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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

        Semiotic Analysis of Children's Literature

        Lee, Hyun-Kyung 한국외국어대학교 통번역연구소 2006 통번역학연구 Vol.10 No.1

        Lee, Hyun-Kyung. (2006). Semiotic Analysis of Children's Literature. Interpreting and Translation Studies 10-1, pp.109-131. 한국의 출판시장도 세계화라는 추세에 부응하기 위해 최근 들어 그 어느때보다도 많은 번역본들이 출간하고 있다. 이에 따라 아동문학시장도 한국부모들의 높은 교육열에 힘입어 좋은 책을 국내에 소개하려는 노력의 일환으로 단행본 번역출간이 눈에 띄게 들고 있다. 미국에서 그 해에 발표된 가장 뛰어난 아동문학에 주어지는 '뉴베리 상' 수상작들은 미국뿐 아니라 전세계 아동문학계의 중요한 위치를 차지하며 여러 언어로 번역되어 전세계 아동들의 사랑을 받고있다. 본 연구에서는 이러한 '뉴베리 상' 수상작품이 한국어로 번역되어졌을 때 미국을 중심으로 하는 서구문화와 언어의 이질성을 어떻게 번역으로 옮기는 것이 바람직한가하는 문제를 다루고자 한다. 그에 대한 이론적 틀로 '기호학적 접근법'을 시도하고자 하며 하부개념으로 상호텍스트성, 내포, 외연, 신화 등도 분석의 도구로 다루고자 한다. 본 연구에서는 언어와 문화의 상이성을 다루는 번역에 있어서 거시적인 관! " 미시적인 관점 두 단계에서 모두 번역사의 역할이 중요시됨을 알 수 있다.

      • 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.

      • KCI등재

        제주도 지하수 질산염 농도의 시·공간적 변화 특성: 장기(1993-2015) 모니터링 자료의 평가

        김호림(Ho-Rim Kim),오준섭(Junseop Oh),도현권(Hyun-Kwon Do),이경진(Kyung-Jin Lee),현익현(Ik-Hyun Hyun),오상실(Sang-Sil Oh),감상규(Sang-Kyu Kam),윤성택(Seong-Taek Yun) 대한자원환경지질학회 2018 자원환경지질 Vol.51 No.1

        1993년부터 2015년까지 관측된 제주도 지하수 장기모니터링 관측정(N = 4,835)에서 수집된 지하수 수질자료(N = 21,568)를 기반으로 질산성질소의 시공간적 변동 특성을 평가하였다. 제주도 지하수의 질산성질소 농도의 중앙값은 2.5 mg/L로서 다른 국가나 대륙의 조사 결과에 비해 다소 높거나 유사한 것으로 나타났다. 또한 지하수 용도, 행정구역 및 고도 별로 유의한 차이를 보였다. 특히, 산간 지역에 비해 저지대 해안가에 위치한 농업 및 주거지역에서 농도가 높음을 확인하였다. Mann-Kendall 및 Sen’s slope 분석을 활용한 질산성질소 농도의 추세 분석 결과, 하류 저지 대에 비해 중산간지역에서의 질산성질소 농도 증가 경향이 뚜렷하였다. 제주도 내 토지 피복의 시계열 변화 특성과 결부 지어 보면, 중산간지역의 오염 증가 추세는 농업지역의 확장 등 인위적 활동 증가에 기인한 결과로 판단된다. 반면,기지정된 지하수자원특별관리구역에서는 전반적으로 질산성질소 농도의 감소 경향이 나타났는데, 이는 지하수 관리 측면에서 수질관리를 위한 적극적인 정책이 유효함을 시사한다. 본 연구에서는 제주도 지하수의 질산성질소 오염관리를 위한 적정 방안을 제안한다. The spatio-temporal variations of nitrate concentrations in groundwater of Jeju Island were evaluated by an analysis of time series groundwater quality data (N = 21,568) that were collected from regional groundwater monitoring (number of wells = 4,835) for up to 20 years between 1993 and 2015. The median concentration of NO 3 -N is 2.5 mg/L, which is slightly higher than those reported from regional surveys in other countries. Nitrate concentrations of groundwater in wells tend to significantly vary according to different water usage (of the well), administrative districts, and topographic elevations: nitrate level is higher in low-lying agricultural and residential areas than those in high mountainous areas. The Mann-Kendall trend test and Sen’s slope analysis show that nitrate concentration in mid-mountainous areas tends to increase, possibly due to the expansion of agricultural areas toward highland. On the other hand, nitrate concentrations in the Specially Designated Groundwater Quality Protection Zones show the temporally decreasing trend, which implies the efficiency of groundwater management actions in Jeju. Proper measures for sustainable groundwater quality management are suggested in this study.

      • KCI등재

        심인성 어지럼증 환자의 정신과적 증상에 관한 연구

        이경규,이지영,김현우,이정엽,백기청,김재일,이근호 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.5

        연구목적 : 어지럼증을 호소하는 환자들 중에 심인성 어지럼증 환자가 상당수 있다는 것은 알려져 있고, 이러한 심인성 어지럼증과 동반되는 정신질환으로는 불안장애, 우울장애, 인격장애 등이 있다. 이에 본 연구에서는 심인성 어지럼증 환자들의 빈도와 정신과적 증상을 알아보고자 하였다. 방 법 : 어지럼증 환자들에게 평형검사, 자세운동측정검사, 자세변화검사, caloric testing을 시행하여 심인성, 말초성 및 중추성의 3군으로 분류한 후 각각 14명, 16명, 32명을 대상으로 하였다. 대상환자들에게 한국판 Beck 우울척도검사(K-BDI), Spielberg의 상태-특성 불안검사(STAI). 간이정신진단검사(SCL-90-R)를 이용하여 정신과적 증상을 측정하여 이들 세 군을 비교분석하였다. 결 과 : 1) 심인성 어지럼증을 가진 환자는 어지럼증을 나타내는 환자 총 62명중에서 14명으로 22.6%를 차지하였다. 2) K-BDI에 따른 세 군간의 비교에서는 세 군간에 유의한 차이를 보이지 않았다. 3) STAI에 따른 세 군간의 비교에서 상태불안(STAI-S) 및 특성불안(STAI-T) 모두에서 세 군간에 유의한 차이를 보이지 않았다. 4) SCL-90-R에 따른 세 군간의 비교에서는 9개의 척도 중에서 공포불안척도에서만 중추성 어지럼증군이 47.56±6.90, 말초성 어지럼증 군이 53.50±13.74, 심인성 어지럼증 군이 58.50±16.05로 심인성 어지럼증 환자군이 중추성 어지럼증 환자군에 비하여 유의하게 높은 것으로 나타났다(p<0.01). 5) 통증 증상에 있어서는 세 군간에 유의한 차이를 보이지 않았고, 위장관 증상과 성기능 장애 증상은 중추성과 말초성 어지럼증 군이 심인성 어지럼증 군에 비하여 유의하게 높은 것으로 나타났다(p<0.01). 결 론 : 상기 결과를 토대로 했을 때 어지럼증 환자들에 대한 정신과적 접근을 위하여 각 군을 나누는 것은 별 의미가 없으며 어지럼증 환자들의 어지럼증 자체에 대한 직접적이고 집중적인 치료가 더욱 필요할 것으로 생각된다. Objectives : This study was aimed to investigate psychiatric symptoms in patients with psychogenic dizziness and compare these findings with those of patients with central and peripheral dizziness. Methods : A total of 62 patients with dizziness was the subject of investigation, and patients were classified into 32 with central type, 16 with peripheral type, and 14 with psychogenic type. Korean standardized Beck Depression Inventory(K-BDI), State and Trait Anxiety Inventory(STAI), and Korean standardized edition of Symptom Checklist 90 Revised(SCL-90-R) were used for the assessment. Statistically, Pearson's chi-square test and one-way ANOVA with Scheffe's test were used with SPSS/PC for windows 6.0. Results : The results were as follows : 1) The proportion of psychogenic dizziness was 22.6% of the total subjects. 2) Total scores of K-BDI were not significantly different among the 3 groups. 3) Total scores of state anxiety and trait anxiety were not significantly different among the 3 groups. 4) In SCL-90-R, psychogenic dizziness group showed significantly higher score of phobic anxiety only(p<0.01) than central dizziness group. And others were not significantly different among the 3 groups. 5) In additional somatic symptoms, pain score was not different among the 3 groups, but gastrointestinal and sexual symptoms scores of central and peripheral dizziness group were significantly higher than those of psychogenic dizziness group(p<0.01). Conclusion : These results suggest that psychiatric symptoms in patients with psychogenic dizziness are not different from those of patients with central or peripheral dizziness. Therefore, the more direct and intensive treatment may be necessary regardless of the type of dizziness.

      • 2자유도 PI 제어기를 이용한 BLDC 전동기의 벡터제어에 관한 연구

        이종현,성낙규,이상집,이승환,오봉환,이훈구,한경희 명지대학교 산업기술연구소 2001 産業技術硏究所論文集 Vol.20 No.-

        This paper describes the speed control method of BLDC Motor using TDOF PI ( Tow-degree of freedom PI ). PI control method generally used has difficulty in efficient speed control because speed response and load torque response interfere each other. It can't decrease the overshoot of motor speed w rm, and shorten the response time of load torque TL, at the same time according to the step alternation of speed reference w rm. Therefore TDOF PI is applied to BLDC Motor in order to supply these weak points of PI control method in this paper. TDOF PI can get the torque characteristic of short response time as well as stable and prompt speed adjustment by separate control for speed response and load torque response. The results from the tests of C program simulation and system construction show that TDOF PI is superior to PI control system in speed adjustment and load torque response.

      • 봉독약침이 류마티스 관절염 환자의 기능회복 및 삶의 질에 미치는 영향

        이상훈,이현종,박상민,김수영,박재경,홍승재,양형인,이재동,최도영,김건식,이두익,이윤호 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

        Objective: To evaluate the effects of bee venom acupuncture(BVA) on the rehabilitation and quality of life in rheumatoid arthritis(RA) patients Methods: Patients with RA were treated with the BVA therapy twice a week for 3 months. Tender joint counts, swollen joint counts, morning stiffness, Erythrocyte Sedimentation Rate(ESR), C-reactive protein(CRP), patient global assessment, physician global assessment, Korean health assessment questionnaire(KHAQ) were estimated and analyzed before and after BVA therapy. Results: Tender joint counts, swollen joint counts, morning stiffness showed significant decrease after BVA therapy. But, as acute inflammatory reactants, ESR showed no significant difference and CRP showed significant increase after BVA therapy. Patient global assessment physician global assessment, and KHAQ index showed significant improvement after BVA therapy. Conclusions: BVA therapy can improve rehabilitation and health-related quality of life RA patients as well as clinical symptom and signs. Further study is required in more population with large scale including acute inflammatory reaction of BVA therapy.

      • 일부 사업장 건강증진사업 실태조사 및 요인분석

        이경화,이원철,이강숙,홍현숙,송연이 가톨릭대학교 산업의학센터 2000 韓國의 産業醫學 Vol.39 No.2

        For the purpose of access the health promotion activities in 138 worksite which had more than 50 workers, we surveyed the questionnaire on May and September 1998. The results of survey were as follows: 1.59 companies(45.1%) were conducting the health promotion activities. Most of them were manufacturing and located Kyung-sang province and had nurses as a health manager. 2.Companies operating the health promotion activities had significant higher degree of satisfaction and usage of welfare facilities than non-operating companies. 3.The level of knowledge for regulations, professional skills, and performance related health promotion was low in all companies. Top manager's interest and will for investment to health promotion was significant lower in non-operating companies. 4.The reasons why the health promotion program was not operated, were low budget, top manager's indifference, lack of information, work overloading, no human resource, an insufficient governmental support in order. 5.The most necessary items for program were education and promotion, budget, and governmental support. Needed personnel were nurses, fitness trainner, and necessary program were health management, exercise, nutrition, and stress counselling. For comparing before and after IMF, amount of budget was decreased. In conclusion, this study suggested that major barriers to conduct health promotion activities were lack of budget, lower interest of top managers, and insufficient professional information, therefore detail health promotion program would be developed and supported by government.

      • 봉독약침이 류마티스 관절염 환자의 관절 통증, 종창 및 급성 염증 반응에 미치는 영향

        이상훈,이현종,백용현,김수영,박재경,홍승재,양형인,김건식,이재동,최도영,이두익,이윤호 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

        Objective In order to study the effects of bee venom(BV) on the pain, edema, and acute inflammatory reactant of rheumatoid arthritis(RA) patients. Methods Patients with RA who met the ACR(American College of Rheumatology) 1987 revised criteria for the diagnosis of RA were treated with the BV therapy twice a week for 3 months. Tender Joint counts, swollen joint counts, Visual analog scale(VAS), morning stiffness, ESR. C-reactive protein(CRP) were analyzed before and after BV therapy. Results The results as follows. 1. Tender joint counts in patients after BV therapy were significantly lower than those before BV therapy(9.0±7.9 vs 15± 11.4, p=0.002). 2. Swollen joint counts of the patients after BV therapy were significantly lower than those before BV therapy(50±61 vs 15±23, p=0.001). 3. VAS in patients after BV therapy was significantly lower than those before BV therapy(608± 17.6 vs 380± 159, p=0.000). 4. Duration of morning stiffness in patients after BV therapy was significantly reduced compared with that before BV therapy(119.1± 112.6 min vs 59.0±89.7 min, p=0.009). 5. ESR and CRP were not significantly changed before and after BV therapy, suggesting BV itself could make inflammatory reaction as well as therapeutic effect. Conclusions BV therapy improved tender joint counts, swollen joint counts and duration of morning stiffness in this study, and further study is needed on long-term effect of BV therapy.

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