{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:28:44Z","timestamp":1787862524313,"version":"build-2784847793"},"reference-count":36,"publisher":"S. Karger AG","issue":"9","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"abstract":"<jats:p>Introduction: Metastatic liver pancreatic neuroendocrine tumors (PNETs) can be treated with ischemia-based trans-arterial embolization\/trans-arterial chemo-embolization or radiation-based trans-arterial radioembolization (TARE). Guidelines for treatment selection are limited. The purpose of this study was to measure the effect of loss of DAXX\/ATRX protein expression on ischemia and radiation sensitivity in Bon-1 and QGP-1 cells, and to compare TARE response in PNETs with and without a DAXX\/ATRX mutation. Methods: This was a laboratory investigation and retrospective review of an institutional database of TARE-treated PNET patients. Ischemia and radiation sensitivity were tested on Bon-1 and QGP-1 cells and CRISPR-generated DAXX (C16\/C45) and ATRX (QAX12\/QAX24) knockouts. Post-ischemia and postradiation cell viability, survival fraction, and caspase-3 expression were measured. Local progression-free survival (LPFS) was measured from time of TARE to local progression or death and estimated using Cox proportional hazards. Results: Post-ischemia DAXX (C16\/C45) and ATRX (QAX12\/QAX24) knockouts had increased cell viability compared with Bon-1 wild-type cells (p &lt; 0.0001, days 3, 5) and QGP-1 wild-type cells (p &lt; 0.0001, days 3, 5, 7). Postradiation C16\/C45 and QAX12\/QAX24 had decreased survival fraction compared with respective wild type (p &lt; 0.0001, all cell lines). C16\/C45 had decreased apoptotic activity post-ischemia and increased apoptotic activity postradiation compared with wild type (p &lt; 0.0001, all cell lines). Presence of DAXX\/ATRX mutation was associated with longer LPFS after TARE (p &lt; 0.001). Median LPFS after TARE was 6 months in wild type compared with 22 months in patients with DAXX\/ATRX mutation. Conclusion: Loss of DAXX\/ATRX protein expression is associated with ischemia resistance and radiation sensitivity in Bon-1 and QGP-1 cells and longer LPFS after TARE in PNET patients.<\/jats:p>","DOI":"10.1159\/000547041","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T16:02:40Z","timestamp":1753372960000},"page":"730-740","source":"Crossref","is-referenced-by-count":2,"title":["Loss of DAXX\/ATRX Protein Expression Results in Ischemia Resistance and Radiation Sensitivity in Pancreatic Neuroendocrine Tumor Cells and Is Associated with Improved Response to Trans-Arterial Radioembolization"],"prefix":"10.1159","volume":"115","author":[{"name":"Puzzuoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Solivio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindy K.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Shenker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-2336","authenticated-orcid":false,"given":"Will","family":"Vista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4111-5165","authenticated-orcid":false,"given":"Himanshu","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Gonzalez-Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Latzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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