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Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites

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Cancer Communications 2024年第1期44卷 47-75页

作者： Ji Eon Kim So-Young park Chulhwan Kwak Yoonji Lee Dae-Geun Song jae Woo Jung Haesong Lee Eun-Ae Shin Yangie Pinanga Kyung-hee Pyo Eun Hae Lee Wonsik Kim Soyeon Kim Chang-Duck Jun Jeanho Yun Sun Choi hyun-Woo Rhee Kwang-Hyeon Liu Jung Weon Lee Department of Pharmacy College of PharmacySeoul National UniversitySeoulRepublic of Korea Research Institute of Pharmaceutical Sciences College of PharmacySeoul National UniversitySeoulRepublic of Korea BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit College of Pharmacy and Research Institute of Pharmaceutical SciencesKyungpook National UniversityDaeguRepublic of Korea Department of Chemistry Seoul National UniversitySeoulRepublic of Korea College of Pharmacy Chung-Ang UniversitySeoulRepublic of Korea Natural Product Informatics Research Center Korea Institute of Science and Technology(KIST)Gangneung-siGangwon-doRepublic of Korea School of Life Sciences Gwangju Institute of Science and Technology(GIST)GwangjuRepublic of Korea Department of Biochemistry College of MedicineDong-A UniversityBusanRepublic of Korea Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea Interdisciplinary Program in Genetic Engineering Seoul National UniversitySeoulRepublic of Korea

Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic *** is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of ***:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution ***:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal *** labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and ***4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-*** mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver ***:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.

关键词： cholesterol fluorescent imaging glucose catabolism hepatocellular carcinogenesis mem-brane contact sites mitochondria function mitophagy oxidative phosphorylation protein-protein interaction tetraspanin

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Crystal reconstruction of V2O3/carbon heterointerfaces via anodic hydration for ultrafast and reversible Mg-ion battery cathodes

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InfoMat 2024年第3期6卷 95-107页

作者： Gun Jang Yun Sang Joe Sang Joon Lee hyun Gyu Cho Sang Ha Baek Peixun Xiong Kang Ho Shin Jeong Seok Yeon Min Su Kang Si Hyoung Oh Ho Seok park School of Chemical Engineering Sungkyunkwan University(SKKU)SuwonRepublic of Korea Advanced Batteries Research Center Korea Electronics Technology InstituteSeongnamRepublic of Korea Korea Institute of Science and Technology SeoulRepublic of Korea SKKU Advanced Institute of Nano Technology(SAINT) Sungkyunkwan UniversitySuwonRepublic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences and Technology(SAIHST)Sungkyunkwan UniversitySuwonRepublic of Korea SKKU Institute of Energy Science and Technology(SIEST) Sungkyunkwan UniversitySuwonRepublic of Korea

Magnesium-ion batteries(MIBs)have promising applications because of their high theoretical capacity and the natural abundance of magnesium ***,the kinetic performance and cyclic stability of cathode materials are limited by the strong interactions between Mg ions and the crystal ***,we demonstrate the unique Mg^(2+)-ion storage mechanism of a hierarchical accordion-like vanadium oxide/carbon heterointerface(V2O3@C),where the V2O3 crystalline structure is reconstructed into a MgV_(3)O_(7)·H_(2)O phase through an anodic hydration reaction upon first cycle,for the improved kinetic and cyclic *** verified by in situ/ex situ spectroscopic and electrochemical analyses,the fast charge transfer kinetics of the V2O3@C cathode were due to the crystal-reconstruction and chemically coupled *** V2O3@C demonstrated an ultrahigh rate capacity of 130.4 mAh g^(-1)at 50000 mA g^(-1)and 1000 cycles,achieving a Coulombic efficiency of 99.6%.The high capacity of 381.0 mA h g^(-1)can be attributed to the reversible Mg^(2+)-ion intercalation mechanism observed in the MgV_(3)O_(7)·H_(2)O phase using a 0.3 M Mg(TFSI)2/ACN(H_(2)O)***,within the voltage range of 2.25 V versus Mg/Mg^(2+),the V2O3@C exhibited a capacity of 245.1 mAh g^(-1)when evaluated with magnesium metal in a 0.3 M Mg(TFSI)^(2+)0.25 M MgCl_(2)/DME *** research findings have important implications for understanding the relationship between the Mg-ion storage mechanism and reconstructed crystal phase of vanadium oxides as well as the heterointerface reconstruction for the rational design of MIB cathode materials.

关键词： anodic hydration reaction magnesium ion battery nano crystal vanadium oxide

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Changes in microorganisms and metabolites during long-term fermentation of commercially manufactured anchovy sauce

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Food Science and Human Wellness 2024年

作者： Daehyeon Kim Seong-Eun park Eun-Ju Kim Seung-Ho Seo Kwang-Moon Cho Sun jae Kwon Hong-Seok Son Department of Biotechnology， College of Life Sciences and Biotechnology， Korea University Sonlab Inc. 3. AccuGene Inc.

This study was performed to investigate the changes in microbial communities and metabolites during the long-term fermentation of commercially manufactured anchovy sauce. Samples of commercial anchovy sauce were collected from large-scale fermentation tanks with fermentation periods of up to 7.87 years. The complex bacterial community was simplified to two genera， Tetragenococcus and Halanaerobium， after approximately 0.55 years of fermentation. Although genera， such as Saccharomyces， Cladosporium， Candida， and Aspergillus， were relatively dominant， no clear pattern was identified in fungal community analysis. The longitudinal metabolite profile demonstrated that approximately half (55.8%) of the metabolites present in anchovy sauce were produced within a year of fermentation due to rapid fermentation. Despite the static microbial community， the contents of several metabolites including amino acids and biogenic amines changed continuously during the long-term fermentation of anchovy sauce. This study provides novel insights into the changes in microbiota and metabolites in fish sauce produced without any starter inoculation.

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Galectin 3-binding protein(LGALS3BP)depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1(TGF-β1)availability and inhibits hepatocarcinogenesis

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Cancer Communications 2024年第10期44卷 1106-1129页

作者： Dae-Hwan Kim Minjeong Sung Myong-Suk park Eun-Gene Sun Sumin Yoon Kyung hyun Yoo Kamalakannan Radhakrishnan Sung Yun Jung Woo-Kyun Bae Sang-Hee Cho Ik-Joo Chung Department of Internal Medicine Division of Hematology and OncologyChonnam National University Medical SchoolHwasunSouth Korea Department of Internal Medicine Division of Hematology and OncologyChonnam National University Hwasun HospitalHwasunSouth Korea Combinatorial Tumor Immunotherapy MRC Center Chonnam National University Medical SchoolHwasunSouth Korea National Immunotherapy Innovation Center HwasunSouth Korea BioMedical Sciences Graduate Program Chonnam National UniversityHwasunSouth Korea Department of Biological Science SookmyungWomen’s UniversitySeoulSouth Korea Clinical Vaccine R&D Center Chonnam National UniversityHwasunSouth Korea Department of Biochemistry and Molecular Pharmacology Baylor College of MedicineHoustonTexasUSA

Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming growth factor-β1(TGF-β1)in the emergence of these diseases,the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling ***:The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis(MASH)and *** omics techniques,such as RNA-sequencing,transposaseaccessible chromatin-sequencing assay,and liquid chromatography-tandem mass spectrometry proteomics,were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 *** effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout ***:In patients with MASH and HCC,the levels of LGALS3BP and TGFB1 exhibited positive *** of LGALS3BP by the inflammatory cytokine interferonαin HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of *** fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice,with increased TGFB1 ***3BP directly bound to and assembled integrinαV,an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin *** released TGF-β1 activated JunB transcription factor,which in turn promoted the TGF-β1 positive feedback ***3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced ***,LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β***:LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway,making it a promising therapeutic target in TGF-β1-related diseases.

关键词： F-actin FAK hepatic carcinogenesis IntegrinαV Interferonα JunB LGALS3BP metabolic dysfuntion-associated steatohepatitis tensile force TGF-β1

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Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer

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World Journal of Clinical Cases 2024年第2期12卷 267-275页

作者： Chae Hwa Kwon hyung Il Seo Dong Uk Kim Sung Yong Han Suk Kim Nam Kyung Lee Seung Baek Hong Ji hyun Ahn Young Mok park Byeong Gwan Noh BioMedical Research Institute Pusan National University HospitalBusan 49241South Korea Department of Surgery Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Internal Medicine Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Radiology Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Pathology and Biomedical Research Institute Pusan National University HospitalBusan 49241South Korea

BACKGROUND Currently,there is no standard adjuvant therapy for patients with resected ampulla of Vater(AoV)*** To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy(CCRT)in patients with advanced AoV cancer who underwent curative *** This single-centered,retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and *** impact of CCRT on advanced AoV cancer was *** The 1-,3-,and 5-yr recurrence-free survival(RFS)rates for patients with advanced AoV cancer were 82.8%,48.3%,and 40.8%,respectively,and the overall survival(OS)rates were 89.7%,62.1%,and 51.7%,***-cular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis,whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate *** to the patients who did not receive adjuvant CCRT,those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS,although they had a significantly lower average age and significantly higher platelet-to-lymphocyte *** Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV *** findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

关键词： Advanced ampulla of Vater cancer Adjuvant concurrent chemoradiotherapy Recurrence Survival Vater cancer

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Zircon U-Pb ages and O-Hf isotopes of Quaternary trachytes from the East Sea:Implications for the genesis of low-δ^(18)O magmas

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Geoscience Frontiers 2024年第2期15卷 41-54页

作者： hyun-Ok Choi Jihye Oh Chang Hwan Kim Soon Young Choi Won Hyuck Kim Chan Hong park Dokdo Research Center East Sea Research InstituteKorea Institute of Ocean Science and TechnologyUljin 36315Republic of Korea Deep-Sea and Seabed Mineral Resources Research Center Korea Institute of Ocean Science and TechnologyBusan 49111Republic of Korea Division of Science Education Kangwon National University1 Gangwondaehak-gilChuncheon-siGangwon-do 24341Republic of Korea

Quaternary intraplate magmatism formed several volcanic islands and seamounts,including Dokdo(DD),Ulleungdo(UD),Simheungtack(ST),Anyongbok,and Isabu in the southwest of the East Sea back-arc *** this study,we present whole-rock geochemical,zircon U–Pb age,and in situ O–Hf isotope data for the submerged volcanic rocks from DD,UD,and ST to provide new insights into the eruption timing of these volcanoes and constrain the magma evolution *** samples used in this study were trachytes and exhibited ferroan,alkalic,and metaluminous to weakly peraluminous *** showed light rare earth element(REE)-enriched patterns with(La/Yb)N ratios of 25.3–31.7 and mostly negative Eu anomalies in a chondrite-normalized REE *** addition,they were enriched in large-ion lithophile elements and high field strength elements;they exhibited positive Pb anomalies and strongly negative Ba,Sr,P,and Ti *** zircons yielded a weighted-mean 206Pb/238U age of 2.61,0.348–0.704,and 2.76–2.94 Ma for the DD,UD,and ST trachytes,*** zircons exhibited lowerδ^(18)O values than normal depleted mantle values,regardless of the crystallization age and spatial distribution of ***δ^(18)O values showed no correlation with U contents or Th/U ratios,indicating that the lowδ^(18)O signatures were of primary magmatic *** Hf isotopic compositions of the zircons were relatively heterogeneous but predominately characterized by positive eHf *** O–Hf mixing modeling revealed that low-δ^(18)O rocks with positive eHf values from the UD and ST volcanoes were derived from a hybrid source of recycled juvenile crustal materials with low-δ^(18)O and positive eHf signatures and an enriched mantle source with normalδ^(18)O and negative eHf *** juvenile oceanic crust in the source was likely metasomatized by seawater at high temperatures prior to *** contrast,the felsic magma that formed the DD volcanoes may have assimilated with regional

关键词： Quaternary intraplate volcanism East Sea Zircon O-Hf isotopes Low-δ^(18)O magma Recycled juvenile oceanic crust

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Effect of CaF2 content in refining slag on formation behavior of spinel inclusion in Ni-Cr-V-alloyed special steel

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Journal of Iron and Steel Research International 2018年第2期25卷 157-163页

作者： jae-hong Shin Joo-hyun park Department of Materials Engineering Hanyang UniversityAnsan 426-791 Korea

The influence of CaF2 content on the formation behavior of spinel inclusions in the Ni-Cr-V-alloyed special steel was presented. The spinel was not formed at CaF2 content lower than 10 wt%. However, it was formed at early stage when the CaF2 content was greater than 30 wt%, followed by a modification to the aluminosilicate-type inclusions. Because the slag was saturated by MgO, the activity of MgO was unity irrespective of CaF2 content in the slag. Thus, Mg was transferred from slag to metal phase. Mg transferred to molten steel reacted with Al2O3-rich inclusions to form ***2O3 spinel. However, the spinel inclusion was modified to aluminosilicate-type inclusions by the reaction with Si and Ca transferred from slag to molten steel about 2-3 h later.

关键词： Spinel inclusion Refining slag CaF2 content Ni-Cr-V-alloyed special steel

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Functionally graded structure of a nitride-strengthened Mg_(2)Si-based hybrid composite

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Journal of Magnesium and Alloys 2024年第3期12卷 1239-1256页

作者： Jeongho Yang Woongbeom Heogh Hogi Ju Sukhyun Kang Tae-Sik Jang hyun-Do Jung Mohammad Jahazi Seung Chul Han Seong Je park Hyoung Seop Kim Susmita Bose Amit Bandyopadhyay Martin Byung-Guk Jun Young Won Kim Dae-kyeom Kim Rigoberto CAdvincula Clodualdo Aranas Jr Sang Hoon Kim School of Mechanical Engineering Pusan National UniversityBusan 46241Republic of Korea Department of Mechanical Design Engineering Hanyang UniversitySeoul 04763Republic of Korea Process Research 3 Team LG Display Co.Ltd.PajuGyeonggi-do 10845Republic of Korea Department of Materials Science and Engineering Chosun UniversityGwangju 61452Republic of Korea Institute of Well-Aging Medicare&Chosun University LAMP Center Chosun UniversityGwangju 61452Republic of Korea Division of Materials Science and Engineering Hanyang UniversitySeoul 04763Republic of Korea Department of Mechanical Engineering École de Technologie SupérieureMontrealQuebec H3C 1K3Canada Material&Component Convergence R&D Center Korea Construction Equipment Technology InstituteGunsanJeollabuk-do 54002Republic of Korea School of Mechanical and Aerospace Engineering Nanyang Technological UniversitySingapore 639798Singapore Graduate Institute of Ferrous&Eco Materials Technology Pohang University of Science and TechnologyPohangGyeongsangbuk-do 37673Republic of Korea Advanced Institute for Materials Research Tohoku UniversitySendai 980-8577Japan Institute for Convergence Research and Education in Advanced Technology Yonsei UniversitySeoul 03722Republic of Korea School of Mechanical and Materials Engineering Washington State UniversityPullmanWashington 99164USA School of Mechanical Engineering Purdue UniversityWest LafayetteIndiana 47907USA Research Institute of Advanced Manufacturing Technology Korea Institute of Industrial TechnologyIncheon 21999Republic of Korea Department of Macromolecular Science and Engineering Case Western Reserve UniversityClevelandOhio 44106USA Department of Chemical and Biomolecular Engineering and Joint Institute for Advanced Materials University of TennesseeKnoxvilleTennessee 37996USA Center for Nanophase Materials and Sciences Oak Ridge National LaboratoryOak RidgeTennessee 37830USA Department of Mechanical Engineering University of New BrunswickFrederictonNew Brunswick E3B 5A3Cana

The ex-situ incorporation of the secondary SiC reinforcement,along with the in-situ incorporation of the tertiary and quaternary Mg_(3)N_(2) and Si_(3)N_(4) phases,in the primary matrix of Mg_(2)Si is employed in order to provide ultimate wear resistance based on the laser-irradiation-induced inclusion of N_(2) gas during laser powder bed *** is substantialized based on both the thermal diffusion-and chemical reactionbased metallurgy of the Mg_(2)Si–SiC/nitride hybrid *** study also proposes a functional platform for systematically modulating a functionally graded structure and modeling build-direction-dependent architectonics during additive *** strategy enables the development of a compositional gradient from the center to the edge of each melt pool of the Mg_(2)Si–SiC/nitride hybrid ***,the coefficient of friction of the hybrid composite exhibits a 309.3%decrease to–1.67 compared to–0.54 for the conventional nonreinforced Mg_(2)Si structure,while the tensile strength exhibits a 171.3%increase to 831.5 MPa compared to 485.3 MPa for the conventional *** outstanding mechanical behavior is due to the(1)the complementary and synergistic reinforcement effects of the SiC and nitride compounds,each of which possesses an intrinsically high hardness,and(2)the strong adhesion of these compounds to the Mg_(2)Si matrix despite their small sizes and low concentrations.

关键词： Laser powder bed fusion Mg_(2)Si-SiC/nitride hybrid composite Both the thermal diffusion-and chemical reaction-based metallurgy Functionally graded structure Compositional gradient Wear resistance.

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Primordial germ cell-mediated transgenesis and genome editing in birds

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Journal of Animal Science and Biotechnology 2018年第2期9卷 257-267页

作者： jae Yong Han Young hyun park Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences College of Agriculture and Life Sciences Seoul National University Institute for Biomedical Sciences Shinshu University

Transgenesis and genome editing in birds are based on a unique germline transmission system using primordial germ cells(PGCs), which is quite different from the mammalian transgenic and genome editing system. PGCs are progenitor cells of gametes that can deliver genetic information to the next generation. Since avian PGCs were first discovered in nineteenth century, there have been numerous efforts to reveal their origin, specification, and unique migration pattern, and to improve germline transmission efficiency. Recent advances in the isolation and in vitro culture of avian PGCs with genetic manipulation and genome editing tools enable the development of valuable avian models that were unavailable before. However, many challenges remain in the production of transgenic and genome-edited birds,including the precise control of germline transmission, introduction of exogenous genes, and genome editing in ***, establishing reliable germline-competent PGCs and applying precise genome editing systems are critical current issues in the production of avian models. Here, we introduce a historical overview of avian PGCs and their application, including improved techniques and methodologies in the production of transgenic and genome-edited birds, and we discuss the future potential applications of transgenic and genome-edited birds to provide opportunities and benefits for humans.

关键词： Avian Genome editing Primordial germ cell Transgenesis

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Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study

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Asian Journal of Urology 2024年第3期11卷 450-459页

作者： Jung Ki Jo Seong Il Seo MinYong Kang Jinsoo Chung Cheol Kwak Sung-Hoo Hong Cheryn Song jae Young park Chang Wook Jeong Seok Hwan Choi Sung Han Kim Eu Chang Hwang Chan Ho Lee Hakmin Lee Department of Urology Medical and Digital EngineeringCollege of MedicineHanyang UniversitySeoulRepublic of Korea Department of Urology Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea Department of Urology National Cancer CenterGoyangRepublic of Korea Department of Urology Seoul National University HospitalSeoulRepublic of Korea Department of Urology Kangnam St Mary’s HospitalSeoulRepublic of Korea Department of Urology Asan Medical CenterSeoulRepublic of Korea Department of Urology Korea University Ansan HospitalAnsanRepublic of Korea Department of Urology Kyungpook National University HospitalDaeguRepublic of Korea Department of Urology Chonnam National University Hwasun HospitalHwasunRepublic of Korea Department of Urology Inje University Busan Paik HospitalBusanRepublic of Korea Department of Urology Seoul National University Bundang HospitalSeongnamRepublic of Korea

Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment ***:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December *** focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study *** generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as *** addition,frequencies of discontinuation and adverse events were compared among the therapy ***:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in *** that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks.

关键词： Tyrosinekinase inhibitor Metastaticrenalcell carcinoma Overall survival Progression-free survival

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