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Sung-Hee Hwang,Hojin Yeom,Michael Lee 대한생리학회-대한약리학회 2020 The Korean Journal of Physiology & Pharmacology Vol.24 No.3
Autophagy regulators are often effective as potential cancer therapeutic agents. Here, we investigated paclitaxel sensitivity in cells with knockout (KO) of ATG5 gene. The ATG5 KO in multidrug resistant v-Ha-ras -transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr) was generated using the CRISPR/Cas9 technology. The qPCR and LC3 immunoblot confirmed knockout of the gene and protein of ATG5, respectively. The ATG5 KO restored the sensitivity of Ras-NIH 3T3/Mdr cells to paclitaxel. Interestingly, ATG5 overexpression restored autophagy function in ATG5 KO cells, but failed to rescue paclitaxel resistance. These results raise the possibility that low level of resistance to paclitaxel in ATG5 KO cells may be related to other roles of ATG5 independent of its function in autophagy. The ATG5 KO significantly induced a G2/M arrest in cell cycle progression. Additionally, ATG5 KO caused necrosis of a high proportion of cells after paclitaxel treatment. These data suggest that the difference in sensitivity to paclitaxel between ATG5 KO and their parental MDR cells may result from the disparity in the proportions of necrotic cells in both populations. Thus, our results demonstrate that the ATG5 KO in paclitaxel resistant cells leads to a marked G2/M arrest and sensitizes cells to paclitaxel-induced necrosis.
Consideration of Cavity Detection Applicability of SASW Technique Through the Model Test
Sung Jin Lee,JinWook Lee,Vu Thanh Ngo,Hojin Cho,Yujin Lim 한국철도학회 2016 한국철도학회 학술발표대회논문집 Vol.2016 No.5
This paper presents a detection technique for determination of the cavity existence under slab track of railway. The detection technique is based on the Spectral Analysis of Surface Wave (SASW) test. The SASW test is a non-destructive seismic method which uses Rayleigh-type waves to measure in situ shear wave velocity (Vs) of soil. It is found form field model tests that underground obstacles or buried objects and soil heterogeneity significantly affect surface (Rayleigh) wave dispersion. Cavities and obstacles looser than the surrounding soil cause a decrease in the shear wave velocity. The theoretical background and field implementation procedures of using SASW for detecting cavity below the slab track are explained.
Parameter Optimization of WAAM with Pulsed GMAW for Manufacturing Propeller-Shaped Blade
Sang-Woo Han,Hojin Yoo,Seungcheol Shin,Hansol Kim,Geonho Lee,Jongho Jeon,Sangjun Han,Jungho Cho 한국정밀공학회 2023 International Journal of Precision Engineering and Vol.24 No.7
The experiments of wire arc additive manufacturing (WAAM) with general pulsed gas metal arc welding (GMAW) machine were performed to optimize process parameters. As optimized conditions, 140A welding current, 34 V welding voltage, 40 cm/min welding speed, and 15 mm contact tip to work distance (CTWD), were selected. Welding current and voltage affected heat input. Lower deposition, short circuit mode, and spatters were obtained by insufficient heat input. The melting of previous layer and lower height were obtained by excessive heat input. Welding speed and CTWD affected surface state and arc stability. Unsound surface and bead shape due to short circuit mode and spatters were observed in slow welding speed and short CTWD conditions. Arc instability were also observed in fast welding speed and long CTWD conditions. With the optimized process parameter, curved propeller shape blade was manufactured by the change of robot arm teaching point. It can be considered that the desired sufficient quality was obtained due to curved shape.
( Hojin Yeom ),( Sung-hee Hwang ),( Byeal-i Han ),( Michael Lee ) 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.4
BRAF inhibitors are insufficient monotherapies for BRAF-mutated cancer; therefore, we investigated which inhibitory pathway would yield the most effective therapeutic approach when targeted in combination with BRAF inhibition. The oncogenic BRAF inhibitor, PLX4720, increased basal autophagic flux in BRAF-mutated cells compared to wild-type (WT) BRAF cells. Interestingly, early autophagy inhibition improved the effectiveness of PLX4720 regardless of BRAF mutation, whereas late autophagy inhibition did not. Although ATG5 knockout led to PLX4720 resistance in both WT and BRAF-mutated cells, the MEK inhibitor trametinib exhibited a synergistic effect on PLX4720 sensitivity in WT BRAF cells but not in BRAF-mutated cells. Conversely, the prolonged inhibition of endoplasmic reticulum (ER) stress reduced basal autophagy in BRAF-mutated cells, thereby increasing PLX4720 sensitivity. Taken together, our results suggest that the combined inhibition of ER stress and BRAF may simultaneously suppress both pro-survival ER stress and autophagy, and may therefore be suitable for treatment of BRAF-mutated tumors whose autophagy is increased by chronic ER stress. Similarly, for WT BRAF tumors, therapies targeting MEK signaling may be a more effective treatment strategy. Together, this study presents a rational combination treatment strategy to improve the efficacy of BRAF inhibitors depending on BRAF mutation status.