Afatinib 표적항암치료를 시행 중인 흉막 전이된 비소세포폐암 환자의 한방치료 증례보고

김균하,강희경,김소연,한창우,박성하,윤영주,이인,권정남,홍진우,최준용 대한한방내과학회 2020 大韓韓方內科學會誌 Vol.41 No.6

Objective: The purpose of this study was to report the effect of Korean medicine on a patient with non-small cell lung cancer with pleural metastasis who had been treated with afatinib. Method: A 61-year old female patient with non-small cell lung cancer with pleural metastasis was treated with acupuncture and herbal medicines, including Yijung-tang, Haengso-tang, Samchulkunbi-tang, Paeamju-bang (Feiai zhu fang), to control various symptoms caused by afatinib. The degree of pain was assessed by a numeric rating scale (NRS) and the quality of life was determined with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) and the EORTC 13-item lung cancer-specific module (EORTC LC-13). Results: After receiving acupuncture and herbal medicines, the patient showed improvement in her back and chest pain, according to the NRS score. Similarly, the Korean medicinal treatments significantly relieved her nausea, vomiting, diarrhea, hemoptysis, and alopecia. However, the EORTC QLQ-C30 assessment suggested that Korean medicinal treatments did not significantly improve the global health status of this patient. Conclusion: Korean medicine could be useful in relieving some of the symptoms occurring after conventional afatinib treatments.

편평상피세포 폐암 환자의 항암화학요법에 의해 유발된 말초신경병증에 대한 한방치험 1례

김균하,김민화,허기윤,이찬,조임학,강희경,김소연,박성하,윤영주,이인,한창우,홍진우,권정남,최준용,Kim, Kyun Ha,Kim, Min-hwa,Heo, Gi-yoon,Lee, Chan,Cho, Im-hak,Kang, Hee-kyung,Kim, So-yeon,Park, Seong-ha,Yun, Young-ju,Lee, In,Han, Chang-woo,Hong 대한한방내과학회 2021 大韓韓方內科學會誌 Vol.42 No.6

The purpose of this study is to report the effect of Korean medicine on a squamous cell lung cancer patient with chemotherapy induction peripheral neuropathy (CIPN). A 61-year old male patient, who had received 4 cycles of chemotherapy after lung surgery from squamous cell lung cancer, was treated with acupuncture and herbal medicines, including Uchasingi-hwan and Samchilchoongcho-capsule, to control CIPN and dyspnea on exertion. The degree of pain was assessed by a numeric rating scale (NRS). After receiving acupuncture and herbal medicines, the NRS score for CIPN symptoms was reduced from 4 to 1 and the NRS score for dyspnea on exertion decreased from 3 to less than 1. Korean medicine could therefore be useful in reducing peripheral neuropathy occurring after chemotherapy and dyspnea after lobectomy.

기업의 위기 커뮤니케이션 전략: 위기 유형과 사과 메시지

김균하,이경탁 경남대학교 산업경영연구소 2020 지역산업연구 Vol.43 No.2

The purpose of this study is to examine the attitudes of the prisoners to the corporateapology message. Many companies face many difficulties because they do not find an effectiveresponse when faced with a crisis. Therefore, this study is to investigate the effective apologymessage according to the crisis type of the company and the adjustment focusing tendency of theaudience. In this study, the experiment design between message appeal, corporate crisis type, andcontrol focus was conducted. A total of 218 students were participated in this study. They wererandomly assigned to one of four conditions in a 2(message type: rational vs. emotional) × 2(crisistype: CA vs. CSR) experimental design. To test proposed hypothesis, we ran an ANOVA and t-testanalysis. As a result of the hypothesis analysis, there was an interaction effect between the apologymessage type and the corporate crisis type(F=13.63, p<.001). As predicted by the hypothesis, theresearch results show the interaction effect between the apology message type and the crisis type. Reasonable messages formed a more positive attitude in subjects exposed to the CA type(M=4.06)than those exposed to the CSR type(M=2.67). Therefore, Hypothesis 1 was supported. However, inthe emotional message, there was no significant difference between the CSR type and the CA type,so Hypothesis 2 was rejected. 본 연구의 목적은 기업의 위기 유형에 따른 사과 메시지의 효과를 알아보기 위한 것이다. 많은 기업들이 위기 상황에 직면하였을 때 효과적인 대응 방안을 찾지 못하여 많은 어려움을 경험한다. 이에 본 연구에서는 기업의 위기 유형과 수용자들의 조절초점 성향에 따른 효과적인 사과메시지가 무엇인지 조사하고자 한다. 본 연구에서는 메시지 소구, 기업 위기 유형, 조절초점 간의 실험설계를 실시하였다. 218명의 학생들이 본 실험에 참여하였다. 그들은 무작위로 사과 메시지 유형(이성적 vs 감성적) × 위기 유형(CA vs CSR)의 4개 조건 중 1개 조건에 할당되었다. 제안된 가설을 검증하기 위하여 분산분석, t-test등의 통계적 기법을 이용하였다. 가설 검증 결과를 살펴보면 사과 메시지 유형과 기업 위기 유형 간의 상호작용 효과가 있는 것으로 나타났다. 가설에서 예측한 것과 동일하게 사과 메시지 유형과 기업 유형 간의 상호작용효과를 보여주고있다(F=13.63, p<.001). 구체적으로 살펴보면, 이성적 메시지는 CSR 유형에 노출된 대상(M=2.67)보다 CA 유형에 노출된 대상(M=4.06)에서 더욱 긍정적인 태도를 형성하였다(t=5.03,p<.001). 따라서 가설 1은 지지되었다. 그러나 감성적 메시지에서는 CSR 유형과 CA 유형 간에는유의적인 차이가 없는 것으로 나타나서 가설 2는 기각되었다.

Tumor necrosis factor α - induced protein3의 발현과 NF-κB 활성 억제를 통한 동과자의 염증반응 억제 효과

김균하,최준용,주명수 한의병리학회 2021 동의생리병리학회지 Vol.35 No.1

Donggwaja (Benincasae Semen), the seed of Benincasa hispida (Thunb.) Cogn., has been used in Korean traditional medicine to control the body heat and water retention caused by various diseases. Both the symptoms targeted by the herbal medicine in clinic and studies with disease mouse models support the potential anti-inflammatory effect of Donggwaja. However, it is less understood how Donggwaja exerts its possible anti-inflammatory effect. Here, we present evidence that Donggwaja suppresses macrophage inflammatory reactions via expressing tumor necrosis factor a-induced protein 3 (TNFAIP3 or A20) and suppressing NF-kB activity. The ethanol extract of Donggwaja (EED) showed no toxicity when added to RAW 264.7 cells less than 100mg/ml. When treating the cells for 16 h, EED significantly suppressed the nuclear localization of NF-kB, suggesting that EED suppresses NF-kB activity. Concordantly, a semi-quantitative RT-PCR analysis showed that EED decreased the expression of prototypic pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-a, IL(interleukin)-6, and IL-1b. EED induced in RAW 264.7 cells the expression of A20, a ubiquitin modulator that suppresses inflammatory signaling cascades initiated from TLR4 and TNF and IL-1 receptors, while not affecting the induction of Nrf2, an anti-inflammatory factor that could suppress the effect of NF-kB. These results suggest that EED exerts its suppressive effect on inflammation, at least in part, by expressing anti-inflammatory factor A20 and suppressing pro-inflammatory factor NF-kB activity.

추출용매 변화에 따른 바나바(Lagerstroemia speciosa Pers.) 잎 추출물의 항당뇨 효과

김균하(Kyun Ha Kim),노상근(Sang Geun Roh),이춘일(Chun-Ri Li),김춘봉(Chun-Feng Jin),김안드레(Andre Kim),최원철(Won Chill Choi) 한국생명과학회 2008 생명과학회지 Vol.18 No.9

본 연구는 바나바 잎 추출 용매에 따른 항당뇨 효과에 관한 것으로 세포 독성 실험을 통하여 인체에 대한 독성이 없음을 확인하였고 β-cell 인슐린 분비 실험을 통하여 항당뇨 효과를 알아보았다. 또한 당뇨 유발쥐를 이용한 인슐린 분비 실험, 체중변화 측정, 혈중 및 혈청의 glucose 농도, 총콜레스테롤 수치, HDL-cholesterol 농도, triglyceride 농도, free fatty acid 농도, langerhans islet에서의 인슐린 분비의 확인을 통해 혈당조절 효과를 비교하였다. 물 혹은 에탄올을 단독으로 이용하여 추출한 추출물이나 70%, 90% 에탄올로 추출한 추출물 보다 열수로 먼저 추출한 후 에탄올로 다시 추출하여 혼합안 추출물이 항당뇨 효과가 더 뛰어남을 알 수 있었다. 이는 친수성(hydrophilic) 유효성분들과 소수성(hydrophobic) 유효성분들의 추출 유무나 함량에 의한 것이다. 특히, 많은 문헌에 언급된 코로소린산이라는 단일 성분(unique)에 의한 항당뇨 효과라기보다는 친수성 및 소수성 폴리페놀 및 항산화성분과 같은 유효성분들이 조합되어(mixture) 항당뇨 효과에 영향을 미치는 것으로 사료된다. This study investigated that the antidiabetic effects of banaba extracts with variety solvents selectivity in vitro and in vivo. Banaba extracts were prepared with water, 70% ethanol, 90% ethanol, 100% ethanol and water-ethanol that of extract twice times sequentially water and ethanol. Cell toxicity and insulin secretion of banaba extracts was tested by MTT (3-[4,5-dimetylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay on hamster insulinoma cell line, HIT-T15. Also we tested that insulin, body weight, blood glucose, total cholesterol, HDL-cholesterol, triglyceride and free fatty acid in streptozotocin diabetic rats. Water-ethanol extract has remarkable antidiabetic effect compare with the other banaba extracts. For water-ethanol extract has both of hydrophilic and hydrophobic antidiabetic materials from banaba. Expecially, corosolic acid, as known as unique polyphenol, has antidiabetic effect studied by many researchers till nowadays. But corosolic acid does not solve in water. Otherwise, we suggest that banaba extract of hydrophilic and hydrophobic materials (polyphenol and antioxidants) mixture more increased antidiabetic effects.

Inhibition of Apoptosis by Nitric Oxide in MCF-7 Cells

Kyun Ha Kim(김균하),Sang Geun Roh(노상근),Hae-Ryun Park(박혜원),Won Chul Choi(최원철) 한국생명과학회 2009 생명과학회지 Vol.19 No.2

Nitric oxide (NO)는 세포 안의 다양한 생리학적, 병리학적 조건에서 확산, 세포 간 messenger와 같은 다양한 기능이 있으며, NO는 암세포나 macrophage 등과 같은 세포에서는 apoptosis를 유도하고, 정상세포나 내피 세포에서는 apoptosis를 억제한다고 보고되어져 있다. NO가 유방암 세포주인 MCF-7 세포에서는 apoptosis를 유도하는지 확인하기 위해 NO donor인 SIN-1을 처리하였다. SIN-1은 48시간 처리 시에도 세포 생존율에 영향을 주지 않았고, 세포주기나 성장 패턴에도 아무런 변화를 주지 않았다. 그러나 p53의 발현은 SIN-1 처리 시간에 따라 증가하였고, bcl-2, MDM2, p21의 발현도 함께 증가하였다. Bax의 발현은 SIN-1 처리 시에 변화가 없었다. MCF-7 세포에서 NO에 의한 apoptosis 억제를 보기 위하여, SIN-1을 선처리한 세포에 CoCl₂를 처리하였다. 세포에 CoCl₂ 만을 처리한 군에서는 확연한 apoptosis를 나타내었지만, SIN-1을 24 시간 선처리한 세포에서는 apoptosis를 관찰할 수 없었다. Cobalt Chloride에 의해 감소되었던 p53, MDM2, bcl-2 발현 역시 SIN-1을 24시간 선처리한 세포에서 증가하였다. 이런 결과들은 SIN-1에 의해 발현된 MDM2가 p53의 기능을 막으며, 또한 p21과 bcl-2의 발현이 유도되어 apoptosis를 억제함을 제시한다. Nitric oxide (NO) is a diffusible, multifunctional and transcellular messenger that has been implicated in numerous physiological and pathological conditions. It has been reported that NO induced apoptosis in tumor cells, macrophage cells and inhibited apoptosis in normal cells, endothelial cells. To examine whether NO could induce apoptosis in MCF-7 cells, cells were treated with SIN-1 (3-morpholinosydnonimine), NO donor. Cell viability did not change in SIN-1 treated cells for 48 h and there was no significantly changes in cell cycle progression or growth pattern by FACS analysis. But p53 protein, an apoptosis-related factor, increased SIN-1 treatment time dependently. Bcl-2, MDM2 and p21 were also accumulated. Bax level did not change. A major role of inhibiting apoptosis by NO in MCF-7 cells, cobalt chloride (CoCl₂) was added to cells preincubated with SIN-1. Whereas CoCl₂ treated cells underwent apoptosis, for 24 h SIN-1 preincubated cells were not induced apoptosis. Inactivated proteins, MDM2 and bcl-2, by CoCl₂ levels also increased in SIN-1 pre-treated cells. These results suggested that SIN-1 blocked p53 by MDM2 activation and inhibited apoptosis by inducing p21 and bcl-2 expression.

신화학물질 HS-1580 유도체(HS-1580 HS-1581 HS-1582)의 항염증 효과

김지영,김균하,서홍석,최원철,Kim, Ji-Young,Kim, Kyun-Ha,Suh, Hong-Suk,Choi, Won-Chul Korean Society of Life Science 2006 생명과학회지 Vol.16 No.7

본 연구는 염증 형성과정에 있어서, 해조류로부터 항염증 효과를 나타내는 물질을 분리하여 그 유도체인 HS-1580 series (HS-1580, HS-1581, HS-1582)를 합성하였다. Nitiric oxide (NO) 생성에 있어 Raw 264.7 cells에서 lipopolysaccharide(LPS) 단독으로 처리하였을 때는 대조군에서보다 4배 이상 NO 생성이 증가하였지만, HS-1580 series를 처리하고 LPS를 처리한 군에서는 농도 의존적으로 NO 생성이 억제되었다. HS-1580 series가 NO 생성 자체를 억제함으로서 NO 함량이 감소되었는지, inducible NOS (iNOS) 단백질 발현을 억제에 기인한 것인지 알아보기 위해서 Western blot으로 조사하였다. iNOS protein 발현이 HS-1580 series에 의해서 억제되었고 HS-1580 series가 cyclooxygenase-2 (COX-2), tumor necrosis factor-a $TNF-{\alpha}$ 와 $interluekin-1{\beta}\;(IL-1{\beta})$ 생성을 농도 의존적으로 억제시켰다. 이상의 결과로 HS-1580 series가 iNOS 단백질 발현 억제에 기인한 NO 생성억제, COX-2 발현 억제 및 pro-inflammatory cytokines인 $TNF-{\alpha}$ 와 $IL-1{\beta}$ 생성을 억제하는 항염증 효과를 가짐을 알 수 있다. HS-1580 series (HS-1580, HS-1581, HS-1582) can produce anti-imflammatory effects were synthesized from the marine algae extraction in 2,3,6-tribromo-4,5-dihydroxy benzyl methyl ether (TDB). Raw 264.7 cells were pre-treated with $1{\mu}g/{\mu}l$ lipopolysaccharide (LPS) and later treated with HS-1580 series. These cells of inflammatory mediators were tested as well. Nitric oxide (NO) is related to autoimmune disease and is produced by inducible NOS (iNOS). When treated with HS-1580 series, the product of NO will reduce in a dose-dependent manner. HS-1580 series significantly inhibit the iNOS protein expression. Cyclooxygenase (COX) involves with the various physiologic events and catalyzes in prostaglandin. HS-1580 series also inhibit the COX-2 protein expression as well as pro-inflammatory cytokines production such as tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})\;and\;interluekin-1{\alpha]\;(IL-1{\beta})$. These upcoming results suggest that HS-1580 series have anti-inflammatory efforts in Raw 264.7 cells by inhibiting such as iNOS, COX-2, $TNF-{\alpha}\;and\;IL-1{\beta}$ as inflammatory mediators.

Field Programmable Gate Array(FPGA) 기반 해상도와 정확도 향상을 위한 Side by side 탭-딜레이 방식의 시간-디지털 변환기

이다원(Dawon Lee),김균하(Gyunha Kim),임한상(Hansang Lim) 대한전자공학회 2017 전자공학회논문지 Vol.54 No.9

Field-Programmable Gate Array (FPGA)기반 탭-딜레이 방식의 시간-디지털 변환기에서 해상도는 FPGA 내부 지연소자의 지연시간에 의존하여 해상도를 향상시키는데 한계가 있다. 또한 각 지연소자의 단위 지연시간(bin width)의 불균일성 때문에 정확도가 저하되는 문제점이 있다. 따라서 두 개의 캐리체인을 단위 지연시간의 절반만큼의 차이를 두고 나란히 배치하여 각각의 출력을 모두 사용하여 해상도를 향상시키는 방법을 제안한다. 제안한 방법은 두 개의 캐리체인상의 효과적인 bin 재배치를 통해 ultra wide bin 및 narrow bin의 사용을 제한할 수 있어서 정확도 향상에도 기여한다. 이 방식은 내부 캐리체인 자원을 두 배로 사용해야 한다는 문제점이 있지만 파인 입력부에서 클럭의 up edge와 down edge 중 측정범위를 줄일 수 있는 edge를 선택하게 하여 파인부의 측정 범위를 클럭의 반주기로 줄임으로써 해결한다. 제안한 시간-디지털 변환기의 성능 측정결과 해상도는 13.02ps에서 8.802ps로 향상되었고, INL(Integral Nonlinearity)은 기존 -27.979~19.283ps에서 -11.557~16.274ps로, DNL(Differential Nonlinearity)은 -7.981~29.022ps에서 -5.879~13.123ps로 향상되었다. In a field-programmable gate array (FPGA)-based tapped-delay-line time-to-digital converter, the delay time of the delay element integrated in the FPGA sets the resolution limit and non-uniformity of the delay time decreases the accuracy. In order to improve the timing resolution in a given FPGA, this study proposes a dual-tapped-delay-type time-to-digital converter (TDC), in which two carry chains are arranged side by side with a finely controlled time difference. By employing effective bin arrangement of the two carry chains, ultra wide or narrow bins are excluded, which improves the measurement accuracy. The selection of the reference clock edge between the up and down edges reduces the required length of carry chains and, consequently, compensates for increase in the consumption of FPGA resources due to the application of dual carry chains. The average resolution of the proposed TDC was improved from 13.02ps to 8.802ps and the integral non-linearity (INL) and diff erential non-linearity (DNL) were improved from -27.979~19.283ps to -11.557~16.274ps and from -7.981~29.022ps to -5.879~13.123ps, respectively.

동과자 에탄올 추출물이 비알코올성 지방간 세포 모델에 미치는 효과

최준용,김소연,권민정,김균하,주명수,한창우,Choi, Jun-Young,Kim, So-Yeon,Kwun, Min-Jung,Kim, Kyun-Ha,Joo, Myung-Soo,Han, Chang-Woo 대한한방내과학회 2012 大韓韓方內科學會誌 Vol.33 No.4

Objectives : In this study, we investigated the effect and the underlying mechanism of ethanol extract of Benincasa seeds on a cellular model of non-alcoholic fatty liver disease (NAFLD) established by treating HepG2 cells with palmitate. Methods : We evaluated ethanol extract of Benincasa seeds (EEBS) for its hepatic lipid-lowering potential in fatty acid overloaded HepG2 cells. After incubation in palmitate containing media with or without EEBS, intracellular neutral lipid accumulations were quantified by Nile red staining. We also investigated the effect of EEBS on lipogenesis and ${\beta}$-oxidation. $LXR{\alpha}$-dependent SREBP-1c activation, expression of lipogenic genes, and expression of ${\beta}$-oxidation related genes were determined with or without pretreatment of EEBS. Results : EEBS significantly attenuated palmitate-induced intracellular neutral lipid accumulation in HepG2 cells. EEBS suppressed fatty acid synthesis by inhibiting $LXR{\alpha}$-dependent SREBP-1c activation. EEBS also repressed SREBP-1c mediated induction of lipogenic genes, including ACC, FAS, and SCD-1. However, EEBS had no effect on ${\beta}$-oxidation related CPT-1 and $PPAR{\alpha}$ gene expression. Conclusions : Our results suggest that EEBS has an efficacy to decrease hepatic lipid accumulation, and this effect was mediated by inhibiting the $LXR{\alpha}$-SREBP-1c pathway that leads to expression of lipogenic genes and hepatic steatosis. Therefore, the Benincasa seeds may have a potential clinical application for treatment of this chronic liver disease.

조협의 부위에 따른 항산화 전사인자 Nrf2 활성 효과

최지연(Jiyeon Choi),김균하(Kyun Ha Kim),최준용(Jun Yong Choi),한창우(Chang Woo Han),하기태(Ki Tae Ha),정한솔(Han-Sol Jeong),주명수(Myungsoo Joo) 한의병리학회 2014 동의생리병리학회지 Vol.28 No.3