RESUMO
The tumor suppressor gene BRCA1 associated protein-1 (BAP1) is frequently mutated in renal cell carcinoma (RCC). BAP1 loss-of-function mutations are associated with poor survival outcomes. However, personalized therapy for BAP1-mutated RCC is currently not available. Previously, we found that BAP1 loss renders RCC cells more sensitive to bromodomain and extra-terminal (BET) inhibitors, as demonstrated in both cell culture and xenografted nude mice models. Here, we demonstrate that BAP1 loss in murine RCC cells enhances sensitivity to BET inhibitors in ectopic and orthotopic allograft models. While BAP1 deletion suppresses RCC cell survival in vitro, it does not impede tumor growth in immunocompetent murine models. Thus, the effect of BAP1 loss on the interactions between tumor cells and host microenvironment plays a predominant role in RCC growth, highlighting the importance of utilizing immunocompetent animal models to assess the efficacy of potential anticancer therapies. Mechanistically, BAP1 deletion compromises DNA repair capacity, rendering RCC cells more vulnerable to DNA damage induced by BET inhibitors. Our results indicate that BET inhibitors show promise as targeted therapy for BAP1-deficient RCC.
RESUMO
PURPOSE: To determine the age and sex characteristics of the children and type of dental procedures performed under dental general anesthesia (DGA) and to assess the results after six months to one year's follow-up. METHODS: A sample of 30 patients treated under dental general anesthesia (DGA) during 2006-2007 in the Department of Pediatric Dentistry of China Medical University was reviewed. All the teeth were treated one time. The dental procedures performed included caries restoration, indirect pulp capping, pulpotomy, root canal therapy (RCT) and dental extraction. Oral prophylaxis and topical fluoride applications were performed on all teeth. Pit and fissure sealing was performed on all healthy premolars and molars. SPSS10.0 software package was used for statistical analysis. Chi-square test was used to analyze the difference of the sex distribution in different age group and the difference of dental procedures performed between the primary teeth and the permanent teeth. RESULTS: The age of the patients ranged from 19 months to 14 years. The mental retardation patients accounted for 10% and mental healthy patients accounted for 90% of the sample studied. Males were more than females with the ratio about 2 to 1 in each age group. The dental procedures performed were caries restoration (18.67%), indirect pulp capping (23.26%), pulpotomy (0.77%), RCT (29.16%), dental extractions (2.05%) and fissure sealants (26.09%). The percentage of RCT was higher than that of caries restoration in the primary teeth, whereas the result was opposite as for the permanent teeth as indicated by Chi-square test (X(2)=11.630, P=0.001). New dental caries was not found except 2 patients who suffered from dysnoesia and were not cooperative to have regular examination. Fillings were lost in 3 cases, with 3 anterior teeth and 2 posterior teeth after RCT. All the children could cooperate except two mental retardation patients during the follow-up visit. CONCLUSIONS: Caries restoration and RCT are the most frequently performed procedures in pediatric patients using DGA. This indicates the need to design and implement integrate control and prevention programs for special pediatric patients. DGA is a safe and effective behavior management technique to treat uncooperative children.