Purpose: Nasopharyngeal carcinoma is prevalent in southern China and Southeast Asia, with distinct geographic and ethnic distribution. One candidate susceptibility locus has been identified at 4p11-14, with the associated candidate gene(s) not identified yet. This study investigated the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in nasopharyngeal carcinoma pathogenesis.Experimental Design: UCHL1 expression and methylation were examined in nasopharyngeal carcinoma. Furthermore, the mechanism of its tumor-suppressive function was elucidated in nasopharyngeal carcinoma cells.Results: Through genomewide expression profiling, we identified UCHL1, a 4p14 gene normally expressed in normal upper respiratory tract tissues, being silenced in all nasopharyngeal carcinoma cell lines. Its silencing is mediated by CpG methylation because UCHL1 promoter methylation was detected in all silenced cell lines, and pharmacologic demethylation reactivated UCHL1 expression along with concomitant promoter demethylation. UCHL1 methylation was also frequently detected in primary tumors but only weakly detected in few normal nasopharyngeal tissues, indicating that the methylation-mediated silencing of UCHL1 is important in nasopharyngeal carcinoma pathogenesis. Ectopic UCHL1 expression dramatically inhibited the growth of nasopharyngeal carcinoma cells through promoting tumor cell apoptosis. We further found that UCHL1 formed a complex with p53/p14 ARF /Mdm2 p53 binding protein homolog (mouse), MDM2 and activated the p53 signaling pathway. UCHL1 expression extended p53 and p14ARF protein half-life and shortened MDM2 protein half-life. Conclusions:These results indicate that UCHL1 could deubiquitinate p53 and p14 ARF and ubiquitinate MDM2 for p53 stabilization to promote p53 signaling, thus involved in nasopharyngeal carcinoma pathogenesis, whereas it is frequently silenced in this tumor.

Intranasal surface anatomy is fundamental to the technique of endoscopic dacryocystorhinostomy. In the current literature the lacrimal sac is described as being situated anterior to the anterior end of the middle turbinate with between 0% and 20% of the sac above the insertion of the middle turbinate on the lateral nasal wall (the axilla of the middle turbinate). The aim of this study was to use CT dacryocystograms (DCGs) and CT scans to establish the relationship of the lacrimal sac to the lateral nasal wall. Forty-seven individual lacrimal sacs were measured in relation to the common canaliculus, and 76 were measured in relation to the insertion of the middle turbinate. Measurements taken from the long axis of the sac showed the mean height of the sac above the middle turbinate insertion was 8.8 mm (SD = 0.2, 95% CI = 1.3) and below it was 4.1 mm (SD = 2.3, 95% CI = 1.1). The average measurement of the sac above the com-mon canaliculus on CT DCGs was 5.3 mm (SD = 1.7, 95% CI = 0.56), whereas the average measurement below the common canaliculus was 7.7 mm (SD = 2, 95% CI = 1.3) (n = 47 CT DCGs). The findings in this study show that a major portion of the sac is locat-ed above the insertion of the anterior end of the middle turbinate and, in addition, that a significant part of the sac lies above the entry point of the common canaliculus. Knowledge of these findings can ensure that the sac is adequately exposed during dacryocystorhinostomy by removal of sufficient bone and mucosa above the anterior insertion of the middle turbinate.