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>

췌장 선방세포암 1예

이화정,지준호,박승찬,박정철,최은정,서혜진,이원식,이정림,배병조,손경락,이경희 영남대학교 의과대학 2008 Yeungnam University Journal of Medicine Vol.25 No.2

Acinar cell carcinoma is a rare tumor that represents 1~2% of al1 pancreatic cancers. Clinical and radiologic findings are inconclusive in this disease Acinar cell carcinoma is characterized by rapid progression and early metastasis, which lead to its poor prognosis. A 41-year-o1d man was admitted to our hospital for abdominal pain. Abdominal computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) showed a splenic mass, which was being invaded by a pancreatic tail mass and which had increased ^(18)F-fluorodeoxyglucose (FDG) uptake Primary radical distal pancreatectomy and splenectomy were performed. Pathologic findings revealed an acinar cell carcinoma of the Pancreas The patient underwent a total gastrectomy three months later because of gastric recurrence Four months later, multiple hepatic metastases were discovered, and the patient underwent a left hepatectomy During treatment with capecitabine, there was no evidence of tumor progression for 14 months. We report a case of metastatic pancreatic acinar cell carcinoma, which did not progress for an extended period while the patient was being treated with capecitabme.

부신피질 자극호르몬 단독결핍 1례

박경식,이승현,최석영,박태규,이동화,이찬우,정성복,이인규 啓明大學校 醫科大學 1997 계명의대학술지 Vol.16 No.3

부신피질 자극호르몬 단독결핍은 국내에서 7례만이 보고된 희귀 질환이며 병인 및 경과 등 아직 불분명한 측면이 많다. 이는 질환지체의 희귀성도 있지만 치료후 자연경과에 대한 장기적인 추적검사가 이루어진 경우가 드물기 때문이기도 하다. 저자들은 비특이적인 전신증상을 주소로 내원한 폐경기후의 56세 여자 환자에서 자가면역질환의 증거없이 고프로릭틴혈증을 보인 부신피질 자극호르몬 단독결핍 1례를 경험하고 1년간의 부신피질호르몬 대치요법후 추적검사를 실시하였기에 문헌 고찰과 함께 보고하는 바이다. Isolated ACTH deficiency is a rare disorder which shows secondary adrenal insufficiency with normal states of other pituitary hormones. A 56-year-old postmenopausal woman complaining general weakness and intermittent mental confusion presented negligible serum cortisol and ACTH level with hyperprolactinemia and mild hyponatremia. Rapid ACTH stimulation test did not show significant increase of serum cortisol level. Combined pituitary stimulation test showed negligible response of cortisol and ACTH, and slightly decreased response of prolactin and gonadotropin. But the responses of TSH and GH were normal. There was no evidence of organic pituitary of hypothalamic lesion in brain MRI and antithyroid autoantibody was not detected in serum. After receiving 12 months of glucocorticoid replacement therapy, she skipped the medicine for 3 weeks and we performed follow-up endocrinologic tests. Serum ACTH and cortisol level was also negligible and prolonged ACTH simulation test showed normal response of serum cortisol. CRF stimulation test showed no response of serum ACTH. Basal prolactin level was decreased to near normal and combined pituitary stimulation test showed normal response of prolactin with slightly blunted response of TSH and GH. We concluded that the case was nonautoimmune origined isolated ACTH deficiency which was accompanied by hyperprolactinemia and resultant deficiency of gonadotropin, so we report this case with review of literatures.

실리카흄을 흔입한 고강도 콘크리트 개발

홍창우,김태경,김경진,김성환,김남윤,심도식,이정호,윤청호,백민경,원치문,박제선,이주형,정경일 강원대학교 석재복합신소재제품연구센터 1996 석재연 논문집 Vol.1 No.-

콘크리트 구조물이 대형화됨에 따라 설계단면이 증대되어 상대적으로 많은 경제적 손실을 부담하게 된다. 따라서 단면을 감소시키면서도 소요의 하중에 안전한 구조물을 건설하기 위해서는 우선적으로 구조물 건설에 기초가 되는 고품질, 고내구성의 고강도 콘크리트 개발이 절실히 요구된다 본 연구에서는 일정 시멘트비 및 혼화재 비율하에서 소요의 워커빌리티가 확보되는 고강도 콘크리트를 시간과 온도의 변화에 따라 증기 양생하여, 압축, 인장, 휨강도 뿐만 아니라 파괴특성을 실험적으로 연구하였다. 시료 제작시 시멘트 입자 사이의 공극 및 불연속 영역을 충전하여 고밀도화하기 위한 콘크리트용 혼화재로 시멘트 비표면적이 상당히 작은 초미립 분말인 실리카흄을 이용하였다. 또한 AE감수제 및 고성능 유동화제를 사용하여 혼화재의 첨가에 의하여 발생될 수 있는 워커빌리티의 감소를 방지하였다. 실험결과에 의하면 일정 양생 지속 시간하에서 온도의 증가에 따라 콘크리트의 압축, 인장 및 휨강도가 전반적으로 증가하였다. 동일하게 일정 온도하에서 양생 지속시간이 커짐에 따라 강도들이 증가됨을 알 수 있었다. 따라서 상대적으로 높은 온도와 긴 지속 양생 조건하에서 파괴에 대한 저항력이 크게 나타났다. The compressible, tensible, and flexibleresistance of the high strength concrete is analyzed by the experimentation in the present study. For the test, we cure several samples with the silica fume as a mixture being become dense the spaces between the particle of cement under the variation of both the temperature and the curing-interval. Then, the superplasticizer and the ezcon are also used to satisfy the required workability for construction. The compressible, tensible, and flexible resistances to a stress are increased as increasing the temperature and the time interval for the curing. Therefore it is concluded that the overal fractural and mechanical properties is improved by mixing the silica fume into the cement.

ISD 모델에 기초한 농업인 안전교육 프로그램 개발

김진모,이택선,이경숙,김경란,길대환,김효철,이찬 한국농업교육학회 2007 농업교육과 인적자원개발 Vol.39 No.3

이 연구의 목적은 ISD 모델에 기초하여 농업인 안전교육 프로그램을 개발하는데 있으며,이를 위해 분석-설계-개발-실행-평가의 다섯 단계로 구성된 개발모형을 설정하였다. 구체적인 프로그램 내용을 개발하기 위해 환경분석,학습자분석,과제분석을 실시하였고,그 결과를 반영하여 ‘안전의식 함양’,‘근골격계질환’,‘농약중독예방’,‘농기계 안전 사용’의 4개 모듈과 10개의 레슨을 설계하였다. 요구분석 및 설계 결과를 바탕으로 농업인 안전교육 프로그램의 교재/보조 자료/매체를 개발하였다. 교재의 경우,학습자용과 강사용을 구분하여 개발하였다. 개발된 프로그램 및 운영체제에 대한 검토 및 보완을 위한 전문가 협의회를 개최하여 프로그램 시연회를 실시한 후 교육프로그램을 수정,보완하였다. 그 후,농작업안전시범마을의 농업인을 대상으로 농업인 안전교육 프로그램을 시험 운영하였고,그 결과를 반영하여 농업인 안전교육 프로그램을 완성하였다. 또한 이상의 프로그램 개발 과정을 통해 나타난 논점을 토대로 향후 교육 프로그램 개발을 위한 시사점을 제공하였다. The purpose of this study was to develop a agricultural safety and health training program based on ISD Model. We set up 5step(Analysis, Design, Development, Implementation, Evaluation) model for developing the program. After analyzing environment, learner and task, four modules(① Safety and Health Mindset, ② Musculoskeletal System Disorders, ③ Agrichemical Poisoning Prevention, and ③ Using Farm Machines Safely) and 10 lessons were designed. We developed teaching materials and supplement materials for the Agricultural Safety and Health Training Program based on need analysis and program design. Teaching materials consisted of the learner's and instructor's. The developed program was examined by expert groups and the weak points were revised through professional workshop. Finally, we tested the Agricultural Safety and Health Training Program at agricultural safety and health model village and fixed the program by reflecting the test results.

원발성 후복막 점액낭샘암종 1예

지준호,이화정,박승찬,박정철,최은정,서혜진,이원식,이정림,배병조,손경락,이경희 영남대학교 의과대학 2008 Yeungnam University Journal of Medicine Vol.25 No.2

Primary retroperitoneal mucinous cystadenocarcinoma is a very rare malignancy, and little is known concerning its Pathogenesis, optimal treatment, and prognosis. A 29-year-o1d pregnant woman (21 weeks) Presented with abdominal discomfort CA 19-9, CA 125, and CEA were normal Abdominal CT scanning revealed a 19x15x13 cm retropentoneal tumor Exploratory laparotomy and tumor excision were performed. Mucinous retropentoneal implants were removed as completely as possible Histologically, the tumor showed focal areas of capsular invasion, but free resection margins The uterus and both ovaries were normal in appearance No adjuvant therapy was pursued. Six months later, Peritoneal and bilateral ovarian metastases were discovered. Hence, we report the details of this case of primary retroperitoneal mucinous Cystadeno-carcinoma and present a review of the literature.

‘임상간호연구’ 학술지 게재논문(1995-2008년)의 연구동향 분석

최명애,정재심,임경춘,김주현,김금순,권정순,김성재,김경희,곽찬영,박광옥,이경은,김을순,이경숙 병원간호사회 2010 임상간호연구 Vol.16 No.2

Purpose: The purpose of this study was to identify the research trend of 341 studies published in Journal of Korean Clinical Nursing Research from 1995 to 2008. Methods: This study was conducted from May to November, 2009. The tool for analysis developed through literature reviews and discussions of researchers consisted of 7 categories such as characteristics of researchers, research designs, subjects, data collection methods, ethical consideration, nursing interventions, and dependent variables. Data were analyzed by frequency and percentage. Results: The mean number of author per study was 4.7, and clinical nurses were the most frequent as the first author (79.7%) and as a corresponding author (67.1%). Quantitative study was 97.6% and nonexperimental study was 51.7%. The most frequently used research designs were quasi-experimental study (73.9%) among experimental studies and survey study (79.1%) among nonexperimental studies. Patients were the most frequent subjects for studies (55.8%). 46.1% of studies gathered data with questionnaire, 57.7% of studies had consent from patients, and 44.3% of studies used nursing skills for nursing interventions, and 60.0% of studies used clinical end points for dependent variables. Conclusion: The research trend of clinical nursing studies shows that clinical nurses mostly perform quasi-experimental researches to solve patients' problem and frequently use nursing skills for nursing intervention and explore the effect of nursing interventions on clinical end points.

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.

독성물질의 세포사 기전 및 세포사 유발물질의 검색법 개발에 관한 연구(Ⅱ) : 망간 신경독성을 이용한 파킨슨증 모델의 세포사 Studies on the Mechanism of Parkinsonism induced by Manganese

김종민,박창원,오정자,이보경,서경원,서수경,김규봉,김종원,김광진,김영옥,전범석,박찬웅,이선희 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

1960년대 이후 파킨슨병의 유발물질 중 한 후보로서 망간이 주목받으면서 많은 역학적, 병러학적 연구가 수행죄브다. 그러나 망간이 파킨슨병을 직접 일으키는지, 혹은 파킨슨병과 관련된 부위의 신경세포를 파괴시쿡 파킨슨증만을 초래하는 것인지가 아직 정립되지 않은 실정이다 본 연구에서는 실험동물모델에서 행등학적 변화 측정 및 병리학적, 샐화학적 연구를 통하여 망간의 과다노출글 따른 파킨슨병 유발 여부를 확인하고자 하였다. Sprague-Datylet· 렛드에 망간을 1, 2, 5, 10 mgAg/day의 응량으로 30일 등안 복강 투여하였을 때 모든 망간투여군에서 운동성 감소가 관찰되었다. 뇌조직의 망간 함량을 ion chromatograph?로 측정한 결과 중뇌 흑질과 기저핵 선조체에서 망간 함량의 뚜렷한 증가 소견이 관찰되었으며, 니슬염색체서 선조체의 신경세포수의 유의성 있는 감소가 관찰되었다. 그러나, 흑질의 TH효소 면역염색, GFAP 면역염색, 흑질과 선조체의 T릿효소 western blot 결과는 대조군과 차이가 없었다. 이상의 결과에서, 망간-파킨슨증 모델에서 파킨슨증어 유발되는 기전은 흑질 도파민성 신경 세포의 신호를 받는 선조체 씬경세포의 사멸에 의한 것으로 생각된다. 결론적으로, 망간 독성에 의한 파킨스증 모델에서는 파킨슨 병과는 달리 흑질 도파민성 신경세포의 세포사는 관여하지 않는 것으로 관찰되었다. Manganese(Mn) intoxication causes a parkinsonian syndrome. It may be difficult to distinguish Mn-induced parkinsonism from idiopathic Parkinson disease(IPD). Neuropathological descriptions on the brains with Mn intoxication showed the perferential damage in the globus pallidus and substantia nigra pars reticularis. Pathological reports on the substantia nigra pars compacta(SNpc), a mafor focus of pathologic changes in IPD, are discordant and controversial. The SNpc involvement is of critical importance for the elucidation of pathogenesis of IPD. Therefore, the neurodegeneration in SNpc was investigated in the experimental model of Mn neurotoxicity. Sprague-Dawley rats were administered with manganese chloride(1, 2, 5, 10 mg/kg/day, i.p.) for 30 days. Treated animals showed low levels of distance-traveled from locomotor activity tests. Ion chromatography revealed that Mn accumulation was significant in SN and basal ganglia in Mn-treated animals. Nissl staining showed neuronal loss of the striatum in all treated animals. The degree of neurodegeneration in SN was determined by immunohistochemical staining of tyrosine hydroxylase(TH). The numbers of TH-positive cells on nigral sections were not different from each groups(P>0.05). The densities of glial fibrillary acidic protein immunoreactivity from SN were similar between groups. TH-westen blotting showed no differences between treated animals and controls. In conclusion, the SNpc remains intact in Mn intoxication, and Mn-induced parkinsonism may be caused by damages of output pathways downstream to the nigrostriatal dopminergic system.

우리나라 現代都市計劃의 變化過程에 관한 硏究

李京贊 圓光大學校 附設 都市地域開發硏究所 1994 都市計劃論文集 Vol.1 No.-

This study aims to inquire into the changing process of modern urban planning in Korea between the year 1945 and 1971. The stage of modern urban planning in korea can be devided into four steps - firstly the transitional period from urban planning under the rule of Japanese Imperialism to Korean between the year 1945 and 1949, secondly the quickening period of modern urban planning between the year 1950 and 1957, thirdly the vacuum of urban planning between the year 1958 and 1961, fourthly the stabilized period of modern urban planning between the year 1962 and 1971. The characteristics of urban planning in time series are as follows. In the first stage, the urban planning is fragmentary policy oriented. In the second and third stage the project oriented urban planning is carried out in terms of reconstructing the war ravaged area. In the fourth stage, the comprehensive urban planning is carried out on the basis of institutional reconstruction and economic development planning.