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        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>

      • KCI등재

        공기청정기의 일부 실내공기 오염물질 제거효율에 관한 연구

        이태형,김윤신,홍승철,이철민,김종철,전형진,김중호 한국환경과학회 2005 한국환경과학회지 Vol.14 No.5

        In this study, we investigated PM_(10), NO₂, and 1-hydroxypyrene(1-OHP) in urine at indoor environments which are 35 houses and 20 hospitals for using air cleaner and non-using air cleaner in Seoul metropolitan area and Kyoung-gi province from April, 2003 to February, 2004. Moreover, we examined effect of improvement for indoor air quality and health effect by concentration of 1-OHP also we investigated removal efficiency by air cleaner for PM_(10), NO₂, and 1-OHP that were 28.5%, 27.4%, and 42.1% respectively. Concentration of PM_(10), NO₂, and 1-OHP were 19.02±18.14μg/m³, 8.66±3.06ppb, and 0.19±0.18μg/g creatinine when air cleaner was no worked. The concentration for PM_(10), NO₂ and 1-OHP were 13.60+10.79μg/m³, 6.29±2.71ppb, and 0.11±0.10μg/g creatinine, respectively. It was significant statistically. Therefore, it is considered using the air cleaner to remove the partial pollutants in indoor environment and is positive effect for health.

      • 폐내 기관지 낭종

        이석열,이숭진,박형주,이철세,이길노,김윤정,나주옥 순천향의학연구소;Soonchunhyang Medical Research Institute 2004 Journal of Soonchunhyang Medical Science Vol.10 No.2

        A 33-year-old female was admitted to our hospital due to removal of lung mass which indicentally detected Chest radiography. Chest computerized tomography revealed lung parenchymal cystic lesion. Open thoracotomy was done for diagnosis and therapy. Cystic lesion was communicated to bronchus and wedge resection including cystic lesion was done. Bronchogenic cyst is congenital disease and mainly locate in mediastinum. It is rare in lung parenchyme. Herein we report a case of intrapulmonary bronchogenic cyst.

      • 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

      • KCI등재

        일 도농복합지역 저소득층 노인의 건강문제 분석 : 보건소 방문간호사업 대상자 중심으로

        고일선,,이태화,이경자,이정렬,임미혜,천의영,주윤미,이계철 노인간호학회 2005 노인간호학회지 Vol.7 No.2

        Purpose: The purpose of this study was to analyze the health problems of low-income aged with chronic illness living in urban-rural composite area. Method: The sample consisted of 440 aged who were receiving home care services from a public health center. MDS-HC was applied to analyze the health problems of the aged. Data were collected through a face- to-face interview by six trained interviewers from June 28 to July 15, 2004. Result: Subjects had average number of 8 health problems in both urban and rural area. Lack of preventive health care measure, pain, and visual function were the most frequent health problem. The rural aged had more pain, bowel management problems, compared to the urban aged having more urinary incontinence and indwelling catheter. There were many health problems related to falls and pressure ulcers with middle-old aged in urban, and old-old aged in rural area. Conclusion: The results of this study showed strategies for care intervention of low-income elderly to put in practice. Therefore, tailored-service for each subject should be provided.

      • KCI등재

        광조사 방법에 따른 치과용 심미수복재의 중합수축

        윤태호,이용근,임범순,김철위 대한치과기재학회 2000 대한치과재료학회지 Vol.27 No.4

        Dental resin composites were introduced commercially in the mid-1960s for the restoration of anterior teeth. Since their advent, resin composites have undergone significant development, which continues to improve the longevity and application of resin composite restorations. Despite the development of new dentin-bonding agents, no system is currently available that completely withstands the formation of contraction gaps at the cementum/dentin-restoration junction, due to the unavoidable polymerization shrinkage of the resin composite during setting, therefore, a major aim of this study was to minimize or control the polymerization shrinkage of composites allowing flow of resin during setting reaction. A thermal dilatometer (DIL 402C, TASC 414/3A Controller, Netzche, Germany) was used to measure and compare conventional continuous cure and pulse cure polymerization shrinkage of seven light curing dental composites and three compomers. For conventional cure, restorative material were polymerized for 2 minutes using VIP (Bisco, U.S.A.) with 400 ㎽/㎠ intensity. After then, further polymerization was allowed for next 12 minutes that total 14 minutes of shrinkage was measured. For pulse cure, material was pre-polymerized irradiating light for 5 seconds with 200 ㎽/㎠ and post-ploymerized 3 minutes later with 400 ㎽/㎠ for 2 minutes. 9 minutes were allowed for further polymerization that total 14 minutes of shrinkage was measured. Polymerization shrinkage ranged from 3.758 ㎛/㎜ (SYC) to 6.897 ㎛/㎜ (P60) for conventional cure and 4.026 ㎛/㎜ (FLT) to 6.996 ㎛/㎜ (SRF) for pulse cure. The highest difference between the two methods was found at EAN (2.713 ㎛/㎜), followed by F20 and CRA which showed significant differences of 2.133, 1.274 ㎛/㎜ respectively (p<0.05). The least difference was found at SYC (0.489 ㎛/㎜). Universal resin composite group showed the highest polymerization shrinkage (6.514±0873 ㎛/㎜), and flowable composite showed the least shrinkage (4.139 ㎛/㎜). Packable composite showed 5.090±1.906 ㎛/㎜, and compomers showed 6.129±2.652 ㎛/㎜.

      • KCI등재

        광원 및 광조사 방법에 따른 심미충전재의 중합수축

        이용근,윤태호,임범순,김철위 대한치과기재학회 2000 대한치과재료학회지 Vol.27 No.4

        The polymerization shrinkage of dental esthetic filling materials of five kinds of resin composite and three kinds of compomer was measured with a thermal dilatometer (Thermal Dilatometer, DIL 402C, TASC 414/3A Controller, Netzche, Germany) during polymerization with a halogen lamp curing unit (VIP, Bisco, U.S.A.) or a plasma arc curing unit (Flipo, Serial No. P03G02221, Lokki, France). The irradiation time of the halogen lamp was 40, 80 and 120 s with the intensity of 400 ㎽/㎠, and that of the plasma arc was 9 s. The pulse-cure mode with a halogen lamp was 5 s pre-polymerization at 200 ㎽/㎠, 3 minutes wait and then 120 s irradiation at 400 ㎽/㎠. From this experiment, the following results were obtained : 1.Depending on the irradiation source and mode, the amount of polymerization shrinkage after 14 minutes from the start of irradiation was significantly different in some materials. However, there was no significant difference in most of materials (p>0.05). 2.Most of the polymerization shrinkage occurred within two minutes from the start of irradiation except for pulse-cure. 3.In all the materials studied, the amount of polymerization shrinkage after 14 minutes from the start of irradiation was not different between the results from 120 seconds irradiation with the halogen lamp and these from pulse-cure (p> 0.05), and the amounts of shrinkage from a plasma arc was generally lower than those from other curing modes. 4.The amount of polymerization shrinkage after 14 minutes from the start of irradiation was not different between the results from 120 seconds irradiation with a halogen lamp and those from plasma arc (p>0.05) in all the eight materials studied.

      • Pipe 및 Hose Ass'y 생산시스템 공정최적화 설계 연구

        윤철호,이수완 선문대학교·중소기업기술지원연구소 1998 선문공대 연구/기술 논문집 Vol.3 No.1

        자동차 에어콘 부품인 Pipe 및 Hose 조립 공정의 생산성을 향상시키기 위하여 공정분석을 실시하였다 시간 연구법에 의해 대상 공정인 5개의 Pipe 및 Hose Ass’y공정에 대한 관측을 하였고. 그 결과 공정별 요소작업및 요소작업별 표준시간을 설정하였다 표준시간을 기초자료로 활용하여 line balancing을 실시한 결과 공정을 재배치 하게되면 공정의 균형 손실이 현저하게 줄어든다는 것을 알 수 있었다. Process analysis was conducted to improve productivity of the automobile airconditioner parts assembly lines. First, five pipe and hose assembly lines were observed by time study methodology. Using the results, element works of target assembly lines and standard time of element works were fixed. Next, line balancing methodology was utilized to evaluate current productivity of target process and layout status The results suggested remarkable line balancing effects when target process relocated

      • 腎臟組織에서 백강잠 抽出物의 抗酸化 作用에 關한 硏究

        李武炯,尹哲浩,鄭智天 동국대학교 한의학연구소 1998 東國韓醫學硏究所論文集 Vol.7 No.1

        白彊蠶 추출물이 신장조직에서 반응성 산소기들에 의한 지질의 과산화와 세포 손상을 방지하는지를 관찰하기 위하여 정상조직과 t-BHP를 처리한 조직에서 白彊蠶 추출물의 효과를 조사하였다. 지질의 과산화와 LDH 유출은 t-BHP의 농도에 비례하여 증가되었으나, 白彊蠶 추출물의 첨가로 유의하게 억제되었다. 그리고, t-BHP에 의한 지질의 과산화 및 LDH 유출은 白彊蠶 추출물의 농도에 비례하여 억제되었다. 또한, 白彊蠶 추출물은 oxidant를 처리하지 않은 정상조직에서도 지질의 과산화 및 LDH 유출을 유의성 있게 감소시켰다. 그리고, catalase 활성에는 영향이 없는 반면, 정상 조직과 t-BHP를 처리한 조직에서는 glutathione peroxidase 활성을 유의성 있게 증가시켰다. 한편, 반응성 산소기의 발생은 白彊蠶 추출물의 농도에 비례하예 억제되었다. 이러한 결과로 볼 때, 白彊蠶 추출물은 신장 조직내 항산화 효소의 활성을 증가시킴과 동시에 직접 반응성 산소기의 발생을 억제하므로 신장 조직에서 지질의 과산화와 세표손상을 방지하는 효과가 있을 것으로 여겨진다. This study was undertaken to determine whether Bombycis Corpus extract (Bom) has antioxidant action. Kidney tissues were exposed to t-butylhydroperoxide (t-BHP) to induce oxidative stress. Lillid peroxidation was estimated by measurimg rnalondialdehyde, a product of lipid peroxidation, and cell injury was estimated by measuring lactate dehydrogenase (LDH) release in rabbit renal cortical slices, t-BHP increased lipid peroxidation and LDH release in a dose-dependent manner over the concentration range of 0.1-1 mM. Such effects of t-BHP on lipid peroxidase and LDH release were prevented by 0.5% Bom. When tissues were treated with t-BHP in the presence of various concentration of Bom, lipid peroxidation and LDH release were dose-dependently inhibited by Bom. Bom at 1 and 2% concentrations inhibited lipid peroxidation and LDH release in normal tissues. Bom at 2% concentration increased glutathione peroxidase activity in tissues treated or untreated with 1.0 mM t-BHP. However, catalase activity was not altered by addition of Bom. Bom inhibited generation of reactive oxygen species. These results indicate that Born inhibits lipid peroxidation and cell injury in tissues treated with or without oxidant and effect is, at Ieast in part, attributed to increased activity of glutathione peroxidase and a direct sacvenging action.

      • SCOPUSSCIEKCI등재

        백서의 실험적 치아 이동시 치주조직내 성장이자 발현에 관한 면역조직화학적 연구

        이준형,김상철,국윤아 대한치과교정학회 1995 대한치과교정학회지 Vol.25 No.1

        교정력에 의한 치아이동시 치주조직의 조직변화를 알아보고 성장인자중의 하나인 Epidemal Growth Factor(EGF)의 시간 경과에 따른 발현정도 및 분포 변화를 알아 보고자, Sprague-Dawley계 백서 23마리를 대조군(3마리)과 실험군(20마리)으로 나누었으며, 실험군은 교정력(75g)을 가한 후 12시간, 1일, 4일, 7일, 14일이 경과한 후 각각 4마리씩 희생시켜, EGF의 발현 분포와 조직학적 변화를 면역조직화학적 및 조직병리학적으로 관찰한바 다음과 같은 결과를 얻었다. 1. 교정력을 가한 후 14일 까지, 견인측의 치주인대 섬유는 신장되었고, 압박측의 치주인대 섬유는 압축되었으며 치주인대섬유 배열의 완전회복은 일어나지 않았다. 2. 대조군의 EGF 발현은 구강상피, 전상아질, 치수와 치주인대내의 혈관에서 진하게 발현되었으나, 파골세포 및 골아세포에서는 미약한 염색상을 보였다. 3. 교정력을 가한지 12시간, 1일, 4일, 7일째 실험군의 치주조직에서의 EGF의 발현은 견인측과 압박측의 차이가 없이, 경미한 미만성의 양성반응을 보였다. 4. 교정력을 가한지 14일째 치주조직에서 EGF의 발현이 현저히 증가되었으며, 압박측보다 견인측이 더 많이 발현되었으며, 치경부 쪽보다 치근단 쪽에서 더 많았다. This study was designed to evaluate the expression of growth factor in periodontal tissue during the experimental movement of rat incisors by LSAB(Labelled strepatavidine Biotin) immunohistochemical staining for EGF(Epidermal growth factor). 23 Sprague-Dawley rats were divided into a control group(3rats0 and experimental groups(20rats), where a force(75g) from helical springs across the maxillary incisors was applied. Experimental groups were sacrificed at 12 hours, 1, 4, 7 and 14 days, after force application, respectively. And Tissue slides of control and experimental groups were studied immunohistochemically and histologically. The results were as follows : 1. In 14days after force application, periodontal fibers were strectched on the tension side, and compressed in pressure side of all experimental groups, and the arrangement of periodontal fibers was not recovered yet. 2. The degree of EGF expression in control group was strongly positive in the oral epithelium, predentin, capillaries in pulp and periodontal spaces. But osteoblasts and osteoclasts were stained mildly positive. 3. EGF expression was mild and diffuse in 12 hours, 1, 4 and 7 days of experimental groups and was not significantly different between the tension and pressure sides. 4. The degree of EGF expression in the 14-day experimental group was higher than any other group. And the tension side showed a more positive EGF expression than the pressure side. The apical area revealed a more positive EGF expression than the cervical area.

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