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>

고성능 마이크로프로세서에서 데이터 값 예측기 개발에 관한 연구

박희룡 ; 추봉조 ; 이강한 김천대학교 2000 김천대학교 논문집 Vol.21 No.-

In order to achieve high performance by exploiting instruction level parallelism aggressively in wide-issue superscalar processors, it is necessary to overcome the limitation imposed by control depen-dences and data dependences which prevent instructions from exe-cuting parallel. The value prediction is a technique that breaks datadependences by predicting the outcome of an instruction and executes speculatively its data dependent instruction based on the predicted outcome. In this paper, an extended hybrid-data-value prediction scheme with dynamic classification mechanism is pro-posed. We design a hybrid predictor by combining the last-value predictor, a stride-value predictor and a two-level-value predictor. The choice of a predictor for each instruction is determined by a dynamic classification mechanism. This makes each data predictor utilized more efficiently than the extended hybrid-data-value pre-dictor mechanism. In order to show performance improvements of our scheme, we have simulated the SPECint95 benchmark set by using execution-driven simulator. The results show that the pro-posed scheme effect reduce of 33.3% 45% hardware cost and about 16% prediction accuracy improvements comparing with the conven tional hybrid data value prediction scheme and it also effects the two-level-data value prediction scheme.

ILP 프로세서에서 2-단계 데이터 값 예측기의 Aliasing에 대한 효과

박희룡,전병찬,이상정 순천향대학교 부설 산업기술연구소 1998 순천향 산업기술연구소논문집 Vol.4 No.2

To exploit instruction level parallelism(ILP) in ILP processor, it is necessary to overcome the limits of data dependency among instructions. The data value prediction is a method to remove the limitation. In this paper, two-level data value predictor and hybrid data value predictor are studied. And the performance of those schemes are compared and analyzed. Also, the effects of aliasing on PHT(Pattern History Table) are measured and analyzed. As a result of experiment, it is shown that is there ware occurred aliasing of about 88%-98% in two-level and hybrid predictor. But the aliasing's hit ratio is reduced about 50% when XOR was applied on PHT.

형광검출 역상 액체크로마토그래피에 의한 Histamine의 정량

유희춘,김형룡,김상현,김대기,이영미,김형민,안년형,신태용 우석대학교 의약품개발연구소 1996 藥學硏究誌 Vol.1 No.-

Histamine을 정확하고 신속하게 정량하기 위해 9.Fiuorenylmethyl chloroformate를 형광유도체화제로 하여 역상 HPLC법으로 정량하였다. 히스타민을 형광유도체화할 때 반응액의 pH, 반응시간, 형광유도체화제의 농도 등 최적 반응 조건을 검토하였다. 이 방법으로 히스타민을 분석한 결과 0.1~0.5ug/ml의 농도범위에서 상관계수가 0.922인 양호한 직선성을 나타내었으며 검출한계는 0.01??/ml였다. A rapid and simple method for the determination of histamine by reverse-phase high performance liquid chromatography with fluorescence detection was established. 9-Fluorenylmethyl chloroformate(FMOC) was used as fluorescent derivative reagent. The optimum conditions for the derivatiation such as pH, reaction time and he concentration of FMOC were investigated. Linearity of calibration curve was obtained between 0.1ug/ml/and 0.5ug/ml(r=0.922) and the limit of detection was 0.01ug/ml.

만성 스트레스에 대한 뇌 및 위장관계의 Polyamine반응 : 단일성 및 복합성 스트레스의 차이 Differences between Single and Complex Type Stress

강영우,김희철,이성룡 대한생물치료정신의학회 2001 생물치료정신의학 Vol.7 No.2

Objectives : There is a hypothesis that subject may adapted to same kind repetitive stress. Polyamine(putrescine, spermidine, and spermine) is one of the stress responses in brain and peripheral organs. Therefore, we designed this study to investigate the differences between single and complex type of chronic stresses by examining the changes of polyamine levels in brain and peripheral tissues. Method : There are four groups in this study. 1) control group(n=5) : animals with no stress, 2) immobilization stress group(n=5) : animals with 10 times of immobilization stress, 3) cold-water swimming stress group(n=5) ; animals with 10 times of swimming stress in cold water, 4) complex stress group(n-5) : animals with immobilization and cold-water swimming stress. For immobilization stress(10 days), rats were placed in restrainers once daily, for 3 hours, For cold water swimming stress, rats were placed in ice-cold water once daily for 3min(10 days). For complex stress, rats were alternately underwant immobilization stress and cold swim stress, for 10 days(5 times, respectively). For polyamine analysis, polyamine extracted from brain tissue(frontal cortex and hippocampus) and gastrointestinal tract(gastric and duodenal mucosa) and measured with high performance liquid chromatography and ultraviolet detector at 242nm. Results : Putrescine levels in frontal cortex were significantly decreased by immobilitation stress and complex stress, respectively. Putrescine levels in hippocampus were significantly decreased by immobilization stress. Spermidine levels in duodenal mucosa were significantly decreased by cold swimming stress. However, spermine levels were not changed by any type of stress. There were no differences in polyamine reponses between single type and complex type stresses. Conlusions : Attenuations of putrescine and spermidine levels after chronic stresses seem to be a adaptation process of polyamine responses. In our experimental conditions, there are no differences in polyamine responses between single type and complex type stresses.

말초혈액에서 Tg mRNA에 대한 역전사 중합효소 연쇄 반응법의 갑상선 재발암의 분자생물학적 진단

권성일,박기룡,김현영,신채희,임영찬,최영식,박요한,이강대,장희경,이재화,염하용 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.4

연구배경: 갑상선암은 다른 조직에 발생한 암에 비해 비교적 천천히 자라므로 대부분 예후가 양호하지만, 일부에서는 주위 조직으로 침윤하거나 혹은 원격 전이로 인하여 치명적인 결과를 초래할 수 있다. 갑상선전절제술 및 131^I 제거술 후 경과 관찰시 갑상선암의 재발과 전이의 진단에 있어 131^I 스캔과 혈청 Tg의 측정이 현재 임상에서 가장 많이 이용되고 있으나 이 방법에는 여러 가지의 결점이 있다. 최근 Tg mRNA에 대한 RT-PCR법을 이용한 여러 연구결과는 131^I 스캔과 혈청 Tg 측정의 결점을 보완할 수 있는 좋은 보조적인 진단법으로 이용할 수 있을 가능성을 제시하였다. 이에 말초혈액에서 측정한 Tg mRNA에 대한 RT-PCR법이 갑상선 절제술 및 방사성요드 치료 후 갑상선암의 재발 및 전이 유무의 진단에 유용한가를 알아보고자 이 연구 시행하였다. 방법: 분화된 갑상선암으로 진단된 후 갑상선전절제술을 시행받고 방사성요드 치료를 받은 환자 중 현재까지 한차례에 이상 추적 방사성요드 전신 스캔을 시행하고 추적관찰이 가능했던 유두선암 35예, 여포선암 5예를 대상으로 연구를 시행하였다. 대상군은 131^I 스캔 소견상 음성인 군(Group Ⅰ), 잔여조직이 있는 군(Group Ⅱ), 국소전이가 있는 군(Group Ⅲ), 및 원격전이 군(Group Ⅳ)으로 구분하였다. 정상 대조군은 갑상선질환이 없는 10예의 건강인으로 하였다. 대상환자의 말초혈액을 이용한 Tg mRNA에 대해 특이적인 primer를 이용하여 RT-PCR 및 nested RT-PCR을 시행하였다. 결과: 본 연구 결과는 다음과 같다. 1) 131^I 스캔 소견상 음성인 군 21예 중 1예에서 Tg가 양성소견을 보였다. Anti Tg Ab가 양성인 4예 모두 Tg가 음성을 보였다. 잔여조직이 있거나 국소전이 및 원격전이를 보인 군 19예 중 Tg가 양성인 경우는 4예였으나, Tg mRNA는 전예에서 양성이었다. 2) 131^I 스캔에서 국소 및 원격전이 소견을 보인 8예 중 4예에서 Tg가 음성으로 131^I 스캔과 혈청 Tg 사이에 불일치 소견을 보였다. 3) 말초혈액에서 특이적인 primer를 이용하여 RT-PCR 및 nested RT-PCR을 시행한 결과 대상군 40예 및 정상 대조군 10예 모두에서 Tg mRNA가 양성을 보였다. 결론: 본 연구에서 갑상선 절제술 및 방사성요드 치료 후 갑상선암의 재발 및 전이 유무를 평가함에 있어 역전사 중합효소 연쇄 반응법을 이용한 Tg mRNA 측정의 의의는 재평가되어야 한다고 생각된다. Background: Differentiated thyroid cancer is the most common endocrine malignancy. Despite advances in the treatment of thyroid cancer, disease recurrence and metastasis may occur in as many as 20% of patients, and so continues to pose major problems in its clinical management. Serum thyroglobulin (Tg) measurements, by immunoassay, are used to detect residual or recurrent thyroid cancer following thyriod ablation. However, the usefulness of immunoassay is limited by both the requirement for thyroid hormone withdrawal, to attain optimal test sensitivity, and interference by the antithyroglobulin antibody (Anti-Tg Ab). Recent studies have reported the clinical usefulness of reverse transcription-polymerase chain reaction (RT-PCR) detection of Tg mRNA in the peripheral blood of patients with differentiated thyroid carcinomas. We performed this study to evaluated the usefulness RT-PCR of Tg mRNA in peripheral blood of patients with thyroid carcinoma following a total thyroidectomy and radioiodine ablation therapy. Methods: Forty cases that underwent a total thyroidectomy and radioiodine ablation therapy were included in this study. Of the 40 patients, 35 were papillary carcinomas and 5 were follicular carcinomas. Ten normal control subjects were also studied. Tg mRNA was extracted. Then RT-PCR and nested RT-PCR, were run with specific Tg primers. Concurrently, DNA sequencing of the isolates was carried out to prove the isolates were identical to the nucleotide sequence of the Tg. Results: The Tg was detected in 4 of 19 patients, with either a residual thyroid bed, or metastasis, on a 131^I whole body scan and in 1 of 21 patients with a negative radioiodine scan. Surprisingly, the Tg mRNA was detected in all the patients and normal controls. Conclusion: From our results we can not recommend Tg mRNA, detected by RT-PCR in peripheral blood, as a tumor marker superior to that of the Tg serum level. We consider an intensive re-evaluation of the method is required before considering its clinical applications (J Kor Soc Endocrinol 17:501∼513, 2002).

광섬유 변형센서 개발과 시뮬레이션

강신원,이상룡,이정희,박재희 경북대학교 센서기술연구소 1997 연차보고서 Vol.1997 No.-

악골에 발생한 악성 섬유성조직구종 2례

정종철,최홍란,오희균,박준아,류선열,이종호,김영운,정숭룡 大韓顎顔面成形再建外科學會 1995 Maxillofacial Plastic Reconstructive Surgery Vol.17 No.3

Malignant fibrous histiocytoma rarely occurs in the jaws. Although the histogenesis of this tumor remains controversal, it is best regarded as a primitive and pleomorphic nature reflected by collagen production and occasional phagocytosis. It is common for metastatic foci to appear in lung and regional lymph node. There are variable treatments such as radiotherapy, surgical excision or combination, therapy of surgical excision, chemotherapy and radiotherapy. With the review of literatures, the authors report the clinical study of two cases of malignant fibrous histiocytoma of the jaw.

국제 경기를 통한 스포츠 산업의 활성화 방안

김인형,최동일,남희은,이근모,김찬룡 釜山大學校 附設 體育科學硏究所 1998 體育科學硏究所 論文集 Vol.14 No.-

This study was mainly focused on the relationship between sports industry and international games. According to the category of both sports information ·service industry and sports technology industry. The way of activating sports industry by international games is proposed as follows; 1. Sports information · service industry 1) Sports Event (1) Expending the inducement of sports event sponsored by domestic international enterprises. (2) Improving image of enterprise by activating character industry. (3) Elevating the mood of international games by pre-event and post-event. (4) Attracting tourist during games session by opening various cultural and artistic events. 2. Media (1) Establishment of Media facilities such as international broadcasting center or media center. (2) Providing best media services by digitalizing every kind of broadcasts. (3) Using aggressive internet advertisement of game's information, cultural events, tourism, and etc. 3. Sports Event Tourism (1) Providing sports event package tourism. (2) Rehabilitating accomodation and convenience facility at the level of advanced country. (3) Building sports theme complex well international sports heros are taken as theme. (4) Building sports mall well every sports-related businesses can be a solved as one-stop service. 2. Sports technology industry 1) Sports Facility (1) Founding the organization of which mission is to induce long-term fund for building and repairing sports facilities. (2) Acquiring economic benefit by selling the right to call sports facilities after company names. (3) Building all weather and multi-purpose sports facilities and practically using after games. 2) Sports Goods (1) Following consumers' demand for design and colors of goods. (2) Developing marketing strategy by opening sports goods expo. (3) Reinforcing the information network among company groups. (4) Acquiring government support for developing sports goods marketers. (5) Developing new kind of leisure goods.

운동형태의 차이가 Alloxan유발 당뇨쥐의 혈당 및 인슐린 농도에 미치는 영향

윤진환,정일규,김종오,이희혁,지용석,오봉석,채정룡 대한스포츠의학회 2003 대한스포츠의학회지 Vol.21 No.1

The Purpose of this study was to investigate the effect of exercise intensity on blood glucose and insulin levels in diabetic rats with alloxan. Twenty sprague-dawley male rats were assigned to power training groups(n=10) and endurance training groups(n=10). Diabetes was induced by single injection of alloxan(50 mg/kg B.W) Blood glucose and insulin were determined every week for 4-weeks. The conclusion of this study follows as below: 1) There was significantly different on blood glucose levels in two groups. 2) There was significantly different on insulin levels in two groups These results suggest that proper exercise intensity in diabetic rats can significantly decrease blood glucose and insulin level and make good glycemic control. In conclusion, it has been found that regular prolonged endurance training with diabetic rats, improves insulin and blood glucose.