Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Añadir filtros








Intervalo de año
1.
Experimental & Molecular Medicine ; : 737-745, 2009.
Artículo en Inglés | WPRIM | ID: wpr-71509

RESUMEN

Paclitaxel is one of the chemotheraputic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor) or z-IETD-FMK (a caspase-8 inhibitor) blocked TOS/paclitaxel cotreatment-induced PARP cleavage and apoptosis, suggesting that TOS potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in H460 cells. Furthermore, the growth suppression effect of TOS/paclitaxel combination on human H460, A549 and H358 NSCLC cell lines were synergistic. Our observations indicate that combination of paclitaxel and TOS may offer a novel therapeutic strategy for improving paclitaxel drug efficacy in NSCLC patient therapy as well as for potentially lowering the toxic side effects of paclitaxel through reduced drug dosage.


Asunto(s)
Humanos , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Caspasa 8/metabolismo , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Sinergismo Farmacológico , Quimioterapia Combinada , Células Madre Neoplásicas , Paclitaxel/farmacología , alfa-Tocoferol/farmacología
2.
Experimental & Molecular Medicine ; : 325-331, 2006.
Artículo en Inglés | WPRIM | ID: wpr-51256

RESUMEN

SC-560, a strucutral analogue of celecoxib, induces growth inhibition in a wide range of human cancer cells in a cyclooxygenase (COX)-independent manner. Since SC-560 suppresses the growth of cancer cells mainly by inducing cell cycle arrest, we sought to examine the role of p21CIP1, a cell cycle regulator protein, in the cellular response against SC-560 by using p21(+/+)and p21(-/-)isogenic HCT116 colon carcinoma cells. In HCT116 (p21(+/+)) cells, SC-560 dose-dependently induced growth inhibition and cell cycle arrest at the G1 phase without significant apoptosis induction. SC-560-induced cell cycle arrest was accompanied by upregulation of p21CIP1. However, the extent of SC-560-induced accumulation at the G1 phase was approximately equal in the p21(+/+)and the p21(-/-)cells. Nonetheless, the growth inhibition by SC-560 was increased in p21(-/-)cells than p21(+/+)cells. SC-560-induced reactive oxygen species (ROS) generation did not differ between p21(+/+)and p21(-/-)cells but the subsequent activaton of apoptotic caspase cascade was more pronounced in p21(-/-)cells compared with p21(+/+)cells. These results suggest that p21CIP1 blocks the SC-560-induced apoptotic response of HCT116 cells. SC-560 combined with other therapy that can block p21 CIP1 expression or function may contribute to the effective treatment of colon cancer.


Asunto(s)
Humanos , Especies Reactivas de Oxígeno/metabolismo , Pirazoles/farmacología , Mutación , Immunoblotting , Células HCT116 , Genotipo , Citometría de Flujo , Relación Dosis-Respuesta a Droga , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Neoplasias del Colon/genética , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología
3.
Korean Journal of Nuclear Medicine ; : 133-139, 2002.
Artículo en Coreano | WPRIM | ID: wpr-118784

RESUMEN

No abstract available.

4.
Korean Journal of Nuclear Medicine ; : 84-93, 1999.
Artículo en Coreano | WPRIM | ID: wpr-15853

RESUMEN

PURPOSE: We investigated the direct labeling method of antibody with 99mTc and 188Re and examined the stability and function of these labeled compounds in in vitro and in vivo. MATERIALS AND METHODS: Disulfide bond of nonspecific human IgG was reduced to -SH group by 2-mercaptoethanol. Stannous ion was used to reduce 99mTc and 188Re. The stability of 99mTc-IgG and 188Re-IgG was estimated upto 24 hrs. Biodistribution was evaluated in abscess bearing rats at 4 and 24 hr post-injection of 99mTc or 188Re labeled IgG. RESULTS: The number of -SH group per reduced IgG molecule was 2.34. The labeling yield of 99mTc-IgG and 188Re-IgG were 90% and 95%, respectively. The stability of 99mTc-IgG at 1, 4, 6 and 24 hr was 91%, 83%, 78%, 7% and that of 188Re-IgG, high uptake was found on kidney, blood, stomach and abscess (9.42+/-0.68, 1.43+/-0.24, 0.86+/-0.18, 0.72+/-0.10 %ID/g, respectively). The uptakes at 24 hr were kidney, abscess, stomach, and blood in descending order. In case of 188Re-IgG, high uptake at 4 hr post injection appeared on kidney, blood, abscess and stomach (3.92+/-0.62, 1.32+/-0.08, 0.88+/-0.01, 0.26+/-0.06, respectively). The upatkes at 24 hr were kidney, abscess, blood abd stomach in descending order. The abscess to blood uptake ratio of 99mTc-IgG was 0.5 at 4 hr and 2.02 at 24 hr and that of 188Re-IgG was 0.67 and 1.29. CONCLUSION: 99mTc-IgG and 188Re-IgG and 188Re-IgG canbe labeled efficiently with direct labeling method. However, 99mTc-IgG and 188Re-IgG, labeled with direct method, was unstable. Further study in needed to enhance the stability of the antibody labeling.


Asunto(s)
Animales , Humanos , Ratas , Absceso , Inmunoglobulina G , Riñón , Mercaptoetanol , Estómago
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA