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

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.

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.

『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.

비가역성 치수염의 임상증상에 따른 임파구 분포에 관한 연구

이우철,임성삼 大韓齒科保存學會 1995 Restorative Dentistry & Endodontics Vol.20 No.1

AbstractThis study was designed to identify the lymphocytes present and to examine the relation between lymphocytes population and clinical symptoms of the pulps clinically diagnosed as normal and irreversible pulpitis. We recorded the history and severity of the pain and performed several clinical tests, before extirpation of vital, irreversibly inflamed pulps in routine endodontic treatment. Then the teeth were divided into two groups. Five teeth, categorized in acute symptom group, had severe spontaneous pain, particularly at night and were extremely sensitive to cold and heat. The other 15 teeth with history of mild to moderate pain and with or without cold or heat responses were categorized as chronic symptom group. Inflamed pulps were also classified into 8 minor groups by presence or absence of signs or symptoms related to the involved teeth, including the presence of pain on percussion, pain on heat and cold stimuli and the periodontal pocket depth. All extirpated pulps were immediately immersed in ultra low-temperature freezer (-74℃), and they were sectioned 6um in thickness. Specimens were stained using three-stage indirect immunoperoxidase techniques(DAKO, LSAB kit) and monoclonal antibodies for detecting the presence ofT lymphocytes (T), B lymphocytes(B) and helper(T4) and suppressor(TS) lymphocytes. Following results were obtained; 1. All the examined normal and inflamed pulp tissues had positive staining for T lymphocy- tes and T helper and T suppressor cells. But B cells were observed only in inflamed pulp. 2. Statistically more T and B cells were observed in acute symptom group as compared with chronic symptom group(p<0.05). 3. Cell ratio of B/T in acute symptom group were significantly higher than that of chronic symptom group(p<0.05). 4. Only B cells were significantly increased in the percussion positive group than the number of B cells in percussion negative group(p<0.05). 5. No differences were observed in the number of different cell types among other minor groups.

PMDI(Polymeric Methylene Diphenyl Diisocyanate)樹脂를 利用한 新聞古紙纖維-木纖維 混合 하드보드의 物理的 및 機械的 性質

李弼宇,李喆周 서울大學校 農業生命科學大學 農業開發硏究所 1996 서울대농학연구지 Vol.21 No.2

Conventional researches have reported that ONP(Old Newspaper) fiber mixed hardboard is inferior to wood fiber hardboard on physical and mechanical properties, specially, internal bond strength and dimensional stability are very poor. It is thought that wetted ONP fiber by using water soluble resin results in poor uniformity of resin distribution. Actually internal bond strength, to a large extent, depends upon the uniformity of resin distribution. The objective of this research was to compare the results from ONP fiber mixed hardboard using water soluble phenol resin with those from ONP fiber mixed hardboard using PMDI(Polymeric Methylene Diphenyl Diisocyanate) which get fiber less wet relatively. Boards were fabricated with ratios of ONP fiber to wood fiber of 0 to 100, 30 to 70, 50 to 50, 70 to 30 and 100 to 0, and tested for static bending strength, internal bond strength, tensile strength, water absorption and thickness swelling. As expected, ONP fiber mixed hardboard using water soluble phenol resin showed that physical and mechanical properties decreased with increasing of ONP fiber mixed level. However, those using PMDI showed opposite results, specially internal bond strength increased, and water absorption and thickness swelling decreased with ONP fiber mixed level ranging from 30% to 70%.

Earth Anchor의 인발저항력에 관한 연구

이유근,김우중,윤용철 진주산업대학교 1994 論文集 Vol.33 No.-

This paper describes the results of an experimental consideration on the uplift capacity of the earth anchor. The earth anchor used in pull-out test is the cylindrical steel with plate and eight earth pressure cells(No.1~No.8). The plate diameter is 120㎜ and embedment ratios(L/B; L=length of embedment, B=diameter) are 1, 2 or 3, Also, we investigated surface displacement of the test ground using two gap sensors. Pull-out test were conducted for dry sand of soil placed at a density of loose. From the results, the following conclusions were drawn ; Uplift capacity of anchor becomes larger due to the increase in the L/B. The earth pressure act upon the upside of the anchor plate is different in according to place of earth pressure cell and L/B. That is to say, the earth pressure of No.1 or No.2 (earth pressure cell) increases as time goes by until the anchor pull-out completely, but the earth pressure of No.3(L/B≤2) becomes smaller No.1 and No.2 after the rate of increase of the earth pressure decreased by boundary a point of time. The intersecting point of the ground(sand) surface and the end of shear bed is about 15㎝(L/B=1), 21㎝(L/B=2) or 27㎝(L/B=3) by distance from anchor center.