RESUMO
In this study, we confirmed that combining HHT with ACR can result in synergistic cytotoxicity to AML cells in vitro and in vivo. Combining HHT and ACR simultaneously inhibited PI3K/AKT and WNT/ß-catenin signaling in AML cells. Significant increases in growth inhibition and apoptosis were induced by an AKT inhibitor when the WNT3A gene of THP-1 cells was silenced. HHT+ACR could synergistically induce the apoptosis of CD34(+)/CD38(-) primary AML cells. These results highlight ß-catenin and AKT are promising targets for combination therapy for AML.
Assuntos
Antineoplásicos/farmacologia , Leucemia Mieloide Aguda/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo , Aclarubicina/administração & dosagem , Aclarubicina/farmacologia , Aclarubicina/toxicidade , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Apoptose/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Inativação Gênica , Glucose/metabolismo , Harringtoninas/administração & dosagem , Harringtoninas/farmacologia , Harringtoninas/toxicidade , Mepesuccinato de Omacetaxina , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/antagonistas & inibidoresRESUMO
To explore the possible oxidative stress induced by lead, heparinized whole blood and urine of 66 secondary smelter lead workers (46 for Comet assay) and 28 controls were collected. The concentrations of blood lead (BPb) and urinary lead (UPb) and alpha-aminolevulinic acid (alpha-ALA), indices of lead exposure level of the body, were determined. Malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activity of plasma were also measured. Single-cell gel (SCG, Comet assay) was used to measure the DNA damage of peripheral blood cells. There was a positive correlation between the presence of Pb in blood and significant increases in MDA levels and SOD activity. Alcohol consumption and smoking with increased exposure to Pb was associated with enhanced DNA damage. A positive correlation was found between MDA and DNA damage.
Assuntos
Dano ao DNA , Chumbo/efeitos adversos , Exposição Ocupacional , Estresse Oxidativo , Adulto , Feminino , Humanos , Masculino , Malondialdeído/análise , Superóxido Dismutase/metabolismo , Distribuição TecidualRESUMO
A vascular bundles specific expressing vector pBAL1 with a promoter AQ630 from rice phenylalanine ammonialyase gene and a gene encoding indoleacetic-lysine synthytase from Pseudomonas syringae subsp. savastanoi was constructed. Affirmed by Southern blotting and RTPCR analysis, the AQ630-iaaL transgenic plants show increasing shoots-regeneration frequency of young stem explants on hormone-free 1/2 MS medium and lower sensibility to IAA when roots were induced from the root explants on the media containing different concentrations of IAA compared to untransformed plants.
Assuntos
Nicotiana/genética , Peptídeo Sintases/genética , Plantas Geneticamente Modificadas , Plantas Tóxicas , Técnicas de Cultura , Expressão Gênica , Raízes de Plantas/crescimento & desenvolvimento , Caules de Planta/crescimento & desenvolvimento , Nicotiana/crescimento & desenvolvimentoRESUMO
Comparisons between x-ray and B-mode ultrasonic examinations were carried out in 32 divers in both shoulders and both hips (128 comparisons in all). The x-rays showed dysbaric osteonecrosis (DON) in 46 sites; in 43 of these, the B-mode ultrasonogram result coincided with the x-ray finding. We suggest that B-mode ultrasonograms can depict the location, form, and size of the lesions. It is an easy, efficient, and noninvasive method of diagnosing DON, worthy of further investigation and application. Similar good agreement between x-rays and ultrasonograms was found with the now-obsolete A-mode technique.
