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.

1740년(영조 16) 이후 영조의 정치 운영

이경구 한국역사연구회 2004 역사와 현실 Vol.- No.53

King Yeongjo is generally known to have concentrated upon the so-called Wanron-Tangpyeong/緩論蕩平 policy based upon the concept of Jojae Bohab/ 調劑保合, Yet that principle was not applied to every situations at every times during the entirety of King Yeongjo's reign. During the latter half period of his reign, King Yeongjo denied the Euiri/의리 concept, at least the version suggested and strongly supported by party politics, and instead reinforced the leadership and authority of the king. For that task, King Yeongjo prepared relevant ideologies and also a new political structure. In essence, he argued the public nature of the Euiri concept, and intended to place it under the King's own authority. This pushed(or forced) the Euiri concepts which were previously upheld by the Scholar- officials, who employed devices like the so-called Samun Shibi/斯文是非, into the realm of ptivate discussions, and led to the eventual weakening of the scholar-officials' position inside the government, Such scholar-officials were replaced by the Saeshin/世臣 officials and the general public as the King's political partner, and also the government's aim in general policies. King Yeongjo's handling of the political arena', which he showed during the latter half period of his reign, reminds us of the actions of the 15th century Chosun kings, and especially King Saejong. But there is also a definitive difference, King Yeongjo was aiming for a political model which was very similar to that of the dynasty's early years, but the political model he was aiming for was also based on a society functioning upon the activities and authorities of the scholar-officials. In essence, he was trying to establish a new model, merging this two distinct kinds of form together. His goal was to sublate the models inherited by the 15th, 16th and 17th centuries, and the result was the Tangpyeong policy which was indeed the terminal state of politics that the Chosun Confucian politics could ever reach.

法典을 통해 본 17~18세기 서울의 변화

이경구 서울시립대학교 부설 서울학연구소 2005 서울학연구 Vol.- No.25

In this article, the changes that happened in the Seoul area during the 17th and 18th centuries, in terms of the size of the city and also the life style of the citizens inside it, are examined through various sources of codified laws(法典). Since the mid-17th century, the damage inflicted upon the Joseon dynasty by two devastating wars(兩亂) with the Japanese and the Ching dynasty had been being healed, and the population of the Seoul area was again starting to increase. The increase in population eventually led to the enlargement of the city itself. The existing 'Prohibition markers' that were based upon the outlines of the Four Mountains(Sasan Geumpyo/四山禁標), which have served as traditional symbols for the dynasty's prohibitive definition of banning further developments in the area, became obsolete, and a new line comprised of new streams and rivers came to serve in presenting a newly recognized area that was called 'Seongjeo Shibri/城底十里'(10 Ri units outside the realm of the Capital). Local districts had to be revised accordingly, and the government incorporated such changes into the administrative system. As the size of the city continued to grow and the population continued to increase, new life styles of the Seoul city residents started to emerge. The entire process of such changes are literally well described in the 『Sugyo Jibrok;受敎輯錄(Compilation of the Sugyo documents)』 and the 『Shinbo Sugyo Jibrok/新補受敎輯錄(Revised version of the Sugyo documents Compilation)』, which were sets of codified laws that were enacted and published during the late 17th and early 18th centuries. Unlike the previous codes of laws, these two new codes of laws had much larger chapters arranged for the Restrictive regulations(禁制) in the Criminal law section(「刑典」). Such restrictive regulations were in most part addressing issues such as accumulating and brandishing luxurious articles, committing economic foul plays, and developing nearby areas of the Seoul city. And the most primary targets of such restrictions were the powerful individuals or Houses inside the Seoul area or the wealthy Jungin/中人 figures. What called for the frequent issuing of restrictive regulations was the general atmosphere of the society that has been continuing to loosen since the 17th century. The people became less alerted against the Chinese Ching dynasty, and became more acceptive to the Ching culture. As a result, entertainment, luxurious articles and a new sub-culture of amusement were introduced to the Joseon people and became a general trend. In the 18th century, the Seoul city literally developed a new phenomenon(referred to as '時體/Shichae', namely the 'Trend of the Time') in which the residents of the Seoul city invented new fashions, and relayed them to other local areas. The scholar-officials(the Sa-Daebu/士大夫 figures) in local areas were fairly critical of this new trend that demonstrated certain social structure-related problems in which the Seoul capital was in solid, almost proprietary lead of the 'Trends of the Time'. The reason that they were so critical of this new fashion was because such trend was representing the birth of a new social structure in which only the Seoul citizens were becoming prominent leading figures of the country thanks to the development of the Seoul city area. For example, in the process of appointing governmental officials, whether someone was from a distinguished family(門閥) in the Seoul area or not became a crucial factor, and subsequently human resources in the Seoul area started to almost monopolize the office seats inside the government. Civilian merchants(私商) were protected by the powerful Houses(㔟家), enlarged their business transactions and shared their new found profits with many partners(from various social classes) in the Seoul area. This led to the formation of a new profit chain that connected the powerful Houses in the Seoul area, the messengers(家人) from those Houses, and the civilian merchants with each other.

심부전증에서 Doppler Tissue Image를 이용한 비동시성 심실수축(Myocardial Dyssynchronicity)의 측정 : 심전도와비교 Comparison with EKG

구소영,조구영,한성우,최승혁,박우정,두영철,홍경순,오동진,이영 대한순환기학회 2004 Korean Circulation Journal Vol.34 No.4

일부 고등학생에서 성(性)적 활동의 위험요인 분석

이무식,김은영,천병철,이석구,전경희,최은주 한국모자보건학회 2000 한국모자보건학회지 Vol.4 No.2

유한요소법을 이용한 연료분사 파이프의 자유진동해석에 관한 연구

이동명,최명진,이경구 경희대학교 산학협력기술연구원 1995 산학협력기술연구논문집 Vol.1 No.-

Engineers have been interested in the vibration analysis of pipes containing fluid flow owing to the complexity related to fluid flow, and have proposed many reports. In this study, finite element program for three dimensional free vibration analysis of fuel distributor pipes was developed considering the complicated shapes and correlation of structure and flued. The obtained results said that natural frequencies of fuel distributor pipes become low as the flow velocity, where the first natural frequency drops suddenly, was observed increase. However, since natural frequencies of real fuel distributor pipe have much higher values than the engine speed, the resonance was not observed. The scheme and program in this study can be applied to any types of three dimensional piping systems containing fluid flow.

줄눈콘크리트포장의 하중응력분포 해석

김태경,박제선,이주형,윤경구 江原大學校 産業技術硏究所 1998 産業技術硏究 Vol.18 No.-

This study focused on the development of an alternative stress estimation procedure to instantly calculate the critical stresses bonded concrete pavement. Closed form analysis is commonly used to analyze pavement structures. This type of analysis assumes linearelastic material properties and static loading conditions. The well-known ILLI-SLAB finite element program was used for the analysis. Bonded concrete overlay analyzed the stress distribution, behavior and load carrying capacity under track load is made evaluation standard of bonded concrete overlay. In the study, the following results were derived; The properties of strength is that compress and 3-point bending strength of existing pavement is deteriorated with 184 kg/㎠, 59kg/㎠ but compress and splitting tensile strength of overlay is satisfied with 464 kg/㎠, 45kg/㎠. Load transfers is happen at adjacent slab by interlocking under track load. The stress distribution under interior, corner and edge load is described high loading position surrounding then loading position.

분만시 발생한 쇄골골절

최경수,정의섭,지성구,이종봉 예수병원 1997 예수병원학술지 Vol.18 No.-

소아에서의 Nd : YAG Laser를 이용한 치은착색제거술 YAG Laser in children

모경희,박헌동,박종휘,김효석,정현구,설재헌,이병채 조선대학교 구강생물학연구소 2003 口腔生物學硏究 Vol.27 No.1

Melanin is normally found in the skin of all people, and normal pigmentation of the intraoral tissues is a relative frequent finding. Gingival hyperpigmentation may cause esthetic problems and embarrassment, especially in patients with a gummy smile. Melanin pigmentation is related to etiologic factor such as hormon, systemic factor, drug, smoking and gingival inflamation. Depigmentation procedure can be Performed by gingival epithelium removing procedure, gingivectomy, free gingival graft, laser therapy, dry ice, Vitamin C and phenol-alcohol method. We could obtain favorable esthetic results by procedures such as Nd: YAG laser. The Nd:YAG laser was set at 4 watt, 50mJ, 80 pulse per second. The procedures were performed with contact mode in all pigmented areas by using a handpiece with a 320㎛ diameter fiber optic. Ablation of the gingival hyperpigmented gingiva appeared healthy, pink, and firm. No recurrence of hyperpigmentation had been found in 6 months of follow-up.