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>

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

심인성 어지럼증 환자의 정신과적 증상에 관한 연구

이경규,이지영,김현우,이정엽,백기청,김재일,이근호 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.5

연구목적 : 어지럼증을 호소하는 환자들 중에 심인성 어지럼증 환자가 상당수 있다는 것은 알려져 있고, 이러한 심인성 어지럼증과 동반되는 정신질환으로는 불안장애, 우울장애, 인격장애 등이 있다. 이에 본 연구에서는 심인성 어지럼증 환자들의 빈도와 정신과적 증상을 알아보고자 하였다. 방 법 : 어지럼증 환자들에게 평형검사, 자세운동측정검사, 자세변화검사, caloric testing을 시행하여 심인성, 말초성 및 중추성의 3군으로 분류한 후 각각 14명, 16명, 32명을 대상으로 하였다. 대상환자들에게 한국판 Beck 우울척도검사(K-BDI), Spielberg의 상태-특성 불안검사(STAI). 간이정신진단검사(SCL-90-R)를 이용하여 정신과적 증상을 측정하여 이들 세 군을 비교분석하였다. 결 과 : 1) 심인성 어지럼증을 가진 환자는 어지럼증을 나타내는 환자 총 62명중에서 14명으로 22.6%를 차지하였다. 2) K-BDI에 따른 세 군간의 비교에서는 세 군간에 유의한 차이를 보이지 않았다. 3) STAI에 따른 세 군간의 비교에서 상태불안(STAI-S) 및 특성불안(STAI-T) 모두에서 세 군간에 유의한 차이를 보이지 않았다. 4) SCL-90-R에 따른 세 군간의 비교에서는 9개의 척도 중에서 공포불안척도에서만 중추성 어지럼증군이 47.56±6.90, 말초성 어지럼증 군이 53.50±13.74, 심인성 어지럼증 군이 58.50±16.05로 심인성 어지럼증 환자군이 중추성 어지럼증 환자군에 비하여 유의하게 높은 것으로 나타났다(p<0.01). 5) 통증 증상에 있어서는 세 군간에 유의한 차이를 보이지 않았고, 위장관 증상과 성기능 장애 증상은 중추성과 말초성 어지럼증 군이 심인성 어지럼증 군에 비하여 유의하게 높은 것으로 나타났다(p<0.01). 결 론 : 상기 결과를 토대로 했을 때 어지럼증 환자들에 대한 정신과적 접근을 위하여 각 군을 나누는 것은 별 의미가 없으며 어지럼증 환자들의 어지럼증 자체에 대한 직접적이고 집중적인 치료가 더욱 필요할 것으로 생각된다. Objectives : This study was aimed to investigate psychiatric symptoms in patients with psychogenic dizziness and compare these findings with those of patients with central and peripheral dizziness. Methods : A total of 62 patients with dizziness was the subject of investigation, and patients were classified into 32 with central type, 16 with peripheral type, and 14 with psychogenic type. Korean standardized Beck Depression Inventory(K-BDI), State and Trait Anxiety Inventory(STAI), and Korean standardized edition of Symptom Checklist 90 Revised(SCL-90-R) were used for the assessment. Statistically, Pearson's chi-square test and one-way ANOVA with Scheffe's test were used with SPSS/PC for windows 6.0. Results : The results were as follows : 1) The proportion of psychogenic dizziness was 22.6% of the total subjects. 2) Total scores of K-BDI were not significantly different among the 3 groups. 3) Total scores of state anxiety and trait anxiety were not significantly different among the 3 groups. 4) In SCL-90-R, psychogenic dizziness group showed significantly higher score of phobic anxiety only(p<0.01) than central dizziness group. And others were not significantly different among the 3 groups. 5) In additional somatic symptoms, pain score was not different among the 3 groups, but gastrointestinal and sexual symptoms scores of central and peripheral dizziness group were significantly higher than those of psychogenic dizziness group(p<0.01). Conclusion : These results suggest that psychiatric symptoms in patients with psychogenic dizziness are not different from those of patients with central or peripheral dizziness. Therefore, the more direct and intensive treatment may be necessary regardless of the type of dizziness.

다요인 모형을 이용한 한․중 주식수익률 결정요인의 비교 *

이상우(Lee, Sang-Woo),이의경(Lee, Eui-Kyung) 글로벌경영학회 2012 글로벌경영학회지 Vol.9 No.3

This study examines an effect of macro economic factors on the Korea and China stock return using multi-factor model based on APT. The study period is from the ten years from 2001 to 2010. The macro economic factors are classified into two groups, financial factors and real factors. The former consists of two variables, interest rate and foreign exchange rate. The real factors consist of two variables, economic growth rate and oil price increase rate. This empirical analysis of Korea and China stock returns showed the following results. First, Korea stock return is mainly affected by financial factors and economic growth rate. But China stock returns are affected by oil price. Second, foreign exchange rate had different sign in affecting on Korea and China Stock returns. Third, this research model is fit to China before the global financial crisis and Korea after global financial crisis. The evident differences between Korea and China stock may explain the reason why the prior studies could not find the coupling between Korea and China stock market. And they show some implications to those who are interested in China stock market. 본 연구는 APT에 기반을 둔 다요인 모형을 이용하여 주식수익률과 거시경제변수들의 관계를 분석한 것이다. 2001년부터 2010년까지의 10년 기간을 대상으로 한국은 KOSPI를, 중국은 상해종합주가지수를 통해 산출한 월별 주식수익률과 금융변수(금리와 환율), 실물변수(경제성장률, 국제유가)들과의 관계를 분석하였다. 분석결과를 비교하여 두 국가 주식수익률 사이의 다음과 같은 차이점을 발견하였다. 첫째, 한국의 경우에는 경제성장률, 환율, 금리 등이 주식수익률에 중요한 영향을 미치는데 비해서 중국의 경우에는 국제유가의 변화가 주식수익률에 중요한 영향을 미치고 있다. 둘째, 두 국가 모두 금리는 음(-) 의 관계를, 경제성장률과 유가상승률은 양(+)의 관계를 갖지만 환율의 경우에는 한국은 음(-), 중국은 양(+)의 관계를 보였다. 셋째, 2007년 글로벌 금융위기를 기준으로 그 이전과 이후 기간에 대해 분석한 결과, 본 연구모형은 글로벌 금융위기 이전의 중국과 글로벌 금융위기 이후의 한국에 적합한 것으로 나타났다. 이러한 뚜렷한 차이점은 학문적으로는 그 동안 선행연구들이 한국과 중국의 증시동조화를 확인할 수 없었던 원인을 설명하는 단서가 될 수 있다. 또한 실무적으로는 중국증시에 투자하거나 중국증시 에서 자금을 조달하는 경우 중요한 고려변수를 제시하는 결과가 될 수 있다고 생각된다.

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.

당뇨병 환자에서 혈장 Thrombin-Antithrombin Ⅲ 및 Plasmin-α_2-Plasmin Inhibitor 복합체의 임상적 의의

김경욱,김은숙,정상수,윤수지,박우일,이준희,남수연,안철우,문병수,김경래,차봉수,송영득,임승길,이현철,허갑범 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.5

연구배경:당뇨병 환자에서 혈액응고 및 섬유소용해 체계의 이상경향이 있어 그 결과로 여러 혈관합병증의 발생위험이 높다는 사실은 널리 알려져 있다. 그 기전은 아직 확실히 밝혀지지 않았으나, 고혈당으로 인한 혈장 단백질들의 비효소성 당화작용이나 산화성 스트레스로 인한 유리 라티칼 작용으로 응고항진이나 섬유소용해 활성의 저하를 유발하는 것으로 생각되고 있다. 최근 응고 및 용해인자와 그 억제자의 복합체들의 증가가 이 상태를 비교적 예민하게 반영한다고 알려져 있다. 방법:본 연구에서는 당뇨병 환자 101명과 정상 대조군 20명에서 혈장내 thrombin­antithrombin complex(TAT)와 plasmin­α₂­plasmin inhibitor complex(PIC)를 측정하여 비교하고, 당뇨병 환자에서 미세혈관 합병증과 대혈관합병증의 유무에 따른 차이와, 이미 혈관 질환의 위험인자로 알려져 있는 인자들간의 상관성을 알아보고자 하였다. 결과:1. 환자의 분포를 살펴보면 혈관합병증이 있는 군은 85명, 혈관합병증이 없는 군은 16명이었고, 평균연령은 각각 57.9±14.1세, 49.9±16.6세로 혈관 합병증이 있는 군에서 더 나이가 많았고, 체질량지수는 23.2±3.4㎏/㎡, 24.1±3.4㎏/㎡로 두 군간 유의한 차이는 없었다. 또 두 군간의 혈압 및 HbA1c, 공복혈당 및 인슐린과 C­peptide, 총 콜레스테롤, 중성지방, HDL­콜레스테롤, Lp⒜는 유의한 차이가 없었고, 미세혈관합병증이 있는 군에서 당뇨병의 유병기간이 길었다. 2. TAT 및 PIC의 농도는 정상 대조군에서는 2.8±1.2 ng/mL, 240.4±69.7 ng/mL이었고, 당뇨병 환자군에서는 9.5±22.6 ng/mL, 472.2±258.7 ng/mL이었다. TAT와 PIC 모두 당뇨병 환자군에서 정상 대조군에 비해 유의하게 증가되어 있었고(p<0.001), TAT/PIC ratio는 두 군간 차이가 없었다. 3. 당뇨병 환자의 혈관합병증에 따른 TAT 및 PIC, fibrinogen 농도는 합병증이 없는 군은 각각 4.1±2.4ng/mL, 362.2±272.0ng/mL, 322.7±102.4mg/mL으로 PIC와 fibrinogen의 증가를 보였으나, 연령을 보정한 후에는 통계학적 유의성은 없었다. 또 대혈관 합병증군에서는 각각 6.0±4.9 ng/mL, 507.4±321.6 ng/mL, 427.1±194.7 mg/dL이었으며 미세·대혈관 합병증군에서는 10.4±6.4 ng/mL, 484.8±269.7 ng/mL, 388.4±132.4 mg/dL으로 TAT의 증가를 보였으나 역시 연령을 보정한 후에는 통계학적 유의성은 없었다. 4. 미세혈관합병증군에서 HbA1c(>8%)가 높은 군의 PIC 농도가 유의하게 높았고(p=0.049), 대혈관합병증군에서 HbA1c(>8%)가 높은 군의 총 콜레스테롤 농도가 유의하게 높았다(p=0.042). 5. 총 당뇨병 환자군에서 PIC는 fibrinogen과 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며(r=0.47, 0.31,-0.25), 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다(r=0.67). 결론:이상의 결과에서 혈장 TAT 및 PIC 농도는 당뇨병 환자에서 정상 대조군에 비해 의미있게 증가되어 있었고, 당뇨병 환자군에서는 연령의 증가와 유병기간이 혈액응고항진 및 용해의 장애에 큰 역할을 함을 알 수 있었으며, 총 당뇨병 환자군에 PIC와 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다. 따라서 당뇨병 환자에서 혈액응고 및 용해의 장애가 동반되어 있다고 볼 수 있으며, 혈장 TAT 및 PIC는 혈관합병증으로의 진행을 예측하는 지표로서 유용하리라 생각된다. 또 혈당조절정도와 상관성이 있으므로 혈당조절후에 추적검사를 시행하여 합병증의 예방이 가능한지 추후 연구가 필요하리라 생각된다. Background : Abnormality of coagulation and fibrinolystic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin Ⅲ complex (TAT) and plasmin-α_2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. Methods : In our study, we measured plasma thrombin-antithrombin Ⅲ compelx (TAT) and plasmin-α_2-plasmin inhibit or complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. Results : 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA_ic, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8±1.2 ng/ mL, 240.4±69.7 ng/ mL in controls and 9.5±22.6 ng/ mL, 472.2±258.7 ng/ mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1±2.4 ng/ mL, 362.2±272.0 ng/ mL, 322.7±102.4 mg/ dL in group without vascular complication and 5.3±4.1 ng/ mL, 529.5±258.7 ng/ mL, 374.9±106.2 mg/ dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 60.±4.9 ng/ mL, 507.4±321.6 ng/ mL, 427.1±194.7 mg/ dL in macrovascular complication, and 10.4±6.7 mg/ mL, 484.8±269.7 ng/ mL, 388.4±132.4 mg/ dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA_1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA_1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA_1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA_1c (r=0.67). Conclusion : In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA_1c. TAT was correlated with HbA_1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients (J Kor Diaabetes Asso 25:354~363, 2001).

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.

림프종 환자에서의 갈륨, TI-201 그리고 Tc-99m MIBI 섭취의 비교

천경아,조인호,원규장,이경희,이형우,현명수,이재태,이규보 영남대학교 의과대학 2002 Yeungnam University Journal of Medicine Vol.19 No.2

Purpose; Ga-67 scintigraphy has been used for the evaluation of tumors, especially lymphoma. Recently, Tl-201 and Tc-99m MIBI were also used to tumor imaging. Tl-201 and Tc-99m MIBI had better physiologic characteristics than Ga-67, so we studied 32 biopsy proven lymphoma patients (male 24, female 8, mean age 46 years) with Ga-67, Tl-201 or Tc-99m MIBI and compared the scan findings. Materials and Methods: Twenty-three of 32 patients were injected 74-111 MBq (2-3 mCi) of Tl-201, before chemotherapy and imaged with dual-headed SPECT (Prism 2000, Picker, USA) at 30 minutes after injection. Delayed images were obtained after 3 hr in 8 patients. Twenty seven of 32 patients were injected 740 MBq (20 mCi) of Tc-99m MIBI and imaged at 30 minutes after injection. 111-185 MBq (3-5 mCi) of Ga-67 was injected in 12 patients and imaged at 48 and 72 hours after injection. Twenty eight patients were diagnosed as non-Hodgkin's lymphoma and others were Hodgkin's lymphoma. Results: Twenty patients were positive on Tl-201 scan and 3 patients showed negative findings. One of these 3 patients, Tc-99m MIBI and Ga-67 scan were positive. Twenty two patients were positive on Tc-99m MIBI scan and 5 patients showed negative findings. One of these 5 patients, Tl-201 was positive and 2 were positive on Ga-67 scan. Ten of 12 patients showed positive findings on Ga-67 scan. The sensitivity of these agents were 83.3%, 87.0% and 81.5% for Ga-67, Tl-201 and Tc-99m MIBI, respectively. The sensitivity was highest in Tl-201 scan, but there were no significant differences among three tests. In this study, there was no significant difference of uptake ratios between early and delayed images of Tl-201. Conclusion: Scintigraphy with Tl-201 and Tc-99m MIBI in lymphoma patients have similar sensitivity with Ga-67.

사후분해 시체에 대한 법의학적 접근

최영식,이상용,김유훈,조갑래,이봉우,양경무,정낙은,서중석,이한영,이원태,강현욱 大韓法醫學會 2000 대한법의학회지 Vol.24 No.2

Disposal of a homicide victim by dismemberment is rare, but individual cases are on record in most major medicolegal departments. Recognition of postmortem mutilation may be of importance in the interpretation of certain murders committed by sexual perverts and other mentally deranged individuals and sometimes performed for the sole reason of easier disposal of the body. Postmortem dismemberment is usually readily recognizable as such; The edges of the injuries are dry and lack evidence of bleeding. The joints may be disarticulated without fracture, or the use of an axe or saw may be evident from examination of bones. Parallel horizontal or oblique furrows in the bone surface are caused by skipping of the saw prior to establishing depth. Such patterns on the bone may assist in identifying the particular saw involved. So we report 25 dismembered corpses that autopsied in National Institute of Scientific Investigation. This paper can help in attempting to establish not only the first criminal investigation steps but also the medicolegal approach methods in unidentified and dismembered deaths.

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>