ArticleNeuro-oncology advances
Permeabilization of tumor margins in brain macrometastases using a type-1 receptor selective tumor necrosis factor mutein.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
Background: 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. Methods: 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. Results: 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 ( Conclusions: 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.
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