• Journal of Nutrition and Health
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• v.35 no.10
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• pp.1053-1059
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• 2002

In post-genome period, the technique for identifying gene expression has been changed to high throughput screening. In the field of molecular nutrition, the need for this technique to clarify molecular function of the specific nutrient is essential. In this study, we have tested the zinc-regulated gene expression in zinc-deficient U937 cells, using cDNA microarray which is the cutting-edge technique to screen large numbers of gene expression simultaneously. The study result can be used for the preliminary gene screening data for clarifying, using monocyte U937 cell line, molecular Zn aspect in atherosclerosis. U937 cells were cultured in Zn-adequate (control, 12 $\mu$M Zn) or Zn-deficient (experimental, 0 $\mu$M Zn) ESMI media during 2 days, respectively. Cells were harvested and RNA was extracted. Total RNA was reverse-transcriptinized and synthesized cDNA probe labeled with Cy-3. fluorescent labeled cDNA probe was applied to microarray slide for hybridization slide, and after then, the slide was scanned using fluorescence scanner. ‘Highly expressed genes’ in Zn-deficient U937 cells, comparing to Zn-adequate group, are mainly about the genes for motility protein, immune system protein, oncogene and tumor suppressor and ‘Less highly expressed genes’ are about the genes for transcription, apoptosis associated protein, cell cycle, and several basic transcription factors. The results of this preliminary study imply the effectiveness of cDNA microarray for expression profiling of a singly nutrient deficiency, specially Zn. Furthur study, using tailored-cDNA array and capillary endothelial cell lines, would be beneficial to clarify molecular Zn function, more in detail.

• Genomics & Informatics
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• v.19 no.1
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• pp.10.1-10.7
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• 2021

Although many models have been proposed to accurately predict the response of drugs in cell lines recent years, understanding the genome related to drug response is also the key for completing oncology precision medicine. In this paper, based on the cancer cell line gene expression and the drug response data, we established a reliable and accurate drug response prediction model and found predictor genes for some drugs of interest. To this end, we first performed pre-selection of genes based on the Pearson correlation coefficient and then used ElasticNet regression model for drug response prediction and fine gene selection. To find more reliable set of predictor genes, we performed regression twice for each drug, one with IC₅₀ and the other with area under the curve (AUC) (or activity area). For the 12 drugs we tested, the predictive performance in terms of Pearson correlation coefficient exceeded 0.6 and the highest one was 17-AAG for which Pearson correlation coefficient was 0.811 for IC₅₀ and 0.81 for AUC. We identify common predictor genes for IC₅₀ and AUC, with which the performance was similar to those with genes separately found for IC₅₀ and AUC, but with much smaller number of predictor genes. By using only common predictor genes, the highest performance was AZD6244 (0.8016 for IC₅₀, 0.7945 for AUC) with 321 predictor genes.

• Molecular & Cellular Toxicology
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• v.1 no.3
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• pp.203-208
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• 2005

Thioacetamide (TA) is potent haptotoxincant that requires metabolic activation by mixed-function oxidases. Micrcarray technology, which is massive parallel gene expression profiling in a single hybridization experiment, has provided as a powerful molecular genetic tool for biological system related toxicant. In this study we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver epithelial cell line WB-F344 (WB). The WB cells was used to assess the toxic effects of TA. WB cells were exposed to two concentrations of TA-doses which caused 20% and 50% cell death were chosen and the cells exposed for periods of 2 and 24 h. Our data revealed that following the 2-h exposure at the both of doses and 24-h exposure at the low doses, few changes in gene expression were detected. However, after 24-h exposure of the cells to the high concentration, multiple changes in gene expression were observed. TA treatment gave rise predominantly to up-regulation of genes involved in cell cycle and cell death, but down-regulation of genes involves in cell adhesion and calcium ion binding. Exposure of WB cells to higher doses of the TA gave rise to more changes in gene expression at lower exposure times. These results show that TA regulates expression of numerous genes via direct molecular signaling mechanisms in liver cells.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.32-43
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• 2009

Acetaminophen (APAP) overdose is known to cause severe hepatotoxicity mainly through the depletion of glutathione. In this study, we compared the cytotoxic effects of APAP on both a normal murine hepatic cell line, BNL CL.2, and its SV40-transformed cell line, BNL SV A.8. Gene expression profiles for APAP-treated cells were also obtained using microarray and analyzed to identify differences in genes or profiles that may explain the differences of susceptibility to APAP in these cell lines. These two cell lines exhibited different susceptibilities to APAP (0-$5,000{\mu}M$); BNL SV A.8 cells were more susceptible to APAP treatment compared to BNL CL.2 cells. A dose of $625{\mu}M$ APAP, which produced significant differences in cytotoxicity in these cell lines, was tested. Microarray analysis was performed to identify significant differentially expressed genes (DEGs) irrespective of APAP treatment. Genes up-regulated in BNL SV A.8 cells were associated with immune response, defense response, and apoptosis, while down-regulated genes were associated with catalytic activity, cell adhesion and the cytochrome P450 family. Consistent with the cytotoxicity data, no significant DEGs were found in BNL CL.2 cells after treatment with $625{\mu}M$ APAP, while cell cycle arrest and apoptosis-related genes were up-regulated in BNL SV A.8 cells. Based on the significant fold-changes in their expression, a genes were selected and their expressions were confirmed by quantitative real-time RT-PCR; there was a high correlation between them. These results suggest that gene expression profiles may provide a useful method for evaluating drug sensitivity of cell lines and eliciting the underlying molecular mechanism. We further compared the genes identified from our current in vitro studies to the genes previously identified in our lab as regulated by APAP in both C57BL/6 and ICR mice in vivo. We found that a few genes are regulated in a similar pattern both in vivo and in vitro. These genes might be useful to develop as in vitro biomarkers for predicting in vivo hepatotoxicity. Based on our results, we suggest that gene expression profiles may provide useful information for elucidating the underlying molecular mechanisms of drug susceptibility and for evaluating drug sensitivity in vitro for extrapolation to in vivo.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.273-286
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• 2021

Background: Prostate carcinoma is the second most common cancer among men worldwide. Developing new therapeutic approaches and diagnostic biomarkers for prostate cancer (PC) is a significant need. The Chinese herbal medicine Panax quinquefolius saponins (PQS) have been reported to show anti-tumor effects. We hypothesized that PQS exhibits anti-cancer activity in human PC cells and we aimed to search for novel biomarkers allowing early diagnosis of PC. Methods: We used the human PC cell line DU145 and the prostate epithelial cell line PNT2 to perform cell viability assays, flow cytometric analysis of the cell cycle, and FACS-based apoptosis assays. Microarray-based gene expression analysis was used to display specific gene expression patterns and to search for novel biomarkers. Western blot and quantitative real-time PCR were performed to demonstrate the expression levels of multiple cancer-related genes. Results: Our data showed that PQS inhibited the viability of DU145 cells and induced cell cycle arrest at the G1 phase. A significant decrease in DU145 cell invasion and migration were observed after 24 h treatment by PQS. PQS up-regulated the expression levels of p21, p53, TMEM79, ACOXL, ETV5, and SPINT1 while it down-regulated the expression levels of bcl2, STAT3, FANCD2, DRD2, and TMPRSS2. Conclusion: PQS promoted cells apoptosis and inhibited the proliferation of DU145 cells, which suggests that PQS may be effective for treating PC. TMEM79 and ACOXL were expressed significantly higher in PNT2 than in DU145 cells and could be novel biomarker candidates for PC diagnosis.

• Nuclear Engineering and Technology
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• v.54 no.8
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• pp.3027-3033
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• 2022

Background: In this study, various types of deep-learning models for predicting in vitro radiosensitivity from gene-expression profiling were compared. Methods: The clonogenic surviving fractions at 2 Gy from previous publications and microarray gene-expression data from the National Cancer Institute-60 cell lines were used to measure the radiosensitivity. Seven different prediction models including three distinct multi-layered perceptrons (MLP), four different convolutional neural networks (CNN) were compared. Folded cross-validation was applied to train and evaluate model performance. The criteria for correct prediction were absolute error < 0.02 or relative error < 10%. The models were compared in terms of prediction accuracy, training time per epoch, training fluctuations, and required calculation resources. Results: The strength of MLP-based models was their fast initial convergence and short training time per epoch. They represented significantly different prediction accuracy depending on the model configuration. The CNN-based models showed relatively high prediction accuracy, low training fluctuations, and a relatively small increase in the memory requirement as the model deepens. Conclusion: Our findings suggest that a CNN-based model with moderate depth would be appropriate when the prediction accuracy is important, and a shallow MLP-based model can be recommended when either the training resources or time are limited.

• Mycobiology
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• v.38 no.2
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• pp.144-148
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• 2010

$\beta$-Glucans have been known to exhibit antitumor activities by potentiating host immunity by an unknown mechanism. The C-type lectin dectin-1, a $\beta$-glucan receptor, is found on the macrophage and can recognize various $\beta$-glucans. Previously, we demonstrated the presence of $\beta$-glucan receptor, dectin-1, on the Raw 264.7 cells as well as on murine mucosal organs, such as the thymus, the lung, and the spleen. In order to investigate immunopotentiation of innate immunity by $\beta$-glucan, we stimulated a murine macrophage Raw 264.7 cell line with $\beta$-glucans from Pleurotus ostreatus, Saccharomyces cerevisiae, and Laminaria digitata. Then, we analyzed cytokines such as tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-6 by reverse transcription-polymerase chain reaction (RT-PCR). In addition we analyzed gene expression patterns in $\beta$-glucan-treated Raw 264.7 cells by applying total mRNA to cDNA microarray to investigate the expression of 7,000 known genes. When stimulated with $\beta$-glucans, the macrophage cells increased TNF-$\alpha$ expression. When co-stimulation of the cells with $\beta$-glucan and lipopolysaccharide (LPS), a synergy effect was observed by increased TNF-$\alpha$ expression. In IL-6 expression, any of the $\beta$-glucans tested could not induce IL-6 expression by itself. However, when co-stimulation occurred with $\beta$-glucan and LPS, the cells showed strong synergistic effects by increased IL-6 expression. Chip analysis showed that $\beta$-glucan of P. ostreatus increased gene expressions of immunomodulating gene families such as kinases, lectin associated genes and TNF-related genes in the macrophage cell line. Induction of TNF receptor expression by FACS analysis was synergized only when co-stimulated with $\beta$-glucan and LPS, not with $\beta$-glucan alone. From these data, $\beta$-glucan increased expressions of immunomodulating genes and showed synergistic effect with LPS.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3259-3264
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• 2012

Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and $40{\mu}M$ for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1028-1035
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• 2004

Imperatorin, a biologically active furanocoumarin from the roots of Angelica dahurica (Umbelliferae), was mutagenic and induced transformation of mouse fibroblast cell lines, whereas it provided inhibiting effects on mutagenesis and carcinogenesis induced by various carcinogens. Furthermore, it has been suggested that imperatorin may have potential anticarcinogenic effects when administered orally in the diet. In addition to its anticarcinogenic properties, imperatorin has been shown to possess anticancer activities. We investigated the macro scale gene expression analysis on the HL-60 cells treated with imperatorin. Imperatorin (10μM) were used to treat the cells for 6h, 12h, 24h, 48h, and 72h. In a human cDNAchip study of 10,000 genes evaluated 6, 12, 24, 48, 72 hours after treated with imperatorin in HL-60 cells. Hierarchical cluster against the genes which showed expression changes by more than 2 fold. Three hundred eighty six genes were grouped into 6 clusters by a hierarchical clustering algorithm. Pathway analysis using gene microarray pathway prof Her that is a computer application designed to visualize gene expression data on screen representing biological pathways and groupings of genes.

• Journal of Microbiology and Biotechnology
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• v.4 no.4
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• pp.274-277
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• 1994

We subcloned two chicken H3 histone genes and transfected them into Rat 3 cell line. One contains 300 bp 5' to its cap site and the other contains 130 bp 5' to its cap site when cloned into plasm ids. Both of them showed 5' phase specific expression of their mRNA about 8 fold higher (during 5' phase) than during Gl phase. This means that only 130 bp 5' to its cap site was enough to confer cell cycle regulated expression of the latter gene. The DNA sequences of their 5' flanking region did not reveal any particular homologies or subtype-specific sequences. The DNA sequence data also showed that even though the protein coding regions of the histone genes have been conserved exceptionally well throughout evolution, their 5' untranslated regions have not been conserved as well.