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Preclinical development of a humanized neutralizing antibody targeting HGF
Kim, Hyori,Hong, Sung Hee,Kim, Jung Yong,Kim, In-Chull,Park, Young-Whan,Lee, Song-Jae,Song, Seong-Won,Kim, Jung Ju,Park, Gunwoo,Kim, Tae Min,Kim, Yun-Hee,Park, Jong Bae,Chung, Junho,Kim, In-Hoo Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.3
<P>Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101. To support clinical development, we also evaluated the preclinical pharmacokinetics and toxicokinetics in cynomolgus monkeys, and human and cynomolgus monkey tissue was stained with YYB-101 to test tissue cross-reactivity. We found that YYB-101 inhibited cMET activation <I>in vitro</I> and suppressed tumor growth in the orthotopic mouse model of human glioblastoma. Combination treatment with YYB-101 and temozolomide decreased tumor growth and increased overall survival compared with the effects of either agent alone. Five cancer-related genes (TMEM119, FST, RSPO3, ROS1 and NBL1) were overexpressed in YYB-101-treated mice that showed tumor regrowth. In the tissue cross-reactivity assay, critical cross-reactivity was not observed. The terminal elimination half-life was 21.7 days. Taken together, the <I>in vitro</I> and <I>in vivo</I> data demonstrated the anti-tumor efficacy of YYB-101, which appeared to be mediated by blocking the HGF/cMET interaction. The preclinical pharmacokinetics, toxicokinetics and tissue cross-reactivity data support the clinical development of YYB-101 for advanced cancer.</P>
유한요소법을 이용한 type 4 수소저장용기용 고정 장치의 구조적 안전성 분석에 관한 연구
김건우(GUNWOO KIM),김혜원(HYEWON KIM),박한민(HANMIN PARK),이정호(JEONGHO LEE),유수진(SUJIN YOON),이한수(HANSU LEE),김종열(JOUNGLYUL KIM),이석진(SEOKJIN LEE),유계형(GYEHYOUNG YOO),윤영길(YOUNGGIL YOUN),김한상(HANSANG KIM) 한국수소및신에너지학회 2024 한국수소 및 신에너지학회논문집 Vol.35 No.2
The study involves a finite element analysis to evaluate the structural integrity of the neck mount block for a type 4 hydrogen storage vessel, with the aim of enhancing its strength and rigidity. The existing neck mount block consists of a fixed part and a sliding part, each comprising a body block for load support, a screw part for neck boss fixation, and bolts. To analyze the vulnerabilities of the neck mount block under bolt fastening and load conditions relative to vehicle travel directions, a structural analysis process was developed. Comparative analysis between the enhanced design and the existing model was performed, resulting in improved strength and rigidity. The objective is to provide guidance for the current product development and to offer fundamental data for the design and structural analysis of future development projects.
Yin, Jinlong,Park, Gunwoo,Kim, Tae Hoon,Hong, Jun Hee,Kim, Youn-Jae,Jin, Xiong,Kang, Sangjo,Jung, Ji-Eun,Kim, Jeong-Yub,Yun, Hyeongsun,Lee, Jeong Eun,Kim, Minkyung,Chung, Junho,Kim, Hyunggee,Nakano, I Public Library of Science 2015 PLoS biology Vol.13 No.5
<▼1><P>Epidermal growth factor receptor variant III (EGFRvIII) has been associated with glioma stemness, but the direct molecular mechanism linking the two is largely unknown. Here, we show that EGFRvIII induces the expression and secretion of pigment epithelium-derived factor (PEDF) via activation of signal transducer and activator of transcription 3 (STAT3), thereby promoting self-renewal and tumor progression of glioma stem cells (GSCs). Mechanistically, PEDF sustained GSC self-renewal by Notch1 cleavage, and the generated intracellular domain of Notch1 (NICD) induced the expression of Sox2 through interaction with its promoter region. Furthermore, a subpopulation with high levels of PEDF was capable of infiltration along corpus callosum. Inhibition of PEDF diminished GSC self-renewal and increased survival of orthotopic tumor-bearing mice. Together, these data indicate the novel role of PEDF as a key regulator of GSC and suggest clinical implications.</P></▼1><▼2><P>A permanently activated mutant form of the epidermal growth factor receptor found in glioblastoma promotes self-renewal and tumor progression by inducing autocrine signalling via pigment epithelium-derived factor (PEDF).</P></▼2><▼3><P><B>Author Summary</B></P><P>Malignant gliomas are among the most lethal types of cancer, due in part to the stem-cell-like characteristics and invasive properties of the brain tumor cells. However, little is known about the underlying molecular mechanisms that govern such processes. Here, we identify pigment epithelium-derived factor (PEDF) as a critical factor controlling stemness and tumor progression in glioma stem cells. We found that PEDF is secreted from glioblastoma expressing EGFRvIII, a frequently occurring mutation in primary glioblastoma that yields a permanently activated epidermal growth factor receptor. We delineate an EGFRvIII-STAT3-PEDF signaling axis as a signature profile of highly malignant gliomas, which promotes self-renewal of glioma stem cells. Our results demonstrate a previously unprecedented function of PEDF and implicate potential therapeutic approaches against malignant gliomas.</P></▼3>
THE BASKET NUMBERS OF LINKS OF 6 CROSSINGS OR LESS
KIM, DONGSEOK,KIM, GUNWOO,LEE, MINWOO,PARK, SUNG-HAN,SON, DONGBUM,BAE, CHEOLMIN The Youngnam Mathematical Society 2016 East Asian mathematical journal Vol.32 No.1
In present article, we find a complete classification theorem of links of basket numbers 2 or less. As an application, we study the basket numbers of links of 6 crossings or less.
Design Research: Transforming Urban Landscape
Kim, Gunwoo(김건우),Mugavin, Damien(무가빈 다미엔) 한국도시설계학회 2013 도시설계 : 한국도시설계학회지 Vol.14 No.4
본 논문은 서울시 관악구 도림천 수계영역 안에 잠재적으로 살기좋은 도시경관 회복을 보고한 디자인 연구이다. 변형되는 도시경관 구조체계는 랜드스케이프 어바니즘과 ‘변형되는 경계’ 이론을 통하여 현재의 지역프로그램들이 변화되어 새로운 이용과 다양한 도시 프로그램들이 가능하게 실험되었다: 경관은 지속적으로 변화하는 과정이다. 중요한 부분은 녹색 인프라와 장기적인계획하에서의 계획적 이동인 역동적 맵핑이다. 계획적 이동의 배열형태와 방향은 현재의 토지이용 배치를 반영하여 보다 최적화 되고, 논리정연한 배치가 개념적으로 이루어 졌다. 비록 열린 개념과 지속적인 과정이 중요한 결론으로 남아있다 하더라도, 특정지역 네 곳의 대상지 설계 또한 탐구되었다. This paper reports a design experiment that potentially reinstates livable urban landscapes within the catchment area of Dorim Stream, Gwanak-Gu, Seoul, South Korea. A framework for transforming urban landscape is examined by applying landscape urbanism values and the ‘transforming border’ ideology to allow existing programs within neighborhoods to be changed to facilitate new uses and diverse urban programs: landscape as a continuous process. The emphasis is on green infrastructure and dynamic mapping of the programmatic shift over extended time-periods. The configuration and direction of programmatic shift is a direct response to the current disposition of land uses, so that a more optimal and coherent layout might conceptually be achieved. Four specific site designs are also explored although emphasis remains on results that are open-ended and an ongoing process.