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>

석견루(石見樓) 이부현(李復鉉) 시(詩) 연구(硏究)

이현일 ( Hyun Il Lee ) 한국고전문학회 2011 古典文學硏究 Vol.40 No.-

이 논문은 아직까지 학계에 잘 알려지지 않은 시인인 石見樓 李復鉉(1767~1853)을 소개하기 위해 씌여졌다. 이복현은 金려(1766~1821)가 편찬한 『潭庭叢書』 전체를 다룬 朴晙遠의 선구적인 업적에서 처음 언급되었을 뿐, 그 뒤로는 본격적인 연구의 대상으로 주목을 받지 못해 왔다. 제1장에서는 선행 연구를 바탕으로 하면서도 관련 자료를 보강하여 이복현의 가계와 생애를 다시 정리하였다. 행장이나 묘지명과 같은 기본적인 자료들이 아직 발견되지 않아 미흡한 점이 있지만, 주어진 상황에서는 최선을 다하려고 하였다. 제2장에서는 지금 남아 있는 이복현의 시문집에 대한 기초적인 조사를 정리한 것이다. 이복현의 시문집은 (1) 후손에 의해 중국에서 인쇄되어 들여온 『石見樓詩초』, (2) 『潭庭叢書』에 실린 『石見樓雜詠』과 『石見樓詩卷』, (3) 고려대 중앙도서관에 소장된 『石見樓』 17책 등으로 나누어 살펴 볼 수 있으며, 사실 좀더 본격적인 연구를 위해서는 각 이본들을 토대로 定本을 만들고 改作 과정을 추적하는 일이 반드시 필요하다. 제3장에서는 주로 『석견루시초』에 수록된 작품들을 중심으로 그의 시세계의 특징적인 면모를 논하였다. 고시, 절구, 율시의 순서로 대표작이라 판단되는 작품들을 뽑아서 詩體에 따라 살펴보았다. 여기서 살펴본 이복현의 시들은 겉보기에는 평범하고 담담한 듯하지만, 시적 기법의 완숙성이 뒷받침 되지 않으면 나올 수 없는 작품들이며, 분명히 시인 나름의 개성을 포착할 수 있다. 요컨대, 이복현은 한 시대를 대표하는 大家가 되기에는 부족하지만, 名家들의 詩友가 되기에는 충분한 역량을 갖춘 시인이었다고 할 수 있다. 마지막으로 餘論에서는 이 글을 마무리하고 앞으로 연구를 심화시키기 위해 필요한 작업들에 대해서 간략히 논하였다. The purpose of this paper is to introduce the unknown poet, Seokgyeonru(石見樓), Lee Bok Hyun(李復鉉). In the first chapter, we deal his life and history of his family based on the study of early scholars. and then we rearrange them with added materials. Although we cannot discover fully the fundamental materials of his life, we do our best under the present circumstances. In the second chapter, we deal the elementary investigation of Lee Bok hyun`s collected poems. His works are classified into (1) The Selected Poems of Seokgyeonru(『石見樓詩초』) edited by his descendants, (2) Miscellaneous songs of Seokgyeonru(『石見樓雜詠』) and The Poetry of Seokgyeonru(石見樓詩卷) in Damjeongchongseo(『潭庭叢書』), and (3) Seokgyeonru, composed of seventeen books. In order to study deeply, we need to edit authorized version based on these various versions. In the third chapter, we deal his characteristic features of his poetic world in The selected poems of Seokgyeonru. We do survey his representative poems in order of old-style poetries, quatrains, and code verses. At first blush we think his poetries are commonplace and plains, but it soon become obvious that his works are created with excellent poetic techniques. In short he is not the representative poet of his days, but second-best poet of his times. In the last chapter, we deal about the necessary work in order to deepen the study of Lee Bok hyun, the poet.

이창동 작가론

이현승(Hyun-Seung Lee),송정아(Jeang-Ah Song) 한국콘텐츠학회 2012 한국콘텐츠학회논문지 Vol.12 No.2

영화작가로서 이창동은 장르적 자장 안에서 영화를 만들고 있는 한국영화계의 대다수 감독들과 구별된다. 그동안 그의 영화는 관객과의 소통을 위해 느와르, 멜로 등의 장르를 차용해왔지만 최근작 〈시〉에 이르러서는 장르적 외피를 벗어던진 것처럼 보인다. 〈초록물고기〉부터 〈시〉에 이르기까지 일관되게 남은 것은 관객의 참여를 요하는 깊은 심도와 시간의 연속을 암시하는 길게 찍은 숏들의 몽타주, 현실성을 강조한 연기 등 리얼리즘적 표현방식이다. 또한 이창동의 영화들은 환영적 동일시를 깨는 방식으로 관객들에게 성찰의 자리를 돌려준다는 측면에서 장르영화의 카운터 시네마로 파악할 수 있다. 이창동의 영화에서 볼 수 있는 ‘낯설게 하기’는 핸드헬드, 판타지, 미장아빔, 응시 되돌려 보내기 등의 영화적 장치로 구현된다. 이 장치들은 텍스트의 재현양식을 폭로함으로써 관객들이 역사적, 정치적 컨텍스트를 성찰하게 한다. 본 연구에서는 〈시〉,〈오아시스〉,〈밀양〉 등의 분석을 통해 이창동의 영화 만들기 행위는 결국 보이지 않는 ‘실재’를 상징화함으로써 ‘윤리를 창조하는 반복충동’이라고 주장할 것이다. As a film maker, Lee Chang Dong stands out from most Korean film makers who work within the trappings of genre films. To be sure, Lee has also used the trappings of genre films, such as noire and melodrama, but primarily as a tool to communicate with film audience. In his most recent film “Poetry”, Lee seems to have even stripped even the minimal trappings of genre film. Lee commands the audience to self-reflect and work towards their own conclusions by denying them the illusory identification on screen. In this way, Lee’s works are counter cinema. Lee achieves a distancing effect using such filmic apparatuses as hand-held camera, fantasy, mise en abyme, and returned gaze. Through these filmic apparatuses, Lee exposes the re-presentation of text and compels his audience to see the historical and political contexts of the text. In this study, I make the case that Lee Chang Dong’s film making is an act of repetition compulsion that cultivates ethical reflection, through symbolization of the invisible realities.

안도 다다오의 이우환 미술관의 개념적 관계성과 공간구성 분석

황인애(Hwang, In-Ae),이현수(Lee, Hyun-Soo) 한국실내디자인학회 2019 한국실내디자인학회 학술대회논문집 Vol.21 No.1

The abandoned island Naoshima was reborn with the will of Chairman Soichiro Fukudake and the efforts of Tadao Ando. Tadao Ando designed the Benesse House Museum, the Chichu Art Museum, and the Lee Ufan Museum, which are called the three major museums of Naoshima. The museum of Ando designed buildings that harmonize with architecture, nature, and human beings. Among them, Lee Ufan of Lee Ufan Museum is a painter who focused on relationality in particular. In this study, the Lee Ufan Museum was selected as an example. This research focuses on the analysis of their conceptual relationship with the Lee Ufan Museum and the spatial composition that it implemented in architecture. The research methods include literature review, drawing analysis and field trip. Lee"s work trends can be seen to be concentrated on the relationship such as ‘objects-objects’, ‘objects-spaces’, and ‘objects-human beings’. From the perspective of Lee Ufan"s conceptual relationships, the architecture of Tadao Ando can be understood as the relationship such as ‘architecture-exposed concrete(matter)’, ‘architecture-human(moving line)’, and ‘architecture-nature(place)’. Through this analysis, the Lee Ufan Museum is not merely a solo work of Tadao Ando, but a successful case in which two outstanding artists to keep in step together as a collaboration between Ando and Lee.

해방 후 李承燁의 ‘統一民族國家’ 건설운동(1945~1953)

이현주(Lee, Hyun-Joo) 인천대학교 인천학연구원 2007 인천학연구 Vol.6 No.-

It was through the process of a merger of three parties that Lee Seung-Yeop rose as a leader of the socialist state movement in South Korea. The inauguration ceremony of the South Korean Worker's Party (남조선노동당) was held under his leadership in November, 1946 after Park Hun-young went to North Korea. He visited secretly PeyongYang accompanied by Kim Sam-yong and achieved the principal that the Opposing Parties individually had to join the South Korean Worker's Party established by centralizing the Korean Communist party. After crossing over the border into North Korea, Lee Seung-Yeop was appointed as a head of judicature of the First Cabinet, North Korea. However, his role was prominent in the Parties. Lee Seung-Yeop rose to the position supervising operations against the South as second secretary of the Party as well as was elected an member of Nine Politics Committeemen of the Korean Workers' Party(조선노동당) which was born due to the merger of Parties. Since then, his activities were concentrated on the leadership for guerrilla war by a partisan. He reorganized a guerrilla unit into three groups in order to develop systematically the guerrilla that was being sporadically progressed in South Korea in July, 1947 and the first group was dispatched to the South in his order. The Korean War was a watershed deciding his fate. He who sent to the South as plenipotentiary of liberated area as soon as the war occurred suddenly was nominated a representative of Seoul city of the Armed Services Committee, North Korea and Seoul temporary Council of People's Commissars the minute that Seoul was occupied. He, an chairman of Council People's Commissars, had to support the People's Army advancing South, recovering ruined product facilities, roads, bridges etc. The management for relief programs, citizens' mobilization, letting volunteer armies go to the war, cultural propaganda programs, land reform, health movement, product power increase was encouraged for about two months. Orders for a guerilla continued. At the same time, Lee Seung-Yeop made people sympathize with the People's Army by infiltrating espionage operators each province, landing the mustered guerrilla to the South through the East Sea on June 25, 1950. Even though his power decreased in the situation an armistice was argued, the first half of 1951, his leadership to the guerrilla was well. The end of the war with Incompletion brought a tragedy to him. Lee Seung-Yeop was arrested with other 11 fellows of the South Korean Worker's Party faction on August 3, 1952. He disappeared in the North, 'a forever strange land', after being sentenced to death and property confiscation upon a quick trial for 4 days, on August from 3 to 6, 1953. The event was not ended in Lee's death. The Purge against the South Korean Worker's Party continued until 1955 and became an overture of the purge against Soviet Union Group(소련파) and Yeon Ahn Group(연안파). His tragic death was not resulted from 'conspiracy of armament riots for the plot against government', but the fact he couldn't clean himself of suspicion even in North Korea, not Kim Il-Sung but Pak Hung-Young whom he assisted as the chief until he died, even if shouting many times 'General Kim Il Sung cheers!' at the official meeting. He failed to free himself from 'a second man of the South Korean Worker's Party until the last moment.

峿堂 李象秀의 『史記』 評述에 대하여

이현호(Lee Hyun-Ho) 동양한문학회(구 부산한문학회) 2010 동양한문학연구 Vol.31 No.-

본고는 峿堂李象秀(1820-1882)가 『사기』에 대해서 남긴 비평적 저술을 살핀 논문이다. 이상수는 텍스트의 선택이나텍스트의 선본에 관심을 갖지않고 독서하는 방법에 주목하였다. 그리하여 대부분의 사람들의 독서법이 잘못되었기에 글을 잘 짓는 자가 드물다 하면서, 맹목적 독서가 아닌 能思의 독서를 해야함을 강조하였다. 이러한 이상수의 독서론은 ‘虛讀’이 아닌 ‘實讀’이라 명명할 수 있는데, 독서에 潛心해야 志向이 정해지고 見識이 분명해져 결국에는 작자의 本心을 파악하며 글 전체의 大義를 구명할 수 있게 된다 하였다. 또한 이상수는 독서를 작문의 기초단계로 파악하지 않고, 오히려 작문 이후에 더 독서를 잘 할 수 있다는 의견을 피력한다. 곧 작문법을 독서론에 적용하여 체계적이고도 분석적으로 글을 읽어야 글에 나타난 작자의 묘처를 알 수 있게 된다고 하였다. 이러한 독서작문론을 『사기』에 적용하여 비평적 언술을 남기게 된다. 혹리열전 에서는 저작의도를 후세의 경계가 아닌 한무제의 어리석고 현명하지 못함을 기롱하고 풍자하는 것이라 하였고, ‘脈理’에 입각하여 입전 순서가 단절되지 않고 연속되어 있음을 논증하고 있다. 화식열전 에서는 작자의 本心과 宗旨를 글의 표면에서 찾지 않고 글에 드러나 있지 않은 곳에서 찾고 있으며, 사람들이 재화의 증식만 추구하여 올바른 가치를 망각하는 모습을 안타까워한 것이 이 傳을 創立한 사마천의 본심이라 하였다. 또한 문장의 ‘摺’과 ‘承’이라는 段落구성에서 접속 기법의 차원으로 화식전 에대하여 수사학적 분석을 하고 있다. 이러한 것들에서 이상수의 독서작문론의 의의와 『사기』에 대한 평술의 실상을 확인할 수 있다. The present study analyzes a critical review by Lee Sang-Soo (pseudonym: eh-dang, 1820-1882) on the Records of the Great Historian (Shiji or 史記, Sima Qian;109 BC - 91 BC). Lee focused on the mode of reading, rather than on the choice and content of text. He pointed that most people employ an improper mode of reading and hence good writers are rare, thereby he urged to exercise truthful and proper reading instead of pointless reading. Such a theory of reading by Lee can be defined as true reading (實讀), as opposed to a vain reading (實讀), where he asserted that being engrossed in reading is what offers the inclination of messages and firmly sets the insight of reader; only then, one can eventually recite the true intention of the writer and be able to define the ultimate message of the whole text. Further, Lee did not identify reading as a prerequisite step for writing but instead expressed that reading can be improved with writing exercise. In other words, applying writing skills to the reading theory that one should read text in an orderly and analytic manner in order to appreciate the writer's merit from the text. He applied this theory of reading-by-writing in his critical review on the Records of the Great Historian. He stated that the Biographies of Cruel Officials (Kuli liezhuan, 酷吏列傳) of the Records is not intended as a discipline for succeeding generations but to deride and satire the Emperor Wu of Han for his folly and poor wisdom, arguing that the contents are connected by the thread of logic in consecutive manner, without disruption. While discussing on the Biographies of Usurers (Huozhi liezhuan, 貨殖列傳), he finds the writer's true intention and ultimate message from the unmentioned context instead of the textual contents, that frustration was the real intention behind Sima Qian's establishment of the Records, for people becoming obsessed with material wealth and in turn oblivious to the value of morals. He also conducted rhetoric analysis on the Biographies of Usurers in terms of conjunctive method on the paragraph composition characterized by remit and receiving. Such are the particulars that present the significance of Lee's reading-bywriting theory, as well as the insight to his critical assessment on the Records of the Great Historian.

이광수와 나쓰메 소세키의 문학교육론이 지닌 근대성 비교연구

권혁건(Kwon,Hyuk-Gun),이호규(Lee,Ho-Gyoo),김주현(Kim,Ju-Hyun) 동북아시아문화학회 2011 동북아 문화연구 Vol.1 No.28

Soseki is representative novelist and theorists of Japanese modern literature, and Lee Gwangsoo (Lee) is known as person who opened doors to Korean modern literature. They are representing not only Korean and Japanese modern literature, but also Oriental modern literature. We focused on the early stages of their literary theories. As well, looked into their arguments based on their ideas of literary education in relation between literature and society. Although Soseki and Lee are both representatives of Korean and Japanese modern literature, we have found their literary theories to have contrasts, as well as undertoned ideal substance. Their findings show identical recognition in defining the workings of human mind as intellect, emotion and volition. Also, their thoughts on the realm of emotion is the characteristic of literature, and explained modern literature by drawing the concepts of rationality and truth. Soseki insisted literary art is not a simple skill; a literary artist could influence others due to their ideals that a literary artist is someone who has the biggest and highest ideals. Lee’s argument resembles Soseki’s argument. Lee contended literary art can be made simply with skill and endeavor. Only highly gifted artist can take charge of a growing self-regulating person who could lead society through literature. Soseki and Lee both, therefore, conclude the Occidental natural science (in other words, education that is logical and substantiate) is modern education, and upcoming Oriental new education need to take after. We found Soseki and Lee have contended education through literature that could produce self-regulating and liberal individuals based on the mentioned Occidental new education.

Light-extraction efficiency control in AlGaN-based deep-ultraviolet flip-chip light-emitting diodes: a comparison to InGaN-based visible flip-chip light-emitting diodes.

Lee, Keon Hwa,Park, Hyun Jung,Kim, Seung Hwan,Asadirad, Mojtaba,Moon, Yong-Tae,Kwak, Joon Seop,Ryou, Jae-Hyun Optical Society of America 2015 Optics express Vol.23 No.16

<P>We study light-extraction efficiency (LEE) of AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs) using flip-chip (FC) devices with varied thickness in remaining sapphire substrate by experimental output power measurement and computational methods using 3-dimensional finite-difference time-domain (3D-FDTD) and Monte Carlo ray-tracing simulations. Light-output power of DUV-FCLEDs compared at a current of 20 mA increases with thicker sapphire, showing higher LEE for an LED with 250-관m-thick sapphire by ~39% than that with 100-관m-thick sapphire. In contrast, LEEs of visible FCLEDs show only marginal improvement with increasing sapphire thickness, that is, ~6% improvement for an LED with 250-관m-thick sapphire. 3D-FDTD simulation reveals a mechanism of enhanced light extraction with various sidewall roughness and thickness in sapphire substrates. Ray tracing simulation examines the light propagation behavior of DUV-FCLED structures. The enhanced output power and higher LEE strongly depends on the sidewall roughness of the sapphire substrate rather than thickness itself. The thickness starts playing a role only when the sapphire sidewalls become rough. The roughened surface of sapphire sidewall during chip-separation process is critical for TM-polarized photons from AlGaN quantum wells to escape in lateral directions before they are absorbed by p-GaN and Au-metal. Furthermore, the ray tracing results show a reasonably good agreement with the experimental result of the LEE.</P>

자궁내 태아사망의 임상적 고찰

이권해,이정재,조현철,이석민,이임순,이해혁,김권대,이순곤,남계현 순천향의학연구소 1999 Journal of Soonchunhyang Medical Science Vol.5 No.2

Objective: This study was designed to evaluate diagnosis and complication, prognosis during clinical study of cases of intrauterine fetal death. Methods and materials: This is a clinical study of 56 cases of the intrauterine fetal death among 8064 deliveries at Seoul Sunchunhyang university hospital during 5 years from January, 1994 to December, 1998. Results: The incidence was 0.7%. The age distribution of mothers was 18 - 44 years and was highest in the 25 - 29 years range(46.4%). The parity was the most highest in the nulliparous group(51.8%). The most common gestational weeks was 20 - 28 weeks gestational period(46.4%), and most common presentation was cephalic(73.5%). The most common weights of the intrauterine fetal death was from 5,00gm to 1,000g(48.2%). The mode of the most common delivery was the induction of delivery(57.2%). The etiologic factors were: unknown(42.9%), preeclampsia(17.9%), chorioamnionitis(14.3%), congenital anomaly(12.5%), abruptio placenta(7.1%), cord complication(3.6%), placenta previa, death of one for twin. There were 2 cases of maternal complication(DIC, Uterine atony). Conclusion : Intrauterine fetal death should be diagnosised early and treated properly to reduce risk of the maternal complication.

폐암과 동반되어 나타난 기관기관지병증 골연골형성증 1예

이영진,전현수,박시형,김모세,김현주,이승헌,이영민,이현욱,이현경 仁濟大學校 白病院 2010 仁濟醫學 Vol.31 No.-

Tracheobronchopathia osteochondroplastica (TPO) is a rare benign disease of unknown etiology characterized by multiple cartilaginous or bony submucosal nodules, which project into the tracheobronchial lumen. Although some disorders were reported combined with TPO, these seemed to be considered casual. We report a case of TPO that combined with adenocarcinoma of lung. She was 50-year-old non smoking woman presented with chronic cough with right chest pain. Lung mass on right lower lobe was found on chest x-ray, so lung cancer was suspected. Multiple scattered whitish small elevations from trachea to bronchial trees were found on bronchoscopic exam. We mistook these lesions for metastases from lung cancer and biopsies of these lesions were done. Transbronchial biopsy for right lower lobe mass lesion was also done. But biopsies from trachea and bronchus revealed TPO rather than lung cancer. Transbronchial lung biopsy of right lower lobe mass was diagnosed adenocarcinoma of lung. So TPO combined with adenocarcinoma of lung was diagnosed.