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>

기관지 방선균증의 임상 1례

이은영,장태원,정만홍,옥철호,이규원,손창배,이지숙,신은경,서정아,백종현,김영옥 고신대학교의과대학 2007 고신대학교 의과대학 학술지 Vol.22 No.2

Actinomycosis is a chronic suppurative infection, whitch infiltrates mucosa-associated tissues. Thoracic, pelvic and cervicofacial infections of actinomyces are not uncommon, but endobronchial actinomycosis is rarely reported. We report a case of a 29 year old man who presented with a recurrent pneumonia and chronic cough. Fiberoptic bronchoscopy revealed occlusion of the right. lower medio-basal segment bronchus with exophytic endobronchial mass. The diagnosis was confirmed histologically by demonstration of sulfur granules in the bronchoscopic biopsy of the mass. Intravenous administration of amoxacillin and clindamycin followed by oral amoxacillin and clindamycin therapy resulted in complete recovery.

제2형 당뇨병 환자에서 적극적 환자 교육이 혈당조절에 미치는 효과

이윤욱,황원선,최선정,이동훈,김도현,이은희,홍은경,노혜림,정윤석,이관우,김현만 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.1

연구배경: 현재까지의 당뇨병 교육에 대한 노력은 제한되었으며, 연구 결과를 보면 식사 조절 교육과 체중 조절 프로그램을 수행한 환자들 중 적극적이고 기간이 긴 교육을 받은 경우, 성공적 결과가 나타남을 알 수 있었다. 자가관리나 체중감량 등의 당뇨병 치료의 중요한 목표는 적극적이고 긴 기간의 교육 없이는 시행되기 어렵다. 본 연구에서는 외래에서 당뇨병 환자를 대상으로 시행할 수 있는 행동 및 식사 교육 등의 적극적 교육 프로그램을 개발하여 제2형 당뇨병 환자들을 대상으로 이들에게 식사 조절 방법에 대한 목표설정과 문제에 직면하였을 때의 해결 방법 등을 교육해서 궁극적으로는 적극적 자아관리에 연결될 수 있도록 도와주는 것을 목적으로 기존의 통상적 교육과 보다 적극적인 교육이 당뇨병 환자의 혈당 조절에 어떠한 영향을 미치는지에 대해 알아보기 위해 다음과 같은 연구를 시행하였다. 방법: 본 연구는 아주대학교 병원 내분비 대사 내과를 처음으로 방문하여 치료받았던 58명의 제2형 당뇨병 환자를 대상으로 하였다. 내원 환자들을 무작위하게 추출하여 진찰권 번호 끝자리에 따라 홀수는 통상적 교육군(conventional education group, CE)과 짝수는 적극적 교육군(intensive education group, IE)으로 나누어 교육하고, 3개월후에 교육의 효과를 평가하였다. 결과: 1) 연구 대상자들의 교육 전과 후의 공복혈당, 식후2시간 혈당 및 HbA_lc 치는 IE군과 CE군 모두 각 그룹 내에서, 유의적으로 감소하였다(p<0.05). IE군에서는 공복혈당이 12.4nmol/L에서 7.7nmol/L로, 식후2시간 혈당이 20.3nmol/L에서 10.9nmol/L으로, HbA_lc치가 9.4%에서 7.0%로 모두 교육 전에 비하여, 교육 후에 감소(p<0.05)하였고, CE군도 공복혈당은 10.9nmol/L에서 9.4nmol/L로, 식후2시간 혈당은 17.1nmol/L에서 14.6nmol/L으로 HbA_lc가 8.5%에서 7.3%으로 모두 교육 후에 감소하였다(p<0.05). 또한, 교육 전에 비하여 교육 후에 공복 혈당 및 HbA_lc치가 감소하는 정도는 IE군에서의 감소가 CE군에 비해 더 현저하였다Op<0.05). 2) 식사에 대한 태도는 3부분으로 나누어 식사에 대한 규칙성, 식사 내용의 균형성, 식사에 대한 태도 등으로 나누어 각각의 점수 및 총점을 비교하였으며 교육 전에 비해 교육 후에 연구 대상자들의 식태도가 향상되었음을 알 수 있었다. 두 그룹간의 차이를 분석한 결과 식사의 균형성 항목에서와 총점에서 유의적으로 두 그룹의 차이를 보여서 IE군에 CE군에 비해 식사의 균형성 측면이 향상되었고, 전체적인 식태도가 좋아졌음을 알 수 있었다(p<0.05). 결론: 비교적 긴 기간은 아니지만 적극적 교육을 받은 당뇨병 환자들이 통상적 교육을 받은 군보다 혈당 및 HbA_lc, 식태도 점수등의 수치의 호전뿐만 아니라 당뇨병 환자의 삶에서 중요한 부분을 차지하는 식사요법 관리 부분에 있어 향상됨을 알 수 있었다. Background: To this date, efforts to develop effective methods for the education of diabetic patients have been limited. The important goal of self-management and weight control for diabetic treatment can not be attained without long and intensive period of education. This study was undertaken to assess the effectiveness of an intensive educational program, of behavior and diet control, which was carried out on subjects with type 2 diabetes, on and out-patient basis. we compared the effectiveness of an intensive education programme with that of a conventional education programme for the self-management of type 2 diabetic patients. Methods: Subjects with type 2 diabetes were randomly selected, and allocated to one of two groups. One group received a conventional education programme of self-management(the CE group), and the second group received an intensive education progammes for three months, after which the effectiveness of the programmes were evaluate. Results: 1) The levels of fasting blood sugar(FBS), postprandial 2 hour blood sugar(PP2h) and HbA1c were significantly lowered in both groups following the intervention(p<0.05). In the IE group, the FBS declined from 12.4nmol/L to 7.7nmol/L, PP2h declined from 20.3nmol/L to 10.9nmol/L, and the HbA_lc showed a similar decline from 9.4 to 7.0% after intervention(p<0.05). In the Ce group, the FBS declined from 10.9 to 9.4nmol/l, the PP2h decreased from 17.1 to 14.6nmol/l, and the HbA_lc also decreased from 8.5 to 7.3% after intervention(p<0.05). The decrease in the FBS and HbA_lc following the educational intervention was more pronounced in the IE group than the CE group(p<0.05). 2) The effectiveness of the education programmes in promoting appropriate dietary behavior in the diabetic subjects was assessed by a scoring system in three parts: a regularity score, a balance score and an attitude score. From a comparative study of the three scores, the patients attitudes were observed to be much improved in both the groups following the intervention compared to before the programmes, but the balance and total scores were significantly higher in the IE group than the CE group(p<0.05). Conclusion: We can conclude that the intensive diabetic education programme is more effective than a conventional programme, not only in improving the patients' levels of glucose, HbA_lc, and dietary score, but also the diabetic patients self-control abilities, promoting behavioral change, and prompting problem solving capabilities in respect to the everyday problems that they have to face throughout their lives(J Kor Soc Endocrinol 18:63∼72, 2003).

관절염 환자의 민속요법이용 형태

은영,강현숙,이은옥,이인숙,이종수 서울대학교 간호대학 간호과학연구소 1997 간호학 논문집 Vol.11 No.1

This sty was undertaken to explore the utilization patterns of medical treatment and herb medicine in patients with arthrits. The data were collected from 995 patients who were registered either in a center of rheumatology or resided in community with arthritis. The data were analyzed by percentile, t-test and chi-square test using SAS PC program. The results of this study were as follows; 1. According to characteristics of sample-population, mean age was 57.7 years, duration of arthritis 9.7 years and mean duration of pain 2.4 hours per day at present. 2. First diagnosis was identified at department of orthopedic surgery or local clinic. But 85.2% of patients have transferred to the center of reumatology currently. But ironically over 70% of patients experienced the herb treatment and herb treatment had hern medicine simultaneous with medical treatment. This indicated that they were shopping around of treatment during the first one year. 3. Mean cost of medical treatment was 67,400 won, while they payed to herb medicine as much as two or three times. The utilization rate of herb medicine was 36.5% of patients per one year. Costs of herb-treatment were 182,000 Won and herb medicine was 36.6% of patients per one year. Costs of herb -treatment were 182,000 Won and herb medicine 149,100 Won. 4. Eighty point six percent of patients were experienced herb medicine during life-time. One hundred and seventy four kinds herb medicine were found to be used by patients, most of which were nutrients, muscle relaxants, andtiphlogistics and analgesics. Thirty two point six percent of users recognized that herb medicine were effective but 51.7% did not. In conclusion, arthritis patients have been experienced various kinds of drug and remedies for treatment. And they wasted their limited medical and economical resources on these unresonable remedies. Therefore, they should be guided for wise decision about treatment. Futher studies in nursing will be required to explore the value system of patients about herb medicine, the determinant factors of shopping-around patterns of treatment, and the coping mechanism for chronic pain or aggravating symptom.

Maximizing Tendency, Purchase Involvement, and Perceptions of Online Bookstores

Lee,Gyudong,Kim,Jang-Hyun,Lee,Jae-Eun 韓國商品學會 2011 商品學硏究 Vol.29 No.6

This paper investigates the effects of the maximizing tendency (i.e., individual differences in pursuing the best option) on purchase involvement and the perceptions of Web sites. By using survey data collected from South Korea and the United States, we analyze the differences in purchase involvement, perceptions of Web sites, and intention to use between satisficers (those with low maximizing tendency) and maximizers (those with high maximizing tendency). In both samples, maximizers show higher purchase involvement than their counterparts. While the perceptions of usefulness and ease of use are significantly different between the two groups in the United States sample, we do not confirm the same pattern in the South Korean sample. We conclude with a discussion of the results and implications.

아동의 物活論的 思考에 관한 연구 : Piaget의 가설을 중심으로

李恩和,尹賢燮 이화여자대학교 한국문화연구원 1976 韓國文化硏究院 論叢 Vol.28 No.-

This study was intended to investigate the Korean child's animism and to test Piaget's hypothesis with Huang-Lee's experimental tools. The experimental hypotheses in this study were: 1) Piagetian animism could be found in Korean children's mentality, and 2) Piaget's hypothesis could be proved not only by Russell-Dennis's tools but also by Huang Lee's. Russell and Dennis have proved Piaget's hypothesis and standardized the experimental procedures to test child's animism; however, M. Mead and Huang-Lee have denied the Piagetian animism in Manusian and Chinese children. Russel and Dennis have also suggested four developmental stages in child's animism. Twenty Korean children, aged between 4-7, were tested individually, the combined experimental procedures of Russell-Dennis and Huang-Lee being used, As a result, the first hypothesis in this study was positively confirmed only by Russell-Dennis's method. This means that the second hypothesis in this study was not confirmed. 90% of the Subjects in this study have had the concept of life or living, and did not regard inanimate objects as having characteristics of "feeling pain." It seems to us that the subjects in this study tend to make some cognitive continuity between their awareness of their living and the being of physical objects. In Piagetian terms, the subjects have not dissociated themselves from their physical and natural environment.

Inducing apoptpsis by the inhibition of c-myb in oral squamous carcinoma cell line, KB cell

Lee,Jung-Chang 대한구강생물학회 2007 International Journal of Oral Biology Vol.32 No.4

Oral squamous cell carcinoma (OSCC) is the most commonmalignancy and is a major cause of worldwide cancer mortality.The proto-oncogene c-myb plays an important role in regulationof cell growth and differentiation, and it is expressed at highlevels in hematopoietic cells and many other types of cancers.However, the function of c-myb is not well known in OSCC.The present study aimed to reveal the function of c-myb and totest the alternation of cell growth and signaling by c-myb inOSCC. In this study, c-myb and dominant-negatibe myb(DN-myb) were expressed in an adenovirus-mediated gene deliverysystem to KB cells. The over-expressed c-myb broughtincreased cellular proliferation compared with control cells.However, DN-myb infected KB cells showed significantreduction of cell growth and enhanced induction of apoptosis toactivate PARP and caspase 9. c-myb induced increase of IGF-I,-II and IGF-IR expressions while DN-myb down-regulatedthese expression. Activation of ERK and Akt/PKB pathwaywas shown only in c-myb transduced cells. These findingssuggest that the role of c-myb in cell growth of oral cancer cellsis partially mediated through the modulation of IGFs, ERK andAkt/PKB. From this results, DN-myb is strongly recommendedas a curable gene for the treatment of c-myb dependentmalignancies such as OSCC.

2003년 국내 중증급성호흡기증후군 진료 현황 및 문제점 분석

이진수,김은실,정문현,백제중,정선화,안주희,최영화,이선희,고철우,김성범,김민자,박승철,기현균,송재훈,최상호,김양수,이상오,조용균,박영훈,정숙인,김연숙,이흥범,손창희,장성희,정희진,김우주 대한감염학회 2004 감염과 화학요법 Vol.36 No.3

목적 : 2002년 말 중국에서 SARS가 발생한 이후 국내에서도 2003년 10월까지 총 3명의 추정환자, 17명의 의심환자가 보고되었다. 향후 추가적인 SARS의 유행이 우려되는 상황에서, 그간의 SARS 환자 진료에 있어서의 실질적인 준비사항, 진료 현황 등에 대한 조사를 통해 문제점을 파악하여, 향후 더 나은 대비가 될 수 있도록 개선점을 제시하고자 하였다. 재료 및 방법 : SARS로 의심되는 환자를 진료 경험이 있는 병원의료진을 대상으로 2003년 10월에 설문조사를 실시하였다. 설문에는 SARS 환자 진료 시의 실질적인 조치, 진료 현황, 병실, 응급실 및 외래에서의 격리 시설과 준비사항, 보건당국의 관리와 지원에 관한 사항을 포함하였다. 결과 : 대상이 되는 22개 병원 중 17개(17/22, 77.2%) 병원이 설문에 응하였다. SARS 환자를 위한 격리실은 응급실, 외래, 일반병실 및 중환자실에서 각각 9개(9/17, 52.9%), 5개(5/17, 29.4%), 15개(15/16, 93.7%), 4개(4/16, 25%) 병원에서 음압처리가 되어있지 않은 일인실 혹은 다인실이 사용되었고, 1개(1/16, 6.3%) 병원에서만 일반병실에서 음압격리실이 운영되었다. 입원환자의 진찰 시 개인보호구의 착용은 거의 모든 의료기관에서 이루어졌다. 보건당국에서 SARS지정병원의 시설 등을 사전에 확인한 곳은 1곳(1/12, 8.3%)이였고, 14개 병원(14/15, 93.3%)에서는 보건당국에 의뢰한 검사결과를 통하 받지 못하였다. 결론 : 의료기관에서 SARS 환자용 격리실뿐만 아니라 기존의 격리실 설비 등이 미흡하였으며, 특히 중환자실 및 외래의 준비가 더욱 부족하였다. 보건당국의 의료기관에 대한 종합적인 지원이 부족하였고, 병원과의 원활한 연계가 잘 이루어지지 않았다. SARS 만이 아닌 격리를 필요로 하는 질환의 적절한 진료를 위해 향후 병원 시설의 정비와 정부차원에서의 보다 구체적이고 실질적인 대책마련이 필요하다. Background : There was an worldwide outbreak of the Severe Acute Respiratory Syndrome (SARS) originated from China in late 2002. During that period three cases of suspected SARS and 17 cases of probable SARS were reported in Korea. With the concerns about the reemergence of SARS-coV transmission, it is important to be prepared for any possibility. So, this study is aimed to analysis the past measures in managing SARS and propose the amendatory plans to improve the preparedness. Materials & Methods : Questionnaires were collected among clinicians with any experience in managing the probable or suspected SARS cases in Oct. 2003. 17 out of 22 hospitals responded to the questionnaire. The contents in the questionnaire were practical activities, personal equipments, response plans, isolation facilities in emergency centers, outpatient clinics, general wards and intensive care units, and relationship with the public health department. Results : The dedicated isolation rooms in emergency centers, outpatient clinics, general wards, and intensive care units were prepared in 9 (9/17, 52.9%), 5 (5/17, 29.4%), 15 (15/16, 93.7%), and 4 (4/16, 25.0%) hospitals, respectively. Except for one hospital that newly made negative pressure room for SARS, single or multi-bed rooms without airborne infection control were used in all the other hospitals. The personal precaution principles were kept quite well in general wards. Before the designation of SARS hospital by the public health department prior evalution to see if the hospital was suitable for managing SARS was conducted in only 1 (1/12, 8.3%) hospital. The results of laboratory diagnosis were reported back in 1 (1/15, 6.6%) hospital. Conclusions : The isolation facilities which can control airborne infection were almost deficient not only for SARS but also for other respiratory transmissible diseases. For the infection control of transmissible diseases including SARS, more investment is needed on medical facilities and comprehensive support from the public health department required.

연골외막세포가 포함된 alginate beads를 이용한 토끼에서의 골연골결손 치료

안현정,김은미,정미현,조현철,이인범,성상철,이명철 대한정형외과연구학회 2003 대한정형외과연구학회지 Vol.6 No.2

Dog leukocyte antigen identity among cloned dogs with same donor cell

Ji Eun Kim,Hyun Ju Oh,Jung Eun Park,Min Jung Kim,Goo Jang,Byeong Chun Lee 한국발생생물학회 2010 한국발생생물학회 학술발표대회 Vol.29 No.-

The canine major histocompatibility complex (MHC) is referred to dog leukocyte antigens (DLA), which is known to be the most polymorphic genetic system in canine species. Many cloned dogs have been produced since Snuppy, first cloned dog, there was no research about genetic identity of MHC among cloned animals. Recently in Lee’s group, two non-transgenic cloned beagles (BG1, 2) were produced by somatic cell nuclear transfer (SCNT) using fetal fibroblast (BF). Also, four transgenic cloned beagles (Ruppy 1-3, 5) were generated using transgenic BF transfected with Red fluorescent protein (RFP) gene. We hypothesize that non-transgenic (BG1, 2) and transgenic (Ruppy 1-3, 5) cloned beagles derived from identical donor cells have the same immunological genetic characteristic except for RFP gene insertion in the genome. Thus, the aim of this study is to confirm the immunological identity of DLA class II in cloned beagles produced using same nuclear donor cell. Genomic DNA was extracted from blood of BG1, BG2, Ruppy 1, 2, 3 and 5. Genomic DNA of normal two control beagle, no correlation with BF was also investigated for rulling out the possibility that beagles were inbred. Forward and reverse primers used for DLA-DQA1 and DQB1 respectively were DQAF: 5’-TAAGGTTCTTTTCTCCCTCT-3’ and DQAR: 5’-GGACAGATTCAGTGAAGAGA-3’ DQBR:5’-CTCACTGGCCCGGCTGTCTC-3’ and DQBR: 5’-CACCTCGC CGCTGCAACGTG-3’. Polymerase Chain Reaction (PCR) products were purified, sequenced directly using the Big Dye Terminator kit. Sequencing analysis was performed on an automated 3730xl DNA analyzer. In experiment 1, sequence of DLA-DQ alpha 1 (DQA1) and DLA-DQ beta 1 (DQB1) exon 2, hypervariabel region, was compared in BG1 and BG2. Experiment 2 also compared the sequence of DQA1 and DQB1 among Ruppy 1, 2, 3 and 5. Experimental 3 compared sequence of DQA1 and DQB1 among all cloned dogs (BG1, BG2 and Ruppy 1-3, 5). As a result, BG1 and BG2 have same allele for DQA1 and DQB1 as we expected. They share DQA1*00101 and DQB1*02901 in experiment 1. In experiment 2, Ruppy 1, 2, 3 and 5 also have identical DQA1*00101 and DQB1*02901 allele. No discrimination between transgenic dogs and cloned dogs was seen in DQA1 and DQB1 Allele in experiment 3. DQA1, DQB1 allele was identified as *00101 and *02901 in all dogs. We provided the allele identity of DQA1and DQB1 in cloned beagles, which can be used as preliminary data for immunological related studies. In conclusion, transgenic cloned dogs despite of red fluorescent protein genes being inserted in their nuclear DNA were immunologically compatible with non-transgenic cloned dogs. We demonstrated that cloned beagles produced using identical nuclear donor were immunologically compatible.