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>

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

An Investigation on the Life of Master Won Guk Lee, the Creator of Chung-Do-Kwan

( Seon Young Jung ),( Jun Ho Lee ),( Seung Woo Shin ),( Chun Hwan Cho ),( Seung Hyun Jang ),( Won Shin ) 경남대학교 기초과학연구소 2014 기초과학지 Vol.31 No.-

The purpose of this study is to review (or, investigate) the life of Won Guk Lee. He is the creator of Chung-Do-Kwan, which is one of the five original Taekwondo kwans. Data was gathered from advanced research, newspapers, documentaries, the Internet, magazines, and journals etc. Thus, we were able to create a sequence of events based on the research data. First, we can say that in Won Guk Lee``s career, he created Chung-Do-Kwan and brought Dangsoodo to Korea. These events have had a significant development on Taekwondo. Second, Taekwondo curriculum, which was published by Won Guk Lee, established the foundation of Taekwondo poomsae, as well as giving us the pure spirit of Korean martial arts.

중증 재생불량성빈혈에서 타인 혹은 HLA 불일치 혈연간 골수이식을 위한 cyclophosphamide와 antithymocyte globulin전처치 요법

이정희,이제환,김신,설미이,이정신,김우건,김상희,지현숙,박찬정,이규형 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: Cyclophosphamide와 ATG의 전처치 요법은 HLA가 일치하는 형제간 골수이식에서는 매우 효과적인 것으로 알려져 있으나, 타인 혹은 HLA 불일치 혈연간 골수이식에서는 전처치 요법으로서 불충분한 것으로 보고되었는데, 주요 문제는 착상 부전이었다. 우리나라를 포함하는 극동아시아 지역의 국가들에서 발표되는 보고에 의하면 타인이식을 포함하여 골수이식 후 착상 부전과 이식편대숙주질환의 발생이 서구 국가들로부터의 보고에서보다 적은 것으로 알려져 있다. 저자 등은 6예의 중증 재생불량성빈혈 환자들에서 질병 초기에 Cyclophosphamide와 ATG만을 이용하여 전처치를 한 후에 타인 혹은 HLA 불일치 혈연간 골수이식을 시행하였다. 방법: 1999년 5월부터 2000년 4월까지 서울중앙병원에서 타인 혹은 HLA 불일치 혈연간 골수이식을 시행 받은 성인 중증 재생불량성빈혈 환자들을 대상으로 하였다. 골수이식을 위한 전처치 요법으로 cyclophosphamide (50 mg/kg/d x 4)와 ATG (30 mg/kg/d x 3)를 투여하였는데, 골수이식 전에 ATG에 대하여 과민 반응을 보였던 한 예 (UPN 120)에서는 ATG 대신에 fludarabine (30 mg/m2/d x 3)을 투여하였다. 이식편대숙주질환의 예방을 위하여 cyclosporine과 methotrexate를 투여하였다. 결과: 연구 기간 중에 모두 6예가 타인 혹은 HLA 불일치 혈연간 골수이식을 시행 받았는데, 5예는 타인으로부터 골수를 공여 받았으며, 1예는 HLA의 표현형이 하나의 유전자좌에서 일치하지 않는 형제로부터 골수를 공여 받았다. 타인 골수이식을 받은 5예 중에서 3예의 공여자는 HLA의 표현형이 일치하였으며, 1예는 하나의 유전자좌가 major mismatch였고, 1예는 하나의 유전자좌가 minor mismatch였다. 추적기간의 중앙값은 406일 (범위, 328-643일)인데, 6예 모두에서 착상된 상태를 유지하면서 생존해있다. 2예에서 3도의 급성 이식편대숙주질환과 전신성 만성 이식편대숙주질환이 발생하였다. 결론: Cyclophosphamide와 ATG의 전처치 요법은 재생불량성빈혈의 초기에 타인 혹은 HLA 불일치 혈연간 골수이식을 시행 받은 한국인 환자들에서 충분히 착상을 가져올 수 있는 요법으로 생각된다. 비록 본 연구의 대상 환자 수가 적지만 결과는 매우 고무적이다. HLA가 일치하는 형제가 없는 중증 재생불량성빈혈 환자의 경우에 타인 골수 공여자에 대한 검색을 조기에 시행해야 하며, 타인 혹은 HLA 불일치 혈연간 골수이식을 질병 초기에 적극적으로 고려해야 할 것으로 생각된다. Background: Cyclophosphamide (CY) and ATG regimen was reported to be insufficient for alternative donor BMT in SAA patients due to high incidence of graft rejection. The rates of graft rejection and GVHD after allogeneic BMT including unrelated donor transplants seemed to be lower in reports from Asian countries of Far East. We applied CY/ATG regimen to six patients with early stage of SAA transplanted with marrow from alternative donors other than HLA-identical siblings. Methods: Three patients were transplanted from HLA-phenotypically identical unrelated donors, two from one-locus mismatched unrelated donors, and one from an one-locus mismatched sibling donor. Four patients received no previous therapy for SAA, and two received one course of immunosuppressive therapy with ATG. Preparative regimen was CY (200 mg/kg) plus ATG (90 mg/kg) in all patients except one who had had an anaphylactic reaction to ATG prior to BMT and received fludarabine (90 mg/m2) in place of ATG. Cyclosporine plus methotrexate were given for GVHD prophylaxis. Results: All six patients engrafted and all are alive with durable engraftment at a median follow-up of 406 days (range, 328 to 643). Two patients developed grade III acute GVHD and extensive chronic GVHD. Conclusions: CY/ATG regimen may be sufficient in Korean patients with early stage of SAA transplanted with marrow from alternative donors. Although the number of patients in present study is small, results are encouraging. Stem cell transplantation using alternative donors may be considered at early stage of aplastic anemia.

성인에서 Haemophilus influenzae 감염증의 임상양상과 미생물학적 특성

이종섭,황병연,정희진,김우주,박승철,이도현,이창규,신종희,황규잠,이영희 대한화학요법학회 2000 대한화학요법학회지 Vol.18 No.2

목적 : H. influenzae는 성인에서 흔히 호흡기 감염을 일으키는 균주로, 최근 ampicillin 내성 β-lactamase 생성 균주들이 지속적인 증가를 보이고 있어, 이에 국내 성인에서 H. influenzae에 의한 감염의 임상양상과 분리된 균주들의 미생물학적 특성을 조사하고자 하였다. 방법 : 1998년 3월부터 1999년 9월까지 고려대 구로병원에 내원한 환자중에서 H. influenzae가 분리된 68명을 대상으로 임상양상을 조사하고 항균제 감수성 검사를 시행하였다. 분리된 33주에 대해서 혈청형, 생물형, 세포외막 단백분석을 시행하였고, β-lactamase 생성여부에 따른 감염 환자군간 임상상 및 예후의 차이를 비교하였다. 결과 : 환자의 평균연령은 68세였고, 지역사회 획득감염이 전체의 85%를 차지하였다. 폐렴과 기관지염과 같은 하기도 감염이 전체환자의 75%를 차지하였고 분리 검체 역시 객담이 84%로 가장 많았다. 환자의 71%가 기저질환을 가지고 있었으며, 그 중에 만성 폐쇄성 폐질환, 심혈관 질환, 악성종양, 당뇨병이 대부분이었다. 혈청형으로는 nontypeable 형이 68%로 가장 많았고 b형은 한 예도 없었다. β-lactamase 생성율은 63.2%였고, β-lactamase 양성균주의 항균제 내성율이 음성균주에 비하여 높았으나 β-lactamase 생성 여부에 관계없이 cefotaxime, azithromycin, ciprofloxacin에 대하여 100%의 감수성을 나타내었고 cefaclor, cefuroxime에 대해서는 10% 이하의 낮은 내성율을 보여 이들 항균제들이 치료에 효과적일 것으로 사료된다. 세포외막 단백분석에서는 C형과 D형이 전체의 64%로 가장 많았으며, 혈청형과의 유의한 연관성은 보이지 않았다. 결론 : 성인에서 H. influenzae는 주로 만성 기저질환자에서 급성 호흡기감염 또는 만성 폐쇄성 폐질환의 급성 악화를 유발한다. 기존의 보고에 비해 β-lactamase 양성율이 증가하였고, 이에 따른 항균제 내성율도 증가하여 항균제의 선택에 유의하여야 할 것으로 생각된다. 세포외막 단백분석상 특정한 유형의 균주에 의해 감염이 집중적으로 발생하고 있어 향후 역학 조사의 도구로 이용할 수 있겠다. Purpose : H. influenzae is one of the common causative microorganisms of respiratory tract infections in adults. Recently. β-lactamase producing, ampicillin-resistant H. infiuenzae has become worldwide problem as well as in Korea. We studied to investigate the clinical features and microbiologic characteristics of H. infiuenzae infections in adults. Materials & Methods : From March 1998 to September 1999, 68 patients were enrolled in this study. Clinical features of H. infiuenzae infections were investigated, 68 isolates were subjected to the β-lactamase test, and 33 isolates were used for serotyping. biotyping, antibiotic susceptibility and outer membrane protein (OMP) analysis. Results : Mean age of study patients was 68 years-old and the acquisition rate in community was 85%. Pneumonia and bronchitis were the most common type of infection such as 80%, sputum was the most common clinical specimen for H. mQuenzae isolation. 70% of patients had chronic underlying diseases. Non-typeable strains were 68% and β-lactamase producing rate was 63%. There was no difference in the clinical features and prognosis of H. influenzae infection between the β-lactamase positivie and -negative groups. The susceptibility of cefotaxime, azithromycin, and ciprofloxacin was 100% and that of cefaclor, cefuroxime was under 10% in spite of β-lactamase positivity. In OMP analysis, C and D types were dominant (64%). Conclusion : H. influenzae caused acute respiratory infections in adults with chronic underlying disorders. This study shows higher β-lactamase producing rate and antibiotic-resistance rate than that were reported previously. OMP analysis shows that two major types of strains cause clinical infections intensively.

심혈관계 질환으로 관상질환 집중치료실에 입원한 환자들의 혜후 측정을 위한 APACHEⅢ점수 체계의 임상적 유용성

이공섭,이창선,최현주,홍종서,강지향,김도형,이민영,오인균,김병엽,김상억,김학찬,한승혜,이재용,지영우,안경주 대한순환기학회 2000 Korean Circulation Journal Vol.30 No.8

심인성 어지럼증 환자의 정신과적 증상에 관한 연구

이경규,이지영,김현우,이정엽,백기청,김재일,이근호 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.5

연구목적 : 어지럼증을 호소하는 환자들 중에 심인성 어지럼증 환자가 상당수 있다는 것은 알려져 있고, 이러한 심인성 어지럼증과 동반되는 정신질환으로는 불안장애, 우울장애, 인격장애 등이 있다. 이에 본 연구에서는 심인성 어지럼증 환자들의 빈도와 정신과적 증상을 알아보고자 하였다. 방 법 : 어지럼증 환자들에게 평형검사, 자세운동측정검사, 자세변화검사, caloric testing을 시행하여 심인성, 말초성 및 중추성의 3군으로 분류한 후 각각 14명, 16명, 32명을 대상으로 하였다. 대상환자들에게 한국판 Beck 우울척도검사(K-BDI), Spielberg의 상태-특성 불안검사(STAI). 간이정신진단검사(SCL-90-R)를 이용하여 정신과적 증상을 측정하여 이들 세 군을 비교분석하였다. 결 과 : 1) 심인성 어지럼증을 가진 환자는 어지럼증을 나타내는 환자 총 62명중에서 14명으로 22.6%를 차지하였다. 2) K-BDI에 따른 세 군간의 비교에서는 세 군간에 유의한 차이를 보이지 않았다. 3) STAI에 따른 세 군간의 비교에서 상태불안(STAI-S) 및 특성불안(STAI-T) 모두에서 세 군간에 유의한 차이를 보이지 않았다. 4) SCL-90-R에 따른 세 군간의 비교에서는 9개의 척도 중에서 공포불안척도에서만 중추성 어지럼증군이 47.56±6.90, 말초성 어지럼증 군이 53.50±13.74, 심인성 어지럼증 군이 58.50±16.05로 심인성 어지럼증 환자군이 중추성 어지럼증 환자군에 비하여 유의하게 높은 것으로 나타났다(p<0.01). 5) 통증 증상에 있어서는 세 군간에 유의한 차이를 보이지 않았고, 위장관 증상과 성기능 장애 증상은 중추성과 말초성 어지럼증 군이 심인성 어지럼증 군에 비하여 유의하게 높은 것으로 나타났다(p<0.01). 결 론 : 상기 결과를 토대로 했을 때 어지럼증 환자들에 대한 정신과적 접근을 위하여 각 군을 나누는 것은 별 의미가 없으며 어지럼증 환자들의 어지럼증 자체에 대한 직접적이고 집중적인 치료가 더욱 필요할 것으로 생각된다. Objectives : This study was aimed to investigate psychiatric symptoms in patients with psychogenic dizziness and compare these findings with those of patients with central and peripheral dizziness. Methods : A total of 62 patients with dizziness was the subject of investigation, and patients were classified into 32 with central type, 16 with peripheral type, and 14 with psychogenic type. Korean standardized Beck Depression Inventory(K-BDI), State and Trait Anxiety Inventory(STAI), and Korean standardized edition of Symptom Checklist 90 Revised(SCL-90-R) were used for the assessment. Statistically, Pearson's chi-square test and one-way ANOVA with Scheffe's test were used with SPSS/PC for windows 6.0. Results : The results were as follows : 1) The proportion of psychogenic dizziness was 22.6% of the total subjects. 2) Total scores of K-BDI were not significantly different among the 3 groups. 3) Total scores of state anxiety and trait anxiety were not significantly different among the 3 groups. 4) In SCL-90-R, psychogenic dizziness group showed significantly higher score of phobic anxiety only(p<0.01) than central dizziness group. And others were not significantly different among the 3 groups. 5) In additional somatic symptoms, pain score was not different among the 3 groups, but gastrointestinal and sexual symptoms scores of central and peripheral dizziness group were significantly higher than those of psychogenic dizziness group(p<0.01). Conclusion : These results suggest that psychiatric symptoms in patients with psychogenic dizziness are not different from those of patients with central or peripheral dizziness. Therefore, the more direct and intensive treatment may be necessary regardless of the type of dizziness.

종합검진센터 내원자에서 관상동맥질환 위험요인들의 분포

이충원,이종영,박종원,윤능기,김영조,이현우,이무식,서석권 啓明大學校 醫科大學 1993 계명의대학술지 Vol.12 No.3

1991년3월부터 8월사이에 대구시에 소재한 1개의 대학병원의 종합검진센타에 내원해서 종합검진을 받은 남자 422명(69.9%)과 여자 182명(30.1%)을 대상으로 하여 심헐관계질환의 위험요인들의 전체적인 분포를 보았다. 평균 연령은 남자가 43.3(표준편차, 10.3), 여자가 44.4(표준편차, 10.8)였다. 남자에서 연령에 따라 0.05 수준에서 통계적인 유의성을 보인 위험인자는 혈청 총콜레스테롤(TC). 트리글리세라이드(TC), 고밀도 지단백콜레스테롤(HDL), 저밀도 지단백콜레스테롤(LDL), 수축기혈압, 비체중, A형행동양상이었으며 생활습관으로서는 음주, 흡연, 규칙적인 운동, 우유와 커피섭취, 수면 등이었다. 여자에서는 TC, TG, LDL, 수축기와 확장기혈압, 비체중 그리고 커피섭취와 수면 등이었다. 남자에서 총콜레스테롤의 평균은 181.7mg/dl(표준편차, 32.2), 여자는 182.5mg/이(표준편차, 42.2)였다. 대부분의 위험인자들은 구미의 수준에 미치지 못했으나 남자에서 흡연율이 전체적으로 61.8%로 높으 수준이었으며 특히, 20~29세가 72.9%, 30~39세가 75.2%로서 다른 연령군에 비해 상대적으로 높았다. 여자에서는 전체적으로 6.0%에 지나지 않았다. 확장기혈압 90mmHg 이상을 고혈압자로 정의했을 때의 유병률이 여자 전체대상자에서 24.7%로 높았으며 50-59세는 표본수가 적어서 문제가 되었으나 53.1%였다. 어떤 인구집단내에서 총콜레스테롤의 평균이 200mg/dl 미만이면 고혈압과 흡연의 인구집단의 수준에 관계없이 관상동맥질환(coronary heart disease)의 발생은 드문 것으로 보고가 되고 있으므로 당분간 관상동맥질환 발생률의 급속한 절대적인 증가는 힘드리라 사료된다. 그러나 이러한 결과는 본 연구의 대상자들이 대표성을 지니지 못하며 건강검진센터에 자발적으로 내원한 사람들이므로 해석에 주의를 요한다. Authors examined the distributions of the risk factors for the coronary heart disease in the 422 male (69.9%) and 182 female (30.1%) visitors to the health examination center of a university hospital located in Taegu March to August 1991. Mean age of males was 43.3(standard deviation, SD 10.3) and that of females was 44.4(SD 10.8). Total cholesterol(TC), triglyceride (TG), high-density lipoprotein and low-density lipoprotein cholesterol(LDL), systolic blood pressure, Quetelet index, and Type A Behavior Pattern, and some of life habit variables(alcohol intake, smoking, regular exercise, milk and coffee intake and sleeping) were statistically significant in age groups of the males(P<0.05). In the females, TC, TG and LDL, systolic and diastolic pressure, Quetelet index, coffee intake and sleeping were statistically significant in age groups (P<0.05). Mean of total cholesterol was 181.7㎎/dl(SD,32.2) in males and that of females was 182.5㎎/dl(SD,42.2). Most of the risk factors levels were lower than the Euro-Americans', while smokers were high with 61.8%, especially 72.9% in 20-29 age group and 75.2% in 30-39 age group in males. In females, smokers were just 6.0%. Hypertensives defined by more than 90mmHg diastolic pressure were 24.7% in females, particularly 53.1% in 50-59 age group, but size of the strata was rather small(N=49). In the light of the report that coronary heart disease is uncommon irrespective of population levels of smoking and hypertension, where average total blood cholesterol level in a population is low(<200mg/dl), it is not likely that the absolute increase of the number of the coronary heart disease will increase markedly in the near future. But cautions should be exercised in interpreting the results of this study due to the lack of representativeness and volunteerism. .

이탈리안 라이그래스의 성숙종자 유래 캘러스로부터 효율적인 식물체 재분화

우현숙,이상훈,이동기,김진수,원성혜,이병현 Plant molecular biology and biotechnology research 2004 Plant molecular biology and biotechnology research Vol.2004 No.-

As an initial step for future genetic manipulations to improve forage characteristics of Italian ryegrass (Lolium multiflorum Lam.), an efficient tissue culture system was established and the factors affecting plant regeneration were evaluated. MS medium containing 5 ㎎/L 2,4-D was optimal for embryogenic callus induction from mature seed and had a strong effect on successive plant regeneration. The plant regeneration frequency was observed at above 70% when embryogenic calli induced were transferred to N6 medium supplemented with 1 ㎎/L 2,4-D and 5 ㎎/L BA. Among several basic media tested, MS and M6 medium were optimal for callus induction and plant regeneration, respectively. Genotype was an important factor in plant regenerability. 'Jeanne' showed the highest regeneration frequency of 73%. A short tissue culture period and high-frequency regeneration system established in this study will be useful for molecular breeding of Italian ryegrass through genetic transformation.

Effects of Pilger Rolling and Heat Treatment on Microstructure and Corrosion Resistance of Ag-electroplated 304 Stainless Steel Tubes

Hyun Park,Woo‑Jin Lee,Jae‑Han Son,Han‑Kyun Shin,Sung‑Kyu Hong,Hyo‑Jong Lee 대한금속·재료학회 2022 METALS AND MATERIALS International Vol.28 No.8

We introduce a cost-effective method that combines electroplating with metal cold working processes to manufacture compositetubes with robust corrosion resistance. First, a 3-step electroplating process was developed to form an adhesive anduniform Ag coating on the outer wall of a 304 stainless steel tube. The process consisted of a Ni-strike step for removing thepassivation layer of the initial 304 tube, Cu deposition for smoothing the surface by adding a buffer layer, and Ag deposition. To reinforce the interfacial adhesion between the electroplated layers and the 304 tube and increase the area of the Ag coating,a pilger rolling or pilger rolling + heat-treatment process was performed after the Ag electroplating process. Scanningelectron microscopy of the composite tubes after each process indicated that the as-deposited Ag coating changed fromhaving a rough to smooth surface after only pilger rolling and with additional heat treatment. Electron backscatter diffractionanalysis of the microstructures and textures of the tubes revealed that dynamic recrystallization occurred extensively duringpilger rolling, resulting in the formation of a relatively defect-free grain structure without heat treatment. Furthermore,electrochemical polarization curves determined that the Ag-coated composite tubes are superior to the uncoated 304 tubein terms of corrosion resistance under Cl−atmosphere, owing to the formation of a AgCl passivation layer during testing. Surface analysis of the composite tubes suggests that the properties of the AgCl passivation layer are related to the grainsize of the Ag coating and the density of plastic-deformation-induced defects.