Biomedical subjects

Seung Yong Hwang

Publications and source records attributed to Seung Yong Hwang.

11 recordsLinked to original sources

PubMed2006

Monitoring the gene expression profiles of doxorubicin-resistant acute myelocytic leukemia cells by DNA microarray analysis.

Acquired drug-resistance phenotype is a key factor in the relapse of patients suffering hematological malignancies. In order to investigate the genes involved in drug resistance, a human leukemia cell line that is resistant to doxorubicin, an anthracycline anticancer agent (AML-2/DX100), was selected and its gene expression profile was analyzed using a cDNA microarray. A number of genes were differentially expressed in the AML-2/DX100 cells, compared with the wild type (AML-2/WT). Pro-apoptotic genes such as TNFSF7 and p21 (Cip1/Waf1) were significantly down-regulated, whereas the IKBKB, PCNA, stathmin 1, MCM5, MMP-2 and MRP1 genes, which are involved in anti-apoptotic or cell cycle progression, were over-expressed. The AML-2/DX100 cells were also resistant to other anticancer drugs, including daunorubicin and camptothecin, and the expression levels of the differentially regulated genes such as STMN1, MMP-2 and CTSG, were constantly maintained. This suggests that the deregulated genes obtained from the DNA microarray analysis in a cell line model of drug resistance might contribute to the acquired drug resistance after chronic exposure.

Antibiotics, Antineoplastic↗

PubMed2006

Identification of gene expression signatures for molecular classification in human leukemia cells.

Although the methods by which leukemia is classified have been improved for effective therapies, leukemia patients occasionally exhibit diverse, sometimes unpredictable, responses to treatment. Consequently, these patients also evidence individually different clinical courses when administered with anti-leukemia drugs. In order to find new, more precise molecular markers for leukemia classification, we have analyzed the gene expression profiles from 65 diagnostic bone marrow specimens of adult patients with AML, ALL, CML or CLL by using high-throughput DNA microarrays harboring approximately 8,300 unique human genes or expression sequence tags. In the present study, we identified a group of leukemia-specific genes, which manifest gene expression profiles distinctly representative of normal bone marrow samples, as determined by a significance analysis of microarray (SAM) and GeneSpring 6.1 programs. We also determined the minimal number of genes showing a difference between acute and chronic leukemia patient groups. Furthermore, the unsupervised cluster analysis revealed a gene subset which can be used to distinguish between AML, ALL, CML and CLL patient groups, based on expression signatures. The expression levels of differentially regulated genes were verified via the principle component analysis (PCA). Our results may provide a novel set of molecular criteria for the classification of leukemia patients, and may also facilitate effects to discovery new targets, allowing for more effective treatment of leukemia patients.

Adolescent↗

PubMed2005

Highly sensitive signal detection of duplex dye-labelled DNA oligonucleotides in a PDMS microfluidic chip: confocal surface-enhanced Raman spectroscopic study.

Rapid and highly sensitive detection of duplex dye-labelled DNA sequences in a PDMS microfluidic channel was investigated using confocal surface enhanced Raman spectroscopy (SERS). This method does not need either an immobilization procedure or a PCR amplification procedure, which are essential for a DNA microarray chip. Furthermore, Raman peaks of each dye-labelled DNA can be easily resolved since they are much narrower than the corresponding broad fluorescence bands. To find the potential applicability of confocal SERS for sensitive bio-detection in a microfluidic channel, the mixture of two different dye-labelled (TAMRA and Cy3) sex determining Y genes, SRY and SPGY1, was adsorbed on silver colloids in the alligator teeth-shaped PDMS microfluidic channel and its SERS signals were measured under flowing conditions. Its major SERS peaks were observable down to the concentration of 10(-11) M. In the present study, we explore the feasibility of confocal SERS for the highly sensitive detection of duplex dye-labelled DNA oligonucleotides in a PDMS microfluidic chip.

Colloids↗

PubMed2004

Application of DNA chip techniques for Yq microdeletion analysis in infertile males.

Our aim was to apply DNA chip technology as a diagnostic tool in infertility research and clinics. Six loci, including a sex-determining region on the Y chromosome and five sequence-tagged sites in azoospermia-factor regions were investigated in infertile male patients. Our method produced a sensitive signal, which showed the presence or absence of the STS regions on the Y chromosome. The results from 93 patients with non- obstructive azoospermia, oligoathenoteratozoospermia, or oligozoospermia were identical when analyzed with either the DNA chip technique or conventional PCR-gel electrophoresis. We have demonstrated its application in the molecular diagnosis of male infertility. This system provides an economic and high-throughput method for detecting the deletion of genomic DNA sequences of large groups of infertile patients, and a completely new approach to male infertility screening. The application of DNA chip technology to identify Yq deletions can also facilitate our understanding of male infertility.

Chromosome Deletion↗

PubMed2004

Gene expression analysis of peroxisome proliferators- and phenytoin-induced hepatotoxicity using cDNA microarray.

The recent DNA microarray technology enables us to understand a large number of gene expression profiling. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, the toxicogenomics through this technology may be very powerful for understanding the effect of unknown toxic mechanisms in biological system. We have studied that the effect of compounds related to hepatotoxin in vivo system using DNA microarray and classified chemicals which have been well characterized. We have studied three compounds; 2 peroxisome proliferators: Clofibrate (ethyl-p-chlorophenoxyisobutyrate), gemfibrozil (5-2[2,5-dimethyl-phenoxy]2-2-dimethyl-pentanonic), and an antiepileptic drug: phenytoin (5,5-diphenylhydantoin). Male Sprague-Dawely VAF(+) albino rats of 5-6 weeks old were treated with each compound for 24 hr and 2 weeks. 4.8 K cDNA microarray in house has been used for gene expression profiling. We found that the clustering of gene expression had similarity like as the toxic phenotype of compounds.

Animals↗

PubMed2004

The intelligent data management system for toxicogenomics.

Toxicogenomics is now emerging as one of the most important genomic application because the toxicity test based on gene expression profiles is expected to be more precise and efficient than current histopathological approaches in a pre-clinical phase. One of the challenging issues in toxicogenomics is the construction of intelligent database management system which can deal with heterogeneous and complex data from many different experimental and information sources. TEST(Toxicogenomics for Efficient Safety Test) database is especially focused on the connectivity of heterogeneous data and the intelligent query system which enable users to obtain relevant useful information from the complex data sets. The database deals with four kinds of information; compound, histopathology, gene expression, and annotation information. Currently, TEST database maintains toxicogenomics information for 16 compounds, 45 microarrays, 190 animal experiments, and customized 4.8 K rat clone set. Our presented system is expected to be a good information source for studying of toxicology mechanism in the genome-wide level and can also be applied to the designing toxicity test chip.

Animals↗

PubMed2004

cDNA microarray gene expression analysis and toxicological phenotype for anticancer drug.

Toxicogenomics, the subdiscipline that merges genomics with toxicology, hold the promise to contributing toward the goal of elucidating mechanism by studying genomic profiling related with various drugs. The application of gene expression profiling technology to examine multiple genes and signaling pathways promises a significant advance in understanding the toxic mechanisms of various drugs and prediction of new drug candidate. Toxicogenomics is emerging field combining genomics and bioinformatics to identify and characterize mechanisms of toxicity of drug and various compounds. The principal hypothesis underlying on this field is that chemical-specific pattern of altered gene expression is related with each chemicals properties, especially toxicological property, and it will be revealed using high-density microarray analysis of sample from exposed organisms. So, in this study we compare the gene expression pattern of two anticancer drugs paclitaxel and orally absorbable paclitaxel, using the cDNA microarray. And from the result of this study, it is possible to provide the new possibility for genome-wide insight into mechanism of their anticancer activity and toxicological phenotype.

Administration, Oral↗

PubMed2003

Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis.

It is now recognized that precise patterns of differentially expressed genes ultimately direct a particular cell toward a given lineage. In this study, we compared the expression profiles of cancer-related genes by cDNA microarray analysis during the differentiation of human promyelocytic leukemia HL-60 cells into either monocytes or granulocytes. RNA was isolated at times 0, 6, 12, 24, 36, 48, and 72 h following stimulation of differentiation with all-trans retinoic acid (all-trans RA) or 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], and hybridized to the microarray gene chips containing 872 genes related to cell-cycles, oncogenes and leukemias. Several genes were commonly or differentially regulated during cell differentiation into either lineage, as demonstrated by both hierarchical and self-organizing map clustering analysis. At 72 h the expression levels of 45 genes were commonly up- or down-regulated at least a twofold in both lineages. Most importantly, 32 genes including alpha-L-fucosidase gene and adducin gamma subunit gene were up- or down-regulated only in all-trans RA-treated HL-60 cells, while 12 genes including interleukin 1beta and hypoxia-inducible factor 1alpha were up- or down-regulated only in 1,25-(OH)(2)D(3)-treated HL-60 cells. The expression of selected genes was confirmed by Northern blot analysis. As expected, some genes identified have not been examined during HL-60 cell differentiation into either lineage. The identification of genes associated with a specific differentiation lineage may give important insights into functional and phenotypic differences between two lineages of HL-60 cell differentiation.

Calcitriol↗

PubMed2003

Identification and differential expression of novel human cervical cancer oncogene HCCR-2 in human cancers and its involvement in p53 stabilization.

Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of this study was to identify unique oncogenes that are differentially expressed in human cancers and characterize their functions in tumorigenesis. To discover new putative oncogenes, the differential display RT-PCR method was applied using normal cervical tissues, cervical cancer cell lines, cervical cancer tissues, and metastatic tissues. We identified a new human cervical cancer oncogene HCCR-2 that was overexpressed in various human tumors including leukemia, lymphoma, and carcinomas of the breast, kidney, ovary, stomach, colon, and uterine cervix. Ectopic expression of HCCR-2 resulted in direct tumorigenic conversions of NIH/3T3 and Rat1 fibroblasts. Nude mice injected with NIH/3T3 cells stably transfected with HCCR-2 formed tumors in 4 weeks. The resultant tumors display characteristics of an epithelial carcinoma. In HCCR-2 transfected NCI-H460 cells and RKO cells, stabilization of the p53 tumor suppressor occurred without genetic mutation and correlated with functional impairment, as indicated by the defective induction of p53-induced p21(WAF1), MDM2, and bax. These results indicate that HCCR-2 probably represents a new oncogene that is related to tumorigenesis, functioning as a negative regulator of the p53 tumor suppressor.

3T3 Cells↗

PubMed2003

Proteomic and transcriptomic analysis of interleukin-1beta treated lung carcinoma cell line.

Mucin hypersecretion is one of the main symptoms of inflammatory disease in the respiratory tract. We previously reported that the pleiotypic pro-inflammatory cytokine, interleukin (IL)-1beta, plays a significant role in respiratory tract inflammation by inducing mucins. However, the molecular mechanism for mucin hypersecretion in the respiratory tract remains still unclear. In order to understand the mechanisms of mucin hypersecretion in the airway epithelium, the differentially expressed proteins and genes in the lung mucoepidermoid carcinoma cell line (NCI-H292 cells), which were treated for 6 and 24 hours with IL-1beta (10 ng/mL) were identified using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) proteomics and cDNA microarray analysis (8.6K). In the 2-D PAGE, eight differentially expressed proteins and 14 post-translational modification proteins were identified at 6 and 24 hours after the IL-1beta-treatment. Four hundred and thirteen genes (6.6%) and 115 genes (2.0%) were differentially expressed, respectively, at 6 and 24 hours after the IL-1beta-treatment by microarray analysis. The differentially expressed genes and proteins that were regulated by the IL-1beta-treatment were mostly in the metabolic pathway rather than in the regulatory pathway. These results clearly show that the transcript levels have little value in predicting the extent of protein expression.

Carcinoma↗

PubMed2003

Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice.

Activating signal cointegrator 2 (ASC-2), a cancer-amplified transcriptional coactivator of nuclear receptors and many other transcription factors, contains two LXXLL-type nuclear receptor interaction domains. Interestingly, the second LXXLL motif is highly specific to the liver X receptors (LXRs). In cotransfection, DN2, an ASC-2 fragment encompassing this motif, exerts a potent dominant-negative effect on transactivation by LXRs, which is rescued by ectopic coexpression of the full-length ASC-2 but not by other LXXLL-type coactivators, such as SRC-1 and TRAP220. In contrast, DN2/m, in which the LXXLL motif is mutated to LXXAA to abolish the interactions with LXRs, is without any effect. Accordingly, expression of DN2, but not DN2/m, in transgenic mice results in phenotypes that are highly homologous to those previously observed with LXRalpha(-/-) mice, including a rapid accumulation of large amounts of cholesterol and down-regulation of the known lipid-metabolizing target genes of LXRalpha in the liver upon being fed a high-cholesterol diet. These results identify ASC-2 as a physiologically important transcriptional coactivator of LXRs and demonstrate its pivotal role in the liver lipid metabolism.

Amino Acid Motifs↗