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Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28\u00a0specimens\u00a0from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (na\u00efve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the na\u00efve Bev group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the na\u00efve Bev group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the na\u00efve Bev group for paired specimens (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.036). PLGF was more abundant in T2 diffuse\/circumscribe patterns (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.\n                  <\/jats:p>","DOI":"10.1007\/s10014-024-00481-0","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T11:02:20Z","timestamp":1713178940000},"page":"61-72","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment"],"prefix":"10.1007","volume":"41","author":[{"given":"Taketo","family":"Ezaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-6317","authenticated-orcid":false,"given":"Toshihide","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Ohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Takei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukina","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryotaro","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kuranai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuharu","family":"Akasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Toda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Murayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"key":"481_CR1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1056\/NEJMoa1308345","volume":"370","author":"OL Chinot","year":"2014","unstructured":"Chinot OL, Wick W, Mason W et al (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. 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Approval was granted by the Ethics Committee of Jikei University School of Medicine Kashiwa Hospital, Keio University School of Medicine, and Kagawa University Graduate School of Medicine. The study was approved by the Institutional Review Board (JKI18-052 for Jikei, N20160036 for Keio, 2018KH046 for Kagawa).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from all the participants.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors affirm that human research participants provided informed consent for publication of the images in Figs.\n                      \n                      and\n                      \n                      .","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}