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      • KCI등재후보

        A Computer-aided Design Tool with Semiautomatic Image-Processing Features for Visualizing Biological Pathways

        함성일,양산덕,Chin-Ting Thong,박현석 한국유전체학회 2009 Genomics & informatics Vol.7 No.3

        The explosion in biological data resulting from highthroughput experiments requires new software tools to manipulate and display pathways in a way that can integrate disparate sources of information. A visual Java-based CAD tool for drawing and annotating biological pathways with semiautomatic image-processing features is described in this paper. The result of the image-editing process is an XML file for the appropriate links. This tool integrates the pathway images and XML file sources. The system has facilities for linking graphical objects to external databases and is capable of reproducing existing visual representations of pathway maps.

      • KCI등재

        Aberrant epigenetic regulation of GABRP associates with aggressive phenotype of ovarian cancer

        성혜윤,양산덕,주웅,안정혁 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

        Metastasis is a major cause of therapeutic failure in ovarian cancer. To elucidate molecular mechanisms of ovarian cancer metastasis, we previously established a metastatic xenograft mouse model using human ovarian carcinoma SK-OV-3 cells. Using gene expression profiling, we found that γ-aminobutyric acid (GABA)A receptor π subunit (GABRP) expression was upregulated (44-fold) in metastatic tissues from our xenograft mice compared with SK-OV-3 cells. Importantly, GABRP knockdown diminished the migration and invasion of SK-OV-3 cells, and reduced extracellular signal-regulated kinase (ERK) activation while overexpression of GABRP exhibited significantly increased cell migration, invasion and ERK activation. Moreover, treatment with the mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor U0126 similarly suppressed the migration and invasion of SK-OV-3 cells, implying that GABRP promotes these cellular behaviors by activating the MAPK/ERK pathway. Using genome-wide DNA methylation profiling, we identified hypomethylated CpG sites in the GABRP promoter in metastatic tissues from the xenograft mice compared with SK-OV-3 cells. Treatment with a DNA methyltransferase inhibitor demonstrated that methylation at − 963 bp from the GABRP transcription start site (−963 CpG site) was critical for the epigenetic regulation of GABRP. Finally, we analyzed human ovarian cancer patient samples and showed DNA hypomethylation at the GABRP − 963 CpG site in advanced stage, but not early-stage, primary tumors compared with their paired normal tissues. These findings suggest that GABRP enhances the aggressive phenotype of ovarian cancer cells, and that the DNA methylation status of the GABRP − 963 CpG site may be useful for predicting the metastatic potential in ovarian cancer patients.

      • KCI등재

        Epigenetic modification of α-N-acetylgalactosaminidase enhances cisplatin resistance in ovarian cancer

        하예나,성혜윤,양산덕,채윤주,주웅,안정혁 대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.1

        Although cisplatin is one of the most effective antitumor drugs for ovarian cancer, the emergence of chemoresistance to cisplatin in over 80% of initially responsive patients is a major barrier to successful therapy. The precise mechanisms underlying the development of cisplatin resistance are not fully understood, but alteration of DNA methylation associated with aberrant gene silencing may play a role. To identify epigenetically regulated genes directly associated with ovarian cancer cisplatin resistance, we compared the expression and methylation profiles of cisplatin-sensitive and -resistant human ovarian cancer cell lines. We identified α-Nacetylgalactosaminidase(NAGA) as one of the key candidate genes for cisplatin drug response. Interestingly, in cisplatin-resistant cell lines, NAGA was significantly downregulated and hypermethylated at a promoter CpG site at position +251 relative to the transcriptional start site. Low NAGA expression in cisplatin-resistant cell lines was restored by treatment with a DNA demethylation agent, indicating transcriptional silencing by hyper-DNA methylation. Furthermore, overexpression of NAGA in cisplatin-resistant lines induced cytotoxicity in response to cisplatin, whereas depletion of NAGA expression increased cisplatin chemoresistance, suggesting an essential role of NAGA in sensitizing ovarian cells to cisplatin. These findings indicate that NAGA acts as a cisplatin sensitizer and its gene silencing by hypermethylation confers resistance to cisplatin in ovarian cancer. Therefore, we suggest NAGA may be a promising potential therapeutic target for improvement of sensitivity to cisplatin in ovarian cancer.

      • KCI등재후보

        J2.5dPathway: A 2.5D Visualization Tool to Display Selected Nodes in Biological Pathways, in Parallel Planes

        함성일,송은하,양산덕,Chin-Ting Thong,이아랑,Bulgan Galbadrakh,이경은,박현석,이산호 한국유전체학회 2009 Genomics & informatics Vol.7 No.3

        The characteristics of metabolic pathways make them particularly amenable to layered graph drawing methods. This paper presents a visual Java-based tool for drawing and annotating biological pathways in twoand- a-half dimensions (2.5D) as an alternative to threedimensional (3D) visualizations. Such visualization allows user to display different groups of clustered nodes, in different parallel planes, and to see a detailed view of a group of objects in focus and its place in the context of the whole system. This tool is an extended version of J2dPathway.

      • KCI등재

        Aberrant Hypomethylation of Solute Carrier Family 6 Member 12 Promoter Induces Metastasis of Ovarian Cancer

        성혜윤,안정혁,양산덕,박애경,주웅 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.1

        Purpose: Ovarian cancer (OC) is the most fatal of gynecological malignancies with a high rate of recurrence. We aimed to evaluatethe expression of solute carrier family 6, member 12 (SLC6A12) and methylation of its promoter CpG sites in a xenograft mousemodel of metastatic OC, and to investigate the regulatory mechanisms that promote aggressive properties during OC progression. Materials and Methods: Expression of SLC6A12 mRNA was determined by reverse-transcription quantitative polymerase chainreaction (RT-qPCR), and DNA methylation status of its promoter CpGs was detected by quantitative methylation-specific PCR. Themetastatic potential of SLC6A12 was evaluated by in vitro migration/invasion transwell assays. Gene expression and DNA methylationof SLC6A12 and clinical outcomes were further investigated from publicly available databases from curatedOvarianDataand The Cancer Genome Atlas. Results: SLC6A12 expression was 8.1–14.0-fold upregulated and its DNA methylation of promoter CpG sites was 41–62% decreasedin tumor metastases. After treatment with DNA methyltransferase inhibitor and/or histone deacetylase inhibitor, the expression ofSLC6A12 was profoundly enhanced (~8.0-fold), strongly supporting DNA methylation-dependent epigenetic regulation of SLC6A12. Overexpression of SLC6A12 led to increased migration and invasion of ovarian carcinoma cells in vitro, approximately 2.0-fold and3.3-fold, respectively. The meta-analysis showed that high expression of SLC6A12 was significantly associated with poor overall survival[hazard ratio (HR)=1.07, p value=0.016] and that low DNA methylation levels of SLC6A12 at specific promoter CpG site negativelyaffected patient survival. Conclusion: Our findings provide novel evidence for the biological and clinical significance of SLC6A12 as a metastasis-promotinggene.

      • KCI등재후보

        A Simple GUI-based Sequencing Format Conversion Tool for the Three NGS Platforms

        Arang Rhie,이경은,Chin Ting Thong,박현석,양산덕 한국유전체학회 2010 Genomics & informatics Vol.8 No.2

        To allow for a quick conversion of the proprietary sequence data from various sequencing platforms, sequence format conversion toolkits are required that can be easily integrated into workflow systems. In this respect, a format conversion tool, as well as quality conversion tool would be the minimum requirements to integrate reads from different platforms. We have developed the Pyrus NGS Sequencing Format Converter, a simple software toolkit which allows to convert three kinds of Next Generation Sequencing reads, into commonly used fasta or fastq formats. The converter modules are all implemented, uniformly, in Java GUI modules that can be integrated in software applications for displaying the data content in the same format.

      • KCI등재후보

        Java DOM Parsers to Convert KGML into SBML and BioPAX Common Exchange Formats

        이경은,장명하,Arang Rhie,Chin Ting Thong,양산덕,박현석 한국유전체학회 2010 Genomics & informatics Vol.8 No.2

        Integrating various pathway data collections to create new biological knowledge is a challenge, for which novel computational tools play a key role. For this purpose, we developed the Java-based conversion modules KGML2SBML and KGML2BioPAX to translate KGML (KEGG Markup Language) into a couple of common data exchange formats: SBML (Systems Biology Markup Language) and BioPAX (Biological Pathway Exchange). We hope that our work will be beneficial for other Java developers when they extend their bioinformatics system into SBML- or BioPAX-aware analysis tools. This is part of our ongoing effort to develop an ultimate KEGG-based pathway enrichment analysis system.

      • KCI등재

        Genome-Wide Association Study of Bone Mineral Density in Korean Men

        배예슬,임선화,강미소,김진희,이순항,조비룡,박진호,남유선,손호영,양산덕,성주헌,오광호,윤재문,김종일 한국유전체학회 2016 Genomics & informatics Vol.14 No.2

        Osteoporosis is a medical condition of global concern, with increasing incidence in both sexes. Bone mineral density (BMD), a highly heritable trait, has been proven a useful diagnostic factor in predicting fracture. Because medical information is lacking about male osteoporotic genetics, we conducted a genome-wide association study of BMD in Korean men. With 1,176 participants, we analyzed 4,414,664 single nucleotide polymorphisms (SNPs) after genomic imputation, and identified five SNPs and three loci correlated with bone density and strength. Multivariate linear regression models were applied to adjust for age and body mass index interference. Rs17124500 (p = 6.42 × 10−7), rs34594869 (p = 6.53 × 10−7) and rs17124504 (p = 6.53 × 10−7) in 14q31.3 and rs140155614 (p = 8.64 × 10−7) in 15q25.1 were significantly associated with lumbar spine BMD (LS-BMD), while rs111822233 (p = 6.35 × 10−7) was linked with the femur total BMD (FT-BMD). Additionally, we analyzed the relationship between BMD and five genes previously identified in Korean men. Rs61382873 (p = 0.0009) in LRP5, rs9567003 (p = 0.0033) in TNFSF11 and rs9935828 (p = 0.0248) in FOXL1 were observed for LS-BMD. Furthermore, rs33997547 (p = 0.0057) in ZBTB and rs1664496 (p = 0.0012) in MEF2C were found to influence FT-BMD and rs61769193 (p = 0.0114) in ZBTB to influence femur neck BMD. We identified five SNPs and three genomic regions, associated with BMD. The significance of our results lies in the discovery of new loci, while also affirming a previously significant locus, as potential osteoporotic factors in the Korean male population.

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