• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7617-7623
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• 2014

Objective: The mechanism of action of fatty acid synthase (FASN) in drug tolerance of breast cancer cells with epithelial-mesenchymal transition (EMT) features was investigated. Methods: The breast cancer cell line MCF-7-MEK5 with stably occurring EMT and tumour necrosis factor-${\alpha}$ (TNF-${\alpha}$) tolerance was used as the experimental model, whereas MCF-7 acted as the control. Tumour cells were implanted into nude mice for in vivo analysis, and cerulenin was used as a FASN inhibitor. RT-PCR, real-time quantitative PCR and Western blot were employed to detect the expression of FASN, TNFR-1, TNFR-2, Wnt-1, ${\beta}$-catenin and cytC at the RNA and protein levels. Results: Compared with MCF-7, TNFR-1 expression in MCF-7-MEK5 was slightly changed, TNFR-2 was decreased, and FASN, Wnt-1, ${\beta}$-catenin and cytC were increased. The expression of Wnt-1 and ${\beta}$-catenin in MCF-7-MEK5 decreased after cerulenin treatment, whereas cytC expression increased. Conclusions: The important function of FASN in the drug tolerance of breast cancer may be due to the following mechanisms: FASN downregulated TNFR-2 expression through lipid rafts to make the cells less sensitive to TNF-${\alpha}$, and simultaneously activated the Wnt-$1/{\beta}$-catenin signalling pathway. Thus, cytC expression increased, which provided cells with anti-apoptotic capacity and induced drug tolerance.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.4 no.2
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• pp.127-136
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• 1994

Diffusional sampling devices offer many advantages for measuring concentration levels of industrial contaminants than the conventional pump and charcoal tubes because they are lightweight, require no power, pump or tubing. This study designed to evaluate and compare the sampling performance of passive sampler to charcoal tube from mixed organic solvent workplace with 181 organic solvent using workers working in different concentration of organic solvents. All study workers kept both devices in their breathing zone simultaneuosly in the workplaces, and the sampling analytical results were compared with those of charcoal tube. The results obtained are as follows: 1. The concentrations of toluene and xylene measured by passive sampler were slightly higher than those of charcoal tube, but there were no significant statistical differences between two methods. 2. The concentrations of MEK and cyclo-hexanone measured by passive sampler in low exposure workplace (below 0.20 of MEK TLV levels and 0.1 of cyclo-hexanone TLV levels) were about 2 times higher than that of charcoal tube sampling. While, absorption efficiency of passive sampler was reduced according to increasing concentration measurements of MEK and cyclo-hexanone in air. 3. The ratios of concentrations of toluene, xylene, MEK and cyc1o-hexanone measured by passive sampler over those measured by charcoal tube were 1.11, 1.07, 1.63 and 3.65 respectively. 4. The percentages of concentration of passive samplers within 0.75 and 1.25 of charcoal tube value as a reference value of 1.0 were 57% in toluene, 74% in xylene, 34% in MEK and 32% in cyclo-hexanone respectively. 5. The correlation coefficients of toluene, xylene, MEK and cyclo-hexanone between passive sampler and charcoal tube sampler were 0.963, 0.957, 0.943 and 0.562 with statistical significance.

• Development and Reproduction
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• v.13 no.4
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• pp.291-296
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• 2009

In most larvae of ascidian, two sensory pigment cells, otolith and ocellus, lie in their brain vesicle. They also have a third type of sensory cells: hydrostatic pressure receptor (Hpr) cells. The Hpr cells were presumed to be hydrostatic pressure-detection cells, but their precise functions is still disputed. In this study, we investigated whether an FGF signaling is involved in formation of Hpr cells. When fertilized eggs were injected with Hr-FGF9/16/20 antisense MO, the resulting larvae showed severe abnormalities with no expression of the Hpr cell-specific Hpr-1 antigen. Similar results were obtained using an FGF receptor inhibitor, SU5402, and an MEK inhibitor, U0126. Embryos treated with SU5402 or U0126 during the 32-cell and hatching stages did not express the Hpr-1 antigen. To elucidate the temporal requirement for the FGF signaling in formation of Hpr cells, embryos were treated with SU5402 for 2 h, or U0126 for 20 min during various embryonic stages. Larvae treated with SU5402 from the 16-cell stage to the 64-cell stage did not express the Hpr-1 antigen, whereas those treated at the early gastrula stage expressed the Hpr-1 antigen. When U0126 treatment was carried out at various stages between the 8-cell and late gastrula stages, larvae scarcely formed the Hpr cells. They showed expression of the Hpr-1 antigen when embryos were placed in U0126 just before the neural plate stage. These results suggest that FGF9/16/20 signaling is involved in formation of Hpr cells from the primary neural induction stage to the late gastrula stage.

• Journal of the Korean Society of Industry Convergence
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• v.8 no.1
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• pp.37-45
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• 2005

Adsorption equilibrium data of pure solvent vapors (n-Hexane, Toluene, MEK) as well as their binary mixtures on activated carbon (sorbonorit $B_4$) were experimentally determined in the range of 293.2~323.2 K and beyond saturated vapor pressure corresponding to experimental temperature. Langmuir, Freundlich, LRC, W-VSM, FH-VSM were estimated for the predication of single component as well as binary mixtuer systems. The isosteric heat of adsorption at infinite dilution of pure n-hexane, toluene, MEK on activated carbon were 45.18, 25.85, 34.62 Kcal/mol, respectively, also, n-hexane-toluene binary adsorption of activated carbon formed an azeotrope at 293.2 K and total pressure 5.1~10.3 mmHg.

• Animal cells and systems
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• v.7 no.3
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• pp.221-225
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• 2003

The tadpole larva of the ascidian Halocynthia roretzi has two sensory pigment cells in its brain vesicle. To elucidate the temporal requirement for FGF signaling in formation of the pigment cells, embryos were treated with an FGF receptor 1 inhibitor, SU5402, or an MEK inhibitor, U0126 during various embryonic stages. In the present study, it is shown that the embryos treated with SU5402 from the 16-cell stage to the early gastrula stage do not form pigment cells, whereas those treated after the early gastrula stage form pigment cells. In pigment cell formation, embryos suddenly exhibited the sensitivity to SU5402 only for 1 h at the neural plate stage(-4 h after the beginning of gastrulation). When U0126 treatment was carried out at various stages between the 8-cell and late neurula stages, the embryos scarcely formed pigment cells. Pigment cell formation occurred when the embryos were placed in U0126 at early tail bud stage. These results indicate that FGF signaling is involved in pigment cell formation at two separate processes during ascidian embryogenesis, whereas more prolonged period is required for MEK signaling.

• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3637-3641
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• 2014

In this study, we analyzed the toxicity of mixtures of dimethylformamide (DMF) and methyl ethyl ketone (MEK) or DMF and toluene (TOL) and predicted their toxicity using quantitative structure-activity relationships (QSAR). A QSAR model for single substances and mixtures was analyzed using multiple linear regression (MLR) by taking into account the statistical parameters between the observed and predicted $EC_{50}$. After preprocessing, the best subsets of descriptors in the learning methods were determined using a 5-fold cross-validation method. Significant differences in physico-chemical properties such as boiling point (BP), specific gravity (SG), Reid vapor pressure (rVP), flash point (FP), low explosion limit (LEL), and octanol/water partition coefficient (Pow) were observed between the single substances and the mixtures. The $EC_{50}$ of the mixture of DMF and TOL was significantly lower than that of DMF. The mixture toxicity was directly related to the mixing ratio of TOL and MEK (MLR $EC_{50}$ equation = $1.76997-1.12249{\times}TOL+1.21045{\times}MEK$), as well as to SG, VP, and LEL (MLR equation $EC_{50}=15.44388-19.84549{\times}SG+0.05091{\times}VP+1.85846{\times}LEL$). These results show that QSAR-based models can be used to quantitatively predict the toxicity of mixtures used in manufacturing industries.

• Radioisotope journal
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• v.15 no.1
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• pp.60-64
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• 2000

• Applied Chemistry for Engineering
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• v.33 no.3
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• pp.328-334
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• 2022

For the study of environmental application of natural zeolites (NZ) and red mud (RM), which are discharged from various industrial fields, the catalytic ozonation of 2-butaone (methyl ethyl ketone, MEK) was performed using the Mn-loaded NZ prepared according to the Mn content of 1, 3, 5, 7, and 10 wt%. By the addition of Mn to NZ, the BET (Brunaure-Emmett-Teller) specific surface area of Mn/NZ catalysts decreased while the ratio of Mn³⁺/[Mn³⁺+Mn⁴⁺] intensively increased. Besides, the addition of Mn component to NZ increased the ratio of adsorbed oxygen (O_adsorbed) toward lattice oxygen (O_lattice), O_adsorbed/O_lattice from 0.076 of NZ to 0.465 of 10 wt% Mn/NZ according to the amount of Mn. It is known that the proportion of two species, Mn³⁺ and O_adsorbed, would greatly affect the catalytic activity. However, the balancing between the paired species, Mn³⁺ vs. Mn⁴⁺ and O_adsorbed vs. O_lattice might be more essential for the catalytic ozonation of MEK at room temperature. Among the Mn-loaded NZ catalysts, the 3 wt% Mn/NZ showed the best activity for the removal of MEK and ozone. The 5, 7, and 10 wt% Mn/NZ catalysts are slightly inferior to the 3 wt% Mn/NZ. Compared to the pristine NZ, the Mn/NZ catalysts showed better activity for the catalytic ozonation of MEK. In addition, the 3 wt% Mn/NZ was confirmed to have the most available acid sites among them by the analysis of NH₃-TPD (temperature programmed desorption). This might be the major reason for the best catalytic activity of 3 wt% Mn/NZ together with the adjusted distribution ratios of Mn³⁺/Mn⁴⁺ and O_adsorbed/O_lattice. Considering the result of 3 wt% Mn/NZ, the 3 wt% Mn/RM was prepared to perform the catalytic activity for the removal of MEK and ozone, but the efficiency of 3 wt% Mn/RM was significantly lower than that of the 3 wt% Mn/NZ.

• Journal of Genetic Medicine
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• v.16 no.1
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• pp.1-9
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• 2019

Noonan syndrome (NS) and NS-related disorders (cardio-facio-cutaneous syndrome, Costello syndrome, NS with multiple lentigines, or LEOPARD [lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth and sensory neural deafness] syndrome) are collectively named as RASopathies. Clinical presentations are similar, featured with typical facial features, short stature, intellectual disability, ectodermal abnormalities, congenital heart diseases, chest & skeletal deformity and delayed puberty. During past decades, molecular etiologies of RASopathies have been growingly discovered. The functional perturbations of the RAS-mitogen-activated protein kinase pathway are resulted from the mutation of more than 20 genes (PTPN11, SOS1, RAF1, SHOC2, BRAF, KRAS, NRAS, HRAS, MEK1, MEK2, CBL, SOS2, RIT, RRAS, RASA2, SPRY1, LZTR1, MAP3K8, MYST4, A2ML1, RRAS2). The PTPN11 (40-50%), SOS1 (10-20%), RAF1 (3-17%), and RIT1 (5-9%) mutations are common in NS patients. In this review, the constellation of overlapping clinical features of RASopathies will be described based on genotype as well as their differential diagnostic points and management.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.37-46
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• 2006

Objectives : The purpose of this study was to investigate the effect of Dangguibohyultang (DB) and its combination (DB-I; Astragali membraneus BUNGE : Angelica gigas NAKAI=5:1, DB-II; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:1, DB-III; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:5,) on apoptosis in human colorectal adenocarcinoma HCT116 cells. Methods : To study the cytotoxic effect of methanol extract of DB-I, DB-II and DB-III on HCT116 cells, the cell viability was determined by XTT reduction method and ttypan blue exclusion assay. To confirm the induction of apoptosis, the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, DB-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome C from mitochondria to cytosol, the level of Bcl-2 and Bax, and the expressions of Raf/MEK/ERK were examined by western blot analysis. Results : DB-I and DB-II reduced proliferation of HCT116 cells in a dose-dependent manner. DB-I and DB-II decreased procaspase-3, -8, -9 levels in a dose-dependent manner and induced the clevage of PARP. DB-I and DB-II also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol, decreasing of anti-apoptotic Bcl-2, and increasing of pro-apoptotic Bax. DB-I and DB-II decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. Conclusion : These results suggest that DB-I and DB-II induce apoptosis via mitochondrial pathway in HCT116 cells. Furthermore, Raf/MEK/ERK cascade is involved in DB-induced apoptosis. These results suggest that DB is potentially useful as a chemotherapeutic agent in human liver cancer.