RESUMEN
AIMS: Nitric oxide (NO), produced by inducible NO synthase (iNOS), has been suggested to cause oxidative stress, leading to 8-hydroxydeoxyguanosine (8-OHdG) accumulation and subsequent transversion mutation of DNA. The aim was to evaluate iNOS expression and the status of oxidative stress in nasopharyngeal carcinoma (NPC). METHODS AND RESULTS: Seventy-three cases of NPC were investigated to examine the immunohistochemical expression of iNOS, 8-OHdG and latent membrane protein-1 (LMP-1) and Epstein-Barr virus-encoded small RNA (EBER) expression using in situ hybridization. iNOS mRNA expression and p53 gene mutations were also assessed. Overexpression of iNOS, LMP-1 and EBER was observed in 62 (84.9%), 28 (38.4%) and 53 (72.6%) cases respectively. p53 gene mutation was found in 10 of 73 (13.7%) cases. Immunohistochemical iNOS expression was associated with the 8-OHdG labelling index, iNOS mRNA expression and p53 gene alteration (P < 0.0001, P = 0.016 and 0.0082 respectively). CONCLUSIONS: Our present findings suggest that the expression of iNOS induces oxidative stress in NPC. Although the presence of p53 mutation was associated with iNOS overexpression, the type of acid-base change of p53 was transition, but not transversion, which suggests that the p53 gene is not the direct target of DNA damage by 8-OHdG accumulation.
Asunto(s)
Desoxiguanosina/análogos & derivados , Neoplasias Nasofaríngeas/metabolismo , Neoplasias de Células Escamosas/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Proteínas Adaptadoras Transductoras de Señales , Adulto , Anciano , Anciano de 80 o más Años , Proteínas del Citoesqueleto , Daño del ADN/genética , ADN de Neoplasias/genética , Desoxiguanosina/genética , Desoxiguanosina/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Estimación de Kaplan-Meier , Proteínas con Dominio LIM , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Nasofaríngeas/patología , Neoplasias de Células Escamosas/patología , Óxido Nítrico Sintasa de Tipo II/genética , Estrés Oxidativo/genética , ARN Mensajero/metabolismo , ARN Viral/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoAsunto(s)
Linfoma Anaplásico de Células Grandes , Linfoma Anaplásico de Células Grandes/patología , Neoplasias de la Parótida , Neoplasias de la Parótida/patología , Proteínas Tirosina Quinasas/metabolismo , Anciano , Quinasa de Linfoma Anaplásico , Biomarcadores de Tumor/metabolismo , Núcleo Celular/enzimología , Núcleo Celular/patología , Citoplasma/enzimología , Citoplasma/patología , Humanos , Linfoma Anaplásico de Células Grandes/enzimología , Linfoma Anaplásico de Células Grandes/cirugía , Masculino , Neoplasias de la Parótida/enzimología , Neoplasias de la Parótida/cirugía , Proteínas Tirosina Quinasas Receptoras , Resultado del TratamientoRESUMEN
Brown Norway kininogen-deficient rats had very low levels of plasma kininogens and lower levels of plasma prekallikrein, compared with those of normal rats of the same strain. Systolic blood pressure, determined by the tail-cuff method, of 5-week-old kininogen-deficient rats (106 +/- 0.4 mm Hg, n = 7) and the rate of systolic blood pressure increase with age were not different from those in normal rats. Weekly injections of deoxycorticosterone acetate (5 mg/kg s.c.) with 1% sodium chloride solution in drinking water after uninephrectomy at 7 weeks of age caused a gradual increase in the blood pressure of normal rats, reaching a plateau at 18 weeks of age, whereas that of deficient rats rose rapidly to 158 +/- 6 mm Hg 2 weeks after the start of treatment and continued to increase slightly, becoming significantly higher than normal rats at 8, 9, 10, 11, and 12 weeks of age (p less than 0.05 or 0.01). The levels of urinary prokallikrein and active kallikrein were slightly higher in deficient rats before deoxycorticosterone acetate-salt treatment but were not significantly increased after this treatment, whereas these levels in normal rats were increased 3.6- and 4.7-fold by this treatment. Urinary free kinin, collected from the ureter in untreated deficient rats, was below the detection limit. The plasma level of low molecular weight kininogen, the substrate of glandular kallikrein, was decreased in normal rats during the treatment. Continuous subcutaneous injection of aprotinin by an osmotic pump to normal rats induced significant increase in blood pressure. These results indicate that glandular kallikrein may play a suppressive role in deoxycorticosterone acetate-salt hypertension.