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1.
Oncogene ; 39(3): 690-702, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31541193

RESUMEN

Many types of cancers have a well-established dependence on glutamine metabolism to support survival and growth, a process linked to glutaminase 1 (GLS) isoforms. Conversely, GLS2 variants often have tumor-suppressing activity. Triple-negative (TN) breast cancer (testing negative for estrogen, progesterone, and Her2 receptors) has elevated GLS protein levels and reportedly depends on exogenous glutamine and GLS activity for survival. Despite having high GLS levels, we verified that several breast cancer cells (including TN cells) express endogenous GLS2, defying its role as a bona fide tumor suppressor. Moreover, ectopic GLS2 expression rescued cell proliferation, TCA anaplerosis, redox balance, and mitochondrial function after GLS inhibition by the small molecule currently in clinical trials CB-839 or GLS knockdown of GLS-dependent cell lines. In several cell lines, GLS2 knockdown decreased cell proliferation and glutamine-linked metabolic phenotypes. Strikingly, long-term treatment of TN cells with another GLS-exclusive inhibitor bis-2'-(5-phenylacetamide-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) selected for a drug-resistant population with increased endogenous GLS2 and restored proliferative capacity. GLS2 was linked to enhanced in vitro cell migration and invasion, mesenchymal markers (through the ERK-ZEB1-vimentin axis under certain conditions) and in vivo lung metastasis. Of concern, GLS2 amplification or overexpression is linked to an overall, disease-free and distant metastasis-free worse survival prognosis in breast cancer. Altogether, these data establish an unforeseen role of GLS2 in sustaining tumor proliferation and underlying metastasis in breast cancer and provide an initial framework for exploring GLS2 as a novel therapeutic target.


Asunto(s)
Neoplasias de la Mama/patología , Carcinogénesis/patología , Glutaminasa/metabolismo , Neoplasias Pulmonares/secundario , Adulto , Anciano , Anciano de 80 o más Años , Bencenoacetamidas/farmacología , Bencenoacetamidas/uso terapéutico , Mama/patología , Mama/cirugía , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Técnicas de Silenciamiento del Gen , Glutaminasa/antagonistas & inhibidores , Humanos , Persona de Mediana Edad , Pronóstico , Sulfuros/farmacología , Sulfuros/uso terapéutico , Tiadiazoles/farmacología , Tiadiazoles/uso terapéutico
2.
Rev Col Bras Cir ; 43(2): 124-8, 2016.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-27275594

RESUMEN

OBJECTIVE: to analyze the chemical components of the smoke from electrocautery from coagulating muscle and liver tissues of pigs. METHODS: we collected smoke produced by electrocautery applied to porcine tissue in previously evacuated bottles, with qualitative and quantitative analysis of the compounds present through the hyphenated technique gas chromatography / mass spectrometry. RESULTS: there was a majority of decanal aldehyde in the fumes from the subcutaneous, muscle and liver tissues. Fumes of subcutaneous and muscular tissues also showed the presence of hexanal and phenol. In the fumes of subcutaneous and liver tissues we also found toluene and limonene and, finally, nonanal smoke was present in the muscle and liver tissues. CONCLUSION: there is increasing evidence showing that smoke from electrocautery used in subcutaneous, muscle and liver tissue is harmful to human health. Thus, there is need to reduce exposure to it or wear masks with filters capable of retaining these particles. OBJETIVO: analisar quimicamente os componentes da fumaça do eletrocautério, provenientes da coagulação de tecidos, muscular e hepático de suino. MÉTODOS: coleta de fumaça produzida por eletrocauterização de tecido porcino em frascos previamente evacuados com análise qualitativa e quantitativa dos compostos presentes, através de técnica hifenada, cromatografia a gás/espectrometria de massas. RESULTADOS: houve presença majoritária do aldeído decanal nas fumaças provenientes dos tecidos subcutâneo, muscular e hepático. Fumaças dos tecidos subcutâneo e muscular mostraram também a presença de hexanal e fenol. Nas fumaças dos tecidos subcutâneo e hepático foram encontrados ainda tolueno e limoneno e, por fim, nonanal estava presente nas fumaças dos tecidos muscular e hepático. CONCLUSÃO: há número crescente de evidências mostrando que fumaça proveniente de eletrocauterização de tecidos subcutâneo, muscular e hepático é nociva à saúde de seres humanos. Portanto, há necessidade de reduzir a exposição a ela ou usar máscara com filtro capaz de reter essas partículas.


Asunto(s)
Electrocoagulación , Cromatografía de Gases y Espectrometría de Masas , Humo/análisis , Animales , Hígado/cirugía , Músculo Esquelético/cirugía , Tejido Subcutáneo/cirugía , Porcinos
3.
Rev. Col. Bras. Cir ; 43(2): 124-128, Mar.-Apr. 2016. tab
Artículo en Inglés | LILACS | ID: lil-782922

RESUMEN

ABSTRACT Objective: to analyze the chemical components of the smoke from electrocautery from coagulating muscle and liver tissues of pigs. Methods: we collected smoke produced by electrocautery applied to porcine tissue in previously evacuated bottles, with qualitative and quantitative analysis of the compounds present through the hyphenated technique gas chromatography / mass spectrometry. Results: there was a majority of decanal aldehyde in the fumes from the subcutaneous, muscle and liver tissues. Fumes of subcutaneous and muscular tissues also showed the presence of hexanal and phenol. In the fumes of subcutaneous and liver tissues we also found toluene and limonene and, finally, nonanal smoke was present in the muscle and liver tissues. Conclusion: there is increasing evidence showing that smoke from electrocautery used in subcutaneous, muscle and liver tissue is harmful to human health. Thus, there is need to reduce exposure to it or wear masks with filters capable of retaining these particles.


RESUMO Objetivo: analisar quimicamente os componentes da fumaça do eletrocautério, provenientes da coagulação de tecidos, muscular e hepático de suino. Métodos: coleta de fumaça produzida por eletrocauterização de tecido porcino em frascos previamente evacuados com análise qualitativa e quantitativa dos compostos presentes, através de técnica hifenada, cromatografia a gás/espectrometria de massas. Resultados: houve presença majoritária do aldeído decanal nas fumaças provenientes dos tecidos subcutâneo, muscular e hepático. Fumaças dos tecidos subcutâneo e muscular mostraram também a presença de hexanal e fenol. Nas fumaças dos tecidos subcutâneo e hepático foram encontrados ainda tolueno e limoneno e, por fim, nonanal estava presente nas fumaças dos tecidos muscular e hepático. Conclusão: há número crescente de evidências mostrando que fumaça proveniente de eletrocauterização de tecidos subcutâneo, muscular e hepático é nociva à saúde de seres humanos. Portanto, há necessidade de reduzir a exposição a ela ou usar máscara com filtro capaz de reter essas partículas.


Asunto(s)
Humo/análisis , Electrocoagulación , Cromatografía de Gases y Espectrometría de Masas , Porcinos , Músculo Esquelético/cirugía , Tejido Subcutáneo/cirugía , Hígado/cirugía
4.
Talanta ; 117: 305-11, 2013 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-24209345

RESUMEN

The Amazon tree Aniba rosaeodora Ducke (rosewood) provides an essential oil valuable for the perfume industry, but after decades of predatory extraction it is at risk of extinction. The extraction of the essential oil from wood implies the cutting of the tree, and then the study of oil extracted from the leaves is important as a sustainable alternative. The goal of this study was to test the applicability of Raman spectroscopy and Partial Least Square Discriminant Analysis (PLS-DA) as means to classify the essential oil extracted from different parties (wood, leaves and branches) of the Brazilian tree A. rosaeodora. For the development of classification models, the Raman spectra were split into two sets: training and test. The value of the limit that separates the classes was calculated based on the distribution of samples of training. This value was calculated in a manner that the classes are divided with a lower probability of incorrect classification for future estimates. The best model presented sensitivity and specificity of 100%, predictive accuracy and efficiency of 100%. These results give an overall vision of the behavior of the model, but do not give information about individual samples; in this case, the confidence interval for each sample of classification was also calculated using the resampling bootstrap technique. The methodology developed have the potential to be an alternative for standard procedures used for oil analysis and it can be employed as screening method, since it is fast, non-destructive and robust.


Asunto(s)
Lauraceae/química , Monoterpenos/aislamiento & purificación , Aceites Volátiles/química , Hojas de la Planta/química , Aceites de Plantas/química , Sesquiterpenos/aislamiento & purificación , Madera/química , Brasil , Análisis Discriminante , Análisis de los Mínimos Cuadrados , Sensibilidad y Especificidad , Espectrometría Raman
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