{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:07:29Z","timestamp":1700698049353},"reference-count":38,"publisher":"Wiley","issue":"3-4","license":[{"start":{"date-parts":[[2013,4,22]],"date-time":"2013-04-22T00:00:00Z","timestamp":1366588800000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The oncolytic adenovirus Delta24\u2010RGD is currently being tested in phase I trials for the treatment of glioblastoma (GBM). Literature suggests that frequently prescribed anticonvulsants for these patients, phenytoin (PHE), valproic acid (VPA) and levetiracetam (LEV), may interfere with cellular mechanisms of cancer or oncolytic virus activity. We therefore investigated the direct effects of these drugs on Delta24\u2010RGD infection and oncolytic activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The anticonvulsants PHE, VPA, and LEV were combined with Delta24\u2010RGD treatment in established glioma cell lines as well as on a panel of patient\u2010derived GBM cultures. Effects on infection efficiency were assessed using luciferase\u2010encoding adenoviral vectors. Oncolytic activity was determined by WST\u20101 assay and viral progeny production was quantified by dilution titration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IC50 values of the anti\u2010epileptic drugs on the four glioma cell lines were far above clinically\u2010relevant concentrations. At therapeutic concentrations, the anti\u2010epileptics generally did not alter the infection efficiency of RGD\u2010modified adenovirus, nor affect progeny production or oncolytic activity of Delta24\u2010RGD. The only exception was found in U373 cells, where VPA slightly antagonised the oncolytic effect of Delta24\u2010RGD (from 29% to 55% viability, p&lt;0.01) as well as viral progeny production (60% decrease, p&lt;0.01). Oncolysis by Delta24\u2010RGD was not inhibited by the anti\u2010epileptics in any of the patient\u2010derived glioma cultures (n=6). In fact, in one culture a slight enhancement of viral oncolysis by PHE and LEV was found, from 89.7% viability to 76% and 62.4%, respectively (p&lt;0.01)<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Therapeutic levels of valproic acid, phenytoin and levetiracetam do not negatively interfere with the infection efficiency or oncolytic activity of Delta24\u2010RGD in patient\u2010derived GBM cells. Therefore, there is no indication that the choice of anticonvulsant for seizure control in glioma patients should take treatment with Delta24\u2010RGD into account. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.2703","type":"journal-article","created":{"date-parts":[[2013,3,14]],"date-time":"2013-03-14T09:20:37Z","timestamp":1363252837000},"page":"134-141","source":"Crossref","is-referenced-by-count":9,"title":["Therapeutic concentrations of anti\u2010epileptic drugs do not inhibit the activity of the oncolytic adenovirus Delta24\u2010RGD in malignant glioma"],"prefix":"10.1002","volume":"15","author":[{"given":"Jonas","family":"de Jonge","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Erasmus MC  Rotterdam The Netherlands"},{"name":"Department of Neurosurgery VU Medical Center  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lotte M. E.","family":"Berghauser Pont","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Erasmus MC  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sander","family":"Idema","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery VU Medical Center  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenneke J.","family":"Kloezeman","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Erasmus MC  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Noske","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery VU Medical Center  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens M. 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