• Biomedical Science Letters
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• v.20 no.2
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• pp.85-95
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• 2014

Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the head and neck tumors. To investigate the mechanism of antiproliferation to EGFR inhibition in oral cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$). We have demonstrated that ZD1839 induces growth arrest and apotosis in oral cancer cell lines by independent of EGFR-mediated signaling. An exposure of oral cancer cells to ZD1839 resulted in a dose dependent up-regulation of the cyclin-dependent kinase inhibitor p21 and p27, down regulation of cyclin D1, inactivation of GSK-$3{\beta}$ and of active MAPK. In resistant cells, GSK-$3{\beta}$ is constitutively active and its activity is negatively regulated primarily through Ser 9 phosphorylation and further enhanced by Tyr216 phosphorylation. These results showed that the resistance to the antiproliferative effects of ZD1839, in vitro was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-$3{\beta}$ activation and degradation of its target cyclin D1 were indicators of high cell sensitivity to ZD1839. In conclusion, our data show that the uncoupling of EGFR with mitogenic pathways can cause resistance to EGFR inhibition in oral cancer.

• The Journal of the Korea institute of electronic communication sciences
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• v.4 no.3
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• pp.236-242
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• 2009

When two-link flexible arm is rotated about an joint axis, transverse vibration may occur. In this paper, vibration dynamics of flexible robot arm is modeled by using Bernoulli-Euler beam theory and Lagrange equation. Using the fact that matrix $\dot{D}$-2C is skew symmetric, new controllers which have a simplified structure with less computational burden is proposed. Lyapunov stability theory is applied to achieve a stable deterministic nonlinear controller for the regulation of joint angle.

• BMB Reports
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• v.47 no.4
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• pp.197-202
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• 2014

SOX3 is one of the earliest neural markers in vertebrates, playing the role in specifying neuronal fate. In this study we have established first functional link between CREB and human SOX3 gene which both have important roles in the nervous system throughout development and in the adulthood. Here we demonstrate both in vitro and in vivo that CREB binds to CRE half-site located -195 to -191 within the human SOX3 promoter. Overexpression studies with CREB or its dominant-negative inhibitor A-CREB indicate that this transcription factor acts as a positive regulator of basal SOX3 gene expression in NT2/D1 cells. This is further confirmed by mutational analysis where mutation of CREB binding site results in reduction of SOX3 promoter activity. Our results point at CREB as a positive regulator of SOX3 gene transcription in NT2/D1 cells, while its contribution to RA induction of SOX3 promoter is not prominent.

• Journal of Radiation Protection and Research
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• v.26 no.3
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• pp.291-298
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• 2001

The designed release rate of liquid effluents from radwaste treatment system should be calculated and evaluated during normal operation, including anticipated operational occurrence and be assured that the release concentration and off-site dose at unrestricted area do not exceed the limits of regulation. The expected annual release rate and off-site dose for the currently operating nuclear power plants in Korea had been calculated and evaluated using PWR-GALE and LADTAP-II which was based on USNRC Regulatory Guide 1.109. Recently, the MOST Notice 2001-2 related to release concentration and off-site dose at unrestricted area was revised to reflect the concept of ICRP-60. It is necessary for KORI 3&4 to re-calculate the release concentration and off-site dose and to compare these results with the limits of regulation. As the results of assessment, we confirmed that the release concentrations were less than its limits of MOST Notice 2001-2 and the off-site dose at unrestricted area using K-DOSE60 was 3.61E-03 mSv/yr to the age of five for the effective dose, and 4.10E-2 mSv/yr to thyroid of the age of five for the organ equivalent dose. We also confirmed the off-site dose was within the limits of MOST Notice 2001-2. Therefore, the release concentration and off-site dose re-evaluated at unrestricted area in KORI 3&4 were well below the regulation limits of MOST Notice 2001-2.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.5
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• pp.363-369
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• 2005

Purpose: To determine the role of Insulin-like Growth Factor-I (IGF-I) in the regulation of Vascular Endothelial Growth Factor (VEGF) expression in MG-63 cells and then to find the mechanism b which this regulation occurs. Materials and methods: MG-63 cells were grown to confluence in 60-mm dishes. To determine the effects of IGF-I on expression of VEGF mRNA according to time and concentration, the cells were treated with 10 nM IGF-I, following isolation of total RNA and Northern blot analysis after 1, 2, 4, 8, 12, 24 hours and after 2 hours of treatment with 0.5, 2, 10, 25, 50 nM IGF-I respectively, isolation of total RNA and Northern blot analysis were followed. To determine the mechanism of action of IGF-I, inhibitors such as hydroxyurea $(76.1\;{\mu}g/ml)$, actinomycin D $(2.5\;{\mu}g/ml)$, cycloheximide $(10\;{\mu}g/ml)$ were added 1 hour after treatment of 10 nM IGF-I. Results: 1. the expression of VEGF mRNA was increased with treatment of IGF-I. 2. The expression of VEGF mRNA was increased according to time-and concentration dependent manner of IGF-I. 3. The effect of IGF-I was decreased by hydroxyuera, actinomycin D, but not by cycloheximide. Conclusion: IGF-I regulate the expression of VEGF mRNA in the level of DNA synthesis and transcription. These results could suggest that IGF-I plays an important role in angiogenesis in the process of new bone formation and remodeling.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3817-3823
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• 2014

Background: The MDM2 oncogene, a negative regulator of p53, has a functional polymorphism in the promoter region (SNP309) that is associated with multiple kinds of cancers including non-melanoma skin cancer. SNP309 has been shown to associate with accelerated tumor formation by increasing the affinity of the transcriptional activator Sp1. It remains unknown whether there are other factors involved in the regulation of MDM2 transcription through a trans-regulatory mechanism. Methods: In this study, SNP309 was verified to be associated with overexpression of MDM2 in tumor cells. Bioinformatics predicts that the T to G substitution at SNP309 generates a stronger E2F1 binding site, which was confirmed by ChIP and luciferase assays. Results: E2F1 knockdown downregulates the expression of MDM2, which confirms that E2F1 is a functional upstream regulator. Furthermore, tumor cells with the GG genotype exhibited a higher proliferation rate than TT, correlating with cyclin D1 expression. E2F1 depletion significantly inhibits the proliferation capacity and downregulates cyclin D1 expression, especially in GG genotype skin fibroblasts. Notably, E2F1 siRNA effects could be rescued by cyclin D1 overexpression. Conclusion: Taken together, a novel modulator E2F1 was identified as regulating MDM2 expression dependent on SNP309 and further mediates cyclin D1 expression and tumor cell proliferation. E2F1 might act as an important factor for SNP309 serving as a rate-limiting event in carcinogenesis.

• Molecules and Cells
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• v.28 no.1
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• pp.1-5
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• 2009

Vascular endothelial growth factor (VEGF) is essential for many angiogenic processes both in normal and pathological conditions. However, the signaling pathways involved in VEGF-induced angiogenesis are incompletely understood. The protein kinase D1 (PKD1), a newly described calcium/calmodulin-dependent serine/threonine kinase, has been implicated in cell migration, proliferation and membrane trafficking. Increasing evidence suggests critical roles for PKD1-mediated signaling pathways in endothelial cells, particularly in the regulation of VEGF-induced angiogenesis. Recent studies show that class IIa histone deacetylases (HDACs) are PKD1 substrates and VEGF signal-responsive repressors of myocyte enhancer factor-2 (MEF2) transcriptional activation in endothelial cells. This review provides a guide to PKD1 signaling pathways and the direct downstream targets of PKD1 in VEGF signaling, and suggests important functions of PKD1 in angiogenesis.

• Transactions of the Korean Society of Automotive Engineers
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• v.24 no.3
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• pp.319-329
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• 2016

Globally, many researchers have been trying to improve the fuel economy of a vehicle for satisfying future $CO_2$ regulation and minimizing air pollution problem. For the same background, diesel engine and vehicle system optimization using simulation models have been key technologies for the improvement of vehicle system efficiency. Therefore, in this study, calibration method for the air breathing system of a WGT diesel engine using mean value model has been composed for efficient engine and vehicle optimization simulation researches. And virtual WGT performances have been calculated for a 2 cylinder downsized diesel engine system. From these researches, the calibration method for the boost pressure and EGR rate of a virtual diesel engine related with WGT performances could be composed and some of technical issue related with downsized diesel engine could be investigated.

• Transactions of the Korean Society for Noise and Vibration Engineering
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• v.25 no.7
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• pp.462-469
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• 2015

This study was carried out to examine characteristics of various acoustic indicators evaluating speech intelligibility such as reverberation time(T₃₀), D₅₀, C₅₀ and speech transmission index(STI) in Korean elementary school classrooms. Results showed that mean T₃₀ at middle frequencies(500 Hz to 2000 Hz) measured in 9 classrooms was about 0.75 s, which exceeds a regulation specified on American National Standards(ANSI); 0.60 s. Mean D₅₀, C₅₀ and STI were 60 % to 66 %, +2 dB to +3 dB, and 0.65, respectively. The maximum difference in D₅₀ and C₅₀ according to different receiver points in a classroom was 13 % and 2.5 dB, while the maximum difference in T₃₀ was 0.03 s. Whereas STI measured in classrooms has relatively low correlation with other indicators, correlation between D₅₀ and C₅₀ was high, R²=.9964. In addition, T₃₀ and C₅₀ were fitted well as logarithmic regression curve with R²=.9610. It was +3.73 dB in C₅₀ and 68 % in D₅₀ which are the value corresponding to 0.60 s in T₃₀ on this curve.

• Clinical and Experimental Pediatrics
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• v.49 no.10
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• pp.1100-1105
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• 2006

Purpose : Because NELL2 expression is strictly restricted only in neurons in developing and post-differentiated neural tissues, it is thought to be involved in the neuronal differentiation during development and in the maintenance of neuronal physiology in the post-differentiated neurons. In this study, we examined whether NELL2 is involved in the regulation of cell cycle and apoptosis in the hippocampal neuroprogenitor HiB5 cells. Methods : Effects of NELL2 on the cultured HiB5 cell numbers, DNA fragmentation, and proteins involved in the regulation of the cell cycle were measured. Results : NELL2 induced a decrease in cell numbers and an increase in G1 phase arrest. Moreover, transfection of NELL2 resulted in an increase of DNA fragmentation that shows an evidence of apoptosis. Contents of proteins involved in the regulation of cell cycle were also changed by transfection of NELL2 expression vectors. Conclusion : This study suggests that NELL2 plays an important role in the regulation of cell cycle and apoptosis of neurons.