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>

Type 4 수소저장용기 복합재료 부 적층 구조별 구조적 성능 분석

김건우(Gunwoo Kim),김혜원(Hyewon Kim),박한민(Hanmin Park),박규환(Gyuhwan Park),김한상(Hansang Kim) 한국가스학회 2023 한국가스학회 학술대회논문집 Vol.2023 No.11

무향칼만필터기반 State-of-Health 변화 추이 예측을 통한 State-of-Life 추정 알고리즘 연구

김건우(Gunwoo Kim),신승화(Seunghwa Sin),백종복(Jongbok Baek),강모세(Mose Kang),김정희(Jeonghui Kim),김종훈(Jonghoon Kim) 전력전자학회 2020 전력전자학술대회 논문집 Vol.2020 No.11

클라우드 환경에서 스마트 관광지원시스템 설계 및 구현

김건우(GunWoo Kim),김용수(YongSoo Kim),이영석(YongSeok Lee),김영균(YoungGyun Kim),김승훈(SeungHoon Kim) 한국정보과학회 2018 한국정보과학회 학술발표논문집 Vol.2018 No.12

최적화설계를 통한 수소 튜브트레일러용 Type 4 복합재료 압력용기의 구조해석 및 낙하충격해석

김건우(GUNWOO KIM),김채현(CHAEHYUN KIM),최인호,김한상(HANSANG KIM) 한국가스학회 2020 한국가스학회 학술대회논문집 Vol.2020 No.10

Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells

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.

Small RNA sequencing of small extracellular vesicles secreted by umbilical cord mesenchymal stem cells following replicative senescence

Kim Chris Gunwoo,Lee Jae Kyung,Cho Geum-Joon,Shin Ok Sarah,Gim Jeong-An 한국유전학회 2023 Genes & Genomics Vol.45 No.3

Background Umbilical cord mesenchymal stem cells (UCMSC) are subsets of multipotent stem cells involved in immune modulation, tissue regeneration, and antimicrobial defense. Cellular senescence is associated with the onset of aging-related diseases and small extracellular vesicles (sEVs) are important mediators of senescence and aging. Objective However, little is known about the role and function of microRNAs (miRNAs) carried by UCMSC-derived sEVs. To analyze the expression profiles of miRNAs secreted by senescent UCMSC, small RNA sequencing of the miRNAs within the sEVs was performed in this study. Methods UCMSC cultures underwent serial passaging beyond passage number 20 to achieve replicative senescence, which was confirmed by various methods, including increased senescence-associated β-gal staining and cytokine secretion levels. sEVs derived from non-senescent and senescent UCMSC were isolated and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblot analysis. Results Small RNA sequencing of the miRNAs within the sEVs revealed senescence-associated differences in the miRNA composition, as shown by the upregulation of miR-122-5p and miR-146a-5p, and downregulation of miR-125b-5p and miR-29-3p. In addition, total RNA sequencing analysis showed that PENK, ITGA8, and TSIX were upregulated, whereas AKR1B10, UNC13D, and IL21R were downregulated by replicative senescence in UCMSC. In sEVs, upregulated genes were linked to downregulated miRNAs, and vice versa. In the gene-concept network analysis, five gynecologic terms were retrieved. Conclusions The study provides an insight into the cellular characteristics of UCMSC following replicative senescence and emphasizes the importance of monitoring passage numbers of UCMSC for further therapeutic use.

Rethinking Economic Sanctions on North Korea: Explaining the Success of Sanctions on BDA

Gunwoo Kim(김건우) 신아시아연구소(구 신아세아질서연구회) 2019 신아세아 Vol.26 No.2

방코델타아시아(BDA) 제재의 성공 요인은 무엇인가? 2005년 미 재무부는 북한의 불법자금유통과 관련하여 BDA를 제재하였다. 이 사건은 복잡한 국제 정치적 맥락 속에서 진행되었으며, 제재의 성과에 대해서도 의견이 분분하다. 그러나 BDA 제재는 북한의 불법 경제활동 중단에 결정적인 효과를 보였으며, 핵협상 차원에서도 북한의 적극적인 반응을 끌어냈던 중요한 사건이었다. 따라서 본 연구에서는 기존 제재이론들을 중심으로 BDA의 성공 요인을 분석하였다. 먼저, 기존 연구들에서 제시하는 제재의 성공요인들을 1) 환경, 2) 설계, 3) 이행 측면으로 구분하여 정리하고, 이 틀을 바탕으로 BDA 제재가 효과적으로 작동 할 수 있게 만든 요인들을 분석하였다. 그 결과, 미국의 BDA 제재는 환경적 측면에서 제재에 유리한 조건은 아니었지만, 설계와 이행측면에서는 많은 성공 요인들을 갖고 있었다. 미 제재팀들은 북한의 정권과 연결된 경제 네트워크를 파악하여 제재 대상을 구체화 하였다. 또한, 금융영역에만 초점을 맞추어 단기간에 이행함으로써 민간경제부문의 불필요한 피해를 줄일 수 있었다. 그리고 미 재무부의 경제적 영향력과 국제금융체제의 투명성에 기반하여, 다양한 국제경제주체들의 참여를 끌어낼 수 있는 효과적 제재 네트워크를 구성할 수 있었다. 마지막으로, 미국의 제재 발표와 동시에 제재 네트워크가 작동하였으며 북한은 이에 대비할 시간이 없었다. What explains the success of sanctions against Banco Delta Asia (BDA)? In 2005, the US Department of Treasury sanctioned BDA for alleged money laundering related to the North Korean regime. Although the sanctions complicated international relations and had a controversial outcome, it prevented North Korea from illegal economic activities and influenced the Six-Party Talks for solving the Korean peninsula nuclear issue. This research analyzes the BDA case based on current theories of economic sanctions. First, the research designs a framework for analysis by reviewing explanatory factors for the success of sanctions in three aspects: environment, design, and execution. Based on the framework, it analyzes critical factors for the success of the BDA sanctions. Ultimately, the BDA case satisfied several conditions for success in the design and execution of sanctions, while it failed to satisfy success conditions regarding the environment. The sanctions were effective because the US clarified the target by identifying the economic network related to the North Korean leadership and it reduced collateral damage by executing financial sanctions in a short period of time. Furthermore, the US was successful in making individual financial institutions participate in the sanctions by organizing an effective sanctions network based on US economic hegemony and the transparency of the international financial system. Finally, swift execution of sanctions did not allow North Korea to prepare to absorb the impact of the measures which made the mechanism more effective.

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.