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>

抗히스타민劑의 吸光度比法에 의한 定量

李允中,李康春,李東宣,李振九 成均館大學校 1980 論文集 Vol.28 No.-

The absorbance ratio method was applied to the quantitative determination of antihistamines, such as chlorpheniramine maleate(CPM), carbinoxamine maleate(CBM) and diphenhydramine hydrochloride. The influences of indicator and solvent concentration on the precision and accutacy of determination were investigated. And it was found that the effects of temperature and wavelength was negligible in case of averaging conditions. The standard deviations for three antihistamines tested were within 0.13%. As the results, the determination of antihistamines could be carried out easily, rapidly and accurately by the absorbance ratio method.

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.

Stereotactic Radiotherapy by 6MV Linear Accelerator

오윤경(Yoon Kyeong Oho),김미희(Mi Hee Kim),길학준(Hak Jun Gil),윤세철(Sei Chul Yoon),이재문(Jae Moon Lee),최규호(Kyu HO Chio),신경섭(Kyung Sub Shinn),박용휘(Yong Whee Bahk),김문찬(Moon Chan Kim),강준기(Joon Ki Kang),송진언(Jin Un Son 대한방사선종양학회 1988 Radiation Oncology Journal Vol.6 No.2

Eight patients with intracranial tumors or arteriovenous malformation (AVM)s which were less than 3cm in diameter were treated by a technique of stereotactic radiotherapy during the 4 months period from July 1988 through October 1988 at the Division of Radiation Therapy, Kang-Nam St. Mary’s Hospital, Catholic University Medical College. The patients were diagnosed as AVMs in 3 cases, acoustic neurinoma, craniopharyngioma (recurrent), hemangioblastoma, pineocytoma, and pituitary microadenoma in each case. There are several important factors in this procedure, such as localization system, portal, field size, radiation dose, and perioperative supportive care. It is suggested that stereotactic radiotherapy may be performed safely with a radiation dose of 12-30 Gy. So this nonivasive procedure can be used to treat unresectable intracranial tumors or AVMs. Of these, clinical symptoms had been regressed in AVMs in 2 cases at 3 months and 2 months after Stereotactic radiotherapy, one of whom was confirmed slightly regressed on the follow-up angiogram. And also craniopharyngioma and pineocytoma was minimally regressed on 3 month follow-up CT. 정위다방향 단일 고선량 조사는 비침습적으로 두개골에 중추신경계 정위수술기구(Stereotactic frame)를 고정시켜 병소부위를 정확히 조준한 후 작은 조사야들을 통하여 단일고선량을 병소부위에 집중시킴으로써 이를 파괴시키거나 생물학적 효과를 유도하는 것으로 정의되고 있다. 이 방법은 비침습적이며 병소부위를 중심으로 여러 방향으로부터 방사선을 조사하므로서 병소부위에는 고선량을 집중시키고 주위성장 뇌조직에 가는 선량을 최소한으로 줄일 수 있다. 또한 1회에 주는 방사선량은 보편적인 다분할 조사방법에 의한것 보다 동일한 선량을 비교해 볼때 그 생물학적 효과가 3~4배로 높다. 이 방법은 크기가 작고 수술이 불가능한 두개내 심부종양 즉, 뇌하수체 종양, 두개인두관종양, 송과체종양, 수막종, 청신경초종 및 혈관기형 등에 주로 시도하여 왔다. 저자들은 1988년 7월부터 10월까지 6MV 선형가속기를 이용하여 병소가 3cm이하로 작고 수술이 불가능한 두개내 심부뇌종양 5예(청신경초종, 재발성 두개인두관종양, 혈관아세포종, 송과체세포종 및 뇌하수체 소선종, 각각 1예)와 동정맥성 기형 3예에 대해서 정위다방향 단일고선량조사를 시행하였기에 그 방법과 중간성적을 보고하는 바이다.

Functional Properties of Permeate Fractions Obtained from Bastard Halibut Roe Extracts by Ultrafiltration and It’s Biological Activities

Gyoon-Woo Lee1,In Seong Yoon,Su Gwang Lee,Jung-Suck Lee,Young-Mi Kang,Jin-Soo Kim,Min Soo Heu 한국수산해양기술학회(구 한국어업기술학회) 2016 한국수산해양기술학회 학술발표대회 Vol.2016 No.10

혈액투석중인 만성신부전 환자에서 골대사 지표로써의 Osteocalcin치

송치운,이진홍,안미애,윤환중,윤상임,성기양,이강현,송민호,이강욱,신영태,김영건,노흥규 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

Background : Serum osteocalcin is synthesized by osteoblast and has been shown to be sensitive indicator of bone turnover inpatients with various metabolic bone disease. In renal osteodystrophy, serum osteocalcin is elevated due to decreased renal clearance and elevated level of PTH. This study was done to evaluate the usefulness of serum osteocalcin as a marker of bone metabolism and the correlation with other biochemical markers of bone metabolism. Methods : We measured serum osteocalcin, calcium, phosphorus, ALP(alkaline phosphatase) and PTH(parathyroid hormone) in 37 patients with end stage renal disease on hemodialysis. Osteocalcin was determined by radioimmunoassay and PTH was determined by radioimmunometric assay. Results : 1) The mean level of serum osteocalcin in ESRD patients was 233.8± 218.2ng/ml which was significantly higher than that of controls(p<0.0001). 2) The mean level of serum PTH in ESRD patients was 40.5± 43.8pg/ml was significantly higher than that of controls(p<0.005). 3) There was a significant positive correlation between the level of serum PTH, ALP and the level of serum osteocalcin in ESRD patients. 4) By using multiple regression, PTH is most reliable factor that affect to elevated level of serum osteocalcin ( beta coefficient = 0.687, Sig T<0.05). Conclusion : Serum osteocalcin as a marker of bone metabolism in ESRD patients is more useful than other biochemical marker such as serum calcium, phosphorus, ALP and PTH is a most reliable factor that affect to elevated level of serum osteocalin.

교사들의 공통과학 실험 · 실습 선호도 조사 분석

정원우,이윤종,강용희,윤일희,이우붕,손종경,김중욱,강동진,권용주 慶北大學校 師範大學 科學敎育硏究所 1999 科學敎育硏究誌 Vol.23 No.-

The purpose of this study is to investigate the status of the experimental and practical education in high school general science. The present status and reasonable management of the experimental and practical education in high school general science were evaluated by the questionaires. To do this, 146 science teachers in Korea are administered questionaires. The frequency of the experimental and practical items in the seven kind of general science text books were investigated. The problems and the reasonable management for experimental and practical education were proposed in this paper.

현행 중등학교 과학 실험 , 실습 교육 실태 조사 및 그 운영 진단 (Ⅱ) : 고등학교 과학 실험 , 실습 교육을 중심으로

김영호,이윤종,정원우,강용희,양승영,윤성효,안병호,윤일희,권용주,임성규,오철한,기우항,전명남,김중욱 한국과학교육학회 1998 한국과학교육학회지 Vol.18 No.3

본 연구는 96년도에 실시한 우리 나라 중학교 과학 실험·실습 교육의 실태 조사 연구에 따른 계속 연구의 일환으로 고등학교 과학 실험·실습 교육의 실태를 조사하기 위한 것이다. 연구내용은 고등학교 과학 교과서의 분석, 실험·실습 실시 현황 분석, 현행 실험·실습 교육의 문제점 분석, 현행 학교 구성원들의 실험·실습 교육 운영 실태 조사 및 현행 실험·실습 교육의 개선을 위한 연구과제 도출을 주요 연구내용으로 다루었다. 연구방법은 전국의 고등학교 80개교를 대상으로 이들 학교의 학생 1,977명, 교사 165명, 학교장 80명에게 적용하였다. 본 연구에서 밝혀진 결과를 중심으로 우리 나라 고등학교 과학 실험 실습 교육의 정상화를 위한 실험 내적인 연구과제를 제시하면 다음과 같다. (1)교재 개발에 대한 연구, (2)실험 킷트 개발에 대한 연구, (3)교사교육 및 재교육 프로그램 개발에 대한 연구, (4)교실 밖 실험·실습 활동 프로그램 개발에 대한 연구, (5)과학 실험·실습 소재의 개발에 대한 연구. This study was accomplished to analysis and survey on the experimental and practical science education of high school in korea for the consecutive study of the an analysis and survey on the experimental and practical science education of middle school in korea(Lee, Yoon-Jong et al., 1997). The status of facilities, management for the experiment, practices, teaching methods in high schools have been investigated. The present status and reasonable management of the high school science education have been grasped from the questionaires. To do this 165 high school science teachers, 1977 students and 80 principals of high schools in Korea are administered questionaires of Science Education Research Institute of Kyungpook National University(1997). The results of this study are as follows : The reasonable management for experiments and practices of science education were scanty in the high school around the urban and rural school owing to the shortage of facilities and equipments, crowded class, excessive class works for teacher, excessive contents of present textbooks and insufficiency of the administrative supports etc. The current teaching method of high school science has emphasized knowledge. This fact does not satisfy the objective of learning due to lack of the teaching method. Desirable directions for the improvement of present status of high school science education were proposed in this paper.

간세포암과 감별이 어려웠던 악성중피종 치험 1예

김선문,허원석,채경훈,강윤세,정재훈,김연수,박기오,문희석,이엄석,김석현,성재규,이병석,이헌영,신경숙,조준식,송인상,강대영 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Malignant peritoneal mesothelioma is a rare neoplasm that arises from the mesothelium of a serosal cavity and is a rapidly fatal disease with a median survival of 4 to 12 months for untreated cases. Recently, we experienced a case with malignant peritoneal mesothelioma who was suspected hepatocelluar carcioma by abdominal CT scan and was confirmed by biopsy including immunohistochemical stain(calretinin) after surgery. We performed tumor excisions and wedge resection of the liver(segment Ⅷ)and inserted Tencoff catheter in abdominal cavity at 25th day of post-operation. We treated with intraperitoneal paclitaxel(25mg/m^(2)/day for 5 days) six courses monthly. She was well tolerable and is still living without any evidence of recurrence for 14th month of post-operation.

GO-62 : Lower extremity edema in patients with endometrial cancer

( Myong Cheol Lim ),( Jeong Seon Lee ),( Jung Nam Joo ),( Sang Soo Seo ),( Sok Bom Kang ),( Sang Yoon Park ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.99 No.-

The objective of this study was to investigate clinical manifestations of lower extremity edema (LEE) in endometrial cancer Medical records for LEE and/or responses to the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) were evaluated in 177 patients with endometrial cancer Patients had a median age of 53 years. Sixty-seven patients (37.9%) had past (9 patients, 13.4%) and/or current patient-reported LEE (58 patients, 86.6%). Symptoms reported on the GCLQ in over 20% of respondents were swelling, numbness, aching , and heaviness. GCLQ total symptoms score was significantly higher in patients with current LEE. Most of the LEE (43/67, 64.2%) developed within 12 months after surgery and LEE lasted more than 6 months in most patients (56/59, 94.9%) Prospective clinical trials are needed to know the clinical significance, impact on quality of life, and preventive strategy of LEE in patients with endometrial cancer