
Cristina Teixidó Rosó Marés Miguel Aracil Santiago Ramón y Cajal Javier Hernández-Losa 《PloS one》2013,8(1)
Elisidepsin (elisidepsin trifluoroacetate, Irvalec®, PM02734) is a new synthetic depsipeptide, a result of the PharmaMar Development Program that seeks synthetic products of marine origin-derived compounds. Elisidepsin is a drug with antiproliferative activity in a wide range of tumors. In the present work we studied and characterized the mechanisms associated with sensitivity and resistance to elisidepsin treatment in a broad panel of tumor cell lines from breast and pancreas carcinomas, focusing on different factors involved in epithelial-mesenchymal transition (EMT) and the use of HER family receptors in predicting the in vitro drug response. Interestingly, we observed that the basal protein expression levels of EMT markers show a significant correlation with cell viability in response to elisidepsin treatment in a panel of 12 different breast and pancreatic cancer cell lines. In addition, we generated three elisidepsin treatment-resistant cell lines (MCF-7, HPAC and AsPC-1) and analyzed the pattern of expression of different EMT markers in these cells, confirming that acquired resistance to elisidepsin is associated with a switch to the EMT state. Furthermore, a direct correlation between basal HER3 expression and sensitivity to elisidepsin was observed; moreover, modulation of HER3 expression levels in different cancer cell lines alter their sensitivities to the drug, making them more resistant when HER3 expression is downregulated by a HER3-specific short hairpin RNA and more sensitive when the receptor is overexpressed. These results show that HER3 expression is an important marker of sensitivity to elisidepsin treatment. 相似文献
93.
94.
Alberto Crespo Guardo Carmen álvarez-Fernández Hodei Arberas Javier García-Pérez Felipe García Manuel Enric Bargalló María José Maleno José María Gatell Beatriz Mothe José Alcami Sonsoles Sánchez-Palomino Montserrat Plana 《PloS one》2013,8(3)
Background
Generation of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy.Methods
We have evaluated the specific T cell response against different types of NL4-3 virions (including NL4-3 aldrithiol-2 treated, NL4-3/ΔRT and R5 envelopes: NL4-3/ΔRT/ΔEnv[AC10] and NL4-3/ΔRT/ΔEnv[Bal]) and against pools of overlapping peptides (15 mer) encompassing the HIV-1 Gag and Nef regions. Cryopreserved PBMC from a subset of 69 chronic asymptomatic HIV positive individuals have been employed using different techniques including IFN-γ ELISPOT assay, surface activation markers and intracellular cytokine staining (ICS) by flow cytometry.Results
The differential response obtained against NL4-3 aldrithiol-2 treated and NL4-3/ΔRT virions (25% vs 55%, respectively) allow us to divide the population in three groups: “full-responders” (positive response against both viral particles), “partial-responders” (positive response only against NL4-3/ΔRT virions) and “non-responders” (negative responses). There was no difference between X4 and R5 envelopes. The magnitude of the total responses was higher against NL4-3/ΔRT and was positively correlated with gender and inverse correlated with viral load. On the contrary CD4+ T cell count was not associated with this response. In any case responses to the viruses tended to be lower in magnitude than those detected by the overlapping peptides tested. Finally we have found an increased frequency of HLA-B27 allele (23% vs 9%) and a significant reduction in some activation markers (CD69 and CD38) on T cells surface in responders vs non-responders individuals.Conclusions
In summary these virions could be considered as alternative and useful reagents for screening HIV-1-specific T cell responses in HIV exposed uninfected people, HIV infected patients and to assess immunogenicity of new prototypes both in vitro and in vaccine trials, by a feasible, simply, effective and low cost assay. 相似文献95.
Leiz M. C. Véras Vanessa R. R. Cunha Filipe C. D. A. Lima Maria A. Guimar?es Marianne M. Vieira Yuri D. M. Campelo Vanessa Y. Sakai David F. Lima Paulo S. Carvalho Jr Javier A. Ellena Paulo R. P. Silva Luciene C. Vasconcelos Markus Godejohann Helena M. Petrilli Vera R. L. Constantino Yvonne P. Mascarenhas José Roberto de Souza de Almeida Leite 《PloS one》2013,8(6)
This paper presents an industrial scale process for extraction, purification, and isolation of epiisopiloturine (EPI) (2(3H)-Furanone,dihydro-3-(hydroxyphenylmethyl)-4-[(1-methyl-1H-imidazol-4-yl)methyl]-, [3S-[3a(R*),4b]]), which is an alkaloid from jaborandi leaves (Pilocarpus microphyllus Stapf). Additionally for the first time a set of structural and spectroscopic techniques were used to characterize this alkaloid. EPI has shown schistomicidal activity against adults and young forms, as well as the reduction of the egg laying adult worms and low toxicity to mammalian cells (in vitro). At first, the extraction of EPI was done with toluene and methylene chloride to obtain a solution that was alkalinized with ammonium carbonate. The remaining solution was treated in sequence by acidification, filtration and alkalinization. These industrial procedures are necessary in order to remove impurities and subsequent application of the high performance liquid chromatography (HPLC). The HPLC was employed also to remove other alkaloids, to obtain EPI purity higher than 98%. The viability of the method was confirmed through HPLC and electrospray mass spectrometry, that yielded a pseudo molecular ion of m/z equal to 287.1 Da. EPI structure was characterized by single crystal X-ray diffraction (XRD), 1H and 13C nuclear magnetic resonance (NMR) in deuterated methanol/chloroform solution, vibrational spectroscopy and mass coupled thermal analyses. EPI molecule presents a parallel alignment of the benzene and the methyl imidazol ring separated by an interplanar spacing of 3.758 Å indicating a π-π bond interaction. The imidazole alkaloid melts at 225°C and decomposes above 230°C under air. EPI structure was used in theoretical Density Functional Theory calculations, considering the single crystal XRD data in order to simulate the NMR, infrared and Raman spectra of the molecule, and performs the signals attribution. 相似文献
96.
Elena González-Sánchez Juan Martín-Caballero Juana María Flores Javier Hernández-Losa Ma ángeles Montero Javier Cortés Roso Mares Mariano Barbacid Juan A. Recio 《PloS one》2013,8(6)
Aberrant activation of MAP kinase signaling pathway and loss of tumor suppressor LKB1 have been implicated in lung cancer development and progression. Although oncogenic KRAS mutations are frequent, BRAF mutations (BRAFV600E) are found in 3% of human non-small cell lung cancers. Contrary to KRAS mutant tumors, BRAFV600E-induced tumors are benign adenomas that fail to progess. Interestingly, loss of tumor supressor LKB1 coexists with KRAS oncogenic mutations and synergizes in tumor formation and progression, however, its cooperation with BRAFV600E oncogene is unknown. Our results describe a lung cell population in neonates mice where expression of BRAFV600E leads to lung adenoma development. Importantly, expression of BRAFV600E concomitant with the loss of only a single-copy of Lkb1, overcomes senencence–like features of BRAFV600E-mutant adenomas leading malignization to carcinomas. These results posit LKB1 haploinsufficiency as a risk factor for tumor progression of BRAFV600E mutated lung adenomas in human cancer patients. 相似文献
97.
José Eduardo Marqués-Gálvez Alfonso Navarro-Ródenas José Javier Peguero-Pina Francisco Arenas Angel Luigi Guarnizo Eustaquio Gil-Pelegrín Asunción Morte 《Physiologia plantarum》2020,170(4):537-549
Predicted increases in atmospheric concentration of carbon dioxide (CO2) coupled with increased temperatures and drought are expected to strongly influence the development of most of the plant species in the world, especially in areas with high risk of desertification like the Mediterranean basin. Helianthemum almeriense is an ecologically important Mediterranean shrub with an added interest because it serves as the host for the Terfezia claveryi mycorrhizal fungus, which is a desert truffle with increasingly commercial interest. Although both plant and fungi are known to be well adapted to dry conditions, it is still uncertain how the increase in atmospheric CO2 will influence them. In this article we have addressed the physiological responses of H. almeriense × T. claveryi mycorrhizal plants to increases in atmospheric CO2 coupled with drought and high vapor pressure deficit. This work reports one of the few estimations of mesophyll conductance in a drought deciduous Mediterranean shrub and evaluates its role in photosynthesis limitation. High atmospheric CO2 concentrations help desert truffle mycorrhizal plants to cope with the adverse effects of progressive drought during Mediterranean springs by improving carbon net assimilation, intrinsic water use efficiency and dispersal of the species through increased flowering events. 相似文献
98.
Grijota Francisco Javier Muñoz Diego Bartolomé Ignacio Siquier-Coll Jesús Robles María Concepción Maynar Marcos 《Biological trace element research》2020,195(1):39-45
Biological Trace Element Research - The aim of the present study was to determine changes occurring in the erythrocyte concentrations of arsenic (As), cadmium (Cd) and lead (Pb) in highly trained... 相似文献
99.
García-Tuñón Ignacio Vuelta Elena Lozano Laura Herrero María Méndez Lucía Palomero-Hernandez Javier Pérez-Caro María Pérez-García Jessica González-Sarmiento Rogelio Sánchez-Martín Manuel 《Molecular biology reports》2020,47(2):1381-1391
Molecular Biology Reports - The Nomo1 gene mediates a wide range of biological processes of importance in embryonic development. Accordingly, constitutive perturbation of Nomo1 function may result... 相似文献
100.
Sanchez Paulina Espinosa Magali Maldonado Vilma Barquera Rodrigo Belem-Gabiño Nayeli Torres Javier Cravioto Adrian Melendez-Zajgla Jorge 《Molecular biology reports》2020,47(7):5175-5184
Molecular Biology Reports - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in humans, with less than 5% 5-year survival rate. PDAC is characterized by a small number of... 相似文献