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

분편 인플루엔자백신(split influenza vaccine)의 임상효과 및 면역원성에 관한 연구

우흥정,김동림,정희진,천병철,이주연,안정배,김지희,박찬,신영규,김우주,김민자,박승철 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.1

목적 : 아단위 인플루엔자 백신 접종 후 백신의 인플루엔자 예방효과, 인플루엔자 방어 항체형성, 인플루엔자 백신의 안전성을 조사하고자 하였다. 방법 : 총 571명을 대상으로 인플루엔자 백신 접종을 하였고, 이들 접종자에서 인플루엔자 양질환의 이환을 조사하여 인플루엔자 백신의 인플루엔자예방효과를 알아보았고, 백신의 접종 전 및 접종 4주 후 혈청에서 혈구응집억제물(Hemagglutination Inhibition : HAI) 항체 검사를 실시하여 백신의 방어항체생성을 조사하였고, 백신의 안전성을 알아보기 위해 백신접종 후 1주일 이내의 부작용을 조사하였다. 결과 :백신 접종군과 백신 비접종군에서 인플루엔자 양 질환의 이환을 조사한 결과 접종군 28.35%, 비접종군 35.88%으로 나왔으며, p 값이 0.001로 통계적으로 접종군에서 유의하게 낮았고, 인플루엔자 양 질환의 예방 효과는 20.97%를 보였다. 백신의 방어항체 형성의 평가를 위해 유럽의 인플루엔자 백신 허가 기준을 조사하였는데 B/Guangdong/5/94균주의 백신접종 후 항체가 40이상의 비율을 제외한 다른 기준은 모두 만족 시켰다. 부작용은 전체 조사자 521명중 149명(29%)으로 주로 접종 부위의 국소 부작용을 호소했고, 전신 부작용은 2% 내외였으며 특별히 심각한 부작용은 발견되지 않았다. 결론 : 분편 인플루엔자 백신은 인플루엔자양질환의 예방과 방어항체생성에 효과 있으며 안전한 것으로 사료된다. Background : The safety and effectiveness of influenza vaccine are well known in developed country. The influenza vaccination has been recommended as one of the tentative immunization schedule for indicated persons since 1997 in Korea. But there are still no available data about them, even though nearly 5 million doses of influenza vaccine were used in 1997-1998 season. So it is immediately needed to investigate the safety. efficacy and immunogenicity of influenza vaccine among Korean. Methods : We studied the clinical efficacy of influenza vaccine by monitoring Occurrence of influenza-like illness in influenza risk group(vaccination ; 300, non-vaccination; 215) from December in 1997 to March in 1998. We used the split quadrivalent influenza vaccine containing 15 microgram of hemagglutinin of A/Beijing/262/95(HlNl), A/Wuhan/359/95(H3N2), B/Mie/1/93 and B/Guangdong/5/94. Hemagglutination inhibition(HA1) antibody titers were determined before immunization and 1 months after vaccination And we evaluated adverse effect of influenza vaccination at 7 days after vaccination. Results : Influenza vaccination was associated with si@icant reductions in influenza-like spptoms(vaccination group; 28.35%, non-vaccination group, 35.88%, p=0.001). The preventive effect of influenza-like i3lne.s among influenza risk goup was 20.97%. And immunogenicity of influenza A and B exceeded all of the European licensure criteria for immunogenicity except postvaccination proportion of titers 240 of B/Guangdong/5/94 strain. And the adverse effects were mainly local injection site problem and no serious adverse effect was noted. Conclusion : Split influenza vaccine is safe, inmunogenic and eff'tive in influenza risk group in Korea.

십이지장과 대장을 동시에 침범한 결핵 1예

이만재,박치영,곽재정,유보열,기장도,박찬국,김만우,김정용 조선대학교 1995 The Medical Journal of Chosun University Vol.20 No.1

Tuberculosis of duodenum is so rare and is usually secondary to pulmonary or intestinal tuberculosis . It is difficult to diagnose duodenal tuberculosis in clinical and radiologic findings due to its non-specific symptoms and inconsistent lesion. The diagnosis was made on the basis of the histological study of the endoscopic biopsy and resected surgical specimen. so we report a case of tuberculosis of duodenal bulb and of ascending colon with, the brief review of the literatures.

총칭형상과 특징형상 기법을 원용한 게이트 설계 방안 연구

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

본 논문은 게이트 설계를 위한 제품의 형상을 정의하기 위해서 전기· 전자분야 제품제조기업에서 실제로 생산했던 사출성형제품을 대상으로, 실제로 제품을 생산할 때 사용되었던 게이트 종류와 제품 용도를 분류기준으로 하여, 총칭형상과 특징형상 기법을 이용해서 제품을 분류하였다.이러한 분류 작업을 통해서 게이트 설계에 영향을 미치는 특징형상을 제시 하였다.

철강용 알칼리탈지제의 제조와 그의 특성화

이찬우,편무실,공유식,박홍수 明知大學校 産業技術硏究所 1993 産業技術硏究所論文集 Vol.12 No.-

Alkaline degreasing agent(ADA) was prepared by blending of POE(6)-2-ethylhexyl ether(PEH-6). Tetronix T-701(T-701). Na2CO3, tetrasodium pyrophosphate(TSPP). Demol N, and MJU-100A. The physical properties of ADA tested with steel specimen showed the following results. The degreasing powers of ADA-6(PEH-6 20g/Na2CO3 40g/TSPP 20g/Demol N 5g/MJU-100A 5g/water 100g mixture) for press-rust preventing oil were 97% and 98% degreasing at 4wt%, 70℃ and 90℃respectively: for quenching oil, the degreasing power of ADA-6 was 94% degreasing at 4wt% and 70℃. From these results, it was confirmed that ADA-6 exhibited a good degreasing power. Foam heights measured immediately after foaming by Rose & Miles method and Ross & Clark method at 6wt%, 60℃ were 20mm and 50mm. respectively. As the result, ADA-6 was proved a good low foaming degreasing agent.

폐 내 병변으로 인한 소아 급성 호흡부전의 원인 질환과 예후

이혜영,박지숙,최희라,서지현,김점수,임재영,최명범,박찬후,우향옥,윤희상 대한소아과학회 2004 小兒科 Vol.47 No.5