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>

업종에 따른 연 취급 사업장의 기중 연 농도 및 연 노출 수준 평가

이병국,김용배,리갑수,안현철,김화성,이용진,황규윤,장봉기,이성수,안규동 순천향대학교 산업의학연구소 1999 순천향산업의학 Vol.5 No.1

In order to obtain an useful information for health management and biological monitoring of lead exposed workers, Authors tried to investigate air lead level and the lead exposed level of workers in lead industry according to occupational category. The subjects in our study were 2074 workers in 7 lead-using industries, and study subjects were divided into 4 occupational categories such as storage battery industry (type 1), primary smelting industry (type 2), secondary smelting industry (type 3) and litharge making industry (type 4). Blood zincprotoporphyrin concentration (ZPP), blood lead concentration (PbB) and urinary δ -aminolevulinic acid (ALAU), hemoglobin (Hb), hematocrit (Hct) were selected as the indices of lead exposure. Personal variables such as age, work duration were also collected. The results were as follows. 1. The geometric mean air lead in 9 lead-using industry was 0.1133±4.3120 ㎎/㎥, and that in type 1, 2, 3 and 4 was 0.1038±3.4952 ㎎/㎥, 0.0429±3.4329 ㎎/㎥, 0.1877±2.5123 ㎎/㎥ and 0.9961±5.2910 ㎎/㎥, respectively. 2. The mean ZPP in 9 lead-using industry was 53.1±28.0 ㎍/㎗, and that in type 1, 2, 3 and 4 was 52.0±24.8 ㎍/㎗, 48.0±16.4 ㎍/㎗, 109.8±85.6 ㎍/㎗ and 74.3±37.8 ㎍/㎗, respectively. There was significant difference in ZPP according to occupational category (P<0.01). The percents of lead workers whose ZPP were above 100 ㎍/㎗ in type 1, 2, 3 and 4 were 4.0%, 1.7%, 34.3% and 21.6%, respectively. 3. The mean PbB in lead-using industry was 26.0±11.2 ㎍/㎗, and that in type 1, 2, 3 and 4 was 25.3±11.1 ㎍/㎗, 26.7±8.8 ㎍/㎗, 50.3±15.2 ㎍/㎗ and 36.4±11.0 ㎍/㎗, respectively. There was significant difference in PbB according to occupational category (P<0.01). The percents of lead workers whose PbB were above 40 ㎍/㎗ in type 1, 2, 3 and 4 were 10.4%, 7.7% 71.9% and 43.2%, respectively. 4. While the correlation of Hb corrected PbB with ZPP was higher than non corrected PbB, the correlation of log-transformed ZPP with PbB was higher than non corrected ZPP. 5. Simple linear regressions of PbB and corrected PbB as independent variable with ZPP, log-transformed ZPP and ALAU as dependent variable were statistically significant (P0.01). Coefficient of determination of corrected PbB with other variables was higher than non corrected PbB. As the result of this study, it was suggested that reconsideration of environmental and biological monitoring program was highly recommended for secondary smelting and litharge making industry.

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.

평면형 Bi-Sb 다중접합 열전변환기의 특성

이현철,유호종,김진섭,함성호,신장규,이종현,이정희,권성원,박세일 경북대학교 센서기술연구소 1997 센서技術學術大會論文集 Vol.8 No.1

A planar Bi-Sb multijunction thermal converter for the precise measurements of ac voltage and current has been fabricated and its characteristics was discussed. In order to convert ac power into heat, a bifilar thin film Pt-heater, which could cancel its Thomson and Peltier effects, was prepared on the Si_(3)N_(4)/SiO_(2)/Si_(3)N_(4) diaphragm for the thermal isolation between heater and silicon substrate. To convert the temperature or the heat generated by the heater into dc voltage and current, hot and cold junctions of the Bi-Sb thermopile, which has a large difference in Seebeck coefficients, were formed on the dielectric diaphragm and the silicon substrate, respectively. The respective thermal sensitivity of the thermal converter with a bifilar heater was about 10.1 mV/mW and 14.8 mV/mW in the air and vacuum, which is about eight times higher than that of commercial 3-dimensional thermal converter. In the case of ac 2 V-input voltage, the ac-dc voltage transfer difference was about ±2.0 ppm, and in the case of ac 10 mA-input current, the ac-dc current transfer difference was about ± 0.6 ppm, in the frequency range from 10 Hz to 10 kHz.

연골외막세포가 포함된 alginate beads를 이용한 토끼에서의 골연골결손 치료

안현정,김은미,정미현,조현철,이인범,성상철,이명철 대한정형외과연구학회 2003 대한정형외과연구학회지 Vol.6 No.2

비모형화 동특성을 고려한 로보트 매니플레이터의 실시간 적응제어

한성현,김휘동,이진,이현철,이희섭 경남대학교 신소재연구소 1994 論文集 Vol.4 No.-

기존의 로봇 매니퓰레이터의 제어방법들을 간단한 고전적 제어방법들의 응용은 가능하지만, 고속운전이나 빈번한 부하변동에 의해 역학적으로 나타나는 각 관절사이의 연성(coupling), 관성파라미터의 불확실성, 모델링오차 등으로 인하여 로봇 제어기의 성능과 응용범위등은 큰 제약을 받게 된다. 본 연구에서는 제어기의 예측불허의 외란 및 파라미터의 불확실성 등에 대한 적응성의 향상을 위하여 적응 모델추종제어기법을 적용하여 로봇 매니퓰레이터 동적모델에서의 매개변수의 불확실성 및 미지의 외란, 존재, 갑자스런 부하변동에서도 좋은 제어성능이 유지 될 수 있는 견실한 로봇 관정 제어방식에 대한 연구를 중점으로 다룬다. 적응제어알고리즘은 초안정도(hyperstability)이론과 적응 모델 추종 제어의 원리를 바탕으로 유도되었고, 적응 제어기의 기온구조를 비선형성의 보상을 위한 내부루프의 MRAC구조와 고정된 게안을 갖는 외부루프와 PID제어기의 조합으로 구성되는 혼성구조의 제어기를 제언한다. In this paper, robust adaptive control approach is presented to inplement of the real time control of the industrial robot manipulator. The purpose of proposed adaptive control scheme is to achieve good tracking performance of desired trajectory tracking of joint position and veloeity under the existence of the payload variation and uncertinity of inertia parameter. The feedback gains of the controller are updated and adaptied in each sampling time to achieve the desired control performance. The proposed adaptive control algorithm is developed within the framework of adaptive model following control scheme using the Lyapunov direct method. To illustrate the performance of the proposed adaptive controller, simulation test is performed in the presence of the parameter uncertainties and payload variations.

크롬(Ⅵ)의 체내 흡수와 소실속도에 관한 연구

김현영,이성배,임철홍,이권섭,정용현,이종성,한정희,전윤석,황호순,이용묵 한국산업위생학회 2003 한국산업보건학회지 Vol.13 No.1

The CrO3 mostly used in plating. metal surface disposal, leather, cosmetic manufacturing, as an experiment material by repeatedly inhaling and exposure the male S.D. rats at a 0.00, 0.2., 0.50, 1.25 mg/㎡ concentration(particle size: 0.5-0.5 aerosol)6hours a day, 5day a week in 13weeks comparing with 2weeks, 8weeks of recovery group about the noxiousness of the experiment animal and the reduce scale of the CrO3 in the internal organ especially in blook and respiratory organ with the period of convalescent and clearance. The experiment results which we received are as follows. 1. In blood the RBC, HGB and HCT experiment, rats with 0.20, 0.50 mg/㎡ concentration showed that there were some decreases but not dependent. The kidneys absolute weight compared with control group was reduced intentionally(p〈0.05) and the lungs absolute weight compared with control group showed intentional increase(p〉0.05). 2. After the exposure of the experiment material, the whole blook, l\blood plasma and red blood cell in blood by (x): the period of convalescent, per (y); the decreasing of Cr concentration, was y=66.51 e -0.057x, y=67.2 e-0.101x, y=70.01 e-0.030 in 0.50 mg/㎡ exposure concentration by calculating the clearance coefficient of correlation, and the half life (day)was estimated 12.0, 6086, 23.0 each. 3, After the exposure of the experiment material, the experiment animals lung, liver and kidneys by(x); the period of convalescent, per (y); the decreasing of Cr conentration, was y=1808 e-0.00493x, y=12.02e-0.0297x, y=67.61 e-0.0292x in 0.50mg/㎡ exposure concentration by calculating the clearance coefficient of correlation, and the half life(day)was estimated 140.6, 23.3, 23.7, each, and including lung, liver with all of the experiment internal organs, the Cr clearance decreased as the exposure concentration increased.

SD Rats를 이용 1-hexene의 흡입독성 연구

김현영,임철홍,정용현,이권섭,이성배,이준연,한정희,전윤석,이용묵 한국환경독성학회 2001 환경독성보건학회지 Vol.16 No.4

The purpose of this study was to investigate the acute (4 hours) and repeated-dose (6 hours a day, 5 days a week, 4 weeks) toxic effects of I -hexene on Sprague- Dawley (SD) rats which were treated by inhalation. The results were as follows; I. The median lethal concentration (LC_(50)) was estimated 52,694 ppm (confidence limit 95%; 49,494~55,447 ppm) in acute inhalation. Abnormal clinical signs related to the l-Hexene were not observed with the acute inhalation dose. Gross findings of necropsy revealed on evidence of specific toxicity related to the 1-hexene, II. By repeated inhalation exposure the body weight of male were more or less reduced by the dose of 2,500 ppm and 5,000 ppm compared with control group. However there were no significant variation hematology and blood biochemistry for the exposed rats compared with the control rats. Abnormal clinical signs and gross findings of necropsy related to the 1-hexene were not shown. In conclusion when we exposed I-hexene to SD rats for 4 weeks, 5 days per week, 6 hours per day, the Lowest observed effect level (LOEL) was over 2,500 ppm and Non observed effect level (NOEL) was below 500 ppm.

Alginate 배양내에서 Transglutaminase가 연골막세포에 미치는 영향

박정선,공차배,김충현,안현정,정미현,성상철,김희중,조현철,이상훈,이명철 대한정형외과연구학회 2003 대한정형외과연구학회지 Vol.6 No.2

악성 림프종 환자에서 발생한 다형홍반

여운철,조광현,이유신,허대석,이승철 ( Un Cheol Yeo,Kwang Hyun Cho,Yoo Shin Lee,Dae Seog Heo,Seung Chul Lee ) 대한피부과학회 1990 대한피부과학회지 Vol.28 No.5

A Case of Erythema Multiforme A ssociated with Malignant Lymphoma Un Cheol Yeo, M.D., Kwang Hyun Cho, M.D., Yoo Shin Lee, M.D., Dae Seog Heo*, M.D., Seoung Chul Lee**, M.D Department of Dermatology and Internal Medicine*, College of Medicine, Seoul National University, Seoul, Korea, Department of Dermatology**, College of Medicine, Inha University, Kyung Gi Do, Korea We report a case of erythema multiforme associated with malignant lymphoma. Fifty-six-year-old male patient visited our clinic complaining generalized skin lesions which were compatible with erythema multiforme clinically and histopathologically. The skin lesions were treatment-resistant, recurrent and persistent for 3 years. In consideration of old age, atypical features of erythema multiforme and no other demonstrable etiology of erythema multiforme, we studied for internal malignancy. Malignant lymphoma at the duodenum was revealed by UGI series, abdominal CT, and endoscopic biopsy. After chemotherapy, the tumor mass and active skin lesions were cleared simultaneously. Erythema multiforme may be regarded as one of the paraneoplastic syndromes.