A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer

Lee, Hyun Joo,Lee, Woo Kyung,Kang, Chan Woo,Ku, Cheol Ryong,Cho, Yoon Hee,Lee, Eun Jig Elsevier 2018 Cancer letters Vol.417 No.-

<P><B>Abstract</B></P> <P>The RB-E2F1 pathway is an important mechanism of cell-cycle control, and deregulation of this pathway is one of the key factors contributing to tumorigenesis. Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as <I>FOXM1, Cyclin A1,</I> and <I>Myc</I> in ATC. Furthermore, LEE011 induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited cell proliferation in ATC. Consistently, oral administration of LEE011 to ATC xenograft models strongly inhibited tumor growth with decreased expressions of pRB, pAKT and Ki-67, and also significantly increased tumor cell apoptosis. Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> pRB and Cyclin D were expressed high in aggressive thyroid cancer. </LI> <LI> LEE011 suppressed pRB and also decreased the expressions of its target genes in ATC. </LI> <LI> LEE011 induced cell cycle G1 arrest and apoptosis, and inhibited cell proliferation. </LI> <LI> LEE011 inhibited in vivo tumor growth with decreased expressions of pRB and Ki-67. </LI> <LI> We could explain the anticancer effects with the RB-E2F pathway. </LI> </UL> </P>

2003년 국내 중증급성호흡기증후군 진료 현황 및 문제점 분석

이진수,김은실,정문현,백제중,정선화,안주희,최영화,이선희,고철우,김성범,김민자,박승철,기현균,송재훈,최상호,김양수,이상오,조용균,박영훈,정숙인,김연숙,이흥범,손창희,장성희,정희진,김우주 대한감염학회 2004 감염과 화학요법 Vol.36 No.3

목적 : 2002년 말 중국에서 SARS가 발생한 이후 국내에서도 2003년 10월까지 총 3명의 추정환자, 17명의 의심환자가 보고되었다. 향후 추가적인 SARS의 유행이 우려되는 상황에서, 그간의 SARS 환자 진료에 있어서의 실질적인 준비사항, 진료 현황 등에 대한 조사를 통해 문제점을 파악하여, 향후 더 나은 대비가 될 수 있도록 개선점을 제시하고자 하였다. 재료 및 방법 : SARS로 의심되는 환자를 진료 경험이 있는 병원의료진을 대상으로 2003년 10월에 설문조사를 실시하였다. 설문에는 SARS 환자 진료 시의 실질적인 조치, 진료 현황, 병실, 응급실 및 외래에서의 격리 시설과 준비사항, 보건당국의 관리와 지원에 관한 사항을 포함하였다. 결과 : 대상이 되는 22개 병원 중 17개(17/22, 77.2%) 병원이 설문에 응하였다. SARS 환자를 위한 격리실은 응급실, 외래, 일반병실 및 중환자실에서 각각 9개(9/17, 52.9%), 5개(5/17, 29.4%), 15개(15/16, 93.7%), 4개(4/16, 25%) 병원에서 음압처리가 되어있지 않은 일인실 혹은 다인실이 사용되었고, 1개(1/16, 6.3%) 병원에서만 일반병실에서 음압격리실이 운영되었다. 입원환자의 진찰 시 개인보호구의 착용은 거의 모든 의료기관에서 이루어졌다. 보건당국에서 SARS지정병원의 시설 등을 사전에 확인한 곳은 1곳(1/12, 8.3%)이였고, 14개 병원(14/15, 93.3%)에서는 보건당국에 의뢰한 검사결과를 통하 받지 못하였다. 결론 : 의료기관에서 SARS 환자용 격리실뿐만 아니라 기존의 격리실 설비 등이 미흡하였으며, 특히 중환자실 및 외래의 준비가 더욱 부족하였다. 보건당국의 의료기관에 대한 종합적인 지원이 부족하였고, 병원과의 원활한 연계가 잘 이루어지지 않았다. SARS 만이 아닌 격리를 필요로 하는 질환의 적절한 진료를 위해 향후 병원 시설의 정비와 정부차원에서의 보다 구체적이고 실질적인 대책마련이 필요하다. Background : There was an worldwide outbreak of the Severe Acute Respiratory Syndrome (SARS) originated from China in late 2002. During that period three cases of suspected SARS and 17 cases of probable SARS were reported in Korea. With the concerns about the reemergence of SARS-coV transmission, it is important to be prepared for any possibility. So, this study is aimed to analysis the past measures in managing SARS and propose the amendatory plans to improve the preparedness. Materials & Methods : Questionnaires were collected among clinicians with any experience in managing the probable or suspected SARS cases in Oct. 2003. 17 out of 22 hospitals responded to the questionnaire. The contents in the questionnaire were practical activities, personal equipments, response plans, isolation facilities in emergency centers, outpatient clinics, general wards and intensive care units, and relationship with the public health department. Results : The dedicated isolation rooms in emergency centers, outpatient clinics, general wards, and intensive care units were prepared in 9 (9/17, 52.9%), 5 (5/17, 29.4%), 15 (15/16, 93.7%), and 4 (4/16, 25.0%) hospitals, respectively. Except for one hospital that newly made negative pressure room for SARS, single or multi-bed rooms without airborne infection control were used in all the other hospitals. The personal precaution principles were kept quite well in general wards. Before the designation of SARS hospital by the public health department prior evalution to see if the hospital was suitable for managing SARS was conducted in only 1 (1/12, 8.3%) hospital. The results of laboratory diagnosis were reported back in 1 (1/15, 6.6%) hospital. Conclusions : The isolation facilities which can control airborne infection were almost deficient not only for SARS but also for other respiratory transmissible diseases. For the infection control of transmissible diseases including SARS, more investment is needed on medical facilities and comprehensive support from the public health department required.

Correction to: Mode‑Change PWM Method for Improving Efficiency of 3‑Level T‑Type PWM Converter

Lee Woo‑Cheol,Kim Tae‑Hun 대한전기학회 2022 Journal of Electrical Engineering & Technology Vol.17 No.1

사면의 안정도 해석을 위한 입체투영법

이성대,이철우,이동우,이성규 公州大學校 基礎科學硏究所 1996 自然科學硏究 Vol.5 No.-

암반 사면의 안정성을 해석하는데 입체투영기법을 이용하였다. 안정도에 영향을 미치는 요인으로는 절리의 경사, 암석의 밀도, 내부마찰각등이 있으나, 가장 중요한 요인은 절리면의 경사이다. 이 연구에서는 암석의 점착력은 무시하고 단지 내부마찰각과 절리의 주향 및 경사만을 이용하였다. 그 결과 입체투영도에서 나타나는 암반사면의 안정도는 이동력과 저항력의 상대적인 크기에 의하여 좌우되는 것으로 나타났다. 동시에, 지반진동에 의한 영향도 입체 투영기법으로 찾아낼수 있다는 것이 밝혀졌다. Stereographic projection technique was used to analyze rock slope stability. Strike and dip of joints, rock strength, and internal frictional angle are major factor on slope stability. Among them, the most important factor is strike and dip of joints. In stereographgic projection technique, only internal frictional angle, and strike and dip of joints were used to interprete slope stability. Cohesion of rock was not considered. It is suggested that the rock slope stability on stereographic projection depends upon only the differential stress between driving and resisting force. At the same time, Stereographic projection technique on seismic loading was proposed in this study.

중환자에서 동맥혈 가스분석 횟수와 그로인한 실혈량에 대한 연구

이석열,전철우,정영수,오희숙,마분란,이정미,정혜영,이만복,이길노 순천향의학연구소;Soonchunhyang Medical Research Institute 2000 Journal of Soonchunhyang Medical Science Vol.6 No.1

Background : Arterial blood gas analysis is the most comon exam in intensive care unit. In this study, the frequency of blood gas analysis and the amount of blood loss after Blood Gas Analysis in Intensive Care Unit were observed. Methods : From November 1999 to February 2000, 115 patients admitted to intensive care unit at Soonchunhyang university Kumi hospital were studied prospectively for the frequency of blood gas analysis and the amount of blood loss after blood gas analysis in Intensive Care Unit. Results : The mean value of frequency of blood gas analysis was 6.41±6.49 and the mean value of amount of blood loss after blood gas analysis was 0.78ml. This was lower than that of other foreign reports. The patients with ventilator therapy above 24 hours showed higher frequency of blood gas analysis than that of not applied ventilator patients. Pulse oxymetry was applied to all patients and the frequency of blood gas analysis was decreased due to the use of strict pulse oxymetry. Conclusion : Doctors and nurses in intensive care unit keep in mind that adequate blood sampling is needed for the decrease of blood loss. Education and protocol for the decrease of blood loss after arterial blood gas analysis may be necessary.

『사랑이 뭐길래』에 나타난 가족의 의미

이철우(Lee Cheol-woo) 고려대학교 한국학연구소 2005 한국학연구 Vol.22 No.-

김수현의 『사랑이 뭐길래』는 대단한 인기를 끈 가정드라마이다. 구도를 명확하게 처리하고 개성적인 인물을 배치하여 드라마는 극적 재미를 높였다. 이질적인 두 집안을 배경으로 대발과 지은의 결혼과 문화교류를 통해 세대 간의 극복과 화합을 그려낸다. 민주적이고 자유분방한 박이사 집안과 남성위주의 권위적인 이사장 집안을 중심으로 세대와 계층의 모습을 통해 현대 사회의 가치관 혼란과 극복을 에피소드를 중심으로 풀어낸다. 두 집안은 각기 나름대로의 질서로 집안을 유지하지만 결국 상대방의 문화를 이해하고 받아들이면서 변모해간다. 가족의 의미 역시 어느 한 편으로 기우는 것이 아니라 장단점을 고루 그려내면서 합리적인 대안을 모색하고자 한다. 그리고 이런 관점이 가장 분명하게 드러나는 것이 결혼관이다. 결국 결혼이라는 제도를 통해 문화의 이질성을 극복하고 발전적인 방향으로 나아가는 셈이다. 제목인 『사랑이 뭐길래』는 바로 이렇게 모든 것을 덮어 버리고 만드는 힘으로 설정된다. 하지만 등장인물들의 성격이 일관되게 표현되지 못한 점과 재미에 치중하여 모순을 감싸고 긍정적인 시선만으로 가족을 그려냄으로써 드라마의 가치지향이 보이지 않는 약점을 노출시킨다는 점이 아쉬움으로 남는다. 결국 가족이란 일방적인 희생 없이는 유지되기 어렵다는 작가의 시선은 모순을 안고 살아갈 수밖에 없는 숙명적인 존재들로 가족 구성원을 만드는 셈이다. What is love? is a very popular home drama, writer is Kim, Su-Hyun. She treats the structure very clear ways and posts well individual characters, so she increased the dramatic interest. Comparing with two opposite families, the play can overcome the conflict among different generations ; through the marriage between Dae-Bal and Ji-Eun, the play urges characters to communicate different family culture. By opposing Mr. Park's family with Mr. Lee's Family, She compares their culture and attitude of life. As a representative of company, Mr. Park is very free and democratic character while Mr. Lee is a president of company, but he is male-centered, authoritative character. Their conflict between different family culture becomes a central theme. Through various aspects of different generation and class, the play exposes the confusing values of modern world by showing many episodes. By developing drama, both families gradually change themselves and understand each other, even though they keep their traditional order. The meaning of family is not slided toward one side, it tries to find out a reasonable alternative which can includes good and bad point at the same time. The primary point is their specific views about marriage. Finally they overcome dissimilar culture, go forward more advanced ways with marriage system So the title "What is Love?" can cover every problem and become a main power of live. But the play doesn't show coherent aspects in the personality of characters but focuses on only interest of drama, so it doesn't represent an unique intention or value through the drama, that will be a fault. After all the members of family must endure sacrifice to keep their union, so that they have to embrace their fortune and irony of life. The writer's view is to make the members of family as fortunate characters in the modern world.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성

김시현,이동건,최수미,권재철,박선희,최정현,유진홍,이성은,조병식,김유진,이석,김희제,민창기,조석구,김동욱,이종욱,민우성,박종원 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

Background: Micafungin, a potent inhibitor of 1,3-β-D-glucan synthase, is a novel antifungal agent of the echinocandin class. In vitro study showed that micafungin was effective against Aspergillus species as well as Candida species, but clinical data on the prophylactic efficacy against invasive fungal infections (IFIs) other than candidiasis are still lacking. Materials and Methods: We identified 60 consecutive adult hematopoietic stem cell transplantation (HSCT) recipients who received at least 3 doses of micafungin during neutropenic period. Micafungin was started as an alternative in patients who were intolerant or had adverse events (AEs) to primary prophylactic antifungal agents. We retrospectively reviewed the medical records and analyzed the efficacy and safety of micafungin for prophylaxis against IFIs. Results: The patients either had autologous (n=9) or allogeneic (n=51: 1 syngeneic, 24 sibling, 26 unrelated donor) HSCT. Itraconazole oral solution (n=58) was the most frequently used first line antifungal agent for prophylaxis and was administered for median 11 days. The most frequent cause of switch to micafungin was vomiting (n=42). The duration of neutropenia and micafungin administration was median 13 and 12 days, respectively. A successful outcome was achieved in 45 (75%) patients. Empirical antifungal therapy was initiated in 13 (22%) patients. There were 2 cases (3.3%) of breakthrough fungal infections which comprised a probable invasive pulmonary aspergillosis and a possible invasive fungal sinusitis. There was no case of invasive candidiasis. A total of 53 (88%) patients experienced at least one AE regardless of causality during micafungin administration. The most frequent AEs were hypokalemia, vomiting, diarrhea, and elevated serum aspartate aminotransferase or alanine aminotransferase. Among the aforementioned AEs, only 1 case of diarrhea could be classified as a probable relation with micafungin when causality was assessed. There was no AEs that caused discontinuation of micafungin. Conclusions: Micafungin seems to be a safe and effective agent for prophylaxis of IFIs including aspergillosis as well as candidiasis in HSCT recipients. However, further large, prospective, and randomized comparative studies are warranted for aspergillosis.

조갑하 외골종 : 1예 보고

이은우,전재명,안병우,김철호 중앙대부설한국의과학연구소 1989 한국의과학 Vol.21 No.3

천수만층의 형성과 진화

이철우,백창훈,이동우 충남대학교 기초과학연구소 1995 연구논문집 Vol.15 No.-

천수만층은 백악기의 육성 퇴적물로 구성되어 있다. 퇴적작용은 주로 선상지에서 이루어졌다. 남북방향으로 발달하는 천수만층은 대규모 좌수향 주향이동 단층에 고각으로 발달하는 이차 단층계에 의하여 생성하는 것으로 추정된다. 전체적인 층후는 약 200∼300 m에 달하는 것으로 보인다. 층의 서측 경계는 단층으로 기반암과 접하며 동측은 바트리스(buttress)부정합과 단층으로 기반암과 접한다. 지질시대는 화산쇄설성 퇴적물이 전 지층에 걸쳐 고루 나타나는 것으로 보아 경상누층군의 하양층군에 대비되는 것으로 보인다. 천수만층 형성 초기의 퇴적작용는 넓은 지역에 걸쳐 박층으로 퇴적되었고 후기 침식 작용에 의하여 좁고 긴 형태로 나타나게 되었다. The Chonsuman Formation consists of Cretaceous non-marine sequences which were deposited in proximal to medial alluvial fan environments. The depression was probably by secondary fault of large-scale sinistral strike-slip fault system trending NE-SE. Distributary pattern of the Chonsuman Formation shows N-S trend. The total thickness of the formation reaches ca. 200-300meters. Western margin of the formation contacts with the Taean Formation by fault. Eastern one shows both fault and buttress unconformity. Based on the volcanogenic components broadly distributed on all sequence, it may be correlated largely with that of the Hayang Group. In the initial stage of the basin-formation, sedimentation was shallow an broad, and occupied in a narrow and long after erosion.

8.3% Carbamide Peroxide 함유 펜 형 자가미백제인 BIancTis Forte의 색조개선 및 안전성에 관한 임상연구

이진경,민선홍,홍성태,오소람,정신혜,황영혜,유성엽,배광식,백승호,이우철,손원준,금기연 대한치과보존학회 2009 Restorative Dentistry & Endodontics Vol.34 No.2

This clinical study evaluated the whitening effect and safety of polymer based-pen type BlancTis Forte(NIBEC) containing 8.3% carbamide peroxide. Twenty volunteers used the BlancTis Forte whitening agent for 2 hours twice a day for 4 weeks As a control. Whitening Effect Pen (LG) containing 3% hydrogen peroxide was used by 20 volunteers using the same protocol. The change in shade (ΔE^(*) color difference) was measured using Shadepilot™ (DeguDent) before, during and after bleaching (2 weeks, 4 weeks and postbleaching 4 weeks). A clinical examination for any side effects (tooth hypersensitivity or soft tissue complications) was also performed at each check-up. The following results were obtained. 1 Both the experimental and control groups displayed a noticeable change in shade (ΔE) of over 2 No significant differences were found between the two group (p>0.05) implying that the two agents have a similar whitening effect. 2 The whitening effect was mainly due to changes in a and b values rather than in L value (brightness). The experimental group showed a significantly higher change in b value thus yellow shade than the control(p < 0.05) 3 None of the participants complained of tooth hypersensitivity or soft tissue complications confirming the safety of both whitening agents 8.3%의 carbamide peroxide를 함유한 펜형 코팅용 미백제인 BlancTis Forte (NIBEC, Seosul & JinCheon)를 실험군으로, 3% hydrogen peroxide를 함유한글 Whitening Effect Pen (LG. Seoul) 제재를 대조군으로 각각 피험자 20명에게 2시간씩 1일 2회 제조사의 지시대로 치아표면에 4주간 적용하도록 지시하고 색조개선 효능과 안전성을 평가하였다. 미백 효과는 미백 전 및 미백 2주, 4주 및 미백 종료 4주 후에 Shadopilot™을 이용하여 색 변화를 측정하였고, 매 내원시기마다 모든 환자는 치수생활력 검사와 치주 및 치태 검사를 통해 부작용 여부 (치아과민증 및 구감 내 연조직의 부작용)를 기록한 후 다음과 같은 결과를 얻었다. 1.실험군 및 대조군의 색 변화량 (ΔE)은 2이상으로 인지할 수 있는 색 변화를 보였으며, 두 제품 간에는 통계적으로 유의한 차이를 보이지 않아 (p > 0.05) 유사한 미백효능을 나타냄을 알 수 있었다. 2,미백효과는 명도의 개선보다는 주로 a. b값의 변화에 의한 것으로 특히 실험군에서 b값의 변화, 즉 황색조의 개선효과가 대조군에 비해 유의성 있게 높은 것으로 나타났다 (p <0.05). 3.치아나 치은의 과민증이나 이상증상을 호소하는 피험자는 없어 두 제품 모두 안전성을 확인할 수 있었다.