{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:50:41Z","timestamp":1786125041504,"version":"build-2736575974"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T00:00:00Z","timestamp":1561075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurosurg.","NEUROS"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>An impermeable blood\u2013brain barrier and drug efflux via ATP-binding cassette (ABC) transporters such as p-glycoprotein may contribute to underwhelming efficacy of peripherally delivered agents to treat diffuse intrinsic pontine glioma (DIPG).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>To explore the pharmacological augmentation of convection-enhanced delivery (CED) infusate for DIPG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>The efficacy of CED dasatinib, a tyrosine kinase inhibitor, in a transgenic H3.3K27M mutant murine model was assessed. mRNA expression of ABCB1 (p-glycoprotein) was analyzed in 14 tumor types in 274 children. In Vitro viability studies of dasatinib, the p-glycoprotein inhibitor, tariquidar, and dexamethasone were performed in 2 H3.3K27M mutant cell lines. Magnetic resonance imaging (MRI) was used to evaluate CED infusate (gadolinium\/dasatinib) distribution in animals pretreated with tariquidar and dexamethasone. Histological assessment of apoptosis was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Continuous delivery CED dasatinib improved median overall survival (OS) of animals harboring DIPG in comparison to vehicle (39.5 and 28.5 d, respectively;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a0.0139). Mean ABCB1 expression was highest in K27M gliomas. In Vitro, the addition of tariquidar and dexamethasone further enhanced the efficacy of dasatinib (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a0.001). In Vivo, MRI demonstrated no difference in infusion dispersion between animals pretreated with dexamethasone plus tariquidar prior to CED dasatinib compared to the CED dasatinib. However, tumor apoptosis was the highest in the pretreatment group (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a0.001). Correspondingly, median OS was longer in the pretreatment group (49 d) than the dasatinib alone group (39 d) and no treatment controls (31.5 d,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a0.0305).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>ABC transporter inhibition plus dexamethasone enhances the efficacy of CED dasatinib, resulting in enhanced tumor cellular apoptosis and improved survival in H3.3K27M mutant DIPG.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuros\/nyz212","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T23:19:54Z","timestamp":1557443994000},"page":"742-751","source":"Crossref","is-referenced-by-count":13,"title":["ABC Transporter Inhibition Plus Dexamethasone Enhances the Efficacy of Convection Enhanced Delivery in H3.3K27M Mutant Diffuse Intrinsic Pontine Glioma"],"prefix":"10.1227","volume":"86","author":[{"given":"Vadim","family":"Tsvankin","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rintaro","family":"Hashizume","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Katagi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Herndon","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lascola","sequence":"additional","affiliation":[{"name":"Department of Radiology, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talaignair N","family":"Venkatraman","sequence":"additional","affiliation":[{"name":"Department of Radiology, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Picard","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"},{"name":"Department of Pediatric Neuro-Oncogenomics, German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brainard","family":"Burrus","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren J","family":"Becher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois"},{"name":"Robert H. 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