RESUMEN
INTRODUCTION: It had been evident that non-alcoholic fatty liver disease (NAFLD) is the new era epidemic. Despite emergence of many drugs on the pipeline that considered candidates to cure NAFLD/NASH, the critical need for defining the cohort liable to fibrosis progression is yet unmet. AIM: Evaluate ABCA1 (rs1800977) genotyping as a noninvasive predictor of liver fibrosis severity. MATERIALS AND METHODS: This study included 118 liver biopsy-proven NAFLD-patients. According to Metavir-fibrosis-staging, cases were divided to early fibrosis (74 cases), and 44 cases with significant fibrosis (>F2), added to 49 healthy control subjects. All patients were subjected to liver function tests, lipids profile, triglyceride TG index, and hepatic steatosis index (HSI) and real-time PCR ABCA1 SNP (rs1800977). RESULTS: Significant differences in transaminases (p > .05), albumin (p < .009), cholesterol (p0.03), low density lipoproteins (LDL) (0.006), triglycerides (p < .001), HSI (p < .001), FIB4 (p < .001) and APRI (p < .001) were reported in those with significant than early fibrosis and control groups. CC was the most prevalent in significant (36.4%) than early fibrosis (13.5%) and control groups (8.2%), with prevalence of C allele in significant fibrosis (p ≤ .003). Univariate analysis revealed that DM (p ≤ .001), TG index (p ≤ .022), cholesterol (p ≤ .03), HSI (p ≤ .006), LDL (p ≤ .02), HDL (p ≤ .01), APRI (p ≤ .02) and CC genotype (p ≤ .005) were the main factors affecting fibrosis progression in NAFLD. However multivariate analysis proved only the role of HSI (p ≤ .005), LDL (p ≤ .02), HDL (p ≤ .003) and CC genotype (p ≤ .03) in predicting fibrosis severity. CONCLUSION: Dyslipidemias, hepatic steatosis index and ABCA1 (rs1800977) gene polymorphism CC genotype; were the only independent predictors of advanced fibrosis in NAFLD-patients.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/genética , Pronóstico , Cirrosis Hepática/genética , Cirrosis Hepática/epidemiología , Polimorfismo Genético , Colesterol , Triglicéridos , Transportador 1 de Casete de Unión a ATP/genéticaRESUMEN
BACKGROUND: Nitazoxanide, approved for the treatment of Cryptosporidium parvum and Giardia lamblia, was found to inhibit hepatitis C virus replication. AIM: The aim of this study was to assess the impact of nitazoxanide as an add-on therapy to pegylated interferon α-2a and ribavirin on sustained virologic response (SVR) in patients with chronic hepatitis C. PATIENTS AND METHODS: A total of 200 patients with chronic hepatitis C were enrolled in the study, assigned randomly in a 1 : 1 ratio to two groups: group A (placebo group) and group B (nitazoxanide group). Five patients withdrew from the study after they signed the consent form.A total of 195 patients were evaluated: 97 patients in group A versus 98 patients in group B at a dose of 500 mg twice daily. Placebo and nitazoxanide were administered as an add-on therapy to pegylated interferon α-2a plus ribavirin following a 12-week lead-in phase. SVR was evaluated. Statistical analysis was carried out using the SPSS software. RESULTS: The mean age of the patients in group A was 46.5 versus 45.7 years in group B. In group A, 85 out of 97 (87.6%) patients were men and in group B, 84 out of 98 (85.7%) patients were men.In group A, 59 out of 97 (60.82%) patients achieved an SVR versus 57 out of 98 (58.16%) patients in group B (P=0.70); this difference was not significant. CONCLUSION: Our data did not show any significant impact of nitazoxanide on SVR.
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Antiparasitarios/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , ARN Viral/sangre , Tiazoles/uso terapéutico , Adulto , Antiparasitarios/efectos adversos , Antivirales/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Egipto , Femenino , Hepatitis C Crónica/sangre , Humanos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Nitrocompuestos , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéutico , Tiazoles/efectos adversos , Carga ViralRESUMEN
OBJECTIVE: To resolve much debated issues surrounding p53 function, expression and mutation in renal cell carcinoma (RCC), we performed the first study to simultaneously determine p53/MDM2 expression, TP53 mutational status (in p53-positive patients) and outcome in RCC. PATIENTS AND METHODS: In total, 90 specimens obtained from patients with RCC, who were treated by radical nephrectomy, were analyzed by immunohistochemistry for p53 and MDM2 on a tissue microarray, and p53 was functionally and genetically analyzed in p53 positive samples. Outcome analysis was by the Kaplan-Meier method and univariate analysis was used to identify variables for subsequent multivariate analysis of correlations between clinical parameters and biomarker expression. RESULTS: Up-regulation of p53 in RCC is strongly linked with MDM2 up-regulation (P < 0.001). Increased coexpression of p53 and MDM2 identifies those patients with a significantly reduced disease-specific survival by univariate (P= 0.036) and Cox multiple regression analysis (P= 0.027; relative risk, 3.20). Functional (i.e. functional analysis of separated alleles in yeast) and genetic analysis of tumours with increased p53 expression shows that most patients (86%) retain wild-type p53. CONCLUSIONS: Coexpression of p53/MDM2 identifies a subset of patients with poor prognosis, despite all of them having organ-confined disease. Up-regulated p53 is typically wild-type and thus provides a mechanistic explanation for the association between p53 and MDM2 expression: up-regulated wild-type p53 likely promotes the observed MDM2 coexpression. The results obtained in the present study suggest that the p53 pathway is altered in a tissue/disease-specific manner and that therapeutic strategies targeting this pathway should be investigated to determine whether the tumour suppressive function of p53 can be rescued in RCC.
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Carcinoma de Células Renales/genética , ADN de Neoplasias/genética , Regulación Neoplásica de la Expresión Génica , Nefrectomía , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Progresión de la Enfermedad , Femenino , Genotipo , Humanos , Inmunohistoquímica , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Proteínas Proto-Oncogénicas c-mdm2/biosíntesis , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/biosíntesis , Adulto JovenRESUMEN
BACKGROUND: Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta-analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous. METHODS: The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses. RESULTS: Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 + ve/MDM2-low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log-rank P = .035) and was an independent prognostic factor (P = .013; HR, 1.705; 95% CI, 1.12-2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log-rank P = .004) and was an independent prognostic factor (P = .004; HR, 2.78; 95% CI, 1.39-5.54) in p53 + ve/MDM2-low patients. CONCLUSIONS: These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status-dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression.