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>

항인지질 항체 증후군에서 항β₂glycoprotein-Ⅰ 항체의 의미

이찬희,서창희,이지수,이수곤 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.5

objective : This study investigated the significance of anti-β₂ glycoprotein-Ⅰ(β₂GPI) antibody in antiphospholipid syndrome from the results of the relationship between the antiphospholipid antibody test and the anti-β₂GPI antibody test. Methods : The IgM, IgG type of the anti-β₂GPI antibody was tested by ELISA in patients with antiphospholipid syndrome or those who were suspected of having antiphospholipid syndrome and compared with the anticardiolipin antibody and lupus anticoagulant results. As a control, the anti-β₂GPI antibody was tested in 12 normal healthy persons and 8 systemic lupus erythematosus patients. Results : In 6 patients with antiphospholipid syndrome, the positive rate of lupus anticoagulant, IgM and IgG anticardiolipin antibody was 33%, 50%, and 67%. However, the positive rate of the IgM and IgG anti-β₂GPI antibody test was 83%, 100%. Among the 6 patients, 3 patients were tested for the anti-β₂GPI antibody before and after treatment. In all 3 patients, the anti-β₂GPI antibody titer was lower after treatment. The anti-β₂GPI antibody test was positive in those patients suspected for having antiphospholipid syndrome, but tested negative to the anticardiolipin antibody or lupus anticoagulant. In the normal and disease controls, the anti-β₂GPI antibody test was negative in all cases. Conclusion : In diagnosing antiphosphotipid syndrome. the anticardiolipin antibody or lupus anticoagulant should be used as a screening test, and if necessary, an anti-β₂GPI antibody should be added. This might improve the sensitivity and specificity. Also, the anti-β₂GPI antibody titer may be used as a marker of disease activity.

Transmission ability of Zika virus with artificially infected Aedes albopictus in Korea

Yang Sung‐Chan,Lee Hee-Il,Kim Hyunwoo,Lee Wook‐Gyo 한국곤충학회 2021 Entomological Research Vol.51 No.8

Zika virus (ZIKV), a virus mainly occurring in South America, is now globally distributed. Understanding the pathogen transmission cycle in a vector is exceptionally important in developing disease control strategies. In this study, we performed ZIKV microinjection in Aedes albopictus (Skuese), to estimate its vertical and horizontal transmission ability. The virus infection rate was confirmed by real-time qPCR in the F1 generation derived from the ZIKV-injected Ae. albopictus. The minimum infection rate (MIR) of the F1 generation was highest when they were injected with the virus at 6–12 h (MIR: 16.1) and lowest at 12–24 h (MIR: 4.7) after feeding. In the developmental stage of the F1 progeny, MIR values were 1.0, 1.3, and 6.7 in each egg, larval, and adult stage, respectively, but ZIKV was not detected in the pupa stage. Virus transmission ability was not significantly different between the collection areas (Tongyeong and Jeju). Ae. albopictus demonstrated a high venereal transmission rate of ZIKV and was detected in males (6 pool/7 pool) and females (6 pool/7 pool), confirming that ZIKV can be transmitted from infected mosquitoes to uninfected mosquitoes via mating. This is the first study of the administration of a ZIKV microinjection to Ae. albopictus in Korea and suggests a possibility of a potential mechanism for the virus to survive during adverse conditions via vertical transmission.

B16 멜라닌 세포에서 해양소재 추출물의 멜라닌 생성 저해 효과

이찬 ( Chan Lee1 ),장정희 ( Jung Hee Jang ),안은미 ( Eun Mi Ahn ),박찬익 ( Chan Ik Park ) 대한본초학회 2012 大韓本草學會誌 Vol.27 No.4

Objectives : Under normal condition melanin protects the skin from extracellular stimuli including ultraviolet (UV)-induced oxidative skin damages, but excess production and accumulation of melanin can induce hyperpigmentation causing esthetic problems. Therefore, in this study we tried to search for natural skin whitening materials from marine natural resources. Methods : Water and ethanol extracts of marine natural resources were prepared from Porphyra thalli (PT), Laminariae thallus (LT), Ostreae concha (OC), Sargassum thallus (ST), Undaria thallus (UT), Codium thalli (CT), Enteromorpha thalli (ET), Syngnathoides biaculeatus (SB), and Hippocampus coronatus (Hc). Their effects against UVB and α-melanocyte stimulating hormone (α-MSH)-induced melanogenesis were investigated based on melanin formation in B16 mouse melanoma cells. The mRNA and protein expression of enzymes involved in the melanogenic process were further examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. Results : Water extract of Ostreae concha (OCW/E) effectively inhibited UVB and α-MSH-induced melanin production in B16 melanocytes, which seemed to be mediated by inhibition of mRNA expression of tyrosinase and tyrosinase-related protein 1 (TRP-1). In another experiment, ethanol extracts from Porphyra thalli (PTE/E), Laminariae thallus (LTE/E), Sargassum thallus (STE/E), Undaria thallus (UTE/E), Codium thalli (CTE/E), Syngnathoides biaculeatus (SBE/E), and Hippocampus coronatus (HcE/E) significantly suppressed UVB and α-MSH-induced melanin formation. Furthermore, ethylacetate fraction isolated form LTE/E (LTE/EEt) decreased UVB and α-MSH-elevated extracellular melanin levels via inhibition of tyrosinase protein expression. Conclutions : These results suggest that marine natural resources such as Porphyra thalli, Laminariae thallus, Ostreae concha, Sargassum thallus, Undaria thallus, Codium thalli, Syngnathoides biaculeatus and Hippocampus coronatus have anti-melanogenic effects, thereby exhibiting high potentials to be utilized as one of the ingredients for the development of new whitening functional cosmetics.

교대로 운전되는 두 개의 UV/광촉매반응기로 구성된 폐가스 처리시스템에서의 광촉매의 비활성화 및 재생 특성

이은주 ( Eun Ju Lee ),정찬홍 ( Chan Hong Chung ),임광희 ( Kwang-hee Lim ) 한국화학공학회 2021 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.59 No.4

본 연구에서는 교대로 운전되는 두 개의 UV/광촉매 반응기로 구성된 폐가스 처리시스템의 운전단계와 단계별 광촉매의 비활성화의 상관관계를 사용된 광촉매에 대한 기기분석을 통하여 규명하였다. 선행연구[Lee와 Lim, Korean Chem. Eng. Research, 59(4), 574-583 (2021)]의 광촉매 반응기 시스템 운전에 사용되지 않은 광촉매를 담지한 다공성 SiO₂ 담체(A4), 1회 운전하는 동안 사용되고 재생을 경험하지 않은 광촉매를 담지한 다공성 SiO₂ 담체(A1), 2회 운전에 사용되고 1회 재생된 광촉매를 담지한 다공성 SiO₂ 담체(A2) 및 3회 운전에 사용되고 2회 재생된 광촉매를 담지한 다공성SiO₂ 담체(A3)와, 1차 재생(AD1) 또는 3차 재생(AD3)된 광촉매를 담지한 다공성 SiO₂ 담체에 대한 BET 분석, SEM, XPS, SEM-EDS 및 FTIR 분석 등을 수행하여, 광촉매를 담지한 다공성 SiO₂ 담체의 비활성화 및 재생 특성을 포함하는 특성 분석을 수행하였다. 그 결과로서, 3회 이상의 여러 번 재생을 수행하는 광촉매의 적정 재생 온도를 200℃ 미만으로 도출하였다. 이러한 광촉매의 적정 재생 온도는 BET 분석결과에서 도출된 기공에 흡착된 에탄올 산화분해 중간생성물의 대부분이 완전 분해가 되어 기공이 재생되는 재생 온도와 거의 일치하였다. 특히, XPS 분석 결과는, 선행 연구[Lee와 Lim, Korean Chem. Eng. Research, 59(4), 574-583 (2021)]에서 광촉매 반응기의 첫 번째 운전 후에 광촉매의 미세한 비활성화가 발생하였음을 나타내었다. 또한, XPS 분석 결과는, 선행연구[Lee와 Lim, Korean Chem. Eng. Research, 59(4), 574-583 (2021)]에서 광촉매 반응기의 두 번째 운전에서 비교적 큰 광촉매의 비활성화가 발생하여 첫번째 운전성능보다 약 5%만큼 못 미치는 에탄올과 황화수소 각각의 제거효율을 초래하였으나, 세 번째 운전에서의 에탄올과 황화수소의 제거효율은 두 번째 운전에서의 에탄올과 황화수소의 제거효율 실험 결과와 거의 비슷하였다는 연구 결과와 일치하였다. 한편, AD3를 사용하여 선행연구[Lee와 Lim, Korean Chem. Eng. Research, 59(4), 574-583 (2021)]에서와 같은 광촉매 반응기의 네 번째 운전을 수행할 것을 가정하면, 두 번째 운전에서보다 더 큰 광촉매의 비가역적 비활성화의 발생으로 인하여 에탄올과 황화수소 제거효율이 가장 크게 저하되리라 예상되었다. In this study, the correlation between operating stages of waste air-treating system composed of two alternatively-operating UV/photocatalytic reactors, and the deactivation of photocatalyst used in each operating stage, was investigated by instrumental analysis thereon. The repeated deactivation and subsequent re-generation of photocatalyst used in the waste air treating system of previous investigation performed by Lee and Lim (Korean Chem. Eng. Research, 59(4), 574-583(2021)), were characterized on virgin photocatalyst-carrying porous SiO₂ media (A4), used photocatalystcarrying porous SiO₂ media (A1, A2 and A3) collected from the corresponding photocatalytic reactor upon 1^st, 2^nd, and 3^rd run, respectively, regenerated photocatalyst-carrying porous SiO₂ media upon 1 time-run (AD1) and 3 times regenerated photocatalyst-carrying porous SiO₂ media upon 3 time-runs (AD3) by instrumental analysis including BET analysis, SEM, XPS, SEM-EDS and FT-IR. As a result, the proper regeneration-temperature for deactivated photocatalyst to be regenerated several times (more than 3 times), was suggested below 200℃. Such temperature of deactivated photocatalystregeneration was almost consistent to the one, according to BET analysis, at which tiny nano-pores blocked by adsorbed ethanol-oxidative and degraded intermediates (AEODI), were regenerated to be reopened through almost complete mineralization of AEODI. In particular, the results of XPS analysis indicated an incurrence of insignificant deactivation of photocatalysis upon 1^st run of UV/photocatalytic reactor (A or C) of the previous investigation. In addition, the results of XPS analysis were consistent with the experimental results of the previous investigation in that 1) deactivation of photocatalyst incurred during 2^nd run of the UV/photocatalytic reactor (A or C) resulted in decreased removal efficiency, by ca. 5% and 5%, of ethanol and hydrogen sulfide, respectively, compared with its 1^st run; 2) there was insignificant difference between the removal efficiencies of its 2^nd run and 3^rd run. Furthermore, the removal efficiencies of ethanol and hydrogen sulfide for hypothetical 4^th run of photocatalytic reactor in the previous investigation, using AD3, were expected to decrease, compared with its 3^rd run, by much more than those for 2^nd run in the previous investigation did, compared with its 1^st run.

우리나라 논 관개용 지하수 수질 특성

김진호,조광래,임수정,이경자,경기천,엄미정,김희권,김찬용,이영한,이신찬,윤순강 한국환경농학회 2003 한국환경농학회지 Vol.22 No.4

This study was carried out to evaluate the status of the groundwater quality for paddy fields irrigation in Korea. Water samples were collected at 130 sites throughout the country. Samples were collected at three seasons-April, July and October-in 2000. According to our survey, the groundwater was found to be suitable for irrigation purpose. Average EC was shown 0.286 dS/m. Nitrate-nitrogen and Cl^(-) concentration was 5.6 ㎎/L, 32.95 ㎎/L which satisfied the Korean Standards for Irrigation Water. Nitrate-nitrogen concentration in each province was shown as following orders: Jeju (11.17 ㎎/L) > Chungnam (8.16 ㎎/L) > Gyeongbuk (6.64 ㎎/L) > Gyounggi (5.91 ㎎/L) > Chungnam (4.95 ㎎/L) > Gyeongnam (3.91 mgk) > Jeonbuk (3.50 ㎎/L) > Jeonnam (3.27 ㎎/L) > Gangwon (2.91 ㎎/L). The concentration by sampling seasons were October (6.62 ㎎/L) > July (5.88 mg&) > April (4.78㎎/L). As the soil of Jeju Province is usually derived from volcanic ash soils mainly used for upland drops, it may influence the nitrate-nitrogen concentration of groundwater. The amount of rainfall also influence the water quality. But the COD_(Cr), were shown April (3.17㎎/L) > July (2.91 ㎎/L) > October (2.40 ㎎/L), it is highly related in the basal dose of organic matter fertilizers. This study demonstrated that groundwater quality was suitable for irrigation, but continuous monitoring is recommended for agricultural policy and developing OECD agricultural environment indicators.

Solid Phase Micro Extraction을 이용한 산초의 휘발성 성분 분석

이재곤,장희진,곽재진,김옥찬,이계호 한국식품영양학회 1999 韓國食品營養學會誌 Vol.12 No.2

Solid phase micro extraction(SPME)법의 최적조건 실험 및 SPME로 추출된 산초(Zanthoxylum schinifolium)의 휘발성 성분을 GC/MSD로 확인하였다. 휘발성 성분 추출에 자주 이용되는 동시증류추출(SDE)법으로 산초의 휘발성분을 분석하여 SP-ME 법에서 확인된 휘발성 성분과 조성비를 비교하였다. SPME 최적조건 시험에서 분자량이 적고 비점이 낮은 성분은 온도가 증가할수록 화이버에 흡착되는 양은 적게 나타났으며, 분자량이 크고 비점이 높은 성분은 추출시간이 증가할수록 흡착되는 양은 증가하였다. SPME 최적조건인 추출시간 30분과 50℃에서 분리된 휘발성 성분에서는 limonene(14.65%), geranyl acetate(11.07%), β-phellandrene(7.42%), 및 phellandral(3.08%) 등의 monoterpenoids 화합물과 caproic acid(11.99%), caprylic acid(8.01%), heptanoic acid(3.49%) 등의 지방산 화합물이 주요 성분으로 확인되었고, SDE법으로 추출된 휘발성 성분에서는 geranyl acetate(13.31%), limonene(12.81%) β-phellandrene(8.86%), trans-geraniol(5.22%) 및 caprylic acid(3.03%) 등의 화합물이 주요 성분으로 확인되었다. 지방산 성분들은 SPME법에서 높게 나타난 반면에 알코올 성분들은 SDE법보다 낮았다. SPME법은 적은 양의 시료로도 매우 신속하고 간단하게 전처리 할 수 있기 때문에 기존의 휘발성분 분석시 주로 사용한 SDE법에 비해 편리하며 경제적인 것으로 생각된다. Test of optimum condition of solid phase micro extraction(SPME) was performed by use of 5 volatile components in dilute aqueous solution. Volatile components of Sancho(Zanthoxylum schinifolium) were isolated by SPME method and were analyzed by GC/MSD, and compared with volatile components isolated by simultaneous distillation extraction(SDE) method. Total 31 components were identified by comparing gas chromatography retention time and mass spectral data. The major compounds were limonene, geranyl acetate, β-phellandrene, phellandral, myrcene, linalool, rose oxide, caproic acid and caprylic acid. SPME sampling procedure was found to be a good method for qualitative analysis of the volatile components.

비스테로이드 항염제의 사용법

이찬희 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.2

Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most widely consumed medications for their anti-inflammatory, anti-pyretic, and anti-inflammatory properties. Aspirin, ibuprofen, naproxen, and ketoprofen are available over the counter. At equipotent doses, the clinical efficacy and tolerability of the various NSAIDs are similar: however, individual responses are highly variable. Therefore, we should try to reduce the adverse effect, especially in long-term usage. So, we reviewed characteristics, classification, mechanism of action, and adverse effects, and practical usage of NSAIDs and specific Cyclooxygenase-2 inhibitor.

우리나라 南西海岸의 海陸風 探究 : Centering around the city of Mokpo and Seochon

李承姬,柳贊洙 조선대학교 사범대학 부설 교과교육연구소 2000 敎科敎育硏究 Vol.3 No.1

Geographically, Three sides of Korea are surrounded by the sea(that is, the Korean Peninsular). Accordingly, the envioronment of our country has been greatly affected by the sea. For this study and taking an observation with AWS. I've selected the Mokpo city to which Taebul industrial complex is adjacent and Seochon, the central part of the western coast to which Asan industrial complex is adjacent. I've utilized the data on the change of the direction and the speed of the breeze of two areas(Mokpo and Seochon) through classifying all the data of the annual breeze into a daily unit, a monthly unit and a seasonal unit. As a result, there was a more vivid sea and land breeze character in Seochon area than in Mokpo area is due to the Mokpo's geographical location. In the frequency of breeze direction, NNW direction which occupied 27% of the whole was prevailing and in the frequency of breeze speed, the range of 0.3∼3.3㎧ appeared frequently, and it showed 48.9%. According to rarity analysis on the relations between breeze direction and breeze speed, a correlation coefficient was 0.56∼0.91 and through it. I could figure out correlation of breeze direction and breeze speed. But iti is matter of regret that this study has a statistical analytic basis mainly, so, from noe on, I intend to do profound research on factors which cause the change of sea and land breeze and I'd like to develop them to be processed as enviornmental factors.

계룡산 구룡사지 당간지주의 기원암, 암석학적 및 보존과학적 진단

이찬희,최석원,김사덕,서만철 공주대학교 문화재보존과학연구소 2003 문화재과학기술 Vol.2 No.1

구룡사지 당간지주의 암석학적 풍화와 훼손를 진단하였으며, 보존처리를 대비한 동일 종류의 기원암을 추적하였다. 이 당간지주는 홍장석 화강암으로 구성되어 있으며 주좌는 흑운모 화강암이다. 왼쪽 지주는 완전히 파괴되어 방치되어 있으며, 오른쪽 지주는 하나의 부재로 구성되어 있으나 계단식으로 절단되어 있어 도괴의 우려가 있다. 이 지주들은 균열 및 탈락과 훼손이 심하여 박리와 박락현상이 발생하였고 석재의 표면은 입상분해 작용이 진행 중이다. 이차적 오염현황도 심각하여, 황갈색 수산화철에 의한 암석의 변색과 강수의 유동흔적을 따라 나타나는 암회색 철과 망간의 침전물이 산재한다. 지주의 주변과 암석의 표면에는 지의류와 선태류의 오염이 심각하며, 기단부는 토양화의 진행에 의하여 잡초가 암석의 생물학적 풍화작용을 가중시키고 있다. 따라서 부지 주변의 나무와 잡초 및 불연속면에 서식하는 부착생물을 제거하기 위한 생화학적 처리도 필요하다. 이 당간지주는 석재자체의 성능이 저하되어 있으므로, 균열부의 장기적인 모니터링과 함께 석재의 표면을 강화할 수 있는 처리방법을 강구해야 할 것이다. 특히 왼쪽 지주는 보존처리도 어려운 상태여서 교체하여야 할 상황이다. 이 당간지주와 동일한 암종은 하신리 무지개 농장 부근의 도로변 노두에 있다. The Flag Pole Supporting Rocks (Dangganjiju) of the Guryongsa temple site, Korea was studied on the basis of petrological weathering, conservational scientific diagnosis and presumed to source area of the original supporting rocks. Constituting rocks of this supporting rocks are pink feldspar granite, and the rounded basement is biotite granite. However, the left supporting rock is remained at perfectly destruction state in situ. The right supporting rock showed also highly fractured as step-like cutting plane which is very dangerous state because of possible collapse. As a whole supporting rocks occurred with fracturing, exfoliation or deterioration, and rock surface appeared to grain dissolution. Host rock of the supporting rocks were highly secondary contaminations, and most rock surface was color changed to the dark black to dark brown due to the clay, iron and manganese hydroxides along the rain water flow. In the vicinity of the supporting rocks and rock surface show partly green and black patchs because of coated by algae, lichen and moss. The lower part of the basement rocks are transition to the some weeds. This biological problems are need for cleaning and chemical treatments. The main materials of the supporting rocks is highly degradation, therefore the supporting rocks need to be long term monitoring in the fracture planes and to prepare for synthetic conservation treatments. Especially, the left supporting rock is difficult to conservation owing to nearly perfect destruction. In the Hashinri Mujigae farm area, the same kind of pink feldspar granitic rocks with this supporting rocks are occurred.