BackgroundNasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China and Southeast Asia, but its molecular mechanisms of pathogenesis are poorly understood. Our previous work has demonstrated that BCAT1 mRNA is over expressed in NPC and knocking down its expression in 5-8F NPC cell line can potently inhibit cell cycle progression and cell proliferation. However, the mechanism of BCAT1 up-regulation and its functional role in NPC development remain to be elucidated yet.MethodsImmunohistochemistry (IHC) method was utilized to detect the expression of BCAT1 protein in NPC at different pathological stages. The roles of gene mutation, DNA amplification and transcription factor c-Myc in regulating BCAT1 expression were analyzed using PCR-sequencing, quantitative polymerase chain reaction (qPCR), IHC, ChIP and luciferase reporter system, respectively. The functions of BCAT1 in colony formation, cell migration and invasion properties were evaluated by RNA interference (RNAi).ResultsThe positive rates of BCAT1 protein expression in normal epithelia, low-to-moderate grade atypical hyperplasia tissues, high-grade atypical hyperplasia tissues and NPC tissues were 23.6% (17/72), 75% (18/24 ), 88.9% (8/9) and 88.8% (71/80), respectively. Only one SNP site in exon1 was detected, and 42.4% (12/28) of the NPC tissues displayed the amplification of microsatellite loci in BCAT1. C-Myc could directly bind to the c-Myc binding site in promoter region of BCAT1 and up-regulate its expression. The mRNA and protein of c-Myc and BCAT1 were co-expressed in 53.6% (15/28) and 59.1% (13/22) of NPC tissues, respectively, and BCAT1 mRNA expression was also down-regulated in c-Myc knockdown cell lines. In addition, BCAT1 knockdown cells demonstrated reduced proliferation and decreased cell migration and invasion abilities.ConclusionsOur study indicates that gene amplification and c-Myc up-regulation are responsible for BCAT1 overexpression in primary NPC, and overexpression of BCAT1 induces cell proliferation, migration and invasion. The results suggest that BCAT1 may be a novel molecular target for the diagnosis and treatment of NPC.

Two ruthenium(II) complexes, Λ-[Ru(phen)2(p-HPIP)]2+ and Δ-[Ru(phen)2(p-HPIP)]2+, were synthesized and characterized via proton nuclear magnetic resonance spectroscopy, electrospray ionization-mass spectrometry, and circular dichroism spectroscopy. This study aims to clarify the anticancer effect of metal complexes as novel and potent telomerase inhibitors and cellular nucleus target drug. First, the chiral selectivity of the compounds and their ability to stabilize quadruplex DNA were studied via absorption and emission analyses, circular dichroism spectroscopy, fluorescence-resonance energy transfer melting assay, electrophoretic mobility shift assay, and polymerase chain reaction stop assay. The two chiral compounds selectively induced and stabilized the G-quadruplex of telomeric DNA with or without metal cations. These results provide new insights into the development of chiral anticancer agents for G-quadruplex DNA targeting. Telomerase repeat amplification protocol reveals the higher inhibitory activity of Λ-[Ru(phen)2(p-HPIP)]2+ against telomerase, suggesting that Λ-[Ru(phen)2(p-HPIP)]2+ may be a potential telomerase inhibitor for cancer chemotherapy. MTT assay results show that these chiral complexes have significant antitumor activities in HepG2 cells. More interestingly, cellular uptake and laser-scanning confocal microscopic studies reveal the efficient uptake of Λ-[Ru(phen)2(p-HPIP)]2+ by HepG2 cells. This complex then enters the cytoplasm and tends to accumulate in the nucleus. This nuclear penetration of the ruthenium complexes and their subsequent accumulation are associated with the chirality of the isomers as well as with the subtle environment of the ruthenium complexes. Therefore, the nucleus can be the cellular target of chiral ruthenium complexes for anticancer therapy.

This study aimed to investigate the potential determining epidemiological and clinical risk factors affecting the survival of esophageal cancer (EC) patients across multiple hospitals in China. Methods: This was a multicenter study comprising of newly diagnosed EC cases from Beijing, Hebei, Henan, Hubei, Zhejiang, and Guangdong Province of China. Their baseline characteristics and treatment methods data were collected from their medical records. The EpiData software was used for data quality control. The Kaplan-Meier method was used to estimate their overall survival (OS), and the Cox's proportional hazard regression model was used to estimate hazard ratios (HR) and 95% confidence interval (CI). Results: The 3-and 5-year OS rates of the 5283 investigated EC patients were 49.98% and 39.07%, respectively. Their median survival was 36.00 months. The median survival time of females was longer than that of males (females vs. males: 45.00 vs. 33.00, P < 0.001). The 5-year OS rate of patients who never-smoked was higher than that of smokers (never-smokers vs smokers: 40.73% vs. 37.84%, P = 0.001). There was no significant difference in the 5-year OS rate between

The residential regions of Yunnan province, canton of Jing Hong, in China were surveyed for Japanese encephalitis virus (JEV) infection in mosquito and swine vectors to determine the frequency of JEV-carrying zoonotic vectors in 2009-2010. A total of 21,500 mosquitoes were collected and divided by species, and brain tissue was collected from 108 stillborn piglets. The infection rates for the different JEV species were 13.2% for Culex tritaeniorhynchus, 2.7% for Anopheles sinensis, 0.7% for Armigeres subalbatus, and 18.5% for stillborn piglets. The complete genomes of two JEV samples that were collected in different seasons and different regions, Yunnan 0901 and Yunnan 0902, were sequenced from a pool of Culex mosquitoes and stillborn piglets that had been collected randomly from several piggeries. Multiple sequence alignment with 24 fully-sequenced genes and 93 complete sequences of the JEV-encoded E gene revealed nucleotide homologies ranging from 97.2-99.6% and 94.5-99.7% in mosquitoes and piglets, respectively, and deduced amino acid homologies ranging from 97.4-98.1% and 96.0-98.2%, respectively. Phylogenetic analyses of the Yunnan 0901 and Yunnan 0902 strains' full-length genomes and E gene sequences indicated that these strains are most closely related to six Chinese SA14-derived viruses, and distantly related to the Australian FU, vellore P20778, and Japanese Ishikawa strains, and the previously isolated YN86-B8639 strains. The phylogenetic relationships based on the full-length genome were similar to those found for the E gene, indicating that phylogenetic analysis of the E gene will be a useful approach for genotyping of JEV, but not to better understand the potential changes in the biological characteristics and genetic relationship of JEV isolates.