Mechanistic insights into differential requirement of receptor dimerization for oncogenic activation of mutant EGFR and its clinical perspective

( Jeonghee Cho ) 생화학분자생물학회(구 한국생화학분자생물학회) 2020 BMB Reports Vol.53 No.3

The epidermal growth factor receptor (EGFR), a member of the ErbB family (EGFR, ErbB2, ErbB3 and ErbB4), plays a crucial role in regulating various cellular responses such as proliferation, differentiation, and survival. As a result, aberrant activation of EGFR, mostly mediated through different classes of genomic alterations occurring within EGFR, is closely associated with the pathogenesis of numerous human cancers including lung adenocarcinoma, glioblastoma, and colorectal cancer. Thus, specific suppression of oncogenic activity of mutant EGFR with its targeted drugs has been routinely used in the clinic as a very effective anti-cancer strategy in treating a subset of tumors driven by such oncogenic EGFR mutants. However, the clinical efficacy of EGFR-targeted therapy does not last long due to several resistance mechanisms that emerge in the patients following the drug treatment. Thus, there is an urgent need for the development of novel therapeutic tactics specifically targeting mutant EGFR with the focus on the unique biological features of various mutant EGFR. Regarding this point, our review specifically emphasizes the recent findings about distinct requirements of receptor dimerization and autophosphorylation, which are critical steps for enzymatic activation of EGFR and signaling cascades, respectively, among wildtype and mutant EGFR and further discuss their clinical significance. In addition, the molecular mechanisms regulating EGFR dimerization and enzymatic activity by a key negative feedback inhibitor Mig6 as well as the clinical use for developing potential novel drugs targeting it are described in this review. [BMB Reports 2020; 53(3): 133-141]

Rhyme of Truce, Training Program for moral psychology in Cyberspace

Cho, JeongHee,Lim, Chan The Institute of Internet 2019 Journal of Advanced Smart Convergence Vol.8 No.1

Rhyme of Truce is an educational program that helps you develop the ability to cope with cyber violence rightly. we aim to produce educational contents that will last a long time in the memory of specially children. By combining the room escape game and Leap motion / VR, the program reflects the user's motion and action in real time. The Keyboard Worrier comes into contact with the user and causes violence, and the user who is attacked by the monster see several negative messages written in red and hears abuses sound. Users enter the virtual space decorated as the cyber world. They can experience cyber-violence indirectly but vividly, and if language violence, which has been overlooked and recognized only as "letters", is executed offline, it will directly wonder if cyber-violence should also be regarded as a means of violence. Users have the opportunity to cope with violence autonomously. When a user is attacked by an in-game monster, there are two ways to choose from. First, fighting against with a keyboard (which is a symbol of language violence) just like a monster. Second, report the abuser to cyber bureau police. Both methods make them to escape the room, but when they get out of the room and return to the home and read the message through the monitor, users can recognize which action was right for.

Rhyme of Truce, Training Program for moral psychology in Cyberspace

JeongHee Cho,Chan Lim 한국인터넷방송통신학회 2019 Journal of Advanced Smart Convergence Vol.8 No.1

Rhyme of Truce is an educational program that helps you develop the ability to cope with cyber violence rightly. we aim to produce educational contents that will last a long time in the memory of specially children. By combining the room escape game and Leap motion / VR, the program reflects the user's motion and action in real time. The Keyboard Worrier comes into contact with the user and causes violence, and the user who is attacked by the monster see several negative messages written in red and hears abuses sound. Users enter the virtual space decorated as the cyber world. They can experience cyber-violence indirectly but vividly, and if language violence, which has been overlooked and recognized only as "letters", is executed offline, it will directly wonder if cyber-violence should also be regarded as a means of violence. Users have the opportunity to cope with violence autonomously. When a user is attacked by an in-game monster, there are two ways to choose from. First, fighting against with a keyboard (which is a symbol of language violence) just like a monster. Second, report the abuser to cyber bureau police. Both methods make them to escape the room, but when they get out of the room and return to the home and read the message through the monitor, users can recognize which action was right for.

Plasma source ion implantations for shallow p+/n junction

Jeonghee Cho,Seunghee Han,Yeonhee Lee,Ok Kyung Kim,Gon-Ho Kim,Young-Woo Kim,Hyuneui Lim,Moojin Suh 한국진공학회 2000 한국진공학회 학술발표회초록집 Vol.- No.-

Autophosphorylation of the carboxyl‐terminal domain is not required for oncogenic transformation by lung‐cancer derived EGFR mutants

Cho, Jeonghee,Kim, Sujin,Du, Jinyan,Meyerson, Matthew Alan R. Liss, Inc 2018 International journal of cancer Vol.143 No.3

<▼1><P>Aberrant activation of cancer‐derived mutants of the epidermal growth factor receptor (EGFR) is closely associated with cancer pathogenesis and is thought to be mediated through multiple tyrosine phosphorylations within the C‐terminal domain. Here, we examined the consequences of the loss of these C‐terminal phosphorylation sites on cellular transformation in the context of lung‐cancer‐derived L858R, exon 19 deletion and exon 20 insertion mutant EGFR. Oncogenic EGFR mutants with substitution of the 10 potential C‐terminal tyrosine autophosphorylation sites for phenylalanine (CYF10) were still able to promote anchorage‐independent growth in soft agar at levels comparable to the parental L858R or exon19 deletion or exon 20 insertion mutants with intact autophosphorylation sites. Furthermore, these CYF10 mutants retained the ability to transform Ba/F3 cells in the absence of IL‐3. Bead‐based phosphorylation and immunoprecipitation analyses demonstrated that key EGFR‐associated proteins—including Grb2 and PLC‐γ—are neither phosphorylated nor bound to CYF10 mutants in transformed cells. Taken together, we conclude that tyrosine phosphorylation is not required for oncogenic activity of lung‐cancer‐derived mutant EGFR, suggesting these mutants can lead to cellular transformation by an alternative mechanism independent of EGFR phosphorylation.</P></▼1><▼2><P><B>What's new?</B></P><P>Mutations in the epidermal growth factor receptor (EGFR) are common cancer‐driving events that result in ligand‐independent receptor activation and autophosphorylation. Whether autophosphorylation of mutant EGFR is required for transformation, however, is unclear. In this study, lung‐cancer‐derived oncogenic mutant EGFRs lacking 10 potential C‐terminal tyrosine autophosphorylation sites were found to retain the ability to transform cells. Transformation occurred in the absence of IL‐3 ligand. The findings indicate that oncogenic EGFR mutants can be activated independently of autophosphorylation, making their mechanisms of activation distinct from wild‐type EGFR. The results provide mechanistic insight for the understanding of mutant EGFR‐mediated cellular transformation.</P></▼2>

Repeated Toxicity of polyhexamethyleneguanidine phophaste in neonatal and adult mice

Jeonghee Cho,Jeong-Ho Hwang,Jeongah Song 환경독성보건학회 2023 한국독성학회 심포지움 및 학술발표회 Vol.2023 No.11

Colorectal adenocarcinoma‐derived EGFR mutants are oncogenic and sensitive to EGFR‐targeted monoclonal antibodies, cetuximab and panitumumab

Kim, Nayoung,Cho, Daseul,Kim, Hyunjin,Kim, Sujin,Cha, Young‐,je,Greulich, Heidi,Bass, Adam,Cho, Hyun‐,Soo,Cho, Jeonghee Alan R. Liss, Inc 2020 International journal of cancer Vol.146 No.8

<P>Somatic mutations of epidermal growth factor receptor (EGFR) occur in ~3% of colorectal cancer (CRC) patients. Here, through systematic functional screening of 21 recurrent EGFR mutations selected from public data sets, we show that 11 colon cancer‐derived EGFR mutants (G63R, E114K, R165Q, R222C, S492R, P596L, K708R, E709K, G719S, G724S and L858R) are oncogenic and able to transform cells in a ligand‐independent manner. We demonstrate that cellular transformation by these mutants requires receptor dimerization. Importantly, the EGF‐induced and constitutive oncogenic potential of these EGFR mutants are inhibited by cetuximab or panitumumab <I>in vivo</I> and <I>in vitro</I>. Taken together, we propose that a subset of EGFR mutations can serve as genomic predictors for response to anti‐EGFR antibodies and that metastatic CRC patients with such mutations may benefit from these drugs as part of the first‐line therapy.</P>

Analysis of Students Use of Multimodal Representations in a Science Formative Assessment (Assessing Pupils' Progress, APP) Task in the UK

Cho, Hye Sook,Nam, Jeonghee Korean Chemical Society 2017 대한화학회지 Vol.61 No.4

The purpose of this study was to examine UK students' use of multimodal representations in science. Students were asked to explain their understandings of the scientific concept and presentation of the multimodal representations in a science Assessing Pupils' Progress (APP) task. Participants of this study were fifty-four Year 7 students taught by the same teacher. Students from one class (27 students) were assigned to the experimental group, and then they received instruction encouraging the using of multimodal representations as evidences to support students' claims. One class (27 students) was assigned to the control group and they received instruction with traditional teaching methods. Both groups performed an APP task for assessment. The samples of APP assessments produced by students both from the experimental and control groups were analyzed using an analysis framework of multimodal representations, embeddedness in evidence and understanding of scientific concepts. Data analysis indicated that the students in the experimental group performed better than that of the control group on embeddedness of multimodal representations in the APP task. In addition, there was a significant difference between the two groups in the evaluation of understand of the scientific concepts.

Outcomes of Completion Lobectomy for Locoregional Recurrence after Sublobar Resection in Patients with Non-small Cell Lung Cancer

Cho Eun Lee,Yun Jeonghee,Jeon Yeong Jeong,이정희,박성용,조종호,김홍관,Choi Yong Soo,김진국,심영목 대한심장혈관흉부외과학회 2024 Journal of Chest Surgery (J Chest Surg) Vol.57 No.2

Background: This retrospective study aimed to determine the treatment patterns and the surgical and oncologic outcomes after completion lobectomy (CL) in patients with locoregionally recurrent stage I non-small cell lung cancer (NSCLC) who previously underwent sublobar resection. Methods: Data from 36 patients who initially underwent sublobar resection for clinical, pathological stage IA NSCLC and experienced locoregional recurrence between 2008 and 2016 were analyzed. Results: Thirty-six (3.6%) of 1,003 patients who underwent sublobar resection for NSCLC experienced locoregional recurrence. The patients’ median age was 66.5 (range, 44–77) years at the initial operation, and 28 (77.8%) patients were men. Six (16.7%) patients underwent segmentectomy and 30 (83.3%) underwent wedge resection as the initial operation. The median follow-up from the initial operation was 56 (range, 9–150) months. Ten (27.8%) patients underwent CL, 22 (61.1%) underwent non-surgical treatments (chemotherapy, radiation, concurrent chemoradiation therapy), and 4 (11.1%) did not receive treatment or were lost to follow-up after recurrence. Patients who underwent CL experienced no significant complications or deaths. The median follow-up time after CL was 64.5 (range, 19–93) months. The 5-year overall survival (OS) and post-recurrence survival (PRS) were higher in the surgical group than in the non-surgical (p<0.001) and no-treatment groups (p<0.001). Conclusion: CL is a technically demanding but safe procedure for locoregionally recurrent stage I NSCLC after sublobar resection. Patients who underwent CL had better OS and PRS than patients who underwent non-surgical treatments or no treatments; however, a larger cohort study and long-term surveillance are necessary.

Role of Knowledge and Risk Tolerance in Emerging Adults’ Financial Planning Behavior

Cho, Soo Hyun,Yeo, JeongHee,Lorna Saboe-Wounded Head 한국소비자정책교육학회 2013 소비자정책교육연구 Vol.9 No.3

본 연구는 미국 내 성인기에 접어드는 세대집단의 위험감수도와 재무지식수준이 재무계획행동에 어떻게 영향을 미치는지를 2009년 금융산업규제기관(FINRA)의 전국재무역량조사를 토대로 분석하였다. 재무지식은 객관적인 지식과 주관적인 지식으로 측정되었으며,재무계획행동은 비상자금 보유여부, 투자계좌 보유여부, 체크계좌 보유여부, 은퇴자금 보유여부, 크레디 리포트 체크여부, 은퇴자금 산출여부를 합한 점수로 측정하였으며 후에 각각의 행동을 따로 분석하였다. 그 결과 위험감수도, 객관적·주관적 재무지식수준은 보편적 재무계획행동에 유의한 영향을 미치는 것으로 나타났다. 구체적으로 위험감수도는 투자행동과, 객관적 지식수준은 은퇴행동과, 주관적 지식수준은 비상자금 소유여부와 관련이 있는 것으로 나타났다. 성인 초기 집단의 재무행동에 관한 국내외 연구가 많지 않은 실정에서 전국적 데이터를 토대로 한 이 연구는 개인의 재무행동 증진을 위한 교육적 정책적 시사점을 가진다는 점에서 의의를 찾을 수 있겠다.