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      • Genetic Epidemiological Analysis of Esophageal Cancer in High-incidence Areas of China

        Wang, Kai-Juan,Yang, Jun-Xia,Shi, Jia-Chen,Deng, Song-Yuan,Cao, Xiao-Qin,Song, Chun-Hua,Wang, Peng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

        Genetic epidemiological studies have shown that genetic susceptibility to esophageal cancer (EC) is an important cause of its high incidence within families in some areas of China. The purpose of this study was to obtain evidence of a genetic basis of EC in Xin-an and Xin-xiang counties in China. Familial aggregation and complex segregation analyses were performed of 79 EC families in these counties. The heritability of EC was examined using Falconer's method and complex segregation analysis was conducted with the SEGREG program in Statistical Analysis for Genetic Epidemiology (SAGE version 5.3.1). The results showed that the distribution of EC in families did not fit well into a binomial distribution. The heritability of EC among first-degree and second-degree relatives was $67.0{\pm}7.31%$ and $43.1%{\pm}9.80%$, respectively, and the summing up powered heritability was $53.2{\pm}6.74%$. The segregation ratio was 0.045. Complex segregation analysis showed that the genetic model of EC was additive. The current results provide evidence for an inherited propensity to EC in certain high-risk groups in China, and support efforts to identify the genes that confer susceptibility to this disease.

      • Hyperthermia Promotes Apoptosis and Suppresses Invasion in C6 Rat Glioma Cells

        Wang, Dong-Chun,Zhang, Yan,Chen, Hai-Yan,Li, Xiao-Li,Qin, Li-Juan,Li, Ya-Juan,Zhang, Hong-Yi,Wang, Shuo Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

        Gliomas are a group of heterogeneous primary central nervous system tumors. Hyperthermia has proven to be a potential therapeutic tool for cancers in the clinic. However, the molecular mechanisms of hyperthermia remain unclear. The objective of this study was to investigate the effects of hyperthermia on the invasiveness in C6 glioma cells and related molecular pathways. Here our data show hyperthermia stimulated the release of tumor necrosis factor-alpha (TNF-${\alpha}$) and decreased C6 glioma cell migration and invasive capability at 30, 60, 120 and 180 min; with increased spontaneous apoptosis in C6 glioma cells at 120 min. We also found mitogen-activated protein kinase (P38 MAPK) protein expression to be increased and nuclear factor-kappa B (NF-${\kappa}B$) protein expression decreased. Based on the results, we conclude that hyperthermia alone reduced invasion of C6 glioma cells through stimulating TNF-${\alpha}$ signaling to activate apoptosis, enhancing P38 MAPK expression and inhibiting the NF-${\kappa}B$ pathway, a first report in C6 rat glioma cells.

      • SCISCIESCOPUS

        FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation

        Xiao, Juan,Zhang, Tao,Xu, Daichao,Wang, Huibing,Cai, Yu,Jin, Taijie,Liu, Min,Jin, Mingzhi,Wu, Kejia,Yuan, Junying Cold Spring Harbor Laboratory Press 2015 Genes & development Vol.29 No.2

        <P>Vps34, the catalytic subunit in the class III phosphatidylinositol 3 kinase complexes, mediates the production of PtdIns3P, a key intracellular lipid involved in regulating autophagy and receptor degradation. Xiao et al. show that DNA damage-activated mitotic arrest and CDK activation lead to the phosphorylation of Vps34. This provides a signal to promote Vps34 ubiquitination and proteasomal degradation mediated by FBXL20, leading to inhibition of autophagy and receptor endocytosis. Importantly, they also find that expression of FBXL20 is regulated by p53-dependent transcription.</P><P>Vacuolar protein-sorting 34 (Vps34), the catalytic subunit in the class III PtdIns3 (phosphatidylinositol 3) kinase complexes, mediates the production of PtdIns3P, a key intracellular lipid involved in regulating autophagy and receptor degradation. However, the signal transduction pathways by which extracellular signals regulate Vps34 complexes and the downstream cellular mechanisms are not well understood. Here we show that DNA damage-activated mitotic arrest and CDK activation lead to the phosphorylation of Vps34, which provides a signal to promote its ubiquitination and proteasomal degradation mediated by FBXL20 (an F-box protein) and the associated Skp1 (S-phase kinase-associated protein-1)–Cullin1 complex, leading to inhibition of autophagy and receptor endocytosis. Furthermore, we show that the expression of FBXL20 is regulated by p53-dependent transcription. Our study provides a molecular pathway by which DNA damage regulates Vps34 complexes and its downstream mechanisms, including autophagy and receptor endocytosis, through SCF (Skp1–Cul1–F-box)-mediated ubiquitination and degradation. Since the expression of FBXL20 is regulated by p53-dependent transcription, the control of Vps34 ubiquitination and proteasomal degradation by FBXL20 and the associated SCF complex expression provides a novel checkpoint for p53 to regulate autophagy and receptor degradation in DNA damage response.</P>

      • Susceptibility Loci Associations with Prostate Cancer Risk in Northern Chinese Men

        Wang, Na-Na,Xu, Yong,Yang, Kuo,Wei, Dong,Zhang, Yao-Guang,Liu, Ming,Shi, Xiao-Hong,Liang, Si-Ying,Sun, Liang,Zhu, Xiao-Quan,Yang, Yi-Ge,Tang, Lei,Zhao, Cheng-Xiao,Wang, Xin,Chen, Xin,Hui, Juan,Zhang, Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

        Background: KLK3 gene products, like human prostate-specific antigen (PSA), are important biomarkers in the clinical diagnosis of prostate cancer (PCa). G protein-coupled receptor RFX6, C2orf43 and FOXP4 signaling plays important roles in the development of PCa. However, associations of these genes with PCa in northern Chinese men remain to be detailed. This study aimed to investigate their impact on occurrence and level of malignancy. Methods: All subjects were from Beijing and Tianjin, including 266 cases with prostate cancer and 288 normal individuals as controls. We evaluated associations between clinical covariates (age at diagnosis, prostate specific antigen, Gleason score, tumor stage and aggressive) and 6 candidate PCa risk loci, genotyped by PCR- high resolution melting curve and sequencing methods. Results: Case-control analysis of allelic frequency of PCa associated with PCa showed that one of the 6 candidate risk loci, rs339331 in the RFX6 gene, was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.73, 95% confidence interval (CI) =0.57-0.94, P = 0.013) in northern Chinese men. In addition, subjects with CX (CC+TC) genotypes had a decreased risk for prostrate cancer compared to those carrying the TT homozygote (OR =0.64, 95% CI = 0.45- 0.90, P = 0.008). The TT genotype of 13q22 (rs9600079, T) was associated with tumor stage (P=0.044, OR=2.34, 95% CI=0.94-5.87). Other SNPs were not significantly associated with clinical covariates in prostate cancer (P > 0.05). Conclusions. rs339331 in the RFX6 gene may be associated with prostate cancer as a susceptibility locus in northern Chinese men.

      • KCI등재
      • KCI등재

        A Meta-Analysis of the Accuracy of Prostate Cancer Studies Which Use Magnetic Resonance Spectroscopy as a Diagnostic Tool

        Peng Wang,You-min Guo,Min Liu,Yong-qian Qiang,Xiao-juan Guo,Yi-li Zhang,Xiao-Yi Duan,Qiu-Juan Zhang,Weifeng Liang 대한영상의학회 2008 Korean Journal of Radiology Vol.9 No.5

        Objective: We aimed to do a meta-analysis of the existing literature to assess the accuracy of prostate cancer studies which use magnetic resonance spectroscopy (MRS) as a diagnostic tool. Materials and Methods: Prospectively, independent, blind studies were selected from the Cochrane library, Pubmed, and other network databases. The criteria for inclusion and exclusion in this study referenced the criteria of diagnostic research published by the Cochrane center. The statistical analysis was adopted by using Meta-Test version 6.0. Using the homogeneity test, a statistical effect model was chosen to calculate different pooled weighted values of sensitivity, specificity, and the corresponding 95% confidence intervals (95% CI). The summary receiver operating characteristic (SROC) curves method was used to assess the results. Results: We chose two cut-off values (0.75 and 0.86) as the diagnostic criteria for discriminating between benign and malignant. In the first diagnostic criterion, the pooled weighted sensitivity, specificity, and corresponding 95% CI (expressed as area under curve [AUC]) were 0.82 (0.73, 0.89), 0.68 (0.58, 0.76), and 83.4% (74.97, 91.83). In the second criterion, the pooled weighted sensitivity, specificity, and corresponding 95% CI were 0.64 (0.55, 0.72), 0.86 (0.79, 0.91) and 82.7% (68.73, 96.68). Conclusion: As a new method in the diagnostic of prostate cancer, MRS has a better applied value compared to other common modalities. Ultimately, large scale RCT randomized controlled trial studies are necessary to assess its clinical value. Objective: We aimed to do a meta-analysis of the existing literature to assess the accuracy of prostate cancer studies which use magnetic resonance spectroscopy (MRS) as a diagnostic tool. Materials and Methods: Prospectively, independent, blind studies were selected from the Cochrane library, Pubmed, and other network databases. The criteria for inclusion and exclusion in this study referenced the criteria of diagnostic research published by the Cochrane center. The statistical analysis was adopted by using Meta-Test version 6.0. Using the homogeneity test, a statistical effect model was chosen to calculate different pooled weighted values of sensitivity, specificity, and the corresponding 95% confidence intervals (95% CI). The summary receiver operating characteristic (SROC) curves method was used to assess the results. Results: We chose two cut-off values (0.75 and 0.86) as the diagnostic criteria for discriminating between benign and malignant. In the first diagnostic criterion, the pooled weighted sensitivity, specificity, and corresponding 95% CI (expressed as area under curve [AUC]) were 0.82 (0.73, 0.89), 0.68 (0.58, 0.76), and 83.4% (74.97, 91.83). In the second criterion, the pooled weighted sensitivity, specificity, and corresponding 95% CI were 0.64 (0.55, 0.72), 0.86 (0.79, 0.91) and 82.7% (68.73, 96.68). Conclusion: As a new method in the diagnostic of prostate cancer, MRS has a better applied value compared to other common modalities. Ultimately, large scale RCT randomized controlled trial studies are necessary to assess its clinical value.

      • SCIEKCI등재
      • KCI등재

        Alu Tandem Sequences Inhibit GFP Gene Expression by Triggering Chromatin Wrapping

        Xiu Fang Wang,Xiao Yan Wang,Jing Liu,Jing Jing Feng,Wen Li Mu,Xiao Juan Shi,Qin Qing Yang,Xiao Cui Duan,Ying Xie,Zhan Jun Lu 한국유전학회 2009 Genes & Genomics Vol.31 No.3

        Alu elements belonging to the short interspersed nuclear elements (SINE) of repetitive elements are present in more than one million copies which altogether represent 10% of the whole human genome. In this study, the roles of Alu tandem sequences in the process of GFP gene (GFP) expression and packing into chromatin of its DNA were studied. To detect the effect of Alu repeats on gene expression, different copies of Alus were inserted GFP downstream respectively in pEGFP-C1 vector. We found that Alu sequences decreased the amount of GFP transcription, the percentage of GFP positive cells and the accessibility to DNase I in length-dependent manner. Inserting Alu caused the production of higher-molecular-mass RNA, indicating Alu sequence did not induce premature transcriptional termination. Tight packing chromatins keep silent and resist to DNase I digestion, which is a general phenomenon. We suggested that head and tail tandem Alu sequences suppressed GFP expression in length dependent manner by triggering chromatin packing.

      • RTN4 3'-UTR Insertion/Deletion Polymorphism and Susceptibility to Non-Small Cell Lung Cancer in Chinese Han Population

        Lu, De-Yi,Mao, Xu-Hua,Zhou, Ying-Hui,Yan, Xiao-Long,Wang, Wei-Ping,Zheng, Ya-Biao,Xiao, Juan-Juan,Zhang, Ping,Wang, Jian-Guo,Ashwani, Neetika,Ding, Wei-Liang,Jiang, Hua,Shang, Yan,Wang, Ming-Hua Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

        Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.

      • KCI등재

        Molecular Characterization of a Thermophilic and Salt- and Alkaline-Tolerant Xylanase from Planococcus sp. SL4, a Strain Isolated from the Sediment of a Soda Lake

        ( Xiao Yun Huang ),( Juan Lin ),( Xiu Yun Ye ),( Guo Zeng Wang ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.5

        To enrich the genetic resource of microbial xylanases with high activity and stability under alkaline conditions, a xylanase gene (xynSL4) was cloned from Planococcus sp. SL4, an alkaline xylanase-producing strain isolated from the sediment of soda lake Dabusu. Deduced XynSL4 consists of a putative signal peptide of 29 residues and a catalytic domain (30-380 residues) of glycosyl hydrolase family 10, and shares the highest identity of 77% with a hypothetical protein from Planomicrobium glaciei CHR43. Phylogenetic analysis indicated that deduced XynSL4 is closely related with thermophilic and alkaline xylanases from Geobacillus and Bacillus species. The gene xynSL4 was expressed heterologously in Escherichia coli and the recombinant enzyme showed some superior properties. Purified recombinant XynSL4 (rXynSL4) was highly active and stable over the neutral and alkaline pH range from 6 to 11, with maximum activity at pH 7 and more than 60% activity at pH 11. It had an apparent temperature optimum of 70oC and retained stable at this temperature in the presence of substrate. rXynSL4 was highly halotolerant, retaining more than 55% activity with 0.25.3.0 M NaCl and was stable at the concentration of NaCl up to 4M. The enzyme activity was significantly enhanced by β-mercaptoethanol and Ca2+ but strongly inhibited by heavy-metal ions and SDS. This thermophilic and alkaline- and salt-tolerant enzyme has great potential for basic research and industrial applications.

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