Low expression of BEX1 predicts poor prognosis in patients with esophageal squamous cell cancer.

The brain expressed x­linked gene 1 (BEX1) is a member of the BEX family and is aberrantly expressed in many cancers. However, the clinical significance of BEX1 expression level and its role in the pathology of esophageal squamous cell cancer (ESCC) remain unknown. In the present study, we determined BEX1 expression in the tumor and adjacent normal tissues from 118 ESCC patients by immunohistochemistry and determined the proliferation and growth of ESCC cells following ectopic overexpression of BEX1 in cultured cells and in mouse­ESCC xenografts. We observed that BEX1 was downregulated in ESCC tissues compared to adjacent normal tissues, and low BEX1 expression was significantly associated with larger ESCC tumor volume (P<0.001), advanced T stage (P=0.011) and advanced clinical stage (P=0.039). Additionally, survival analysis revealed that low expression of BEX1 significantly predicted poor prognosis in patients with ESCC (P<0.001). Multivariate analysis revealed that low BEX1 expression was an independent prognostic factor of poor survival (P=0.039). In vitro analysis revealed that overexpression of BEX1 inhibited ESCC cell proliferation and colony formation. Furthermore, in vivo tumorigenesis assays revealed that ectopic overexpression of BEX1 suppressed ESCC tumor growth in mice. Further immunoblotting analysis demonstrated that BEX1 upregulation led to reduced expression and phosphorylation of NF­κB p65, indicating inhibition of the NF­κB signaling pathway by BEX1. Our findings indicated that low BEX1 expression may be an independent prognostic marker for poor survival and may serve as a potential target for ESCC therapy.

Efficacy and safety of transdermal fentanyl for the treatment of oral mucositis pain caused by chemoradiotherapy in patients with esophageal squamous cell carcinoma.

PURPOSE: Oral mucositis is one of the most painful side effects found in esophageal squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy. The transdermal route of administration is worthy of investigation for patients who suffer from dysphagia due to severe oral mucositis. In this phase 2 study, we investigated the efficacy and safety of transdermal fentanyl (TDF) for mucositis pain caused by chemoradiotherapy in ESCC patients. METHODS: Forty-six ESCC patients who experienced moderate to severe oral mucosal pain during chemoradiotherapy received TDF for pain relief. The assessment of pain was made according to the Numeric Rating Scale (NRS). Efficacy and safety of TDF was collected and conducted in an open-label fashion. The analgesic effect, quality of life, and side effects were evaluated after the administration of transdermal fentanyl using the paired sample Wilcoxon signed rank test. RESULTS: The mucositis-induced pain disappeared in 31 (67.4 %) patients during the treatment with transdermal fentanyl with the median time of onset at day 6.6 (range 3-14). The median Numeric Rating Scale (NRS) score was reduced from 6 (range 3-9) before treatment to 4.5 (range 2-9), 3 (range 2-8), 2.5 (range 1-8), 2 (range 0-6), and 0 (range 0-4) on days 3, 6, 9, 11, and 15, respectively, after treatment (P < 0.001). The patients' quality of life also improved significantly (P < 0.01). The side effects of treatment were mild and disappeared within several days. CONCLUSION: Transdermal fentanyl is an effective, convenient, and well-tolerated treatment for mucositis pain caused by chemoradiotherapy, which can improve ESCC patients' quality of life.