{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:44:46Z","timestamp":1792075486739,"version":"4.4.0"},"reference-count":33,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Wenzhou Science and Technology Bureau basic research project","award":["Y20210091"],"award-info":[{"award-number":["Y20210091"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Biotherapy and Radiopharmaceuticals"],"abstract":"<jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>\n                      The objective of this study was to assess the anticancer efficacy of ED5, a new oleanolic acid (OA) analogue and selective casein kinase 1\u03b1 (CK1\u03b1) inhibitor, and to ascertain if focused ultrasound (FUS) can improve its delivery and therapeutic effect against glioma. The authors carried out\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      , and mechanistic studies incorporating ultrasound-mediated drug delivery, building on the chemical synthesis of ED5 with OA as the main ingredient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      The intratumoral penetration of ED5 in glioma cells and xenograft-bearing mice was enhanced by focused ultrasonic exposure. Cell counting kit-8 assays were used to measure cell viability to calculate IC\n                      <jats:sub>20<\/jats:sub>\n                      values and proliferative capability. Clonogenic survival was evaluated using crystal violet staining. Kinase activity was assessed by kinome profiling. Molecular docking, isothermal titration calorimetry, and surface plasmon resonance were used to confirm the binding between ED5 and CK1\u03b1. Changes in molecular expression brought on by ED5 with or without FUS were measured using quantitative polymerase chain reaction and immunohistochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      When compared with OA, ED5 dramatically reduced the ability of human glioma cell lines U118MG and LN229 to proliferate and form colonies. The antiproliferative effects of ED5 were further amplified by FUS, which increased its absorption in glioma cells. Without causing any discernible systemic toxicity, the combination of ED5 and FUS\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      resulted in a greater suppression of tumor growth than ED5 alone. According to mechanistic research, ED5 selectively binds CK1\u03b1 and inhibits its kinase activity. Endoplasmic reticulum stress (ERS), reactive oxygen species (ROS) buildup, and activation of the JNK\/c-Jun branch of the Mitogen-activated protein kinase (MAPK) signaling pathway were all brought on by this suppression. By increasing the effectiveness of ED5 administration, FUS further enhanced these molecular effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      ED5 targets CK1\u03b1 and modulates the\n                      <jats:italic toggle=\"yes\">MAPK\u2013ROS\u2013ERS<\/jats:italic>\n                      signaling pathway to demonstrate strong anticancer efficacy against glioblastoma. A novel ultrasound-enhanced biotherapy approach for glioma care is highlighted by FUS, which dramatically increases ED5 intratumoral delivery and therapeutic efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10849785261476936","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:28:20Z","timestamp":1791869300000},"source":"Crossref","is-referenced-by-count":0,"title":["Focused Ultrasound\u2013Enhanced Delivery of ED5, a CK1\u03b1-Targeting Oleanolic Acid Analogue, Suppresses Glioma Growth via MAPK\u2013ROS\u2013ERS Pathway Modulation"],"prefix":"10.1177","author":[{"given":"Yongqi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengpeng","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Quzhou Hospital affiliated to Wenzhou Medical University (Quzhou People\u2019s Hospital), Quzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Quzhou Hospital affiliated to Wenzhou Medical University (Quzhou People\u2019s Hospital), Quzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Quzhou Hospital affiliated to Wenzhou Medical University (Quzhou People\u2019s Hospital), Quzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjiang","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Quzhou Hospital affiliated to Wenzhou Medical University (Quzhou People\u2019s Hospital), Quzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yongkang First People\u2019s Hospital of Wenzhou Medical University, Jinhua, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Quzhou Hospital affiliated to Wenzhou Medical University (Quzhou People\u2019s Hospital), Quzhou, 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