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>

김치유래 젖산균의 균체지방산 분석을 이용한 분류학적 연구

이정숙,정민철,김우식,이근철,김홍중,박찬선,이헌주,주윤정,이근종,안종석,박완,박용하,민태익 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 1996 한국미생물·생명공학회지 Vol.24 No.2

표준균주를 포함한 230여개의 김치유래 젖산균에 대한 균체지방산(FAMEs)을 분석하였다. FAMEs profiles는 Euclidian Distance 17.5에 의해 7개의 Major Cluster와 1개의 Single Cluster로 나뉘어졌다. 이중 A, B, C 및 Cluster는 Leuconostoc속으로 분석되어졌고, F는 Lactobacillus속으로 분석되어졌다. 그리고 E와 G cluster는 두개의 Genus가 혼재되어 나타났으며 보충적인 연구가 필요하다. 앞으로 김치유래 젖산균의 균체지방산 분석결과를 기반으로 한 데이타베이스에 95가지 탄소원을 이용하는 수치분류학적 접근방법 및 Pyrolysis Mass Spectrometry 등의 화학적 분석 방법과 분자친화적 연구를 통한 종합적 분류정보 체계가 갖추어지면 젖산균의 신속, 정확한 동정 및 연구에 활발히 이용되어질 것이다. Two hundreds and thirty lactic acid bacteria, mostly isolated from Kimchi, including type strains were sued for analysis of cellular fatty acids. The 230 test strains were recoverd in 7 major and 1 single clusters defined a Euclidian distance of 17.5. These aggregate taxa were equivalent to the genus Leuconostoc (aggregate group A, B, C and D), and the genera Leuconostoc and Lactobacillus (aggregate group G). It is concluded as evident that FAMEs (Fatty Acid Methyl Esters) profile of cell can be used as a criterion in classification of lactic acid bacterial from kimchi. Additional comparative taxonomic studies need to be carried out on well chosen representative strains to determine the most appropriate methods of value.

벼, 콩 및 채소류에 대한 Mn-54, Co-60, Zn-65, Cs-137의 토양-작물체간 전이계수

박찬걸,조용우,최용호,김국찬,이창우,이강석,이정호 대한방사선 방어학회 1991 방사선방어학회지 Vol.16 No.2

벼, 콩, 상치, 당근, 호박의 가식부위에 대하여 몇가지 토양에 있어서 토양-작물체간 Mn-54, Co-60, Zn-65, Cs-137의 전이계수를 포트 재배에 의한 방사성 추적자 흡수실험을 통하여 조사하였다. 핵종간 전이계수는 거의 모든 경우 Zn-65>Mn-54>Cs-137>Co-60의 순이었다. 콩이 벼보다 전반적으로 한 자리 정도 높은 값을 보였고 채소류의 경우에는 대체로 상치에서 가장 높고 호박에서 가장 낮은 값을 보였다. 강산성 토양에서는 약산성 토양에서보다 전이계수가 훨씬 높았다. 본 조사결과에 입각하여 한국인의 섭식경로 피폭선량 평가에 이용하기 위한 각 핵종의 전이계수치가 작물별로 제안되었다. Soil-to plant transfer coefficients of Mn-54, Co-60, Zn-65 and Cs-137 were estimated for the edible parts of the rice, soybean, lettuce, carrot, and squash grown in different soils by radiotracer uptake experiments using pot cultures. The transfer coefficients of radionuclides were n the order of Zn-65>Mn-54>Cs-137>Co-60 in most of the cases studied. The coefficients for soybean were roughly and order of magnitude higher than those for rice. Among vegetables, lettuce mostly showed the highest value and squash, the lowest. In the strongly acidic soils. From the data obtained, crop-specific transfer coefficients of the four nuclides were proposed for the use in Korean food-radiation dose assessment.

부신피질 자극호르몬 단독결핍 1례

박경식,이승현,최석영,박태규,이동화,이찬우,정성복,이인규 啓明大學校 醫科大學 1997 계명의대학술지 Vol.16 No.3

부신피질 자극호르몬 단독결핍은 국내에서 7례만이 보고된 희귀 질환이며 병인 및 경과 등 아직 불분명한 측면이 많다. 이는 질환지체의 희귀성도 있지만 치료후 자연경과에 대한 장기적인 추적검사가 이루어진 경우가 드물기 때문이기도 하다. 저자들은 비특이적인 전신증상을 주소로 내원한 폐경기후의 56세 여자 환자에서 자가면역질환의 증거없이 고프로릭틴혈증을 보인 부신피질 자극호르몬 단독결핍 1례를 경험하고 1년간의 부신피질호르몬 대치요법후 추적검사를 실시하였기에 문헌 고찰과 함께 보고하는 바이다. Isolated ACTH deficiency is a rare disorder which shows secondary adrenal insufficiency with normal states of other pituitary hormones. A 56-year-old postmenopausal woman complaining general weakness and intermittent mental confusion presented negligible serum cortisol and ACTH level with hyperprolactinemia and mild hyponatremia. Rapid ACTH stimulation test did not show significant increase of serum cortisol level. Combined pituitary stimulation test showed negligible response of cortisol and ACTH, and slightly decreased response of prolactin and gonadotropin. But the responses of TSH and GH were normal. There was no evidence of organic pituitary of hypothalamic lesion in brain MRI and antithyroid autoantibody was not detected in serum. After receiving 12 months of glucocorticoid replacement therapy, she skipped the medicine for 3 weeks and we performed follow-up endocrinologic tests. Serum ACTH and cortisol level was also negligible and prolonged ACTH simulation test showed normal response of serum cortisol. CRF stimulation test showed no response of serum ACTH. Basal prolactin level was decreased to near normal and combined pituitary stimulation test showed normal response of prolactin with slightly blunted response of TSH and GH. We concluded that the case was nonautoimmune origined isolated ACTH deficiency which was accompanied by hyperprolactinemia and resultant deficiency of gonadotropin, so we report this case with review of literatures.

골다공성 척추 압박골절에서 경피적 척추성형술 후 강화된 척추체에 의한 합병증 : Hammer Effect Preliminary Report

전은오,이상구,유찬종,김우경,박찬우,이언 The Korean Neurosurgical Society 2003 Journal of Korean neurosurgical society Vol.34 No.6

사출성형제품의 런너시스템 설계 지식베이스화에 관한 연구

이찬우,허용정 호서대학교 반도체제조장비국산화연구센터 2001 반도체장비학술심포지움 Vol.2001 No.-

본 논문은 사출성형제품의 런너시스템 설계를 합리적으로 수행하기 위해 사출금형설계전문가의 축적된 지식과 경험을 발췌 정리하여 지식베이스를 작성하였으며, 설계에 필요한 제품의 형상정보를 제공하기 위해 총칭형상과 특징형상 개념을 이용하여 특징형상을 정의하였다.또한 지식베이스를 통해 산출된 설계결과를 기하학적 모델러와의 인터페이스를 통해 3차원 형상으로 보여지도록 하였으며, 최종 생성된 3차원 기하학적 형상정보는 CAE 모듈이나 CAPP 모듈에서의 후속작업을 위해 제공될 수 있도록 구축되었다.

중증 재생불량성 빈혈 환자의 동종골수이식 후에 병발한 간정맥폐색질환(Hepatic Veno-Occlusive Disease)의 임상 경과 및 혈액응고 인자들의 변화

이제환,이규형,최성준,민영주,김신,이정신,김상희,박찬정,지현숙,김우건 대한조혈모세포이식학회 1999 대한조혈모세포이식학회지 Vol.4 No.2

연구배경: 재생불량성 빈혈 경우에는 조혈모세포 이식 후 VOD의 발생에 관한 보고가 거의 없는 실정이다. 저자 등은 cyclophosphamide와 antithymocyte globulin으로 전처치 후에 동종골수이식을 시행한 재생불량성 빈혈 환자들을 대상으로 하여 VOD의 발생과 임상 양상, 혈액응고 인자들의 변화에 관하여 분석하여 보았다. 방법: 재생불량성 빈혈로 동종골수이식을 시행 받은 13예 환자를 대상으로 하였다. 임상적 기준에 따라 VOD를 진단하였으며 임상 경과에 따라서 경중을 분류하였다. Protein C, protein S, antithrombin Ⅲ, tPA, PAI-1 등의 혈액응고 인자들을 전처치 투여전, 골수 주입당일, 이식 후 제7, 14, 21일에 측정하였다. 결과: 7예(53.8%)에서 VOD가 발생하였으며, 경증 5예, 중등도 2예였다. VOD군에서 혈소판치가 20.000/㎕ 이상을 유지하는 데까지 걸리는 시간이 더 길었다(p=0.026). 또한 VOD군에서 적혈구 및 혈소판의 수혈 요구량이 각각 유의하게 많았다(p=0.025, 0.015). 혈액응고 인자들의 변화를 보면, 제 0일에 VOD군에서 PAI-1의 혈중 농도가 유의하게 더 높았다.(p=0.034). 결론: 재생불량성 빈혈환자에서도 조혈모세포 이식 후에 VOD의 높은 발생률을 관찰하였으며, 대부분이 경증이었다. VOD 환자에서의 혈액응고 인자들의 변화는 PAL-1이 VOD의 감별 진단을 위하여 이용될 수 있음을 시사하고 있다. Background: There are few reports about the occurrence of hepatic veno-occlusive disease(VOD) after bone marrow transplantation (BMT) for severe aplastic anemia (SAA). We analyzed the incidence and clinical outcomes of VOD and changes of coagulation factors in patients with SAA who were conditioned with cyclophosphamide plus ATG and underwent allogeneic BMT. Methods: Thirteen patients with SAA who underwent allogeneic BMT were included. A diagnosis of VOD was made according to clinical criteria, and severity of VOD was classified according to clinical course. Plasma levels of protein C, protein S, antithrombin Ⅲ, t-PA, and PAI-1 were determined before preparative chemotherapy, in the day of marrow infusion, and days 7, 14, and 21. Results: VOD occurred in 7/13(53.8%). Five were mild VOD and two were moderate VOD. Time to platelet ≥20,000/L was slower (p=0.026) and red cell and platelet transfusion requirements were higher (p=0.025,0.015) in patients with VOD . The mean plasma level of PAI-1 at 0 were higher in patients with VOD (p=0.034). Conclusion: We observed the high incidence of VOD after allogeneic BMT in patients with SAA. A majority of cases of VOD were mild. The changes of PAI-1 after BMT may be useful marker of hepatic VOD

인장부재를 이용하는 건축구조의 구성형식과 특성

이주나,박선우,박찬수 대한건축학회 2003 대한건축학회논문집 Vol.19 No.12

Tension members have a lot of advantages because they have high strength and can use flexible materials like cables which are able to enforce pre-stress force. The structure systems composed with tension members seem to be called the Tension Structure System, their formations and characteristics in architectures were investigated. The tension structure system were classified into tension main system, vector system and tension supported bending system, comprehensively. And they were also set up several types with respect to composition of line members and surface members each in detail. The following characteristics of architecture with tension structure was presented through investigation of constructed examples. Tension structures have good structural capacity and were accomplished in various scale and purposes since 1950's. Especially, each type of tension structure system has distinguishable architectural characteristics in their scales and purposes, respectively. And the characteristics were also presented by distribution of constructed years.

상부위장관 출혈을 일으킨 Warfarin Sodium에 의한 위점막내 혈종 1예

이봉규,김태원,박찬국,김만우 조선대학교 부설 의학연구소 1998 The Medical Journal of Chosun University Vol.23 No.2

A case of warfarin sodium-induced intramural hematoma and upper gastrointestinal bleeding is described, and the literature on this adverse effect is reviewed. A 83-year-old woman who has been receiving warfarin came to a emergency room because of hematemesis. She had a history of cerebral infarction. Physical examination was anemic conjunctiva, no abdominal mass and melena. The emergency gastroscopic finding was submucosal mass. Her hemoglobin and hematocrit concentration had falled to 6.7g/㎗ and 20%, Her prothrombin time (PT) was 130 sec and partial prothrombin time (aPTT) was 133 sec. The patient underwent an emergency exploratory laparotomy. The name of operation was hemigastrectomy with gastrojejunostomy(Billorth-Ⅱ). The pathology report indicated the presence of submucosal hematoma formation with mucosal ischemic necrosis and mucosal ulceration and regenerating epithelium.

사출금형설계를 위한 전문가시스템에 관한 연구

이찬우,허용정 호서대학교 반도체제조장비국산화연구센터 2001 반도체장비학술심포지움 Vol.2001 No.-

본 논문은 사출금형설계 관련 지식과 경험을 전산정보화 하고 유동해석프로그램과 기계적 성능예측 프로그램을 결합시켜 전문가시스템을 구축하였다.전문가시스템은 주어진 설계에 대해 유동해석프로그램을 구동시켜 열기계적 데이터베이스를 얻고, 필요에 따라 기계적 성능예측 프로그램을 수행시켜 설계의 최종적인 진단을 수행하게 된다.이러한 과정으로 설계에 대한 평가를 수행하며, 만일 설계가 잘못된 것으로 판정이 되면 그에 해당하는 대안을 제시토록하여 합리적인 설계가 가능하도록 하였다.