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>

일반논문 : 예(禮)와 덕(德)

이장희 ( Jang Hee Lee ) 한서대학교 동양고전연구소 2015 동방학 Vol.32 No.-

전통사회에서 예는 사덕(四德)의 하나이며 인간들 사이에 지켜져야 마땅한 규범인 까닭에 예의 “윤리적” 성격이 의심되어본 적은 없었다. 하지만 오늘날 예의 “윤리성”에 대해 그것이 무엇인지 확연히 손에 잡히게 느끼는 사람은 드물 것이다. 예를 윤리적인 것이라고 부르기에는 현대적 감수성으로 쉽게 받아들여지지 않는 요소들이 있는 것이다. 이는 앞서 언급한 계급적이고 가부장적인 요소 이외에도, 단순한 관습성을 넘어선 윤리성을 예의 어디에서 담보할 수 있는지 쉽게 떠오르지 않기 때문이다. 이 글은 예의 ‘윤리적 성격’에 대한 탐구를 기존 연구에 기대어 하고자 한다. 공자의 사상에서 ‘예’의 중요성을 새삼 부각시킨 허버트 핑가레트의 글에서 시작하여 예의 성격을 인(仁)과의 관계를 통해 파악하고자 시도한 뚜웨이밍과 신광래의 글, 그리고 의(義)와의 관계에서 예를 바라본 이명한의 글을 통하여 예의 성격을 고찰할 것이다. 그리고 마지막으로 덕(德)으로서의 예와 규범으로서의 예라는 두 층위에서 예를 검토해봄으로써 예의 ‘윤리적 성격’에 대해 종합적이고 포괄적인 시야를 확보하고자 시도할 것이다. In traditional society there has never been a doubt about the value of li as one of the four virtues as well as the norm people should abide by. However, today there are few people who can clearly understand li``s "ethical validity." We can point to some elements that are not considered desirable in today``s society. In addition to being classiest and patriarchical, it is not easy to think of ethical elements in li that can go beyond simple conventionality. This paper aims to explore the ethical nature of li based on previous studies, namely, Herbert Fingarett``s study on the significance of li in Confucius``s thought, Tu Wei-ming``s exploration of the relation between jen 仁 and li, Kwong- loi Shun``s careful examination on the subject of li``s relation jen, and Myeong-hwan Lee``s understanding of li in terms of the concept of yi 義. Finally, characterizing li as objective norm and subjective virtue as well, I will attempt to gain some comprehensive perspective on the ethical nature of li.

향원(鄕原)은 왜 덕(德)의 적(賊)인가?

이장희(Lee, Jang-Hee) 사회와철학연구회 2012 사회와 철학 Vol.0 No.24

‘향원’은 맹자가 ‘덕의 적’으로 명명된 인물이다. ‘향원’의 어떤 특성이 맹자로 하여금 그처럼 강도 높은 비난을 하게 되었는지를 궁구해 보는 게 이 논문의 목적이다. 선행 연구의 하나로 이혜경은 그 이유를 향원의 ‘위선성’에서 찾았다. 향원이 완벽한 덕성을 갖추지 않은 자임에도 불구하고 군자처럼 굴었던 것이 비난의 표적이라는 것이다. 이혜경은 흥미롭게도 이러한 맹자의 비난이 ‘마음의 윤리’라는 잣대에 기댄 불공정한 비난이라고 비판한다. 완벽한 덕성을 구현했다고 자부하기 힘든 많은 사람들이 그럼에도 불구하고 ‘선’을 이루려고 노력하는 것을 어떤 면에서 더 높이 평가해야 한다는 것이다. 유학의 역사에서 맹자를 위시한 대부분의 주류 유학자들은 ‘마음의 윤리’에 기대어 지나치게 높은 윤리적 기준을 강요한 것이 오히려 ‘위선자’를 양산하게 만들었다는 것이다 본 논문은 맹자 ‘향원장’에 대한 치밀한 분석을 토대로 이혜경의 이와 같은 해석이 잘못되었으며 향원에 대한 맹자 비판의 핵심은 ‘위선성’이 아니라 ‘사이비성’임을 강조할 것이다. 또 이러한 맹자의 비판 근저에 높여 있는 맹자 윤리학의 성격을 ‘덕 윤리학(virtue ethics)’의 시각에서 파악하는 것이 맹자의 향원에 대한 비판을 이해하는 데 중요한 실마리를 제공할 수 있음을 보여주고자 한다. A ‘village honest man’ is called ‘the enemy of virtue’ by Mencius. This paper aims to explore the central features of the village honest man that lead Mencius to criticize him so harshly Lee Hye Kyong has attributed the criticism to the ‘hypocrisy’ of the village honest man. Although he has not perfected his virtues, the village honest man pretends to be an ‘examplary person(君子),’ and that"s the reason Mencius attacked him. Interestingly, Lee does not endorse Mencius"s criticism. She, rather, criticizes Mencius an ordinary person who strive to be virtuous is more likely to be like the village honest man, and hence it is more proper to encourage him or her rather than to devalue him or her. According to Lee, the mainstream Confucianism adopt the ethical standard from the viewpoint of ‘the ethics of mind,’ and this standard is almost beyond attainable for ordinary people. And in turn this lofty standard easily makes one to be a hypocrite. Based on the careful examination of the chapter, ‘the Village Honest Man,’ in the Mencius, this paper will show that Lee"s analysis is mistaken for the core of Mencius"s criticism lies not in ‘hypocrisy’ but in ‘that which seems but is not.’ And it also shows that Mencius"s ethical thought can be best characterized and understood in terms of ‘virtue ethics.’

CO전화반응에 관한 연구

이태진,김장희,김윤갑 嶺南大學校 工業技術硏究所 1989 연구보고 Vol.17 No.2

The experimental rate equation and optinum operating of CO shift reaction over the industrial CuO/ZnO/Al₂O₃catalyst ICI 52-1 was investigated with process variables (temperature, space velocity, and H₂O/CO ratio). The activation energy of the reaction to 150℃~200℃ is 14˚Kcal/mole. Reaction rate model expressions are derived, to allow optimization of reactor design. And this model is shown to fit the experimental results well.

만성정신질환의 욕구에 대한 수요자와 공급자 측면의 비교연구(Ⅰ) : 만성정신질환자의 정신보건 욕구사정 도구 개발 예비 연구 The Development of Needs Assessment Tool for Mental Health of Chronically Mentally Ill(Preliminary Study)

이종국,한은선,안강호,김명식,김장배,손봉희,이주호 용인정신의학연구소 1999 용인정신의학보 Vol.6 No.2

대구보건대학 재학생의 정보화교육 실태에 관한 연구

이재도,이장희 대구보건대학 2000 대구보건대학 論文集 Vol.20 No.-

This paper has analyzed about the computer use, the information use, and the computer information education 870(33.4%) first-year students at Taegu Health College. There was no big distinction between students from different departments in the level of obtaining information and in the ability of using information, but the use of internet (7.67) showed much higher than that of computer(3.38). In the evaluation on the level of softwares used in the computer, the difference between softwares is significantly big, and the softwares for game or entertainment are used the most(8.71). Their ability to use computer(3.06) revealed lower than university students ´ ability(4.39), and their level of using internet does not exceed the level of intermediate(4.08). Whereas the taken credits for computer information education recorded less than the average satisfaction in general, the earned credits between the departments were severe. Especially, public health division relative to non-medical fields showed the lowest(68.00%). For main reasons for not having taken computer information involved lack of time and cost, and more than 70% of the students hoped to take the education if they were free from the above obstacles. With regard to distance information education, more than 81.73% of the students positively responded to its necessity. In conclusion, it is hoped that our students need to be equipped with the fundamental ability to use computer and internet in oprder to actively face with the knowledge-based socity of the 21th century.

부산시 소재 각급 학교에 대한 대기오염도의 비교분석

이현희,정장표,장영환,이무강 慶星大學校 環境問題硏究所 2002 環境硏報 Vol.12 No.1

According to the conclusion of this study, air pollution concentration of Youngdo-gu belong to Seobu educational institution was in the lowest density.(SO_2 : 0.002 ppm, PM-10 : 32 ㎍/㎥, No_2 : 0.016 ppm) and Dongnae-gu belong to Dongnae educational institution was in the highest.(SO_2 : 0.002 ppm, PM-10 : 88㎍/㎥, No_2 : 0.047 ppm) Air pollution level by classification of each educational institution about elementary schools, middle schools, high schools in Busan appeared that the pollution level about all air pollutants appeared high in Dongnae, Dongbu, Bukbu, Haeundae, Nambu, Seobu in due order. Air pollution level by classification of each Gu about elementary schools, middle schools, high schools in Busan appeared that the pollution level of Geumjeong-gu was very high (SO_2 : 0.002 ppm, No_2 : 0.047 ppm, PM-10 : 89 ㎍/㎥) and level of pollution around high school in Busan was the highest. To improve air quality getting worse day by day, steady and systematic control of observing the air quality standards should be continued. The more effective and active method of air quality improvement should be considered.

6시그마 방법론을 활용한 부춤 수명 개선 사례 연구

이장희,이문수 한국기술교육대학교 2006 論文集 Vol.13 No.1

This paper presented a case study of a six sigma application for improving part lifetime. We implemented Guage R&R study, Process Capability Analysis, 4-Step Diagram and Lifetime Estimation based on Accelerated Life Test data according to the DMAIC procedure of six sigma in order to find significant fail modes and their main causes and set up corrective action plans for improving lifetime of part such as motor. Through the use of six sigma methodology, we could systematically improve the lifetime of motor and establish an effective motor's lifetime control system.

Integrated Human-Robot Ergonomics의 일환으로써 TOES/WCS에 의한 로보트의 동작제어개선에 관한 연구

이순요,한장희,김태원 한국경영과학회 1989 한국경영과학회 학술대회논문집 Vol.- No.1

The purpose of this study, as a part of an intergrated human-robot ergonomics, is to improve robot motion control in a teaching and operating expert system / world coordinate system (TOES / WCS) constructed in the previous study. The major contribution of this study reduces the inaccuracy in coordinate reading and the movement time of robots in macro motion control. This study also reduces undesirable teaching time required by using a unit control (UC) and micro unit control (MUC) in micro motion control.

정신분열병 환자의 인지기능 평가

장계호,이철,조희수,이창욱,백인호 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.5

목 적 : 본 연구의 목적은 정신분열병 환자의 인지적 결함을 정상 대조군과 비교하여 평가하고, 환자의 인지적 결함과 다른 임상변인들과의 연관성을 알아보고자 함이다. 방 법 : 총 25명의 환자들과 19명의 정상 대조군이 전산화 신경심리 검사를 완수하였다. 환자들은 양성 및 음성 증상평가척도와 추체외로증상평가척도를 사용한 반구조화된 정신과적 면담을 통하여 평가되었다. 환자의 나이, 성별, 교육수준, 유병기간, 임상아형, 약물투여 상대 및 유전적 소인들에 대해서도 조사하였다. 결 과 : 정신분열병 환자들은 인식력검사, 주의력검사, 표준도형지능검사에서 정상 대조군보다 낮은 수행능력을 보였고 이것은 환자의 성별, 유전적 소인, 추체외로 증상, 양성 및 음성증상, 유병기간과 무관하였다. 정신분열병 환자의 인지적 결함은 주로 이들의 교육수준 및 임상아형과 상관있었다. 결 론 : 정신분열병 환자들 중 일부는 인지적 결함을 보이며, 이러한 결함은 주로 교육수준 및 임상아형과 상관있다고 판단된다. 정신분열병 환자들의 적절한 치료를 위해서는 이들의 인지적 기능에 대한 주의깊은 평가가 필요하다. Objectives : This study was designed to evaluate the cognitive function in schizophrenic pathents. We also examined the correlation of cognitive impairment with other clinical variables. Methods : A total of 25 patients and 19 normal controls completed Vienna Test System, a computerized neuropsychological test. These included Cognitrone test, continuous attention test, standard progressive matrices. We separately assessed the patient group on the Positive and Negative Syndrome Scale(PANSS) and Extrapyramidal Symptom Rating Scale(EPS scale). The other clinical variables included in this study were age, sex, education level, disease duration, clinical subtype, medication state and genetic factor. Results : Schizophrenic patients had poorer performance than normal controls on the tests of cognitrone, continuous attention, and standard progressive matrices, independent of sex, genetic factors, EPS scale scores, PANSS scores, disease duration . The cognitive impairment in schizophrenics was mainly associated with their education levels and clinical subtypes. Conclusion : In light of our results, it seemed that some schizophrenics perform poorly on cognitive tasks, and this poor performance may be associated with education levels and clinical subtypes. The more careful evaluation of cognitive function in schizophrenic patients would be needed for their proper management.