{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:20:40Z","timestamp":1790709640243,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,8,11]],"date-time":"2014-08-11T00:00:00Z","timestamp":1407715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Associazione Italiana per la Ricerca sui Tumori Cerebrali del Bambino, Genova, Italy.","award":["12730-13"],"award-info":[{"award-number":["12730-13"]}]},{"name":"Compagnia San Paolo, Turin, Italy","award":["2010.1944"],"award-info":[{"award-number":["2010.1944"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:p>\n                    We have recently reported that glioblastoma (GB)\u2010initiating cells (GIC) with low expression and\/or mutation of\n                    <jats:italic>TP53<\/jats:italic>\n                    and high expression of\n                    <jats:italic>PI3K<\/jats:italic>\n                    (\u201cresponder\u201d genetic profile) can be effectively and safely radiosensitized by the ATM inhibitor KU60019. We report here on drug's diffusion and elimination from the animal body and brain, its effects on orthotopic GB and efficacy toward pediatric GIC. Healthy mice were infused by convection enhanced delivery (CED) with KU60019 and the drug kinetics followed by high performance liquid chromatography\u2013mass spectrometry. Already at the end of CED, KU60019 had diffused from the injection site to the ipsilateral and, to a lower extent, controlateral hemisphere. After 24 hr, no drug could be detected all over the brain or in other organs, indicating rapid draining and excretion. After intraperitoneal injection, traces only of KU60019 could be detected in the brain, indicating inability to cross the brain\u2013blood barrier. Consistent with the induction of cell cycle progression previously observed\n                    <jats:italic>in vitro<\/jats:italic>\n                    , KU60019 stimulated proliferation of orthotopic GB cells with the highest effect observed 96 hr after drug delivery. Adult GIC with high expression of\n                    <jats:italic>TP53<\/jats:italic>\n                    and low expression of\n                    <jats:italic>PI3K<\/jats:italic>\n                    could be radiosensitized by KU60019, although less promptly than GIC bearing the \u201cresponder\u201d profile. Consistent with the kinetics of proliferation induction, the highest radiosensitizing effect was observed 96 hr after delivery of KU60019 to GIC. Pediatric GIC could be similarly radiosensitized after exposure to KU60019. The results indicate that ATM inhibition may allow to radiosensitize a wide range of adult and pediatric high\u2010grade gliomas.\n                  <\/jats:p>","DOI":"10.1002\/ijc.29121","type":"journal-article","created":{"date-parts":[[2014,8,4]],"date-time":"2014-08-04T07:54:09Z","timestamp":1407138849000},"page":"1445-1457","source":"Crossref","is-referenced-by-count":52,"title":["Pharmacokinetics, pharmacodynamics and efficacy on pediatric tumors of the glioma radiosensitizer\n                    <scp>KU<\/scp>\n                    60019"],"prefix":"10.1002","volume":"136","author":[{"given":"Donatella","family":"Vecchio","sequence":"first","affiliation":[{"name":"Mutagenesis Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Daga","sequence":"additional","affiliation":[{"name":"Gene Transfer Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Carra","sequence":"additional","affiliation":[{"name":"Gene Transfer Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Marubbi","sequence":"additional","affiliation":[{"name":"Gene Transfer Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"},{"name":"Department of Experimental Medicine (DIMES) University of Genova Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Raso","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Mascelli","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Nozza","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Garr\u00e8","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pitto","sequence":"additional","affiliation":[{"name":"Pathological Anatomy and Histology Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Louis","family":"Ravetti","sequence":"additional","affiliation":[{"name":"Pathological Anatomy and Histology Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Vagge","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Corv\u00f2","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Profumo","sequence":"additional","affiliation":[{"name":"Biopolymers and Proteomics Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Baio","sequence":"additional","affiliation":[{"name":"Diagnostic Imaging and Interventional Oncology Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Marcello","sequence":"additional","affiliation":[{"name":"Mutagenesis Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Frosina","sequence":"additional","affiliation":[{"name":"Mutagenesis Unit IRCCS AOU San Martino \u2010 IST Istituto Nazionale per la Ricerca sul Cancro Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.280319"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28680"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0707"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3408"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1607"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-08-0409"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.08.024"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-012-0925-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/18.1.1"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.05.003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.6.5.709"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2012.87"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07618"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900019"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2010.07.003"}],"container-title":["International 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