Please use this identifier to cite or link to this item: https://olympias.lib.uoi.gr/jspui/handle/123456789/24275
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dc.contributor.authorUhm, J. H.en
dc.contributor.authorDooley, N. P.en
dc.contributor.authorKyritsis, A. P.en
dc.contributor.authorRao, J. S.en
dc.contributor.authorGladson, C. L.en
dc.date.accessioned2015-11-24T19:39:51Z-
dc.date.available2015-11-24T19:39:51Z-
dc.identifier.issn1078-0432-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/24275-
dc.rightsDefault Licence-
dc.subjectAntibodies, Monoclonal/pharmacologyen
dc.subject*Apoptosisen
dc.subjectCell Survival/drug effects/physiologyen
dc.subjectFibronectins/pharmacologyen
dc.subjectGlioma/*pathologyen
dc.subjectHumansen
dc.subjectIn Situ Nick-End Labelingen
dc.subjectIntegrins/antagonists & inhibitors/immunology/physiologyen
dc.subjectProto-Oncogene Proteins c-bcl-2/biosynthesisen
dc.subjectReceptors, Fibronectin/antagonists & inhibitors/immunology/physiologyen
dc.subjectReceptors, Vitronectin/antagonists & inhibitors/immunology/physiologyen
dc.subjectTopotecan/pharmacologyen
dc.subjectTumor Cells, Cultureden
dc.subjectVitronectin/*physiologyen
dc.subjectbcl-X Proteinen
dc.titleVitronectin, a glioma-derived extracellular matrix protein, protects tumor cells from apoptotic deathen
heal.typejournalArticle-
heal.type.enJournal articleen
heal.type.elΆρθρο Περιοδικούel
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/10389948-
heal.identifier.secondaryhttp://clincancerres.aacrjournals.org/content/5/6/1587.full.pdf-
heal.languageen-
heal.accesscampus-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.publicationDate1999-
heal.abstractVitronectin (VN) is an extracellular matrix (ECM) protein, the synthesis of which in vivo by glioma cells correlates with tumor grade. Although the role of VN as a permissive substrate for glioma migration has been well characterized, its role in conferring a survival advantage for tumor cells has not been addressed previously. By using an in vitro assay of DNA fragmentation as a quantitative measure of apoptotic cell death, we sought to determine whether the sensitivity of two human glioma cell lines (D54 and U251) to drug-induced apoptosis could be inhibited by VN. As well, the extent to which apoptosis could be inhibited was correlated with the levels of the Bcl-2 family of proteins that are known to modulate apoptosis and chemoresistance. Results of the study were: (a) VN coatings, in a dose-dependent manner, inhibited topoisomerase (Topo)-induced apoptosis by up to 50% (optimal coating density, 500 ng/cm2); in contrast, fibronectin (FN), an ECM protein present in abundance in the brain, demonstrated no protection; (b) in a dose-response study, VN clearly conferred a survival advantage (LD50 of Topo: on VN, 120 ng/ml; on FN, 35 ng/ml); (c) the protective effect of VN was not due to enhanced cell adhesion or alterations in the cell cycle distribution; (d) both of the classic integrin receptors that bind VN (alpha(v)beta3, alpha(v)beta5) were capable of mediating this protective effect, because ligation of either of the two classic integrins conferred chemoresistance to Topo; and (e) chemoresistance observed with VN was associated with an increase in expression of two antiapoptotic proteins, Bcl-2 and Bcl-X(L), with a consequent increase in the ratios for Bcl-2:Bax and Bcl-X(L):Bax. VN, an ECM protein preferentially expressed at the tumor-brain interface in vivo, may confer a survival advantage to glioma cells at the advancing tumor margin and may thus, in part, underlie the high level of tumor recurrence at this interface.en
heal.journalNameClin Cancer Resen
heal.journalTypepeer-reviewed-
heal.fullTextAvailabilityTRUE-
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά) - ΙΑΤ

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