• Journal of Korean Neurosurgical Society
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• v.60 no.1
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• pp.21-29
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• 2017

Objective : The purpose of this study was to analyze outcomes and identify prognostic factors in patients with cerebral metastases from non-small cell lung cancer (NSCLC) treated with gamma knife radiosurgery (GKS) particularly, focusing on associations of biomarkers and systemic treatments. Methods : We retrospectively reviewed the medical records of 134 patients who underwent GKS for brain metastases due to NSCLC between January 2002 and December 2012. Representative biomarkers including epidermal growth factor receptor (EGFR) mutation, K-ras mutation, and anaplastic lymphoma kinase (ALK) mutation status were investigated. Results : The median overall survival after GKS was 22.0 months (95% confidence interval [CI], 8.8-35.1 months). During follow-up, 63 patients underwent salvage treatment after GKS. The median salvage treatment-free survival was 7.9 months (95% CI, 5.2-10.6 months). Multivariate analysis revealed that lower recursive partition analysis (RPA) class, small number of brain lesions, EGFR mutation (+), and ALK mutation (+) were independent positive prognostic factors associated with longer overall survival. Patients who received target agents 30 days after GKS experienced significant improvements in overall survival and salvage treatment-free survival than patients who never received target agents and patients who received target agents before GKS or within 30 days (median overall survival: 5.0 months vs. 18.2 months, and 48.0 months with p-value=0.026; median salvage treatment-free survival: 4.3 months vs. 6.1 months and 16.6 months with p-value=0.006, respectively). To assess the influence of target agents on the pattern of progression, cases that showed local recurrence and new lesion formation were analyzed according to target agents, but no significant effects were identified. Conclusion : The prognosis of patients with brain metastases of NSCLC after GKS significantly differed according to specific biomarkers (EGFR and ALK mutations). Our results show that target agents combined with GKS was related to significantly longer overall survival, and salvage treatment-free survival. However, target agents were not specifically associated with improved local control of the lesion treated by GKS either development of new lesions. Therefore, it seems that currently popular target agents do not affect brain lesions themselves, and can prolong survival by controlling systemic disease status.

• Korean Journal of Microbiology
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• v.47 no.2
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• pp.110-116
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• 2011

In the previous study with the Saccharomyces cerevisiae S288c strains, no known function of the dual specificity kinase, ScKns1, was reported because its gene deletion did not show any noticeable phenotypic changes. Recent study with fission yeast, however, revealed the involvement of the LAMMER kinase in flocculation, filamentous growth, oxidative stress, and so on. Therefore we made Sckns1-deletion mutants with the ${\Sigma}1278b$-background, with which one can induce filamentous and adhesive growth in contrast to those of the S288c-background. The $Sckns1{\Delta}$ strains of both haploid and diploid showed defect in filamentous growth under conditions for inducing the filamentous growth such as nitrogen starvation and butanol treatment. Both kinds of the deletion mutants also showed decrease in adhesive growth on agar surface. Interestingly enough the defects of the $Sckns1{\Delta}$ strains were suppressed by the over-expression of each gene for the components of the MAPK signaling pathway such as STE11, STE12, and TEC1, respectively, but not by the upstream components, RAS2 and STE20, respectively. Although further investigations are required, these results indicate that the ScKns1 may act in place between the Ste20 and the Ste11 of the S. cerevisiae MAPK cascade.

• Herbal Formula Science
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• v.15 no.2
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• pp.127-137
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• 2007

The purpose of this study was to investigate the effect of Yong-dam-sa-gan-tang (YST) on apoptosis in HepG2 cells, First of all. to study the cytotoxic effect of methanol extract of YST on HepG2 cells, the cells were treated with various concentrations of YST and then cell viability was determined by XTT reduction method and trypan blue exclusion assay. YST reduced proliferation of HepG2 cells in a dose-dependent manner. To confirm the induction of apoptosis, HepG2 cells were treated with various concentrations of YST. The cleavage of poly AD P-ribose polymerase (P ARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of caspase-3, procaspase-8 and procaspase-8 were examined by western blot analysis. YST decreased procaspase-3, procaspase-8 and procaspase-9 levels in a dose-dependent manner and induced the clevage of PARP. YST triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome c from mitochondria to cytosol. Furthermore, YST also downregulated the anti-apoptotic Bcl-2 and upregulated the pro-apoptotic-Bax. Therefore, this result suggest that YST induced HepG2 cell death through the mitochondrial pathway. Sustained activation of the Ras/Raf/MEK/ERK cascade in cells results in a cell cycle arrest and has been implicated in the differentiation of certain cell types, in many cases acting to promote differentiation. YST decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. These results suggest that YST is potentially useful as a chemo-therapeutic agent in HepG2.

• Journal of Preventive Medicine and Public Health
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• v.35 no.3
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• pp.245-254
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• 2002

Objective : To test if the intake of $H_2$ receptor antagonists ($H_2$-RAs) increases the risk of gastric cancer in the elderly. Methods : The source population for this study was drawn from the responders to a questionnaire survey administered to the Korea Elderly Pharmacoepidemiological Cohort (KEPEC), who were beneficiaries of the Korean Medical Insurance Corporation, were at least 65 years old, and residing in Busan in 1999. The information on $H_2$-RAs exposure was obtained from a drug prescription database compiled between inn. 1993 and Dec. 1994. The cases consisted of 76 gastric cancer patients, as confirmed from the KMIC claims data, the National Cancer Registry and the Busan Cancer Registry. The follow-up period was from Jan. 1993 to Dec. 1998. Cancer free controls were randomly selected by 1:4 individual matching, which took in to consideration the year of birth and gender. Information on confounders was collected by a mail questionnaire survey. The odds ratios, and their 95% confidence intervals, were calculated using a conditional logistic regression model. Results : After adjusting for a history of gastric ulcer symptoms, medication history, and body mass index, the adjusted OR (aOR) was 4.6 (95% CI=1.72-12.49). The odds ratio of long term use (more than 7 days) was 2.3 (95% CI=1.07-4.82). The odds ratio of short term use was 4.6 (95% CI=1.26-16.50). The odds ratio of parenteral use was 4.4 195% CI=1.16-17.05) and combination use between the oral and parenteral routes (aOR, 16.8; 95% CI=1.21-233.24) had the high risk of gastric cancer. The aOR of cimetidine was 1.7 (95% CI=1.04-2.95). The aOR of ranitidine was 2.0 (95% CI=1.21-3.40). The aOR of famotidine was 1.7 (95% CI=0.98-2.80). Conclusion : The intake of $H_2$-RAs might increase the risk of gastric cancer through achlorhydria in the elderly.

• Environmental Mutagens and Carcinogens
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• v.26 no.3
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• pp.77-85
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• 2006

2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although TCDD is recognized as potent carcinogens, relatively little is known about their role in the tumor promotion and carcinogenesis. It is known that TCDD can increase of cancer risk from various types of tissue by a mechanism possibly involving the aryl hydrocarbon receptor (AhR) activation. In this study, effects of TCDD on cellular proliferation of normal human skin and lung fibroblasts, Detroit551 and WI38 cells were investigated. In addition, to enhance our understanding of TCDD-mediated carcinogenesis, we have investigated process in which expression of Erk1/2, cyclinD1, oncogene such as Ha-ras and c-myc, and their cognate signaling pathway. TCDD that are potent activators of AhR-mediated activity was found to induce significant increase of cytochrome P4501A1 mRNA expression, suggesting a presence of functional AhR. These results support that CYP1A1 enzyme may be involved in the generation of TCDD-induced toxicity. Moreover mitogen-activated protein kinases (MARKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Ha-ras and c-myc mRNA expression. Taken together, it seems that TCDD are could be a part of cellular proliferation in non-tumorigenic normal human cells such as Detroit551 and WI38 cells through the upregulation of MAPKs signaling pathway regulating growth of cell population. Therefore, AhR-activating TCDD could potentially contribute to tumor promotion and Detroit551 and WI38 cells have been used as a detection system of tumorigenic effects of TCDD.

• Journal of Korea Water Resources Association
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• v.42 no.12
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• pp.1113-1124
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• 2009

The abandoned channel restoration is one of methods to enhance the environmental function and ecological habitat as well as the functions of water-utilization and flood control. The channel-forming or dominant discharge must be evaluated and defined to design the cross-sectional and plane geometries of the stable and equilibrium channel for the abandoned channel restoration project. In general, bankfull discharge, specified recurrence interval discharge, and effective discharge have been used to decide the channel-forming discharge. In this study, bankfull discharge, specified recurrence interval discharge, and effective discharge were calculated and compared for the abandoned channel restoration site of Cheongmi Stream and their relations to historical bed changes were analyzed. The bankfull discharge, 488 $m^3/s$, of the abandoned channel restoration site of Cheongmi Stream was calculated using HEC-RAS data and ranged between 1.5-year and 2-year recurrence discharges. Also, the effective discharge evaluated with the sediment rating curve and mean daily discharge data is greater than the bankfull discharge. According to the survey data of 1994 and 2008, the bed elevation of the study reach was decreased over time. It is indicated that the channel bed is changing to the stable condition to allow the effective discharge.

• Journal of Korean Society of Environmental Engineers
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• v.38 no.2
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• pp.47-55
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• 2016

In this study, WUA (Weighted Usable Area) based on the Instream Flow Incremental Methodology (IFIM) was calculated to determine ecological flow at JeonJu-Cheon by using River2D model. To calibrate River2D, simulation results for low flow conditions of River2D were compared with calibrated HEC-RAS simulation results and the optimum parameters were determined. The results were RMSE (0.18), NSE (0.71) and coefficient of determination (0.78) for velocity and RMSE (0.02), NSE (0.71), coefficient of determination (0.73) for water depth. The result shows that the model successfully simulates the water flows. A selected target fish species to build the habitat suitability index were composed of Zaccoplatypus and Coreoleuciscus splendidus. These species showed the highest occurrences over the past decade in f ish monitoring. Also, The WUA-Discharge curve was calculated with the suitability index in a medium flow conditions. From the result, WUA is changed according to flowrate. In the flowrate-WUA/A graph, ecological flow can be determined at $1.8{\sim}2.0m^3/s$ for Zaccoplatypus $2.0m^3/s$ and Coreoleuciscus splendidus $1.8m^3/s$ at JeonJu-Cheon upstream. When compared with flow-duration analysis, it is demonstrative that simulation results fitted ecological flow considering quantity of available habitat for each fish species.

• KSCE Journal of Civil and Environmental Engineering Research
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• v.39 no.6
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• pp.691-702
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• 2019

Flood inundation map has various important roles in terms of municipal planning, timely dam operation, economic levee design, and building flood forecasting systems. Considering that the riparian areas adjacent to national rivers with high potential flood vulnerability conventionally imposed special cares to justify applications of recently available two- or three-dimensional flood inundation numerical models on top of digital elevation models of dense spatial resolution such as LiDAR irrespective of their high costs. On the contrary, local streams usually could not have benefits from recent technological advances, instead they inevitably have relied upon time-consuming manual drawings or have accepted DEMs with poor resolutions or inaccurate 1D numerical models for producing inundation maps due mainly to limited budgets and suitable techniques. In order to efficiently and cost-effectively provide a series of flood inundation maps dedicatedly for the local streams, this study proposed an OpenGIS-based flood mapping tool named Open Flood Mapper (OFM). The spatial accuracy of flood inundation map derived from the OFM was validated throughout comparison with an inundation trace map acquired after typhoon Nari in Hancheon basin located in Jeju Island. Also, a series of inundation maps from the OFM were comprehensively investigated to track the burst of flood in the extreme flood events.

• BMB Reports
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• v.30 no.5
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• pp.303-307
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• 1997

Grb2, which is composed of a Src homology 2 (SH2) domain and two Src homology 3 (SH3) domains, is known to serve as an adaptor protein in signaling for Ras activation. Thus, a blocker of the Grb2 interactions with other proteins can be a potential candidate for an anticancer drug. In this study, we have developed a high throughput screening method for SH3 domain binding ligands and blockers. Firstly, we made and purified the glutathione S-transferase (GST)-fusion proteins with the Grb2 SH2 and SH3 domains, and the entire Grb2. This method measures the binding of a biotin-labeled oligopeptide, derived from a Grb2/SH3 binding motif in the hSos, to the GST-fusion proteins, which are precoated as glutathione S-transferase fusion protein on a solid phase. When $1\;{\mu}g$ of each fusion protein was used to coat the wells, both N- and C- terminal SH3 the domains as well as the whole of Grb2 were able to interact with the biotin-conjugated ligand peptide, while the SH2 domain and GST alone showed no binding affinity. Although N- and C- terminal SH3 domains showed an increase of binding to the ligand peptide in proportion to the amount of peptide, the GST fusion protein with Grb2 demonstrated much higher binding affinity. GST-Grb2 coating on the solid phase showed a saturation curve; 66 and 84% of the maximal binding was observed at 100 and 300 ng/$100\;{\mu}l$, respectively. This binding assay system was peptide sequence-specific, showing a dose-dependent inhibition with the unlabeled peptide of SH3 binding motif. Several other peptides, such as SH2 domain binding motifs and PTB domain binding motif, were ineffective to inhibit the binding to the biotin-conjugated ligand peptide. These results suggest that our method may be useful to screen for new anticancer drug candidates which can block the signaling pathways mediated by SH3 domain binding.

• Journal of the Korean Association of Geographic Information Studies
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• v.10 no.3
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• pp.1-12
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• 2007

This study was conducted in order to analyze a flooded area by the overflow of a stream using hydrological and hydraulic models and to estimate the utility of the SAR satellite image by comparing a protected lowland inundation area with a past inundation area map. The research area selected for this study is Sapkyocheon, which was flooded in August 1999. The flood stage was analyzed to select an inundation area by applying flood events in August 1999. By importing analyzed flood stage data into TIN data of WMS, the inundation area of a protected lowland was selected and then compared with an flood hazard map of WAMIS. An inundation area is selected by the SAR satellite image in comparing the image of August 4, 1999 (inundation time) with the image of September 8, 2002 (after inundation). The method of selecting an inundation area with the hydraulic model of HEC-RAS can be used to select an inundation area of external overflow, but it has the limit of selecting an inundation area concerning the internal drainage. The method of using the SAR satellite image can complement the limit of an inundation area of an internal drainage but accuracy of inundation area depends on using SAR satellite image acquired at time of maximum depth.