RESUMEN
AIM: We conducted a trial to evaluate whether eight-week oral administration of meloxicam, a non-steroidal anti-inflammatory drug, would decrease the rate of the patients who required dose reduction of pegylated interferon alpha-2a in the treatment of chronic hepatitis C. METHODS: Sixty patients given weekly subcutaneous administration of pegylated interferon alpha-2a at a dose of 180 mug for 48 weeks were allocated into the meloxicam group (n = 22) and the control group (n = 38) before interferon treatment. Meloxicam was given orally at a dose of 10 mg once a day for eight weeks from the start of interferon treatment. RESULTS: The cumulative rate of dose-reduction-free patients was significantly higher in the meloxicam group (P < 0.05). Until week eight, 44.7% of the control group and 9.1% of the meloxicam group required dose reduction. Dose was modified by neutropenia in 31.6% and 18.2% of the control and meloxicam groups, respectively. Meloxicam relieved a declineof neutrophil count within the first eight weeks from 54.2% to 44.2% (P < 0.05). Multivariate analysis revealed that greater pretreatment neutrophil count and the use of meloxicam were independent factors associated with avoiding dose reduction. Sustained virological response was obtained in 52.6% of the patients. The multivariate logistic analysis revealed that viral serotype and viral load were the only independent factors associated with sustained virological response. CONCLUSION: Eight-week administration of meloxicam prevented dose reduction of pegylated interferon by relieving a decline of neutrophil count in the treatment of chronic hepatitis C.
RESUMEN
The levels of expression of various genes were altered in cellular transformants with manipulation of expression of single genes. Vascular endothelial growth factor A (VEGF-A) is a key molecule for tumor progression, although it is unclear how VEGF-A expression regulates various genes. Multiple gene expression levels were evaluated using cDNA arrays in a human hepatocellular carcinoma cell line (HLF) with suppression of the VEGF-A gene by anti-VEGF-A ribozyme (alphaVRz). The ribozyme-mediated suppression of VEGF-A gene solely up-regulated matrix metalloproteinase 1 (MMP1) gene level in HLF/alphaVRz. Levels of expression of other members of MMP family or tissue inhibitors of MMPs did not show any alteration. These results suggested that intracellular suppression of VEGF-A gene was specifically linked to up-regulation of MMP1 in human hepatocellular carcinoma cells.
Asunto(s)
Carcinoma Hepatocelular/enzimología , Factores de Crecimiento Endotelial/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Hepáticas/enzimología , Metaloproteinasa 1 de la Matriz/metabolismo , ARN Catalítico/farmacología , Carcinoma Hepatocelular/genética , Factores de Crecimiento Endotelial/antagonistas & inhibidores , Perfilación de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Metaloproteinasa 1 de la Matriz/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Transformación Genética , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: To determine predictors for virological response to lamivudine, a retrospective-cohort study was designed. METHODS: Seventy HBV positive patients who received lamivudine were classified according to virological response into responders and non-responders. Background conditions and normalization and flare-up of hepatitis were compared using student-t test and chi-square test. Logistic regression analysis was performed to determine the effect of explanatory variables, age, sex, ALT, HBV-DNA, hepatic fibrosisi, presence of absence of HBeAg, former IF non-response on the response to lamivudine. RESULTS: There were no difference in gender, age, observed period, ALT level, liver fibrosis, former response to Interferon in background but viral titer and rate of HBeAg (+) was higher in non-responders. Hepatitis normalization rates were not different but flare-up rates were significantly higher in non-responders. Multivariate analysis showed HBeAg is the relevant factor for the response to lamivudine. CONCLUSIONS: The presence of HBeAg was a risk for non-response to lamivudine therapy.