Original Articles : Effect of aldosterone on the amplification of oncolytic vaccinia virus in human cancer Lines

( Hyun Ju Lee ),( Ja Sung Rho ),( Shao Ran Gui ),( Mi Kyung Kim ),( Yu Kyoung Lee ),( Yeon Sook Lee ),( Jeong Eun Kim ),( Eu Na Cho ),( Mong Cho ),( Tae Ho Hwang ) 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.3

Background/Aims: JX-594 is an oncolytic virus derived from the Wyeth vaccinia strain that causes replication-dependent cytolysis and antitumor immunity. Starting with a cross-examination of clinical-trial samples from advanced hepatocellular carcinoma patients having high levels of aldosterone and virus amplification in JX-594 treatment, we investigated the association between virus amplification and aldosterone in human cancer cell lines. Methods: Cell proliferation was determined by a cell-counting-kit-based colorimetric assay, and vaccinia virus quantitation was performed by quantitative polymerase chain reaction (qPCR) and a viral plaque assay. Also, the intracellular pH was measured using a pH-sensitive dye. Results: Simultaneous treatment with JX-594 and aldosterone significantly increased viral replication in A2780, PC-3, and HepG2 cell lines, but not in U2OS cell lines. Furthermore, the aldosterone treatment time altered the JX-594 replication according to the cell line. The JX-594 replication peaked after 48 and 24 hours of treatment in PC-3 and HepG2 cells, respectively. qPCR showed that JX-594 entry across the plasma membrane was increased, however, the changes are not significant by the treatment. This was inhibited by treatment with spironolactone (an aldosterone-receptor inhibitor). JX-594 entry was significantly decreased by treatment with EIPA [5-(N-ethyl-N-isopropyl)amiloride; a Na+/H+-exchange inhibitor], but aldosterone significantly restored JX-594 entry even in the presence of EIPA. Intracellular alkalization was observed after aldosterone treatment but was acidified by EIPA treatment. Conclusions: Aldosterone stimulates JX-594 amplification via increased virus entry by affecting the H+ gradient. (Korean J Hepatol 2011;17:213-219)

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Gefitinib circumvents hypoxia-induced drug resistance by the modulation of HIF-1alpha.

Rho, Jin Kyung,Choi, Yun Jung,Lee, Jin Kyung,Ryoo, Baek-Yeol,Na, Im Ii,Yang, Sung Hyun,Kim, Cheol Hyeon,Yoo, Young Do,Lee, Jae Cheol National Hellenic Research Foundation 2009 ONCOLOGY REPORTS Vol.21 No.3

<P>Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcriptional factor which is activated by hypoxia and associated with cell survival, proliferation and drug resistance. Recent studies have shown that the down-stream molecules of the epidermal growth factor receptor (EGFR) signal are involved in the hypoxia-dependent or -independent HIF-1alpha protein accumulation. Thus, we hypothesized that an EGFR-TK inhibitor, gefitinib, might circumvent the hypoxia-induced drug resistance via the regulation of HIF-1alpha expression. In our data, treatment of gefitinib suppressed induced HIF-1alpha by hypoxia. This action of gefitinib was caused by reduced protein stability without any change in the level of HIF-1alpha mRNA. The effect of gefitinib on down-regulation of HIF-1alpha was reversed by transfection of constitutively active form of Akt. The cellular response to gefitinib was similar in both normoxia and hypoxia condition. However, the response to conventional chemotherapeutic drugs decreased >50% under hypoxia condition and they did not change HIF-1alpha expression. In addition, the suppression of HIF-1alpha using siRNA overcame partially hypoxia-induced drug resistance. In conclusion, gefitinib was able to circumvent hypoxia-induced drug resistance suggesting that the effective suppression of HIF-1alpha by the inhibition of EGFR-Akt pathway may overcome the hypoxia-induced drug resistance.</P>

The role of MET activation in determining the sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors.

Rho, Jin Kyung,Choi, Yun Jung,Lee, Jin Kyung,Ryoo, Baek-Yeol,Na, Im Il,Yang, Sung Hyun,Lee, Seung Sook,Kim, Cheol Hyeon,Yoo, Young Do,Lee, Jae Cheol American Association for Cancer Research 2009 Molecular Cancer Research Vol.7 No.10

<P>The development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) seems almost inevitable, even in patients with lung cancer that initially respond well to EGFR-TKIs. MET amplification was recently found to be a mechanism of escape from the anticancer effect of EGFR inhibitors. In the present study, we investigated the means whereby MET affects sensitivity to EGFR-TKIs in PC-9 cells. Gefitinib- or erlotinib-resistant sublines were established by exposing the parental PC-9 cell line to chronic, repeated treatments with these drugs. These resistant sublines showed more than 100-fold more resistance to gefitinib and erlotinib and acquired cross-resistance to other EGFR-TKIs. The T790M EGFR mutation was found by pyrosequencing, and this seemed to be the cause of drug resistance. Resistant cells also showed MET activation, although gene amplification was not detected. Furthermore, the induction of MET activity was not found to be associated with sensitivity to EGFR-TKIs. Interestingly, increased passage number without exposure to gefitinib or erlotinib caused MET activation, but this did not affect sensitivity to EGFR-TKIs. In addition, hepatocyte growth factor was found to block the ability of EGFR-TKIs to inhibit MET activation. However, sustained MET activation by hepatocyte growth factor did not modulate the cellular effects of gefitinib or erlotinib. Rather, activated MET enhanced migration and invasion abilities. Summarizing, MET activation may be acquired during cancer cell proliferation and enhances migratory and invasive abilities without affecting cellular sensitivity to EGFR-TKIs. Accordingly, the present study suggests that MET activation caused by factors other than MET gene amplification is not a suitable surrogate marker of resistance to EGFR-TKIs.</P>

LVDC 선로용 4kW급 사고구간 분리용 보호장치의 설계 및 구현

이나경(Na-Kyung Lee),한병길(Byeong-Gill Han),김지명(Ji-Myung Kim),김경화(Kyung-Hwa Kim),노대석(Dae-Seok Rho) 한국산학기술학회 2023 한국산학기술학회논문지 Vol.24 No.4

소규모 DC 배전계통에서 사고가 발생할 경우, 기존 AC 배전계통에 비해 사고전류가 매우 가파르게 상승하게 되어, 메인컨버터가 내장된 소자를 보호하기 위하여 탈락하여 수용가에 정전을 유발시킬 가능성이 있다. 따라서, 본 논문에서는 LVDC 배전계통에서 사고에 의한 메인컨버터의 탈락을 방지하기 위하여, 사고전류를 제한시킬 수 있는 LVDC선로용 4kW급 사고구간 분리용 보호장치를 구현한다. 이 장치는 반도체 스위치와 게이트 드라이브, 전류제한 저항, 전압 및 전류센서로 구성된 H/W부와 TM320F28335를 기반으로 한 S/W부 등으로 구성되며, 동작 메커니즘은 초기 동작모드, 보조 동작모드, 주 동작모드, 회복 동작모드의 4가지 모드로 운용된다. 여기서, H/W부는 IGBT(insulated gate bipolar transistor)와 전류제한 저항, 센서 등을 이용하여 주 통전부와 전류 제한부를 구성하고, S/W부는 CCS(code compose studio) 프로그램과 DSP(digital signal processor), A/D(analog/digital) 변환기 등을 이용하여 스위치의 제어를 수행한다. 상기에서 제시한 사고구간 분리용 보호장치의 동작 특성을 분석한 결과, 350V DC 계통에서 사고가 발생한 경우 사고구간 분리용 보호장치가 55.2~72.5[μs] 이내로 사고전류를 신속하게 제한하여 사고구간을 분리할 수 있는 시간을 확보할 수 있고, 이를 통하여 메인컨버터의 탈락을 방지하여 LVDC 배전계통의 정전을 최소화시킬 수 있음을 알 수 있다. When a fault occurs in an LVDC distribution system, the fault region may be extended due to shutdown of the main converter to protect internal devices. Therefore, this paper presents a 4-kW scaled-protection device for isolating a fault section to limit the fault current and prevent this shutdown. The proposed device is composed of a hardware system and a software system and has four operation modes: initial mode, auxiliary mode, main mode, and restoration mode. The hardware system is composed of a main path, current limit path using an IGBT, current limit resistor, sensors, etc. The software system performs monitoring and controlling of the switches using a code composition studio (CCS) program, DSP, A/D converter, etc. From the test results based on 4-kW 350-V DC distribution, it was confirmed that the proposed protection device for isolating a fault section can limit the fault current within 55.2-72.5 [μs] of the reference value in the LVDC distribution system and ensures isolation time for the fault section. Therefore, it is clear that the proposed device could be a useful tool to isolate a fault section by preventing shutdown of the main converter and minimizing a fault region in an LVDC distribution system.

독립형 마을단위 마이크로그리드의 보호협조 운용방안에 관한 연구

이나경(Na-Kyung Lee),곽충근(Chung-Guen Kwak),김세진(Se-Jin Kim),노성은(Seong-Eun Rho),노대석(Dae-Seok Rho) 대한전기학회 2023 대한전기학회 학술대회 논문집 Vol.2023 No.10-2

계통연계형 마을단위 마이크로그리드의 보호협조 운용방안에 관한 연구

이나경(Na-Kyung Lee),김지명(Ji-Myung Kim),김경화(Kyung-Hwa Kim),김윤호(Yun-Ho Kim),이일무(Il-Moo Lee),노대석(Dae-Seok Rho) 한국산학기술학회 2024 한국산학기술학회논문지 Vol.25 No.1

Micro-grid research is being performed due to installation of renewable energy sources and ESSs, and demonstration projects on a community micro-grid for the self-energy supply rate are being carried out in Jeollanam-do province in South Korea. A community micro-grid may be operated as a type of grid-connected micro-grid when the self-energy supply rate is 50%. An operation method for protection devices is required because the magnitude and direction of the fault current may be changed depending on the location and type of the fault. Therefore, this paper proposes an operation algorithm for protection devices that considers the location and type of the fault in order to properly perform protection coordination in grid-connected micro-grid. We modeled a grid-connected micro-grid, which was composed of an ESS, PV system, and geothermal plant, and we used PSCAD/EMTDC S/W in order to analyze the fault current characteristics in the case of a short circuit and single-line ground faults. The simulation results confirmed that the proposed algorithm is useful to operate protection devices in a grid-connected micro-grid because the coordination time intervals were properly obtained.

Gene expression profiling from insulin-sensitive tissues of ZDF rats, animal model for T2DM after anti-diabetic drug treatment

Yo Na Kim,Il Yong Kim,Kyung Jin Rho,Sae Jin Oh,Sun Sin Yi,Yu Hee Lee,Kyung Sup Kim,Je-Kyung Seong 한국실험동물학회 2007 한국실험동물학회 학술발표대회 논문집 Vol.2007 No.-

p53 Enhances Gefitinib-Induced Growth Inhibition and Apoptosis by Regulation of Fas in Non-Small Cell Lung Cancer

Rho, Jin Kyung,Choi, Yun Jung,Ryoo, Baek-Yeol,Na, Im II,Yang, Sung Hyun,Kim, Cheol Hyeon,Lee, Jae Cheol American Association for Cancer Research 2007 Cancer research Vol.67 No.3

<P>Treatment with gefitinib, a specific inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), has resulted in dramatic responses in some patients with non-small cell lung cancer (NSCLC). Most patients who respond to gefitinib have EGFR-TK mutations; however, >10% of patients with EGFR-TK mutations do not respond. Similarly, some patients without EGFR-TK mutations respond to this drug, suggesting that other factors determine sensitivity to gefitinib. Aberrations of the tumor suppressor gene p53 are frequently associated with drug resistance. In this study, we investigated the role of p53 in growth-inhibitory and apoptotic effects of gefitinib in the human NSCLC cell lines NCI-H1299 and A549, which have no EGFR-TK mutations. NCI-H1299 cells, which had a p53-null genotype, were more resistant to gefitinib compared with A549 cells, which were wild-type p53 (IC(50), 40 micromol/L in NCI-H1299 and 5 micromol/L in A549). Treatment of A549 with gefitinib resulted in the translocation of p53 from cytosol to nucleus and the up-regulation of Fas, which was localized to the plasma membrane. In the stable H1299 cell line with tetracycline-inducible p53 expression, induced p53 enhanced growth inhibition and apoptosis by gefitinib through the up-regulation of Fas and restoration of caspase activation. A caspase inhibitor, Z-VAD-fmk, reduced these effects. Conversely, inhibition of p53 using antisense oligonucleotide in A549 caused a significant decrease in apoptosis by gefitinib and down-regulation of Fas under the same conditions. In conclusion, p53 may play a role in determining gefitinib sensitivity by regulating Fas expression in NSCLC.</P>

계통연계형 마을단위 마이크로그리드의 운용 방안에 관한 연구

김경화(Kyung-Hwa Kim),이세연(Se-Yeon Lee),한병길(Byeong-Gill Han),이나경(Na-Kyung Lee),노대석(Dae-Seok Rho) 대한전기학회 2022 대한전기학회 학술대회 논문집 Vol.2022 No.10