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Euchromatin histone methyltransferase II (EHMT2) regulates the expression of ras-related GTP binding C (RRAGC) protein

  • Hwang, Supyong;Kim, Soyoung;Kim, Kyungkon;Yeom, Jeonghun;Park, Sojung;Kim, Inki
    • BMB Reports
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    • v.53 no.11
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    • pp.576-581
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    • 2020
  • Dimethylation of the histone H3 protein at lysine residue 9 (H3K9) is mediated by euchromatin histone methyltransferase II (EHMT2) and results in transcriptional repression of target genes. Recently, chemical inhibition of EHMT2 was shown to induce various physiological outcomes, including endoplasmic reticulum stress-associated genes transcription in cancer cells. To identify genes that are transcriptionally repressed by EHMT2 during apoptosis, and cell stress responses, we screened genes that are upregulated by BIX-01294, a chemical inhibitor of EHMT2. RNA sequencing analyses revealed 77 genes that were upregulated by BIX-01294 in all four hepatic cell carcinoma (HCC) cell lines. These included genes that have been implicated in apoptosis, the unfolded protein response (UPR), and others. Among these genes, the one encoding the stress-response protein Ras-related GTPase C (RRAGC) was upregulated in all BIX-01294-treated HCC cell lines. We confirmed the regulatory roles of EHMT2 in RRAGC expression in HCC cell lines using proteomic analyses, chromatin immune precipitation (ChIP) assay, and small guide RNA-mediated loss-of-function experiments. Upregulation of RRAGC was limited by the reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC), suggesting that ROS are involved in EHMT2-mediated transcriptional regulation of stress-response genes in HCC cells. Finally, combined treatment of cells with BIX-01294 and 5-Aza-cytidine induced greater upregulation of RRAGC protein expression. These findings suggest that EHMT2 suppresses expression of the RRAGC gene in a ROS-dependent manner and imply that EHMT2 is a key regulator of stress-responsive gene expression in liver cancer cells.

A novel mutation in XLRS1 gene in X-linked juvenile retinoschisis

  • Kim, Da Hyun;Heo, Sun Hee;Seo, Go Hun;Oh, Arum;Kim, Taeho;Kim, Gu-Hwan;Yoon, Young Hee;Yoo, Han-Wook;Lee, Beom Hee
    • Journal of Genetic Medicine
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    • v.15 no.1
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    • pp.13-16
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    • 2018
  • X-linked juvenile retinoschisis (XLRS) is characterized by the progressive loss of visual acuity and vitreous hemorrhage. XLRS is caused by a mutation of retinoschisin 1 (RS1) gene at Xp22.13. In the current report, a 2-year-old Korean patient with XLRS was described. The germline deletion of exon 1 was identified in the RS1 gene. Considering X-linked inheritance pattern, validation of a carrier state of a patient's mother is important for the genetic counseling of other family members and for the future reproductive plan. To confirm the carrier state of his mother, the multiplex ligation-dependent probe amplification analysis was done using peripheral leukocytes and found the heterozygous deletion of exon 1 in his mother.

Postoperative Complications and Their Risk Factors of Completion Total Gastrectomy for Remnant Gastric Cancer Following an Initial Gastrectomy for Cancer

  • Park, Sin Hye;Eom, Sang Soo;Eom, Bang Wool;Yoon, Hong Man;Kim, Young-Woo;Ryu, Keun Won
    • Journal of Gastric Cancer
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    • v.22 no.3
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    • pp.210-219
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    • 2022
  • Purpose: Completion total gastrectomy (CTG) for remnant gastric cancer (RGC) is a technically demanding procedure and associated with increased morbidity. The present study aimed to evaluate postoperative complications and their risk factors following surgery for RGC after initial partial gastrectomy due to gastric cancer excluding peptic ulcer. Materials and Methods: We retrospectively reviewed the data of 107 patients who had previously undergone an initial gastric cancer surgery and subsequently underwent CTG for RGC between March 2002 and December 2020. The postoperative complications were graded using the Clavien-Dindo classification. Logistic regression analyses were used to determine the risk factors for complications. Results: Postoperative complications occurred in 34.6% (37/107) of the patients. Intra-abdominal abscess was the most common complication. The significant risk factors for overall complications were multi-visceral resections, longer operation time, and high estimated blood loss in the univariate analysis. The independent risk factors were multi-visceral resection (odds ratio [OR], 2.832; 95% confidence interval [CI], 1.094-7.333; P=0.032) and longer operation time (OR, 1.005; 95% CI, 1.001-1.011; P=0.036) in the multivariate analysis. Previous reconstruction type, minimally invasive approach, and current stage were not associated with the overall complications. Conclusions: Multi-visceral resection and long operation time were significant risk factors for the occurrence of complications following CTG rather than the RGC stage or surgical approach. When multi-visceral resection is required, a more meticulous surgical procedure is warranted to improve the postoperative complications during CTG for RGC after an initial gastric cancer surgery.

Design and Fabrication of V-band Up-Mixer and Drive Amplifier for 60 GHz Transmitter (60 GHZ 통신 시스템 송신단의 구현을 위한 V-band MIMIC 상향 주파수 혼합기와 구동 증폭기 설계 및 제작)

  • Jin Jin-Man;Lee Sang-Jin;Ko Du-Hyun;An Dan;Lee Mun-Kyo;Lee Seong-Dae;Lim Byeong-Ok;Cho Chang-Shik;Baek Yong-Hyun;Park Hyung-Moo;Rhee Jin-Koo
    • Proceedings of the IEEK Conference
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    • 2004.06b
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    • pp.339-342
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    • 2004
  • 본 논문은 밀리미터파 대역 무선통신 시스템 송신부의 응용을 위해 CPW 구조를 이용하여 V-band용 상향 주파수 혼합기와 2단 구동증폭기를 설계$\cdot$제작하였다. 능동소자는 본 연구실에서 제작한 $0.1{\mu}m$ 게이트 GaAs Pseudomorphic HEMTs(PHEMTs)를 사용하였으며 입$\cdot$출력단은 CPW를 사용해 정합 회로를 설계하였다. 제작된 상향 주파수 혼합기는 LO power 5.4 dBm, 2.4 GHz IF 신호를 -10.25 dBm으로 입력하였을 때 Conversion Loss 1.25 dB, LO-to-RF Isolation은 58 GHz에서 13.2 dB의 특성을 나타내었다 2단 구동 증폭기는 측정결과 60 GHz에서 S21 이득 13 dB, $58\;GHz\;\~\;64\;GHz$ 대역에서 S21 이득 12 dB 이상을 유지하는 광대역 특성을 얻었고 증폭기의 Pl dB는 3.8 dBm, 최대 출력전력은 6.5 dBm의 특성을 얻었다.

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High LO-RF Isolation 94 GHz MMIC Single-balanced Mixer (높은 LO-RF 격리 특성의 94 GHz MMIC Single-balanced Mixer)

  • An, Dan;Lee, Bok-Hyung;Lim, Byeong-Ok;Kim, Sung-Chan;Lee, Sang-Jin;Lee, Mun-Kyo;Shin, Dong-Hoon;Park, Hyung-Moo;Park, Hyun-Chang;Kim, Sam-Dong;Rhee, Jin-Koo
    • Proceedings of the IEEK Conference
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    • 2005.11a
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    • pp.765-768
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    • 2005
  • In this paper, high LO-RF isolation 94 GHz MMIC single-balanced mixer was designed and fabricated using a branch line coupler and a ${\lambda}/4$ transmission line. The 94 GHz MMIC single-balanced mixer was designed using the 0.1 ${\mu}m$ InGaAs/InAlAs/GaAs Metamorphic HEMT(MHEMT) diode. The fabricated MHEMT was obtained the cut-off frequency($f_T$) of 189 GHz and the maximum oscillation frequency($f_{max}$) of 334 GHz. The designed MMIC single-balanced mixer was fabricated using 0.1 ${\mu}m$ MHEMT MMIC process. From the measurement, the conversion loss of the single-balanced mixer was 23.1 dB at an LO power of 10 dBm. The LO-RF isolations of single-balanced mixer was obtained 45.5 dB at 94.19 GHz. We obtained in this study a higher LO-RF isolation compared to some other balanced mixers in millimeter-wave frequencies.

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A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab

  • Lee, Sang-Kyu;Cho, Yong-Hee;Cha, Pu-Hyeon;Yoon, Jeong-Soo;Ro, Eun Ji;Jeong, Woo-Jeong;Park, Jieun;Kim, Hyuntae;Kim, Tae Il;Min, Do Sik;Han, Gyoonhee;Choi, Kang-Yell
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.12.1-12.12
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    • 2018
  • Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

Long-Term Efficacy and Safety of Golimumab for Ulcerative Colitis in a Pediatric Inflammatory Bowel Disease Center in Japan

  • Tokita, Kazuhide;Shimizu, Hirotaka;Takeuchi, Ichiro;Shimizu, Toshiaki;Arai, Katsuhiro
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.25 no.6
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    • pp.461-472
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    • 2022
  • Purpose: Golimumab (GLM) is an anti-tumor necrosis factor (TNF)-α antibody preparation known to be less immunogenic than infliximab (IFX) or adalimumab. Few reports on GLM in pediatric patients with ulcerative colitis (UC) are available. This study aimed to review the long-term durability and safety of GLM in a pediatric center. Methods: The medical records of 17 pediatric patients (eight boys and nine girls) who received GLM at the National Center for Child Health and Development were retrospectively reviewed. Results: The median age at GLM initiation was 13.9 (interquartile range 12.0-16.3) years. Fourteen patients had pancolitis, and 11 had severe disease (pediatric ulcerative colitis activity index ≥65). Ten patients were biologic-naive, and 50% achieved corticosteroid-free remission at week 54. Two patients discontinued prior anti-TNF-α agents because of adverse events during remission. Both showed responses to GLM without unfavorable events through week 54. However, the efficacy of GLM in patients who showed primary nonresponse or loss of response to IFX was limited. Four of the five patients showed non-response at week 54. Patients with severe disease had significantly lower corticosteroid-free remission rate at week 54 than those without severe disease. No severe adverse events were observed during the study period. Conclusion: GLM appears to be safe and useful for pediatric patients with UC. Patients with mild to moderate disease who responded to but had some adverse events with prior biologics may be good candidates for GLM. Its safety and low immunogenicity profile serve as favorable options for selected children with UC.

Real-world Nationwide Outcomes of Minimally Invasive Surgery for Advanced Gastric Cancer Based on Korean Gastric Cancer Association-Led Survey

  • Sin Hye Park;Mira Han;Hong Man Yoon;Keun Won Ryu;Young-Woo Kim;Bang Wool Eom;The Information Committee of the Korean Gastric Cancer Association
    • Journal of Gastric Cancer
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    • v.24 no.2
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    • pp.210-219
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    • 2024
  • Purpose: The study aimed to investigate real-world surgical outcomes of minimally invasive surgery (MIS) for advanced gastric cancer using Korean Gastric Cancer Association (KGCA)-led nationwide data. Materials and Methods: A nationwide survey of patients who underwent surgical treatment for gastric cancer in 2019 was conducted by the KGCA. A total of 14,076 patients from 68 institutions underwent surgery, and 4,953 patients diagnosed with pathological stages IB-III gastric cancer were included. Among them, 1,689 patients who underwent MIS (MIS group) and 1,689 who underwent the open approach (open group) were matched using propensity score in a 1:1 ratio. Surgical outcomes were compared, and multivariate analysis was performed to identify the independent factors for overall morbidity. Results: The MIS group had a lower proportion of D2 lymphadenectomy, total omentectomy, and combined resection. However, the number of harvested lymph nodes was higher in the MIS group. Better surgical outcomes, including less blood loss and shorter hospital stay, were observed in the MIS group, and the overall morbidity rate was significantly lower in the MIS group (17.5% vs. 21.9%, P=0.001). The mortality rates did not differ significantly between the 2 groups. In the multivariate analysis, the minimally invasive approach was a significant protective factor against overall morbidity (odds ratio, 0.799; P=0.006). Conclusions: Based on the Korean nationwide data, MIS for stage IB-III gastric cancer had better short-term outcomes than the open approach, including lower rates of wound complications, intra-abdominal abscesses, and cardiac problems.

Prediction of Loss of Life in Downstream due to Dam Break Flood (댐 붕괴 홍수로 인한 하류부 인명피해 예측)

  • Lee, Jae Young;Lee, Jong Seok;Kim, Ki Young
    • Journal of Korea Water Resources Association
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    • v.47 no.10
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    • pp.879-889
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    • 2014
  • In this study, to estimate loss of life considered flood characteristics using the relationship derived from analysis of historical dam break cases and the factors determining loss of life, the loss of life module applying in LIFESim and loss of life estimation by means of a mortality function were suggested and applicability for domestic dam watershed was examined. The flood characteristics, such as water depth, flow velocity and arrival time were simulated by FLDWAV model and flood risk area were predicted by using inundation depth. Based on this, the effects of warning, evacuation and shelter were considered to estimate the number of people exposed to the flood. In order to estimate fatality rates based on the exposed population, flood hazard zone is assigned to three different zones. Then, total fatality numbers were predicted after determining lethality or mortality function for each zone. In the future, the prediction of loss of life due to dam break floods will quantitatively evaluate flood risk and employ to establish flood mitigation measures at downstream applying probabilistic flood scenarios.

A fundamental study on the installation methods of automatic identification buoy on coastal gill net (연안자망 부이에 어구자동식별 장치 설치방안에 관한 기초적 연구)

  • HEO, Nam-Hee;KANG, Kyoung-Bum;KOO, Myeong-Seong;KIM, Keun-Hyong;KIM, Jong-Bum;JWA, Min-Seok;KIM, Jun-Teck;JOUNG, Joo-Myeong;KIM, Byung-Yeob;KIM, Suk-Jong
    • Journal of the Korean Society of Fisheries and Ocean Technology
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    • v.55 no.4
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    • pp.294-302
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    • 2019
  • As a series of fundamental researches on the development of an automatic identification monitoring system for fishing gear. Firstly, the study on the installation method of automated identification buoy for the coastal improvement net fishing net with many loss problems on the west coast was carried out. Secondly, the study was conducted find out how to install an automatic identification buoy for coastal gill net which has the highest loss rate among the fisheries. GPS for fishing was used six times in the coastal waters around Seogwipo city in Jeju Island to determine the developmental status and underwater behavior to conduct a field survey. Next, a questionnaire was administered in parallel on the type of loss and the quantity and location of fishing gear to be developed and the water transmitter. In the field experiment, the data collection was possible from a minimum of 13 hours, ten minutes to a maximum of 20 hours and ten minutes using GPS, identifying the development status and underwater behavior of the coastal gillnet fishing gear. The result of the survey showed that the loss of coastal net fishing gear was in the following order: net (27.3%), full fishing gear (24.2%), buoys, and anchors (18.2%). The causes were active algae (50.0%), fish catches (33.3%) and natural disasters (12.5%). To solve this problem, the installation method is to attach one and two electronic buoys to top of each end of the fishing gear, and one underwater transmitter at both ends of the float line connected to the anchor. By identifying and managing abnormal conditions such as damage or loss of fishing gear due to external factors such as potent algae and cutting of fishing gear, loss of fishing gear can be reduced. If the lost fishing gear is found, it will be efficiently collected.