{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:48:25Z","timestamp":1792788505342,"version":"4.5.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:00:00Z","timestamp":1495670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Functional Neurosurgery Research Fund"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0176855","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T13:29:36Z","timestamp":1495718976000},"page":"e0176855","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma"],"prefix":"10.1371","volume":"12","author":[{"given":"Clare L.","family":"Killick-Cole","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G. B.","family":"Singleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison S.","family":"Bienemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Asby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella J.","family":"Wyatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa J.","family":"Boulter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil U.","family":"Barua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6243-3835","authenticated-orcid":true,"given":"Steven S.","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,5,25]]},"reference":[{"issue":"5","key":"ref1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/ng.2936","article-title":"Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations","volume":"46","author":"P Buczkowicz","year":"2014","journal-title":"Nature genetics"},{"issue":"6","key":"ref2","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s00401-015-1478-0","article-title":"Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes","volume":"130","author":"D Castel","year":"2015","journal-title":"Acta neuropathologica"},{"issue":"2","key":"ref3","doi-asserted-by":"crossref","first-page":"e30313","DOI":"10.1371\/journal.pone.0030313","article-title":"Mesenchymal transition and PDGFRA amplification\/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas","volume":"7","author":"S Puget","year":"2012","journal-title":"PLoS One"},{"issue":"5","key":"ref4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/ng.2925","article-title":"Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma","volume":"46","author":"KR Taylor","year":"2014","journal-title":"Nat Genet"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00401-012-0998-0","article-title":"K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas","volume":"124","author":"DA Khuong-Quang","year":"2012","journal-title":"Acta neuropathologica"},{"issue":"20","key":"ref6","doi-asserted-by":"crossref","first-page":"6219","DOI":"10.1158\/0008-5472.CAN-13-1491","article-title":"Novel oncogenic PDGFRA mutations in pediatric high-grade gliomas","volume":"73","author":"BS Paugh","year":"2013","journal-title":"Cancer research"},{"issue":"8","key":"ref7","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1200\/JCO.2005.04.6599","article-title":"Advances toward an understanding of brainstem gliomas","volume":"24","author":"SS Donaldson","year":"2006","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"issue":"2","key":"ref8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1586\/14737140.2015.974563","article-title":"A twenty-year review of diagnosing and treating children with diffuse intrinsic pontine glioma in The Netherlands","volume":"15","author":"SE Veldhuijzen van Zanten","year":"2015","journal-title":"Expert review of anticancer therapy"},{"issue":"7384","key":"ref9","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nature10833","article-title":"Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma","volume":"482","author":"J Schwartzentruber","year":"2012","journal-title":"Nature"},{"issue":"3","key":"ref10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/ng.1102","article-title":"Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas","volume":"44","author":"G Wu","year":"2012","journal-title":"Nat Genet"},{"issue":"12","key":"ref11","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/nm.3716","article-title":"Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma","volume":"20","author":"R Hashizume","year":"2014","journal-title":"Nat Med"},{"issue":"24","key":"ref12","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.1093\/emboj\/20.24.6969","article-title":"Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells","volume":"20","author":"M Gottlicher","year":"2001","journal-title":"The EMBO journal"},{"issue":"10","key":"ref13","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1097\/00001813-199711000-00007","article-title":"Sodium valproate inhibits in vivo growth of human neuroblastoma cells","volume":"8","author":"J Cinatl Jr.","year":"1997","journal-title":"Anti-cancer drugs"},{"issue":"5","key":"ref14","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0145-2126(01)00151-5","article-title":"Valproic acid induces apoptosis in human leukemia cells by stimulating both caspase-dependent and -independent apoptotic signaling pathways","volume":"26","author":"R Kawagoe","year":"2002","journal-title":"Leukemia research"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/cncr.21132","article-title":"Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid","volume":"104","author":"C Pilatrino","year":"2005","journal-title":"Cancer"},{"issue":"6","key":"ref16","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nm.3855","article-title":"Functionally defined therapeutic targets in diffuse intrinsic pontine glioma","volume":"21","author":"CS Grasso","year":"2015","journal-title":"Nat Med"},{"issue":"3","key":"ref17","doi-asserted-by":"crossref","first-page":"e0118926","DOI":"10.1371\/journal.pone.0118926","article-title":"A high-thorughput in vitro drug screen in a genetically engineered mouse model of diffuse intrinsic pontine glioma identifies BMS-754807 as a promising therapeutic agent","volume":"10","author":"KG Halvorson","year":"2015","journal-title":"PLoS One"},{"issue":"3","key":"ref18","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1210\/jc.2004-1355","article-title":"valproic acid induces apoptosis and cell cycle arrest in poorly differentiated thyroid cancer cells","volume":"90","author":"MG Catalano","year":"2004","journal-title":"The journal of clinical endocrinology & metabolism"},{"issue":"3","key":"ref19","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1158\/0008-5472.CAN-03-0799","article-title":"Histone deacetylase is a target of valproic acid-mediated cellular differentiation","volume":"64","author":"N Gurvich","year":"2004","journal-title":"Cancer research"},{"issue":"2","key":"ref20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s11060-007-9402-7","article-title":"Valproic acid induces p21 and topoisomerase-II (\u03b1\/\u03b2) expression and synergistically enhances etoposide cytotoxicity in human glioblastoma cell lines","volume":"85","author":"CM Das","year":"2007","journal-title":"Journal of Neuro-Oncology"},{"issue":"5","key":"ref21","first-page":"104","article-title":"Valproic acid as a potent substance for increasing efficacy of topoisomerase I inhibitors","volume":"39","author":"S Wagner","year":"2009","journal-title":"Turk J Cancer"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/bpa.12082","article-title":"Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations","volume":"24","author":"NU Barua","year":"2014","journal-title":"Brain pathology (Zurich, Switzerland)"},{"issue":"8","key":"ref23","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s00701-013-1700-6","article-title":"Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma","volume":"155","author":"NU Barua","year":"2013","journal-title":"Acta Neurochirurgica"},{"issue":"1","key":"ref24","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3109\/10717544.2014.908248","article-title":"A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma","volume":"23","author":"NU Barua","year":"2016","journal-title":"Drug delivery"},{"issue":"suppl 3","key":"ref25","first-page":"iii131","article-title":"NS-21 Multi-catheter intermittent convection-enhanced delivery of carboplatin as a treatment for Diffuse Intrinsic Pontine Glioma (DIPG): Pre-clinical rationale and early clinical experience","volume":"18","author":"WGB Singleton","year":"2016","journal-title":"Neuro-Oncology"},{"issue":"3","key":"ref26","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s11060-012-0973-6","article-title":"Characterization of a diffuse intrinsic pontine glioma cell line: implications for future investigations and treatment","volume":"110","author":"R Hashizume","year":"2012","journal-title":"J Neurooncol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"TC Chou","year":"1984","journal-title":"Advances in enzyme regulation"},{"issue":"7","key":"ref28","doi-asserted-by":"crossref","first-page":"e0132266","DOI":"10.1371\/journal.pone.0132266","article-title":"Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma","volume":"10","author":"A Arshad","year":"2015","journal-title":"PLoS One"},{"key":"ref29","first-page":"58","article-title":"Enhanced Cytotoxic Effects of Combined Valproic Acid and the Aurora Kinase Inhibitor VE465 on Gynecologic Cancer Cells","volume":"3","author":"Y Li","year":"2013","journal-title":"Frontiers in oncology"},{"issue":"10","key":"ref30","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1038\/sj.bjc.6603132","article-title":"Potentiation of the anticancer effect of valproic acid, an antiepileptic agent with histone deacetylase inhibitory activity, by the kinase inhibitor Staurosporine or its clinically relevant analogue UCN-01","volume":"94","author":"WS Yeow","year":"2006","journal-title":"British journal of cancer"},{"issue":"5","key":"ref31","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1159\/000441849","article-title":"Cytotoxic Effects of Valproic Acid on Neuroendocrine Tumour Cells","volume":"103","author":"Y Arvidsson","year":"2016","journal-title":"Neuroendocrinology"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"e0169485","DOI":"10.1371\/journal.pone.0169485","article-title":"Pre-Clinical Study of Panobinostat in Xenograft and Genetically Engineered Murine Diffuse Intrinsic Pontine Glioma Models","volume":"12","author":"T Hennika","year":"2017","journal-title":"PLOS ONE"},{"issue":"19","key":"ref33","doi-asserted-by":"crossref","first-page":"13548","DOI":"10.1074\/jbc.M510023200","article-title":"Histone Deacetylase 3 (HDAC3) and Other Class I HDACs Regulate Colon Cell Maturation and p21 Expression and Are Deregulated in Human Colon Cancer","volume":"281","author":"AJ Wilson","year":"2006","journal-title":"Journal of Biological Chemistry"},{"issue":"18","key":"ref34","doi-asserted-by":"crossref","first-page":"10014","DOI":"10.1073\/pnas.180316197","article-title":"Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation","volume":"97","author":"VM Richon","year":"2000","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"3","key":"ref35","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.bbrc.2011.06.186","article-title":"Discrimination between primary necrosis and apoptosis by necrostatin-1 in Annexin V-positive\/propidium iodide-negative cells","volume":"411","author":"H Sawai","year":"2011","journal-title":"Biochemical and biophysical research communications"},{"issue":"2","key":"ref36","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.canlet.2007.10.006","article-title":"Valproic acid is a selective antiproliferative agent in estrogen-sensitive breast cancer cells","volume":"259","author":"N Fortunati","year":"2008","journal-title":"Cancer letters"},{"issue":"1\u20132","key":"ref37","doi-asserted-by":"crossref","first-page":"20","DOI":"10.2119\/2007-00084.Bokelmann","article-title":"Valproic acid sensitizes chronic lymphocytic leukemia cells to apoptosis and restores the balance between pro- and antiapoptotic proteins","volume":"14","author":"I Bokelmann","year":"2008","journal-title":"Molecular medicine (Cambridge, Mass)"},{"issue":"7","key":"ref38","doi-asserted-by":"crossref","first-page":"556","DOI":"10.3109\/08880018.2011.563774","article-title":"Potential Role for Valproate in the Treatment of High-Risk Brain Tumors of Childhood\u2014Results from a Retrospective Observational Cohort Study","volume":"28","author":"FHC Felix","year":"2011","journal-title":"Pediatric Hematology and Oncology"},{"issue":"3","key":"ref39","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s11060-016-2054-8","article-title":"Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II\/III gliomas treated with temozolomide","volume":"127","author":"N Redjal","year":"2016","journal-title":"J Neurooncol"},{"issue":"12","key":"ref40","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1158\/1078-0432.CCR-07-0162","article-title":"Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies","volume":"13","author":"SS Ramalingam","year":"2007","journal-title":"Clinical cancer research: an official journal of the American Association for Cancer Research"},{"issue":"12","key":"ref41","doi-asserted-by":"crossref","first-page":"e29144","DOI":"10.1371\/journal.pone.0029144","article-title":"Chromatin Remodeling, Cell Proliferation and Cell Death in Valproic Acid-Treated HeLa Cells","volume":"6","author":"MB Felisbino","year":"2011","journal-title":"PLoS ONE"},{"issue":"9","key":"ref42","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1158\/0008-5472.CAN-04-2478","article-title":"Valproic acid alters chromatin structure by regulation of chromatin modulation proteins","volume":"65","author":"DC Marchion","year":"2005","journal-title":"Cancer research"},{"issue":"5","key":"ref43","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1007\/s10637-013-0003-3","article-title":"Methylation and histone deacetylase inhibition in combination with platinum treatment in patients with advanced malignancies","volume":"31","author":"GS Falchook","year":"2013","journal-title":"Investigational new drugs"},{"issue":"2","key":"ref44","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/sj.bjc.6603851","article-title":"Valproic acid (VPA) in patients with refractory advanced cancer: a dose escalating phase I clinical trial","volume":"97","author":"A Atmaca","year":"2007","journal-title":"British journal of cancer"},{"issue":"2","key":"ref45","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/0920-1211(91)90028-E","article-title":"Comparison of valproate concentrations in human plasma, CSF and brain tissue after administration of different formulations of valproate or valpromide","volume":"9","author":"HG Wieser","year":"1991","journal-title":"Epilepsy research"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0176855","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T00:06:30Z","timestamp":1569369990000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0176855"}},"subtitle":[],"editor":[{"given":"Marta M.","family":"Alonso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,5,25]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,5,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0176855","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,25]]}}}