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.

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

Kim, Hee Kyung,Kim, Sun Young,Lee, Su Jin,Kang, Mihyeon,Kim, Seung Tae,Jang, Jiryeon,Rath, Oliver,Schueler, Julia,Lee, Dong Woo,Park, Woong Yang,Kim, Sung Joo,Park, Se Hoon,Lee, Jeeyun Neoplasia Press 2016 Translational oncology Vol.9 No.3

<P><I>BACKGROUND:</I> Although pazopanib treatment has become the standard chemotherapy in salvage setting for metastatic sarcoma patients, most patients progress after pazopanib treatment in 4 to 6 months. After failure to pazopanib, patients have limited options for treatment. Therefore, subsequent therapy in patients who failed to pazopanib is urgently needed and the use of patient derived cells or patient derived tumors for accompanying testing with various pharmacological inhibitors could offer additional treatment options for these patients. <I>METHODS:</I> Patient derived tumor cells were collected from ascites at the time of progression to pazopanib and a 13-drug panel was tested for drug sensitivity. We confirmed the results using <I>in vitro</I> cell viability assay and immunoblot assay. We also performed the genomic profiling of PDX model. <I>RESULTS:</I> The growth of patient derived tumor cells was significantly reduced by exposure to 1.0 μM AZD2014 compared with control (control versus AZD2014, mean growth = 100.0% vs 16.04%, difference = 83.96%, 95% CI = 70.01% to 97.92%, <I>P</I> = .0435). Similarly, 1.0 μM BEZ235 profoundly inhibited tumor cell growth <I>in vitro</I> when compared to control (control versus BEZ235, mean growth = 100.0% vs 7.308%, difference = 92.69%, 95% CI = 78.87% to 106.5%, <I>P</I> < .0001). Despite the presence of CDK4 amplification in the patient-derived tumor cells, LEE011 did not considerably inhibit cell proliferation when compared with control (control vs LEE011, mean growth = 100.0% vs 80.23%, difference = 19.77%, 95% CI = 1.828% to 37.72%, <I>P</I> = .0377). The immunoblot analysis showed that BEZ235 treatment decreased pAKT, pmTOR and pERK whereas AZD2014 decreased only pmTOR. <I>CONCLUSION:</I> Taken together, upregulation of mTOR/AKT pathway in sarcoma patient derived cells was considerably inhibited by the treatment of AZD2014 and BEZ235 with downregulation of AKT pathway (greater extent for BEZ235). These molecules may be considered as treatment option in STS patient who have failed to pazopanib in the context of clinical trials.</P>

노인의 영적 간호요구

최미혜,김경희,김귀옥,김기숙,김수강,김정신,김춘숙,노흥진,박지연,성혜연,오명선,이선희,이원옥,이윤영,이현수,장명재,차혜경,채정선,홍상희 중앙대학교 의과대학 간호학과 간호과학연구소 2001 중앙간호논문집 Vol.5 No.1

This study was designed to exam the aged's needs for spiritual nursing care. The purpose was to serve as a basis for the development of spiritual nursing practice. The major findings are as follows : 1. The degree of needs for spiritual nursing care as area was that needs of love and relationship mean 22.0, needs of meaning and object mean 28.2, needs of forgiving mean 13.5. Total needs for spiritual nursing care mean 63.7, which was on the upper middle level. The needs of meaning and object was rated highest. 2. Among the general characteristics of the subjects, needs of love and relatiohship wasn't significanlty different. 3. Among the general characteristics of the subjects, needs of meaning and object was significantly different according to two factors : age(F=7.260, p=0.001), religion(F=5.275, p=0.001). Higher needs of meaning and object was possessed by the older than the younger, by the one who have religion than the other. 4. Among the general characteristics of the subjects, four factors made a significantly difference to needs of forgiving : sex(t=-2.851, p=0.006), age(F=8.201, p=0.001), religion(F=6.928, p=0.000), disease(t=2.327, p=0.024). Higher needs of forgiving was possessed by man than woman, by the older than the younger, by the one who have religion than the other, by the one who have disease than the other.

췌장 선방세포암 1예

이화정,지준호,박승찬,박정철,최은정,서혜진,이원식,이정림,배병조,손경락,이경희 영남대학교 의과대학 2008 Yeungnam University Journal of Medicine Vol.25 No.2

Acinar cell carcinoma is a rare tumor that represents 1~2% of al1 pancreatic cancers. Clinical and radiologic findings are inconclusive in this disease Acinar cell carcinoma is characterized by rapid progression and early metastasis, which lead to its poor prognosis. A 41-year-o1d man was admitted to our hospital for abdominal pain. Abdominal computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) showed a splenic mass, which was being invaded by a pancreatic tail mass and which had increased ^(18)F-fluorodeoxyglucose (FDG) uptake Primary radical distal pancreatectomy and splenectomy were performed. Pathologic findings revealed an acinar cell carcinoma of the Pancreas The patient underwent a total gastrectomy three months later because of gastric recurrence Four months later, multiple hepatic metastases were discovered, and the patient underwent a left hepatectomy During treatment with capecitabine, there was no evidence of tumor progression for 14 months. We report a case of metastatic pancreatic acinar cell carcinoma, which did not progress for an extended period while the patient was being treated with capecitabme.

경희대학교 국제캠퍼스 걷고 싶은 거리 조성계획

김동찬,김영준,마원,김충희,노경식,이가영 경희대학교 부설 디자인연구원 2008 예술· 디자인학연구 Vol.11 No.1

Kyung-Hee University Global Campus accepted changing of education environment to adapt to the World's information technology society so that school has been preparing the Master plan to grow up campus's vision since 2007. However, realization of the Master plan need a lot of financial resources, much times and phases in improvement. Especially, our university needs symbolized business in 2009 due to the 60th anniversary of our university. Based on this we want to improve the main entrance road environment from school gate to the school of international management and reconstruct the spatial environment beside the main road. The purpose of this research is to construct a pedestrian space environment and reconstruct the campus environment which adapt to the new times' demands. That is why the Master plan is trying to find the landscape scenic which adapts to our school' s main entrance space and the improvement method about the pedestrian space of the Global campus to congratulate of our university's 60th anniversary.

간호계와 비간호계 대학생의 AIDS관련 지식 조사연구 : 경기지역 일개 전문대 재학생을 중심으로

이애경,김영희 경복대학 1997 京福論叢 Vol.1 No.-

후천성 면역결핍 증후군(AIDS)는 전세계적으로 그 심각성이 더해가고 있으며, 인류의 복지를 위협하는 무서운 질병이다. 최근들어 한국에서도 HIV감염지수가 증가하고 있는 추세이며, 1996년말 현재까지 608명의 환자가 발생되었다. 그러므로 본 연구에서는 경기지역 일개 전문대 재학생을 중심으로 에이즈 예방교육을 실시하기에 앞서 그들이 갖고 있는 사전지식을 조사하고자 에이즈관련 지식에 대한 서술적 조사연구를 시도하였다. 연구대상자는 경기지역에 소재하는 일개 전문대 18세에서 26세까지의 재학생 242명으로 연구도구로 34문항의 질문지에 의하여 자가보고법으로 자료수집을 하였으며 실수, 백분율, 평균값, 유사성검정, t-test, ANOVA, 2-way ANOVA를 이용하여 자료를 분석하였다. 연구결과는 다음과 같다 : 1. 전체 대상자의 에이즈관련 지식점수는 평균17.67점이었고, 정답율의 범주는 47.2%-94.6%이었다. 2. 평균점수가 가장 낮은 문항은 '일단 에이즈균이 몸에 있으면 에이즈환자가 된다(47.2%)' 였는데, 이는 에이즈의 잠복기간을 잘 알고있지 못함을 보여주고 있다. 3. 비간호계 집단의 에이즈관련 지식정도는 간호계 집단에 비해 낮은 평균값을 보였는데, 이는 에이즈예방교육시 건강관련과목을 전공하지 않는 일반대학생들을 중심으로 하는 에이즈예방교육이 강조되어야함을 나타내주고 있다. 4. 대상자의 인구사회학적 특성에 따른 대상군의 에이즈관린 지식정도의 차이를 확인한 결과 전체 대상군에서 일반잡지를 통한 교육경험이 있는 집단이 교육경험이 없는 집단에 비해 지식점수가 높게 나타났으며, 비간호계 집단에서는 건강정보잡지를 통한 교육경험이 있는 집단이 교육경험이 없는 집단에 비해 지식점수가 높게 나타났고, 간호계에서는 통계적으로 유의한 차이를 보이지 않았다. 육이 강조되어야함을 나타내주고 있다. 4. 대상자의 인구사회학적 특성에 따른 대상군의 에이즈관련 지식정도의 차이를 확인한 결과 전체 대상군에서 일반잡지를 통한 교육경험이 있는 집단이 교육경험이 없는 집단에 비해 지식점수가 높게 나타났으며, 비간호계 집단에서는 건강정보잡지를 통한 교육경험이 있는 집단이 교육경험이 없는 집단에 비해 지식점수가 높게 나타났고, 간호계에서는 통계적으로 유의한 차이를 딘이지 않았다. Acquired immunodeficiency syndrome(AIDS) is threatened to human being's welfare is a far greater serious disease than most other disease. Recently HIV infectious clients are increasing tendency in Korea and the number of AIDS patients are 608 peoples in 1996. Therefore the purpose of this study was to identify the level of AIDS related knowledge before the eduaction of AIDS prevention of the college students at Kyung-gi area and the research design utilized in this study was a descriptive survey research. The subject were 242 college students where is at Kyung-gi area and they were 18-26 years old. The data were collected by self reporting with a questionnaire of 34 items and were analized by frequency, percentage, means, qui-square test, t or ANOVA test, and 2-way ANOVA. The results were as follows : 1. The Mean score of AIDS related knowledge was 17.67 and the correct answer rate of it was from 47.2% to 94.6%. 2. The lowest item was 'The person who has HIV get AIDS soon(47.2%).' and it was shown that the subject didn't know well about latent period of AIDS. 3. The mean score of a group who was majoring in non-nursing was lower than who was majoring in nursing and it must be empasized to AIDS preventive education for the group who was majoring of non-medicals. 4. The level of AIDS related knowledge as to demographic facter was revealed that the total group who had an learning experience through the magazine was high score of AIDS related knowledge than who had no experience, while the non-nursing group who had an learning experience through the jounal of health topics was high score of it than who had no experience., and it was not significant statistically in the nursing group.

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.

Pseudomonas 層에 依한 芳香族化合物의 分解에 關한 硏究

李相烈,李京熙 부산대학교 환경문제 연구소 1985 環境硏究報 Vol.3 No.-

The effects of carbon and nitrogen sources on the growth of sodium benzoate-utilizing bacteria, Pseudomonas sp. ATCC 27330, were experimentally investigated in batch culture and the characteristic values were estimated by using the Kono model. The optimun culture conditions for the growth of the strain were 30℃, pH 7.0, sodium benzoate as carbon source and ammonium sulfate as nitrogen source. When the strain was cultivated in 0.08%-sodium benzoate as optimum concentration, the characteristic values estimated by using the Kono model from the data obtained were as follows; the coefficient of growth rate (k), critical cell concentration (Cxc) and theoretical maximum cell concentration (Cxm) were 0.225 h??, 0.123 UOD/ml and 0.235 UOD/ml respectively.

경희대학교 서울캠퍼스 진입로 및 주변 보행공간 기본계획

김동찬,김영준,마원,김충희,노경식,이가영 경희대학교 부설 디자인연구원 2008 예술· 디자인학연구 Vol.11 No.1

Kyung-Hee University in Seoul accept changing of education environment to deal with World's information technology society so that school had preparing the Masterplan to grow up campus's vision since 2006th. Finally we finish up this plan. However, realization of the Masterplan need a lot of financial resources, much times and phases in improvement. Especially, our school needs symbolized business in 2009 due to school of 60th anniversary. So we made a plan that to construct by design which is going to reshape campus's main road and westside afforest place for future. As a result, purpose of research is to improve an atmosphere conducive to academic pursuit, to show up greatness of school and to deal with changing school's environment rapidlly. That is why the Masterplan is trying to find school of superb scenic and developing of environment to congratulate of our school's 60th anniversary main approach and walking spaces.