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Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3521-3528页

作者： Shin Woo kang Sung Hee Lim Min-Ji kim Jeeyun Lee Young Suk Park Ho Yeong Lim won ki kang Seung Tae kim Division of Hematology Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Samsung Biomedical Research Institute Samsung Medical CenterSeoul 06351South Korea

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor *** VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab *** cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and *** To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of *** This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with *** A total of 124 patients was included in this *** all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line *** 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line *** numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),*** results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

关键词： Bevacizumab Colorectal cancer Programmed cell death ligand 1 expression First-line chemotherapy Metastatic colorectal cancer

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Gastric leptomeningeal carcinomatosis: Multi-center retrospective analysis of 54 cases

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World Journal of Gastroenterology 2009年第40期15卷 5086-5090页

作者： Sung Yong Oh Su-Jin Lee Jeeyun Lee Suee Lee Sung-Hyun kim Hyuk-Chan Kwon Gyeong-won Lee Jung Hun kang In Gyu Hwang Joung-Soon Jang Ho Yeong Lim Young Suk Park won ki kang Hyo-Jin kim Department of Internal Medicine and Medical Research Center for Cancer Molecular Therapy Dong-A University College of Medicine Division of Hematology/Oncology Department of MedicineSamsung Medical Center Department of InternalMedicine Gyeongsang National University School of Medicine Department of Internal Medicine College of MedicineChung-Ang University

AIM： To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis （LMC） of gastric ***： We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to ***： The male-to-female ratio was 32：22, and the patients ranged in age from 28 to 78 years （median,48.5 years）. The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients （70%）.The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 （51%） of the patients were Bormann typeand 15 （33%） patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache （85%） and nausea/vomiting （58%） were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases （82%）. Intrathecal （IT） chemotherapy was administered to 36 patients-primarily methotrexate alone （61%）, but also in combi-nation with hydrocortisone/± Ara-C （39%）. The median number of IT treatments was 7 （range, 1-18）. Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients （46%） achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk （95% CI： 4.3-9.1 wk）. In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration （P = 0.038, P = 0.010, and P = 0.002, respectively）. However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer sur

关键词： Carcinomatosis Gastric cancer Intrathecal chemotherapy Leptomeningeal

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Towards high-performance and robust anion exchange membranes(AEMs)for water electrolysis:Super-acid-catalyzed synthesis of AEMs

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Journal of Energy Chemistry 2024年第6期93卷 478-510,I0012页

作者： Geun Woong Ryoo Sun Hwa Park ki Chang Kwon Jong Hun kang Ho won Jang Min Sang Kwon Department of Materials Science and Engineering Research Institute of Advanced Materials(RIAM)Seoul National UniversitySeoul 08826Republic of Korea Interdisciplinary Materials Measurement Institute Korea Research Institute of Standards and Science(KRISS)Daejeon 34113Republic of Korea Department of Chemical and Biological Engineering and Institute of Chemical ProcessSeoul National UniversitySeoul 08826Republic of Korea Department of Applied Measurement Science University of Science and TechnologyDaejeon 34113Republic of Korea

The increasing demand for hydrogen energy to address environmental issues and achieve carbon neutrality has elevated interest in green hydrogen production,which does not rely on fossil *** various hydrogen production technologies,anion exchange membrane water electrolyzer(AEMWE)has emerged as a next-generation technology known for its high hydrogen production efficiency and its ability to use non-metal ***,this technology faces significant challenges,particularly in terms of the membrane durability and low ionic *** address these challenges,research efforts have focused on developing membranes with a new backbone structure and anion exchange groups to enhance durability and ionic ***,the super-acid-catalyzed condensation(SACC)synthesis method stands out due to its user convenience,the ability to create high molecular weight(MW)polymers,and the use of oxygen-tolerant organic *** the synthesis of anion exchange membranes(AEMs)using the SACC method began in 2015,and despite growing interest in this synthesis approach,there remains a scarcity of review papers focusing on AEMs synthesized using the SACC *** review covers the basics of SACC synthesis,presents various polymers synthesized using this method,and summarizes the development of these polymers,particularly their building blocks including aryl,ketone,and anion exchange *** systematically describe the effects of changes in the molecular structure of each polymer component,conducted by various research groups,on the mechanical properties,conductivity,and operational stability of the *** review will provide insights into the development of AEMs with superior performance and operational stability suitable for water electrolysis applications.

关键词： Green hydrogen production Water electrolysis Anion exchange membrane water electrolyzer(AEMWE) Anion exchange membranes(AEMs) Super-acid-catalyzed condensation(SACC)

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Comprehensive molecular analysis to predict the efficacy ofchemotherapy containing bevacizumab in patients with metastaticcolorectal cancer

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肿瘤学研究(英文) 2023年第6期31卷 855-866页

作者： SUNG HEE LIM HEE JIN CHO KYOUNG-MEE kiM HO YEONG LIM won ki kang JEEYUN LEE YOUNG SUK PARK HEE CHEOL kiM SEUNG TAE kiM Division of Hematology/Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineGangnam-guSeoul06351Korea Precision Medicine Research Institute Samsung Medical CenterGangnam-guSeoul06351Korea Department of Biomedical Convergence Science and Technology Kyungpook National UniversityDaegu41566Korea Department of Pathology and Translational Genomics Samsung Medical CenterSungkyunkwan University School of MedicineSeoul06351Korea Department of Surgery Samsung Medical CenterSungkyunkwan University School of MedicineGangnam-guSeoul06351Korea

Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been ***:We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identifybiomarkers for a response to bevacizumab-containing *** molecular analysis comprised whole-exomesequencing,ribonucleic acid sequencing,and a methylation array on patient ***:Genomic and molecularcharacterization was successfully conducted in 103 *** of 103 CRC samples were hypermutated,and none ofthe non-hypermutant tumors were microsatellite *** those 103 patients,89 had adenocarcinoma(ADC),15 were diagnosed with mucinous ADC,and six had signet-ring cell carcinoma(SRCC).Consensus molecular subtype(CMS)2 was unique to *** the four SRCCs,two were CMS1,one was CMS4,and the other was *** status was a significantly enriched factor in responders to bevacizumab *** growth factorreceptor(FGFR)1/2 signaling was upregulated in non-responders,whereas cell cycle,transfer ribonucleic acidprocessing,nucleotide excision repair,and oxidative phosphorylation pathways were enriched in ***,IGF1 was differentially expressed in non-responders(log2 fold change=−1.43,p=4.11×10^(−5),falsediscovery rate=0.098),and FLT1 was highly methylated in non-responders(p=7.55×10^(−3)).When the molecularpathways were reanalyzed separately according to the backbone chemotherapy(FOLFOX ***),thesignificance of the molecular pathways varied according to the backbone ***:This studysought a subset of CRC patients with a distinct clinical response to chemotherapy containing *** need to be validated in a large group of homogenous patient cohort and examined according to the differentchemotherapy backbones to create personalized therapeutic oppor

关键词： Bevacizumab Whole-exome sequencing Ribonucleic acid sequencing Methylation array Colorectal cancer

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Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressionsin Pancreas and Liver Tissues

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Chinese Journal of Integrative Medicine 2024年第2期30卷 125-134页

作者： Piao Wang Yi Liu Seok Yong kang Chenzi Lyu Xiang Han Tianjun Ho Kyung Jae Lee Xianglong Meng Yong-ki Park Hyo won Jung Department of Herbology College of Korean MedicineDongguk UniversityGyeongju 38066Korea College of Pharmacy&Graduate School of Pharmaceutical Sciences Ewha Womans UniversitySeoul 03760Korea Korean Medicine R&D Center Dongguk UniversityGyeongju 38066Korea Shanxi Key Laboratory of Traditional Herbal Medicines Processing Shanxi University of Chinese MedicineJinzhong(030619)ShanxiProvinceChina

Objective:To investigate the effects of Clean-DM1(C-DM1),a polyherbal formulation of Radix Scrophulariae,Radix Astragali,Rhizoma Atractylodis,and Radix Salviae Miltiorrhizae,on high-fat diet(HFD)-induced diabetes ***:The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology *** compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry(HPLC-MS)analysis were conducted for quality *** in vivo study,mice were induced diabetes by HFD for 12 *** mice in the normal group(Nor)were maintained with a regular diet and treated with saline by *** HFD model mice were randomly divided into 3 groups,including a HFD diabetic model group,a C-DM1 extract-administered group(C-DM1,500 mg/kg),and metformin-administered groups(Met,500 mg/kg),8 mice in each *** intake,body weight(BW),and fasting blood glucose(FBG)levels were recorded weekly for 4 *** 4 weeks of treatment,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood glucose,low-density lipoprotein cholesterol(LDL-C)were determined using an automated clinical chemistry analyzer,and homeostatic model for assessing insulin resistance(HOMA-IR)levels and oral glucose tolerance test(OGTT)were *** histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin *** receptor substrate(IRS)/phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)and adenosine 5'-monophosphate-activated protein kinase(AMPK)expressions in liver and pancreas tissues were detected by Western blot ***:HPLC-MS identified dihydroisotanshinone,dihydroisotanshinone I,cryptotanshinone,harpagoside,and atractyloside A in C-DM1 *** administration of C-DM1 extract significantly decreased body weight,calorie intake,and the levels of blood glucose and insulin in the diabetic mice(P<0.05 or P<0.01).The C-DM1 extract administration improved the im

关键词： high-fat diet type 2 diabetes mellitus herbal formulation insulin receptor substrate/phosphatidylinositol 3 kinase/protein kinase B adenosine 5'-monophosphate-activated protein kinase network pharmacology high performance liquid chromatography-mass spectrometry analysis

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Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： kang-Gu Lee Bong-ki Hong Saseong Lee Naeun Lee Seung-Whan kim Donghyun kim Wan-Uk kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of Pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical Institute of Technology University of UlsanSeoul 05505Republic of Korea Department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea Institute of Infectious Diseases Seoul National University College of MedicineSeoul 03080Republic of Korea Division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the *** receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains ***,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory ***,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic ***,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active *** note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in *** ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in *** with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling ***,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

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Ionizing terahertz waves with 260 MV/cm from scalable optical rectification

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Light(Science & Applications) 2024年第6期13卷 1075-1087页

作者： Hyeongmun kim Chul kang Dogeun Jang Yulan Roh Sang Hwa Lee Joong Wook Lee Jae Hee Sung Seong Ku Lee ki-Yong kim Advanced Photonics Research Institute GISTGwangju61005Korea Department of Physics and Optoelectronics Convergence Research Center Chonnam National UniversityGwangju61186Korea Pohang Accelerator Laboratory POSTECHPohang37673Korea Center for Relativistic Laser Science Institute for Basic ScienceGwangju61005Korea Institute for Research in Electronics and Applied Physics Department of PhysicsUniversity of MarylandCollege ParkMaryland20742USA

Terahertz(THz)waves,known as non-ionizing radiation owing to their low photon energies,can actually ionize atoms and molecules when a sufficiently large number of THz photons are concentrated in time and ***,we demonstrate the generation of ionizing,multicycle,15-THz waves emitted from large-area lithium niobate crystals via phase-matched optical rectification of 150-terawatt laser pulses.A complete characterization of the generated THz waves in energy,pulse duration,and focal spot size shows that the field strength can reach up to 260 megavolts per *** particular,a single-shot THz interferometer is employed to measure the THz pulse duration and spectrum with complementary numerical *** intense THz pulses are irradiated onto various solid targets to demonstrate THz-induced tunneling ionization and plasma *** study also discusses the potential of nonperturbative THz-driven ionization in gases,which will open up new opportunities,including nonlinear and relativistic THz physics in plasma.

关键词： optical interferometer matched

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Establishment of a chicken intestinal organoid culture system to assess deoxynivalenol‑induced damage of the intestinal barrier function

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1119-1130页

作者： Tae Hong kang Sang In Lee Department of Animal Science and Biotechnology Kyungpook National UniversitySangjuGyeong‑Sangbuk‑Do 37224Republic of Korea Research Institute for Innovative Animal Science Kyungpook National University37224SangjuGyeong‑Sangbuk‑DoRepublic of Korea

Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in *** DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small *** We established a culture system using chicken organoids and characterized the organoids at passages 1 and *** confirmed the mRNA expression levels of various cell markers in the organoids,such as ki67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small *** results showed that the organoids displayed functional similarities in permeability compared to the small *** damaged the tight junctions of the organoids,which resulted in increased *** Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine *** on these similarities,we confirmed that DON causes small intestine *** organoids offer a practical model for the research of harmful substances.

关键词： Barrier function Deoxynivalenol Organoids

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The SARS-CoV-2 spike protein induces lung cancer migration and invasion in a TLR2-dependent manner

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Cancer Communications 2024年第2期44卷 273-277页

作者： Mi-Jeong kim Ji Young kim Ji Hye Shin Juhee Son Yeeun kang Soo-Kyung Jeong Duk-Hwan kim Kyun-Hwan kim Eunyoung Chun ki-Young Lee Department of Immunology Samsung Biomedical Research InstituteSungkyunkwan University School of MedicineSuwonRepublic of Korea Research and Development Center CHA Vaccine InstituteSeongnam-siRepublic of Korea Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Precision Medicine Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences&TechnologySamsung Medical CenterSungkyunkwan UniversitySeoulRepublic of Korea

Dear editor,Severe acute respiratory syndrome coronavirus2(SARS-CoV-2)infection can lead to severe outcomes in patients with cancer[1].It has been reported that patients with lung cancers disproportionately manifest severe COVID-19 with a high rate of hospitalization and death[2].Notably,the SARS-CoV-2 Spike(S)protein can induce hyper-inflammation in both epithelial cells and macrophages through toll-like receptor(TLR)1/TLR2 or TLR2/6-dependent nuclear factor-kappaB(NF-κB)path-way[3].However,molecular and cellular evidence on whether the SARS-CoV-2 virus affects the severity of lung cancer patients through TLR1/2 or TLR2/6 signaling remains unclear.

关键词： lung TLR2 invasion

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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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