• BMB Reports
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• v.51 no.5
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• pp.255-260
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• 2018

Wntless/GPR177 functions as WNT ligand carrier protein and activator of $WNT/{\beta}$-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103-2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049-1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits $WNT/{\beta}$-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients.

• BMB Reports
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• v.51 no.2
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• pp.92-97
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• 2018

B cell leukemia/lymphoma 3 (Bcl3) plays a pivotal role in immune homeostasis, cellular proliferation, and cell survival, as a co-activator or co-repressor of transcription of the $NF-{\kappa}B$ family. Recently, it was reported that Bcl3 positively regulates pluripotency genes, including Oct4, in mouse embryonic stem cells (mESCs). However, the role of Bcl3 in the maintenance of pluripotency and self-renewal activity is not fully established. Here, we report the dynamic regulation of the proliferation, pluripotency, and self-renewal of mESCs by Bcl3 via an influence on Nanog transcriptional activity. Bcl3 expression is predominantly observed in immature mESCs, but significantly decreased during cell differentiation by LIF depletion and in mESC-derived EBs. Importantly, the knockdown of Bcl3 resulted in the loss of self-renewal ability and decreased cell proliferation. Similarly, the ectopic expression of Bcl3 also resulted in a significant reduction of proliferation, and the self-renewal of mESCs was demonstrated by alkaline phosphatase staining and clonogenic single cell-derived colony assay. We further examined that Bcl3-mediated regulation of Nanog transcriptional activity in mESCs, which indicated that Bcl3 acts as a transcriptional repressor of Nanog expression in mESCs. In conclusion, we demonstrated that a sufficient concentration of Bcl3 in mESCs plays a critical role in the maintenance of pluripotency and the self-renewal of mESCs via the regulation of Nanog transcriptional activity.

• Journal of the Korean Society of Radiology
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• v.9 no.5
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• pp.307-314
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• 2015

This study was conducted in reducing the involuntary motion artifacts because of lungs and heart movements as well as the aliasing artifacts generated during the use of the reduced-FOV EPI technique while performing breast MRI. Performed on a total of 38 obesity female subjects who visited the clinic for pre-examination before surgery within the period from August 1 to November 30, 2014. The 3.0T MRI scanner equipped with a breast scanning coil. Qualitative and quantitative analyses were each used for the evaluation of the acquired images while an Paired T-test and Wilcoxon rank test were performed to check the statistical significance. The variation ratio rose by 15.69% with the additional application of a pre-saturation pulse in the lesion, by 13.72% near the lesion, and 20.63% in the fat and the contrast-to-noise ratio rose by 10.58% in and near the lesion and by 12.03% in the lesion and fat, respectively. there were increases of 22.05% and 21.42% at 0 and 1000 respectively in qulitative evaluation and growth of 16.10% in apparent diffusion coefficient. it showed a statistically significant result(p<0.05) in signal to noise ratio, contrast to noise ratio, diffusion slope coefficient and apparent diffusion coefficient. The involuntary movements artifacts that occur in the phase encoding direction and the aliasing artifacts are considered to be reduced to obtain the best image in the additional use of the pre-saturation pulse as DWI is acquired.

• Journal of the Korean Society of Radiology
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• v.8 no.7
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• pp.383-387
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• 2014

In this paper, for a new detection system development with the better accurate dose evaluation and beam distribution imaging using the small field irradiation of linear accelerator, the compound semiconductor based detection sensors were fabricated and the performance evaluation was investigated. The special particle-in-binder sedimentation was used for a large area film sensor fabrication. The detection properties for high energy x-rays were investigated from a dark current, an output current, a rising time, a falling time, and response delay measurement. The experimental results, the $TiO_2$ mixed $HgI_2$ sensor showed the best electrical characteristics than $PbI_2$, PbO, pure $HgI_2$. Linearity, repeatability, and accuracy tests from LINAC were tested, the $TiO_2$ mixed $HgI_2$ sensor showed the better performance than the commercially available dosimetry devices.

• Journal of the Korean Society of Radiology
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• v.8 no.7
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• pp.461-466
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• 2014

The advantages and disadvantages of the various models of crushed ESWL (Extracorporeal Shock Wave Lithotripsy) and their various side effects due to pre-treatment have been reported. We look for the appropriate intensity of the shock wave in the electromagnetic ESWL treatment of patients with lower Inferior Ureter Stones and measure the total running time of C-arm saw. This study is based on the January-June 2014 launch of 65 patients of C university hospital located in Gyeongbuk, who conducted ESWL without pre-treatment. Patients are composed of 48 male and 17 female which were more common in men, while the most common age is 50s. The occurrence of lower urinary tract stones were left and they were more absent than 5mm in size in 39 of the most common. Optimal intensity is one of the suitable intensity of pain, and it is possible to switch the strength of impact to C if one appeals pain. In addition, the C-arm of the total operating time showed $241.73{\pm}30.37$ seconds, which is the size of the lower urinary tract that showed a significant difference (p <0.05). Therefore, ESWL treatment without pre-enforce treatment, the standard for the impact frequency and impact strength depending on the site of ureteral stones is required. The standard for total operating time of C-arm generated for ureteral stones is needed in order to reduce radiation exposure, and the standard for the total operating time for the criteria is needed depending on the site in order to minimize the exposure.

• Parasites, Hosts and Diseases
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• v.49 no.4
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• pp.385-398
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• 2011

A large-scale survey was conducted to investigate the infection status of fresh water fishes with Clonorchis sinensis metacercariae (CsMc) in 3 wide regions, which were tentatively divided by latitudinal levels of the Korean peninsula. A total of 4,071 freshwater fishes were collected from 3 regions, i.e., northern (Gangwon-do: 1,543 fish), middle (Chungcheongbuk-do and Gyeongsangbuk-do: 1,167 fish), and southern areas (Jeollanam-do, Ulsan-si, and Gyeongsangnamdo: 1,361 fish). Each fish was examined by the artificial digestion method from 2003 to 2010. In northern areas, only 11 (0.7%) fish of 2 species, Pungtungia herzi and Squalidus japonicus coreanus from Hantan-gang, Cheolwon-gun, Gangwon-do were infected with av. 2.6 CsMc. In middle areas, 149 (12.8%) fish were infected with av. 164 CsMc. In southern areas, 538 (39.5%) fish were infected with av. 159 CsMc. In the analysis of endemicity in 3 regions with an index fish, P. herzi, 9 (6.2%) of 146 P. herzi from northern areas were infected with av. 2.8 CsMc. In middle areas, 34 (31.8%) of 107 P. herzi were infected with av. 215 CsMc, and in southern areas, 158 (92.9%) of 170 P. herzi were infected with av. 409 CsMc. From these results, it has been confirmed that the infection status of fish with CsMc is obviously different among the 3 latitudinal regions of the Korean peninsula with higher prevalence and burden in southern regions.

• Parasites, Hosts and Diseases
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• v.55 no.3
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• pp.295-304
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• 2017

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, IFN-${\gamma}$, LT-${\alpha}$, and TNF-${\alpha}$ were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-$1{\beta}$-511C/T, IL-6-174G/C, IFN-${\gamma}$+874T/A, LT-${\alpha}$+252A/G, and TNF-${\alpha}$-308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-${\alpha}$+252A/G and TNF-${\alpha}$-308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-${\gamma}$+874T/A were significantly higher than the variants in CCA cases. IFN-${\gamma}$+874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6-174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

• 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 Life Science
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• v.20 no.9
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• pp.1299-1305
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• 2010

Cardiac troponin-I (cTnI), creatine kinase-MB (CK-MB), and C-reactive protein (CRP) are routine cardiac markers for the diagnosis of cardiovascular disease. Recently, brain natriuretic peptide (BNP) has garnered attention as a marker of heart failure. This study was retrospectively designed to investigate the relationships between preoperative BNP, other cardiac markers levels and perioperative parameters in seventy-four adult patients that underwent off-pump coronary artery bypass grafting (OPCAB) and to assess its usefulness for predicting postoperative outcomes. Preoperative levels of BNP, cTnI, CK-MB, and CRP had significantly positive or negative correlations with echocadiographic parameters. There were significantly positive relationships between BNP, cTnI, CK-MB, and CRP concentration. Postoperative mechanical ventilation time had a positive correlation to preoperative levels of cTnI, CK-MB, and CRP, while ICU-staying period had a positive correlation with BNP, cTnI and CK-MB. These results reveal that a preoperative level of BNP is a good predictor and that its combination with cTnI, CK-MB, and CRP might be useful for diagnosis and comprehensive risk stratification of patients with coronary heart diseases, as well as prognosis of perioperative outcomes in OPCAB patients.

• Journal of Life Science
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• v.19 no.9
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• pp.1209-1217
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• 2009

Many cancer cells are sensitive to the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. However, some cancer cells show either partial or complete resistance to TRAIL. Human colon carcinoma KM12 cells have been shown to be insensitive to TRAIL-induced apoptosis. To overcome TRAIL resistance in KM12 cells, we targeted key anti-apoptotic molecules involved in the modulation of TRAIL resistance in the cells, and evaluated the effects of quercetin as a TRAIL sensitizer in the cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in KM12 cells by the down-regulation of c-FLIP and DNA-PKcs/Akt and up-regulation of death receptors (DR4/DR5), which led to the enhancement of TRAIL-mediated activation of caspases and subsequent cleavage of PARP, as well as up-regulation of Bax. These findings suggest that the DNA-PKcs/Akt signaling pathway, as well as c-FLIP, play essential roles in regulating cells in the escape from TRAIL-induced apoptosis. Based on these results, this study provides a potential application of quercetin in combination with TRAIL in the treatment of human colon cancer.