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>

대학생 흡연자의 금연경험에 따른 건강신념차이

구정일,김민정,김동희,백정희,안현실,은가희,우혜령,이명희,이수현,김수지 이화여자대학교 간호과학대학 2003 이화간호학회지 Vol.- No.37

It has been generally known that smoking is one of the worst factor increasing disease and mortality in human health since in 1950's and nowadays. But regardless of various proofs about social or economical problems due to smoking, current smoking rate has not been decreased in our country. Until now, most of tobacco use and its addiction researches have been focused on the adolescent or adult women smokers not on the university students. Therefore, the purpose of this study was to investigate smoking cessation of university smokers and analyze the health belief-perceived sensitivity, severity, benefits and barriers- difference, then to provide basic data for effective smoking cessation strategy for university smokers. The subjects were comprised of 181 university smokers from 15 universities in Seoul. The data were collected by structured questionaires. The questionaires were designed to measure general characteristics, smoking cessation and health belief, based on Ahn(2003)'s result on the Study of Smoking attitude, Behavior and Smoking Cessation of Adult Male and Lee(1987)'s result on Relationships Between the Health Belief Model and Smoking Habits. The data were collected from May 5 to 16. The collected data were analyzed by SPSS program. The actual number, percentiles, means, standard deviation, t-test and ANOVA were done. The result of this study were as follows; 1. The general characteristics of the subjects of this study The range of age was from 18 to 34 and the averaging age was 23. The subjects of this study were 141 males and 40 females. The religions were Christianity 25.4%(46), Buddhism 12.7%(23), Catholic 23.2%(42), no religion 37.0%(67). The residential forms were living with family 59.1%(107), cooking food for oneself 28.7%(52), dormitory 5.0%(9), boarding house 1.7%(3). Smoking starting age were university 43.1 %(78), high school 29.8%(54), middle school 14.9%(27), in the army 6.1 %(11), elementary school 1.1 %(2). 2. The smoking cessation of the subjects 80% of current smokers showed quitting smoking decision and 20% have not tried. The frequency of quitting smoking decision were from 1 to above 8 and mean was 3.06. As for smoking cessation plan, 54.7%(99) current smokers answered yes, 3.9%(7) said no, 35.4%(64) had no idea and 6.1 %(11) didn't answer. As for the reason of never quitting smoking decision, 71.42%(25 among total 35) have no need to quit smoking and the others said difficulty of smoking cessation. As for the main reason of smoking cessation decision, 54.7%(99) answered for the health, 7.2%(13) family advice, 15.5%(28) girl/boy friend's advice, 1.7%(3) to save money. As for the reason to fail smoking cessation, 56.7%(68) were will-lack, 17.5%(21) stress, 15%(18) smoking mood, 10%(12) withdrawl symptom. As for the smoking cessation method, 85.0%(125) were oneself-will, 2.7%(4) way acquired by mass-media, 2%(3) doctor's prescription, 2%(3) religion's help, 0.7%(1) smoking cessation school. As for the difficulty in smoking cessation, 42.2%(62) were drinking meeting, 23.1 %(34) no alternative of stress release, 12.2%(18) withdrawl symptom, 11.6%(17) having nothing to do, 7.5%(11) friend's encouragement. As for the most difficult cigarette to quit, 67.8%(99) were all-day smoking except the first smoking in the morning, 32.2%(47) the first smoking in the morning. 3. Health belief as for general characteristics Gender - The total point in benefits showed higher in male(28.5177) than female(26.6750). There was significant difference(t=.778, p<.05). The total point in health belief showed higher in male (105.8298) than female(l00.5000). So there was significant difference(t=.345, p<.05). Age - There was significant difference in benefits between age(10's-25.83, 20's-28.39, 30's-32.00)(F=3.73, p<.05). Smoking starting age - There was significant difference in total point of sensitivity and health belief(sensitivity F=4.00, p<.Ol, health belief F=2.843, p<.05). As for sensitivity, subjects who started smoking in the army showed the highest(33.36) and ones in high school showed the lowest(26.96). The total point in health belief showed the highest in elementary school(l19.00) and the lowest in high school(100.98). 4. Health belief as for smoking cessation There was significant difference in health belief as for smoking cessation(t=0.189, p=0.OO2). Sensitivity point showed higher in smoking quitting trial smokers(29.2) than non-trial smoker (26.9). Severity point showed higher in trial smokers (30.7) than non-trial smokers(28.9). Benefit point showed higher in trial smokers(28.6) than non-trial smokers(26.2). There was no significant difference in barriers point.

Pendulum 장치의 상악대구치의 원심이동에 대한 효과

이창섭,김재광,강덕일,송광철,정현구,이상호 대한소아치과학회 2001 大韓小兒齒科學會誌 Vol.28 No.3

Ⅱ급 치성교합을 가진 환자에서는 I급 구치부 교합관계를 형성하기 위하여 상악 대구치의 원심이동이 필요하다 본 연구에서는 pendulum장치를 이용한 상악 대구치의 원심이동시 대구치의 이동양상과 고정원의 전방이동 및 정출정도 등 치아와 골격에 미치는 영향을 평가하기 위하여 시행되었다. 상악 제1대구치를 원심이동시켜 1급 구치관계가 형성된 19명의 환자 (남: 8명. 여: 11명, 평균연령 11.68±1.52세)에서 장치 장착 전과 장치제거 직후에 얻어진 측면두부방사선사진을 비교 ·분석하여 다음과 같은 결과를 얻었다. 1.I급 교합관계를 형성하기 위해서 제 1대구치는 평균 2.94± 1.54mm 원심이동하였으며 . 1.17±0.97mm 함입되었고, 소요기간은 평균 18.13±7.95일이었다. 2.고정 원으로 사용된 치아는 1.34± 1.40mm로 유의하게 전방 이동하였으며, 0.48±0.99mm 정출되었다. 또한 절치는 유의한 전방이동 및 순측경사가 발생하였다(P<0.05) . 3.구개평면과 하악평면이 이루는 각은 유의한 증가를 보였다(P(0.05). 4.제1소구치 또는 제1유구치가 고정 원으로 이용된 경우 제2소구치 또는 제2유구치가 이용된 경우 보다 전방이동이 증가하였다(P<0.005). 5. 제2대구치의 발육단계에 따른 제1대구치 및 제2대구치의 이동양상은 어떤 항목과도 유의성이 없었다(P<0.05). 6.얻어진 총 공간 중 74%는 제1대구치의 원심이동이,26%는 소구치의 전방이동에 의하여 얻어졌다. 이상의 결과를 종합하여 볼 때 pendulum appliance는 상악 대구치의 원심이동에 매우 효과적이었으며. 고정원의 소실을 최소화하기 위해 제2유구치 또는 제 2소구치가 포함되어야 한다. 또한 제1대구치의 원심경사는 필연적으로 일어나며. 이를 최소화하기 위한 노력이 계속되어야 할 것으로 사료된다. Treatment of class Ⅱ malocclusions require distalization of maxillary molars into class I relationship. Intra-arch distal molar movement techniques have recently assumed an important role in young patients. In this study, the dental and skeletal effects of the pendulum appliance were evaluated by means of cephalometric radi-ographs. The samples were consisted of 19 patients: 11 females and 8 males, mean age 11.68± 1.52 years. Measurements were obtained from cephalometric prior to and the day of removal of the pendulum appliance. Treatment changes were analyzed. The following results were obtain : 1. The pendulum appliance produced 2.94±1.54mm distal molar movement with a mean intrusion of 1 17± 0.97mm, mean period 18.13±7.95 weeks. 2. The anchor tooth was 1.34± 1.40mm forward movement and 0.48±0.99mm extrusion, and labial tilting of incisors. 3. The angle between palatal plane and mandibular plane increased significantly 4 There was no significant difference in according to 2nd molar position. 5. Total movement was consisted of 74% distal movement of 1st molar and 26% forward movement of the an-chor tooth

크로이츠펠트-야콥 병

구본대,신동익,한현정,나덕렬,,이상복 관동대학교 의과대학 의과학연구소 2005 關東醫大學術誌 Vol.9 No.1

Creutzfeldt-Jacob disease (CJD) is one of the fatal prion diseases. Diagnosis of CJD is mainly based on clinical symptomatology of established criteria, characteristic electroencephalogram, specific cerebrospinal fluid protein measurement, prion protein gene analysis, prion protein isoform detection, and neuropathology. But spongiform change of brain pathology is the only definitive diagnosis of CJD. Clinical symptomatology of CJD includes behavioral disturbances, progressive dementia, cerebellar, pyramidal, and extrapyramidal signs. Most patients show progressive myoclonic jerks that involve either limbs or the entire body. The approximate incidence of CJD is 1 per million and occurs as sporadic, familial and iatrogenic forms. Variant CJD has the strong possibility of cross species transmission between human and cow. It has some differences in clinical and pathological aspects from sporadic CJD. Protease resistant prion protein of scrape isoform may lead to diverse neuronal death in CJD. Recent advannces in CJD reveal that apoptosis, proinflammatory cytokine expression and oxidative stress may play an important role of CJD pathogenesis. There areseveral therapeutic trials in CJD but no therapeutic regimensshow effective results. Although there is much progression about CJD in recent days, a lot of things still remained to be reveled.

TFM 방식을 이용한 건물의 동적 열성능해석 기법 연구(Ⅰ)

구현덕,이순화,이진숙,송인춘 忠南大學校 産業技術硏究所 1993 산업기술연구논문집 Vol.8 No.1

This study presents the methodology application of hour-by-hour computation for an extensive analysis in building. The approach to equipment selection based on air-conditioning equipment and air distribution systems with sufficient capacity to cope with maximum design load evolved when all design calculations were performed manually. At that time, extensive design analysis was impractical: now, computers, used frequently for rountine design calculations, make anaysis practical. Consequently, this study describes the fundamental methodology used in calculating a space load and gives basic equations for determining hour-by-hour load factors given in tabular forms in the ASHRAE FUNDAMENTALS, 1985 and 1989. It is possible to construct computerized routines to duplicate results obtained with the tabular data, and to examine the effect of various systems and operating schedules on the space energy analysis. This study deals with fundamental calculation procedures for 1. Heat gain through exterior walls and roofs using transfer function coefficients. 2. Hrat gain through interior patitions, ceilings and floors using transfer function coefficients. 3. Conversion of all heat gain components into appropriate room/space loads. 4. Extention of the procedures to calculate the space air temperature and heat extraction rate obtained with a particular type and size of terminal unit. By applicating this procedures to computerization, three basical calcualtion routines are made and verified as the proper simulation methodology. As results. 1. Houry conduction rate has only 0.48% err in average. 2. Houry radiation rate has only 0.041% err in average. 3. Houry temperature variation has only 0.001% err in average. 4. Houry predicted heat extration rate has only 0.005% err in average. From the above results, it is possible to use TFM computerization methodology for energy analysis in building. By applicating three basical comuper calculations, more complicate computer simulation can be interpreted to be needed for annual energy analysis.

기능적 방법을 이용한 소아의 하악과두 골절의 처치 : 증례 보고 A case report

이정하,박성규,위유민,정현구,이봉규,이창섭 조선대학교 구강생물학연구소 2002 Oral Biology Research (Oral Biol Res) Vol.26 No.2

The pediatric condylar fracture occurs very frequently in the mandible, but this injury is occasionally ignored due to difficulty of diagnosis and no cooperation of patient. The adequate initial diagnosis and active treatment must be performed because delayed and improper treatment lead to possible severe complication such as TMJ ankylosis and retardation of mandibular development. Most pediatric condylar fracture is mainly performed by the conservative or functional treatment. but it may be required open reduction according to cases. In this study, Activator is applied for functional treatment of pediatric condylar fracture and fair recovery of jaw function is acquired.

ZSM-5 촉매상에서의 메탄올 전환반응에 관한 연구

우명우,이현구 순천대학교 기초과학연구소 1990 基礎科學硏究誌 Vol.1 No.-

ZSM-5 촉매를 제조하고 메탄올 전환반응에 적용하여 반응 속도에 관한 실험연구를 수행하였다. ZSM-5 촉매상에서 메탄올 전환반응에서는 많은 종류의 탄화수소들이 생성되는 데, 본 연구에서는 접촉시간을 조절하여 주로 C_2, C_3 및 C_4 탄화수소들이 생성되는 조건하에서 반응실험을 수행하였으며 lumping의 개념을 적용하여 이 경우의 반응 경로와 각 반응의 속도 상수들을 결정하였다. 이로부터 메탄올이 dimethyl ether로 변환되어 평형상태를 유지하면서 C_2 및 C_4 탄화수소들이 병행반응으로 생성되고, 생성된 C_2 및 C_4 탄화수소들로부터 C_3 탄화수소가 생성되는 것으로 추정되었다.

내동정맥루술후의 수지운동이 동정맥루의 혈류와 개존에 미치는 영향

신현석,조원현,이성문,우성구,김현철 大韓脈管外科學會 1995 大韓脈管外科學會誌 Vol.11 No.1

혈액형에 따른 자기이미지와 의복가치

김현아;지영은;구영아;이규혜 한양대학교 2005 韓國 生活 科學 硏究 Vol.25 No.1

This study examined empirical differences of self‐image and clothing values (hedonic/utilitarian) by consumers’ blood types. One hundred and eighty one undergraduate students with diverse majors were respondents of the empirical study. A questionnaire was developed to measure students’ self image, clothing values and demographic variables including blood types. Dimensions of self‐images for undergraduate students were classified into optimistic futuristic, self‐centeredness, social, safety/ conservative, feminine, and indifferent. For hedonic aspects of clothing values four factors were extracted: novelty/ enjoyment/ charm, fashion value orientation, clothing‐confidence, and mix and match. Utilitarian aspects of clothing values consisted of five factors: symbolic/social recognition, comfortable, economic, practical, and ease of care. ANOVA results indicated no major difference of self‐images by blood type. The only significant result was found in the safe/conservative image. People of the blood type A, B and O showed lower level of safety seeking and conservatism. However, comparatively, people of type AB blood are holding back their emotion, not expressive, watchful against other people, and pursuing safety. No major differences were found in clothing value sub dimensions in conjunction with the blood types. The research findings are suggestive of existence of insufficient evidence of self‐image and clothing values by the individual’s blood style.

벼의 혹명나방의 성 유인 물질의 합성과 생물활성시험

강석구,박정민,이정운,고현관 成均館大學校 科學技術硏究所 1983 論文集 Vol.34 No.2

벼의 혹명나방의 성 유인 물질인 (Z)-13-옥타데센-1-올 아세테이트를 새로운 방법으로 합성하였다. 즉, 1-헥신의 리튬 음이온을 보호된 12-브로모-1-도데칸을 THP 에테르와 반응시켜, 13-옥타데신-1-올 THP에테르를 만든후 Lindlar 촉매에 의한 수소화 반응을 시켜 (Z)-13-옥타데센-1-올 THP에테르를 얻는다. 산촉매하에서 보호기를 제거한 후 피리딘 용매하에서 무수아세트산을 반응시켜 최종 생성물인 (Z)-13-옥타데센-1-올 아세테이트를 좋은 수율로 얻었다. 농촌진흥청의 곤충과와 공동으로 상기에서 합성된 성 유인 물질을 이용하여 혹명 나방의 숫컷에 대한 성 유인 효과를 실험해본 결과 성 유인 작용이 있는 것으로 나타났다. A new method is described for the synthesis of (Z)-13-octadecen-1-ol acetate(1), the sex pheromone of the Rice Leaf Folder moth. Lithium acetylide of 1-hexyne was alkylated with 12-bromo-1-dodecanol THP ether. 13-Octadecyn-1-ol THP ether was stereoselectively reduced over Lindlar catalyst(Pd/BaSO_4) to give (Z)-13-octadecen-1-ol THP ether. (Z)-13-octadecen-1-ol THP ether was deprotected and acetylated with acetic anhydride and pyridine to afford the final product, (Z)-13-octadecen-1-ol acetate. Biological activity test of the synthetic compound, (Z)-13-octadecen-1-ol acetate was tested in the field using polyethylene capsules as containers. The numbers of moths trapped with pheromone vials were counted.