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The clinical correlations between S1PR1\/5 expression and glioma prognosis were analyzed using the GEPIA and HPA databases. The effects of BAF312 on tumor growth, cell cycle progression, apoptosis, and vascular remodeling were evaluated using orthotopic GL261 glioma models and glioma cell lines (U118MG, T98G, GL261). Techniques such as bioluminescent imaging, flow cytometry, Western blot analysis, and immunofluorescence staining were employed. High expression of S1PR1\/5 was associated with improved survival in glioma patients. BAF312 inhibited glioma proliferation both in\u00a0vitro and in\u00a0vivo by arresting the G1\u2010S transition through modulation of the Skp2\u2010p27 axis and inducing apoptosis through p53\u2010independent mitochondrial pathways. Additionally, BAF312 promoted tumor vascular normalization by enhancing pericyte coverage (PDGFR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    ), reducing vessel leakage (TER119\n                    <jats:sup>+<\/jats:sup>\n                    RBCs), and altering vessel diameter distribution. Notably, BAF312 reduced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration, suggesting that its efficacy is predominantly mediated by tumor\u2010intrinsic mechanisms. BAF312 exhibits significant anti\u2010glioma activity through mechanisms involving cell cycle arrest, apoptosis induction, and vascular normalization, highlighting its potential as a repurposed therapeutic agent. This study offers preclinical evidence supporting the anti\u2010glioma effects of BAF312; though further investigation is warranted to evaluate combinatorial efficacy with conventional therapies and address immunosuppressive effects limiting monotherapy application.\n                  <\/jats:p>","DOI":"10.1096\/fj.202501098rr","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T14:59:04Z","timestamp":1755010744000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>BAF312<\/scp>\n                    Inhibits the Growth of Glioma and Promotes the Normalization of Tumor Blood Vessels"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2349-6355","authenticated-orcid":false,"given":"Qi","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"},{"name":"Research Center for Protein and Cell\u2010Based Drugs, Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Research Center for Protein and Cell\u2010Based Drugs, Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhao","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7777-7755","authenticated-orcid":false,"given":"Min","family":"Yu","sequence":"additional","affiliation":[{"name":"Research Center for Protein and Cell\u2010Based Drugs, Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Zhengzhou University, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.11.010"},{"key":"e_1_2_10_3_1","first-page":"2569","article-title":"Current Status of Cerebral Glioma Surgery in China","volume":"124","author":"Wu J. 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