RESUMEN
BACKGROUND: The polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) family of enzymes regulates the initial steps of mucin-type O-glycosylation. N-acetylgalactosaminyltransferases might show novel patterns of GalNAc-T glycosylation on tumour-derived proteins, which could influence cancer biology, but its mechanisms are unclear. We investigated the association of GalNAc-T3 and -T6 expressions with clinicopathological features and prognoses of patients with renal cell carcinomas (RCCs). METHODS: Expressions of GalNAc-T3/6 and cell-adhesion molecules were analysed immunohistochemically in 254 paraffin-embedded tumour samples of patients with RCC. RESULTS: Of 138 GalNAc-T3+ cases, 46 revealed significant co-expression with GalNAc-T6. N-acetylgalactosaminyltransferases-3+ expression showed a close relationship to poor clinical performance and large tumour size, or pathologically high Fuhrman's grading, and presence of vascular invasion and necrosis. The GalNAc-T3-positivity potentially suppressed adhesive effects with a significantly low ß-catenin expression. Univariate and multivariate analyses showed the GalNAc-T3+ group, but not the GalNAc-T6+ group, to have significantly worse survival rates. CONCLUSION: N-acetylgalactosaminyltransferases-3 expression independently predicts high-grade tumour and poor prognosis in patients with RCC, and may offer a therapeutic target against RCC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , N-Acetilgalactosaminiltransferasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/enzimología , Línea Celular Tumoral , Estudios de Cohortes , Femenino , Humanos , Neoplasias Renales/enzimología , Masculino , Persona de Mediana Edad , N-Acetilgalactosaminiltransferasas/genética , Clasificación del Tumor , Pronóstico , Estudios Retrospectivos , Polipéptido N-AcetilgalactosaminiltransferasaRESUMEN
Education and counselling for people with drug-resistant tuberculosis (DR-TB) is recommended by the World Health Organization, given the arduous treatment journey. A model of education and counselling involving counsellors and peer counsellors, standard sessions and novel education tools was piloted in the high DR-TB burden context of Daru, Papua New Guinea. The pilot contributed to high retention in care, highlighting the need for investment in scalable models. Future models will need to be adapted as better tolerated regimens are introduced. A focus on patient-centred care requires prioritisation in order to meet the End TB Strategy targets.
L'éducation et le conseil aux personnes atteintes de tuberculose pharmacorésistante (DR-TB) sont recommandés par l'Organisation Mondiale de la Santé, étant donné les difficultés du parcours thérapeutique. Un modèle d'éducation et de conseil impliquant des conseillers et des pairs éducateurs, des sessions standard et de nouveaux outils d'éducation a été expérimenté dans le contexte de taux élevé de DR-TB de Daru en Papouasie Nouvelle Guinée. Ce projet pilote a contribué à un taux élevé de maintien en soins et a mis en lumière le besoin d'investir dans des modèles évolutifs. Les modèles futurs devront s'adapter aux protocoles mieux tolérés qui seront introduits. Une concentration sur les soins centrés sur le patient requiert une priorisation afin d'atteindre les objectifs de la stratégie Mettre fin à la TB.
La Organización Mundial de la Salud recomienda actividades de educación y orientación dirigidas a las personas con diagnóstico de tuberculosis farmacorresistente (DR-TB), habida cuenta de la trayectoria ardua del tratamiento. En el contexto de Daru, donde la carga de morbilidad por DR-TB es alta, se ensayó un modelo de educación y orientación. El proyecto piloto comportó la participación de consejeros, la orientación entre pares, sesiones ordinarias y nuevas herramientas pedagógicas. El proyecto contribuyó a lograr una alta retención en el servicio de atención y destacó la necesidad de inversión en modelos que se puedan ampliar. Será necesario adaptar los modelos futuros a medida que se introduzcan esquemas terapéuticos mejor tolerados. Un enfoque centrado en el paciente exige la definición de prioridades con miras a cumplir las metas de la Estrategia Fin a la Tuberculosis.
RESUMEN
OBJECTIVES: Papua New Guinea has among the highest prevalences of sexually transmissible infections (STIs) globally with no services able to accurately test for anorectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections. Here we prospectively evaluated the diagnostic performance of a molecular CT/NG assay used at the point-of-care (POC) with the aim of enhancing anorectal STI screening and same-day treatment. METHODS: Men who have sex with men, transgender women and female sex workers taking part in Papua New Guinea's first large-scale biobehavioural study were enrolled and asked to provide a self-collected anorectal swab for POC GeneXpert CT/NG testing. Same-day treatment was offered if positive. A convenience sample of 396 unique and randomly selected samples were transported to Australia for comparison using the Cobas 4800 CT/NG test (Roche Molecular Diagnostics, Pleasanton, CA, USA). RESULTS: A total of 326 samples provided valid results by Cobas whereas 70 samples provided invalid results suggesting inhibition. The positive, negative and overall percentage agreements of GeneXpert CT/NG for the detection of C. trachomatis were 96.7% (95% CI 92.3%-98.9%), 95.5% (95% CI 91.3%-98.0%) and 96.0% (95% CI 93.3%-97.8%), and for N. gonorrhoeae were 93.0% (95% CI 86.1%-97.1%), 100.0% (95% CI 98.3%-100.0%) and 97.8% (95% CI 95.6%-99.1%), respectively. CONCLUSIONS: The overall rate of agreement between the GeneXpert and Cobas CT/NG assays was high with 96.0% for C. trachomatis and 97.8% for N. gonorrhoeae. Results from this study data suggest that the GeneXpert CT/NG assay is suitable for testing self-collected anorectal specimens at the POC and that same-day treatment was feasible.