{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T10:38:30Z","timestamp":1793270310623,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173279"],"award-info":[{"award-number":["82173279"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472981"],"award-info":[{"award-number":["82472981"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) remains difficult to treat despite multimodal therapy. Tumor Treating Fields (TTF) disrupts mitosis and provides clinical benefit in GBM, but the molecular responses associated with TTF and the effects of combining TTF with temozolomide (TMZ) remain incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TMZ, TTF, and TMZ\u2009+\u2009TTF were evaluated in U251 and SHG140 GBM cells and patient\u2010derived organoids. TTF was applied at 200\u2009kHz and 1.75\u2009V\/cm RMS. Viability, colony formation, migration\u2010related phenotypes, apoptosis, cell\u2010cycle distribution, Western blotting, qRT\u2010PCR, RNA\u2010seq, and organoid morphology\/immunofluorescence analyses were performed. SB525334 was used to assess SMAD\u2010associated signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Combined TMZ\u2009+\u2009TTF treatment more strongly suppressed cell viability, clonogenic growth, and migration\u2010related phenotypes than either monotherapy, produced greater disruption of organoid structural integrity, and was accompanied by increased cleaved caspase\u20103 activation and apoptotic populations. RNA\u2010seq identified TTF\u2010associated transcriptomic changes involving chromatin\u2010associated processes, DNA replication, and cell\u2010cycle pathways. TTF was associated with selected SMAD\u2010related signaling changes, G2\/M accumulation, altered checkpoint signaling, and enhanced proapoptotic signaling. SB525334 partially attenuated TTF\u2010associated SMAD phosphorylation, growth suppression, and cleaved caspase\u20103 induction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TTF enhances TMZ\u2010associated antitumor responses in GBM cell lines and organoids, accompanied by cell\u2010cycle blockade, apoptosis\u2010associated changes, and selected SMAD\u2010related signaling responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71195","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:00:47Z","timestamp":1791550847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Treating Fields Enhance Temozolomide\u2010Associated Growth Suppression in Glioblastoma Cells and Patient\u2010Derived Organoids Through Cell\u2010Cycle Blockade, Apoptosis, and\n                    <scp>SMAD<\/scp>\n                    \u2010Associated Signaling"],"prefix":"10.1002","volume":"32","author":[{"given":"Haiping","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The Fourth Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingbo","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Fourth Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuetao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Fourth Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Fourth Affiliated Hospital of Soochow University  Suzhou 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