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        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>

      • KCI등재

        플롯의 의미와 진실의 발견 - 『소문의 벽 』론-

        이하은(Lee, Ha-eun) 한국언어문학회 2018 한국언어문학 Vol.107 No.-

        The purpose of this study is to consider the relationship between form and content and view of the novel in “Wall of Rumors.” This study deals with the function and the effect of detective plot and multiple-layered structure and then the relationship between the function and the content. Lastly, this study considers Lee’s view of novels. Plot is a design to find out what suppressed desire is. Detective plot in “Wall of rumors” is generated by the narrator’s curiosity about Park Jun’s life. The speaker collects clues to trace Park’s secrets and constructs them into narrative to understand why Park’s desire is suppressed. Though the structure in “Wall of rumors” is layered, it is a kind of story-within-a story. While the speaker recollects the past, the speaker―outside the narrative―reflects and explores himself. The detective plot and multiple-layered structure makes readers overlap themselves with the speaker, so readers can explore what their oppressed desires are as the speaker. “Wall of Rumors” describes the process to find out the meaning of sign. Anyone who encounters sign is forced to interpret its meaning. To interpret it, the one makes use of all information he can use. After interpreting, the one finds out current meaning of sign and comprehends why sign cause him to feel something. Tracing Park’s life, the speaker finds out the hidden truth inside of himself. This is only possible in literature to find out the truth of life. This is the reason why narrator follows Park Jun’s life. As for Lee Chung-Jun, novel is kind of mental experiment to give matters of life to the readers. Lee describes process to explore what real suppression is in his novels. However Lee does not give a clear answer to the readers. Therefore, readers can form their own conclusion. This is similar to the view of Lee’s novel that can be interpreted the meaning of his works variously. The function of forms is to speculate the matters of live with the readers. And the readers follow the process of learning to face the truth. In the process, Lee makes the readers form their own meaning to the works not follow the fixed meaning.

      • 김우진 희곡에 나타난 죽음의 의미

        이은경 숙명여자대학교 2002 숙명語文論集 Vol.4 No.-

        The death appearing in Woojin Kim's dramas, is established in being closely connected with the life. In Youngnyeo Lee Youngnyeo Lee is a victim for women of the next generation who are represented by Lee's daughter, Myungsoon. So Lee's death ensures the social meaning of a martyrdom for the redemption. In A wreck the poet gets to death, i.e. wreck, in order to get born for a new human being. And the death is understood as a precondition in order for taking over father's task, by Wonbong in A wild boar. But the protagonists' attitudes for understanding the death are not same. Youngnyeo Lee in Youngnyeo Lee has a self-consciousness for a true female life before her death. Therefore she receives her death in a dignified manner. The poet in A wreck understands that death is a process of getting born for a new human being. The result is that he receives the death with a joy. But Wonbong in A wild boar is so weak that he can not take over the given task. So he escapes from the pressure of death and chooses a resigning life. As a result, the death is understood, by Woojin Kim, as a process of redeeming the social irrationalityand making birth of a new human being.

      • KCI등재

        여성작가가 재현한 신여성이라는 현실 -이선희,박화성, 강경애를 대상으로

        이은주 ( Eun Ju Lee ) 한국문학연구학회 2013 현대문학의 연구 Vol.0 No.49

        이선희, 박화성, 강경애는 1930년대라는 동시대를 산 여성작가들이다. 하지만 그들이 작품 속에 재현하고 있는 여류문사(신여성)의 모습은 다르 다. 계몽이 필요한 아이 혹은 속물적 인간으로 재현되거나 자기 욕망과 내 면에 집중하는 근대 개인으로 체현되기도 한다. 박화성은 1930년대 연애 담과 사치, 허영 등의 부정적 에피소드들로 담론화되었던 여류문사에 대 한 소문들을 그대로 받아쓰기하지는 않았지만 당대 가부장 문화에서의 일탈을 욕망하던 신여성을 담아내지는 못 했다. 강경애가 보여주는 여류문사는 1930년 당대 매체를 통해 형성되었던, 조롱과 반감의 대상으로서의 여류문사(신여성)의 모습과 일치한다. 자기 반성을 모르는 사람, 지적 허영 등은 강경애가 포착한 당대 여류문사의 일 면이다. 박화성과 강경애는 신교육을 받은 여성작가로 살았지만, 작품에 서 한 인간으로서의 신여성에 대해서는 특별한 관점을 드러내고 있지 않 다. 부르주아적 감성을 드러낸다고 이야기되는 이선희의 작품 속에 등장하 는 신여성들에게 중요한 것은 자기의 욕망, 감정, 내면의 변화이다. 이선 희의 작품에서 재현된 신여성들은 식민지 근대를 살아야 하는 도시인들의 양면성, 즉 근대 문화를 향유하면서도 그 속에서 느끼는 소외감과 내 것이 될 수 없음에서 느끼는 고독을 육화하고 있다. 1930년대 여성작가들이 신여성을 재현하는 눈은, 조선의 빈궁한 삶(과 공간)을 바라보는 신여성의 시선에도 그대로 투영된다. 박화성의 신여성 은 놀라고 배우는 자세로 조선 하층 현실을 수용한다면, 강경애의 여류문 사는 자기가 사는 세계와 다른 세계, 인간들이 사는 곳이라고 할 수 없는, 그래서 내가 있어서는 안 되는 공간으로 위계화한다. 한편 이선희의 신여 성들에게 농촌과 어촌은 생활과 삶의 공간이 아니라 개인의 욕망과 자아 가 투영되는 배경(자연)이 될 뿐이다. 부르주아 신여성들에게는 나(의 욕 망) 자신에 대한 몰두가 곧 삶이고 생활이었기 때문에 외부세계는 중요한 것으로 선택되지 못 한다. 그들의 현실은 조선 민중의 현실과 다른 것이었 다. Lee Sun Hee, Park Hwa Seong, and Kang Kyeong Ae are female writers who lived contemporarily in the 1930`s. However, the ways they represent female writers (modern women) in their works are distinct. They are reproduced as a girl or a snob who needs enlightening, or they are embodied as a modern individual who concentrates on the personal desire and inner side. Park, Hwaseong did not take down the rumors of female writers who had been discussed on such negative episodes as love stories, extravagance, and vanity in the 1930`s. She, however, failed to show a modern woman who longed to break away from the contemporary culture of patriarchism. The modern woman that Kang, Kyeongae showed corresponds to the image of modern women as a figure of mockery and hostility which was presented on the media of the 1930`s. A woman who does not know self-reflection and possesses intellectual vanity is an aspect of the contemporary female writer that Kang captured. Park and Kang were female writers who received new education, but they do not reveal any particular stance on modern women as a human being in their works. What is important to the modern woman in Lee, Sunhee`s works that have been said to expose bourgeois sentiment is her own desire, emotion, and inner variation. The modern women represented in Lee`s works incarnate ambilaterality of urbanites who had to live in colonial modernism; that is, they bask in the modern culture but they feel a sense of alienation and solitude due to the fact that they cannot actually have it. The perspective of the female writers` in the 1930`s on modern women is starkly reflected on the modern women`s eyes that view Joseon`s penurious life (and space). Park`s modern woman accepts the reality of Joseon`s lower class in a surprised and educational way, whereas Kang`s modern woman hierarchizes it into a disparate space where people cannot live and therefore she should not belong. Meanwhile, for Lee`s modern woman farming and fishing villages are not a space for life and living, but they are just a background (nature) on which an individual`s desire and ego are projected. For bourgeois modern women, engrossment in themselves (their desires) is equal to life and livelihood, and thus the outside world cannot be considered significant. Their reality was different from that of Joseon`s general public.

      • KCI등재

        Collective “We” and the Communal Consciousness of Diaspora Identity in Chang-rae Lee`s On Such a Full Sea

        이지은 ( Ji Eun Lee ) 서울대학교 미국학연구소 2014 미국학 Vol.37 No.2

        This paper examines how Change-rae Lee`s On Such a Full Sea imagines a communal consciousness of diaspora identity through the use of a collective narrative voice that creates a narrative sense of split identity in readers` minds. The novel`s use of heroine figure, Fan, as a locus of communal consciousness very much corresponds to the conventional framework of the Bildungsroman narrative, which builds a communal consciousness incorporated into a progressive history through a depiction of the individual hero`s or heroine`s reconciliation with social norms. The narrative consciousness grounded in this individual hero/heroine invites readers to experience the sense of community congruent with the linear development of history. Lee`s novel, however, complicates the narrative consciousness through a collective narrative voice “we,” by shifting the referent from “we” inside the narrative frame to “we” outside the narrative frame and by dislocating the main figure Fan from society. The sense of disjointedness manifested by the narrative sense of split identity and the heroine`s displacement in society conceptualizes diaspora identity. Diaspora identity configured in this way propounds a more liberating version of communal consciousness as it allows deviations from norms and exploration of new possibilities not bound by nation or ethnicity. The communal consciousness of diaspora identity depicted in Lee`s novel challenges the homogeneous sense of community merged with history and gestures toward heterogeneous deviations from history.

      • KCI등재

        Repellent efficacy of essential oils and plant extracts against Tribolium castaneum and Plodia interpunctella

        Lee Hwa‐Eun,Hong Su Jung,Hasan Najmul,Baek Eun Joo,Kim Jun Tae,Kim Young‐Duk,Park Mi‐Kyung 한국곤충학회 2020 Entomological Research Vol.50 No.9

        This study was conducted to investigate the repellent efficacy of essential oils (Origanum vulgare, Pimpinella anisum, and Tanacetum cinerariifolium) and four plant extracts (Agastache rugosa, Capsicum annuum, Citrus reticulata, and Ginkgo biloba) against Tribolium castaneum (adults and larvae) and Plodia interpunctella (larvae). Gas chromatography/mass spectrometry analysis revealed the presence of carvacrol, anethole, and jasmolin I as the predominant constituent in O. vulgare, P. anisum, and T. cinerariifolium, respectively. Furthermore, ethyl hexopyranoside, 9,12‐octadecadienoic acid, cyclopentanol, and 2‐cresol were identified in A. rugosa, C. annuum, C. reticulata, and G. biloba, respectively. The repellent efficacy of each essential oil, plant extract, and the combination of oils was evaluated using a specially designed cylinder trap for 120 h. Among the three oils, O. vulgare and T. cinerariifolium had greatest repellent efficacy against P. interpunctella larvae. T. cinerariifolium exhibited effective repellence against the adults and larvae of T. castaneum. Therefore, O. vulgare (O) and T. cinerariifolium (T) were selected for further investigation of combined effects. Two essential oils were mixed in three different ratios of OT1 (1:3), OT2 (1:1), and OT3 (3:1). The repellent efficacies of OT1 and OT2 against the adults of T. castaneum were significantly greater than that of OT3. OT1 was effective against the larvae of T. castaneum, whereas OT2 was effective against the larvae of P. interpunctella. OT1 enhanced the repellent efficacy by approximately five times against larvae of T. castaneum, compared with that of T. cinerariifolium. Overall, OT1 was selected as the best repellent substance against all the tested insects.

      • Reported speech in conversation : A discourse analytic approach

        Lee, Eun-Joo 이화여자대학교 사범대학 교과교육연구소 2003 East west education Vol.20 No.-

        The study examines two different types of reported speech: explicit reported speech and nonexplicit speech in an attempt to analyze how reported speech is produced and interpreted in daily conversations. The results of the analysis clearly support the claim that what is reported in the reported speech is not only the speech itself but also the mental state description. The analysis also shows that factors such as linguistic and paralinguistic features as well as circumstances in which conversation takes place all play an important role in correct interpretation of the reported speech in natural conversations.

      • 제2형 당뇨병 환자에서 적극적 환자 교육이 혈당조절에 미치는 효과

        이윤욱,황원선,최선정,이동훈,김도현,이은희,홍은경,노혜림,정윤석,이관우,김현만 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.1

        연구배경: 현재까지의 당뇨병 교육에 대한 노력은 제한되었으며, 연구 결과를 보면 식사 조절 교육과 체중 조절 프로그램을 수행한 환자들 중 적극적이고 기간이 긴 교육을 받은 경우, 성공적 결과가 나타남을 알 수 있었다. 자가관리나 체중감량 등의 당뇨병 치료의 중요한 목표는 적극적이고 긴 기간의 교육 없이는 시행되기 어렵다. 본 연구에서는 외래에서 당뇨병 환자를 대상으로 시행할 수 있는 행동 및 식사 교육 등의 적극적 교육 프로그램을 개발하여 제2형 당뇨병 환자들을 대상으로 이들에게 식사 조절 방법에 대한 목표설정과 문제에 직면하였을 때의 해결 방법 등을 교육해서 궁극적으로는 적극적 자아관리에 연결될 수 있도록 도와주는 것을 목적으로 기존의 통상적 교육과 보다 적극적인 교육이 당뇨병 환자의 혈당 조절에 어떠한 영향을 미치는지에 대해 알아보기 위해 다음과 같은 연구를 시행하였다. 방법: 본 연구는 아주대학교 병원 내분비 대사 내과를 처음으로 방문하여 치료받았던 58명의 제2형 당뇨병 환자를 대상으로 하였다. 내원 환자들을 무작위하게 추출하여 진찰권 번호 끝자리에 따라 홀수는 통상적 교육군(conventional education group, CE)과 짝수는 적극적 교육군(intensive education group, IE)으로 나누어 교육하고, 3개월후에 교육의 효과를 평가하였다. 결과: 1) 연구 대상자들의 교육 전과 후의 공복혈당, 식후2시간 혈당 및 HbA_lc 치는 IE군과 CE군 모두 각 그룹 내에서, 유의적으로 감소하였다(p<0.05). IE군에서는 공복혈당이 12.4nmol/L에서 7.7nmol/L로, 식후2시간 혈당이 20.3nmol/L에서 10.9nmol/L으로, HbA_lc치가 9.4%에서 7.0%로 모두 교육 전에 비하여, 교육 후에 감소(p<0.05)하였고, CE군도 공복혈당은 10.9nmol/L에서 9.4nmol/L로, 식후2시간 혈당은 17.1nmol/L에서 14.6nmol/L으로 HbA_lc가 8.5%에서 7.3%으로 모두 교육 후에 감소하였다(p<0.05). 또한, 교육 전에 비하여 교육 후에 공복 혈당 및 HbA_lc치가 감소하는 정도는 IE군에서의 감소가 CE군에 비해 더 현저하였다Op<0.05). 2) 식사에 대한 태도는 3부분으로 나누어 식사에 대한 규칙성, 식사 내용의 균형성, 식사에 대한 태도 등으로 나누어 각각의 점수 및 총점을 비교하였으며 교육 전에 비해 교육 후에 연구 대상자들의 식태도가 향상되었음을 알 수 있었다. 두 그룹간의 차이를 분석한 결과 식사의 균형성 항목에서와 총점에서 유의적으로 두 그룹의 차이를 보여서 IE군에 CE군에 비해 식사의 균형성 측면이 향상되었고, 전체적인 식태도가 좋아졌음을 알 수 있었다(p<0.05). 결론: 비교적 긴 기간은 아니지만 적극적 교육을 받은 당뇨병 환자들이 통상적 교육을 받은 군보다 혈당 및 HbA_lc, 식태도 점수등의 수치의 호전뿐만 아니라 당뇨병 환자의 삶에서 중요한 부분을 차지하는 식사요법 관리 부분에 있어 향상됨을 알 수 있었다. Background: To this date, efforts to develop effective methods for the education of diabetic patients have been limited. The important goal of self-management and weight control for diabetic treatment can not be attained without long and intensive period of education. This study was undertaken to assess the effectiveness of an intensive educational program, of behavior and diet control, which was carried out on subjects with type 2 diabetes, on and out-patient basis. we compared the effectiveness of an intensive education programme with that of a conventional education programme for the self-management of type 2 diabetic patients. Methods: Subjects with type 2 diabetes were randomly selected, and allocated to one of two groups. One group received a conventional education programme of self-management(the CE group), and the second group received an intensive education progammes for three months, after which the effectiveness of the programmes were evaluate. Results: 1) The levels of fasting blood sugar(FBS), postprandial 2 hour blood sugar(PP2h) and HbA1c were significantly lowered in both groups following the intervention(p<0.05). In the IE group, the FBS declined from 12.4nmol/L to 7.7nmol/L, PP2h declined from 20.3nmol/L to 10.9nmol/L, and the HbA_lc showed a similar decline from 9.4 to 7.0% after intervention(p<0.05). In the Ce group, the FBS declined from 10.9 to 9.4nmol/l, the PP2h decreased from 17.1 to 14.6nmol/l, and the HbA_lc also decreased from 8.5 to 7.3% after intervention(p<0.05). The decrease in the FBS and HbA_lc following the educational intervention was more pronounced in the IE group than the CE group(p<0.05). 2) The effectiveness of the education programmes in promoting appropriate dietary behavior in the diabetic subjects was assessed by a scoring system in three parts: a regularity score, a balance score and an attitude score. From a comparative study of the three scores, the patients attitudes were observed to be much improved in both the groups following the intervention compared to before the programmes, but the balance and total scores were significantly higher in the IE group than the CE group(p<0.05). Conclusion: We can conclude that the intensive diabetic education programme is more effective than a conventional programme, not only in improving the patients' levels of glucose, HbA_lc, and dietary score, but also the diabetic patients self-control abilities, promoting behavioral change, and prompting problem solving capabilities in respect to the everyday problems that they have to face throughout their lives(J Kor Soc Endocrinol 18:63∼72, 2003).

      • 아동의 物活論的 思考에 관한 연구 : Piaget의 가설을 중심으로

        李恩和,尹賢燮 이화여자대학교 한국문화연구원 1976 韓國文化硏究院 論叢 Vol.28 No.-

        This study was intended to investigate the Korean child's animism and to test Piaget's hypothesis with Huang-Lee's experimental tools. The experimental hypotheses in this study were: 1) Piagetian animism could be found in Korean children's mentality, and 2) Piaget's hypothesis could be proved not only by Russell-Dennis's tools but also by Huang Lee's. Russell and Dennis have proved Piaget's hypothesis and standardized the experimental procedures to test child's animism; however, M. Mead and Huang-Lee have denied the Piagetian animism in Manusian and Chinese children. Russel and Dennis have also suggested four developmental stages in child's animism. Twenty Korean children, aged between 4-7, were tested individually, the combined experimental procedures of Russell-Dennis and Huang-Lee being used, As a result, the first hypothesis in this study was positively confirmed only by Russell-Dennis's method. This means that the second hypothesis in this study was not confirmed. 90% of the Subjects in this study have had the concept of life or living, and did not regard inanimate objects as having characteristics of "feeling pain." It seems to us that the subjects in this study tend to make some cognitive continuity between their awareness of their living and the being of physical objects. In Piagetian terms, the subjects have not dissociated themselves from their physical and natural environment.

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