Background: Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and $6.25{\mu}M$ concentrations of sorafenib and 200, 100, 50 and $25{\mu}M$ concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and $IC_{50}$ values are calculated according to the absorbance data Results: Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an $IC_{50}$ value of $32.0{\mu}M$; in contrast with lapatinib the $IC_{50}$ was $136.6{\mu}M$. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells. Conclusions: Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.
Kim, Taewan;Kim, Taehyung;Choi, Soonyoung;Ko, Hyeran;Park, Deokbae;Lee, Youngki
Development and Reproduction
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v.22
no.2
/
pp.133-142
/
2018
Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.
Purpose : The purpose of this study was to determine a conversion coefficient for Hounsfield Units(HU) to material density ($g\;cm^{-3}$) obtained from cone-beam computed tomography ($CBMercuRay^{TM}$) data and to measure the hard tissue density based on the Hounsfield scale on dental head phantom. Materials and Methods : CT Scanner Phantom (AAPM) equipped with CT Number Insert consists of five cylindrical pins of materials with different densities and teflon ring was scanned by using the $CBMercuRay^{TM}$ (Hitachi, Tokyo, Japan) volume scanner. The raw data were converted into DICOM format and the HU of different areas of CT number insert measured by using $CBWorks^{TM}$. Linear regression analysis and Student t-test were performed statistically. Results : There was no significant difference (P > 0.54) between real densities and measured densities. A linear regression was performed using the density, $\rho$($g\;cm^{-3}$), as the dependent variable in terms of the HU (H). The regression equation obtained was $\rho=0.00072H-0.01588$ with an $R^2$ value of 0.9968. Density values based on the Hounsfield scale was $1697.1{\pm}24.9\;HU$ in cortical bone, $526.5{\pm}44.4\;HU$ in trabecular bone, $2639.1{\pm}48.7\;HU$ in enamel, $1246.1{\pm}39.4\;HU$ in dentin of dental head phantom. Conclusion : CBCT provides an effective option for determination of material density expressed as Hounsfield Units.
Journal of the Earthquake Engineering Society of Korea
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v.15
no.3
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pp.65-72
/
2011
Extensive computer simulations to account for the randomness in the process of seismic demand estimation have been a serious obstacle to the adoption of probabilistic performance assessments for the decision of applying seismic intervention schemes. In this study, a method for rapid fragility assessments based on a response database and the fragility contour method are presented. By the comparison of response contours in different formats, it is shown that representing maximum responses in ductility demand is better for the investigation of the effect of structural parameter changes on seismic demands than representations in absolute values. The presented fragility contour enables designers to practically investigate the probabilistic performance level of every possible retrofit option in a convenient manner using visualized data sets. This example demonstrates the extreme efficiency of the proposed approach in performing fragility assessments and successful application to the seismic retrofit strategies based on limit state probabilities.
Aerobic granular sludge (AGS) can be classified as a type of self-immobilized microbial aggregates measuring more than 0.2 mm. It offers the option to simultaneously remove COD, N, and P that occur in different zones inside a granule. Also, AGS is characterized by high precipitability, treatability with high organic loading, and high tolerance to low temperature. In this study, a sequencing batch reactor inoculated with AGS (AGS-SBR) is a new advanced wastewater treatment process that was proven to grow AGS with integrated nutrient removal and low C/N ratio. A pilot plant, AGS-SBR with a capacity of 225 ㎥/d was installed at an S sewage treatment plant in Gyeonggi-do. The results of the operation showed that the water quality of the effluent indicated that the value of BOD5 was 1.5 mg/L, CODMn was 11.4 mg/L, SS was 6.2 mg/L, T-N was 13.2 mg/L, and T-P was 0.197 mg/L, and all of these values reliably satisfied an effluent standard (I Area). In winter, the T-N treatment efficiency at a lower temperature of less than 11℃ also showed reliability to meet the effluent standard of the I Area (20 mg/L or less). Analysis of microbial community in AGS showed a higher preponderance of beneficial microorganisms involved in denitrification and phosphorus accumulation compared with activated sludge. The power consumption and sludge disposal cost were reduced by 34.7% and 54.9%, respectively, compared to the domestic SBR type sewage treatment plant with a processing capacity of 1,000 ㎥/d or less.
Yoo, Sin Yee;Song, Yoon Jin;Oh, Hee Joo;Kim, You Jin;Yoo, Ga Young
Journal of Climate Change Research
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v.7
no.3
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pp.351-356
/
2016
The carbon capture and storage (CCS), which collects and stores carbon dioxide in a geological site, is a promising option to mitigate climate change. However, there is the possibility of carbon dioxide leakage from the soil in the steps of collecting, transporting, and storing. To ensure the feasibility of this technology, it is important to monitor the leakage of carbon dioxide and to assess the potential impacts. As plants are sensitive to the changes in carbon dioxide in the soil environment, we can utilize plant parameter to detect the carbon dioxide leakage. Currently, chlorophyll a content is a conventional index indicating the changes in plants, however, this method is labor intensive and it only utilizes a small portion of leaves. To overcome its limitations, a simple spectroscopic parameter, DGCI (dark green color index), was suggested as an easy and quick indicator. In this study, we compared the values of chlorophyll a contents with DGCI from the experiment investigating the impacts of high underground $CO_2$ on grape plants. Results suggest that DGCI had high correlation with chlorophyll a contents and it has high potential to be utilized as an easy indicator to monitor plants' responses to $CO_2$ treatment.
Han, Seunghoon;Lim, Byounghee;Lee, Hyemi;Bae, Soo Hyun
Translational and Clinical Pharmacology
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v.26
no.4
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pp.166-171
/
2018
Although there are many commercially available training software programs for pharmacokinetics, they lack flexibility and convenience. In this study, we develop simulation software to facilitate pharmacokinetics education. General formulas for time courses of drug concentrations after single and multiple dosing were used to build source code that allows users to simulate situations tailored to their learning objectives. A mathematical relationship for a 1-compartment model was implemented in the form of differential equations. The concept of population pharmacokinetics was also taken into consideration for further applications. The source code was written using R. For the convenience of users, two types of software were developed: a web-based simulator and a standalone-type application. The application was built in the JAVA language. We used the JAVA/R Interface library and the 'eval()' method from JAVA for the R/JAVA interface. The final product has an input window that includes fields for parameter values, dosing regimen, and population pharmacokinetics options. When a simulation is performed, the resulting drug concentration time course is shown in the output window. The simulation results are obtained within 1 minute even if the population pharmacokinetics option is selected and many parameters are considered, and the user can therefore quickly learn a variety of situations. Such software is an excellent candidate for development as an open tool intended for wide use in Korea. Pharmacokinetics experts will be able to use this tool to teach various audiences, including undergraduates.
Kim, Yang Seok;Na, Young Cheon;Yoon, Hyun Sik;Huh, Woo Hoe;Kim, Ji Min
Archives of Craniofacial Surgery
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v.20
no.1
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pp.10-16
/
2019
Background: Physicians tend to overcorrect when applying the acellular dermal matrix for reconstructive option because of volume decrement problem after absorption comparing with initial volume. However, there are no studies on the exact volume decrement and absorption rate with commercial products in South Korea. To figure out absorption rate of acellular dermal matrix product in South Korea (Megaderm), authors designed this experiment. Methods: Nine mice were used and randomly divided into three groups by the time with sacrificing. The implant (Megaderm) was tailored to fit a cuboid form ($1.0cm{\times}1.0cm$ in length and width and 2.0 mm in thickness). A skin incision was made at anterior chest with blade #15 scalpel with exposing the pectoralis major muscle. As hydrated Megaderm was located upon the pectoralis major muscle, the skin was sutured with Ethilon #5-0. After the surgical procedure, each animal group was sacrificed at 4, 8, and 12 weeks, respectively, for biopsies and histological analysis of the implants. All samples were stained with routine hematoxylin and eosin staining and Masson's trichrome staining and the thickness were measured. A measurements were analyzed using Friedman test. Statistically, the correlation between thicknesses of Megaderm before and after implantation was analyzed. Results: After sacrificing the animal groups at postoperative 4, 8, 12 weeks, the mean tissue thickness values were $2.10{\pm}1.03mm$, $2.17{\pm}0.21mm$, and $2.40{\pm}0.20mm$ (p= 0.368), respectively. The remaining ratios after absorption comparing with after initial hydrated Megaderm were 82.7%, 85.4%, and 94.5%, respectively. In histopathological findings, neovascularization and density of collagenous fiber was increased with time. Conclusion: Author's hypothesis was absorption rate of implant would be increased over time. But in this experiment, there is no statistical significance between mean absorption thickness of implant and the time (p= 0.368). Also it can be affected by graft site, blood supply, and animals that were used in the experiment.
Journal of The Korean Society of Grassland and Forage Science
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v.40
no.4
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pp.274-278
/
2020
Pig slurry (PS) is the most applicable recycling option as an alternative organic fertilizer. The application of pig slurry has the risk of air pollution via atmospheric ammonia (NH3) and nitrous oxide (N2O) emission. The zeolite has a porous structure that can accommodate a wide variety of cations, thus utilizing for the potential additive of deodorization and gas adsorption. This study aimed to investigate the possible roles of zeolite in mitigating NH3 and N2O emission from the pig slurry applied to the maize cropping. The experiment was composed of three treatments: 1) non-N fertilized control, 2) pig slurry (PS) and 3) pig slurry mixed with natural zeolite (PZ). Both of NH3 and N2O emission from applied pig slurry highly increased by more than 3-fold compared to non-N fertilized control. The NH3 emission from the pig slurry was dominant during early 14 days after application and 20.1% of reduction by zeolite application was estimated in this period. Total NH3 emission through whole period of measurement was 0.31, 1.33, and 1.14 kg ha-1. Nitrous oxide emission in the plot applied with pig slurry was also reduced by zeolite treatment by 16.3%. Significant increases in forage and ear yield, as well as nutrient values were obtained by pig slurry application, while no significant effects of zeolite were observed. These results indicate that the application of zeolite and pig slurry efficiently reduces the emission of ammonia and nitrous oxide without negative effects on maize crop production.
Background and Objectives: Bilateral microphones with contralateral routing of signal (BiCROS) hearing aid is an option for hearing rehabilitation in individuals with asymmetric sensorineural hearing loss (ASNHL). The clinical factors influencing the trial and purchase of BiCROS were investigated. Subjects and Methods: We reviewed the medical records of 78 patients with ASNHL who were recommended to use BiCROS and analyzed the demographic and audiological factors influencing the trial and purchase of BiCROS. Results: Among the 78 patients, 52 (66.7%) availed of the free BiCROS trial and 21 (26.9%) purchased BiCROS. The mean pure tone audiometry (PTA) air conduction (AC) threshold of the better- and worse-hearing ears were 44.2±12.8 dB and 90.7±22.5 dB HL, respectively. The decision for trial or purchase of BiCROS was not influenced by age, sex, duration of hearing loss of the worse-hearing ear, or PTA AC threshold or speech discrimination score of both ears. The first and third quartiles of the PTA AC thresholds for the better-hearing ear of BiCROS buyers were 38.75 dB and 53.75 dB HL, respectively. The counterpart values for the worse-hearing ear were 72.50 dB and 118.75 dB HL, respectively. Conclusions: The clinical factors analyzed in this study were found to be irrelevant to the trial and purchase of BiCROS in patients with ASNHL. Nevertheless, the distribution range of the auditory thresholds of the subjects using BiCROS can be a useful basis for the counseling of patients with ASNHL and selection of candidates for BiCROS use.
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