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>

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Protective Effects of N-acetylcystenine and Selenium against Doxorubicin Toxicity in Rats

Yeo-sung Yoon,Sun-don Kim,Min-hye Lee,Heung-shik S.Lee,In-se Lee,Je-kyung Sung,Eun-sung Park 대한수의학회 2003 Journal of Veterinary Science Vol.4 No.2

Effects of N-acetylcysteine and Selenium against Doxorubicin Toxicity in RatsEun-sung Park, Sun-don Kim1, Min-hye Lee, Heung-shik S. Lee, In-se Lee, Je-kyung Sung and Yeo-sung Yoon*

Gilbert 증후군에서 열량 제한 시험과 Phenobarbital 자극 시험의 의의(14예)

이헌영,채경훈,정재훈,강윤세,김연수,문희석,박기오,이엄석,김선문,김석현,성재규,이병석,이강욱 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Gilbert 증후군은 인구의 7%에서까지 나타날 수 있는 매우 흔한 증후군으로서 비진행성인 양성의 만성적 경과를 치하며, 간질환의 증상과 징후가 없는 경한 비포합형 고빌리루빈혈증이 특징인 일종의 체질적인 증상으로서 혈장 빌리루빈 농도에 대한 사춘기의 영향 때문에 10대와 20대에 자주 진단이 된다. 따라서 임상적인 중요성은 미약하지만 높은 빈도가 예상되는 점에 그 중요성이 부여되어야 할 것이다. 따라서 적정한 임상적 진단법으로 기왕에 소개된 열량제한 시험과 phenobarbital 유도 시험을 시행하고 이들의 진단적 가치를 알아보기 위하여 본 연구를 시행하였다. 1990년 7월부터 1999년 4월까지 충남대학교병원에 내원하여 HBsAg, IgG anti-HBc 및 anti-HCV가 음성이고, 간 초음파 스캔에서 이상이 없으며, 혈청 AST, ALT 및 AP가 정상인 비음주자에서 경한 비포합형 고빌리루빈혈증이 있는 14예의 환자들을 대상으로 ^(99m)Tc-DISID 스캔을 시행하였으며, 기저 치 총빌리루빈 및 포합형 빌리루빈 치를 측정한 다음에 하루에 400Kcal로 48시간동안 제한한 열량 제한 시험을 시행하였고, phenobarbital을 하루 60mg씩 5일간 투여한 후에도 각각 총빌리루빈과 포합형 빌리루빈 치를 검사하여 비포합형을 구하였다. 대상 환자들은 모두 14예로서 남자가 11예(78.6%)였고 여자가 3예(21.4%)여서 3.7:1로 남자에서 많았으며, 20대가 6예(42.9%), 30대가 역시 6예(42.9%) 및 40대가 2예(14.2%)로서 2,30대가 대부분(85.8%)이었다. 열량 제한 시험 후의 총빌리루빈 치, 비포합형 및 포합형 빌리루빈 치들은 평균 각각 5.5±2.7, 4.2±2.3 및 1.3±10mg/dL 로서, 시험 전 치들인 3.0±0.8, 2.2±0.8 및 0.7±0.4mg/dL 보다 유의하게(p=0.001, p=0.001, p=0.023) 상승하였다. 포합형 빌리루빈 치도 유의하게 상승하였으나 비포합형의 상승보다는 훨씬 낮아서 주로 비포합형이 증가하였다. phenobarbital 투여 중 설사가 발생하여 중단한 1예를 제외한 13예에서 열량 제한 시험 후에 상승하였던 총, 비포합형 및 포합형 빌리루빈 치가 phenobarbital 유도 시험후에는 2.0±1.1, 1.5±0.8 및 0.5±0.4mg/dL로서 열량 제한 시험 결과보다 유의하게 낮아졌고(p=0.00, p=0.000, p=0.001), 열량 제한 시험 전의 기초치들인 3.0±0.8, 2.2±0.8 및 0.7±0.4mg.dL 보다도 더욱 낮아졌으며 유의한 차이(p=0.001, p=0.02, p=0.005)를 나타내었다. 14예에서 시행한 ^(99m)-Tc DISIDA 스캔에서 9예(64.3%)가 정상이었고, 5예(35.7%)에서는 심장 및 신장으로의 간외 섭취가 3예였고, 60분까지 소장 배출이 없는 배설 지연 예와 담낭 수축 불량 예가 각각 1예 씩 발견되었다. Phenobarbital 투여시험에서 민감도가 열량제한시험에 비해 더 높았다(92.3%와 50.0%). Gilbert 증후군에서 1일 400 Kcal로 48시간의 열량제한 시험과 1일 60mg의 phenobarbital을 5일간 투여하는 유도 시험은 편리하고 유용한 임상적인 진단법으로 이용할 수 있다고 생각된다. 그러나 열량 제한 시험에서는 증가 기준의 통일이 필요하다고 유추되며 phenobarbital 유도 시험이 민감도가 더 높은 것으로 생각된다. Gilbert's syndrome is very frequent and benign chronic process characterized by mild, intermittent, unconjugated hyperbilirubinemia without any symptom and sign of liver disease. Previously intoduced caloric restriction test and phenobarbital stimulation test as two appropriate clinical tests had been examined and their diagnostic values were reevaluated. Fourteen patients with mild, persistent, unconjugated hyperbilirubinemia were included. Subsequently caloric restriction has been applicated by 400 Kcal/day for 48 hours and phenobarbital has been prescribed by 60 mg/day for 5 days. Therafter serum levels of total and direct bilirubin were measured. Most of the patients were third and fourth decade(85.8%) and male predominant. Each basal serum levels of total, indirect and direct bilirubin were 3.0±0.8, 2.2±0.8 and 0.7±0.4 mg/dL. After caloric restriction test, each levels were increased significantly to 5.5±2.7, 4.2±2.3 and 1.3±1.0 mg/dL(p=0.001, p=0.001, p=0.023). After phenobarbital stimulation test for 13 patients had been practiced, increased levels of each bilirubin after caloric restriction test were decreased significantly to 2.0±1.0, 1.5±0.8 and 0.5±0.4 mg/dL(p=0.000, p=0.000, p=0.001) and these levels were significantly lower than basal levels(p=0.001, p=0.02, p=0.005). The sensitivities of caloric restriction test were 85.7%, 50.0%, and 71.4%, 35.7%(1.0, 1.5 mg increase of total bilirubin and 1.0, 1.5 mg/dL increase of indirect bilirubin). The sensitivities of phenobarbital stimulation test were 93.2% and 92.3% at criteria of 1.5 mg/dL increase of total bilirubin and indirect bilirubin. On the diagnosis of Gilbert syndrome, caloric restriction test and phenobarbital stimulation test are convenient and useful diagnostic tools in clinical face. And also phenobarbital stimulation test has higher sensitivity than caloric restriction test. Furthermore, standardization of bilirubin increment would be necessary in caloric restriction test.

ATHB12, an ABA-lnducible Homeodomain-Leucine Zipper (HD-Zip) Protein of Arabidopsis, Negatively Regulates the Growth of the Inflorescence Stem by Decreasing the Expression of a Gibberellin 20-Oxidase Gene

Ora Son,허윤선,김윤경,이현정,김성한,김미란,남경희,이명석,김부용,박종범,박정안,이석찬,Atsushi Hanada,Shinjiro Yamaguchi,이인정,김승기,윤대진,Eva So¨derman,천충일 Sookmyung Women's University Research Institute of 2010 여성과 건강 Vol.6 No.1

The First Case of Pure 3D Laparoscopic Living Donor Hepatectomy in Kazakhstan

( Kyung Chul Yoon ),( Kaliev Aset ),( Zhanadil Almyrzauly ),( Yerlan-sultangereyev ),( Bazylbek Zhakiev ),( Kwang-woong Lee ),( Kyung Chul Yoon ),( Kaliev Aset ),( Zhanadil Almyrzauly ),( Bazylbek Zha 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Laparoscopic living donor hepatectomy is performed selectively in some countries because of the small sized structures and anatomic variations which requires more precise technique. In Kazakhstan about 200 cases of living donor liver transplantation were performed starting from December 2011.We now present the first case of laparoscopic living donor hepatectomy in Kazakhstan using a 3D laparoscopic device with colleagues from Seoul National University Hospital, Korea by professor KwangWoong Lee. Methods: A 23-year-old male volunteered for living donor to his older brother who had combined hepatitis B, D and C related cirrhosis without any history of antiviral treatment. The recipient age was 36 and His model for end-stage liver disease score was 22. Brief morphologic characteristics of donor and recipient were as follows: donor - height 177 cm, weight 74 kg, BMI 23.64 kg/m²standard liver volume 1348 ml; recipient - height 172 cm, weight 78 kg, BMI 26.44 kg/m², standard liver volume 1350ml.Donor graft volume was 820ml and left remnant liver volume was 32%. Results: The surgery was performed in October 2016 with 5 port insertion using an ultrasonic dissector, Cabitron Ultrasonic Aspirator, and clips. The liver was extracted via 10 cm sized suprapubic incision. V5 and V8 were reconstructed to the right hepatic vein using the PTFE graft. The Donor’s operation time was 295 minutes and estimated bleeding was 700ml. The recipient had sanguinous drain and bleeding control was performed postoperative day 1 due to bleeding from hilar plate. Both donor and recipient were discharged after 15 and 28 days and the donor was not eventful. Conclusions: 3D laparoscopic hepatectomy has been progressively developed along the past decade. High quality studies allied with high-level surgical training are required to base surgical practice and to disseminate the benefits of to many centers as possible. Future applicability of new technologies such as robot assistance and 3D surgery is still under investigation in Kazakhstan.

요골동맥을 이용한 관동맥 조영술의 유용성

윤정한,이승환,이한요,김장영,김일회,최윤종,이형준,이명옥,김승년,황성오,홍인수,최경훈 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.10

ATHB12, an ABA-lnducible Homeodomain-Leucine Zipper (HD-Zip) Protein of Arabidopsis, Negatively Regulates the Growth of the Inflorescence Stem by Decreasing the Expression of a Gibberellin 20-Oxidase Gene

Ora Son,허윤선,김윤경,이현정,김성한,김미란,남경희,이명석,김부용,박종범,박정안,이석찬,Atsushi Hanada,Shinjiro Yamaguchi,이인정,김승기,윤대진,Eva So¨derman,천충일 Sookmyung Women's University Research Institute of 2010 여성과 건강 Vol.6 No.1

레이저 가공에서 빔변수가 미치는 영향에 관한 연구

강경구,방세윤,윤경구,황경현,이성국 동국대학교 산업기술연구원 1997 산업기술논문집 Vol.9 No.-

레이저 가공시 조사되는 레이저 빔의 특성을 나타내는 변수 - 예를 들면, 빔의 형상, 초점면과 소재사이의 거리, 빔 강도 분포, 빔의 발산각, 실제 빔이 퍼져가는 양상이 이상적인 Gaussian 빔에 비해 얼마나 큰지를 나타내는 beam quality factor 등 - 이 가공결과에 큰 영향을 미치는 것은 경험적으로 잘 알려져 있다. 특히 원적외선 레이저로 천공, 에칭 또는 엑사이머 레이저로 ablation 가공을 수행할 때는 이러한 빔특성 변수의 영향이 극대화된다. 본 연구에서는 중요한 빔특성 변수의 영향을 가능한 독립시켜 정성적 및 정량적으로 파악하기 위해 연속발진 모드의 레이저빔 사용시 열전도에 의한 손실을 고려하였으며, 문제를 단순화해 빔 또는 가공소재의 상대적인 움직임이 없는 천공 (또는 에칭제거)의 경우에 대하여, 수치모사를 통해 여러 가지 빔 변수의 변화가 가공결과에 미치는 영향을 살펴보았다. 레이저 빔의 초점의 위치를 표면에서 멀리하면 가공깊이는 감소하게 되며, 같은 간격일 때는 소재의 내부에 위치시키는 것이 다소 유리하다. 또한 빔의 발산각이 작고, beam quality factor 값이 1에 가까울수록 깊은 가공을 얻을 수 있음을 파악하였다. In laser machining such as drilling with CO_2 or Nd:YAG laser, and etching or ablation with Excimer laser, one of the most important parameters affecting the machining results is known to be beam characteristics. In this paper a study is performed through a numerical simulation with the appropriate model to investigate the effects of beam parameters qualitatively and quantitatively, especially in the process of laser drilling of ceramics and ceramic composites. Results of different beam conditions reveal that the machined hole becomes deeper as (ⅰ) the beam divergence gets smaller,(ⅱ) beam quality factor approaches unity, and (ⅲ) beam focus lies nearer to the surface of the workpiece.

『딕테』에 나타난 디아스포라의 언어 고찰

윤향기(Yoon hyang-ki),이경영(Lee Kyung-young) 한국비평문학회 2008 批評文學 Vol.- No.29

This paper is an analysis about Dictee written by Cha, Hak-Kyung, a Korean-American, who tried for works beyond genre focusing on matters of diaspora and language. Until he passed away at age of 31, he was a writer who solidly dealt with images, text relations, implication of women and bodies, and substance of diaspora by moving about most energetically in many sorts of medias such as books, films, videos, mail arcs, ad criticism, stamp arts, and performing arts. Dictee has some difference from existing books that we've seen so far. This book tells stories about shunned strangers, existence of minor races, experience of women, suffering as Japanese colony, longing of innocent love, and vivid self-awareness of himself, within a dispersed world that he starred from himself. She already expressed a multicultural ideal in which all the diversity can harmonize beyond the walls of races, religions, languages, and ideology. The root of multiculturalism is based on pluralism. In this paper, the author deeply scrutinized the non-existence and transcendence of time and space and their eternity. And he also accepted Cha Hak Kyung's mythological recognition as historical consciousness replaced by lives with wings and free flight. Kim, Kyum-Hyang expressed Dictee as voice of shaman or voice of The Princess Bari in Comparison Study of Mythologies Appeared in Dictee Written by Cha, Hak-Kyung and Comfort Woman Written by Nora Okja Keller. However, this paper places more weight on the image of 'Butterfly' of Chuang-tzu, that is, restoration or transcendence. In other words, it is seen that women independently in their own language of Diaspora speaks about women's identity, which is even further expanding to the voice that Koreans make toward the world. In particular, Dictee is an example that resurrects Diaspora's linguistic outsiders' view into even strong points. This paper analyses and talks about the identity of Diaspora on the work beyond genre or mixed one. Especially, this unusual success is due to author's excellence in artistic talent and study of diverse cultural theories. However, more originally speaking, this is just because the author was able to experience by himself his disruption and dismantlement through his unique antecedent and thus reform this into artistic works.