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Abstract
Minimally invasive ablation strategies enable locoregional treatment of tumors. One such strategy, electrolytic ablation, functions through the local delivery of direct current without thermal effects, facilitating enhanced precision. However, the clinical application of electrolytic ablation is limited by an incompletely characterized mechanism of action. Here we show that acid and base production at the electrodes precipitates local pH changes causing the rapid cell death that underlies macroscopic tumor necrosis at pH > 10.6 or < 4.8. The extent of cell death can be modulated by altering the local buffering capacity and antioxidant availability. These data demonstrate that electrolytic ablation is distinguished from other ablation strategies via its ability to induce cellular necrosis by directly altering the tumor microenvironment. These findings may enable further development of electrolytic ablation as a curative therapy for primary, early stage tumors.
Nicholas Perkons et al. investigate the mechanism by which electrolytic ablation induces cell death in the localized treatment of tumors. They find that electrolytic ablation alters the pH buffering capacity of the tumor microenvironment to induce cellular necrosis.
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1 Penn Image-Guided Interventions Laboratory, Philadelphia, USA; Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); Department of Bioengineering, Philadelphia, USA (GRID:grid.25879.31)
2 Penn Image-Guided Interventions Laboratory, Philadelphia, USA (GRID:grid.25879.31); Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
3 Penn Image-Guided Interventions Laboratory, Philadelphia, USA (GRID:grid.25879.31); Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, USA (GRID:grid.411115.1) (ISNI:0000 0004 0435 0884)
4 Penn Image-Guided Interventions Laboratory, Philadelphia, USA (GRID:grid.411115.1); Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, USA (GRID:grid.411115.1) (ISNI:0000 0004 0435 0884)
5 Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, USA (GRID:grid.411115.1) (ISNI:0000 0004 0435 0884)
6 Penn Image-Guided Interventions Laboratory, Philadelphia, USA (GRID:grid.411115.1); Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, USA (GRID:grid.411115.1) (ISNI:0000 0004 0435 0884)
7 Penn Image-Guided Interventions Laboratory, Philadelphia, USA (GRID:grid.411115.1); Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); Department of Bioengineering, Philadelphia, USA (GRID:grid.25879.31); Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, USA (GRID:grid.411115.1) (ISNI:0000 0004 0435 0884); Department of Cancer Biology, Philadelphia, USA (GRID:grid.411115.1)