000127854 001__ 127854
000127854 005__ 20240228140953.0
000127854 0247_ $$2doi$$a10.18632/oncotarget.3171
000127854 0247_ $$2pmid$$apmid:25846752
000127854 0247_ $$2pmc$$apmc:PMC4496413
000127854 0247_ $$2altmetric$$aaltmetric:6228474
000127854 037__ $$aDKFZ-2017-03876
000127854 041__ $$aeng
000127854 082__ $$a610
000127854 1001_ $$0P:(DE-HGF)0$$aZhang, Yiyao$$b0$$eFirst author
000127854 245__ $$aAspirin counteracts cancer stem cell features, desmoplasia and gemcitabine resistance in pancreatic cancer.
000127854 260__ $$a[S.l.]$$bImpact Journals LLC$$c2015
000127854 3367_ $$2DRIVER$$aarticle
000127854 3367_ $$2DataCite$$aOutput Types/Journal article
000127854 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1524143141_24105
000127854 3367_ $$2BibTeX$$aARTICLE
000127854 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000127854 3367_ $$00$$2EndNote$$aJournal Article
000127854 520__ $$aPancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis. An inflammatory microenvironment triggers the pronounced desmoplasia, the selection of cancer stem-like cells (CSCs) and therapy resistance. The anti-inflammatory drug aspirin is suggested to lower the risk for PDA and to improve the treatment, although available results are conflicting and the effect of aspirin to CSC characteristics and desmoplasia in PDA has not yet been investigated. We characterized the influence of aspirin on CSC features, stromal reactions and gemcitabine resistance. Four established and 3 primary PDA cell lines, non-malignant cells, 3 patient tumor-derived CSC-enriched spheroidal cultures and tissues from patients who did or did not receive aspirin before surgery were analyzed using MTT assays, flow cytometry, colony and spheroid formation assays, Western blot analysis, antibody protein arrays, electrophoretic mobility shift assays (EMSAs), immunohistochemistry and in vivo xenotransplantation. Aspirin significantly induced apoptosis and reduced the viability, self-renewal potential, and expression of proteins involved in inflammation and stem cell signaling. Aspirin also reduced the growth and invasion of tumors in vivo, and it significantly prolonged the survival of mice with orthotopic pancreatic xenografts in combination with gemcitabine. This was associated with a decreased expression of markers for progression, inflammation and desmoplasia. These findings were confirmed in tissue samples obtained from patients who had or had not taken aspirin before surgery. Importantly, aspirin sensitized cells that were resistant to gemcitabine and thereby enhanced the therapeutic efficacy. Aspirin showed no obvious toxic effects on normal cells, chick embryos or mice. These results highlight aspirin as an effective, inexpensive and well-tolerated co-treatment to target inflammation, desmoplasia and CSC features PDA.
000127854 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0
000127854 588__ $$aDataset connected to CrossRef, PubMed,
000127854 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000127854 650_7 $$00W860991D6$$2NLM Chemicals$$aDeoxycytidine
000127854 650_7 $$0B76N6SBZ8R$$2NLM Chemicals$$agemcitabine
000127854 650_7 $$0R16CO5Y76E$$2NLM Chemicals$$aAspirin
000127854 7001_ $$0P:(DE-He78)0144e4bf6eab6053de5a445069012063$$aLiu, Lizhen$$b1$$udkfz
000127854 7001_ $$0P:(DE-HGF)0$$aFan, Pei$$b2
000127854 7001_ $$0P:(DE-He78)bf58bfc5eb550025e7f1f64520b68feb$$aBauer, Nathalie$$b3$$udkfz
000127854 7001_ $$0P:(DE-HGF)0$$aGladkich, Jury$$b4
000127854 7001_ $$aRyschich, Eduard$$b5
000127854 7001_ $$aBazhin, Alexandr V$$b6
000127854 7001_ $$aGiese, Nathalia A$$b7
000127854 7001_ $$aStrobel, Oliver$$b8
000127854 7001_ $$aHackert, Thilo$$b9
000127854 7001_ $$aHinz, Ulf$$b10
000127854 7001_ $$0P:(DE-HGF)0$$aGross, Wolfgang$$b11
000127854 7001_ $$aFortunato, Franco$$b12
000127854 7001_ $$0P:(DE-HGF)0$$aHerr, Ingrid$$b13$$eLast author
000127854 773__ $$0PERI:(DE-600)2560162-3$$a10.18632/oncotarget.3171$$gVol. 6, no. 12, p. 9999 - 10015$$n12$$p9999 - 10015$$tOncoTarget$$v6$$x1949-2553$$y2015
000127854 909CO $$ooai:inrepo02.dkfz.de:127854$$pVDB
000127854 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000127854 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)0144e4bf6eab6053de5a445069012063$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000127854 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000127854 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)bf58bfc5eb550025e7f1f64520b68feb$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000127854 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000127854 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ
000127854 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b13$$kDKFZ
000127854 9131_ $$0G:(DE-HGF)POF3-317$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vTranslational cancer research$$x0
000127854 9141_ $$y2015
000127854 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bONCOTARGET : 2015
000127854 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000127854 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000127854 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000127854 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000127854 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000127854 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000127854 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000127854 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bONCOTARGET : 2015
000127854 9201_ $$0I:(DE-He78)G403-20160331$$kG403$$lMolekulare Onkochirurgie$$x0
000127854 980__ $$ajournal
000127854 980__ $$aVDB
000127854 980__ $$aI:(DE-He78)G403-20160331
000127854 980__ $$aUNRESTRICTED