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Zhang R.-L.,Xinjiang Medical University | Zhang R.-L.,Key Laboratory of Infection and Cancer | Peng L.-X.,Sun Yat Sen University | Yang J.-P.,Sun Yat Sen University | And 9 more authors.
International Journal of Oncology | Year: 2016

Nasopharyngeal carcinoma (NPC) has the highest metastasis potential among head and neck cancers. Distant metastasis is the major cause of treatment failure. Recent studies from our laboratory have revealed that IL-8 promotes NPC metastasis via activation of AKT signaling and induction of epithelial-mesenchymal transition (EMT) in the cells. In the present study, we found that IL-8 treatment for NPC cells resulted in an accumulation of DNMT1 protein through activating AKT1 pathway and consequent DNMT1 protein stabilization. Then DNMT1 suppressed E-cadherin expression by increasing the methylation of its promoter region. LY-294002 blocked IL-8-induced p-AKT1 activation resulting in reduction of DNMT1 and increase of E-cadherin expression, whereas forced demethylation using 5-aza-2'-deoxycytidine restored E-cadherin expression. In conclusion, our study, for the first time, shows that the IL-8/AKT1 signaling pathway stabilizes DNMT1 protein, consequently enhancing hypermethylation of E-cadherin promoter regions and downregulating E-cadherin protein level in NPC cells. Upon blockage of the IL-8/AKT pathway and inhibition of DNMT1, E-cadherin expression can be reversed. These data suggest that targeting the IL-8/AKT1 signaling pathway and DNMT1 may provide a potential therapeutic approach for blocking NPC metastasis. Source


Xiao L.,Xinjiang Medical University | Xiao L.,Key Laboratory of Infection and Cancer | Zhang R.-L.,Xinjiang Medical University | Zhang H.,Xinjiang Medical University | And 5 more authors.
Chinese Journal of Cancer Research | Year: 2015

Objective: To compare the clinical characteristics and prognosis between hepatitis virus-related hepatocellular carcinoma (viral HCC) and non-B, non-C HCC (NBC-HCC) among Uyghur patients in Xinjiang province, China. Methods: Between 01/01/2000 and 31/12/2012, 319 Uyghur HCC patients were treated at the Cancer Centre of The First Affiliated Hospital of Xinjiang Medical University. The data for the patients were obtained from a retrospective review of the patients’ medical records. A total of 18 patients were excluded from the study because of incomplete information. The patients were classified into two groups: viral HCC and NBC-HCC. The clinical characteristics and prognostic factors were statistically analysed. Results: For all 301 patients, gender (P=0.000), area of residence (P=0.002), diabetes mellitus (P=0.009), BMI (P=0.000), cirrhosis (P=0.000), tumour stage (P=0.004), Child-Pugh class (P=0.000), the TBIL level (P=0.000), and the alpha-fetoprotein (AFP) level (P=0.000) were significantly different between the NBC-HCC and viral HCC groups. The NBC-HCC patients tended to be diagnosed at advanced stages; however, the NBC-HCC patients exhibited lower Child-Pugh scores than the viral HCC patients. In all patients examined, the 0.5-, 1-, 3- and 5-year overall survival (OS) rates were 35.6%, 20.3%, 12.6% and 4.5%, respectively. No significant difference in OS was observed between the two groups (P=0.124). Cox multivariate analysis revealed that age (RR =1.539, P=0.001), TNM stage (RR =12.708, P=0.000), portal vein tumour thrombus (PVTT) (RR =2.003, P=0.000), Child-Pugh class (RR =1.715, P=0.000), and TACE + radiotherapy/RFA (RR =0.567, P=0.000) were significant independent prognostic factors for HCC patients. Conclusions: The clinical characteristics differ between Uyghur patients with NBC-HCC and viral HCC. HCC in the Xinjiang region displays specific regional characteristics. Age, TNM stage, PVTT, Child-Pugh class and TACE + radiotherapy/RFA are significant risk factors that influence patient survival. © Chinese Journal of Cancer Research. All rights reserved. Source

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