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dc.contributor.authorGravina, Giovanni Luca
dc.contributor.authorColapietro, Alessandro
dc.contributor.authorAndrea, Mancini
dc.contributor.authorRossetti, Alessandra
dc.contributor.authorMartelucci, Stefano
dc.contributor.authorVentura, Luca
dc.contributor.authorDi Franco, Martina
dc.contributor.authorMarampon, Francesco
dc.contributor.authorMattei, Vinvenzo
dc.contributor.authorBiordi, Leda Assunta
dc.contributor.authorOtterlei, Marit
dc.contributor.authorFestuccia, Claudio
dc.description.abstractCell proliferation requires the orchestrated actions of a myriad of proteins regulating DNA replication, DNA repair and damage tolerance, and cell cycle. Proliferating cell nuclear antigen (PCNA) is a master regulator which interacts with multiple proteins functioning in these processes, and this makes PCNA an attractive target in anticancer therapies. Here, we show that a cell-penetrating peptide containing the AlkB homolog 2 PCNA-interacting motif (APIM), ATX-101, has antitumor activity in a panel of human glioblastoma multiforme (GBM) cell lines and patient-derived glioma-initiating cells (GICs). Their sensitivity to ATX-101 was not related to cellular levels of PCNA, or p53, PTEN, or MGMT status. However, ATX-101 reduced Akt/mTOR and DNA-PKcs signaling, and a correlation between high Akt activation and sensitivity for ATX-101 was found. ATX-101 increased the levels of γH2AX, DNA fragmentation, and apoptosis when combined with radiotherapy (RT). In line with the in vitro results, ATX-101 strongly reduced tumor growth in two subcutaneous xenografts and two orthotopic GBM models, both as a single agent and in combination with RT. The ability of ATX-101 to sensitize cells to RT is promising for further development of this compound for use in GBM.en_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastomaen_US
dc.title.alternativeATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastomaen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal