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.

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.

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.

중증 재생불량성 빈혈 환자의 동종골수이식 후에 병발한 간정맥폐색질환(Hepatic Veno-Occlusive Disease)의 임상 경과 및 혈액응고 인자들의 변화

이제환,이규형,최성준,민영주,김신,이정신,김상희,박찬정,지현숙,김우건 대한조혈모세포이식학회 1999 대한조혈모세포이식학회지 Vol.4 No.2

연구배경: 재생불량성 빈혈 경우에는 조혈모세포 이식 후 VOD의 발생에 관한 보고가 거의 없는 실정이다. 저자 등은 cyclophosphamide와 antithymocyte globulin으로 전처치 후에 동종골수이식을 시행한 재생불량성 빈혈 환자들을 대상으로 하여 VOD의 발생과 임상 양상, 혈액응고 인자들의 변화에 관하여 분석하여 보았다. 방법: 재생불량성 빈혈로 동종골수이식을 시행 받은 13예 환자를 대상으로 하였다. 임상적 기준에 따라 VOD를 진단하였으며 임상 경과에 따라서 경중을 분류하였다. Protein C, protein S, antithrombin Ⅲ, tPA, PAI-1 등의 혈액응고 인자들을 전처치 투여전, 골수 주입당일, 이식 후 제7, 14, 21일에 측정하였다. 결과: 7예(53.8%)에서 VOD가 발생하였으며, 경증 5예, 중등도 2예였다. VOD군에서 혈소판치가 20.000/㎕ 이상을 유지하는 데까지 걸리는 시간이 더 길었다(p=0.026). 또한 VOD군에서 적혈구 및 혈소판의 수혈 요구량이 각각 유의하게 많았다(p=0.025, 0.015). 혈액응고 인자들의 변화를 보면, 제 0일에 VOD군에서 PAI-1의 혈중 농도가 유의하게 더 높았다.(p=0.034). 결론: 재생불량성 빈혈환자에서도 조혈모세포 이식 후에 VOD의 높은 발생률을 관찰하였으며, 대부분이 경증이었다. VOD 환자에서의 혈액응고 인자들의 변화는 PAL-1이 VOD의 감별 진단을 위하여 이용될 수 있음을 시사하고 있다. Background: There are few reports about the occurrence of hepatic veno-occlusive disease(VOD) after bone marrow transplantation (BMT) for severe aplastic anemia (SAA). We analyzed the incidence and clinical outcomes of VOD and changes of coagulation factors in patients with SAA who were conditioned with cyclophosphamide plus ATG and underwent allogeneic BMT. Methods: Thirteen patients with SAA who underwent allogeneic BMT were included. A diagnosis of VOD was made according to clinical criteria, and severity of VOD was classified according to clinical course. Plasma levels of protein C, protein S, antithrombin Ⅲ, t-PA, and PAI-1 were determined before preparative chemotherapy, in the day of marrow infusion, and days 7, 14, and 21. Results: VOD occurred in 7/13(53.8%). Five were mild VOD and two were moderate VOD. Time to platelet ≥20,000/L was slower (p=0.026) and red cell and platelet transfusion requirements were higher (p=0.025,0.015) in patients with VOD . The mean plasma level of PAI-1 at 0 were higher in patients with VOD (p=0.034). Conclusion: We observed the high incidence of VOD after allogeneic BMT in patients with SAA. A majority of cases of VOD were mild. The changes of PAI-1 after BMT may be useful marker of hepatic VOD

스포츠種目別運動選手의 體格, 體型 및 體組成에 관한 硏究

李相于,趙在基,朴贊熙,朴俊東,辛尙根 東亞大學校附設스포츠科學硏究所 1989 스포츠科學硏究論文集 Vol.7 No.-

임신과 전신성 홍반성 루푸스

이찬희 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.2

Systemic lupus erythematosus (SLE) is an autoimmune disease that dominantly affects young women who are capable of having children. Although the survival and prognosis of SLE patients is improved, the outcome of pregnancy is worse than that of healthy women. So, we reviewed the problems which related with pregnancy in SLE patients: fertility rate, risk of lupus flares during pregnancy, optimal timing of conception, obstetric and fetal outcome, safety of various drugs used for disease control during pregnancy and lactation, and contraception device.

이온교환법에 의한 탈질소 공정개발의 기초연구 (Ⅴ) : 질산성 질소 선택적인 이온교환수지의 합성 Synthesis of Nitrate-Selective lon Exchange Resines

이동환,김승일,전진희,박찬영,이민규 한국환경과학회 2000 한국환경과학회지 Vol.9 No.4

Nitrate-selective ion exchange resin which have bulky tertiary amine as functional group have been synthesized by the reaction of chloromethylated polystyrene-divinylbenzene copolymer and the corresponding tertiary amine [NR_3=NEt_3 1, N(C_2H_4OH)_3 2] in ethanol, while commercial resin has NMe_3 as functional group. The fundamental properties such as bulk density, water content, appearance index, exchange capacity, effective size, uniformity coefficient of synthesized anion exchange resin (1) have been measured. The ion exchange resin (1) and (2) exhibited the better selectivity for nitrate than sulfate in both batch and continuous column experiments.