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>

Development of a Chest‑Belt‑Type Biosignal‑Monitoring Wearable Platform System

Joo‑Hyeon Lee,Hyun‑Seung Cho,Jin‑Hee Yang,Sang‑Min Kim,Jeong‑Whan Lee,Hwi‑Kuen Kwak,Je‑Wook Chae 대한전기학회 2020 Journal of Electrical Engineering & Technology Vol.15 No.4

The purpose of this study was to develop a wearable platform system that can detect and acquire a soldier’s biosignals (i.e., heart activity signal, respiration rate, etc.) in a nonrestrained, unconscious manner. These detected biosignals are transmitted to a processing device to analyze and monitor the soldier’s physical status. To achieve this, textile-based heart activity electrodes and a strain gauge sensor for the respiration signal measurement were developed, and their performances in detecting each signal were verifed. These sensors were embedded in a chest belt to design a wearable platform that can simultaneously measure heart activity and respiration signals. The sensor part of the chest belt has a dual layer structure to detect high-quality signals. Stretch fabric was used on the outer layer and a respiration sensor was attached to the belt. On the inside layer, a non-stretch fabric was used as the base fabric and a heart activity-sensing electrode, that is capable of taking measurements using a modifed lead-II heart activity signal induction method, was embroidered onto the fabric. Subjects were asked to wear the chest belt, and a biosignal processor module was attached to verify the system’s performance while simultaneously acquiring the heart activity and respiration signals. More specifcally, it was confrmed that the two signals were detected in a stable. It is expected that the biosignal-monitoring wearable platform system developed in this study will be able to efectively analyze and monitor soldiers’ biosignals.

국내 시판 항생제의 허가 용량 및 용법의 적정성에 대한 고찰 : 국내 약제사용설명서(package insert)와 미국 Physicians' Desk Reference의 비교 Comparison of Domestic Package Inserts with Physicians' Desk Reference

이재갑,이연주,황병연,정혜원,정성주,김성범,정희진,김우주,김민자,박승철 대한감염학회 2003 감염과 화학요법 Vol.35 No.5

목적 : 국내 시판중인 항생제의 1일 투여량과 투여간격의 적정성을 확인하고 적응증 및 중증도에 따른 항생제 용량 제시 여부를 확인하기 위하여 항생제 시판시 KFDA의 허가사항을 담은 약제사용설명서을 미국 FDA 공인 약제에 대한 사용지침으로 쓰이고 있는 PDR(Physicians' Desk Peference)과 비교하였다. 방법 : PDR에 등재되어 있는 항생제 중에서 시럽 및 도포용 항생제를 제외한 총 61종에서, 국내에 시판되어 있는 51종 항생제의 약제사용설명서를 대상으로 1일 투여량, 투약횟수, 적응증 및 중증도에 따른 설명 정도를 비교하였다. 결과 : 1) 1일 투여량 비교 : 비교 가능한 전체 항생제에서, 약제사용설명서가 PDR보다 적은 용량을 제시한 경우는 경구용 8종, 주사용 11종으로 총 19종(37%)였으며, 많은 용량을 제시한 경우는 경구용만 2(4%)종이었고, 동일하거나 비슷한 용량을 제시한 경우는 경구용 15종, 주사용 15종으로 총 30(59%)종이었다. 약제사용설명서에서 적은 용량이 제시된 항생제 중 경구용인 cefdnir, cefixime, cefpodoxime, ofloxacin, levofloxacin, norfloxacin(6종), 주사용인 cefazolin, cefotetan, ceftizoxime, meropenem (4종) 등 반수이상의 약제가 일본제약회사로부터 국내에 수입된 약들이었으며 일본의 약제 사용설명서와 동일한 용량을 제시한 것을 알 수 있다. 2) 투여간격 비교 : 비교가능한 항생제 51종 중에서 국내약제사용설명서가 PDR과 동일한 투약횟수, 투여간격을 제시한 항생제는 30종(59%)이었다. 국내 약제사용설명서가 PDR보다 적은 투약횟수, 긴 투여간격을 제시한 항생제는 9종(17%)이었다. 오히려 많은 투약횟수, 짧은 투여간격을 제시한 항생제가 12종(24%)이나 되었다. 경구용만 비교하였을 경우 국내 약제사용설명서가 PDR보다 적은 투약횟수를 제시한 항생제는 없었으며, 동일하세 제시한 경우는 15종, 빈번한 투약횟수를 제시한 경우는 10종이었다. 주사용 항생제에서 국내 약제사용설명서가 PDR보다 긴 투여간격을 제시한 항생제는 9종, 동일한 경우는 15종, 짧은 투여간격을 제시한 경우는 2종이었다. 3) 적응증 및 중증도에 따른 비교 : 약제사용설명서에서 적응증 또는 중증도에 따른 용량에 대한 설명이 부족한 경우는 경구용 13종, 주사용 7종으로 총 20종(39%)이었으며, PDR에서는 경구용 1종, 주사용 2종으로 총 3종(6%)이었다. 결론 : 항생제에 첨부되는 약제사용설명서 및 약제사용설명서를 바탕으로 편집되는 의약품집이 항생제를 처방하는 의사들이 용법과 용량을 결정함에 있어 참고 역할을 하고 있으나, 국내의 시판 허가사항을 담은 약제사용설명서가 많은 수에서 적응증 또는 중증도에 따른 1일 투여량과 투여간격에 대한 정확한 정보를 제공하고 있지 못하고 있다. Background : The appropriate usage of antibiotics needs informations such as its effectiveness for a given infection, administration route, the amount of effective dose, and the dose intervals. In this study, in order to find any significant discrepancy regarding to the details of explanation of the necessary information for appropriate antibiotic usages, we compares informations about 51 antibiotics, one from package inserts in Korea and the other from physician's desk reference (PDR) certified by FDA in the United States of America. Materials and Methods : Package inserts about antibiotics, only oral or parenteral agent, wereperused to collect three categories of data: the recommended dosage, dose interval, and adjustment of dose to indications or the severity of infection. These data available in Korea were compared with 61 antibiotics (32 oral and 29 parenteral agents) cited in PDR. Results : Package inserts for 51 antibiotics were gathered, because the remaining 10 antibiotics in PDR are not domestically commercialized. Among data on antibiotics comparable with those in PDR, 59% (30 cases: 15 oral and 15 parenteral agents) suggested the dose similar to that of PDR, 37% (19 cases: 8 oral and 11 parenteral agents) recommend less dose, and 4% in only 2 oral agents showed more dose. About half of the drugs recommending lower dosage were imported from Japanese pharmaceutical company, and the recommended doses of these antimicrobial agents were similar to those in Japan. About 59% (30 cases: 15 oral and 15 parenteral agents) directed dose interval or duration similar to those of PDR and 17% (9 parenteral agents) suggested less administration or longer duration. Surprisingly, in contrast to only 6% (3 cases) of PDR, 24% (12 cases : 10 oral and 2 parenteral agents) recommended more administration or shorter duration. About 39% (24 cases: 13 oral and 7 parenteral agents) revealed no information for dose adjustment commons to indications or the severity of infection. Conclusion : This study revealed that many guidelines in Korea recommend lower doses and/or unreasonable dose intervals. In future studies, improved antibiotic usage guidelines should be established based on pharmacokinetic and pharmacodynamic researches, on the aspect of optimal dosage, dose interval, and dose adjustment commensurate to the indications and the severity of the infection.

성인에서 Haemophilus influenzae 감염증의 임상양상과 미생물학적 특성

이종섭,황병연,정희진,김우주,박승철,이도현,이창규,신종희,황규잠,이영희 대한화학요법학회 2000 대한화학요법학회지 Vol.18 No.2

목적 : H. influenzae는 성인에서 흔히 호흡기 감염을 일으키는 균주로, 최근 ampicillin 내성 β-lactamase 생성 균주들이 지속적인 증가를 보이고 있어, 이에 국내 성인에서 H. influenzae에 의한 감염의 임상양상과 분리된 균주들의 미생물학적 특성을 조사하고자 하였다. 방법 : 1998년 3월부터 1999년 9월까지 고려대 구로병원에 내원한 환자중에서 H. influenzae가 분리된 68명을 대상으로 임상양상을 조사하고 항균제 감수성 검사를 시행하였다. 분리된 33주에 대해서 혈청형, 생물형, 세포외막 단백분석을 시행하였고, β-lactamase 생성여부에 따른 감염 환자군간 임상상 및 예후의 차이를 비교하였다. 결과 : 환자의 평균연령은 68세였고, 지역사회 획득감염이 전체의 85%를 차지하였다. 폐렴과 기관지염과 같은 하기도 감염이 전체환자의 75%를 차지하였고 분리 검체 역시 객담이 84%로 가장 많았다. 환자의 71%가 기저질환을 가지고 있었으며, 그 중에 만성 폐쇄성 폐질환, 심혈관 질환, 악성종양, 당뇨병이 대부분이었다. 혈청형으로는 nontypeable 형이 68%로 가장 많았고 b형은 한 예도 없었다. β-lactamase 생성율은 63.2%였고, β-lactamase 양성균주의 항균제 내성율이 음성균주에 비하여 높았으나 β-lactamase 생성 여부에 관계없이 cefotaxime, azithromycin, ciprofloxacin에 대하여 100%의 감수성을 나타내었고 cefaclor, cefuroxime에 대해서는 10% 이하의 낮은 내성율을 보여 이들 항균제들이 치료에 효과적일 것으로 사료된다. 세포외막 단백분석에서는 C형과 D형이 전체의 64%로 가장 많았으며, 혈청형과의 유의한 연관성은 보이지 않았다. 결론 : 성인에서 H. influenzae는 주로 만성 기저질환자에서 급성 호흡기감염 또는 만성 폐쇄성 폐질환의 급성 악화를 유발한다. 기존의 보고에 비해 β-lactamase 양성율이 증가하였고, 이에 따른 항균제 내성율도 증가하여 항균제의 선택에 유의하여야 할 것으로 생각된다. 세포외막 단백분석상 특정한 유형의 균주에 의해 감염이 집중적으로 발생하고 있어 향후 역학 조사의 도구로 이용할 수 있겠다. Purpose : H. influenzae is one of the common causative microorganisms of respiratory tract infections in adults. Recently. β-lactamase producing, ampicillin-resistant H. infiuenzae has become worldwide problem as well as in Korea. We studied to investigate the clinical features and microbiologic characteristics of H. infiuenzae infections in adults. Materials & Methods : From March 1998 to September 1999, 68 patients were enrolled in this study. Clinical features of H. infiuenzae infections were investigated, 68 isolates were subjected to the β-lactamase test, and 33 isolates were used for serotyping. biotyping, antibiotic susceptibility and outer membrane protein (OMP) analysis. Results : Mean age of study patients was 68 years-old and the acquisition rate in community was 85%. Pneumonia and bronchitis were the most common type of infection such as 80%, sputum was the most common clinical specimen for H. mQuenzae isolation. 70% of patients had chronic underlying diseases. Non-typeable strains were 68% and β-lactamase producing rate was 63%. There was no difference in the clinical features and prognosis of H. influenzae infection between the β-lactamase positivie and -negative groups. The susceptibility of cefotaxime, azithromycin, and ciprofloxacin was 100% and that of cefaclor, cefuroxime was under 10% in spite of β-lactamase positivity. In OMP analysis, C and D types were dominant (64%). Conclusion : H. influenzae caused acute respiratory infections in adults with chronic underlying disorders. This study shows higher β-lactamase producing rate and antibiotic-resistance rate than that were reported previously. OMP analysis shows that two major types of strains cause clinical infections intensively.

뇌사환자의 갑상선 기능, 전신대사 및 중증도에 관한 연구

이영주,정금희,왕희정,문봉기,한연희,이영석 아주대학교 의과학연구소 1999 아주의학 Vol.4 No.1

Background and Objectives : Brain death may lead to hormonal depletion, metabolic derangement and multiple organ dysfunction. We have carried out present study to examine the effects of brain death on the thyroid function, metabolic indices, and the severity scoring systems. Methods : 13 adults patients admitted for organ donation or brain death evaluation were examined after brain death was confirmed. Thyroid hormones measured were .thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and free thyroxine (FT4). The metabolic indices measured were arterial ketone body ratio (AKBR), lactic acid (LA), and base defiat (BD). as for reference to the severity scoring systems, APACHE Ⅲ and multiple organ failure score (MOFS) were assessed on the day of brain death confirmation. Arterial blood was drawn for all measurements. Results : As for the thyroid function, there were significant decreases in T3 (40.48±20.96 ng/dL) and T4 (3.47±2.15 ㎍/dL), but no significant change in FT4 (0.75±0.31 ng/dL) and TSH (1.12±1.37 uIU/mL) compared to the normal range. Significant decreases in AKBR (0.39±0.31) and BD (-9.46±5.83 m㏖/L), and significant increase in LA (2.57±2.46 m㏖/L) In metabolic indices, were shown, as for severity scoring systems, APACHE Ⅲ score (101.54±19.41) and MOF score (9.11±2.57) indicated a high mortality. There were significant correlation between thyroid hormones (r=0.565 -0.781) but no correlation among other indices. Also, significant inverse correlations were shown between base deficit and lactic acid (r=-0.660), APACHE Ⅲ score (r=-0.726) and MOF score (r=-0.604). The highest correlation was observed between APACHE Ⅲ score and MOF score (r=0.851). Conclusions : As for the thyroid function, significant decrease in T3 and T4, and almost normal range of FT4 and TSH imply the euthyroid sick syndrome. Abnormal finding of the metabolic parameters indicates an inhibition of the aerobic metabolic rate of the body as a whole. And the severity scoring parameters are compatible with high mortality.

마라도(제주특별자치도, 서귀포시)의 거미상

김주필(Joo-Pil Kim),예용택(Yong-Taek Ye),최한석(Han-Seok Choi),장지현(Jee-Hyeon Jang):예성훈(Seong-Hun Ye),김태우(Tae-Woo Kim),김대희(Dae-Hee Kim),지승환(Seung-Hwan Ji),이형민(Hyung-Min Lee),이형진(Hyung-Jin Lee) 한국거미연구소 2016 한국거미 Vol.32 No.2

2016년 8월 3일부터 5일까지 제주특별자치도 서귀포시 대정읍 마라도 일대를 한국거미연구회 하계 합동채집회에 김주필, 예용택, 최한석, 장지현, 예성훈, 김태우, 김대희, 지승환, 이형민, 이형진, 신정애, 허양미, 이영경, 최라미, 이윤정 등이 채집조사한 결과 15과, 39속, 45종의 거미류가 조사연구되어 이에 보고하는 바이다. The authors investigated the spiders of the Mara Island in Jeju Island. In the present paper 45 species of 39 genera belong to 15 families were identified. These specimens are deposited at the Joo-Pil Spider Museum, Namyangju-Si, Kyunggi-Do.

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

Kim, Hee Kyung,Kim, Sun Young,Lee, Su Jin,Kang, Mihyeon,Kim, Seung Tae,Jang, Jiryeon,Rath, Oliver,Schueler, Julia,Lee, Dong Woo,Park, Woong Yang,Kim, Sung Joo,Park, Se Hoon,Lee, Jeeyun Neoplasia Press 2016 Translational oncology Vol.9 No.3

<P><I>BACKGROUND:</I> Although pazopanib treatment has become the standard chemotherapy in salvage setting for metastatic sarcoma patients, most patients progress after pazopanib treatment in 4 to 6 months. After failure to pazopanib, patients have limited options for treatment. Therefore, subsequent therapy in patients who failed to pazopanib is urgently needed and the use of patient derived cells or patient derived tumors for accompanying testing with various pharmacological inhibitors could offer additional treatment options for these patients. <I>METHODS:</I> Patient derived tumor cells were collected from ascites at the time of progression to pazopanib and a 13-drug panel was tested for drug sensitivity. We confirmed the results using <I>in vitro</I> cell viability assay and immunoblot assay. We also performed the genomic profiling of PDX model. <I>RESULTS:</I> The growth of patient derived tumor cells was significantly reduced by exposure to 1.0 μM AZD2014 compared with control (control versus AZD2014, mean growth = 100.0% vs 16.04%, difference = 83.96%, 95% CI = 70.01% to 97.92%, <I>P</I> = .0435). Similarly, 1.0 μM BEZ235 profoundly inhibited tumor cell growth <I>in vitro</I> when compared to control (control versus BEZ235, mean growth = 100.0% vs 7.308%, difference = 92.69%, 95% CI = 78.87% to 106.5%, <I>P</I> < .0001). Despite the presence of CDK4 amplification in the patient-derived tumor cells, LEE011 did not considerably inhibit cell proliferation when compared with control (control vs LEE011, mean growth = 100.0% vs 80.23%, difference = 19.77%, 95% CI = 1.828% to 37.72%, <I>P</I> = .0377). The immunoblot analysis showed that BEZ235 treatment decreased pAKT, pmTOR and pERK whereas AZD2014 decreased only pmTOR. <I>CONCLUSION:</I> Taken together, upregulation of mTOR/AKT pathway in sarcoma patient derived cells was considerably inhibited by the treatment of AZD2014 and BEZ235 with downregulation of AKT pathway (greater extent for BEZ235). These molecules may be considered as treatment option in STS patient who have failed to pazopanib in the context of clinical trials.</P>

식품 기준·규격의 합리적 관리 ·운영에 관한 연구(Ⅰ) : 두부,식용유지, 전분의 분말상 원료에 관하여 Powdered marerials of Tofu, Edible oil, Starch

김희연,홍진환,박혜경,한상배,박종석,이은주,이정성,송경희,최은희,최영준,소경아,성영제,이주엽 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

본 연구는 분말상 원료(전분, 대두분)의 저장유통시 품질변화를 건전성과 안전성 측면에서 검토하여 식품의 기준 ·규격 설정f.」 합지적으로 반영하고자 하였다. 전분과 패두분의 이물을 검사하고, 2종 대두분(중국산, 미국산)을 ?0일간 IS'c와 30t에 저장하면서 성상, 수분, 산가, 과산화물가, 지방산 조성,아플라톡신 BB의 생성여부를 분석하였다. 중국산 대두분 30'』 저장군에서 50일 이후 곰팡이가 발생한 것 이외에 모든 시료에서 양호한 성상을 나타내었고, 전분과 대두닥 모든 시료에서 이물은 검출되지 않았다. 산가는 중국산과 미국산 시료간에 편차를 보여 증국산 30"C, 50일 저장시료에서 약 10배끙도 증가하였고, 과산화물가는 저장 90일후 15'E 저장군은 약 2.3배, 30'c 저장군은 3배정도 증가하였다. 대두분의 주요 지방산은 linoleic acidf18. 2), oleic acid(18 : 1), palmitic acid(16 : 0)이었으며, 3개월 저장에 따른 지방산 함량의 변화는 미미하였다. 아플라톡신 B₁은 모든 시료에서 검출되지 않았다. The objective of this study was to investigate auality changes of type raw materials(starch, soy flour) during various storage conditions. Starchflour(source of China, U.S.A) were slfred under two temperature(15'C, 30'c) forSensory evaluation, (o.reign material test, moisture content, acid value, peroxide ualue,composition, aflatorin Bi were analyzed. China soy flour(stor·ed 30'f) was contaminated by fungj on 50 days. Except for soy flour contardnated by fungi, sensory characteristics were not changed and foreign mater;als were notdetected. Acid value of China soy flour(stored at 30'C, 90 days) was about 10 times higherlevel before storage and acid value was more influenced by source(China, USA). Peroxide valuewas in proportion with the storage period slightly. The major fatty acid of soy flour waslinoleic acid(18 . 2), an(3 the change of fatty acid composition was not observed. Aflatoxlrl Blwas not detected.

안산시화호 갈대습지공원(경기도 안산시)의 거미상

김주필(Joo Pil Kim),최한석(Han Seak Choi),예용택(Yong Taek Ye),예성훈(Seong Hun Ye),김태우(Tae Woo Kim),김대희(Dae Hee Kim),지승환(Seung Hwan Ji),지성현(Sung Hyun Ji),이형민(Hyung Min Lee),변진관(Jin Kwan Byun),조주완(Joo Whan Jo),박솔 한국거미연구소 2017 한국거미 Vol.33 No.2

한국거미연구회 회원들은 2017년 8월 3일부터 4일까지 경기도 안산시 소재 시화호 갈대습지공원을 김주필, 최한석, 예용택, 예성훈, 김태우, 김대희, 지승환, 지성현, 변진관, 이형민, 조주완, 박솔민, 이형진, 이태후, 이승후, 조윤규, 조원규, 이준이, 신정애, 이영경, 최라미, 이윤정, 이용호, 한주연, 윤혜원, 김형주 등 26명이 주야로 채집한 결과 18과 49속 71종을 발표 보고하는 바이다. From August 3 to 4 in 2017. Koran Arachnological Study members investigated the Spiders in the whole area Gyeonggi-do Ansan-si, and reported 18 Families, 49 Genus 71 Species of spiders. The collected spiders are placed (stored) in the Joo-Pil Spider museum.

육백산(강원도, 삼척시)의 거미상

김주필(Joo Pil Kim),예용택(Yong Taek Ye),오종화(Jong Hwa Oh),예성훈(Seong Hun Ye),성민규(Min Gyu Seong),이정준(Jeong Jun Lee),김태우(Tae Woo Kim),김대희(Dae Hee Kim),지승환(Seung Hwan Ji),이형민(Hyeong Min Lee) 한국거미연구소 2016 한국거미 Vol.32 No.1

2015년 8월 3일부터 5일까지 한국거미연구회 회원들은 강원도 삼척시 육백산을 채집 조사한 결과 22과 49속 63종이 채집 조사되어 이에 보고하는 바이다. The authors investigated the spiders of the Mt. Yukbaek from August 3th to August 5th, 2015. In the present paper 63 species of 49 genera belong to 22 families were identified. These specimens are deposited at the Joo-Pil Spider Museum, Namyangju-Si, Gyeonggi-Do.