{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:57:23Z","timestamp":1790773043796,"version":"4.1.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":251,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/V005995\/1"],"award-info":[{"award-number":["MR\/V005995\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Brain metastasis remains a major clinical challenge. The blood-brain barrier, which persists in the margins even in late-stage macrometastases, is a major impediment to effective drug delivery, surgery, or radiotherapy. The aim of this study was to determine whether a mutein of human tumor necrosis factor (TNF) that is selective for the TNFR1 receptor could increase permeabilization in the margins of brain metastases, enabling better delineation and more complete treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Intracerebral xenograft mouse models of breast cancer (MDA231Br-GFP), melanoma (H1_DL2), and lung cancer (SEBTA) brain metastasis were used to test the efficacy of the TNF mutein (mutTNF) in permeabilizing the margins of well-established macrometastases. Changes in tumor permeabilization were assessed in vivo by gadolinium-enhanced magnetic resonance imaging (MRI) and ex vivo by IgG immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tumor margin permeabilization was increased following mutTNF treatment in all 3 models. The MDA231Br-GFP model showed a significant increase in the extent of both gadolinium enhancement (P\u2009&amp;lt;\u20090.01) and IgG extravasation (P\u2009&amp;lt;\u20090.05), whilst significant effects were detected by MRI alone in the SEBTA (P\u2009&amp;lt;\u20090.01) and H1_DL2 (P\u2009&amp;lt;\u20090.05) models. Although a strong trend toward increased IgG extravasation was found in the SEBTA model (P\u2009=\u20090.076). Consistent with these findings, the models showed differing degrees of both infiltration and vascular TNFR1 expression at the margins (MDA231Br-GFP\u2009&amp;gt;\u2009SEBTA\u2009&amp;gt;\u2009H1_DL2), suggesting a greater sensitivity to mutTNF with increasing marginal invasiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work demonstrates the potential of TNFR1-selective mutTNF as an adjuvant strategy to improve tumor margin delineation and enhance therapeutic access in brain metastases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/noajnl\/vdag239","type":"journal-article","created":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T11:20:52Z","timestamp":1788693652000},"source":"Crossref","is-referenced-by-count":0,"title":["Permeabilization of tumor margins in brain macrometastases using a type-1 receptor selective tumor necrosis factor 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