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>

사례연구 : 가업승계와 가족기업의 경쟁력: 에스엘 사례

이장우 ( Jang Woo Lee ),마윤주 ( Yoon Joo Ma ),정수철 ( Su Chul Jung ) 한국중소기업학회 2010 中小企業硏究 Vol.32 No.4

본 연구의 목적은 가족기업의 핵심역량 축적과정을 살펴보고 성공적인 가업승계의 중요성을 논의하는 것이다. 이를 위해 가족기업의 경쟁우위를 설명한 Miller and Le Breton-Miller (2005)의 4C(Continuity, Community, Connection, Command)모델을 기반으로 3대에 걸친 성공적인 가업승계를 기반으로 한 에스엘의 핵심역량 축적과정을 조사했다. 국내 자동차부품회사인 에스엘의 성장과정에 관한 2차 자료를 분석하고, 대표이사와의 심층인터뷰를 통해 그 연관성을 구체적으로 살펴보았다. 분석결과 창업자 가족이 공유한 가치관과 비전, 노하우, 경험 등은 장기적인 지향성을 가지고 지속적으로 핵심역량을 개발하는데 큰 역할을 하였다. 또한 신뢰의 가치관이라는 사회적 자본을 효과적으로 전달받은, 다음 세대의 후계자는 가족 가치관을 토대로 대외 네트워크를 더욱 견고히 하고 지속적으로 발전시켰다. 에스엘은 성공적인 가업승계로 소유와 지배구조를 집중화 할 수 있었고, 이에 따라 외부 이해관계자들의 압력 없이, 가족 내부 조화를 통해 독립적이고 과감한 의사결정이 가능하였다. 이는 가족기업의 경우 고유한 공동체적 문화와 신뢰에 기반 한 외부 네트워크 형성을 통해 경쟁력 구축에 힘쓸 필요가 있으며, 일반기업의 경우에도 공동체 적 조직문화와 중장기적 관점의 외부 협력관계가 기업의 영속성 유지에 중요하다는 시사점을 제공한다. 또한 가엽승계가 기업경쟁력의 유지와 세대 간 이전에 중요한 기능을 함에 따라 이에 대한 적절한 정책적 배려가 필요하다. The purpose of this study is to examine the process of accumulating com-petences and competitiveness by family companies, and discuss the importance of successful succession of a family business. The core competence accumulation process and competitiveness sources of SL, which is based on successful succession of the family business for three generations, was examined based on the 4C (Continuity, Community, Connection, Command) model of Miller and Le Breton-Miller (2005), which explains the competitive superiority of family companies. Secondary data on the growth process of SL, a domestic auto-mobile parts company, was analyzed and their strategic implications were examined in detail through an in-depth interview with the CEO. The 4C factors, which are antecedent variables of a successful family business, played an important role on the growth process of SL. The continuity factor existed through continuous research and development that focuses on and invests in improving technology quality such as mold pro-duction, lamp production, sash production, and design automation. 2 to 3 percent of the sales amount each year was spent on research and development, regardless of the condition of the economy. As a result, the intellectual property of the company reached 1,108 items (583 applications, 440 registered properties, 47 in review, 38 trademarks) by 2006. From a long-term perspective, the company is improving their technical power to an international standard through technical investments. The continuity of investments in research and development is apparent through three generations, and it can be said that this reflects the characteristics of family business management that shares a goal, and confirms and develops the core capacities of the company. The factor of community started with the "people first" business, management philosophy of the late presi-dent, Hae-joon Lee. Then, it expanded to "human respect" during the president Choong-kon Lee`s generation, and to "ethical management" for the CEO Sung-yup Lee`s generation. The sense of community was revealed to be in the form of a community corporate culture based on a good welfare system for employees and com-munity awareness. Diverse benefits including a housing support system, housing fund support system, child-ren`s education fee support system, scholarship system, and company clubs support system were used to make people feel like "the company and I are one" and work with a sense of ownership. The fact that there has not been one conflict between labor and management since 1968, when the labor union was first established, is especially a noteworthy point. The business management based on "people first" stresses the responsibility and roles of employees and reflects the belief that a workplace should not simply be a place to make a living, but a part of life where you can cultivate character and fulfill your role as a member of society. The connection factor appears as continuous partnerships and networks with domestic and international parts suppliers and technologically advanced companies. The late honorary chairman Hae-joon Lee maintained partnerships and networks with Hyundai Motor Company and Daewoo Motors. Then, chairman Choong-kon Lee expanded the network to include KIA and Ssangyong Motors and maintained long-term relationships with domestic automobile makers. In addition, the company is maintaining cooperative relations with the Japanese company Stanley and German company Hella, and has started dealing with the U.S. company GM, too. CEO Sung-yup Lee`s generation improved the company`s relationship with GM and made the achievement of re-ceiving the QSTP Award (an award GM gives to selected skilled companies out of all the parts companies in the world) from GM for 14 consecutive years (1997-2010), solidifying its position as a skilled partner of GM. SL is also advancing into China through collaborations with the local branch to extract new cooperative relations. The value of "trust" is the motivation that helped SL maintain and strengthen relationships and networks. This value started with the founder of the company and was handed down to chairman Choon-kon Lee and CEO Sung-yup Lee, and worked as a core factor to strengthen external cooperative relationships. The factor of command is apparent from the decisions of business managers who take on a challenge, structural management that includes an endless will for innovation, and leadership. When the late honorary chairman Hae-joon Lee could not cultivate a road for the automobile parts industry because of smuggled goods, he recognized the importance of the automobile parts industry and folded his bicycle parts business, which was number one in the market at the time, without hesitation thanks to his owner-focused independent and bold decision-making skills. In the mid-1990s, when most automobile production companies experienced difficulties because of the economic crisis where Korea was dependent on the IMF, and the aftershocks of restructuring affected automobile parts manufacturing companies, chairman Choong-kon Lee considered the crisis an opportunity and acquired and merged with Seogu Industry (currently known as SL Litech), Oriental Construction and Poongi Building (currently known as SL Seo Bong Co., Ltd. Shiheung factory), creating a turning point to develop further after the crisis. CEO Sung-yup Lee pursues continuous innovation including a corporate culture that places importance on learning and admitting mistakes, change of the structural system to a project based system, and a human resources system that focuses on human resources management, and is emphasizing corporate changes according to the situation of the times. An examination of the SL core competence accumulation process based on the 4C model shows that it is establishing positive relationships and continuity based on connection and trust, leading to a cooperation sys-tem based on the value of trust. It also establishes a positive relationship with command focusing on a com-munity structure culture, which leads to structure capacity based on community culture. The factors of con-nection and community were found to be especially strong at SL. The factor of connection was a core growth motivation, influenced by the key values of family. SL reveals its growth motivation to be "unification of all employees," shares the goals and visions of family with its employees, and offers a variety of different benefits. The active will of employees to participate in this community is seen to be the background behind big accomplishments such as innovations in the field, which are still being pursued. Successful succession of the family company and family business management are strengths that lie in the center of the motivation that allowed SL to continue to grow for three generations, starting with the founder, the late honorary chairman Hae-joon Lee, who provided a foundation of growth with values of trust and peo-ple first, moving on to the second generation chairman Choong-kon Lee, who accomplished a rapid development of the company based on technological developments and respect for people, and finally through to the third generation CEO Sung-yup Lee, who is making efforts for globalization and innovation based on ethical management and change. This shows that the values of trust set by the founder have continued on for a long time, through his son, chairman Choong-kon Lee, and grandson, CEO Sung-yup Lee. Chairman Lee, CEO Lee and executive director Lee Seung-hoon are learning corporate culture and management know-how through a great will to participate and actual participation in management. SL was able to gain competitiveness and continuously reach excellent management performance through cooperation based on the value of trust and structural management that focuses on community culture. As a result of analyzing the company through the 4C model and conducting in-depth interviews with man-agement, it can be said that the values, vision, know-how and experience the founder shared with his family largely contributed to continuous development of core competence with a long-term goal. This in turn had a positive effect on establishment of a corporate community based on trust. By inducing loyalty, participation, and focus on employees in the organizational structure with something more than just financial incentives, the core values of the company are relayed through generations and play an important role in maintaining the community, and also emotionally motivating members of the community. Another point is that the successor who effectively received the social capital of trust as a value, strengthened and continued to develop the ex-ternal network based on the family values. The value of "trust" started by the founder played a key role in strengthening external cooperative relations as it was succeeded through generations. This had a positive ef-fect on connection based on the value of trust, and especially decisively contributed to maintaining close rela-tions of cooperation in the external network and long-term cooperative relationships. SL was able to focus the possession and domination structure through successful succession of the family business, and make in-dependent bold decisions through internal harmony of the family, without pressure from people involved externally. The results above lead to the following points of discussion regarding corporate management. From a busi-ness management perspective, first, a family company needs to establish an external network based on a unique community culture and trust to work on establishing competitiveness. Second, there is a need to reflect the fact that a community-like structural culture and external cooperative relations from a mid- to 0long-term perspective have an important effect on maintenance of corporate continuity, even for companies that are not family businesses, on business management. Third, there is a need to focus on the fact that a structural man-agement method that uses values such as community help secure continuity of a company. From a policy per-spective, since succession of a family business can be not succession of wealth but succession of accumulated technological core competence and good management philosophy and know-how, it is important for improve-ing national competitiveness, to maintain corporate competitiveness, and transfer the competitiveness between generations. Therefore, there is a need for appropriate policies that support the successful transgenerational succession of family businesses.

화야산(경기도 가평군)의 거미상

김주필(Joo Pil Kim),최한석(Han Seak Choi),이형민(Hyung Min Lee),이형진(Hyung Jeen Lee),이태후(Tae Hoo Lee),심주영(Ju Young Sim),조윤규(Yoon Kyu Jo),조원규(Won Kyu Jo),이준이(Joon Lee Lee) 한국거미연구소 2018 한국거미 Vol.34 No.2

2018년 10월 13일부터 14일까지 경기도 가평군 소재 화야산을 주야로 한국거미연구회 회원 13명(김주필, 최한석, 이형민, 이형진, 심주영, 이태후, 조윤규, 조원규, 이준이, 이현동, 윤혜원, 이광섭, 김형주)이 채집한 결과 18과 41속 48종이 채집되어 이에 보고 발표하는 바이다. From October 13 to 14 in 2018. Koran Arachnological Study members investigated the Spiders in the whole area Gyeonggi-do Gapyeong-gun, and reported 18 Families 41 Genus 48 Species of spiders. The collected spiders are placed (stored) in the Joo-Pil Spider museum.

검단산(경기도 하남시)의 거미상

김주필(Joo Pil Kim),최한석(Han Seak Choi),이형민(Hyung Min Lee),이형진(Hyung Jeen Lee),이태후(Tae Hoo Lee),심주영(Ju Young Sim),조윤규(Yoon Kyu Jo),조원규(Won Kyu Jo),이준이(Joon Lee Lee) 한국거미연구소 2018 한국거미 Vol.34 No.2

2018년 10월 2일부터 3일까지 경기도 하남시 소재 검단산을 주야로 한국거미연구회 회원 13명(김주필, 최한석, 이형민, 이형진, 심주영, 이태후, 조윤규, 조원규, 이준이, 이현동, 윤혜원, 이광섭, 김형주)이 채집한 결과 22과 43속 56종이 채집되어 이에 보고 발표하는 바이다. From October 2 to 3 in 2018. Koran Arachnological Study members investigated the Spiders in the whole area Gyeonggi-do Hanam-si, and reported 22 Families, 43 Genus 56 Species of spiders. The collected spiders are placed (stored) in the Joo-Pil Spider museum.

GO-62 : Lower extremity edema in patients with endometrial cancer

( Myong Cheol Lim ),( Jeong Seon Lee ),( Jung Nam Joo ),( Sang Soo Seo ),( Sok Bom Kang ),( Sang Yoon Park ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.99 No.-

The objective of this study was to investigate clinical manifestations of lower extremity edema (LEE) in endometrial cancer Medical records for LEE and/or responses to the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) were evaluated in 177 patients with endometrial cancer Patients had a median age of 53 years. Sixty-seven patients (37.9%) had past (9 patients, 13.4%) and/or current patient-reported LEE (58 patients, 86.6%). Symptoms reported on the GCLQ in over 20% of respondents were swelling, numbness, aching , and heaviness. GCLQ total symptoms score was significantly higher in patients with current LEE. Most of the LEE (43/67, 64.2%) developed within 12 months after surgery and LEE lasted more than 6 months in most patients (56/59, 94.9%) Prospective clinical trials are needed to know the clinical significance, impact on quality of life, and preventive strategy of LEE in patients with endometrial cancer

폐내 기관지 낭종

이석열,이숭진,박형주,이철세,이길노,김윤정,나주옥 순천향의학연구소;Soonchunhyang Medical Research Institute 2004 Journal of Soonchunhyang Medical Science Vol.10 No.2

A 33-year-old female was admitted to our hospital due to removal of lung mass which indicentally detected Chest radiography. Chest computerized tomography revealed lung parenchymal cystic lesion. Open thoracotomy was done for diagnosis and therapy. Cystic lesion was communicated to bronchus and wedge resection including cystic lesion was done. Bronchogenic cyst is congenital disease and mainly locate in mediastinum. It is rare in lung parenchyme. Herein we report a case of intrapulmonary bronchogenic cyst.

울릉도(경상북도 울릉군)의 거미상

김주필(Joo Pil Kim),최한석(Han Seak Choi),김대희(Dae Hee Kim),지승환(Seung Hwan Ji),이형민(Hyung Min Lee),변진관(Jean Koan Byun),이형진(Hyung Jeen Lee),조형진(Hyung Jeen Jo),한정혁(Jung Huk Han),이태후(Tae Hoo Lee),조윤규(Yoon Kyu Jo 한국거미연구소 2018 한국거미 Vol.34 No.2

2018년 7월 26일부터 28일까지 울릉도 나리분지, 독도 지역을 주야로 한국거미연구회 회원 17명(김주필, 최한석, 김대희, 지승환, 이형민, 변진관, 조형진, 이형진, 이태후, 한정혁, 조윤규, 조원규, 이현동, 이윤정, 조용하, 윤혜원, 이용화)이 채집한 결과 20과 43속 60종이 채집되어 이에 보고 발표하는 바이다. From July 26 to 28 in 2018. Koran Arachnological Study members investigated the Spiders in the Ulleung Island (Gyeongsangbuk-do, Ulleung-gun), and reported 20 Families, 43 Genus 60 Species of spiders. The collected spiders are placed (stored) in the Joo-Pil Spider museum.

독도(경상북도 울릉군)의 거미상

김주필(Joo Pil Kim),최한석(Han Seak Choi),지승환(Seung Hwan Ji),김대희(Dae Hee Kim),변진관(Jean Koan Byun),이형민(Hyung Min Lee),조형진(Hyung Jeen Jo),이형진(Hyung Jeen Lee),이태후(Tae Hoo Lee),한정혁(Jung Huk Han),조윤규(Yoon Kyu Jo 한국거미연구소 2018 한국거미 Vol.34 No.2

2018년 7월 27일부터 독도 지역을 한국거미연구회 회원 17명(김주필, 최한석, 김대희, 지승환, 이형민, 변진관, 조형진, 이형진, 이태후, 한정혁, 조윤규, 조원규, 이현동, 이윤정, 조용하, 윤혜원, 이용화)이 채집한 결과 7과 9속 12종이 채집되어 이에 보고 발표하는 바이다. 2018 July 27th, Koran Arachnological Study members investigated the Spiders in the whole area Dok Island (Gyeongsangbuk-do, Ulleung-gun), and reported 7 Families, 9 Genus 12 Species of spiders. The collected spiders are placed (stored) in the Joo-Pil Spider museum.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

하악골 골절 정복술후 악간 고정을 시행하지 않은 치험례

이윤주,이장근 충남대학교 의과대학 지역사회의학연구소 1994 충남의대잡지 Vol.21 No.2

We studied about 106 cases of mandible fracture patients from May. 1990 to April. 1994, who had treated at chungnam national university plastic surgery department. They are divided into two groups by treatment methods which are compared by, with intermaxillary fixation(IMF) vs. without IMF. There was no statistically significant difference in the complications between the two groups. Rigid internal fixation(RIF) without intermaxillary fixation(IMF) generally results in greater patient satisfaction because of decreased postoperative discomfort, earlier return to normal jaw function, easier maintenance of oral hygiene, and better nutrition. So, we concluded that RIF without IMF was considerable method for indicated patients. Indication( by authors' experiences) : 1. simple fractures without severe displacement 2. favorable fractures 3. no problem about occlusion 4. well cooperative patients