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>

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.

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.

직업인으로서의 과학기술자 및 여성 과학기술자, 그리고 역할모델에 대한 중·고등학생들의 인식 조사

이혜숙,최경희,이재경,마경희,이기순 한국과학교육학회 2005 한국과학교육학회지 Vol.25 No.2

본 연구에서는 이공계 위기를 극복하고 또한 여학생의 이공계 진출을 위한 방안 모색의 기초 자료로서, 중고등 학생을 대상으로 직업인으로서 과학기술자에 대한 인식, 여성의 이공계열 진학 및 과학기술 관련 직업을 갖는 것에 대한 인식, 그리고 국내외의 남녀과학기술자의 인지도와 존경하는 남녀과학기술자를 조사하였다. 조사 결과, 직업인으로서의 과학기술자에 대한 고등학생들의 인식은 긍정적이라고 볼 수 있으나, 대학 전공과 직업 선택에 대한 관심이 보다 구체화되는 2학년이 1학년보다 그리고 이러한 부정적 인식을 자신의 일로 심각하게 고려할 가능성이 높은 이학공학정보과정 학생이 인문사회어문과정 학생보다 부정적 인식이 높다. 또한 여학생의 이공계 진학과 여성 과학기술자에 대한 인식도 전반적으로 긍정적이었으나 문항에 따라 인식에 차이가 있었는데, 남학생과 여학생 모두 '여성의 사고나 신체적 차이로 인한 이공계 진학의 부적합성'에 대해서는 동의하는 정도가 낮았지만, '취업과 근무조건 등 비교적 현실적 측면'을 반영하는 항목에 대해서는 상대적으로 부정적 의식이 높게 나타났다. 국내외의 남녀과학기술자의 인지도는 남성과학기술자에 비해 여성과학기술자, 특히 여성과학기술자 중에서도 국내 여성과학기술자에 대한 인지도가 훨씬 낮게 나타났다. 또한 높은 비율의 여학생들이 존경하는 여성 과학기술자의 상을 갖지 못하고 있었다. The purpose of this study is to identify various issues contributing to the current issues of students not wanting to major in science and engineering, and further explore various strategies to encourage their higher education in the science and engineering area. The study administered survey on students' perception towards the science related profession including respondents' gender, grade, their attitude towards woman scientists, perception on the woman scientists, scientists as profession, their level of knowledge on the scientists, and if there is any they respect. The results indicated that overall perceptions on the scientists as career for high school students was positive. but there was more negative acceptance for the juniors since they are more concerned with their majors at the university; higher for students who are in the natural science area than the ones in the social science school since they are more directly related than others. The perception on the woman scientists and girls in the science and engineering majors was positive. However. there were some differences in the response level among the items. Among these. considering the job availability and conditions, the perception was more negative than the others. Also the result indicated that both boys and girls disagree that the science-related profession may be gender-inappropriate for girls due to physical and cognitive characteristics. Results also indicated the level of awareness among scientists, they had higher awareness for male scientists than that of the female, and also international ones than the national ones. And many girls did not have positive image of a successful woman scientists.

The Effect of Power Walking Exercise on Body Mass Index and Positive and Negative Symptoms in Patients with Schizophrenia

Lee,Jung Hee,Lee,Kyung Hee 계명대학교 간호과학연구소 2009 계명간호과학 Vol.13 No.1

Purpose : This study was designed to evaluate the effects of power walking exercise on Body Mass Index(BMI) and Positive and Negative Symptoms in inpatients with schizophrenia. Method : The study was conducted from February 1 to April 10, 2005 at the S mental hospital in Gimcheon. Sixty schizophrenic patients were allocated into intervention group (n= 30) and control group (n=30). Intervention group received routine care and power walking exercise 3 times a week for 8 weeks whereas control group received only routine care. Data were analyzed by descriptive statistics, χ2_test, and independent t-test using SPSS/WIN 11.0 version. Result : Hypothesis I, "the BMI of the intervention group will be lower than that of control" was supported(t=-6.845, p=.000). Hypothesis II, "the scores of positive and negative symptoms of the intervention group will be lower than those of the control" was rejected(t=-1.418. p=.161). Conclusion : Results of the study showed that power walking exercise was effective for the reduction of BMI but did not show statistically significant improvement in PANSS. Further study may be necessary to determine the long term effects of the current power walking exercise.

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 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.

Impedance를 이용한 전도성고분자 센서의 가스감응특성

이경문,유준부,이병수,전희권,이상태,이덕동,허증수 경북대학교 센서기술연구소 2002 센서技術學術大會論文集 Vol.13 No.1

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in management of peritoneal carcinomatosis: Single center experience in Korea

Hee Ju Lee1,HyungJoo Baik1,박요한,서상혁,김광희,Ki Beom Bae,Kwan Hee Hong,김기향,변정미,Dae Hoon Jeong,Kyung Bok Lee,오민경,조광래,안민성 대한종양외과학회 2019 Korean Journal of Clinical Oncology Vol.15 No.2

Purpose: Peritoneal carcinomatosis (PC) has been considered a terminal condition and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIEPC) is regarded as an alternative therapeutic option. This study aimed to evaluate the 30-day clinical outcomes of CRS/HIPEC and the feasibility of the surgery by investigating the morbidity and mortality in Inje University Hospital. Methods: Data were retrospectively collected from 19 patients with PC who underwent CRS/HIPEC at Inje University Hospital in 2018. We evaluated pre-, intra-operative parameters and postoperative clinical outcomes and early complications. Results: The mean operating time was 506.95 minutes and the mean blood loss was 837.11 mL. Six cases (31.58%) had morbidity of grade III or above. A longer operating time (≥560 minutes, P=0.038) and large blood loss (≥700 mL, P=0.060) were positively correlated with grade III or worse postoperative complications. Conclusion: Our early experience with CRS/HIPEC resulted in a 31.58% morbidity rate of grade III and above, with risk factors being longer operating time and greater intraoperative blood loss. As the surgical team’s skills improve, a shorter operating time with less intraoperative blood loss could result in better short-term outcomes of CRS/HIPEC.

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.