000289478 001__ 289478
000289478 005__ 20240425122533.0
000289478 0247_ $$2doi$$a10.1016/j.lfs.2024.122631
000289478 0247_ $$2pmid$$apmid:38621585
000289478 0247_ $$2ISSN$$a0024-3205
000289478 0247_ $$2ISSN$$a0300-9653
000289478 0247_ $$2ISSN$$a0300-9637
000289478 0247_ $$2ISSN$$a1879-0631
000289478 037__ $$aDKFZ-2024-00800
000289478 041__ $$aEnglish
000289478 082__ $$a570
000289478 1001_ $$aGeng, Haigang$$b0
000289478 245__ $$aTargeting cellular senescence as a therapeutic vulnerability in gastric cancer.
000289478 260__ $$aNew York, NY [u.a.]$$bElsevier Science$$c2024
000289478 3367_ $$2DRIVER$$aarticle
000289478 3367_ $$2DataCite$$aOutput Types/Journal article
000289478 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1714038024_1930
000289478 3367_ $$2BibTeX$$aARTICLE
000289478 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000289478 3367_ $$00$$2EndNote$$aJournal Article
000289478 500__ $$aVolume 346, 1 June 2024, 122631
000289478 520__ $$aCellular senescence (CS) represents an intracellular defense mechanism responding to stress signals and can be leveraged as a 'vulnerability' in cancer treatment. This study aims to construct a CS atlas for gastric cancer (GC) and uncover potential therapeutics for GC patients.38 senescence-associated regulators with prognostic significance in GC were obtained from the CellAge database to construct Gastric cancer-specific Senescence Score (GSS). Using eXtreme Sum algorism, GSS-based drug repositioning was conducted to identify drugs that could antagonize GSS in CMap database. In vitro experiments were conducted to test the effect of combination of palbociclib and exisulind in eliminating GC cells.Patients with high GSS exhibited CS-related features, such as CS markers upregulation, adverse clinical outcomes and hypomethylation status. scRNA-seq data showed malignant cells with high GSS exhibited enhanced senescence state and more immunosuppressive signals such as PVR-CD96 compared with malignant cells with low GSS. In addition, the GSS-High cancer associated fibroblasts might secrete cytokines and chemokines such as IL-6, CXCL1, CXCL12, and CCL2 to from an immunosuppressive microenvironment, and GSS could serve as an indicator for immunotherapy resistance. Exisulind exhibited the greatest potential to reverse GSS. In vitro experiments demonstrated that exisulind could induce apoptosis and suppress the proliferation of palbociclib-induced senescent GC cells.Overall, GSS offers a framework for better understanding of correlation between senescence and GC, which might provide new insights into the development of novel therapeutics in GC.
000289478 536__ $$0G:(DE-HGF)POF4-314$$a314 - Immunologie und Krebs (POF4-314)$$cPOF4-314$$fPOF IV$$x0
000289478 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000289478 650_7 $$2Other$$aCellular senescence
000289478 650_7 $$2Other$$aDrug repositioning
000289478 650_7 $$2Other$$aExisulind
000289478 650_7 $$2Other$$aGastric cancer
000289478 650_7 $$2Other$$aImmunosuppressive microenvironment
000289478 650_7 $$2Other$$aMulti-omics
000289478 7001_ $$aHuang, Chen$$b1
000289478 7001_ $$aXu, Lei$$b2
000289478 7001_ $$aZhou, Yangyang$$b3
000289478 7001_ $$aDong, Zhongyi$$b4
000289478 7001_ $$aZhong, Yiqing$$b5
000289478 7001_ $$aLi, Qian$$b6
000289478 7001_ $$0P:(DE-He78)8b693edfb7c78bb156cc92812eec1c55$$aYang, Chen$$b7$$udkfz
000289478 7001_ $$aHuang, Shaozhuo$$b8
000289478 7001_ $$aLiao, Weixin$$b9
000289478 7001_ $$aLin, Yuxuan$$b10
000289478 7001_ $$aLiu, Zhicheng$$b11
000289478 7001_ $$aLi, Qing$$b12
000289478 7001_ $$aZhang, Zizhen$$b13
000289478 7001_ $$aZhu, Chunchao$$b14
000289478 773__ $$0PERI:(DE-600)2013911-1$$a10.1016/j.lfs.2024.122631$$gp. 122631 -$$p122631$$tLife sciences$$v346$$x0024-3205$$y2024
000289478 909CO $$ooai:inrepo02.dkfz.de:289478$$pVDB
000289478 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)8b693edfb7c78bb156cc92812eec1c55$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000289478 9131_ $$0G:(DE-HGF)POF4-314$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vImmunologie und Krebs$$x0
000289478 9141_ $$y2024
000289478 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2023-08-24$$wger
000289478 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bLIFE SCI : 2022$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-08-24
000289478 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bLIFE SCI : 2022$$d2023-08-24
000289478 9201_ $$0I:(DE-He78)D250-20160331$$kD250$$lNWG Krebs-Immunregulation$$x0
000289478 980__ $$ajournal
000289478 980__ $$aVDB
000289478 980__ $$aI:(DE-He78)D250-20160331
000289478 980__ $$aUNRESTRICTED