RESUMEN
OBJECTIVE: An important issue in cancer therapy is to investigate the mechanism for cellular sensitivity to anticancer agents such as cisplatin. Cisplatin is one of the DNA-damaging agents and several factors including p53 are related to the sensitivity to cisplatin in cancer. Protein kinase C (PKC) delta is known as a positive regulator for cisplatin-induced cell death. In our present study, we examined whether overexpression of PKCdelta and p53 increases the sensitivity of the human gastric cancer cell line, MKN28, which has a mutation of p53 gene, to cisplatin. METHODS: Cell viability and DNA content were measured in MKN28 with adenovirus-mediated expression of PKCdelta and p53 after exposure to cisplatin. In addition, the active form of caspase-3 was detected by Western blotting. RESULTS: Overexpression of exogenous PKCdelta did not induce cell death in MKN28 but inhibited cell growth at 1 microg/ml cisplatin as compared to that by cisplatin alone. Moreover, overexpression of both wild-type p53 and exogenous PKCdelta in MKN28 increased cisplatin-induced cell death in MKN28. CONCLUSION: These results suggest that PKCdelta, in cooperation with p53, possibly regulates cisplatin-induced caspase-3-mediated cell death in gastric cancer.
Asunto(s)
Cisplatino/farmacología , Proteína Quinasa C/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adenoviridae/genética , Antineoplásicos/farmacología , Western Blotting , Caspasa 3 , Caspasas/metabolismo , División Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Humanos , Proteína Quinasa C/genética , Proteína Quinasa C-delta , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , TransfecciónAsunto(s)
LDL-Colesterol/aislamiento & purificación , Hemoperfusión/métodos , Hiperlipoproteinemia Tipo II/terapia , Adsorción , Anticolesterolemiantes/uso terapéutico , Atorvastatina , LDL-Colesterol/sangre , Hemoperfusión/instrumentación , Ácidos Heptanoicos/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipoproteinemia Tipo II/sangre , Pirroles/uso terapéuticoRESUMEN
We investigated the clinical efficacy of direct hemoperfusion with a beta2-microglobulin (beta2-m) adsorption column for the treatment of patients with dialysis-related amyloidosis. A 2-year prospective controlled study was performed to compare the effects of passaging blood through a (beta2-m) adsorption column (Lixelle) before it is passaged through the dialysis polysulfone membrane on the severity of amyloidosis in these individuals. Patients (n = 22) whose blood went through the Lixelle column prior to dialysis had a higher beta2-m removal rate compared to an equal number of controls, and they showed earlier improvement in their symptoms which included impaired daily activities, joint stiffness, and pain. The appearance of additional bone cysts was prevented in pre-adsorbed patients but not in the controls. Thus, the Lixelle column is useful in preventing the progression of dialysis-related amyloidosis and in ameliorating or arresting the progression of the symptoms of this disorder.