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.

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.

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.

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.

산간 계곡 지역 경지정리 사업의 평가

이창수,박승기,양승희 공주대학교 자원과학연구소 2000 資源科學硏究論文集 Vol.8 No.-

This study has appraised land consolidation project in the mountain stream region by way of the appraisement model of Potential Productivity Index (PPI) using GIS. PPI will provide basic elements for large-scale gathering of farm land and a substitute lot of farm land consolidation, and will maximize productivity of paddy. This study was carried out to determine relative error and correlative analysis for verifiable fitness of using cadastral map GIS DB compares determined area using GIS DB with protocol area at each project region. NPI was determined by overlapping Poly Grid of land properties in analyzed project region. NPI of the Masu region was 0.882 TPI that was estimated by additional productive wages ratio of the total of direct productive cost. Additional productive wages were determined by GIS Network analysis of the working distance from each farm house to paddy. PPI was determined at each analyzed farm house and paddy by weighted NPI and TPI. NPI'S and TPI'S weights for PPI were 80%, 20% respectively. PPI variation of each analyzed paddy of the Masu region was 0.967~0.712, and could show the relative PPI value.

대한신경정신의학회 학술대회의 과거, 현재, 미래

이영식,오강섭,노경선,김찬형,한진희,이민수 大韓神經精神醫學會 2003 신경정신의학 Vol.42 No.4

The Korean Neuropsychiatic Association (KNPA) was founded in 1945 and has now grown to over 2000 members as of 2003. The Association's academic meeting has also been increasing in size every year. To further develop the academic meeting of the KNPA, the task force team conducted this project. We suggest several points based on analysing the abstracts of the meeting that has conducted during the last 5 years, the survey results performed at the 2002 annual meeting, the annual meeting of the American Psychiatric Association, and the academic activities of a Korean medical assoction, the Korean Society of Otolaryngology.

함안 방어산 마애삼존불의 보존처리를 위한 암석학적 연구

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

방어산 마애삼존불의 풍화와 훼손도를 진단하였으며, 보존처리를 위한 암석학적 연구를 수행하였다. 이 마애불의 기반암은 니질기원의 퇴적암이 접촉변성을 받아 생성된 치밀견고한 청회색 호온펠스이다. 마애불 주변의 풍화면은 암갈색에서 황갈색을 보이나, 삼존불은 적갈색 또는 암흑색으로 갖는 것으로 보아 인위적 및 자연적인 훼손이 심각한 것으로 나타났다. 본존불 좌중단에는 음각선이 사라지고 없으며 암상의 변색 및 암편의 박락에 따른 계단식 풍화도 관찰된다. 마애불의 표면과 암석의 공극에는 선태류, 조류 및 지의류의 모근과 포자류가 기생하고 있으며, 절리대에서는 이미 토양화의 진행에 의하여 잡초와 잡목이 서식하고 있다. 따라서 식생과 표면의 오염물질을 제거하기 위한 세정작업이 있어야 할 것이다. 또한 마애불 본체의 구조적 안정을 위해 주변에 분포하는 불안정한 암괴의 제거가 필수적이며, 불균형의 재발생과 전면으로 발생하는 응력을 최소화하기 위한 암석지지공법이 필요하다. 균열이 심한 절리면에는 암석용 충전제를 이용한 보존처리가 가해져야 하며, 마애불에 미치는 기상변화를 저감하기 위한 차수벽과 보호각의 설치를 제안한다. The rock standing sculptured Triple Buddha of the Bangeo mountain, Korea was studied on petrological weathering and deterioration diagnosis for the future conservational treatments. Host rock of this Triple Buddha is bluish grey hornfels originated muddy sedimentary rock, which rock is very hard and compact due to the contact metamorphism. Weathered rock surface around the Triple Buddha is yellowish to dark brown color, but main Triple Buddha surface shows reddish brown to dark black because of the severely artificial and natural deteriorations. In the central left-side of the main Buddha, the carved lines are eliminated by weathering, and well developed step-like exfoliations and discoloring of lithology. Rock surface of the Triple Buddha shows partly covered with green algae and lichen. The joint planes occur some weeds and trees. This biological weathering and contaminations need for conservational cleaning and chemical treatments. The unstable rock block around the Triple Buddha most be to remove for the structural stability from the main body, and need to geotechnical methods for the minimum stress against the frontal toppling and reoccurrence of instability. For the conservation of the Triple Buddha, we suggest that fracture systems in the host rock should be to reinforce by petro-epoxy treatments, and set up a water curtain and protection house for attenuation of climatic changes.

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.