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        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>

      • KCI등재후보

        후두적출자의 의사소통 태도

        강수균,박선희,백은아,이현혜,최경희,강은희,박은실 대구대학교 특수교육재활과학연구소 2005 특수교육재활과학연구 Vol.44 No.3

        본 연구는 후두적출자의 주된 발성방법과 후두적출 경과 시기에 따른 의사소통 태도를 살펴보고자 하였다. 연구의 대상은 성인 남자 55명으로 후두암으로 인한 후두적출자들로 구성되었다. 이들에게 실시한 의사소통 태도 설문지는 Erickson의 의사소통 태도 척도-수정판(Modified Erickson Scale of Communication Attitudes: S-24)을 본 연구에 맞게 수정 보완하여 사용하였다. 본 연구의 결과는 첫째, 주된 발성방법에 따라서는 인공후두기 사용자와 식도발성자간의 의사소통 태도에 차이가 없었다. 둘째, 후두적출 경과 시기에 따라 10년 초과된 후두적출자들과 10년 이하의 후두 적출자들 간의 의사소통 태도에 차이가 없었다. 그러므로 이들의 의사소통 태도의 긍정적 태도를 증가시키기 위하여 다양한 방법을 활용하고 습득하여 이들의 의사소통 능력을 빠르게 재습득 하여 긍정적인 의사소통 능력을 가질 수 있도록 해야 한다. The purpose of this study was to determine laryngectomee's communication attitude. 55 laryngectomees, who were in the range of 40 years old to 80 years old participated in the study. Communication attitude measurements were taken by S-24(Modified Erickson Scale of Communication Attitudes). The results showed as follows: First, score of laryngectomees with artificial larynx and esophageal speakers were no significant. Second, score of laryngectomees with over 10 years after latyngectomy and 10 years after latyngectomy were no significant.

      • 관절염 환자의 민속요법이용 형태

        은영,강현숙,이은옥,이인숙,이종수 서울대학교 간호대학 간호과학연구소 1997 간호학 논문집 Vol.11 No.1

        This sty was undertaken to explore the utilization patterns of medical treatment and herb medicine in patients with arthrits. The data were collected from 995 patients who were registered either in a center of rheumatology or resided in community with arthritis. The data were analyzed by percentile, t-test and chi-square test using SAS PC program. The results of this study were as follows; 1. According to characteristics of sample-population, mean age was 57.7 years, duration of arthritis 9.7 years and mean duration of pain 2.4 hours per day at present. 2. First diagnosis was identified at department of orthopedic surgery or local clinic. But 85.2% of patients have transferred to the center of reumatology currently. But ironically over 70% of patients experienced the herb treatment and herb treatment had hern medicine simultaneous with medical treatment. This indicated that they were shopping around of treatment during the first one year. 3. Mean cost of medical treatment was 67,400 won, while they payed to herb medicine as much as two or three times. The utilization rate of herb medicine was 36.5% of patients per one year. Costs of herb-treatment were 182,000 Won and herb medicine was 36.6% of patients per one year. Costs of herb -treatment were 182,000 Won and herb medicine 149,100 Won. 4. Eighty point six percent of patients were experienced herb medicine during life-time. One hundred and seventy four kinds herb medicine were found to be used by patients, most of which were nutrients, muscle relaxants, andtiphlogistics and analgesics. Thirty two point six percent of users recognized that herb medicine were effective but 51.7% did not. In conclusion, arthritis patients have been experienced various kinds of drug and remedies for treatment. And they wasted their limited medical and economical resources on these unresonable remedies. Therefore, they should be guided for wise decision about treatment. Futher studies in nursing will be required to explore the value system of patients about herb medicine, the determinant factors of shopping-around patterns of treatment, and the coping mechanism for chronic pain or aggravating symptom.

      • 상염색체우성 다낭신의 임상경과 및 합병증

        이상주,이영모,이한규,최대은,박기현,이강욱,신영태 충남대학교 의학연구소 2001 충남의대잡지 Vol.28 No.2

        Autosomal dominant polycystic kidney disease(ADPKD) is one of most common hereditary disorder. It is potentially fatal and the major mobilities are hypertension and renal failure. To elucidate clinical characteristics and outcomes of ADPKD, 67 ADPKD patients were analyzed retrospectively. The male to female ratio was 48 years for males and 42 years for females. The factors leading to the dignosis of ADPKD were flank or abdominal pain (46%), palpable abdominal mass (24%), incidental findings (18%), gross hematuria and headache. Urinalysis result showed hematuria (31%), proteinuria (19%), pyuria (18%). Among renal complications hypertension (67%) was the most common. Other complications were urolithiasis (16%) upper urinary tract infection (9%), cyst infection (7%). Azotemia was observed in 24% of cases. Echocardiography showed left ventricular hypertrophy in 24% and valvular regurgitation in 18% of cases, but there was no mital valve prolapse. Cerebrovascular events occurred in 6 cases (2 cases of intervertebral hemorrhage and 4 cases of cerebral infarction). Hipatic cyst were observed in 64% of cases. Eighteen cases culminated in end stage renal failure (ESRF) at an of 47. According to this study, the most common complications of ADPKD was hypertension (67%), ESRF (27%), and cerebrovascular event (9%). Hypertension was more frequently observed in increased creatinine group than normal.

      • Investigation of the April 2000 forest fire damage in Kang-won Province, Korea, using RADARSAT data

        Kang, Sung Chul,Seo, Jin Won,Lee, Tae Hee,Park, Sang Eun,Hong, Suk Young,Moon, Wooil M. 대한원격탐사학회 2000 International Symposium on Remote Sensing Vol.16 No.1

        The series of forest Fires in Kangwon Province in April, 2000, were one of the mast serious ones in the Kang-won Province in recent years. The fire damaged areas are extensive and this paper investigates the utility of the satellite image data, particularly the RADARSAT SAR data. One of the main objectives of this study included evaluation of potential usefulness of the C-band RADARSAT data in the detection of forest fires in mountainous areas. Among several fire damaged sites, the area near Samchuk (city) was selected as the main study area and mufti-temporal RADARSAT(raw) data were acquired and the processed results were comparatively investigated with the IRS-1c data acquired shortly after the fire. To identify the burnt area from the undamaged background in the optical imagery, supervised classification and NDVI processing were carried out and tested with the IRS-1C data. For this experiment, several sets of raw RADARSAT standard and Fine mode (S4, F3, ascending orbit) data were processed and the final image was formed. In addition to the final image, sigma nought (σ°) was catnputed and compared for the burnt area against the undamaged areas. Because of the steep slopes in the study area and subsequent deviation from the flat surface scattering models, the fire scars in the sigma nought (σ°) image were not apparent. However, fire scars are slightly detected in the difference and ratio images obtained from the signal intensity data acquired at different dates (bath before and after fire). Texture analysis of the image data including the burnt areas were carried out using the Multiplicative Markov Random-Field (MMRF) algorithm. The detection of the fire damaged area from both standard mode and fine mode RADARSAT was not as straightforward as in optical data. However, Previous studies with ERS-1 S_AR and RADARSAT data in Indonesia and in the North American Plains indicate that C-band SAR data provide us with an effective tool for studying the forest fire damages. However, the application of C-band SAR data to the analysis of the forest fire areas requires careful processing of the data with realistic scattering models.

      • 횡문근융해증과 급성 신부전 및 범발성 혈관내 응고장애를 동반한 열사병 1예

        최대은,박수진,권오경,이한규,이영모,이상주,나기량,이강욱,신영태 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

        Heat stroke is a life-threatening illness characterized by an elevated core body temperature that rises above 40% and central nervous system dysfunctions that results in delirium, convulsions, or coma. Heat stroke is subdivided into two forms, classic and exertional. Since strenuous exercise is one of the major exacerbating and precipitating factors, the incidence of exertional heat stroke is high among young adult, especially military personnel undergoing military training. Exertional heat stroke commonly causes rhabdomyolysis, lactic acidosis, acute renal failure, shock and pulmonary edema. We report a case of heat stroke with rhabdomyolysis, acute renal failure, disseminated intravascular coagulopathy(DIC) after strenuous exercise. A 18 year old man was admitted to the hospital because of loss of consciousness. He was a wrestler and he had tried to lose 6kg in weight by jogging and strenuous exercise on that summer day with hot temperature. The development of this illness was favoured by much clothes inappropriate for that environmental condition with a purpose to enhance sweating, and by restricted intake of water and food. On admission, the blood pressure was 80/50mmHg, and body temperature was 39.4℃ with stuporous mentality. Laboratory finding were as follows : in complete blood cell count, hemoglobin was 16.7g/dL and platelet count was 158,000/ mm³. In blood chemistry, AST 1061U/L, ALT 201U/L, BUN 30mg/dL, Cr 2.2mg/dL, LDH 941IU/L, CK 696IU/L were resulted. In arterial blood gas analysis, pH 7.39, pCO₂ 30mmHg pO₂ 86mmHg, HCO₃ 18.4mEq/L, O₂ saturation 96.7% were resulted. In urinalysis, specific gravity 1.025, protein 3+, erythrocyte 2+ were resulted. In brain imaging study, brain CT finding was normal. After appropriate treatments with rapid cooling, hydration and supportive care, he improved with alert mental status. On 2nd hospital day, in laboratory result, thrombocytopenia and coagulopathy were appeared and renal insufficiency was aggravated. So he was treated with platelet concentrate and fresh frosen plasma for DIC, and enough hydration for appropriate urine volume preservation. After all, On 22nd hospital day, he fully recovered and discharged. Nowadays, with followed for some duration, he is wellbeing with no complications.

      • 당뇨병과 동반된 화농성 간농양의 임상상 및 예후인자

        오은숙,강무일,이원영,오기원,임동준,이소영,이정민,고승현,김성래,안유배,손현식,윤건호,차봉연,이광우,손호영,강성구 대한당뇨병학회 2000 임상당뇨병 Vol.1 No.1

        연구배경: 감염질환은 혈관질환과 함께 당뇨병의 중요한 사망원인의 하나이며, 혈당조절이 불량할수록 감염 빈도가 증가됨은 잘 알려져 있다. 간농양의 발생이 있어서도 당뇨병은 중요한 기저질환 중의 하나이다. 일반적으로 간농양의 가장 흔한 원인균은 Escherichi coli라고 알려져 있으나, 최근 당뇨병을 가진 간농양 환자에서 Klesiella pneumoniae의 검출이 증가되고 있다. 또 최근 연구에 의하면 K.pneumonie가 간농양의 가장 흔한 원인균이며, K. pneumoniae에 의한 간농양은 K.pneumoniae 이외의 균주에 의한 간농양보다 당뇨병과 밀접히 관련되어 있다고 보고된 바 있다. 이에 저자들은 간농양 환자를 대상으로 당뇨병환자의 빈도를 알아보고, 그 원인균 및 특징을 비당뇨병 환자들의 경우와 비교해 보고자 하였다. 방법: 1992년 1월부터 1999년 6월까지 방사선학적 검사 혹은 수술에 의해 간농양이 확인되거나, 경피적 천자나 수술을 통한 배농액 배양, 혹은 혈액 검사에서 원인균이 증명된 182명의 환자를 대상으로 후향적 임상고찰을 실시하였다. 결과: 화농성 농양을 가진 167명의 환자(남:94명, 여:73명)중 당뇨병을 가진 환자는 54명 (남:30명, 여:24명)으로 32.3%를 차지하였다. 환자의 평균나이는 당뇨군에서 62.1 ± 13.4세, 비당뇨군에서는 55.1 ±15.5세로 당뇨군에서 높았으며(p=0.0021), 남녀간의 평균나이 비교 시 두 군 모두 여성의 나이가 의미있게 높았다. 비당뇨군에 비하여 당뇨군의 경우 저알부민혈증의 빈도와 aspartate transaminase가 증가되어있었다. 원인균주는 K. pneumoniae (당뇨군54%, 비당뇨군 39.1%), E. coli(당뇨군 17.5%, 비당뇨군 18.8%), Pseudomonas aeruginosa, Streptococcus viridans, Enterococcus 순이었으며 두 군간의 의미는 차이는 없었으나 K. pneumoniae의 경우 다른 균종에 비해 단독감염의 빈도가 높았다(82.8%). 사망률은 당뇨군에서 16.7%, 비당뇨군에서 7.1%로 당뇨군에서 의미있게 높았으며(p=0.019), 당뇨군에서의 사망환자는 모두 패혈증이 동반되어 있었다. 당뇨환자의 사망군은 생존군에 비해 당뇨병 이환기간이 길고 혼합감염의 빈도가 높았다(p=0.046). 검사실 소견에서는 총 빌리루빈 및 알카리성 포스파타제의 증가가 관찰되어 있었다. 결론: E. coli가 간농양의 주된 원인균이라는 기존 보고와는 달리 당뇨군과 비당뇨군 모두 K. pneumoniae가 간농양의 주된 원인균이었다. 또한 당뇨 유병기간이 길고 당뇨조절이 불량한 환자에서 혼합감염이며 총 빌리루빈 및 알카리성 포스파타제의 증가등과 같은 위험인자가 존재할 경우 사망률이 증가될 수 있으므로 이들 군에서는 적극적인 치료가 필요할 것으로 사료된다. Background: Liver abscesses are commonly associated with underlying disease, particularly diabete mellitus. The number of the liver abscesses caused by Klebslella pneumoniae in diabetic patient has been increased in Korea nowadays. This study was conducted to clarify the clinical presentation and prognostic factors of pyogenic liver abscesses, especially in diabetic patients and to determine the proportion of K. pneunomiae as a pathogen in liver abscess in Korea. Methods: Medical records of 167 patients treated for pyogenic liver abscess from January, 1992 through June, 1999 were reviewed retrospectively in detail. Major Pathogenic organism, clinical manifestations, prognostic factors, the importance of diabetes mellilus as an underlying disease and its effect on clinical features and prognosis were analyzed. Results: Among 167 cases of pyogenic liver abscess, underlying diabetes mellitus was present in 32.3%. The mean age of patients was 62.7 13.4 years in diabetic liver abscess group and 55.1 15.5 years in non-diabetic liver abscess group. Most liver abscesses were cryptogenic in origin or secondary to the billary tree diseases. The clinical presentations among the two groups were not significantly different. When compared to patients without diabetes, patients with diabetes had significantly higher proportions of hypoalbuminemia and elevated aspartate transaminase level. The most common organism of the pyogenic abscess was K. pneumoniae in both groups. Percutaneous drainage of the abscess with appropriate antibiotics was the most commonly used therapeutic modality in liver abscess. The mortality rate of diabetic liver abscess is 16.1 % and 7.1% in nondiabetic liver abscess. Complications, especially septicemla, were found more frequently in patients with diabetes than in patients without diabetes (64.8% vs 28.3%, septicemia : 31.5% vs 9.7%). The factors influencing mortality in the diabetic liver abscess were disease duration, mixed infection, presence of septicemia, elevated bilirubin and alkaline phosphatase. Conclusions: In contrast to prior report that the E. coli was the most common pathogen in liver abscess, we found that K. pneumoniae was the most common organism cultured in liver abscess. Diabetic patients have more complications and higher mortality than patients without diabetes. Early detection and proper treatment are needed to improve the outcome for diabetic patient with liver abscess.

      • KCI등재
      • KCI등재후보

        위절제술 환자의 표준진료지침 개발 및 적용 효과

        김은희,김철규,이순교,김순덕,이혜옥,권정순,이경미,이민미,심순미,유용만,신종식,강은희,이상일,김병식,오성태,육정환,박수길 한국의료QA학회 2003 한국의료질향상학회지 Vol.10 No.2

        Background : Gastric cancer is the most common malignant tumor in Korea. surgical operation is one of the major treatment modalities for gastric cancer patients. Therefore, gastrectomy is one of the most common procedures in General Surgery. There were variation in length of hospital stay and medical treatment for gastrectomy between three surgeons at Asan Medical Center. Clinical pathways have received considerable attention as a tool for recucing the medical practice variation, increasing the efficiency of care process, and improving the quality of care. The aim of this study was to evaluate the effect of a clinical pathway for gastrectomy in gastric cancer patients. Methods : The clinical pathway for gastrectomy was developed and implemented by a multidisciplinary group in Asan Medical Center. A computerized clinical pathway program was developed and revised after a pilot test. A total of 145 patients underwent gastrectomy by three surgeons at Asan Medical Center. We compared the length of hospital stay, patient satisfaction, and unplanned readmission rate between the pre-pathway group(n=67) and the post-pathway group(n=78). We also investigated the degree of satisfaction among the physicians and nurses who were main end-users of the clinical pathway. Results : The clinical pathway was applied to all target patients. The average length of hospital stay was shortened from 12.7days to 10.6days(p<0.01). The degree of patient satisfaction with the care process changed from 90.3% to 89.2% after the implementation of the clinical pathway, but the difference was of satistically significant(p=0.761). Unplanned readmission rate was 2.9% in the pre-pathway group. More than 90% of physicians and nurses answered that the clinical pathway had been a useful tool in their medical practice. Conclusions : The findings of the study demonstrated that implementation of the clinical pathway for gastrectomy produced substantial reduction in the length of hospital stay while improving the quality of patient outcomes. The computerized clinical pathway program can be used as one of the powerful patient management tools for reducing the practice variations and increasing the efficiency of care process in Korea hospital settings.

      • SCIEKCI등재

        Predicting postoperative total calcium requirements after parathyroidectomy in secondary hyperparathyroidism

        ( Byung Heon Kang ),( Soon Young Hwang ),( Jeong Yeop Kim ),( Yu Ah Hong ),( Mi Yeon Jung ),( Eun Ah Lee ),( Ji Eun Lee3 ),( Jae Bok Lee ),( Gang Jee Ko ),( Heui Jung Pyo ),( Young Joo Kwon ) 대한내과학회 2015 The Korean Journal of Internal Medicine Vol.30 No.6

        Background/Aims: To prevent hypocalcemia after parathyroidectomy (PTX), parenteral calcium is required in addition to oral calcitriol and calcium. After switching to oral calcium, patients can be discharged from the hospital. The aim of this study was to analyze the clinical characteristics and outcomes of PTX performed at a single Korean center and to investigate the associated laboratory factors used to analyze the total amount of postoperative calcium required. Methods: We enrolled 91 hemodialysis patients undergoing PTX from November 2003 to December 2011. We collected clinical and laboratory data preoperatively, 12 and 48 hours postoperatively, at discharge, and 3 and 6 months postoperatively. Results: In total, 59 patients underwent PTX with autotransplantation (AT), 6 underwent total PTX without AT, 11 underwent subtotal PTX, and 15 underwent limited PTX. Total PTX without AT showed the lowest recurrence rate. At all postoperative time points, the mean levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) decreased significantly, compared with preoperative levels; however, alkaline phosphatase (ALP) increased significantly from 48 hours postoperatively to discharge (p < 0.001). On multiple linear regression analysis, the total amount of injected calcium during hospitalization showed a significant correlation with preoperative ALP (p < 0.001), preoperative iPTH (p = 0.037), and Δphosphorus at 48 hours (p < 0.001). We developed an equation for estimating the total calcium requirement after PTX. Conclusions: Preoperative ALP, preoperative iPTH, and Δphosphorus at 48 hours may be significant factors in estimating the postoperative calcium requirement. The formula for postoperative calcium requirement after PTX may help to predict the duration of postoperative hospitalization.

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