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>

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.

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.

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.

경주 남리사지에 사용된 석재의 암석학적 특성과 원산지 해석

이찬희,정연삼,정민호,이명성,김영택 공주대학교 문화재보존과학연구소 2004 문화재과학기술 Vol.3 No.1

이 연구는 경주 남리사지에 이용된 석재를 대상으로 암석의 성인적 분류, 광물 및 지구화학적 특성을 검토하여 석재의 기원지 추정과 고고지질학적 의미를 해석한 것이다. 남리사지에서 출토된 암석은 5종의 화강암질암 (알카리 화강암, 흑운모 화강암, 미문상 화강암, 등립질 화강암, 홍장석 화강암), 세립질 퇴적암 (셰일, 미사암), 호온펠스, 옹회암질암, 염기성 맥암 등이 있다. 이 중에서 서탑에 이용된 암석은 유백색의 중립질 알카리 화강암과 담홍색의 흑운모 화강암이 주류를 이룬다. 각 석재들의 대자율 값은 흑운모 화강암이 4.94~7.59 (평균 6.47)로서 제일 높았으며 미문상 화강암이 0.86~1.54 (평균 1.13)로 제일 낮았다. 알카리 화강암은 3.51, 홍장석 화강암이 5.88, 등립질 화강암이 4.89로서 분화경로와 산출상태에 따라 조금씩 다른 값을 보였다. 이 화강암류는 화학조성으로 볼 때, 거의 동일한 마그마 기원의 칼크-알카리 계열 화강암 영역에 해당된다. 이 석재의 화학적 풍화지수와 풍화 잠재지수는 각각 49.87~61.64와 4.12~8.46 범위로서, 현재 암석이 화학적 풍화작용이 왕성하게 발생하는 정도는 아니나 풍화잠재력은 매우 높은 것으로 나타났다. 이 화강암질암의 암석학적 및 지구화학적 특징으로 볼 때, 이들의 성인적 유형은 남산 일대에 분포하는 화강암과 동일하다. 따라서 남리사지의 석조문화재 건축에 사용된 석재는 현지에서 재료를 구하고 현장에서 제작한 자급자족형 석재와 수계의 상류지역에서 도입된 외래형 석재가 공준하고 있는 것으로 해석된다. 자급형 석재가 현지의 원료를 이용한 것은 확실하나 어느 지역에서 채석하여 어디서 가공을 하였는지는 불분명하다. Rock properties around the Namri temple site was studied source area and archaeogeological interpretations based on petrology, mineralogy and geochemistry. Excavated rocks from the area composed of granitic rocks (alkali granite, biotite granite, micrographic granite, eqigranular granite, pink feldspar granite), fine grained sedimentary rocks (shale and siltstone), hornfels, tuffaceous and basic dyke rocks. Almost rock materials of the west pagoda made of white medium grained alkali granite and biotite granite. As the magnetic susceptibility (MS), biotite granite ranges from 4.94 to 7.59 (mean 6.47), and micrographic granite is lowest value of 0.86 to 1.54 (mean 1.13). The mean MS values revealed that alkali granite = 3.51, pink feldspar granite = 5.88, eqigranular granite = 4.89, which are little variatins because of differentiation process and field occurrences. In the geochemical data, the granitic rocks represent a comagmatic calc-alkali series granite. The values of WPI and CIA for rock properties from the Namri temple site range from 49.87 to 61.64 and 4.12 to 8.46, respectively, which values don't going active weathering right now, but weathering potential represents very high. On the basis of petrology and geochemistry of the rock properties from the Namri temple site, the genetic types are the similar as those of the Namsan granite. Therefore, the using rocks of the Namri temple site suggested that domestic type rock properties getting material in the actual place and making in situ, and foreign type rock properties getting from the upstream area are coexisted. Domestic types are sure of making the actual place material, but unclear where is a quarry and working.

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.

가옥 및 실험실내 라돈평형인자, 비 흡착 라돈자손 비율의 일일 변동 특성

이승찬,김창규,이동명,강희동 대한방사선 방어학회 2001 방사선방어학회지 Vol.26 No.4

일반가옥 및 실험실에서 라돈농도, 평형등가농도 및 평형인자의 농도 변화를 검토하였으며, 환기조건에 따른 평형인자, 비흡착 라돈자손 비율의 변동 특성을 검토하였다. 가옥 7개 지점에서의 평균 라돈농도, 평형등가농도 및 평형인자는 각각 30 Bq m^-3, 19.6 Bq m^-3 0.65였다. 한편, 실험실 3개 지점에서의 평균 라돈농도, 평형등가농도 및 평형인자는 55.0 Bq m^-3, 31.9 Bq m^-3 , 0.58였다. 실내에서의 라돈농도, 평형등가농도 및 평형인자는 새벽 및 아침시간에 높고 오후 4시부터 밤 10시 사이에 낮아지는 주기적인 특성을 나타내었다. 환기상태가 좋은 경우가 환기상태가 나쁜 경우에 비해 평형인자는 낮아지는 반면, 비 흡착 라돈자손 비율이 증가하는 경향을 나타내었으며, 평형인자는 기압, 습도에 비례하는 반면, 온도에는 반비례하는 관계를 나타내었다. The variation characteristics of radon concentration, equilibrium equivalent concentration and equilibrium factor in some houses and laboratory buildings have been studied. The variation of equilibrium factor and the unattached fraction of radon progeny with ventilation condition have been also estimated. The averages of radon concentration, equilibrium equivalent concentration and equilibrium factor were 30 Bq m^-3, 19.6 Bq m^-3 and 0.65 in seven houses, while 55.0 Bq m^-3, 31.9 Bq m^-3 and 0.58 in three laboratory buildings, respectively. The diurnal variation of radon concentration, equilibrium equivalent concentration and equilibrium factor in indoor showed a typical pattern that the radon concentration, equilibrium equivalent concentration and equilibrium factor increased at dawn and morning, while decreased at midday and evening. While the equilibrium factor rate deceased in the indoor environment which was well ventilated, the unattached fraction of radon progeny increased. The equilibrium factor was in proportion to air pressure and humidity of indoor, whereas in inverse proportion to temperature.

솔잎혹파리 피해임지의 수세변동에 관한 연구

이찬용,채희문,김종국 강원대학교 삼림과학연구소 2000 Journal of Forest Science Vol.16 No.-

솔잎혹파리 피해임지의 특성에 따른 수세변동을 구명하였다. 솔잎혹파리 피해도(「심), 「중), 「경))별로 구분하여 수세를 조사한 결과 피해가 심한 지역의 수목은 수세가 현저하게 약화되었으며, 수목의 임분밀도(「밀), 「중),「소」)별로 구분한 경우는 피해도와 관계없이 임분밀도가 낮은 임분에서 수목의 수세가 강하게 나타났다. 수목의 외형적 인자중 수관폭과, 흉고직경이 작은 개체에 비하여 큰 개체의 수세가 모든 임분에서 강하게 나타났다. 각 임분에서 전기저항치와 수관면적과의 관계는 피해도 「심」 임분에서는 수관면적이 13.4m2, 「중」 임분에서는 10.9m2, 「경」 임분에서는 7.9m2로 피해가 심할수록 수관면적이 넓어야 임목이 생존할 가능성이 높은 전기저항치(15kΩ이하)가 나타나는 것으로 파악되었다. This study investigated tree vigor of damaged forest by Thecodiplosis japonensis Uchida et Inouye. In damaged forest by pine gall midge, the investigation result of damaged rate section(severe, moderate, light) indicated that severe stand showed higher value of electric resistance(kΩ) than that of light stand, the investigation result of tree density section(crowed, middle, little) indicated that crowed stand showed higher value of electric resistance than that of little stand(the value of electric resistance at which low reading show high vigor tree and high reading low vigor tree). The crown width and DBH(diameter of breast height) of external factors showed lower value of electric resistance than that of small size. The results of comparative between Crown area and value of electric resistance in each stand were 13.4m2 in severe stand, 10.9m2 in moderate stand and 7.9m2 in light stand. Therefore, the tree which have big crown showed low value of electric resistance(below 15kΩ)that has high possible of survial. Key word : Thecodiplosis japonensis, electric resistance, crown area