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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>
Hyori Kim,Gahye Kim,Yeonghun Kim,Jiyeon Ha 한국간호과학회 2021 한국간호과학회 학술대회 Vol.2021 No.10
Aim(s): This systematic literature review and meta-analysis was conducted to integrate and analyze intervention studies dealing with the effects of information and communication technology (ICT)-based interventions on the physical mobility of older adults in the community. Method(s): The CENTRAL, MEDLINE, CINAHL, and EMBASE databases were searched for studies published from January 2000 to August 2020. The risk of bias in randomized studies was assessed using the RoB 2 tool for randomized studies. To estimate the effect size, a meta-analysis of the studies was performed using R version 4.0.4. Three researchers independently analyzed the selected literature to identify important themes and findings. Result(s): Seventeen randomized controlled trials were included (1,578 participants), of which 7 were included in the meta-analysis. ICT interventions significantly improved timed up-and-go (TUG) as a physical mobility variable in older adults (effect size: -0.266; 95% CI: -0.474 to -0.058). A sensitivity analysis was performed on 5 studies using exergame interventions, which were also found to be effective in improving TUG (effect size: -0.30, 95% CI: -0.53 to -0.07). The findings of this study confirmed that exergames, telecommunication, e-health, information applications, and robots were used as ICT-based interventions that were effective for improving the physical mobility and in improving cognitive function of older adults. Conclusion(s): It is necessary to develop and apply more diverse ICT-based interventions that will prevent impairments of mobility and encourage older adults to live more independently, with a higher quality of life, based on extensive research on ICT-based interventions.
Kim, Eunjoo,Yoon, Ju Young,Woo, Kyungmi,Kim, Aeri,Kim, Hyori,Lee, Juna 한국간호과학회 2021 한국간호과학회 학술대회 Vol.2021 No.10
Aim(s): This study aims to develop and evaluate the problem-based learning (PBL) simulation program for nursing students. Four times of PBL group sessions were applied before the simulation so that the student participants can pre-learn about simulation context and contents. The simulation program reflected home visiting healthcare programs for vulnerable households by public health centers in Korea. Method(s): The scenario was developed for students to provide comprehensive nursing care for the frail elderly in the community as a home visiting nurse in the public health center. The draft was developed by the researchers and revised after experts’ reviews (3 academic experts and 2 clinical experts). We measured the effect quantitatively and qualitatively. A total of 29 students completed survey questionnaires after the simulations. Additionally, 2 focus group interviews were conducted with 10 students who participated in the program. Verbatim transcripts were analyzed using Giorgi’s phenomenological approach. Result(s): The Simulation Design Scale mean scores were in the order of feedback/guided reflection (4.81 ± 0.40), problem-solving (4.76 ± 0.41), fidelity (4.76 ± 0.46), objectives and information (4.59 ± 0.58) and support (4.48 ± 0.50). The Educational Practices in Simulation Scale mean scores were in the order of active learning (4.78 ± 0.35), collaboration (4.76 ± 0.53), diverse ways of learning (4.71 ± 0.54), and high expectation (4.69 ± 0.56). Three major themes emerged from the interview: immersive learning experiences, enhancing nursing competency, and changes in perspectives on nursing. Conclusion(s): This PBL simulation module was effective to inspire active learning in the student participants. The program was evaluated as a systematic learning process where students could be self-directed learners interacting and collaborating with other colleagues, instructors, and environments. It also provided opportunities to obtain holistic view of nursing, communication skills, and confidence. More diverse PBL simulations need to be developed in nursing education.
Hyori Kim,Sunyoung Park,Hwa Kyoung Lee,정준호 생화학분자생물학회 2013 Experimental and molecular medicine Vol.45 No.9
We present a bispecific antibody that recognizes an antigen and a hapten and can be applied to various biological assays,including immunoblotting and immunoprecipitation. In immunoblot analysis of serum, an anti-C5anti-cotinine bispecific tandem single-chain variable fragment (scFv)-Fc fusion protein and cotinine-conjugated horseradish peroxidase (HRP) generated a clean signal without the high background that was observed in a parallel experiment using HRP-conjugated goat anti-rabbit immunoglobulin G (Fc-specific) antibody. In immunoprecipitation analysis of serum, use of the bispecific tandem scFv-Fc fusion protein and cotinine-crosslinked magnetic beads significantly reduced the amount of protein contaminants compared with a parallel experiment done with protein A agarose beads. In subsequent immunoblot analysis, use of cotinine–HRP as the secondary probe instead of HRP-conjugated goat anti-rabbit IgG (Fc-specific) antibody successfully eliminated the band corresponding to the bispecific tandem scFv-Fc fusion protein.
Kim, Soohyun,Lee, Hyunho,Noh, Jinsung,Lee, Yonghee,Han, Haejun,Yoo, Duck Kyun,Kim, Hyori,Kwon, Sunghoon,Chung, Junho MDPI 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.2
<P>YYB-101 is a humanized rabbit anti-human hepatocyte growth factor (HGF)-neutralizing antibody currently in clinical trial. To test the effect of HGF neutralization with antibody on anti-cancer T cell immunity, we generated surrogate antibodies that are reactive to the mouse homologue of the epitope targeted by YYB-101. First, we immunized a chicken with human HGF and monitored changes in the B cell repertoire by next-generation sequencing (NGS). We then extracted the <I>V<SUB>H</SUB></I> gene repertoire from the NGS data, clustered it into components by sequence homology, and classified the components by the change in the number of unique <I>V<SUB>H</SUB></I> sequences and the frequencies of the <I>V<SUB>H</SUB></I> sequences within each component following immunization. Those changes should accompany the preferential proliferation and somatic hypermutation or gene conversion of B cells encoding HGF-reactive antibodies. One component showed significant increases in the number and frequencies of unique <I>V<SUB>H</SUB></I> sequences and harbored genes encoding antibodies that were reactive to human HGF and competitive with YYB-101 for HGF binding. Some of the antibodies also reacted to mouse HGF. The selected <I>V<SUB>H</SUB></I> sequences shared 98.3% identity and 98.9% amino acid similarity. It is therefore likely that the antibodies encoded by them all react to the epitope targeted by YYB-101.</P>
지역사회 방문간호사의 가정방문 안전관리를 위한 실무교육 요구 분석
김은주(Kim, Eunjoo),김효리(Kim, Hyori) 한국간호교육학회 2023 한국간호교육학회지 Vol.29 No.2
Purpose: This study aimed to identify the concrete educational needs of visiting nurses working in a community health setting in Korea. Methods: We conducted four focus group interviews from October 7 to October 18, 2021. Twenty-five visiting nurses who worked in public health centers were recruited through purposive sampling. A qualitative content analysis was used to analyze the interview data. Results: The demands of educational contents for visiting nurse safety management practical training were: (1) coping with physical and verbal violence, (2) coping with sexual violence, (3) infection control for infectious diseases with a high prevalence in the community, and (4) preventing and coping with animal bites during home visits. In addition, visiting nurses suggested training programs that comprised: (1) case-based learning, (2) short video clips, and (3) recurrent integrated education. Conclusion: Safety management training programs for visiting nurses should be implemented to the extent that they add no burden on their workload and are easily accessible at any time. In addition, training programs should be based on actual cases and be focused on contents that can be applied in home visit situations. A practical safety management training program should be developed based on the educational needs of visiting nurses, as identified through this study.