{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T08:52:52Z","timestamp":1783155172217,"version":"3.54.6"},"reference-count":26,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health\u2013Ricerca Corrente Annual Program 2023","award":["EURONANOMED2019-75\/GLIOSILK"],"award-info":[{"award-number":["EURONANOMED2019-75\/GLIOSILK"]}]},{"name":"Technological Development Projects in Nanomedicine, ERA-NET EuroNanoMed III, project \u201cSilk-fibroin interventional nano-trap for the treatment of glioblastoma\u201d","award":["EURONANOMED2019-75\/GLIOSILK"],"award-info":[{"award-number":["EURONANOMED2019-75\/GLIOSILK"]}]},{"name":"University of Modena and Reggio Emilia, FAR2021 Mission Oriented \u201cNano-Immuno Targeting for the Treatment of Glioblastoma Multiforme\u201d","award":["EURONANOMED2019-75\/GLIOSILK"],"award-info":[{"award-number":["EURONANOMED2019-75\/GLIOSILK"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Epilepsy is reported in 29\u201352% of patients with glioblastoma (GBM) and has an important role in the natural history of this tumor and patients\u2019 life quality. Although GBM is less epileptogenic than lower-grade gliomas, seizures are usually more difficult to control with common antiseizure medications; drug resistance is found in 20% of cases. Recent studies suggest that seizures at the onset of GBM could be a possible favorable independent prognostic factor in patients. Moreover, a growing body of evidence shows that many molecular mechanisms that influence epileptogenesis often regulate GBM growth and invasiveness, sometimes favoring or counteracting the tumor, respectively. The better-characterized players include glutamate, \u03b3-aminobutyric acid, aquaporin-4, and hypoxia-activated molecules. However, currently available data on the molecular basis of epileptogenesis, tumorigenesis, and their relationship is incomplete or discordant and further research is urgently needed on this topic.<\/jats:p>","DOI":"10.3390\/medicina58101349","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T01:51:49Z","timestamp":1664329909000},"page":"1349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Epileptogenesis and Tumorigenesis in Glioblastoma: Which Relationship?"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1856-7422","authenticated-orcid":false,"given":"Jessica","family":"Rossi","sequence":"first","affiliation":[{"name":"Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cavallieri","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-2511","authenticated-orcid":false,"given":"Giuseppe","family":"Biagini","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Russo","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8890-3460","authenticated-orcid":false,"given":"Salvatore","family":"Cozzi","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, Oncological Department and Advanced Technologies, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Giaccherini","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, Oncological Department and Advanced Technologies, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pisanello","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Valzania","sequence":"additional","affiliation":[{"name":"Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.clineuro.2016.10.001","article-title":"Biomarkers related with seizure risk in glioma patients: A systematic review","volume":"151","author":"Zhou","year":"2016","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1001\/jama.2013.280319","article-title":"Glioblastoma and Other Malignant Gliomas: A Clinical Review","volume":"310","author":"Omuro","year":"2013","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0360-3016(92)91021-E","article-title":"Supratentorial malignant glioma: Patterns of recurrence and implications for external beam local treatment","volume":"24","author":"Gaspar","year":"1992","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rossi, J., Giaccherini, L., Cavallieri, F., Napoli, M., Moratti, C., Froio, E., Serra, S., Fraternali, A., Ghadirpour, R., and Cozzi, S. (2020). Extracranial metastases in secondary glioblastoma multiforme: A case report. BMC Neurol., 20.","DOI":"10.1186\/s12883-020-01959-y"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"881","DOI":"10.3390\/curroncol29020075","article-title":"Delayed Effect of Dendritic Cells Vaccination on Survival in Glioblastoma: A Systematic Review and Meta-Analysis","volume":"29","author":"Cozzi","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Radin, D.P., and Tsirka, S.E. (2020). Interactions between tumor cells, neurons, and microglia in the glioma microenvironment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228476"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1093\/neuonc\/nov238","article-title":"Prognostic relevance of epilepsy at presentation in glioblastoma patients","volume":"18","author":"Berendsen","year":"2016","journal-title":"Neuro. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.clineuro.2017.11.015","article-title":"Quantifying the prognostic significance in glioblastoma of seizure history at initial presentation: A systematic review and meta-analysis","volume":"164","author":"Lu","year":"2018","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"903115","DOI":"10.3389\/fnmol.2022.903115","article-title":"Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma","volume":"15","author":"Hills","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/epi.12440","article-title":"Tumoral epileptogenicity: How does it happen?","volume":"54","author":"Pallud","year":"2013","journal-title":"Epilepsia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1172\/JCI133316","article-title":"Pathogenesis of peritumoral hyperexcitability in an immunocompetent CRISPR-based glioblastoma model","volume":"130","author":"Hatcher","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.yebeh.2017.10.027","article-title":"IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy","volume":"78","author":"Neal","year":"2018","journal-title":"Epilepsy Behav."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e539","DOI":"10.1016\/j.wneu.2017.12.112","article-title":"Association Between IDH1 and IDH2 Mutations and Preoperative Seizures in Patients with Low-Grade Versus High-Grade Glioma: A Systematic Review and Meta-Analysis","volume":"111","author":"Phan","year":"2018","journal-title":"World Neurosurg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11060-018-2785-9","article-title":"High expression of cystine\u2013glutamate antiporter xCT (SLC7A11) is an independent biomarker for epileptic seizures at diagnosis in glioma","volume":"138","author":"Mellegaard","year":"2018","journal-title":"J. Neurooncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1212\/WNL.0b013e318266fa89","article-title":"Glutamate is associated with a higher risk of seizures in patients with gliomas","volume":"79","author":"Yuen","year":"2012","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s11060-008-9794-z","article-title":"Epilepsy in glioblastoma multiforme: Correlation with glutamine synthetase levels","volume":"93","author":"Rosati","year":"2009","journal-title":"J. Neurooncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1093\/neuonc\/nos338","article-title":"Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme","volume":"15","author":"Rosati","year":"2013","journal-title":"Neuro. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/onc.2016.245","article-title":"Endogenous GABAA receptor activity suppresses glioma growth","volume":"36","author":"Blanchart","year":"2017","journal-title":"Oncogene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.2119\/molmed.2012.00015","article-title":"Different aquaporin-4 expression in glioblastoma multiforme patients with and without seizures","volume":"18","author":"Isoardo","year":"2012","journal-title":"Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"32345","DOI":"10.18632\/oncotarget.16017","article-title":"The potential roles of aquaporin 4 in malignant gliomas","volume":"8","author":"Lan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Behling, F., Barrantes-Freer, A., Behnes, C.L., Stockhammer, F., Rohde, V., Adel-Horowski, A., Rodr\u00edguez-Villagra, O.A., Barboza, M.A., Br\u00fcck, W., and Lehmann, U. (2020). Expression of Olig2, Nestin, NogoA and AQP4 have no impact on overall survival in IDH-wildtype glioblastoma. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0229274"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Berendsen, S., Spliet, W.G.M., Geurts, M., Van Hecke, W., Seute, T., Snijders, T.J., Bours, V., Bell, E.H., Chakravarti, A., and Robe, P.A. (2019). Epilepsy Associates with Decreased HIF-1\u03b1\/STAT5b Signaling in Glioblastoma. Cancers, 11.","DOI":"10.3390\/cancers11010041"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1016\/j.ajpath.2012.01.040","article-title":"The Tumor Microenvironment Strongly Impacts Master Transcriptional Regulators and Gene Expression Class of Glioblastoma","volume":"180","author":"Cooper","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/nop\/npab030","article-title":"Efficacy of antiepileptic drugs in glioma patients with epilepsy: A systematic review","volume":"8","author":"Dirven","year":"2021","journal-title":"Neuro-Oncol. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.3171\/2016.4.JNS16245","article-title":"Prophylactic antiepileptic drug administration following brain tumor resection: Results of a recent AANS\/CNS Section on Tumors survey","volume":"126","author":"Dewan","year":"2017","journal-title":"J. Neurosurg."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/10\/1349\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:39:35Z","timestamp":1760143175000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/10\/1349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,26]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["medicina58101349"],"URL":"https:\/\/doi.org\/10.3390\/medicina58101349","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,26]]}}}