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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon kim Deok ryong kim Department of Biochemistry and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea Department of Anatomy and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

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Ethanolic extract of dandelion(Taraxacum mongolicum) induces estrogenic activity in MCF-7 cells and immature rats

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Chinese Journal of Natural Medicines 2015年第11期13卷 808-814页

作者： Seung Min Oh ha ryong kim Yong Joo Park Yong Hwa Lee Kyu Hyuck Chung Fusion Technology Laboratory Hoseo University School of Pharmacy Sungkyunkwan University

Plants of the genus Taraxacum, commonly known as dandelions, are used to treat breast cancer in traditional folk medicine. However, their use has mainly been based on empirical findings without sufficient scientific evidence. Therefore, we hypothesized that dandelions would behave as a Selective estrogen receptor modulator(SERM) and be effective as hormone replacement therapy(HRT) in the postmenopausal women. In the present study, in vitro assay systems, including cell proliferation assay, reporter gene assay, and RT-PCR to evaluate the m RNA expression of estrogen-related genes(p S2 and progesterone receptor, PR), were performed in human breast cancer cells. Dandelion ethanol extract(DEE) significantly increased cell proliferation and estrogen response element(ERE)-driven luciferase activity. DEE significantly induced the expression of estrogen related genes such as p S2 and PR, which was inhibited by tamoxifen at 1 μmol·L-1. These results indicated that DEE could induce estrogenic activities mediated by a classical estrogen receptor pathway. In addition, immature rat uterotrophic assay was carried out to identify estrogenic activity of DEE in vivo. The lowest concentration of DEE slightly increased the uterine wet weight, but there was no significant effect with the highest concentration of DEE. The results demonstrate the potential estrogenic activities of DEE, providing scientific evidence supporting their use in traditional medicine.

关键词：药理学药物性质生化化学

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Enriching Middle School Students’Learning Through Digital Storytelling:A Multimodal Analytical Framework

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ECNU Review of Education 2024年第2期7卷 357-383页

作者： Deoksoon kim Ho-ryong Park Oksana Vorobel Boston College Lynch School of Education-Teaching Curriculumand SocietyI40 Commonwealth AvenueChestnut HillMassachusetts 02467-3800US Murray State University City University of New York

Purpose This study investigates middle school students’learning experiences through digital storytelling,applying a multimodal analytical framework to uncover patterns in digital *** study explores how participants engage in pedagogical activities,reflect on their learning experiences,and articulate their voices through digital ***/Approach/Methods Employing qualitative case study methods,we purposefully selected three 12-year-old female students at an urban school in the northern *** of digital stories and other data sources(interviews,classroom observations,and reflective journals)show that the students were engaged in both teaching and *** The findings describe(1)participants and their learning experiences,(2)students’representational and interpersonal constructs as used in their digital stories,and(3)their participation as teachers as well as ***/Value Our multimodal analytical framework illuminates how students express themselves through digital *** discussion focuses on students’learning,their identity development,the effectiveness of the analytical framework,and pedagogical implications.

关键词： Analytical framework digital stories identity middle school students multimodality

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A pipeline to characterize p53 effectors by integrative cistrome and transcriptome analysis in a genetically-defined organoid model

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Genes & Diseases 2024年第2期11卷 512-515页

作者： June-ha Shin Hwa-Ryeon kim Jae-Seok Roe Department of Biochemistry College of Life Science and BiotechnologyYonsei UniversitySeoul 120-749Republic of Korea

Tumor-protein 53(p53)is a transcription factor(TF)encoded by TP53(Trp53 in mice)and is a master regulator of tumor-suppressive programs'.Importantly,TP53 is the most frequently mutated gene in human cancer,and its loss of function contributes to tumor development,exemplified by variable p53 mutations detected in 50%-75%of pancreatic cancers.2 From these perceptions,a number of targets transcribed by p53 that confer tumor suppression have been ***,our understanding of how p53 prevents normal cells from initiating tumorigenesis is still *** complement this limitation,herein,we established a new approach to identify underlying effectors transcribed by p53 in normal physiology.

关键词： incomplete initiating herein

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Nanoparticle Exsolution on Perovskite Oxides:Insights into Mechanism,Characteristics and Novel Strategies

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Nano-Micro Letters 2024年第2期16卷 312-346页

作者： Yo han kim Hyeongwon Jeong Bo‑Ram Won Hyejin Jeon Chan‑ho Park Dayoung Park Yeeun kim Somi Lee Jae‑ha Myung Department of Materials Science and Engineering Incheon National UniversityIncheon 22012Republic of Korea

Supported nanoparticles have attracted considerable attention as a promising catalyst for achieving unique properties in numerous applications,including fuel cells,chemical conversion,and *** demonstrate high activity by expanding the number of active sites,but they also intensify deactivation issues,such as agglomeration and poisoning,*** for bottomup synthesis of supported nanoparticles has emerged as a breakthrough technique to overcome limitations associated with conventional *** are uniformly exsolved from perovskite oxide supports and socketed into the oxide support by a one-step reduction *** uniformity and stability,resulting from the socketed structure,play a crucial role in the development of novel ***,tremendous research efforts have been dedicated to further controlling exsolution *** effectively address exsolution at a more precise level,understanding the underlying mechanism is *** review presents a comprehensive overview of the exsolution mechanism,with a focus on its driving force,processes,properties,and synergetic strategies,as well as new pathways for optimizing nanocatalysts in diverse applications.

关键词： Supported nanoparticle Exsolution In situ growth Mechanism Perovskite oxide Catalyst

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Effect of Meteorological Data Assimilation on Regional Air Quality Forecasts over the Korean Peninsula

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Journal of Meteorological Research 2024年第2期38卷 262-284页

作者： Yunjae CHO Hyun Mee kim Eun-Gyeong YANG Yonghee LEE Jae-Bum LEE Soyoung ha Department of Atmospheric Sciences Yonsei UniversitySeoul 03722Republic of Korea Air Quality Forecasting Center National Institute of Environmental ResearchIncheon 22689Republic of Korea National Center for Atmospheric Research BoulderCO 80305USA University of Maryland Baltimore County BaltimoreMD 21250USA Global Modeling and Assimilation Office NASA Goddard Space Flight CenterGreenbeltMD 20771USA

The Weather Research and Forecasting model coupled with Chemistry(WRF-Chem),a type of online coupled chemistry-meteorology model(CCMM),considers the interaction between air quality and meteorology to improve air quality *** data assimilation(DA)can be used to reduce uncertainty in meteorological field,which is one factor causing prediction uncertainty in the *** this study,WRF-Chem and three-dimensional variational DA were used to examine the impact of meteorological DA on air quality and meteorological forecasts over the Korean *** nesting model domains were configured over East Asia(outer domain)and the Korean Peninsula(inner domain).Three experiments were conducted by using different DA domains to determine the optimal model domain for the meteorological *** the meteorological DA was performed in the outer domain or both the outer and inner domains,the root-mean-square error(RMSE),bias of the predicted particulate matter(PM)concentrations,and the RMSE of predicted meteorological variables against the observations were smaller than those in the experiment where the meteorological DA was performed only in the inner *** indicates that the improvement of the synoptic meteorological fields by DA in the outer domain enhanced the meteorological initial and boundary conditions for the inner domain,subsequently improving air quality and meteorological *** to the experiment without meteorological DA,the RMSE and bias of the meteorological and PM variables were smaller in the experiments with *** effect of meteorological DA on the improvement of PM predictions lasted for approximately 58-66 h,depending on the ***,the uncertainty reduction in the meteorological initial condition by the meteorological DA contributed to a reduction of the forecast errors of both meteorology and air quality.

关键词： meteorological data assimilation regional air quality forecast particulate matter concentration optimal model domain forecast error WRF-Chem

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Body-Shaping Membrane to Regenerate Breast Fat by Elastic Structural Holding

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Research 2024年第1期2023卷 165-180页

作者： Hye-Seon kim Jeongeun Park Hyun-Su ha Sewoom Baek Chan Hee Lee Kyubae Lee Suji Park Jueun kim Se Won Yi hak-Joon Sung Department of Medical Engineering Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoul 03722Republic of Korea TMD LAB Co.Ltd. 6th Floor31Gwangnaru-ro 8-gilSeongdong-guSeoul 04799Republic of Korea

Tissue regeneration requires structural holding and movement support using tissue-type-specific aids such as bone casts,skin bandages,and joint ***,an unmet need exists in aiding breast fat regeneration as the breast moves following continuous body motion by exposing the breast fat to dynamic ***,the concept of elastic structural holding is applied to develop a shape-fitting moldable membrane for breast fat regeneration(“adipoconductive”)after surgical defects are *** membrane has the following key characteristics:(a)It contains a panel of honeycomb structures,thereby efficiently handling motion stress through the entire membrane;(b)a strut is added into each honeycomb in a direction perpendicular to gravity,thereby suppressing the deformation and stress concentration upon lying and standing;and(c)thermo-responsive moldable elastomers are used to support structural holding by suppressing large deviations of movement that occur *** elastomer became moldable upon a temperature shift above T_(m).The structure can then be fixed as the temperature *** a result,the membrane promotes adipogenesis by activating mechanotransduction in a fat miniature model with pre-adipocyte spheroids under continuous shaking in vitro and in a subcutaneous implant placed on the motion-prone back areas of rodents in vivo.

关键词： thereby shaking Elastic

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Etanercept-synthesizing adipose-derived stem cell secretome:A promising therapeutic option for inflammatory bowel disease

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 882-892页

作者： Say-June kim Ok-Hee kim ha-Eun Hong Ji Hyeon Ju Do Sang Lee Department of Surgery Seoul St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Catholic Central Laboratory of Surgery Institute of Biomedical IndustryCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Division of Rheumatology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BACKGROUND Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract,with tumor necrosis factor(TNF)-αplaying a key role in its ***,a decoy receptor for TNF,is used to treat inflammatory *** secretome derived from adipose-derived stem cells(ASCs)has anti-inflammatory effects,making it a promising therapeutic option for *** To investigate the anti-inflammatory effects of the secretome obtained from ASCs synthesizing etanercept on colon cells and in a dextran sulfate sodium(DSS)-induced IBD mouse *** ASCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing *** secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a DSS-induced IBD mouse *** This study revealed promising results indicating that the group treated with the secretome derived from etanercept-synthesizing ASCs[Etanercept-Secretome(Et-Sec)group]had significantly lower expression levels of inflammatory mediators,such as interleukin-6,Monocyte Chemoattractant Protein-1,and TNF-α,when compared to the control secretome(Ct-Sec).Moreover,the Et-Sec group exhibited a marked therapeutic effect in terms of preserving the architecture of intestinal tissue compared to the *** These results suggest that the secretome derived from ASCs that synthesize etanercept has potential as a therapeutic agent for the treatment of IBD,potentially enhancing treatment efficacy by merging the anti-inflam-matory qualities of the ASC secretome with etanercept's targeted approach to better address the multifaceted pathophysiology of IBD.

关键词： Adipose-derived stem cells Etanercept Inflammatory bowel disease Secretome Tumor necrosis factor-α

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Malignant triton tumor in the abdominal wall:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1467-1473页

作者： Ho Jik Yang Donghyun kim Won Suk Lee Sang-ha Oh Department of Plastic and Reconstructive Surgery Chungnam National University Sejong HospitalSejong 30099South Korea Department of Plastic and Reconstructive Surgery Chungnam National University HospitalDaejeon 35015South Korea Department of Emergency Eulji University HospitalDaejeon 35233South Korea Department of Plastic and Reconstructive Surgery Chungnam National University College of MedicineDaejeon 35015South Korea

BACKGROUND Malignant triton tumors(MTTs)comprise a subgroup of malignant peripheral nerve sheath tumors(MPNSTs)that exhibits rhabdomyosarcomatous differen-tiation and follow an aggressive *** are primarily located along peripheral *** of MTTs in the abdominal wall have not been *** has a poorer prognosis than classic MPNSTs,and accurate diagnosis necessitates a keen understanding of the clinical history and knowledge of its differential diagnosis *** for MTTs mirrors that for MPNSTs and is predominantly *** SUMMARY A 49-year-old woman presented with a subcutaneous mass in her lower abdo-minal wall and a pre-existing surgical scar that had grown slowly over 3-4 months before the *** had previously undergone radical hysterectomy and concurrent chemo-radiotherapy for cervical cancer approximately 5 years prior to the *** computed tomography(CT)showed a 1.3 cm midline mass in the lower abdomen with infiltration into the rectus abdominis *** was no sign of metastasis(T1N0M0).An incisional biopsy identified sporadic MTT of the lower abdomen.A comprehensive surgical excision with a 3 cm margin inclusive of the peritoneum was ***-quently,the general surgeon utilized an approach akin to the open peritoneal onlay mesh *** patient underwent additional treatment with an excision shaped as a mini-abdominoplasty for the skin *** complications arose,and annual follow-up CTs did not show signs of recurrence or *** An abdominal MTT was efficaciously treated with extensive excision and abdominal wall reconstruction,eliminating the need for postoperative radiotherapy.

关键词： Malignant triton tumor Abdominal wall Surgical excision Reconstruction Case report

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RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

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Bone Research 2024年第2期12卷 407-420页

作者： Minhee kim Jin Hee Park Miyeon Go Nawon Lee Jeongin Seo hana Lee Doyong kim Hyunil ha Taesoo kim Myeong Seon Jeong Suree kim Taesoo kim han Sung kim Dongmin Kang Hyunbo Shim Soo Young Lee Department of Life Science Ewha Womans UniversitySeoul 03760South Korea The Research Center for Cellular Homeostasis Ewha Womans UniversitySeoul 03760South Korea Department of Biomedical Engineering Yonsei UniversityWonju 26493South Korea KM Convergence Research Division Korea Institute of Oriental MedicineDaejeon 34054South Korea Chuncheon Center Korea Basic Science InstituteChuncheon 24341South Korea Fluorescence Core Imaging Center and Bioimaging Data Curation Center Ewha Womans UniversitySeoul 03760South Korea Multitasking Macrophage Research Center Ewha Womans UniversitySeoul 03760South Korea

Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled ***,the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely ***,we show with GeneChip analysis that RUN and FYVE domain-containing protein 4(RUFY4)is strongly upregulated during *** lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in ***,deleting Rufy4 did not affect osteoclast differentiation,but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes,their trafficking to the membrane,and their secretion of cathepsin K into the extracellular ***,RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary ***,Rufy4-deficient mice were highly protected from lipopolysaccharide-and ovariectomy-induced bone ***,RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.

关键词： osteoclast inhibited traffic

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