• Genomics & Informatics
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• v.20 no.1
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• pp.13.1-13.4
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• 2022

A major issue in the use of immune checkpoint inhibitors is their lack of efficacy in many patients. Previous studies have reported that the T cell inflamed signature can help predict the response to immunotherapy. Thus, many studies have investigated mechanisms of immunotherapy resistance by defining the tumor microenvironment based on T cell inflamed and non-T cell inflamed subsets. Although methods of calculating T cell inflamed subsets have been developed, valid screening tools for distinguishing T cell inflamed from non-T cell inflamed subsets using gene expression data are still needed, since general researchers who are unfamiliar with the details of the equations can experience difficulties using extant scoring formulas to conduct analyses. Thus, we introduce TcellInflamedDetector, an R package for distinguishing T cell inflamed from non-T cell inflamed samples using cancer gene expression data via bulk RNA sequencing.

• Proceedings of the Botanical Society of Korea Conference
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• 2001.04a
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• pp.7-7
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• 2001

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9335-9339
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• 2014

Background: To determine the frequency of primary circulating prostate cells (CPC) detection according to age and serum PSA levels in a cohort of men undergoing screening for prostate cancer and to determine the diagnostic yield in those men complying with the criteria for prostate biopsy. Materials and Methods: A prospective study was carried out to analyze all men evaluated in a hospital prostate cancer screening program. Primary CPCs were obtained by differential gel centrifugation and detected using standard immunocytochemistry using anti-PSA, positive samples undergoing a second process with anti-P504S. A malignant primary CPC was defined as PSA+ P504S+, and a test positive if 1 cell/4ml was detected. The frequency of primary CPC detection was compared with age and serum PSA levels. Men with a PSA >4.0ng/ml and/or abnormal rectal examination underwent 12 core prostate biopsy, and the results were registered as cancer/no-cancer and compared with the presence/absence of primary CPCs to calculate the diagnostic yield. Results: A total of 1,117 men participated; there was an association of primary CPC detection with increasing age and increasing serum PSA. Some 559 men underwent initial prostate biopsy of whom 207/559 (37.0%) were positive for primary CPCs and 183/559 (32.0%) had prostate cancer detected. The diagnostic yield of primary CPCs had a sensitivity of 88.5%, a specificity of 88.0%, and positive and negative predictive values of 78.3% and 94.9%, respectively. Conclusions: The use of primary CPCs for testing is recommended, since its high negative predictive value could be used to avoid prostate biopsy in men with an elevated PSA and/or abnormal DRE. Men positive for primary CPCs should undergo prostate biopsy. It is a test that could be implemented in the routine immunocytochemical laboratory.

• Korean Journal of Veterinary Pathology
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• v.1 no.2
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• pp.97-106
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• 1997

This study was carried out to investigate the testicular toxicity of environmental toxicant, 2-bromopropane(2-BP) recently caused occupational intoxication in Korea by light microscopy and electron microscopy. To evaluate the effect on spermatogenesis and find target germ cell 10 weeks old male Sprague-Dawley rats were treated with 5g/10m ℓ/kg/day of 2-bromopropane for 3 consecutive days orally and observed on day 1 or day 7 after treatment. 2-BP induced depletion of spermatogonia and early spermatocytes on stages I-IX or extensive degeneration of germ cells on the other stages on day 1. But extensive degeneration of germ cells without stage specificity was observed and round spermatid formed multinucleated giant cells in the lumen of seminiferous tubules on day 7. Electron microscopically Sertoli cells showed irregular shape of nucleus and cytoplasmic vauolation. And spermatocyte showed a extensive heterochromatin and cytoplasmic vacuolation. But there was no histopathological changes in the interstial cells. On the base of the results the target germ cell was spermatogonia in the early of the study but Srtoli cells also effected by high-dosed 2-BP in the late of the study.

• Journal of Microbiology and Biotechnology
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• v.32 no.10
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• pp.1262-1274
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• 2022

Cholangiocarcinoma (CCA) is a complex and refractor type of cancer with global prevalence. Several barriers remain in CCA diagnosis, treatment, and prognosis. Therefore, exploring more biomarkers and therapeutic drugs for CCA management is necessary. CCA gene expression data was downloaded from the TCGA and GEO databases. KEGG enrichment, GO analysis, and protein-protein interaction network were used for hub gene identification. miRNA were predicted using Targetscan and validated according to several GEO databases. The relative RNA and miRNA expression levels and prognostic information were obtained from the GEPIA. The candidate drug was screened using pharmacophore-based virtual screening and validated by molecular modeling and through several in vitro studies. 301 differentially expressed genes (DEGs) were screened out. Complement and coagulation cascades-related genes (including AHSG, F2, TTR, and KNG1), and cell cycle-related genes (including CDK1, CCNB1, and KIAA0101) were considered as the hub genes in CCA progression. AHSG, F2, TTR, and KNG1 were found to be significantly decreased and the eight predicted miRNA targeting AHSG, F2, and TTR were increased in CCA patients. CDK1, CCNB1, and KIAA0101 were found to be significantly abundant in CCA patients. In addition, Molport-003-703-800, which is a compound that is derived from pharmacophores-based virtual screening, could directly bind to CDK1 and exhibited anti-tumor activity in cholangiocarcinoma cells. AHSG, F2, TTR, and KNG1 could be novel biomarkers for CCA. Molport-003-703-800 targets CDK1 and work as potential cell cycle inhibitors, thereby having potential for consideration for new chemotherapeutics for CCA.

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.85-91
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• 2015

Purpose: Noninvasive prenatal test (NIPT) by massively parallel sequencing (MPS) of cell-free fetal DNA in maternal plasma marks a significant advancement in prenatal screening, minimizing the need for invasive testing of fetal chromosomal aneuploidies. Here, we report the initial clinical performance of NIPT in Korean pregnant women. Materials and Methods: MPS-based NIPT was performed on 910 cases; 5 mL blood samples were collected and sequenced in the Shenzhen BGI Genomic Laboratory to identify aneuploidies. The risk of fetal aneuploidy was determined by L-score and t-score, and classified as high or low. The NIPT results were validated by karyotyping for the high-risk cases and neonatal follow-up for low-risk cases. Results: NIPT was mainly requested for two clinical indications: abnormal biochemical serum-screening result (54.3%) and advanced maternal age (31.4%). Among 494 cases with abnormal biochemical serum-screening results, NIPT detected only 9 (1.8%) high-risk cases. Sixteen cases (1.8%) of 910 had a high risk for aneuploidy: 8 for trisomy 21, 2 for trisomy 18, 1 for trisomy 13, and 5 for sex chromosome abnormalities. Amniocentesis was performed for 7 of these cases (43.8%). In the karyotyping and neonatal data, no false positive or negative results were observed in our study. Conclusion: MPS-based NIPT detects fetal chromosomal aneuploidies with high accuracy. Introduction of NIPT as into clinical settings could prevent about 98% of unnecessary invasive diagnostic procedures.

• The Journal of Korean Medicine
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• v.32 no.3
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• pp.35-43
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• 2011

Objectives: This study was performed to screen target-specific inhibitors of ${\beta}$-catenin/TCF signaling whose functional activation plays an important role in early events in carcinogenesis. Methods: To investigate the activation or suppression of ${\beta}$-catenin/TCF transcription, we established a transiently transfected cell line with a constitutively active ${\beta}$-catenin mutant gene whose product is not degraded. This cell line was also co-transfected with luciferase reporter gene constructs containing either an optimized (TOPflash) or mutant (FOPflash) TCF-binding element. We investigated cytotoxic effects using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay. To find effective inhibitors of ${\beta}$-catenin/TCF signaling from medicinal herbs, the crude extracts of 99 types of medicinal herbs were screened using a luciferase assay system in HEK-293 and SH-SY5y cells. Results: At a concentration of $50{\mu}g$/ml, extracts of Angelica koreanae radix, Cannabis sativa semen, Ephedrae intermedia Schrenk radix, and Vitis rotundifolia fruit showed the following inhibitory effects on ${\beta}$-catenin/TCF signaling: $40{\pm}5.6%$, $23{\pm}6.1%$, $8{\pm}5.1%$, and $22{\pm}9.8%$ in ${\beta}$-catenin-activated HEK-293 cells and $9{\pm}4.7%$, $39{\pm}8.1%$, $39{\pm}6.4%$, and $42{\pm}10.1%$ in ${\beta}$-catenin-activated SH-SY5y cells, respectively. Crude extracts of E. radix were isolated by silica gel column chromatography, and two non-polar fractions of these extracts showed inhibitory effects on ${\beta}$-catenin/TCF signaling. Conclusions: In this study, we established a transiently transfected cell line as a screening system and found that various medicinal herb extracts had inhibitory effects on ${\beta}$signaling.

• BMB Reports
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• v.43 no.12
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• pp.818-823
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• 2010

Plk 1 is overexpressed in many human malignancies including laryngeal carcinoma. However, its therapeutic potential has been never examined in laryngeal carcinoma. In the present study, a simple cellular morphology-based strategy was firstly proposed for rapidly screening the effective siRNAs against Plk1. Furthermore, we investigated the effects of Plk1 depletion via a novel identified effective siRNA against Plk1, Plk1 siRNA-607, on human laryngeal carcinoma Hep-2 cells. The results indicated that Plk1 siRNA-607 transfection resulted in a significant inhibition in Plk1 expression in cells, and subsequently caused a dramatic mitotic cell cycle arrest followed by massive apoptotic cell death, and eventually resulted in a significant decrease in growth and viability of the laryngeal carcinoma cells. Taken together, our present study not only suggests a simple strategy for rapidly screening effective siRNAs against Plk1 but also implicates that Plk1 may serve as a potential therapeutic target in human laryngeal carcinoma.

• The Journal of the Korea Contents Association
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• v.10 no.4
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• pp.19-27
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• 2010

In recent years, high-throughput genome-wide RNA interference screening is emerging as an essential tool to biologists in understanding complex cellular processes. The manual analysis of the large number of images produced in each study spends much time and the labor. Hence, automatic cellular image analysis becomes an urgent need, where segmentation is the first and one of the most important steps. However, those factors such as the region overlapping, a variety of shapes, and non-uniform local characteristics of cellular images become obstacles to efficient cell segmentation. To avoid the problem, a new watershed-based cell segmentation algorithm using a localized segmentation method and a feature vector is proposed in this paper. Localized approach in segmentation resolves the problems caused by a variety of shapes and non-uniform characteristics. In addition, the poor performance of segmentation in overlapped regions can be improved by taking advantage of a feature vector whose component features complement each other. Simulation results show that the proposed method improves the segmentation performance compared to the method in Cellprofiler.

• YAKHAK HOEJI
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• v.50 no.1
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• pp.52-57
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• 2006

The activation of cyclin dependent kinase 4 (CDK4) is found in more than half of all human cancers. Therefore CDK4 is an attractive target for the development of a novel anticancer agent. For mass screening of CDK4 inhibitor, we set up in vitro kinase assay for CDK4 activity using a cyclin D1-CDK4 fusion protein, which is constitutively active and exhibits enhanced stability. From the screening of representative compound library of Korea Chemical Bank, we found that 7-chloro-4-nitro-benzo[1,2,5]oxadiazole 1-oxide (FBP-1248) selectively inhibited CDK4 activity in vitro by ATP competitive manner. This compound prevented the phosphorylation of retinoblatsoma tumor suppressor protein, Rb, and inhibited cell growth through cell cycle arrest. In summary, we developed an efficient assay system for CDK4 activity in vitro and identified the CDK4 inhibitory compound, FBP-1248.